IP Library › Granted Patent US 10,428,050

Granted Patent B2

US 10,428,050 · App. 14/443,911 · Granted Oct 1, 2019

Substituted reverse pyrimidine Bmi-1 inhibitors

Inventors: Chang-Sun Lee (Belle Mead, NJ); Ramil Baiazitov (East Brunswick, NJ); Liangxian Cao (East Brunswick, NJ); Thomas W Davis (South Orange, NJ); Wu Du (Cranbury, NJ); Ronggang Liu (Berwyn, PA); Young-choon Moon (Belle Mead, NJ); Steven D. Paget (Hillsborough, NJ); Hongyu Ren (Florence, NJ); Nadiya Sydorenko (Princeton, NJ); Richard Gerald Wilde (Somerville, NJ)

Assignee: PTC THERAPEUTICS, INC.

C07D403/12 A61K31/506 A61K45/06 A61N5/10 C07D403/04 C07D471/04 C07D487/04 Y02A50/411

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Quick Facts

Patent No.: US 10,428,050
App. No.: 14/443,911
Granted: Oct 1, 2019
Kind: B2

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Abstract

Amine substituted reverse pyrimidine compounds and forms thereof that inhibit the function and reduce the level of B-cell specific Moloney murine leukemia virus integration site 1 (Bmi-1) protein and methods for their use to inhibit Bmi-1 function and reduce the level of Bmi-1 to treat a cancer mediated by Bmi-1 are described herein.

Claims (437)

1. A compound of Formula (I):

or a form thereof, wherein

R 1 is bicyclic heteroaryl or bicyclic heterocyclyl substituted on a carbon atom ring member with one, two, three or four R 5 substituents, or on a nitrogen atom ring member with an oxygen atom substituent to form an N-oxide;

X is N or N substituted with an oxygen atom substituent to form an N-oxide;

R 2 is amino;

R 3 is hydrogen, cyano, halo, C 1-8 alkyl, amino, C 1-8 alkyl-amino or (C 1-8 alkyl) 2 -amino;

R 4 is phenyl, optionally substituted with one, two, three or four R 6 substituents;

R 5 is independently selected from the group consisting of cyano, halo, hydroxyl, nitro, oxo, C 1-8 alkyl, cyano-C 1-8 alkyl, halo-C 1-8 alkyl, hydroxyl-C 1-8 alkyl, C 1-8 alkoxy, C 1-8 alkoxy-C 1-8 alkyl, halo-C 1-8 alkoxy, C 2-8 alkenyl, C 1-8 alkoxy-C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkoxy-C 2-8 alkynyl, carboxyl, amino, C 1-8 alkyl-amino, (C 1-8 alkyl) 2 -amino, amino-C 1-8 alkyl, C 1-8 alkyl-amino-C 1-8 alkyl, (C 1-8 alkyl) 2 -amino-C 1-8 alkyl, hydroxyl-C 1-8 alkyl-amino, hydroxyl-C 1-8 alkyl-amino-C 1-8 alkyl, hydroxyl-C 1-8 alkyl-amino-C 1-8 alkyl-amino, C 1-8 alkyl-thio, C 1-8 alkyl-carbonyl, C 1-8 alkyl-carbonyl-amino, C 1-8 alkyl-carbonyl-oxy, C 1-8 alkyl-carbonyl-oxy-C 1-8 alkyl, C 1-8 alkoxy-carbonyl, C 1-8 alkoxy-carbonyl-C 1-8 alkyl, C 1-8 alkoxy-carbonyl-amino, C 1-8 alkyl-sulfonyl, C 3-14 cycloalkyl, aryl, aryl-C 1-8 alkyl, aryl-amino, aryl-C 1-8 alkyl-amino, heteroaryl, heteroaryl-C 1-8 alkyl and heterocyclyl, wherein C 3-14 cycloalkyl, aryl, heteroaryl or heterocyclyl and the aryl and heteroaryl portions of aryl-C 1-8 alkyl, aryl-amino, aryl-C 1-8 alky-amino and heteroaryl-C 1-8 alkyl are each optionally substituted with one, two, three or four halo, C 1-8 alkyl, halo-C 1-8 alkyl, hydroxyl-C 1-8 alkyl, C 1-8 alkoxy, halo-C 1-8 alkoxy, hydroxyl-C 1-8 alkoxy or carboxyl substituents;

R 6 is independently selected from the group consisting of cyano, halo, nitro, C 1-8 alkyl, halo-C 1-8 alkyl, hydroxyl-C 1-8 alkyl, C 1-8 alkoxy, halo-C 1-8 alkoxy, C 2-8 alkenyl, C 1-8 alkoxy-C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkoxy-C 2-8 alkynyl, carboxyl, formyl, formyl-oxy, C 1-8 alkyl-carbonyl, halo-C 1-8 alkyl-carbonyl, C 1-8 alkyl-thio, halo-C 1-8 alkyl-thio, amino, C 1-8 alkyl-amino, (C 1-8 alkyl) 2 -amino, C 1-8 alkyl-carbonyl, C 1-8 alkyl-carbonyl-oxy, C 1-8 alkyl-carbonyl-oxy-C 1-8 alkyl, C 1-8 alkoxy-carbonyl, halo-C 1-8 alkoxy-carbonyl, C 1-8 alkoxy-carbonyl-C 1-8 alkyl, C 1-8 alkoxy-carbonyl-amino, C 1-8 alkoxy-carbonyl-amino-C 1-8 alkyl, amino-carbonyl, C 1-8 alkyl-amino-carbonyl, (C 1-8 alkyl) 2 -amino-carbonyl, C 1-8 alkyl-carbonyl-amino, C 1-8 alkyl-carbonyl-amino-C 1-8 alkyl, amino-C 1-8 alkyl, C 1-8 alkyl-amino-C 1-8 alkyl, (C 1-8 alkyl) 2 -amino-C 1-8 alkyl, amino-C 1-8 alkyl-amino, C 1-8 alkyl-amino-C 1-8 alkyl-amino, (C 1-8 alkyl) 2 -amino-C 1-8 alkyl-amino, hydroxyl-C 1-8 alkyl-amino, hydroxyl-C 1-8 alkyl-amino-C 1-8 alkyl, hydroxyl-C 1-8 alkyl-amino-C 1-8 alkyl-amino, imino-C 1-8 alkyl, hydroxyl-imino-C 1-8 alkyl, C 1-8 alkoxy-imino-C 1-8 alkyl, C 1-8 alkyl-sulfonyl, halo-C 1-8 alkyl-sulfonyl, amino-sulfonyl, C 1-8 alkyl-amino-sulfonyl, (C 1-8 alkyl) 2 -amino-sulfonyl, B(OR 8 ) 2 , C 3-14 cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein C 3-14 cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted with one, two, three or four halo or C 1-8 alkyl substituents;

R 8 is independently hydrogen or C 1-8 alkyl;

wherein the form of the compound is selected from the group consisting of a free acid, free base, salt, ester, hydrate, solvate, chelate, clathrate, isotopologue, stereoisomer, racemate, enantiomer, diastereomer and tautomer thereof.

2. The compound of claim 1 , or form thereof, wherein R 1 is substituted bicyclic heteroaryl or bicyclic heterocyclyl selected from the group consisting of 1H-indolyl, 2H-indazolyl, 4,5,6,7-tetrahydro-2H-indazolyl, 1H-benzimidazolyl, imidazo[2,1-b][1,3]thiazolyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-c]pyrimidinyl, imidazo[1,2-a]pyridinyl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyridinyl, 1H-imidazo[4,5-b]pyridinyl, 1H-imidazo[4,5-c]pyridinyl, 4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridinyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-a]pyrimidinyl, 7H-purinyl and quinolinyl.

3. The compound of claim 2 , or form thereof, wherein R 1 is substituted bicyclic heteroaryl selected from the group consisting of 1H-indolyl, 1H-benzimidazolyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyrazinyl and imidazo[1,2-a]pyrimidinyl.

4. A compound or form thereof, selected from the group consisting of:

2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidine-4,6-diamine,

2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(trifluoromethoxy)phenyl]-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidine-4,6-diamine,

2-(6-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(6-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidine-4,6-diamine,

N-[4-(trifluoromethyl)phenyl]-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-N-[3-fluoro-4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoroimidazo[1,2-a]pyridin-3-yl)-N-[4-(difluoromethoxy)-3-fluorophenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(2-ethyl-6-fluoro-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)-3-fluorophenyl]pyrimidine-4,6-diamine,

N-[4-(trifluoromethyl)phenyl]-2-(2,5,6-trimethyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[3-fluoro-4-(trifluoromethyl)phenyl]-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-ethyl-6-fluoro-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-5-fluoro-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

[3-(4-amino-6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-2-yl)-6-fluoroimidazo[1,2-a]pyridin-2-yl]methanol,

2-(6-bromo-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2,6-dimethyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-ethyl-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-N-[3-fluoro-4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-ethenyl-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-fluoro-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[3-fluoro-4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]pyrimidine-4,6-diamine,

2-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[3-fluoro-4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]pyrimidine-4,6-diamine,

2-(6-fluoro-2-methylimidazo[1,2-a]pyrimidin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(difluoromethoxy)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-ethyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoropyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-imidazo[4,5-b]pyridin-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

2-(2-ethyl-4,6-difluoro-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(2-ethyl-4,6-difluoro-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-4,6-difluoro-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

5-fluoro-2-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(4-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)pyrimidine-4,6-diamine,

2-(2-cyclopropyl-4-fluoro-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-4-fluoro-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

2-(2-cyclopropyl-4-fluoro-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoropyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-6-fluoro-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-[2-(difluoromethyl)-6-fluoro-1H-benzimidazol-1-yl]pyrimidine-4,6-diamine,

2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(methylsulfanyl)phenyl]pyrimidine-4,6-diamine,

2-[2-(1-methylcyclopropyl)-1H-benzimidazol-1-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-[2-(1-methylcyclopropyl)-1H-benzimidazol-1-yl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-[2-(methoxymethyl)-1H-benzimidazol-1-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-[2-(propan-2-yl)-1H-benzimidazol-1-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-ethyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-cyclopropyl-6-fluoro-1H-imidazo[4,5-b]pyridin-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(2-ethyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(5-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(6-chloro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

2-(2-ethyl-5-fluoro-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-5-fluoro-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

2-(2-ethyl-6-fluoro-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-6-fluoro-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

5-chloro-2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-chloro-2-(2-ethyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-chloro-N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methylimidazo[1,2-a]pyridin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidine-4,6-diamine,

5-methyl-2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)pyrimidine-4,6-diamine,

5-fluoro-N-[4-(trifluoromethyl)phenyl]-2-(2,6,8-trimethylimidazo[1,2-a]pyrazin-3-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2,6,8-trimethylimidazo[1,2-a]pyrazin-3-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(2,6,8-trimethylimidazo[1,2-a]pyrazin-3-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-[6-fluoro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

2-(2-cyclopropylpyrazolo[1,5-a]pyridin-3-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

[3-(4-amino-6-{[4-(difluoromethoxy)phenyl]amino}-5-fluoropyrimidin-2-yl)-5-fluoropyrazolo[1,5-a]pyridin-2-yl]methanol,

2-[2-(methylsulfanyl)-1H-benzimidazol-1-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-5-fluoropyrazolo[1,5-a]pyridin-3-yl)-5-fluoropyrimidine-4,6-diamine,

2-(2-ethyl-5-fluoropyrazolo[1,5-a]pyridin-3-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(2-ethyl-5-fluoropyrazolo[1,5-a]pyridin-3-yl)-5-fluoropyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(3-methoxyphenyl)pyrimidine-4,6-diamine,

N-(3-chlorophenyl)-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

4-{[6-amino-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-yl]amino}benzonitrile,

methyl 4-{[6-amino-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-yl]amino}benzoate,

5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)-N-(3-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-N-(3-methoxyphenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(2-methyl-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

N-(4-methoxyphenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(dimethylamino)phenyl]-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-N-(4-methoxyphenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

4-{[6-amino-5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-yl]amino}benzonitrile,

5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

N-(3-fluoro-4-methoxyphenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

4-{[6-amino-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-yl]amino}benzonitrile,

2-(2-methyl-1H-benzimidazol-1-yl)-N-(4-nitrophenyl)pyrimidine-4,6-diamine,

N-(4-bromophenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methylphenyl)pyrimidine-4,6-diamine,

2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-2-(5,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-[2-(methoxymethyl)-1H-benzimidazol-1-yl]pyrimidine-4,6-diamine,

5-fluoro-2-[2-(methoxymethyl)-1H-benzimidazol-1-yl]-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-2-[2-(methoxymethyl)-1H-benzimidazol-1-yl]-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-5-fluoro-2-[2-(methoxymethyl)-1H-benzimidazol-1-yl]pyrimidine-4,6-diamine,

5-fluoro-2-[2-(methoxymethyl)-1H-benzimidazol-1-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

1-(4-amino-5-fluoro-6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-2-yl)-2-methyl-1H-benzimidazole-6-carbonitrile,

1-(4-amino-6-{[4-(difluoromethoxy)phenyl]amino}-5-fluoropyrimidin-2-yl)-2-methyl-1H-benzimidazole-6-carbonitrile,

1-{4-amino-5-fluoro-6-[(4-methylphenyl)amino]pyrimidin-2-yl}-2-methyl-1H-benzimidazole-6-carbonitrile,

1-{4-amino-5-fluoro-6-[(4-methoxyphenyl)amino]pyrimidin-2-yl}-2-methyl-1H-benzimidazole-6-carbonitrile,

1-(4-amino-6-{[4-(difluoromethoxy)phenyl]amino}-5-fluoropyrimidin-2-yl)-2-methyl-1H-benzimidazole-5-carbonitrile,

1-{4-amino-5-fluoro-6-[(4-methylphenyl)amino]pyrimidin-2-yl}-2-methyl-1H-benzimidazole-5-carbonitrile,

1-{4-amino-5-fluoro-6-[(4-methoxyphenyl)amino]pyrimidin-2-yl}-2-methyl-1H-benzimidazole-5-carbonitrile,

1-(4-amino-5-fluoro-6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-2-yl)-2-methyl-1H-benzimidazole-5-carbonitrile,

1-{4-amino-6-[(4-chlorophenyl)amino]-5-fluoropyrimidin-2-yl}-2-methyl-1H-benzimidazole-5-carbonitrile,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2-methyl-6-nitro-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methyl-6-nitro-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-N-(4-methoxyphenyl)-2-(2-methyl-6-nitro-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)-3-fluorophenyl]-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methyl-6-nitro-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

5-fluoro-N-(4-methoxyphenyl)-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)pyrimidine-4,6-diamine,

2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methylphenyl)pyrimidine-4,6-diamine,

2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

2-(5,7-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

N-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-5-fluoro-2-(6-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

5-fluoro-2-(6-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-2-(2-methyl-5-nitro-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-N-(4-methoxyphenyl)-2-(2-methyl-5-nitro-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(6-amino-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

2-(6-amino-2-methyl-1H-benzimidazol-1-yl)-N-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine,

2-(6-amino-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methylphenyl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chloro-3-fluorophenyl)-5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chloro-3-fluorophenyl)-5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chloro-3-fluorophenyl)-5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

N-[4-(dimethylamino)phenyl]-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-chloro-3-fluorophenyl)-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(3-methylphenyl)pyrimidine-4,6-diamine,

2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methylphenyl)pyrimidine-4,6-diamine,

2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-(4-chloro-3-fluorophenyl)-2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methylphenyl)pyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-5-fluoro-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

2-(2-cyclopropyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine,

N-(4-chlorophenyl)-2-(2-cyclopropyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-(4-chloro-3-fluorophenyl)-2-(2-cyclopropyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(4-methylphenyl)pyrimidine-4,6-diamine,

5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-(4-methoxyphenyl)pyrimidine-4,6-diamine,

5-fluoro-2-(5-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine, and

2-(6-amino-2-methyl-1H-benzimidazol-1-yl)-5-fluoro-N-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine;

wherein the form of the compound is selected from the group consisting of a salt, ester, hydrate, solvate, chelate, clathrate, isotopologue, stereoisomer, racemate, enantiomer, diastereomer and tautomer thereof.

5. A pharmaceutical composition for use in treating a cancer mediated by Bmi-1 comprising an effective amount of the compound of claim 1 , of form thereof, in admixture with a pharmaceutically acceptable excipient.

6. A pharmaceutical composition for use in treating a cancer mediated by Bmi-1 comprising an effective amount of the compound of claim 4 , or form thereof, in admixture with a pharmaceutically acceptable excipient.

7. A compound or form thereof, selected from the group consisting of:

N-(4-methoxyphenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-amine,

N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine,

2-(2-methylimidazo[1,2-a]pyridin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

N-(4-methoxyphenyl)-2-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine,

N-(4-chlorophenyl)-2-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine,

2-(2-methylimidazo[1,2-a]pyridin-3-yl)-N-phenylpyrimidin-4-amine,

2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

N-(4-chlorophenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(4-methylphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(4-bromophenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-[4-(difluoromethoxy)phenyl]-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(4-methoxyphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

2-[6-chloro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

2-[6-chloro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethoxy)phenyl]pyrimidin-4-amine,

N-(4-bromophenyl)-2-[6-chloro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

2-[6-chloro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(difluoromethoxy)phenyl]pyrimidin-4-amine,

N-(4-chlorophenyl)-2-[6-chloro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

2-[2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

N-(4-bromophenyl)-2-[2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(4-methylphenyl)-2-[2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

2-[6-fluoro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-(4-methylphenyl)pyrimidin-4-amine,

2-[6-fluoro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-(4-methoxyphenyl)pyrimidin-4-amine,

2-[5-chloro-1-methyl-2-(trifluoromethyl)-1H-indol-3-yl]-N-(4-methoxyphenyl)pyrimidin-4-amine,

2-[5-chloro-1-methyl-2-(trifluoromethyl)-1H-indol-3-yl]-N-[4-(difluoromethoxy)phenyl]pyrimidin-4-amine,

N-(4-bromophenyl)-2-[5-chloro-1-methyl-2-(trifluoromethyl)-1H-indol-3-yl]pyrimidin-4-amine,

N-(4-bromophenyl)-2-(6-fluoro-2-phenylimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine,

2-(6-fluoro-2-phenylimidazo[1,2-a]pyridin-3-yl)-N-(4-methylphenyl)pyrimidin-4-amine,

N-(1,3-benzodioxol-5-yl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(6-methoxypyridin-3-yl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N 2 ,N 2 -dimethyl-N 5 -{2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-yl}pyridine-2,5-diamine,

2-[6-bromo-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

2-[6-bromo-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-(4-methoxyphenyl)pyrimidin-4-amine,

N-(3-fluoro-4-methoxyphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(3-chloro-4-methoxyphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(3-chloro-4-methylphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(4-ethoxyphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-[4-(propan-2-yl)phenyl]-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-[4-(1H-pyrazol-1-yl)phenyl]-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(3-chloro-4-methoxyphenyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-amine,

2-(2-methyl-1H-benzimidazol-1-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

N-(3-chloro-4-methoxyphenyl)-2-[2-(trifluoromethyl)-1H-benzimidazol-1-yl]pyrimidin-4-amine,

5-fluoro-N-(4-methylphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

5-chloro-N-(4-methylphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-(4-methoxyphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl]pyrimidin-4-amine,

2-[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

N-(4-chlorophenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl]pyrimidin-4-amine,

2-[6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

2-[6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethoxy)phenyl]pyrimidin-4-amine,

N-(4-methoxyphenyl)-2-[6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-[4-(difluoromethoxy)phenyl]-2-[6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

2-{[6-{[4-(difluoromethoxy)phenyl]amino}-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-yl]amino}ethanol,

N-[4-(difluoromethoxy)phenyl]-2-[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl]pyrimidin-4-amine,

2-[6-fluoro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

N-[4-(difluoromethoxy)phenyl]-2-[6-fluoro-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine,

N-[4-(trifluoromethyl)phenyl]-2-[2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-4-amine,

2-{[2-(2-methyl-1H-benzimidazol-1-yl)-6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-4-yl]amino}ethanol,

N 4 -(2-methoxyethyl)-2-(2-methyl-1H-benzimidazol-1-yl)-N 6 -[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine,

N 4 -[4-(difluoromethoxy)phenyl]-N 6 -(2-methoxyethyl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(4-methoxyphenyl)-2-[2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-4-amine,

N-[4-(difluoromethoxy)phenyl]-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidin-4-amine,

N-(4-methylphenyl)-2-[2-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl]pyrimidin-4-amine,

2-{[2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-6-{[4-(trifluoromethyl)phenyl]amino}pyrimidin-4-yl]amino}ethanol,

2-(imidazo[1,2-a]pyridin-3-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine,

5-fluoro-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)-N-[6-(trifluoromethyl)pyridin-3-yl]pyrimidine-4,6-diamine,

N-(1,3-benzodioxol-5-yl)-5-fluoro-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(1,3-benzodioxol-5-yl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(2,2-difluoro-1,3-benzodioxol-5-yl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(6-methoxypyridin-3-yl)-2-(2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(1,3-benzodioxol-5-yl)-2-(4,6-difluoro-2-methyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine,

N-(1,3-benzodioxol-5-yl)-5-fluoro-2-(6-methoxy-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine,

N-(2,2-difluoro-1,3-benzodioxol-5-yl)-2-(6-fluoro-2-methyl-1H-benzimidazol-1-yl)pyrimidine-4,6-diamine, and

N-(1,3-benzodioxol-5-yl)-2-(2-ethyl-1H-benzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine

wherein the form of the compound is selected from the group consisting of salt, ester, hydrate, solvate, chelate, clathrate, isotopologue, stereoisomer, racemate, enantiomer, diastereomer and tautomer thereof.

8. The compound or form thereof of claim 4 , selected from the group consisting of