# US 6,531,479 B2 · Anti-cancer compounds

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- Number: US 6,531,479 B2
- Document ID: US6531479B2
- Status: Granted
- Kind: B2
- Application number: 09/823,075
- Filed: 2001-03-29
- Published: 2002-02-14
- Granted: 2003-03-11
- Earliest claimed: 2000-03-29
- Assignees: Cyclacel Limited
- Inventors: Shudong Wang; Peter M. Fischer
- Web page: https://patentgrep.com/patent/US6531479B2

## CPC

- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/10: Antimycotics
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

## Claims

### Claim 1

A compound of general formula I:
wherein
one of X1 and X2 is S, and the other of X1 and X2 is N;
Z is NH, NHCO, NHSO2, NHCH2, CH2, CH2CH2, or CH═CH;
R1, R2, and R3 are independently H, alkyl, aryl, aralkyl, heterocycle, halogen, NO2, CN, OH, alkoxy, aryloxy, NH2, NH—R′, N—(R′)(R″), NH—COR′, NH-aryl, N-(aryl)2, COOH, COO—R′, COO-aryl, CONH2, CONH—R′, CON—(R′)(R″), CONH-aryl, CON-(aryl)2, SO3H, SO2NH2, CF3, CO—R′, or CO-aryl, wherein alkyl, aryl, aralkyl, heterocycle and NH-aryl groups may be further substituted with one or more groups selected from halogen, NO2, CN, OH, O-methyl, NH2, COOH, CONH2 and CF3; at least one of the groups R1 and R2 being other than H when either X1 or X2 is S;
R4, R5, R6, R7, and R8 are independently from each other H, substituted or unsubstituted lower alkyl, halogen, amino, carbamoyl, sulfamyl, NO2, CN, OH, substituted or unsubstituted alkoxy, NH2, NH—R′, alkyl-aryl, alkyl-heteroaryl, NH(C═NH)NH2, N(R′)3+, N—(R′)(R″), COOH, COO—R′, CONH2, CONH—R′, CON—(R′) (R″), SO3H, SO2NH2, CF3 or (CH2)nO(CH2)mNR′R″, (CH2)nCO2(CH2)mOR′″ wherein n is 0, 1, 2 or 3 and m is 1, 2 or 3;
wherein R′, R″ and R′″ are each independently alkyl groups that may be the same or different;
and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein
X1 and X2 are S and N respectively;
R1, R2 and R3 are each independently selected from the group consisting of: H, alkyl, aryl, aralkyl, halogen, NO2, CN, OH, alkoxy, aryloxy, NH2, NHCOR′, NHCOR′, NH-aryl, NH—R′, N—(R′)(R″), COOH, COO—R′, CONH2, CONH—R′, CON—(R′)(R″), SO3H, SO2NH2, CF3, and CO—R′ wherein alkyl, aryl, NH-aryl and aralkyl groups may be further substituted with one or more groups selected from halogen, NO2, CN, OH, O-methyl, NH2, COOH, CONH2 and CF3;
Z is selected from the group consisting of: NH, NHSO2 and NHCH2;
R4, R5, R6, R7, and R8 are each independently selected from the group consisting of: H, OH, halogen, nitro, amino, alkoxy, carbamoyl, sulfamyl, C1-4 alkyl, substituted C1-4 alkyl, COOH, COOR′, CN, CF3, (CH2)nO(CH2)mNR′R″, alkyl-aryl, alkyl-heteroaryl, NH(C═NH)NH2, N(R′)3−, N(R′)(R″) and (CH2)nCO2(CH2)mOR′″.

### Claim 3 (depends on 1)

A compound according to claim 1, wherein X1 and X2 are S and N respectively.

### Claim 4 (depends on 1, 2)

A compound according to claim 1, 2, or 3, wherein Z is NH and R3 is H.

### Claim 5 (depends on 1, 2)

A compound according to claim 1, 2, or 3, wherein R1 and R2 are each independently one or more of halogen, a C1-4 alkyl group, H, aryl, heterocycle or NH(R′).

### Claim 6 (depends on 5)

A compound according to claim 5, wherein R1 and R2 are chloro or methyl.

### Claim 7 (depends on 1, 2)

A compound according to claim 1, 2, or 3, wherein R3 is selected from the group consisting of: H, aryl, substituted aryl, halogen, C1-4 alkoxy and OH.

### Claim 8 (depends on 1, 2)

A compound according to claim 1, 2, or 3, wherein R4, R5, R6, R7, and R8 are selected independently from the group consisting of: F, NH2, NO2, OH, Cl, Br, I, CF3, OMe, COOH, COOR′, CN, H, C1-4 alkyl, C1-4 alkoxy, CH2CO2CH2CH2OMe, NH(C═NH)NH2, and CO2CH2CH2OMe, CH2OCH2CH2NEt2, CH2-heteroaryl, NMe3+, NMe2.

### Claim 9 (depends on 1)

A compound according to claim 1 selected from the group consisting of:
2-{N-(phenyl)}-4-(2,4-dimethylthiazol-5-yl)pyrimidineamines in which the phenyl group is 2-, 3- or 4-substituted by at least one of Me, F, NH2, NO2, OH, Cl, Br, I, CF3, OMe, CN, COOH, CH2OH, COOMe, COOEt, NH(C═NH)NH2, CH2CO2CH2CH2OMe, CH2-pyridyl, CH2OCH2CH2NEt2, CO2CH2CH2OMe, NMe3+ and NMe2.

### Claim 10 (depends on 9)

A compound according to claim 9, wherein the phenyl group is mono-substituted by F, NH2, NO2, OH, Cl, Br, I, CF3, OMe, CN, CH2OH, COOH, COOMe, COOEt, CH2CO2CH2CH2OMe or CO2CH2CH2OMe at any of the 2, 3 or 4-positions, or di-substituted by 2,4-difluoro, 3,5-difluoro, 3,4-difluoro, 2,4-dichloro, 3,5-dichloro, 3,4-dichloro, 4-hydroxy-2-nitro, 4-hydroxy-3-nitro, 6-chloro-3-carboxy, 4-chloro-3-carboxy, 6-chloro-2-carboxy, 2-fluoro-4-iodo, 2-hydroxy-4-methoxy, 3-chloro-4-iodo, 3-chloro-4-hydroxy, 3-chloro-4-methyl, 3-chloro-4-methoxy, 4-fluoro-3-nitro, 6-chloro-3-methoxycarbonyl, 3-chloro-4-methoxcarbonyl, 3-chloro-4-ethoxcarbonyl, 2-hydroxy-4-methoxy, 2-chloro-5-methoxycarbonyl, 4-chloro-3-methoxycarbonyl, 6-chloro-3-(CO2CH2CH2OMe), 3-chloro-4-(CO2CH2CH2OMe), 4-chloro-3-trifluoromethyl, or 3-(CO2CH2CH2OMe)-4-fluoro.

### Claim 11 (depends on 9)

A compound according to claim 9 wherein for group (a) the phenyl group is monosubstituted by Br, I or CF3.

### Claim 12 (depends on 1)

A compound according to claim 1 selected from the group consisting of
(2-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-nitro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-nitro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-fluoro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
(2,4-Difluoro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3,5-Difluoro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3,5-Dichloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(2,4-Dichloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-trifluoromethyl-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-trifluoromethyl-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-trifluoromethyl-phenyl)-amine,
(2-Bromo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Bromo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Bromo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-iodo-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-iodo-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-iodo-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-pyridin-2-yl-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-fluoro-phenyl)-amine,
(3,4-Difluoro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-methoxy-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-methoxy-phenyl)-amine,
3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-3-nitro-benzenesulfonamide,
4-Chloro-N-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-benzenesulfonamide,
N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-4-fluoro-benzenesulfonamide,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-2-nitro-phenol,
N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-4-nitro-benzenesulfonamide,
N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-benzene-1,3-diamine,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzonitrile,
3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzonitrile,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
(3-Chloro-4-methyl-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Chloro-4-methoxy-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid,
{4-Bromo-6-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-6-phenyl-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-6-phenyl-pyrimidin-2-ylamino}-phenol,
(3,4-Difluoro-phenyl)-{4-(4-methyl-2-phenyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(4-Methyl-2-phenyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
{4-(2,4-Dimethyl-thiazol-5-yl)-6-phenyl-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
(4-Fluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
{4-(2,4-Dimethyl-thiazol-5-yl)-6-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
(4-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-6-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl}-amine,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-6-(4-trifluoromethyl-phenyl)-pyrimidin-2-ylamino}-2-nitro-phenol,
(4-Fluoro-phenyl)-{4-(4-methyl-2-pyridin-3-yl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-6-(3-trifluoromethyl-phenyl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
4-{6-(2,4-Dimethyl-thiazol-5-yl)-2-(4-fluoro-phenylamino)-pyrimidin-4-yl}-2,6-dimethoxy-phenol,
4-{6-(2,4-Dimethyl-thiazol-5-yl)-2-(4-fluoro-phenylamino)-pyrimidin-4-yl}-phenol,
{4-(4-Methyl-2-pyridin-3-yl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
(4-Iodo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{2-Amino-6-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-4-yl}-2,6-dimethoxy-phenol,
4-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-2-nitro-phenol,
2-Chloro-4-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
{4-(2-Ethylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
{4-(4Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
3-{4-(2-Ethylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
2-Chloro-4-{4-(2-ethylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
4-Chloro-3-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid 2-methoxy-ethyl ester,
2-Chloro-4-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid 2-methoxy-ethyl ester,
4-Chloro-3-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid,
2-Chloro-5-{3-(2,4-dimethyl-thiazol-5-yl)-phenylamino}-benzoic acid,
{4-(2-Allylamino-4-methylthiazol-5-yl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
(3-Bromo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2-Allylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
3-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
(4-Bromo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Chloro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Methoxy-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(4-trifluoromethyl-phenyl)-amine,
{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3trifluoromethyl-phenyl)-amine,
{4-(2-Allylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
2-Chloro-5-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
3-Chloro-2-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-fluoro-4-iodo-phenyl)-amine,
2-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-5-methoxy-phenol,
(3-Chloro-4-iodo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
2-Chloro-4-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
5-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-2-fluoro-benzoic acid 2-methoxy-ethyl ester,
2-Chloro-5-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
4-Chloro-3-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
2-Chloro-4-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
(3-Iodo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Fluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3,4-Difluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(2,4-Difluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3,5-Difluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Chloro-3-trifluoromethyl-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Chloro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Methoxy-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Fluoro-3-nitro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-{2-(4-Nitro-phenylamino)-thiazol-5-yl}-pyrimidin-2-ylamino}-phenol,
N-{5-{2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl}-4-methyl-thiazol-2-yl}-acetamide,
(4-Fluoro-phenyl)-{4-{2-(4-nitro-phenylamino)-thiazol-5-yl}-pyrimidin-2-yl}-amine,
4-{4-(2-Amino-4-methyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
N-{3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenyl}-guanidine,
{3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenyl}-methanol,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-pyridin-4-ylmethyl-phenyl)-amine,
{3-(2-Diethylamino-ethoxymethyl)-phenyl}-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
N,N-Dimethyl-N′-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-benzene-1,4-diamine, and
{4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenyl}-trimethyl-ammonium.

### Claim 13 (depends on 1)

A compound according to claim 1 selected from the group consisting of:
(4-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-nitro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-fluoro-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
(2,4-Difluoro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3,5-Difluoro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-trifluoromethyl-phenyl)-amine,
(3-Bromo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Bromo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-iodo-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-fluoro-phenyl)-amine,
(3,4-Difluoro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-methoxy-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-methoxy-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-methoxy-phenyl)-amine,
3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-2-nitro-phenol,
N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-benzene-1,3-diamine,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzonitrile,
3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzonitrile,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
(3-Chloro-4-methyl-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Chloro-4-methoxy-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid,
{4-Bromo-6-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
4-{4-(4-Methyl-2-phenyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
(4-Fluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
(4-Iodo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-2-nitro-phenol,
2-Chloro-4-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
{4-(2-Ethylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
{4-(2-Allylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-fluoro-phenyl)-amine,
(3-Bromo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2-Allylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
3-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol,
(4-Bromo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Chloro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Methoxy-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(4-trifluoromethyl-phenyl)-amine,
{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3-trifluoromethyl-phenyl)-amine,
5-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-2-fluoro-benzoic acid 2-methoxy-ethyl ester,
2-Chloro-5-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
(3,5-Difluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Chloro-3-trifluoromethyl-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3-Chloro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Methoxy-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
2-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-5-methoxy-phenol,
(3-Fluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(3,4-Difluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine,
N-{3-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenyl}-guanidine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-pyridin-4-ylmethyl-phenyl)-amine,
N,N-Dimethyl-N′-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-benzene-1,4-diamine, and
{4-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenyl}-trimethyl-ammonium.

### Claim 14 (depends on 1)

A compound according to claim 1 selected from the following:
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-trifluoromethyl-phenyl)-amine,
(4-Bromo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol, and
(4-Fluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine.

### Claim 15 (depends on 1)

A compound according to claim 1 selected from the group consisting of:
(3,5-Dichloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(2,4-Dichloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(3-trifluoromethyl-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-trifluoromethyl-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-iodo-phenyl)-amine,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-iodo-phenyl)-amine,
N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-3-nitro-benzenesulfonamide,
{4-(2,4-Dimethyl-thiazol-5-yl)-6-phenyl-pyrimidin-2-yl}-(3-nitro-phenyl)-amine,
(3,4-Difluoro-phenyl)-{4-(4-methyl-2-phenyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
(4-Chloro-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-6-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl}-amine,
4-{6-(2,4-Dimethyl-thiazol-5-yl)-2-(4-fluoro-phenylamino)-pyrimidin-4-yl}-2,6-dimethoxy-phenol,
4-{6-(2,4-Dimethyl-thiazol-5-yl)-2-(4-fluoro-phenylamino)-pyrimidin-4-yl}-phenol,
2-Chloro-5-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
3-Chloro-2-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid ethyl ester,
{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(2-fluoro-4-iodo-phenyl)-amine,
(3-Chloro-4-iodo-phenyl)-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-amine,
4-Chloro-3-{4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino}-benzoic acid methyl ester,
(3-Iodo-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine, and
(2,4-Difluoro-phenyl)-{4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-amine.

### Claim 16 (depends on 1)

The compound of claim 1 that is {4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-(4-iodo-phenyl)-amine.

### Claim 17 (depends on 1)

The compound of claim 1, wherein said compound is selected from the group consisting of 2-{N-(phenyl)}-4-(4-methyl-2-methylamino-thiazol-5-yl)pyrimidineamines in which the phenyl group is 2-, 3- or 4-substituted by at least one of F, OH, I, NO2, Cl, COOR′, Br, OMe or CF3.

### Claim 18 (depends on 17)

The compound of claim 17, wherein the phenyl group is mono-substituted by chloro, bromo, iodo, fluoro, OH, nitro, CF3 or OMe at any of the 2, 3 or 4 positions, or disubstituted by 4-hydroxy-3-nitro, 3-chloro-4-ethoxycarbonyl, 3,4-difluoro, 2,4-difluoro, 4-chloro-3-trifluoromethyl or 4-fluoro-3-nitro.

### Claim 19 (depends on 1, 2)

Pharmaceutical compositions comprising a compound as defined in claims 1, 2, or 3 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable excipient.

### Claim 20 (depends on 1, 2)

A method of treating a CDK dependent or sensitive disorder in a subject, comprising administering to the subject one or more compounds of claims 1, 2, or 3 or pharmaceutically acceptable salts thereof to the subject, thereby treating the CDK dependent or sensitive disorder in the subject, and wherein said compounds are administered in an amount sufficient to inhibit at least one CDK enzyme.

### Claim 21 (depends on 20)

The method of claim 20, wherein the CDK dependent or sensitive disorder is cancer or leukemia.

### Claim 22 (depends on 20)

The method of claim 20, wherein the CDK enzyme is CDK2or CDK4.

### Claim 23 (depends on 21)

The method of claim 21, wherein the CDK enzyme is CDK2or CDK4.