CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 62/951,221, filed Dec. 20, 2019 and U.S. Provisional Patent Application No. 63/064,502, filed Aug. 12, 2020 the disclosures of which is incorporated herein by reference in their entirety.

FIELD

Aspects and embodiments described herein relate to compounds active towards nuclear receptors, pharmaceutical compositions comprising the compounds, and methods of treating inflammatory, metabolic, oncologic and autoimmune diseases or disorders using the compounds.

BACKGROUND

Nuclear receptors are a family of transcription factors involved in the regulation of physiological functions, such as cell differentiation, embryonic development, and organ physiology. Nuclear receptors have also been identified as important pathological regulators in diseases such as cancer, diabetes, and autoimmune disorders.

Examples of nuclear receptors include the nuclear retinoic acid receptor-related orphan receptors (RORs). RORs contain four principal domains: an N-terminal A/B domain, a DNA-binding domain, a hinge domain and a ligand binding domain. Binding of ligands to the ligand-binding domain is believed to cause conformational changes in the domain resulting in downstream actions. Different isoforms exist and these isoforms differ in their N-terminal A/B domain only (Jetten, 2009, Nuclear Receptor Signaling).

RORs consist of three members, namely ROR alpha (RORα or RORa), ROR beta (RORβ or RORb) and ROR gamma (RORγ or RORc).

RORα is expressed in many tissues such as cerebellar Purkinje cells, the liver, thymus, skeletal muscle, skin, lung, adipose tissue and kidney. RORα regulates neuronal cell development, bone metabolism, and arteriosclerosis (Jetten, 2009, Nuclear Receptor Signaling). Additionally, RORa plays a role in the immune responses, such as in the regulation interleukin (IL) 17A expression in T helper (Th) 17 cells and the function of T regulatory (Treg) cells (Castro PLOS 2017; Malhotra 2018).

RORβ exhibits a restriction pattern of expression limited to certain regions of brain (cerebral cortex, thalamus, hypothalamus and pineal gland) as well as retina (Jetten, 2009, Nuclear Receptor Signaling). RORβ has been related to epilepsy and together with RORa also to bipolar disease (Rudolf 2016; Lai 2015).

RORγ shows a broad expression pattern and was the most recently discovered of the three members. To date two different protein isoforms have been recorded: RORγ1 and RORγ2 (RORγ2 is also known as RORγt). Generally RORγ is used to describe RORγ1 and/or RORγt. RORγ1 is expressed in many tissues and is predominantly expressed in the kidneys, liver, and skeletal muscle. In contrast, expression of RORγt is restricted to some cell types of the immune system and to lymphoid organs such as the thymus and secondary lymphoid tissues (Hirose 1994; Jetten, 2009, Nuclear Receptor Signaling).

RORγt has been identified as a key regulator of Th17 cell differentiation and IL-17 production by γδ T cells, Th17 cells, T cytotoxic (Tc) 17 cells and innate lymphoid cells type 3 (ILC3) cells (Gaffen 2014). Th17 cells are a subset of T helper cells which preferentially produce the cytokines IL-17A, IL-17F, IL-21 and IL-22 (Castro PLOS 2017). T cells lacking RORγt failed to differentiate into Th17 cells even under Th17-polarizing culture conditions, while over-expression of RORγt in naïve CD4+ T cells was sufficient to accelerate the expression of Th17-related cytokines and chemokines (Gaffen 2014, Nat Rev Immunol; Yang 2014, Trend Pharmacol Sci). IL-23 is a vital checkpoint in the generation, maintenance and activation of pathogenic Th17 cells. In response to IL-23 signals, RORγt cooperates with a network of transcription factors (STAT3, IRF4 and BATF) to initiate the complete differentiation program of Th17 cells (Gaffen 2014, Nat Rev Immunol).

Th17 cells and IL-17 immune response have been shown to be associated with the pathology of many human inflammatory and autoimmune disorders. Therapeutic strategies targeting the IL-23-IL-17 axis are being developed in many autoimmune diseases, and some of them have already demonstrated to provide clinical efficacy some diseases (Patel 2015; Krueger 2018 Exp Dermatol).

There is thus evidence that RORa, RORβ and RORγ play a role in the pathogenesis of many diseases.

It would be desirable to provide compounds that modulate the activity of RORa and/or RORγ for use in treating inflammatory, metabolic and autoimmune diseases. WO2016020288 and WO2016020295 describe compounds that modulate the activity or RORgamma receptors. However, a need still exists for potent RORgamma modulators having improved physico-chemical properties.

SUMMARY

In one aspect provided herein are compounds of Formula (I)

[Image Omitted]

a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein:

- Y₁, Y₂and Y₃are independently N or CR₈;

R is selected from the group consisting of hydrogen, C_1-6alkyl, and C_1-4hydroxyalkyl;

- R_0aand R_0bindependently are selected from the group consisting of hydrogen, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4haloalkyl, CN, substituted or unsubstituted heteroalicyclyl and substituted or unsubstituted heteroaryl;
- R_1aand R_1bare independently selected from the group consisting of hydrogen, hydroxyl, halogen, amino, C_1-4alkyl, C_1-4hydroxyalkyl, and C_1-4haloalkyl;

R₂is selected from the group consisting of hydrogen, hydroxyl, amino, cyano, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C(═O)OH, C(═O)NH₂, C(═O)O—C_1-4alkyl, and substituted or unsubstituted heteroaryl;

R₃is selected from the group consisting of C_1-4alkyl, C_2-4alkenyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, C_1-4alkylene-C_1-4alkoxy, substituted or unsubstituted C_3-7cycloalkyl, and substituted or unsubstituted C_3-7cycloalkenyl;

R₄and R₅are each independently hydrogen or C_1-4alkyl, or R₄and R₅are taken together with the carbon atom to which they are attached to form a C_3-4cycloalkyl;

R₆is selected from the group consisting of hydrogen, CN, halogen, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, C_1-4haloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl;

R₇is selected from the group consisting of hydrogen, hydroxyl, CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl;

each R₈independently is selected from the group consisting of hydrogen, hydroxyl, CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl; and

whenever R₇is hydrogen and each R₈present is hydrogen, then R₆is selected from the group consisting of CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl; and

when substituted, a heteroalicyclyl is substituted with 1 to 3 substituents independently selected from the group consisting of C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, hydroxy, C_1-4alkoxy, and halogen; and

when substituted, a heteroaryl is substituted with 1 to 3 substitutents independently selected from the group consisting of C_1-4alkyl, C_1-4hydroxyalkyl, C_2-4alkenyl, C_2-4alkynyl, hydroxy, C_1-4alkoxy, cyano, halogen, C_1-4haloalkyl, C_1-4haloalkoxy and C_1-6hydroxyhaloalkyl; and

when substituted, a cycloalkyl or cycloalkenyl is substituted with 1 to 3 substituents independently selected from the group consisting of C_1-4alkyl and halogen.

In one aspect provided herein are pharmaceutical compositions comprising a compound of Formula (I) or a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer of Formula (I) and at least one pharmaceutical acceptable excipient.

In one aspect provided herein are compounds of Formula (I) or a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer of Formula (I), or pharmaceutical compositions thereof for use in treatment and/or prevention of a disease or disorder or a symptom thereof selected from the group consisting of asthma, acne, chronic obstructive pulmonary disease (COPD), bronchitis, atherosclerosis, Helicobacter pylori infection, allergic diseases including allergic rhinitis, allergic conjunctivitis and uveitis, sprue and food allergy, atopic dermatitis, lichen planus, cystic fibrosis, lung allograph rejection, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, ichthyoses, bullous diseases, hidradenitis suppurativa, steatosis, steatohepatitis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), lupus erythematosus, Hashimoto's disease, pancreatitis, autoimmune diabetes, autoimmune ocular disease, ulcerative colitis, colitis, Crohn's disease, inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), Sjogren's syndrome, optic neuritis, type I diabetes, neuromyelitis optica, Myastehnia Gravis, Guillain-Barre syndrome, Graves' disease, scleritis, obesity, obesity-induced insulin resistance, type II diabetes, and cancer.

Further, advantageous features of various embodiments are defined in the dependent claims and within the detailed description below.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Definitions

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. All patents, applications, published applications and other publications referenced herein are incorporated by reference in their entirety. In the event that there are a plurality of definitions for a term herein, those in this section prevail unless stated otherwise.

As used herein, any “R” group(s) such as, without limitation, R, R_0a, R_0b, R_1a, R_1b, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, and R₁₀, represent substituents that can be attached to the indicated atom. Examples of R groups includes but is not limited to hydrogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and heteroalicyclyl. If two “R” groups are covalently bonded to the same atom or to adjacent atoms, then they may be “taken together” or “combined” as defined herein to form a cycloalkyl, aryl, heteroaryl or heteroalicyclyl group. For example, without limitation, if R_aand R_bof an NR_aR_bgroup are indicated to be “taken together” or “combined”, it means that they are covalently bonded to one another at their terminal atoms to form a ring that includes the nitrogen:

[Image Omitted]

As readily recognized by the skilled person, any given group disclosed herein may comprise further hydrogen(s) than the one(s) provided by a R-group, being hydrogen, attached to the group.

Whenever a group is described as being “unsubstituted or substituted,” if substituted, the substituent(s) (which may be present one or more times, such as 1, 2, 3 or 4 times) are independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, hydroxyalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. When a substituent on a group is deemed to be “substituted,” the substitutent itself is substituted with one or more of the indicated substitutents. When the referenced substituent is substituted, it is meant that one or more hydrogen atoms on the referenced substituent may be replaced with a group(s) individually and independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, hydroxyalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. The protecting groups that may form the protective derivatives of the above substituents are known to those of skill in the art and may be found in references Greene and Wuts, Protective Groups in Organic Synthesis, 3^rdEd., John Wiley & Sons, New York, N.Y., 1999, which is hereby incorporated by reference in its entirety.

As used herein, “C_mto C_n,” “C_m-C_n” or “C_m-n” in which “m” and “n” are integers refers to the number of carbon atoms in the relevant group. That is, the group can contain from “m” to “n”, inclusive, carbon atoms. Thus, for example, a “Ci to C₆alkyl” group refers to all alkyl groups having from 1 to 6 carbons, that is, CH₃—, CH₃CH₂—, CH₃CH₂CH₂—, (CH₃)₂CH—, CH₃CH₂CH₂CH₂—, CH₃CH₂CH(CH₃)—, CH₃CH(CH)₃CH₂—, CH₃CH(CH)₃CH₂— and (CH₃)₃C—. If no “m” and “n” are designated with regard to a group, the broadest range described in these definitions is to be assumed.

As used herein, “alkyl” refers to a straight or branched hydrocarbon chain group that is fully saturated (no double or triple bonds). The alkyl group may have 1 to 20 carbon atoms (whenever it appears herein, a numerical range such as “1 to 20” refers to each integer in the given range; e.g., “1 to 20 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated). The alkyl group may also be a medium size alkyl having 1 to 10 carbon atoms, such as “C_1-6”. The alkyl group could also be a lower alkyl having 1 to 4 carbon atoms. The alkyl group of the compounds may be designated as “C₁-C₄alkyl,” “C_1-4alkyl” or similar designations. By way of example only, “C₁-C₄alkyl” or “C_1-4alkyl” indicates that there are one to four carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, and the like. When substituted, the substituent group(s) is(are) one or more group(s) individually and independently selected from alkenyl, alkynyl, cycloalkyl including but not limited to cyclopropyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy including but not limited to methoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen including but not limited to fluoro, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, hydroxyalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof.

As used herein, “alkenyl” refers to an alkyl group that contains in the straight or branched hydrocarbon chain one or more double bonds. If more than one double bond is present, the double bonds may be conjugated or not conjugated. The alkenyl group may have 2 to 20 carbon atoms (whenever it appears herein, a numerical range such as “2 to 20” refers to each integer in the given range; e.g., “2 to 20 carbon atoms” means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, etc., up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no numerical range is designated). When substituted, the substituent group(s) is(are) one or more group(s) individually and independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, mercapto, alkylthio, cyano, halogen, nitro, haloalkyl, hydroxyalkyl, haloalkoxy, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof.

As used herein, “alkynyl” refers to an alkyl group that contains in the straight or branched hydrocarbon chain one or more triple bonds. The alkynyl group may have 2 to 20 carbon atoms (whenever it appears herein, a numerical range such as “2 to 20” refers to each integer in the given range; e.g., “2 to 20 carbon atoms” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, etc., up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated). An alkynyl group may be unsubstituted or substituted. When substituted, the substituent(s) may be selected from the same groups disclosed above with regard to alkenyl group substitution.

As used herein, “hetero” may be attached to a group and refers to one or more carbon atom(s) and the associated hydrogen atom(s) in the attached group have been independently replaced with the same or different heteroatoms selected from nitrogen, oxygen, phosphorus and sulfur.

As used herein, “heteroalkyl,” by itself or in combination with another term, refers to a straight or branched alkyl group consisting of the stated number of carbon atoms, where one or more carbon atom(s), such as 1, 2, 3 or 4 carbon atom(s), and the associated hydrogen atom(s) have been independently replaced with the same or different heteroatoms selected from nitrogen, oxygen and sulfur. The carbon atom(s) being replaced may be in the middle or at the end of the alkyl group. Examples of heteroalkyl include C_1-6heteroalkyl wherein one or more of the carbon atom(s) has been replaced by a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, examples are, —S-alkyl, —O-alkyl, —NH-alkyl, -alkylene-O-alkyl, etc. A heteroalkyl may be substituted.

As used herein, “aryl” refers to a carbocyclic (all carbon) ring or two or more fused rings (rings that share two adjacent carbon atoms) that have a fully delocalized pi-electron system. In some embodiments described herein the aryl group is a C_1-10aryl, which may be substituted or unsubstituted. Examples of aryl groups include, but are not limited to, benzene, naphthalene and azulene. An aryl group may be substituted. When substituted, hydrogen atoms are replaced by substituent group(s) that is(are) one or more group(s) independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, hydroxyalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. When substituted, substituents on an aryl group may form a non-aromatic ring fused to the aryl group, including a cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclyl.

As used herein, “heteroaryl” refers to a monocyclic or multicyclic aromatic ring system (a ring system with fully delocalized pi-electron system), in which at least one of the atoms in the ring system is a heteroatom, that is, an element other than carbon, including but not limited to, nitrogen, oxygen and sulfur. In some embodiments described herein the heteroaryl includes, but is not limited to, C_6-10heteroaryl, wherein one to four carbon atoms is/are replaced by one to four heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. Examples of monocyclic “heteroaryl” include, but are not limited to, furan, thiophene, phthalazine, pyrrole, oxazole, oxadiazole including but not limited to 1, 2, 4-oxadiazole and 1, 3, 4-oxadiazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, triazole including but not limited to 1, 2, 4-triazole and 1, 2, 3-triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, tetrazole, and triazine. Examples of multicyclic “heteroaryl” include, but are not limited to, quinoline, isoquinoline, quinazoline, quinoxaline, indole, purines, benzofuran, benzothiophene, benzopyranones (e.g. coumarin, chromone, and isocoumarin). A heteroaryl may be substituted. When substituted, hydrogen atoms are replaced by substituent group(s) that is(are) one or more group(s) independently selected from alkyl including but not limited to methyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, hydroxyalkyl including but not limited to 2-hydroxyethyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. When substituted, substituents on a heteroaryl group may form a non-aromatic ring fused to the aryl group, including a cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclyl.

An “aralkyl” or “arylalkyl” is an aryl group connected, as a substituent, via an alkylene group. The alkylene and aryl group of an aralkyl may be substituted. Examples include but are not limited to benzyl, substituted benzyl, 2-phenylethyl, 3-phenylpropyl, and naphthylalkyl. In some cases, the alkylene group is a lower alkylene group.

A “heteroaralkyl” or “heteroarylalkyl” is heteroaryl group connected, as a substituent, via an alkylene group. The alkylene and heteroaryl group of heteroaralkyl may be substituted.

Examples include but are not limited to 2-thienylmethyl, 3-thienylmethyl, furylmethyl, thienylethyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, pyrazolylalkyl and imidazolylalkyl, and their substituted as well as benzo-fused analogs. In some cases, the alkylene group is a lower alkylene group.

An “alkylene” is a straight-chained tethering group, forming bonds to connect molecular fragments via their terminal carbon atoms. The alkylene may have 1 to 20 carbon atoms. The alkylene may also be a medium size alkylene having 1 to 10 carbon atoms, such as “Ci-6” The alkylene could also be a lower alkylene having 1 to 4 carbon atoms. The alkylene may be designated as “C₁-C₄alkylene”, “C_1-4alkylene” or similar designations. Non-limiting examples include, methylene (—CH₂—), ethylene (—CH₂CH₂—), propylene (—CH₂CH₂CH₂—), and butylene (—(CH₂)₄—) groups. In the case of methylene, the two connected fragments are connected to the same carbon atom. A lower alkylene group may be substituted.

As used herein, “heteroalkylene” by itself or in combination with another term refers to an alkylene group consisting of the stated number of carbon atoms in which one or more of the carbon atoms, such as 1, 2, 3 or 4 carbon atom(s), are independently replaced with the same or different heteroatoms selected from oxygen, sulfur and nitrogen. Examples of heteroalkylene include, but not limited to —CH₂—O—, —CH₂—CH₂—O—, —CH₂—CH₂—CH₂—O—, —CH₂—NH—, —CH₂—CH₂—NH—, —CH₂—CH₂—CH₂—NH—, —CH₂—CH₂—NH—CH₂—, —O—CH₂—CH₂—O—CH₂—CH₂—O—, —O—CH₂—CH₂—O—CH₂—CH₂—, and the like.

As used herein, “alkylidene” refers to a divalent group, such as ═CR′R″, which is attached to one carbon of another group, forming a double bond. Alkylidene groups include, but are not limited to, methylidene (═CH₂) and ethylidene (═CHCH₃). As used herein, “arylalkylidene” refers to an alkylidene group in which either R′ or R″ is an aryl group. An alkylidene group may be substituted.

As used herein, “alkoxy” refers to the group —OR wherein R is an alkyl, e.g. methoxy, ethoxy, n-propoxy, cyclopropoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, amoxy, tert-amoxy and the like. An alkoxy may be substituted.

As used herein, “alkylthio” refers to the formula —SR wherein R is an alkyl is defined as above, e.g. methylmercapto, ethylmercapto, n-propylmercapto, 1-methylethylmercapto (isopropylmercapto), n-butylmercapto, iso-butylmercapto, sec-butylmercapto, tert-butylmercapto, and the like. An alkylthio may be substituted.

As used herein, “aryloxy” and “arylthio” refers to RO- and RS-, in which R is an aryl as defined above, e.g., phenoxy, naphthalenyloxy, azulenyloxy, anthracenyloxy, naphthalenylthio, phenylthio and the like. Both an aryloxy and arylthio may be substituted.

As used herein, “alkenyloxy” refers to the formula —OR wherein R is an alkenyl as defined above, e.g., vinyloxy, propenyloxy, n-butenyloxy, iso-butenyloxy, sec-pentenyloxy, tert-pentenyloxy, and the like. The alkenyloxy may be substituted.

As used herein, “acyl” refers to a hydrogen, alkyl, alkenyl, alkynyl, or aryl connected, as substituents, via a carbonyl group. Examples include formyl, acetyl, propanoyl, benzoyl, and acryl. An acyl may be substituted.

As used herein, “cycloalkyl” refers to a completely saturated (no double bonds) mono- or multi-cyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro-connected fashion. Cycloalkyl groups may range from C₃to C₁₀, such as from C₃to C₆. A cycloalkyl group may be unsubstituted or substituted. Typical cycloalkyl groups include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. If substituted, the substituent(s) may be independently selected from an alkyl, including but not limited to methyl, or a halogen, including but not limited to fluoro, or may be selected from those indicated above with regard to substitution of an alkyl group unless otherwise indicated. When substituted, substituents on a cycloalkyl group may form an aromatic ring fused to the cycloalkyl group, including an aryl and a heteroaryl.

As used herein, “cycloalkenyl” refers to a cycloalkyl group that contains one or more double bonds in the ring although, if there is more than one, they cannot form a fully delocalized pi-electron system in the ring (otherwise the group would be “aryl,” as defined herein). When composed of two or more rings, the rings may be connected together in a fused, bridged or spiro-connected fashion. Cycloalkenyl groups may range from C₃to C₁₀, such as from C₃to C₈or from C₅to C₁₀. For example, C_3-8cycloalkenyl includes C_4-8cycloalkenyl, C₅-8 cycloalkenyl or C_6-8cycloalkenyl. A cycloalkenyl group may be unsubstituted or substituted.

When substituted, the substituent(s) may be an alkyl or selected from the groups disclosed above with regard to alkyl group substitution unless otherwise indicated. When substituted, substituents on a cycloalkenyl group may form an aromatic ring fused to the cycloalkenyl group, including an aryl and a heteroaryl.

As used herein, “cycloalkynyl” refers to a cycloalkyl group that contains one or more triple bonds in the ring. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro-connected fashion. Cycloalkynyl groups may range from C₈to CU. A cycloalkynyl group may be unsubstituted or substituted. When substituted, the substituent(s) may be an alkyl or selected from the groups disclosed above with regard to alkyl group substitution unless otherwise indicated. When substituted, substituents on a cycloalkynyl group may form an aromatic ring fused to the cycloalkynyl group, including an aryl and a heteroaryl.

As used herein, “heteroalicyclic” or “heteroalicyclyl” refers to a 3- to 18 membered ring which consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. The heteroalicyclic or heteroalicyclyl groups may range from C₂to C₁₀, in some embodiments it may range from C₂to C₉, and in other embodiments it may range from C₂to C₈. In some embodiments The “heteroalicyclic” or “heteroalicyclyl” may be monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be joined together in a fused, bridged or spiro-connected fashion; and the nitrogen, carbon and sulfur atoms in the “heteroalicyclic” or “heteroalicyclyl” may be oxidized; the nitrogen may be quaternized; and the rings may also contain one or more double bonds provided that they do not form a fully delocalized pi-electron system throughout all the rings, examples are 2H-benzo[b][1,4]oxazin-3(4H)-one, 3,4-dihydroquinolin-2(1H)-one, 1,2,3,4-tetrahydroquinoline, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3-dihydrobenzo[d]oxazole, 2,3-dihydro-1H-benzo[d]imidazole, indoline, and 1,3-dihydro-2H-benzo[d]imidazol-2-one, and benzo[d]oxazol-2(3H)-one. Heteroalicyclyl groups may be unsubstituted or substituted. When substituted, the substituent(s) may be one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, haloalkyl, hydroxyalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. Examples of such “heteroalicyclic” or “heteroalicyclyl” include but are not limited to, azepinyl, dioxolanyl, imidazolinyl, morpholinyl, oxetanyl, oxiranyl, piperidinyl N-Oxide, piperidinyl, piperazinyl, pyrrolidinyl, pyranyl, 4-piperidonyl, pyrazolidinyl, 2-oxopyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, thiamorpholinyl, thiamorpholinyl sulfoxide, and thiamorpholinyl sulfone. When substituted, substituents on a heteroalicyclyl group may form an aromatic ring fused to the heteroalicyclyl group, including an aryl and a heteroaryl.

A “(cycloalkyl)alkyl” is a cycloalkyl group connected, as a substituent, via an alkylene group. The alkylene and cycloalkyl of a (cycloalkyl)alkyl may be substituted. Examples include but are not limited cyclopropylmethyl, cyclobutylmethyl, cyclopropylethyl, cyclopropylbutyl, cyclobutylethyl, cyclopropylisopropyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, cycloheptylmethyl, and the like. In some cases, the alkylene group is a lower alkylene group.

A “(cycloalkenyl)alkyl” is a cycloalkenyl group connected, as a substituent, via an alkylene group. The alkylene and cycloalkenyl of a (cycloalkenyl)alkyl may be substituted. In some cases, the alkylene group is a lower alkylene group.

A “(cycloalkynyl)alkyl” is a cycloalkynyl group connected, as a substituent, via an alkylene group. The alkylene and cycloalkynyl of a (cycloalkynyl)alkyl may be substituted. In some cases, the alkylene group is a lower alkylene group.

As used herein, “halo” or “halogen” refers to F (fluoro), C₁(chloro), Br (bromo) or I (iodo).

As used herein, “haloalkyl” refers to an alkyl group in which one or more of the hydrogen atoms are replaced by halogen. Such groups include but are not limited to, chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1-difluoroethyl, 2-fluoroethyl, 1-chloro-2-fluoromethyl and 2-fluoroisobutyl. A haloalkyl may be substituted or unsubstituted, and some embodiments relate to a medium size haloalkyl having 1 to 10 carbon atoms, such as C_1-6haloalkyl.

As used herein, “haloalkoxy” refers to a RO-group in which R is a haloalkyl group. Such groups include but are not limited to, chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy and 1-chloro-2-fluoromethoxy, 2-fluoroisobutyoxy. A haloalkoxy may be substituted.

As used herein, the term “hydroxyalkyl” refers to an alkyl group in which one of more of the hydrogen atoms are replaced by a hydroxyl group. Such groups include but are not limited to hydroxymethyl, hydroxyethyl, including but not limited to 2-hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl and hydroxyhexyl. A hydroxyalkyl group may be substituted or unsubstituted, and some embodiments relate to a medium size hydroxyalkyl having 1 to 10 carbon atoms, such as C_1-6hydroxyalkyl; when substituted the substituents may be one or more groups independently selected from the group consisting of halogen, including but not limited to fluoro, and haloalkyl, including but not limited to trifluoromethyl; such substituted “hydroxyalkyl” groups include but are not limited to 1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl and 1,1-difluoro-2-hydroxyethyl.

An “O-carboxy” group refers to a “RC(═O)O—” group in which R can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, or (heteroalicyclyl)alkyl, as defined herein. An O-carboxy may be substituted.

A “C-carboxy” group refers to a “—C(═O)OR” group in which R can be the same as defined with respect to O-carboxy. A C-carboxy may be substituted.

A “trihalomethanesulfonyl” group refers to an “X₃CSO₂—” group” wherein X is a halogen.

A dashed bond, [Image Omitted] , represents an optional unsaturation between the atoms forming the bond. This bond may be unsaturated (e.g. C═C, C═N, C═O) or saturated (e.g. C—C, C—N, C—O). When a dashed bond is present in a ring system it may form part of an aromatic ring system.

As used herein, a straight (unwedged) bolded or hashed bond, [Image Omitted] or , refers to relative stereochemistry inclusive of all possible stereoisomers at that position.

As used herein, and unless otherwise indicated, a wedged-bond (bolded, hashed, or otherwise), [Image Omitted] , , or refers to absolute stereochemistry referring to the particular stereoisomer as depicted at that position.

A “nitro” group refers to a “—NO₂” group.

A “cyano” group refers to a “—CN” group.

A “cyanato” group refers to an “—OCN” group.

An “isocyanato” group refers to a “—NCO” group.

A “thiocyanato” group refers to a “—SCN” group.

A “carbonyl” group refers to a “—C(═O)—” group.

A “thiocarbonyl” group refers to a “—C(═S)—” group.

An “oxo” group refers to a “═O” group.

A “hydroxy” group or “hydroxyl” group refers to an “—OH” group.

An “isothiocyanato” group refers to an “—NCS” group.

A “sulfinyl” group refers to an “—S(═O)—R” group in which R can be the same as defined with respect to O-carboxy. A sulfinyl may be substituted.

A “sulfonyl” group refers to an “SO₂R” group in which R can be the same as defined with respect to O-carboxy. A sulfonyl may be substituted.

An “S-sulfonamido” group refers to a “—SO₂NR_AR_B” group in which R_Aand R_Bindependently of each other can be the same as defined with respect to the R group as defined for O-carboxy, or combined to form a ring system selected from the group consisting of substituted or unsubstituted C_3-8cycloalkyl, substituted or unsubstituted C_3-8cycloalkenyl, substituted or unsubstituted C_3-8cycloalkyl, substituted or unsubstituted C_3-8cycloalkenyl substituted or unsubstituted heteroalicyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. A S-sulfonamido may be substituted.

An “N-sulfonamido” group refers to a “RSO₂N(R_A)—” group in which R and R_Aindependently of each other can be the same as defined with respect to the R group as defined for O-carboxy. An N-sulfonamido may be substituted.

A “trihalomethanesulfonamido” group refers to an “X₃CSO₂N(R)—” group with X as halogen and R can be the same as defined with respect to O-carboxy. A trihalomethanesulfonamido may be substituted.

A “C-amido” group refers to a “—C(═O)NR_AR_B” group in which R_Aand R_Bindependently of each other can be the same as defined with respect to the R group as defined for O-carboxy, or combined to form a ring system selected from the group consisting of substituted or unsubstituted C_3-8cycloalkyl, substituted or unsubstituted C_3-8cycloalkenyl, substituted or unsubstituted C_3-8cycloalkyl, substituted or unsubstituted C_3-8cycloalkenyl substituted or unsubstituted heteroalicyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. A C-amido may be substituted.

An “N-amido” group refers to a “RC(═O)NR_A—” group in which R and R_Aindependently of each other can be the same as defined with respect to the R group as defined for O-carboxy. An N-amido may be substituted.

An “ester” refers to a “—C(═O)OR” group in which R can be the same as defined with respect to O-carboxy. An ester may be substituted.

A lower alkoxyalkyl refers to an alkoxy group connected via a lower alkylene group. A lower alkoxyalkyl may be substituted.

An “amine” or “amino” refers to “RNH₂” (a primary amine), “R₂NH” (a secondary amine), “R₃N” (a tertiary amine). An amino group may be substituted.

A lower aminoalkyl refers to an amino group connected via a lower alkylene group. A lower aminoalkyl may be substituted.

Any unsubstituted or monosubstituted amine group on a compound herein can be converted to an amide, any hydroxyl group can be converted to an ester and any carboxyl group can be converted to either an amide or ester using techniques well-known to those skilled in the art (see, for example, Greene and Wuts, Protective Groups in Organic Synthesis, 3^rdEd., John Wiley & Sons, New York, N.Y., 1999).

As used herein, the abbreviations for any protective groups, amino acids and other compounds, are, unless indicated otherwise, in accord with their common usage, recognized abbreviations, or the IUPAC-IUB Commission on Biochemical Nomenclature (See, Biochem. 11:942-944 (1972)).

LIST OF ABBREVIATIONS

- DMF dimethylformamide
- DMSO dimethylsulfoxide
- MeOH methanol
- EtOH ethanol
- THF tetrahydrofurane
- DCM dichloromethane, methylene chloride
- DCE 1,2-dichloroethane
- LRMS low resolution mass spectrometry
- HPLC high pressure liquid chromatography
- Prep-HPLC preparative high pressure liquid chromatography
- h hour
- min minutes
- EA ethyl acetate
- EDC.HCl 3-((ethylimino)methyleneamino)-N,N-dimethylpropan-1-aminium chloride
- DIEA diisopropylethyamine
- TEA triethylamine
- TFA trifluoroacetic acid
- HCl hydrochloric acid, hydrogen chloride
- HOBt 1-hydroxybenzotriazole hydrate
- HOAt 1-hydroxy-7-azabenzotriazole
- HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate
- DMAP 4-(dimethylamino)pyridine
- DAST (diethylamino)sulfur trifluoride
- DIAD Diisopropyl azodicarboxilate
- DMP Dess-Martin Periodinane, 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one
- TBAF tetrabutylammonium fluoride trihydrate
- TBDMSC₁tert-butyldimethylsilyl chloride
- MsC₁methanesulfonyl chloride
- NAS nucleophilic aromatic substitution
- nBuLi n-Butyllithium
- iPr isopropyl
- Boc tert-Butyloxycarbonyl
- Flash CC Flash Column Chromatography
- on overnight
- rt room temperature
- aq aqueous
- ND Not Determined
- Cbz Carboxybenzyl
- Hex hexane
- Hept heptane
- DEA diethylamine
- PE petroleum ether
- DAD Diode Array Detector
- TOF Time of Flight
- IPA isopropanol
- Pg Protective group
- ″ Enantiomeric ally enriched

It is understood that, in any compound disclosed herein having one or more chiral centers, if an absolute stereochemistry is not expressly indicated, then each center may independently be of R-configuration or S-configuration or a mixture thereof. Thus, the compounds provided herein may be enantiomerically pure or be stereoisomeric mixtures. Further, compounds provided herein may be scalemic mixtures. In addition, it is understood that in any compound having one or more double bond(s) generating geometrical isomers that can be defined as E or Z each double bond may independently be E or Z or a mixture thereof. Likewise, all tautomeric forms are also intended to be included.

As used herein, the term “rac” refers to “racemic”, “racemate”, etc., as is understood by one of ordinary skill in the art. For example, a racemate comprises a mixture of enantiomers of a chiral molecule in equivalent amounts. Typically, a racemate does not exhibit optical activity.

As used herein, the term “rel” refers to the relative, but not absolute, configuration of a stereogenic center with respect to any other stereogenic center within the same compound, as is understood by one of ordinary skill in the art.

As used herein, “tautomer” and “tautomeric” refer to alternate forms of a compound disclosed herein that differ in the position of a proton. Non-limiting examples include enol-keto and imine-enamine tautomers, or the tautomeric forms of heteroaryl groups containing a ring atom attached to both a ring —NH— moiety and a ring ═N— moiety such as pyrazoles, imidazoles, benzimidazoles, triazoles, and tetrazoles.

It is understood that isotopes may be present in the compounds described herein. Each chemical element as represented in a compound structure may include any isotope of said element. For example, in a compound described herein a hydrogen atom can be any isotope of hydrogen, including but not limited to hydrogen-1 (protium) and hydrogen-2 (deuterium). Thus, reference herein to a compound encompasses all potential isotopic forms unless the context clearly dictates otherwise.

As used herein, reference to an element, whether by description or chemical structure, encompasses all isotopes of that element unless otherwise described. By way of example, the term “hydrogen” or “H” in a chemical structure as used herein is understood to encompass, for example, not only ¹H, but also deuterium (²H), tritium (³H), and mixtures thereof unless otherwise denoted by use of a specific isotope. Other specific non-limiting examples of elements for which isotopes are encompassed include carbon, phosphorous, iodine, and fluorine.

As used herein, “pharmaceutically acceptable salt” refers to a salt of a compound that does not abrogate the biological activity and properties of the compound. Pharmaceutical salts can be obtained by reaction of a compound disclosed herein with an acid or base. Base-formed salts include, without limitation, ammonium salt (NH₄⁺); alkali metal, such as, without limitation, sodium or potassium, salts; alkaline earth, such as, without limitation, calcium or magnesium, salts; salts of organic bases such as, without limitation, dicyclohexylamine, piperidine, piperazine, methylpiperazine, N-methyl-D-glucamine, diethylamine, ethylenediamine, tris(hydroxymethyl)methylamine; and salts with the amino group of amino acids such as, without limitation, arginine and lysine. Useful acid-based salts include, without limitation, acetates, adipates, aspartates, ascorbates, benzoates, butyrates, caparate, caproate, caprylate, camsylates, citrates, decanoates, formates, fumarates, gluconates, glutarate, glycolates, hexanoates, laurates, lactates, maleates, nitrates, oleates, oxalates, octanoates, propanoates, palmitates, phosphates, sebacates, succinates, stearates, sulfates, sulfonates, such as methanesulfonates, ethanesulfonates, p-toluenesulfonates, salicylates, tartrates, and tosylates.

Pharmaceutically acceptable solvates and hydrates are complexes of a compound with one or more solvent of water molecules, or 1 to about 100, or 1 to about 10, or one to about 2, 3 or 4, solvent or water molecules.

As used herein, a “prodrug” refers to a compound that may not be pharmaceutically active but that is converted into an active drug upon in vivo administration. The prodrug may be designed to alter the metabolic stability or the transport characteristics of a drug, to mask side effects or toxicity, to improve the flavor of a drug or to alter other characteristics or properties of a drug. Prodrugs are often useful because they may be easier to administer than the parent drug. They may, for example, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have better solubility than the active parent drug in pharmaceutical compositions. An example, without limitation, of a prodrug would be a compound disclosed herein, which is administered as an ester (the “prodrug”) to facilitate absorption through a cell membrane where water solubility is detrimental to mobility but which then is metabolically hydrolyzed to a carboxylic acid (the active entity) once inside the cell where water-solubility is beneficial. A further example of a prodrug might be a short peptide (polyaminoacid) bonded to an acid group where the peptide is metabolized in vivo to release the active parent compound. By virtue of knowledge of pharmacodynamic processes and drug metabolism in vivo, those skilled in the art, once a pharmaceutically active compound is known, can design prodrugs of the compound (see, e.g. Nogrady (1985) Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, pages 388-392).

As used herein, to “modulate” the activity of a receptor means either to activate it, i.e., to increase its cellular function over the base level measured in the particular environment in which it is found, or deactivate it, i.e., decrease its cellular function to less than the measured base level in the environment in which it is found and/or render it unable to perform its cellular function at all, even in the presence of a natural binding partner. A natural binding partner is an endogenous molecule that is an agonist for the receptor.

An “agonist” is defined as a compound that increases the basal activity of a receptor (i.e. signal transduction mediated by the receptor).

As used herein, “partial agonist” refers to a compound that has an affinity for a receptor but, unlike an agonist, when bound to the receptor it elicits only a fractional degree of the pharmacological response normally associated with the receptor even if a large number of receptors are occupied by the compound.

An “inverse agonist” is defined as a compound, which reduces, or suppresses the basal activity of a receptor, such that the compound is not technically an antagonist but, rather, is an agonist with negative intrinsic activity.

As used herein, “antagonist” refers to a compound that binds to a receptor to form a complex that does not give rise to any response, as if the receptor was unoccupied. An antagonist attenuates the action of an agonist on a receptor. An antagonist may bind reversibly or irreversibly, effectively eliminating the activity of the receptor permanently or at least until the antagonist is metabolized or dissociates or is otherwise removed by a physical or biological process.

As used herein, a “subject” refers to an animal that is the object of treatment, observation or experiment. “Animal” includes cold- and warm-blooded vertebrates and invertebrates such as birds, fish, shellfish, reptiles and, in particular, mammals. “Mammal” includes, without limitation, mice; rats; rabbits; guinea pigs; dogs; cats; sheep; goats; cows; horses; primates, such as monkeys, chimpanzees, and apes, and, in particular, humans.

As used herein, a “patient” refers to a subject that is being treated by a medical professional such as an M.D. or a D.V.M. to attempt to cure, or at least ameliorate the effects of, a particular disease or disorder or to prevent the disease or disorder from occurring in the first place.

As used herein, a “carrier” refers to a compound that facilitates the incorporation of a compound into cells or tissues. For example, without limitation, dimethyl sulfoxide (DMSO) is a commonly utilized carrier that facilitates the uptake of many organic compounds into cells or tissues of a subject.

As used herein, a “diluent” refers to an ingredient in a pharmaceutical composition that lacks pharmacological activity but may be pharmaceutically necessary or desirable. For example, a diluent may be used to increase the bulk of a potent drug whose mass is too small for manufacture or administration. It may also be a liquid for the dissolution of a drug to be administered by injection, ingestion or inhalation. A common form of diluent in the art is a buffered aqueous solution such as, without limitation, phosphate buffered saline that mimics the composition of human blood.

As used herein, an “excipient” refers to an inert substance that is added to a pharmaceutical composition to provide, without limitation, bulk, consistency, stability, binding ability, lubrication, disintegrating ability etc., to the composition. A “diluent” is a type of excipient.

A “receptor” is intended to include any molecule present inside or on the surface of a cell that may affect cellular physiology when it is inhibited or stimulated by a ligand. Typically, a receptor comprises an extracellular domain with ligand-binding properties, a transmembrane domain that anchors the receptor in the cell membrane, and a cytoplasmic domain that generates a cellular signal in response to ligand binding (“signal transduction”). A receptor also includes any intracellular molecule that in response to ligation generates a signal. A receptor also includes any molecule having the characteristic structure of a receptor, but with no identifiable ligand. In addition, a receptor includes a truncated, modified, mutated receptor, or any molecule comprising partial or all of the sequences of a receptor.

“Ligand” is intended to include any substance that interacts with a receptor.

“Selective” or “selectivity” is defined as a compound's ability to generate a desired response from a particular receptor type, subtype, class or subclass while generating less or little response from other receptor types. “Selective” or “selectivity” of one or more particular subtypes of a compound means a compound's ability to increase the activity of the subtypes while causing less, little or no increase in the activity of other subtypes.

As used herein, “coadministration” of pharmacologically active compounds refers to the delivery of two or more separate chemical entities, whether in vitro or in vivo. Coadministration means the simultaneous delivery of separate agents; the simultaneous delivery of a mixture of agents; as well as the delivery of one agent followed by delivery of a second agent or additional agents. Agents that are coadministered are typically intended to work in conjunction with each other.

The term “an effective amount” as used herein means an amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation or palliation of the symptoms of the disease being treated.

When used herein, “prevent/preventing” should not be construed to mean that a condition and/or a disease never might occur again after use of a compound or pharmaceutical composition according to embodiments disclosed herein to achieve prevention. Further, the term should neither be construed to mean that a condition not might occur, at least to some extent, after such use to prevent said condition. Rather, “prevent/preventing” is intended to mean that the condition to be prevented, if occurring despite such use, will be less severe than without such use.

Compounds

In one embodiment the present disclosure relates to a compound of Formula (I)

[Image Omitted]

a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein

- Y₁, Y₂and Y₃are independently N or CR₈;
- R is selected from the group consisting of hydrogen, C_1-6alkyl, and C_1-4hydroxyalkyl;
- R_0aand R_0bindependently are selected from the group consisting of hydrogen, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-4haloalkyl, CN, substituted or unsubstituted heteroalicyclyl and substituted or unsubstituted heteroaryl;
- R_1aand R_1bare independently selected from the group consisting of hydrogen, hydroxyl, halogen, amino, C_1-4alkyl, C_1-4hydroxyalkyl, and C_1-4haloalkyl;
- R₂is selected from the group consisting of hydrogen, hydroxyl, amino, cyano, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C(═O)OH, C(═O)NH₂, C(═O)O—C_1-4alkyl, and substituted or unsubstituted heteroaryl;
- R₃is selected from the group consisting of C_1-4alkyl, C_2-4alkenyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, C_1-4alkylene-C_1-4alkoxy, substituted or unsubstituted C_3-7cycloalkyl, and substituted or unsubstituted C_3-7cycloalkenyl;
- R₄and R₅are each independently hydrogen or C_1-4alkyl, or R₄and R₅are taken together with the carbon atom to which they are attached to form a C_3-4cycloalkyl;
- R₆is selected from the group consisting of hydrogen, CN, halogen, C_1-4alkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, C_1-4haloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl;
- R₇is selected from the group consisting of hydrogen, hydroxyl, CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl;
- each R₈independently is selected from the group consisting of hydrogen, hydroxyl, CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl; and
  
  whenever R₇is hydrogen and each R₈present is hydrogen, then R₆is selected from the group consisting of CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, and substituted or unsubstituted heteroaryl; and
  
  when substituted, a heteroalicyclyl is substituted with 1 to 3 substituents independently selected from the group consisting of C_1-4alkyl, C_1-4haloalkyl, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl, hydroxy, C_1-4alkoxy, and halogen; and
  
  when substituted, a heteroaryl is substituted with 1 to 3 substitutents independently selected from the group consisting of C_1-4alkyl, C_1-4hydroxyalkyl, C_2-4alkenyl, C_2-4alkynyl, hydroxy, C_1-4alkoxy, cyano, halogen, C_1-4haloalkyl, C_1-4haloalkoxy and C_1-6hydroxyhaloalkyl; and
  
  when substituted, a cycloalkyl or cycloalkenyl is substituted with 1 to 3 substituents independently selected from the group consisting of C_1-4alkyl and halogen.

In some embodiments disclosed herein, R is hydrogen.

In some embodiments disclosed herein, R₆is selected from the group consisting of hydrogen, CN, halogen, C_1-4haloalkyl, C_1-4haloalkoxy, C_1-4hydroxyalkyl, C_1-6hydroxyhaloalkyl; 5 membered heteroaryl, and 5-membered heteroaryl substituted with 1 or 2 substituents independently selected from methyl or hydroxyethyl, and whenever R₇is hydrogen and each R₈present is hydrogen, then R₆cannot be hydrogen. In other embodiments, R₆is selected from the group consisting of hydrogen, CN, chloro, CF₃, CHF₂, CCH₃F₂, OCF₃, and OCHF₂, OCH₂F, C(CF₃)₂₀H, CF₂CH₂OH, pyrazolyl, and pyrazolyl substituted with 1 substituent selected from methyl or 2-hydroxyethyl, and whenever R₇is hydrogen and each R₈present is hydrogen, then R₆cannot be hydrogen. In other embodiments, R₆is selected from the group consisting of hydrogen, CF₃, CCH₃F₂, OCHF₂, C(CF₃)₂₀H, pyrazolyl, and methyl-pyrazolyl, and whenever R₇is hydrogen and each R₈present is hydrogen, then R₆cannot be hydrogen. In other embodiments, R₆is selected from the group consisting of CF₃, C(CF₃)₂₀H, 1-methyl-1H-pyrazol-4-yl, and 1H-pyrazol-1-yl. In other embodiments, R₆is CF₃.

In some embodiments disclosed herein, R₇is selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, CH₃, OCH₃, CF₃, CHF₂, OCF₃and OCHF₂. In other embodiments, R₇is hydrogen or fluoro.

In some embodiments disclosed herein, Y₁, Y₂and Y₃are each CH. In some embodiments, Y₁is N and Y₂and Y₃are each CH. In some embodiments, Y₂is N and Y₁and Y₃are each CH. In some embodiments, Y₃is N and Y₁and Y₂are each CH. In some embodiments; Y₃is CH— and Y₁and Y₂are each N.

In some embodiments disclosed herein, Y₁and Y₂are each CH—, and Y₃is CR₈wherein R₈is selected from the group consisting of hydrogen, hydroxyl, methyl, OCH₃, fluoro, chloro, and CF₃.

In some embodiments disclosed herein, R₈is hydrogen or fluoro.

In some embodiments disclosed herein Y₂is N and Y₁and Y₃independently are CH. In some embodiments, Y₃is N and Y₁and Y₂independently are each CH.

In some embodiments disclosed herein, R₆is hydrogen, at least one of Y₂or Y₃is CR₈, and R₈is selected from the group consisting of CN, halogen, C_1-4alkyl, C_1-4haloalkyl, C_1-4alkoxy, and C_1-4haloalkoxy. In some embodiments, R₆is hydrogen, and Y₂is C(OCF₃).

In some embodiments disclosed herein, R₄and R₅independently are hydrogen or methyl. In some embodiments, R₄and R₅are taken together with the carbon atom to which they are attached to form a cyclopropyl.

In some embodiments disclosed herein, R₄is hydrogen or methyl, and R₅is hydrogen.

In some embodiments disclosed herein, R₄and R₅are each hydrogen.

In some embodiments disclosed herein, R₃is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, tert-butyl, CH₂CH₂F, CH₂CH₂OCH₃, cyclopropyl-CH₂—, cyclopropyl, methylcyclopropyl, cyclobutyl, and fluorocyclobutyl. In some embodiments, R₃is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, and 3-fluorocyclobutyl. In some embodiments, R₃is selected from the group consisting of methyl, ethyl, isopropyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, (1r,3S)-3-fluorocyclobutyl, and (1s,3R)-3-fluorocyclobutyl. In some embodiments, R₃is selected from the group consisting of methyl, ethyl, and cyclopropyl. In some embodiments, R₃is ethyl. In some embodiments, R₃is cyclopropyl.

In some embodiments disclosed herein, R₂is selected from the group consisting of hydrogen, hydroxyl, amino, CN, halogen, methyl, ethyl, CH₂OH, CH₂CH₂OH, C(═O)OC_1-2alkyl, C(═O)NH₂, and unsubstituted or substituted 5 membered heteroaryl. In some embodiments, R₂is selected from the group consisting of hydrogen, hydroxyl, CN, fluoro, methyl, CH₂OH, C(═O)OCH₃, C(═O)NH₂, oxadiazolyl, and triazolyl. In some embodiments, R₂is selected from the group consisting of hydrogen, hydroxyl, CN, methyl, CH₂OH, C(═O)OCH₃, C(═O)NH₂, 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, 1H-1,2,4-triazol-3-yl, and 1H-1,2,3-triazol-5-yl. In some embodiments, R₂is selected from the group consisting of hydrogen, CN, methyl, CH₂OH, and hydroxyl. In some embodiments, R₂is hydrogen or hydroxyl. In some embodiments, R₂is hydrogen. In some embodiments, R₂is hydroxyl.

In some embodiments disclosed herein, R_1ais selected from the group consisting of hydrogen, hydroxyl, fluoro, and CF₃, and R_1bis selected from the group consisting of hydrogen, fluoro, and methyl.

In some embodiments disclosed herein, R_1ais selected from the group consisting of hydroxyl, fluoro, and CF₃, and R_1bis selected from the group consisting of hydrogen, fluoro, and methyl.

In some embodiments disclosed herein, R_1ais hydroxyl or fluoro. In some embodiments, R_1ais hydroxyl.

In some embodiments disclosed herein, R_1bis hydrogen. In some embodiments, R_1bis methyl.

In some embodiments disclosed herein, at least one of R_1a, R_1b, and R₂is not hydrogen.

In some embodiments disclosed herein, R_1ais selected from the group consisting of hydrogen, hydroxyl, and fluoro; R_1bis selected from the group consisting of hydrogen, fluoro, and methyl; and R₂is selected from the group consisting of hydrogen, hydroxyl, methyl, CN, CH₂OH, and CH₂CH₂OH. In some embodiments, R_1ais selected from the group consisting of hydroxyl and hydrogen. In some embodiments, R_1bis hydrogen and R₂is selected from the group consisting of hydrogen, hydroxyl, CH₂OH, and CH₂CH₂OH, provided either R_1ais hydroxyl or R₂is selected from the group consisting of hydroxyl, CH₂OH, and CH₂CH₂OH.

In some embodiments disclosed herein, R_0ais selected from the group consisting of hydrogen, methyl, CH₂OH, CH₂CH₂OH, CH₂F, and CHF₂; and R_0bis selected from the group consisting of hydrogen, C_1-4alkyl, C_1-4hydroxyalkyl, and C_1-4haloalkyl.

In some embodiments disclosed herein, R_0ais selected from the group consisting of hydrogen, methyl, CH₂OH, and CH₂CH₂OH. In some embodiments, R_0ais hydrogen. In some embodiments, R_0bis hydrogen.

In some embodiments, provided herein is a compound having a structure of Formula (II) or Formula (III):

[Image Omitted]

a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein

R_1ais fluoro or hydroxyl, R_1bis hydrogen or fluoro, R₂is hydrogen or hydroxyl, R₆is CF₃, Y₂and Y₃are independently N or CR₈, and R₈is hydrogen or fluoro. In some embodiments Y₂and Y₃are each CH, or Y₂is CH and Y₃is CF. In some embodiments, R_1ais hydroxyl and R_1bis hydrogen. In some embodiments, R₂is hydrogen. In some embodiments R₂is hydroxyl.

In some embodiments disclosed herein, R_0ais selected from the group consisting of hydrogen, methyl, CH₂OH, and CH₂CH₂OH; R_0bis selected from the group consisting of hydrogen and methyl; R_1ais selected from the group consisting of hydrogen, hydroxyl, fluoro, and CF₃; R_1bis selected from the group consisting of hydrogen, fluoro, and methyl; R₂is selected form the group consisting of hydrogen, hydroxyl, amino, CN, fluoro, methyl, CH₂—OH, C(═O)—NH₂, C(═O)O—CH₃, 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, 1H-imidazol-2-yl, 1H-1,2,3-triazol-5-yl, 1H-1,2,4-triazol-3-yl, and 4-methyl-4H-1,2,4-triazol-3-yl; R is selected from the group consisting of hydrogen and CH₂OH; R₃is selected from the group consisting of methyl, ethyl, isopropyl, isobutyl, CH₂CH₂F, CH₂CH₂OCH₃, cyclopropyl-CH₂—, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, and 3-fluorocyclobutyl; R₄is hydrogen or methyl; R₅is hydrogen; R₆is selected from the group consisting of hydrogen, chloro, CN, CF₃, CHF₂, CCH₃F₂, OCH₃, OCF₃, OCH₂F, OCHF₂, C(CF₃)₂₀H, CF₂CH₂OH, 1H-pyrazol-1-yl, 1-methyl-1H-pyrazol-4-yl, and 1-(2-hydroxyethyl)-1H-pyrazol-4-yl; R₇is hydrogen or chloro; Y₁, Y₂and Y₃are each CH; or Y₁is CH, Y₂is CH, and Y₃is selected from the group consisting of N, C(F), C(OCH₃), C(CH₃), C(C₁), and C(CF₃); or Y₁is CH, Y₂is selected from the group consisting of N, C(CN), C(1H-1,2,4-triazol-1-yl), C(OCF₃), C(OCH₃), C(F), C(OCHF₂), and C(C₁), and Y₃is CH; or Y₁is CH, Y₂is C(C₁) and Y₃is C(C₁); or Y₁is C(CH₃), Y₂is CH and Y₃is C(CH₃); or Y₁is C(CH₃), Y₂is C(CH₃) and Y₃is CH; or Y₁is C(CF₃), Y₂is C(CF₃) and Y₃is CH; or Y₁is C(C₁), Y₂is C(C₁) and Y₃is CH; or Y₁is N, Y₂is N and Y₃is CH. In some cases; when R₇is H and Y₁, Y₂and Y₃are CH, R₆is selected from the group consisting of chloro, CN, CF₃, C(CH₃)F₂, OCF₃, OCH₂F, OCHF₂, C(CF₃)₂₀H, CF₂CH₂OH, 1H-pyrazol-1-yl, 1-methyl-1H-pyrazol-4-yl, and 1-(2-hydroxyethyl)-1H-pyrazol-4-yl.

In some embodiments disclosed herein, R_0ais selected from the group consisting of hydrogen, methyl, CH₂OH, and CH₂CH₂OH; R_0bis hydrogen or methyl; R_1ais selected from the group consisting of hydrogen, hydroxyl, CF₃, and fluoro; R_1bis selected from the group consisting of hydrogen, fluoro, and methyl; R₂is selected from the group consisting of hydrogen, hydroxyl, CN, CH₂OH, methyl, CO₂Me, CONH₂, 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, 1H-1,2,3-triazol-5-yl, and 1H-1,2,4-triazol-3-yl; R is hydrogen; R₃is selected from the group consisting of methyl, ethyl, isopropyl, cyclopropyl-CH₂—, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, (1r,3S)-3-fluorocyclobutyl, and (1s,3R)-3-fluorocyclobutyl; R₄is hydrogen; R₅is hydrogen; R₆is selected from the group consisting of hydrogen, CF₃, CF₂CH₃, OCHF₂, C(CF₃)₂₀H, 1H-pyrazol-1-yl, and 1-methyl-1H-pyrazol-4-yl; R₇is hydrogen; Y₁, Y₂and Y₃are each CH; or Y₁is CH, Y₂is CH and Y₃is C(F); or Y₁is CH, Y₂is C(OCF₃) or C(OCH₃), and Y₃is CH; or Y₁is CH, Y₂is CH, and Y₃is N; or Y₁is CH, Y₂is N, and Y₃is CH; or Y₁is N, Y₂is N, and Y₃is CH. In some cases, when R₇is H and Y₁, Y₂and Y₃are each CH, R₆is selected from the group consisting of CF₃, CF₂CH₃, OCHF₂, C(CF₃)₂₀H, 1H-pyrazol-1-yl, and 1-methyl-1H-pyrazol-4-yl.

In some embodiments, R_0ais selected from the group consisting of hydrogen, methyl, and CH₂OH; R_0bis hydrogen or methyl; R_1ais selected from the group consisting of hydrogen, hydroxyl, and fluoro; R_1bis selected from the group consisting of hydrogen, fluoro, and methyl; R₂is selected from the group consisting of hydrogen, hydroxyl, CN, CH₂OH, methyl, 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, and 1H-1,2,3-triazol-5-yl; R is hydrogen; R₃is ethyl or cyclopropyl; R₄is hydrogen; R₅is hydrogen; R₆is selected from the group consisting of hydrogen, CF₃, CF₂CH₃, OCHF₂, C(CF₃)₂₀H, 1H-pyrazol-1-yl, and 1-methyl-1H-pyrazol-4-yl; R₇is hydrogen; Y₁, Y₂and Y₃are each CH; or Y₁is CH, Y₂is CH, and Y₃is C(F); or Y₁is CH, Y₂is C(OCF₃), and Y₃is CH. In some cases; when R₇is H and Y₁, Y₂and Y₃are each CH, R₆is selected from the group consisting of CF₃, CF₂CH₃, OCHF₂, C(CF₃)₂₀H, 1H-pyrazol-1-yl, and 1-methyl-1H-pyrazol-4-yl.

In some embodiments disclosed herein, R_0ais selected from the group consisting of CN, substituted or unsubstituted heteroalicyclyl, and substituted or unsubstituted heteroaryl;

and R_0bis hydrogen or C_1-4alkyl. In some embodiments, R_0ais unsubstituted or substituted heteroaryl. In some embodiments, R_0ais substituted or unsubstituted pyridinyl.

In some embodiments disclosed herein, R_0bis hydrogen.

In one embodiment disclosed herein, the compound, stereoisomer, or salt of Formula (I) is selected from the group consisting of:

A7-1

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-1-1

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-1-2

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-2

2-(4-(((6-(cyclopropyl(2-methyl-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-3-1

rel-(R)-2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-3-2

rel-(R)-2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-4-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-4-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide 2^ndeluting isomer,

A7-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-5-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-6-1

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-6-2

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-7-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 1^steluting isomer,

A7-7-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-7-3

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 3^rdeluting isomer,

A7-7-4

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 4^theluting isomer,

A7-8

methyl 1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxylate,

A7-9

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-10

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-11

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-14

rac-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-14-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-14-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-15

rac-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-15-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-15-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-16

rac-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-16-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-16-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-17

rac-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-17-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-17-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-18

rac-2-((3R,4R)-4-(((6-(cyclobutyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-18-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-18-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-19

rac-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-19-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-19-2

rel-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-20

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-20-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-20-2

rel-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-21

rac-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-21-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-21-2

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-22

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-22-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-22-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide 1^steluting isomer,

A7-23

rac-2-((3R,4R)-4-(((6-(cyclobutyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-23-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-23-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-24

rac-2-((3R,4R)-4-(((6-(cyclobutyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-24-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-24-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-25

rac-2-((3R,4R)-4-(((6-(cyclopropyl((6-(difluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-25-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(difluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-26

rac-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-26-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-26-2

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-27

rac-2-((3R,4R)-4-(((6-(ethyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-27-1

rel-2-((3R,4R)-4-(((6-(ethyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-27-2

rel-2-((3R,4R)-4-(((6-(ethyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer.

A7-28

rac-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-28-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-28-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-29

rac-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

A7-29-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-29-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-30

rac-2-((3R,4R)-4-(((5-fluoro-6-((2-fluoroethyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-31

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1r,3S)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-32

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1s,3R)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-33

2-(4-(((6-(cyclopropyl(1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-34

2-(4-(((6-(cyclopropyl(1-(4-(trifluoromethyl)phenyl)ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-35

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-36

2-(4-(((6-((3-cyanobenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-38

2-(4-(((6-((3-(1H-1,2,4-triazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-39

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-40

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-41

rac-2-((3R,4R)-4-(((5-fluoro-6-((1-methylcyclopropyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-42

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-43

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-44

1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxamide,

A7-45

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-46

2-(4-(((6-((4-chloro-2,5-dimethylbenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-47

2-(4-(((6-(cyclopropyl(2,5-dimethylbenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-49

rac-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-50

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-51

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-52

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-53

2-(4-(((6-((4-chloro-3,5-dimethylbenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-54

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-54-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-54-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-55″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide, enantiomeric ally enriched,

A7-56

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl) acetamide,

A7-57″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide, enantiomerically enriched,

A7-58

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl) acetamide,

A7-60

rac-2-((3R,4R)-4-(((5-fluoro-6-((methyl-d₃)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl) acetamide,

A7-61

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl) acetamide,

A7-64

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-65

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-66-1

rel-(R)-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide or

rel-(R)-2-((3 S,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide, 1^steluting major isomer,

A7-66-2

rel-(R)-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide or

rel-(R)-2-((3S,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2^ndeluting major isomer,

A7-67″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-4-hydroxybutanamide, enantiomerically enriched,

A7-68

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-69″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂, enantiomerically enriched,

A7-70

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-72

rac-2-((3R,4R)-4-(((6-(ethyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-73

rac-2-((3R,4R)-4-(((6-(ethyl(4-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-74

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-75

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-76

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-77

rac-2-((3R,4R)-4-(((6-((4-(1H-Pyrazol-1-yl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-78

rac-2-((3R,4R)-4-(((6-((4-cyanobenzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-79

rac-2-((3R,4R)-4-(((6-((4-(1,1-difluoro-2-hydroxyethyl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-80

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

A7-81

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

A7-82

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

A7-83

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

A7-84

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-imidazol-2-yl)piperidin-1-yl)acetamide,

A7-85

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

A7-86

rac-2-((3R,4R)-4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-87

2-(4-(1-((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)-2-hydroxyethyl)piperidin-1-yl)acetamide,

B4-1-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 1^steluting isomer, B4-1-1-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

B4-1-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 1^steluting isomer,

B4-1-2-2

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

B4-2-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide, 1^steluting isomer

B4-2-1-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

C4-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 1^steluting isomer,

C4-1-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 2^ndeluting isomer,

C4-2-1

2-(4-(((6-((3,5-bis(trifluoromethyl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 1^steluting isomer,

D5-1-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1st eluting isomer,

D5-1-1-2

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-1-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-1-2-2

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-2-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1st eluting isomer,

D5-2-1-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-2-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-2-2-2

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-3-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-3-1-2

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-3-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-3-2-2

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide

2^ndeluting isomer,

D5-4″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

enantiomerically enriched,

D5-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, major isomer,

D5-5-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, minor isomer,

D5-6″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched,

D5-9″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

enantiomerically enriched,

D5-10″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched,

E6-1

2-(4-Amino-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

F2-1

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(2-methylbenzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-2

rac-2-((3R,4R)-4-(((6-((2,6-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-3

rac-2-((3R,4R)-4-(((6-((2,3-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-4

rac-2-((3R,4R)-4-(((6-((2,6-dichlorobenzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-5

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(1-(o-tolyl)ethyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-6

rac-2-((3R,4R)-4-(((6-((1-(2-chlorophenyl)ethyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-7

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-8

rac-2-((3R,4R)-4-(((6-((3-cyanobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-9

rac-2-((3R,4R)-4-(((5-fluoro-6-(isobutyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-10

rac-2-((3R,4R)-4-(((6-((cyclopropylmethyl)(2-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-11

rac-2-((3R,4R)-4-(((6-((4-cyanobenzyl)(isobutyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-12

rac-2-((3R,4R)-4-(((6-((4-chloro-3-fluorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-13

rac-2-((3R,4R)-4-(((6-((4-(difluoromethoxy)benzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-14

rac-2-((3R,4R)-4-(((6-((4-(difluoromethoxy)-3-methoxybenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-15

rac-2-((3R,4R)-4-(((6-((4-chlorobenzyl)(isopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-16

rac-2-((3R,4R)-4-(((5-fluoro-6-((2-methoxyethyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-17

rac-2-((3R,4R)-4-(((6-((2,4-dichlorobenzyl)(isobutyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-18

rac-2-((3R,4R)-4-(((6-((4-cyanobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-19

rac-2-((3R,4R)-4-(((5-fluoro-6-(((6-methoxypyridin-3-yl)methyl)(methyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-20

rac-2-((3R,4R)-4-(((6-((3-(difluoromethoxy)benzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-21

rac-2-((3R,4R)-4-(((6-((3,5-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-22

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-23

rac-2-((3R,4R)-4-(((6-((3-chlorobenzyl)(isopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In some cases, the compound, stereoisomer, or salt has a structure of Formula (I) is selected from the group consisting of:

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-methyl-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide,

methyl1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxylate,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((6-(difluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-((((5-fluoro-6-((2-fluoroethyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-((3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(1-(4-(trifluoromethyl)phenyl)ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-((3-cyanobenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-((3-(1H-1,2,4-triazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-((1-methylcyclopropyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxamide,

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-((4-chloro-2,5-dimethylbenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2,5-dimethylbenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-((4-chloro-3,5-dimethylbenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

2-(4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

2-(4-(((6-(cyclopropyl(3-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-((methyl-d₃)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-4-hydroxybutanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(ethyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-cyanobenzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-(1,1-difluoro-2-hydroxyethyl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-imidazol-2-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

2-(4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(1-((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)-2-hydroxyethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-((3,5-bis(trifluoromethyl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-((3R,4R)-4-(((6-(cyclopropyl(2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-Amino-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(methyl(2-methylbenzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((2,6-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((2,3-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((2,6-dichlorobenzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(methyl(1-(o-tolyl)ethyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((1-(2-chlorophenyl)ethyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((3-cyanobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(isobutyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((cyclopropylmethyl)(2-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-cyanobenzyl)(isobutyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-chloro-3-fluorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-(difluoromethoxy)benzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-(difluoromethoxy)-3-methoxybenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-chlorobenzyl)(isopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-((2-methoxyethyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((2,4-dichlorobenzyl)(isobutyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((4-cyanobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(((6-methoxypyridin-3-yl)methyl)(methyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((3-(difluoromethoxy)benzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-((3,5-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(methyl(4-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, and 2-(4-(((6-((3-chlorobenzyl)(isopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In some cases, the compound, salt, stereoisomer, or salt of a stereoisomer according to Formula (I) is selected from the group consisting of:

A7-1

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-1-1

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-2

2-(4-(((6-(cyclopropyl(2-methyl-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-3-1

rel-(R)-2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

A7-4-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

A7-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

A7-6-1

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

A7-7-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide,

A7-8

methyl 1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxylate,

A7-9

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-10

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-11

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-14

rac-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-14-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-15

rac-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-15-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-16

rac-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-16-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-17-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-18

rac-2-((3R,4R)-4-(((6-(cyclobutyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-18-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-19

rac-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-19-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-20

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-20-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-21

rac-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-21-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-22

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-22-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-23

rac-2-((3R,4R)-4-(((6-(cyclobutyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-23-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-24

rac-2-((3R,4R)-4-(((6-(cyclobutyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-24-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-25

rac-2-((3R,4R)-4-(((6-(cyclopropyl((6-(difluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-25-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(difluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-26

rac-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-26-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-27

rac-2-((3R,4R)-4-(((6-(ethyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-27-1

rel-2-((3R,4R)-4-(((6-(ethyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-28-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-29

rac-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-29-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-30

rac-2-((3R,4R)-4-(((5-fluoro-6-((2-fluoroethyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-31

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1r,3S)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-32

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1s,3R)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-33

2-(4-(((6-(cyclopropyl(1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-34

2-(4-(((6-(cyclopropyl(1-(4-(trifluoromethyl)phenyl)ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-35

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-36

2-(4-(((6-((3-cyanobenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-38

2-(4-(((6-((3-(1H-1,2,4-triazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-39

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-40

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-41

rac-2-((3R,4R)-4-(((5-fluoro-6-((1-methylcyclopropyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-42

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-43

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-44

1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxamide,

A7-45

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-46

2-(4-(((6-((4-chloro-2,5-dimethylbenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-47

2-(4-(((6-(cyclopropyl(2,5-dimethylbenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-49

rac-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-50

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-51

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-52

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-53

2-(4-(((6-((4-chloro-3,5-dimethylbenzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-54

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-54-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-55″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

A7-56

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-57″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

A7-58

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-60

rac-2-((3R,4R)-4-(((5-fluoro-6-((methyl-d₃)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-64

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-65

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-66-1

rel-(R)-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide, or

rel-(R)-2-((3S,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-67″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-4-hydroxybutanamide,

A7-68

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-69″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂,

A7-70

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-72

rac-2-((3R,4R)-4-(((6-(ethyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-73

rac-2-((3R,4R)-4-(((6-(ethyl(4-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-74

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-75

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-76

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-77

rac-2-((3R,4R)-4-(((6-((4-(1H-Pyrazol-1-yl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-78

rac-2-((3R,4R)-4-(((6-((4-cyanobenzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-79

rac-2-((3R,4R)-4-(((6-((4-(1,1-difluoro-2-hydroxyethyl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-80

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

A7-81

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

A7-82

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

A7-83

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

A7-84

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-imidazol-2-yl)piperidin-1-yl)acetamide,

A7-85

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-87

2-(4-(1-((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)-2-hydroxyethyl)piperidin-1-yl)acetamide,

B4-1-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

B4-1-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

B4-2-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide,

C4-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

C4-2-1

2-(4-(((6-((3,5-bis(trifluoromethyl)benzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

D5-1-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-1-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-2-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-2-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-3-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-3-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-4″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-6″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-9″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-10″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, E6-1

2-(4-Amino-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

F2-1

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(2-methylbenzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-2

rac-2-((3R,4R)-4-(((6-((2,6-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-3

rac-2-((3R,4R)-4-(((6-((2,3-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-4

rac-2-((3R,4R)-4-(((6-((2,6-dichlorobenzyl)(ethyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-5

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(1-(o-tolyl)ethyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-6

rac-2-((3R,4R)-4-(((6-((1-(2-chlorophenyl)ethyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-7

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-8

rac-2-((3R,4R)-4-(((6-((3-cyanobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-9

rac-2-((3R,4R)-4-(((5-fluoro-6-(isobutyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-10

rac-2-((3R,4R)-4-(((6-((cyclopropylmethyl)(2-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-11

rac-2-((3R,4R)-4-(((6-((4-cyanobenzyl)(isobutyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-12

rac-2-((3R,4R)-4-(((6-((4-chloro-3-fluorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-13

rac-2-((3R,4R)-4-(((6-((4-(difluoromethoxy)benzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-14

rac-2-((3R,4R)-4-(((6-((4-(difluoromethoxy)-3-methoxybenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-15

rac-2-((3R,4R)-4-(((6-((4-chlorobenzyl)(isopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-16

rac-2-((3R,4R)-4-(((5-fluoro-6-((2-methoxyethyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-17

rac-2-((3R,4R)-4-(((6-((2,4-dichlorobenzyl)(isobutyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-18

rac-2-((3R,4R)-4-(((6-((4-cyanobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-19

rac-2-((3R,4R)-4-(((5-fluoro-6-(((6-methoxypyridin-3-yl)methyl)(methyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-20

rac-2-((3R,4R)-4-(((6-((3-(difluoromethoxy)benzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-21

rac-2-((3R,4R)-4-(((6-((3,5-dichlorobenzyl)(methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-22

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

F2-23

rac-2-((3R,4R)-4-(((6-((3-chlorobenzyl)(isopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In other preferred embodiment disclosed herein, the compound, salt, stereoisomer, or salt of a stereoisomer according to Formula (I) is selected from the group consisting of:

A7-1-1

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-1-2

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-3-1

rel-(R)-2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-3-2

rel-(R)-2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-4-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-4-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-5-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-6-1

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-6-2

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-7-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 1^steluting isomer,

A7-7-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-7-3

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 3^rdeluting isomer,

A7-7-4

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide, 4^theluting isomer,

A7-8

methyl 1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxylate,

A7-9

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-10

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-14-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-14-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer

A7-15-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-15-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide 2^ndeluting isomer,

A7-16-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-16-2

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-17-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-17-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-19-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-19-2

rel-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-20-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-20-2

rel-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-21-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-21-2

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-22-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-22-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-26-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-26-2

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-28-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-28-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-29-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-29-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-31

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1r,3S)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-32

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1s,3R)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-39

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-40

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-41

rac-2-((3R,4R)-4-(((5-fluoro-6-((1-methylcyclopropyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-43

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-44

1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxamide,

A7-45

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-50

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-51

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-52

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-54-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-54-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-55″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide, enantiomerically enriched,

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-57″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide, enantiomerically enriched,

A7-58

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-60

rac-2-((3R,4R)-4-(((5-fluoro-6-((methyl-d₃)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-65

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-66-1

rel-(R)-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide or rel-(R)-2-((3S,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

1^steluting major isomer,

A7-66-2

rel-(R)-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide

OR

rel-(R)-2-((3S,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide, 2^ndeluting major isomer,

A7-67″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-4-hydroxybutanamide, enantiomerically enriched,

A7-68

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-69″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂, enantiomerically enriched,

A7-70

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-72

rac-2-((3R,4R)-4-(((6-(ethyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-74

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-75

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-76

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-80

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

A7-81

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

A7-82

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

A7-85

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

A7-86

rac-2-((3R,4R)-4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

B4-1-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 1^steluting isomer,

B4-1-1-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

B4-1-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 1^steluting isomer,

B4-1-2-2

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

B4-2-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide, 1^steluting isomer,

B4-2-1-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

C4-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 1st eluting isomer,

C4-1-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-1-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-1-1-2

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-1-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-1-2-2

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-2-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-2-1-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-2-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-2-2-2

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-3-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-3-1-2

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-3-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-3-2-2

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-4″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched,

D5-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, major isomer,

D5-5-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, minor isomer,

D5-6″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched,

D5-9″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched,

F2-7

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In some cases, the compound, salt, stereoisomer, or salt of a stereoisomer according to Formula (I) is selected from the group consisting of:

A7-1-1

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-3-1

rel-(R)-2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

A7-4-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

A7-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

A7-6-1

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

A7-7-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide,

A7-8 methyl 1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxylate,

A7-9

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-10

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-14-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-15-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-16-1

rel-2-((3R,4R)-4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-17-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-19-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-20-1

rel-2-((3R,4R)-4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-21-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-22-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-26-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-28-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-29-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-31

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1r,3S)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-32

rac-2-((3R,4R)-4-(((5-fluoro-6-(((1s,3R)-3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-39

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-40

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-41

rac-2-((3R,4R)-4-(((5-fluoro-6-((1-methylcyclopropyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-42

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-44

1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxamide,

A7-45

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-50

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-51

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-52

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-54-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-55″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

A7-56

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-57″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

A7-58

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((5-fluoro-6-((methyl-d₃)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-65

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-66-1

rel-(R)-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide, or

rel-(R)-2-((3S,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-67″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-4-hydroxybutanamide,

A7-68

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-69″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂,

A7-70

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-72

rac-2-((3R,4R)-4-(((6-(ethyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-74

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-75

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-76

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-80

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

A7-81

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

A7-82

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

A7-85

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

A7-86

rac-2-((3R,4R)-4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

B4-1-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

B4-1-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

B4-2-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide,

C4-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

D5-1-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-1-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-2-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-2-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-3-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-3-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-4″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-6″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-9″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

F2-7

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In some cases, the compound, salt, or salt of a stereoisomer is selected from the group consisting of

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-(trifluoromethyl)piperidin-1-yl)acetamide,

methyl 1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxylate,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclobutyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((2-(trifluoromethyl)pyrimidin-5-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(isopropyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(methyl(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((6-(1,1-difluoroethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-(3-fluorocyclobutyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-((1-methylcyclopropyl)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(difluoromethoxy)-2-fluorobenzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

1-(2-amino-2-oxoethyl)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-4-carboxamide,

2-(4-(((6-(cyclopropyl((6-(trifluoromethyl)pyridin-3-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl((5-(trifluoromethyl)pyridin-2-yl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

2-(4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

2-(4-(((6-(cyclopropyl(3-methoxy-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((5-fluoro-6-((methyl-d₃)(4-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-4-hydroxybutanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(ethyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,4-triazol-3-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

2-(4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, and

2-(4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In some cases, the compound, salt, stereoisomer, or salt of a stereoisomer according to Formula (I) is selected from the group consisting of:

A7-1-1

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-1-2

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-5-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-6-1

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 1^steluting isomer,

A7-6-2

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-10

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-21-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-21-2

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-22-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-22-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-26-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-26-2

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-40

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-43

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-50

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-51

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-54-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

A7-54-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

A7-55″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide, enantiomerically enriched,

A7-56

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-57″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide, enantiomerically enriched,

A7-65

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-69″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂, enantiomerically enriched,

A7-70

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-74

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-75

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-76

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-81

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

A7-82

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

A7-85

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

rac-2-((3R,4R)-4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

B4-1-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 1^steluting isomer,

B4-1-1-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

B4-2-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide, 1^steluting isomer,

B4-2-1-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide, 2^ndeluting isomer,

C4-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 1^steluting isomer,

C4-1-2

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-1-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-1-1-2

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-2-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-2-1-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-2-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-2-2-2

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-3-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 1^steluting isomer,

D5-3-1-2

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, 2^ndeluting isomer,

D5-4″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched

D5-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, major isomer,

D5-5-2

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, minor isomer,

D5-6″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched,

D5-9″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, enantiomerically enriched.

In some cases, the compound, salt, stereoisomer, or salt of a stereoisomer according to Formula (I) is selected from the group consisting of:

A7-1-1

rel-2-((3R,4R)-4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

A7-6-1

rel-(R)-2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

A7-10

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

A7-21-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-22-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-26-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-40

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-43

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-50

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

A7-51

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

A7-54-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-55″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

A7-56

rac-2-((3R,4R)-4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-57″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

A7-65

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

A7-69″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂,

A7-70

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

A7-74

rac-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-75

rac-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-76

rac-2-((3R,4R)-4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

A7-81

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

A7-82

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

A7-85

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

A7-86

rac-2-((3R,4R)-4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

B4-1-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

B4-1-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

B4-2-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide,

C4-1-1

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

D5-1-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-1-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide

D5-2-1-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-2-2-1

rel-2-((3R,4S)-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-3-1-1

rel-2-((3R,4R)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-3-2-1

rel-2-((3R,4S)-4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-4″

rel-2-((3R,4R)-4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-5-1

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-6″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

D5-9″

rel-2-((3R,4R)-4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, and.

F2-7

rac-2-((3R,4R)-4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In some cases, the compound, stereoisomer, or salt of the disclosure is selected from the group consisting of

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-fluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,3-difluoropiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1-difluoroethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(difluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-cyano-4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

2-(4-(((6-(cyclopropyl(3-(trifluoromethoxy)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-2-methylpropanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide-2,2-d₂,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(hydroxymethyl)piperidin-1-yl)-3-hydroxypropanamide,

2-(4-(((6-(cyclopropyl(4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoro pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,2,4-oxadiazol-3-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1,3,4-oxadiazol-2-yl)piperidin-1-yl)acetamide,

2-(4-(((6-(Cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-4-(1H-1,2,3-triazol-5-yl)piperidin-1-yl)acetamide,

2-(4-(((6-((4-(1H-pyrazol-1-yl)benzyl)(cyclopropyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-3-methylpiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-methylpiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3-hydroxy-4-(hydroxymethyl)piperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(2-fluoro-4-(trifluoromethyl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(ethyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide,

2-(4-(((6-(cyclopropyl(2-fluoro-4-(1H-pyrazol-1-yl)benzyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide, and

2-(4-(((5-fluoro-6-(methyl(3-(trifluoromethoxy)benzyl)amino)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)acetamide.

In an embodiment, the compound has a structure selected from the group consisting of:

[Image Omitted]

or a stereoisomer or salt or salt of a stereoisomer thereof.

In an embodiment, the compound has a structure selected from the group consisting of:

[Image Omitted]

or a stereoisomer or salt or salt of a stereoisomer thereof.