IP Library › Granted Patent US 8,354,420

Granted Patent B2

US 8,354,420 · App. 13/150,929 · Granted Jan 15, 2013

Aminopyrimidine derivatives as LRRK2 inhibitors

Inventors: Charles Baker-Glenn (Puckeridge, GB); Daniel Jon Burdick (Burlingame, CA); Mark Chambers (St. Neots, GB); Bryan K. Chan (Burlingame, CA); Huifen Chen (Burlingame, CA); Anthony Estrada (San Carlos, CA); Janet Gunzner-Toste (Piedmont, CA); Daniel Shore (San Francisco, CA); Zachary Sweeney (Redwood City, CA); Shumei Wang (Foster City, CA); Guiling Zhao (San Mateo, CA)

Assignee: Genentech, Inc.

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 8,354,420
App. No.: 13/150,929
Granted: Jan 15, 2013
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R 1 , R 2 , R 3 , R 5 , R 6 and R 7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

Claims (455)

1. A compound of formula I:

or pharmaceutically acceptable salts thereof,

wherein:

m is from 0 to 3;

X is: —NR a —; —O—; or —S(O) n — wherein n is from 0 to 2 and R a is hydrogen or C 1-6 alkyl;

R 1 is: C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; halo-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; hydroxy-C 1-6 alkyl; amino-C 1-6 alkyl; C 1-6 alkylsulfonyl-C 1-6 alkyl; C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydropyranyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

or R 1 and R a together with the atoms to which they are attached may form a three to six membered ring that may optionally include an additional heteroatom selected from O, N and S, and which is substituted with oxo, halo or C 1-6 alkyl;

R 2 is: halo; C 1-6 alkoxy; cyano; C 2-6 alkynyl; C 2-6 alkenyl; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; C 3-6 cycloalkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; acetyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 3 is: —OR 4 ; halo; cyano; C 1-6 alkyl; halo-C 1-6 alkyl; C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 4 is: hydrogen; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl or halo; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl or halo; tetrahydrofuranyl;

tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 5 is: hydrogen; or C 1-6 alkyl;

n is 0 or 1;

R 6 is: hydrogen; C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; hydroxy-C 1-6 alkyl; amino-C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; heterocyclyl; or heterocyclyl-C 1-6 alkyl; wherein the C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, heterocyclyl and heterocyclyl-C 1-6 alkyl each may be optionally substituted with one, two, three or four groups independently selected from: C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy; hydroxy-C 1-6 alkyl; halo; nitrile; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring;

or R 5 and R 6 together with the nitrogen atom to which they are attached form a three- to seven-membered ring that optionally includes an additional heteroatom selected from O, N and S(O) n , and which is optionally substituted with one, two, three or four groups independently selected from: C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy; C 1-6 alkoxy-C 1-6 alkyl; hydroxy-C 1-6 alkyl; halo, nitrile; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring; and

R 7 is: halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; or halo-C 1-6 alkoxy.

2. The compound of claim 1 , wherein said compound is of formula II:

or a pharmaceutically acceptable salt thereof,

wherein:

m is from 0 to 3;

X is: —NR a —; —O—; or —S(O) n — wherein n is from 0 to 2 and R a is hydrogen or C 1-6 alkyl;

R 1 is: C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; halo-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; hydroxy-C 1-6 alkyl; amino-C 1-6 alkyl; C 1-6 alkylsulfonyl-C 1-6 alkyl; C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 3 is: —OR 4 ; halo; cyano; C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 4 is: C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; C 3-6 cycloalkyl optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 5 is: hydrogen; or C 1-6 alkyl;

R 6 is: hydrogen; C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; amino-C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; heterocyclyl; or heterocyclyl-C 1-6 alkyl; wherein the C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, heterocyclyl and heterocyclyl-C 1-6 alkyl each may be optionally substituted with one, two or three groups independently selected from: C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy; hydroxy-C 1-6 alkyl; halo; nitrile; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring;

or R 5 and R 6 together with the nitrogen atom to which they are attached form a three- to seven-membered ring that optionally includes an additional heteroatom selected from O, N and S(O) n , and which is optionally substituted with one, two or three groups independently selected from: C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy; hydroxy-C 1-6 alkyl; halo, nitrile; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring; and

R 7 is: halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; or halo-C 1-6 alkoxy.

3. The compound of claim 2 wherein m is 0 or 1.

4. The compound of claim 2 wherein X is —NR a — or —O—.

5. The compound of claim 2 wherein X is —NR a .

6. The compound of claim 2 wherein R 1 is C 1-6 alkyl.

7. The compound of claim 2 wherein R 2 is: halo; halo-C 1-6 alkyl; or cyano.

8. The compound of claim 2 wherein R 2 is: chloro, trifluoromethyl or cyano.

9. The compound of claim 2 wherein R 3 is: halo; or —OR 4 .

10. The compound of claim 2 wherein R 3 is: halo; C 1-6 alkoxy; or halo-C 1-6 alkoxy.

11. The compound of claim 2 wherein R 3 is: R 3 is: methoxy; chloro; or fluoro.

12. The compound of claim 2 wherein m is 1 and R 7 is halo or methoxy.

13. The compound of claim 2 wherein R 5 and R 6 together with the nitrogen atom to which they are attached form a three- to six-membered ring that is optionally includes an additional heteroatom selected from O, N and S, and which is optionally substituted with one, two or three groups independently selected from C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, hydroxy, hydroxy-C 1-6 alkyl, halo, nitrile, C 1-6 alkyl-carbonyl, C 1-6 alkyl-sulfonyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, C 3-6 cycloalkyl-carbonyl, amino, or heterocyclyl, or two of the groups together with the atoms to which they are attached may form a five or six-membered ring.

14. The compound of claim 2 wherein R 5 and R 6 together with the nitrogen atom to which they are attached form a morpholinyl group that is optionally substituted once or twice with groups independently selected from C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, hydroxy, hydroxy-C 1-6 alkyl, halo, nitrile, C 1-6 alkyl-carbonyl, C 1-6 alkyl-sulfonyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, C 3-6 cycloalkyl-carbonyl, amino, or heterocyclyl, or the two groups together with the atoms to which they are attached may form a five or six-membered ring.

15. A compound of formula III

or a pharmaceutical salt thereof,

wherein:

m is from 0 to 3;

n is 0 or 1;

p is from 0 to 2;

X is: —NR a —; —O—; or —S(O) n — wherein n is from 0 to 2 and R a is hydrogen or C 1-6 alkyl;

Y is: —O—; —S(O) n —; —NR 10 ; or —CR 11 R 12 — when p is 1 or 2; and Y is —CR 11 R 12 — when p is 0;

R 1 is: C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; halo-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; hydroxy-C 1-6 alkyl; amino-C 1-6 alkyl; C 1-6 alkylsulfonyl-C 1-6 alkyl; C 3-6 cycloalkyl; optionally substituted with C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkyl wherein the C 3-6 cycloalkyl portion is optionally substituted with C 1-6 alkyl; tetrahydropyranyl; tetrahydrofuranyl; tetrahydrofuranyl-C 1-6 alkyl; oxetanyl; or oxetan-C 1-6 alkyl;

R 7 is: halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; or halo-C 1-6 alkoxy;

R 8 and R 9 each independently is: hydrogen; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy; hydroxy-C 1-6 alkyl; halo; nitrile; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; amino; or heterocyclyl;

or R 8 and R 9 together with the atoms to which they are attached form a five- or six-membered ring;

R 10 is: hydrogen; C 1-6 alkyl; hydroxy-C 1-6 alkyl; halo-C 1-6 alkyl; hydroxy-C 1-6 alkyl; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; heterocyclyl; or heterocyclyl-C 1-6 alkyl;

or one of R 8 and R 9 together with R 10 and the atoms to which they are attached form a five- or six-membered ring;

R 11 is: hydrogen; C 1-6 alkyl; or halo; and

R 12 is: hydrogen; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy; hydroxy-C 1-6 alkyl; halo; nitrile; C 1-6 alkyl-carbonyl; C 1-6 alkyl-sulfonyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 3-6 cycloalkyl-carbonyl; amino; heterocyclyl; or heterocyclyl-C 1-6 alkyl;

or R 11 and R 12 together with the atom to which they are attached may form a 3- to six-membered ring that optionally includes a heteroatom selected from O, N and S;

or one of R 8 and R 9 together with R 10 the atoms to which they are attached form a five- or six-membered ring;

or one of R 8 and R 9 together with R 12 and the atoms to which they are attached form a five- or six-membered ring.

16. The compound of claim 15 wherein p is 1.

17. The compound of claim 16 wherein R 2 is trifluoromethyl.

18. The compound of claim 17 wherein Y is —O—.

19. A composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of claim 1 .

20. A method for treating Parkinson's disease, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

21. The compound of claim 18 wherein R 1 is methyl, ethyl or cyclopropyl.

22. The compound of claim 21 wherein R 3 is methoxy or halo.

23. The compound of claim 22 wherein R 7 is methoxy or halo.

24. A compound selected from:

[4-(5-Fluoro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Fluoro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-hydroxy-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N,N-dimethyl-benzamide;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-N-cyclopropyl-3-methoxy-benzamide;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-hydroxy-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-difluoromethoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(octahydro-pyrido[1,2-a]pyrazin-2-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-hydroxy-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4,4-dimethyl-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3,5-dimethyl-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(1-hydroxy-1-methyl-ethyl)-piperidin-1-yl]-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-hydroxy-pyrrolidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methyl-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-piperidin-1-yl-methanone;

Azetidin-1-yl-[4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4,4-difluoro-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-methyl-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methoxy-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3,3-difluoro-piperidin-1-yl)-methanone;

1-[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-benzoyl]-piperidine-4-carbonitrile;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-fluoro-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-methoxy-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-ethyl-piperazin-1-yl)-methanone;

1-{4-[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-benzoyl]-piperazin-1-yl}-ethanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-trifluoromethyl-piperidin-1-yl)-methanone;

(4-tert-Butyl-piperidin-1-yl)-[4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-methanone; [4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-methyl-pyrrolidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-hydroxymethyl-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-methyl-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-pyrrolidin-1-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methanesulfonyl-piperazin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-trifluoromethyl-pyrrolidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-methyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2,6-dimethyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2,2-diethyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-hydroxymethyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-isobutyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-hydroxymethyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3,3-dimethyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methyl-piperazin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-isopropyl-piperazin-1-yl)-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-piperazin-1-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-difluoromethoxy-phenyl]-(4-hydroxy-piperidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-ethoxy-phenyl]-morpholin-4-yl-methanone;

[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-benzamide;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-N-ethyl-3-methoxy-benzamide;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-N-isopropyl-3-methoxy-benzamide;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N-methyl-benzamide;

[4-(5-Chloro-4-propoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-ethylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)-methanone;

[4-(5-Chloro-4-ethoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-isopropoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((S)-3-methyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((R)-3-methyl-morpholin-4-yl)-methanone;

N-(3-Amino-propyl)-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-benzamide;

[4-(5-Cyclopropyl-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-isobutylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-propylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-isopropylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-cyclopropanecarbonyl-piperazin-1-yl)-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(1-hydroxy-1-methyl-ethyl)-piperidin-1-yl]-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-trifluoromethyl-pyrrolidin-1-yl)-methanone;

1-[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-benzoyl]-piperidine-4-carbonitrile;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-cyclobutyl-piperazin-1-yl)-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-methoxy-piperidin-1-yl)-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((R)-3-hydroxy-pyrrolidin-1-yl)-methanone;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-oxetan-3-yl-piperazin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-isopropoxy-phenyl]-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(cyclopropylmethyl-amino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Chloro-4-cyclobutylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-hydroxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-ethyl-piperazin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-cyclobutoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-cyclobutoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-ethylamino-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-morpholin-4-yl-azetidin-1-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3-morpholin-4-yl-azetidin-1-yl)-methanone;

[4-(5-Chloro-4-cyclopentylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(1-methyl-cyclobutylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Chloro-4-cyclohexylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

(4-{5-Chloro-4-[(tetrahydro-furan-3-ylmethyl)-amino]-pyrimidin-2-ylamino}-3-methoxy-phenyl)-morpholin-4-yl-methanone;

[4-(5-Iodo-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-isopropoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-ethoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4,4-difluoro-piperidin-1-yl)-methanone;

(4-{5-Chloro-4-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-2-ylamino}-3-methoxy-phenyl)-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(cyclobutylmethyl-amino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Iodo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Cyclobutyl-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Cyclopropyl-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2-cyclopropyl-ethylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(cyclopentylmethyl-amino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((R)-2,2-di-deutero-3-methyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-(2,2,2-trifluoro-ethoxy)-phenyl]-morpholin-4-yl-methanone;

[4-[5-Chloro-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-(2,2,2-trifluoro-ethoxy)-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-((S)-2,2-di-deutero-3-methyl-morpholin-4-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-trifluoromethoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Cyclobutyl-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[3-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-ethoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(3,3-difluoro-azetidin-1-yl)-methanone;

{4-[5-Bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-ethoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-dimethylamino-piperidin-1-yl)-methanone;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N-oxetan-3-yl-benzamide;

4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N-(tetrahydro-pyran-3-yl)-benzamide;

{4-[5-Chloro-4-(tetrahydro-pyran-3-ylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-cyclobutoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-cyclobutoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(4-piperidin-4-yl-piperazin-1-yl)-methanone;

{4-[5-Chloro-4-(2,2,2-trifluoro-ethylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2,2-difluoro-ethylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-isopropoxy-phenyl]-morpholin-4-yl-methanone;

[3-Bromo-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-[4-(1-hydroxy-1-methyl-ethyl)-piperidin-1-yl]-methanone;

(4-(5-bromo-4-methoxypyrimidin-2-ylamino)-3-methoxyphenyl)(3-(trifluoromethyl)pyrrolidin-1-yl)methanone;

1-(4-(5-bromo-4-methoxypyrimidin-2-ylamino)-3-methoxybenzoyl)piperidine-4-carbonitrile;

(3-methoxy-4-(5-methoxy-4-(methylamino)pyrimidin-2-ylamino)phenyl) (morpholino)methanone;

N-(3-aminopropyl)-4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxybenzamide;

[3-Methoxy-4-(4-methylamino-5-prop-1-ynyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Methoxy-4-(4-methoxy-5-prop-1-ynyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-morpholin-4-yl-methanone;

{4-[5-Bromo-4-(2-methoxy-ethoxy)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N,N-dimethyl-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-(2-hydroxy-ethyl)-2-methoxy-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N-(2-methoxy-ethyl)-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N-methyl-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-cyclopropyl-2-methoxy-benzamide;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(4,4-difluoro-piperidin-1-yl)-methanone;

[5-Chloro-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-methoxy-phenyl]-morpholin-4-yl-methanone;

5-Chloro-N-cyclopropyl-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-methoxy-benzamide;

5-Chloro-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-methoxy-N-(2-methoxy-ethyl)-benzamide;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-piperazin-1-yl-methanone;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(4-dimethylamino-piperidin-1-yl)-methanone;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(3-hydroxy-pyrrolidin-1-yl)-methanone;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N-oxetan-3-yl-benzamide;

5-Chloro-N-cyclopropyl-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-pyrrolidin-1-yl-methanone;

N-tert-Butyl-5-chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-benzamide;

5-Chloro-2-methoxy-N,N-dimethyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N-(2-methoxy-ethyl)-N-methyl-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-(2-hydroxy-2-methyl-propyl)-2-methoxy-benzamide;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(4-hydroxy-piperidin-1-yl)-methanone;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(2-hydroxymethyl-morpholin-4-yl)-methanone;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-(2-hydroxy-ethyl)-2-methoxy-N-methyl-benzamide;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-N-(1-methyl-cyclobutyl)-benzamide;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-[1,4]oxazepan-4-yl-methanone;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-methanone;

1-[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-benzoyl]-piperidine-4-carbonitrile;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-(2-hydroxy-propyl)-2-methoxy-benzamide;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-(3-hydroxy-azetidin-1-yl)-methanone;

5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-N-(1-cyano-cyclopropyl)-2-methoxy-benzamide;

1-[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-benzoyl]-pyrrolidine-3-carbonitrile;

[5-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-((3R,5S)-dimethyl-piperazin-1-yl)-methanone;

5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide;

5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-N-oxetan-3-yl-benzamide;

5-Chloro-N-(2-hydroxy-2-methyl-propyl)-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

[5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-piperazin-1-yl-methanone;

1-[5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzoyl]-pyrrolidine-3-carbonitrile;

1-[2-Fluoro-5-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzoyl]-pyrrolidine-3-carbonitrile;

[5-Chloro-2-ethoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

2-Fluoro-5-methoxy-N-methyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

5-Chloro-N-(2-hydroxy-2-methyl-propyl)-2-methoxy-N-methyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

(4-(5-cyclopropyl-4-methoxypyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone;

1-{2-[2-Methoxy-4-(morpholine-4-carbonyl)-phenylamino]-4-methylamino-pyrimidin-5-yl}-ethanone;

{4-[5-Chloro-4-(2-methoxy-ethoxy)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-2-fluoro-5-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-isopropoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2-methoxy-ethoxy)-pyrimidin-2-ylamino]-3-cyclobutoxy-phenyl}-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-cyclopentyloxy-phenyl]-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-cyclopentyloxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-(2-oxa-6-aza-spiro[3,3]hept-6-yl)-methanone;

2-(2-methoxy-4-(2,2,6,6-tetrafluoromorpholine-4-carbonyl)phenylamino)-4-(methylamino)pyrimidine-5-carbonitrile;

2-(4-(4,4-difluoropiperidine-1-carbonyl)-2-methoxyphenylamino)-4-(methylamino)pyrimidine-5-carbonitrile;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-cyclopropyl-phenyl]-morpholin-4-yl-methanone;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-(3,3-difluoro-cyclobutyl)-3-methoxy-benzamide;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-cyclopropylmethyl-3-methoxy-benzamide;

2-[4-((S)-3-Fluoro-pyrrolidine-1-carbonyl)-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N-methyl-benzamide;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-N,N-dimethyl-benzamide;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N,N-diethyl-3-methoxy-benzamide;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-isopropyl-3-methoxy-benzamide;

2-[2-Methoxy-4-(pyrrolidine-1-carbonyl)-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

2-[4-(3-Fluoro-azetidine-1-carbonyl)-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-ethyl-3-methoxy-benzamide;

2-[2-Methoxy-4-(piperidine-1-carbonyl)-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-(2,2-difluoro-ethyl)-3-methoxy-benzamide;

N-tert-Butyl-4-(5-cyano-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-benzamide

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-ethyl-N-isopropyl-3-methoxy-benzamide;

2-[4-(3,3-Difluoro-pyrrolidine-1-carbonyl)-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

2-[4-(3,3-Difluoro-azetidine-1-carbonyl)-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

2-[4-((R)-3-Fluoro-pyrrolidine-1-carbonyl)-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-ethyl-3-methoxy-N-methyl-benzamide;

2-[4-(Azetidine-1-carbonyl)-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-N-isopropyl-3-methoxy-N-methyl-benzamide;

{4-[5-Chloro-4-(tetrahydro-furan-3-ylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

[3-Isopropoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Ethoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-cyclopropoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-cyclopropoxy-phenyl]-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2-methanesulfonyl-ethylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

2-[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1-morpholin-4-yl-ethanone

2-[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1-morpholin-4-yl-ethanone;

2-[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-methoxy-phenyl]-1-morpholin-4-yl-ethanone;

2-[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-1-morpholin-4-yl-ethanone;

2-[4-(5-Chloro-4-methoxy-pyrimidin-2-ylamino)-2,5-dimethoxy-phenyl]-1-morpholin-4-yl-ethanone;

2-[4-(5-Chloro-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-1-morpholin-4-yl-ethanone;

2-[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-3-methoxy-phenyl]-1-morpholin-4-yl-ethanone;

2-[2,5-Dimethoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-1-morpholin-4-yl-ethanone;

N-(3-Amino-propyl)-5-chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-2-methoxy-benzamide;

{4-[5-Bromo-4-(2-methoxy-ethylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(2-methoxy-propylamino)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-N,N,3-trimethylbenzamide;

(4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methylphenyl)(morpholino)methanone;

(4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methylphenyl)(4-hydroxypiperidin-1-yl)methanone;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-(trifluoromethoxy)phenyl)(morpholino)methanone;

(4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-(trifluoromethoxy)phenyl)(morpholino)methanone;

(5-chloro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(perdeuteromorpholino)methanone;

(5-fluoro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-5-fluoro-2-methoxyphenyl)(morpholino)methanone;

[2-Fluoro-5-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

4-(5-Cyano-4-ethylamino-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-N,N-dimethyl-benzamide;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-methoxyphenyl)(morpholino)methanone;

(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-methoxyphenyl)methanone;

(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl(2-fluoro-3-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)methanone;

5-chloro-4-(5-chloro-4-methoxypyrimidin-2-ylamino)-2-methoxy-N-methylbenzamide;

2-(4-((3S,4S)-3,4-difluoropyrrolidine-1-carbonyl)-2-methoxyphenylamino)-4-(methylamino)pyrimidine-5-carbonitrile;

(5-chloro-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(3-methoxypyrrolidin-1-yl)methanone;

(2-fluoro-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(3-methoxypyrrolidin-1-yl)methanone;

2-fluoro-N-(2-hydroxy-2-methylpropyl)-5-methoxy-N-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzamide;

((2S,6R)-2,6-dimethylmorpholino)(2-fluoro-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)methanone;

(2-fluoro-5-methoxy-4-(4-(2-methoxyethoxy)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;

(2-ethoxy-5-fluoro-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-isopropoxyphenyl)(morpholino)methanone;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-3-isopropoxyphenyl)(morpholino)methanone;

(4-(5-chloro-4-(piperidin-1-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone;

(4-(5-chloro-4-(pyrrolidin-1-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone;

[4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-phenyl]-morpholin-4-yl-methanone;

[5-Chloro-4-(5-chloro-4-ethylamino-pyrimidin-2-ylamino)-2-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Chloro-4-methoxy-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-morpholin-4-yl-methanone;

[5-Chloro-4-(5-chloro-4-methoxy-pyrimidin-2-ylamino)-2-methoxy-phenyl]-morpholin-4-yl-methanone;

[3-Chloro-4-(5-chloro-4-methoxy-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[2-Chloro-5-methoxy-4-(4-methoxy-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Methoxy-4-(4-methoxy-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

{4-[5-Chloro-4-(tetrahydro-pyran-4-yloxy)-pyrimidin-2-ylamino]-3-methoxy-phenyl}-morpholin-4-yl-methanone;

5-Chloro-N-(1-cyano-cyclopropyl)-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

[5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-(2,6-dimethyl-morpholin-4-yl)-methanone;

[3-Methoxy-4-(4-pyrrolidin-1-yl-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Cyclobutoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

N-(3,3-Difluoro-cyclobutyl)-3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-N-oxetan-3-yl-benzamide;

[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-methanone;

[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl)-methanone;

[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-pyrrolidin-1-yl-methanone;

N,N-Diethyl-3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

(4-Dimethylamino-piperidin-1-yl)-[3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-methanone;

(2,6-Dimethyl-morpholin-4-yl)-[3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-methanone;

1-[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzoyl]-piperidine-4-carbonitrile;

[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-methanone;

[3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-(4-methoxy-piperidin-1-yl)-methanone;

3-Methoxy-N-(2-methoxy-ethyl)-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

3-Methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide

N-(4,4-Difluoro-cyclohexyl)-; 3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

[4-(5-Chloro-4-methylamino-pyrimidin-2-ylamino)-3-(oxetan-3-yloxy)-phenyl]-morpholin-4-yl-methanone;

[3-Cyclopropylmethoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Cyclobutylmethoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

N-Ethyl-3-methoxy-N-methyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

[4-(5-Bromo-4-methylamino-pyrimidin-2-ylamino)-5-chloro-2-methoxy-phenyl]-morpholin-4-yl-methanone;

[3-Cyclopropyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Bromo-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-Chloro-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[2-Chloro-5-methoxy; -4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[2-Chloro-4-(5-chloro-4-methylamino-pyrimidin-2-ylamino)-5-methoxy-phenyl]-morpholin-4-yl-methanone;

[4-(5-Bromo-4-methoxy-pyrimidin-2-ylamino)-2-chloro-5-methoxy-phenyl]-morpholin-4-yl-methanone;

(5-chloro-4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-2-methoxyphenyl)(morpholino)methanone;

[5-Chloro-2-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[2-Fluoro-3-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

[3-(2-Fluoro-ethoxy)-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

(4-(5-chloro-4-methoxypyrimidin-2-ylamino)-3-methoxyphenyl)(pyrrolidin-1-yl)methanone;

[5-Ethoxy-2-fluoro-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholin-4-yl-methanone;

3-Methoxy-N-(2-methoxy-ethyl)-N-methyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-N-(2-methoxy-ethyl)-N-methyl-benzamide;

2-Fluoro-5-methoxy-N-(2-methoxy-ethyl)-N-methyl-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-N-(2-methoxy-ethyl)-N-methyl-benzamide;

[2-Fluoro-5-methoxy-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-((S)-2-methoxymethyl-pyrrolidin-1-yl)-methanone;

[4-(4-Ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-phenyl]-((S)-2-methoxymethyl-pyrrolidin-1-yl)-methanone;

N-Ethyl-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-N-(2-methoxy-ethyl)-benzamide;

N-Ethyl-2-fluoro-5-methoxy-N-(2-methoxy-ethyl)-4-(4-methylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide;

[5-Ethoxy-4-(4-ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino)-2-fluoro-phenyl]-morpholin-4-yl-methanone;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl-amino)-3-isopropoxyphenyl)(morpholino)methanone;

(2-fluoro-3-isopropoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;

(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3-(trifluoromethoxy)phenyl)(morpholino)methanone;

(2-fluoro-3-isopropoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;

2-(2-methoxy-4-(morpholine-4-carbonyl)phenylamino)-4-(methylamino)pyrimidine-5-carbonitrile;

4-Methoxy-2-[2-methoxy-4-(morpholine-4-carbonyl)-phenylamino]-pyrimidine-5-carbonitrile;

4-Ethylamino-2-[5-fluoro-2-methoxy-4-(morpholine-4-carbonyl)-phenylamino]-pyridine-5-carbonitrile;

2-[5-Fluoro-2-methoxy-4-(morpholine-4-carbonyl)-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

2-[4-((2R,6S)-2,6-Dimethyl-morpholine-4-carbonyl)-5-fluoro-2-methoxy-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile;

2-[4-((2R,6S)-2,6-Dimethyl-morpholine-4-carbonyl)-5-fluoro-2-methoxy-phenylamino]-4-ethylamino-pyrimidine-5-carbonitrile; and

4-(5-Cyano-4-methylamino-pyrimidin-2-ylamino)-2-fluoro-5-methoxy-N,N-dimethyl-benzamide;

or a pharmaceutically acceptable salt thereof.

25. The compound of claim 24 , wherein said compound selected from: