1,3-Thiazole-5-Carboxamides Useful as Cancer Chemotherapeutic Agents

1 . A compound of formula (I)

wherein

Ar is selected from the group consisting of

X is CH or N;

R 1 is selected from the group consisting of

H,

halogen,

wherein

R 1-2 is selected from the group consisting of

H,

(C 1 -C 4 )alkyl,

wherein said (C 1 -C 4 )alkyl can be substituted with 0, 1, or 2 groups independently selected from hydroxy,

(C 1 -C 4 )alkylamino,

(C 1 -C 4 )acyloxy,

(C 1 -C 4 )alkoxy, and

(C 2 -C 4 )alkoxy substituted with 0, 1 or 2 (C 1 -C 4 )alkoxy groups,

5- or 6-membered heteroaryl,

and

phenyl substituted with 0, 1, or 2 groups independently selected from the group consisting of (C 1 -C 4 )alkyl, halo, nitro, (C 1 -C 4 )alkoxy and cyano,

and

wherein said (C 1 -C 4 )alkyl is independently optionally substituted with F up to the perfluoro level;

R 1-3 is H or (C 1 -C 4 )alkyl;

R 1-4 , R 1-5 and R 1-6 are selected from the group consisting of

H,

indan-5-yl,

phenyl substituted with 0, 1, or 2 groups independently selected from the group consisting of (C 1 -C 4 )alkyl, halo, nitro, (C 1 -C 4 )alkoxy and cyano,

5- or 6-membered heteroaryl substituted with 0, 1 or 2 groups selected from the group consisting of

cyano,

halo,

nitro,

(C 1 -C 4 )alkyl,

 wherein said (C 1 -C 4 )alkyl is optionally substituted with 0, 1, or 2 groups selected

 from

 (C 1 -C 4 )alkylamino,

 (C 1 -C 4 )acyloxy,

(C 1 -C 4 )alkoxy,

and

(C 2 -C 4 )alkoxy substituted with up to 0, 1 or 2 (C 1 -C 4 )alkoxy groups,

(C 3 -C 6 )cycloalkyl substituted with 0, 1 or 2 groups selected from (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, cyano, and halo,

and

(C 1 -C 6 )alkyl,

wherein said (C 1 -C 6 )alkyl is independently substituted with 0 or 1 group selected from the group consisting of

NH 2 ,

(C 1 -C 4 )alkoxy,

(C 2 -C 4 )alkoxy independently substituted with 0, 1, 2 or 3 (C 1 -C 4 )alkoxy and OH groups,

 and

 independently optionally substituted with fluorine up to the perfluoro level,

carboxyl,

(C 1 -C 4 )alkoxycarbonyl

(C 1 -C 4 )alkylamino,

aminocarbonyl,

(C 1 -C 4 )alkylsulfonyl,

phenyl substituted with 0, 1, or 2 groups independently selected from the group consisting of (C 1 -C 4 )alkyl, halo, nitro, (C 1 -C 4 )alkoxy and cyano, 5- or 6-membered heteroaryl independently substituted with 0, 1, 2 or 3 groups selected from the group consisting of (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy,

cyano, halo, and nitro

and

heterocyclyl independently substituted with 0, 1, 2 or 3 groups selected from the group consisting of (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, cyano, and halo,

and

wherein said (C 1 -C 6 )alkyl is independently substituted with 0, 1 or 2 OH or halo groups,

and

wherein said (C 1 -C 6 )alkyl is independently optionally substituted with F up to the perfluoro level;

and

R 1-3 and R 1-4 , R 1-3 and R 1-5 , and R 1-3 and R 1-6 , when attached to the same nitrogen atom, may form, together with the N atom to which they are attached, a 5- or 6-membered saturated heterocyclic ring selected from pyrrolidinyl, morpholinyl, thiomorpholinyl and piperizinyl optionally substituted on N with (C 1 -C 4 )alkyl,

R 1-7 is independently selected from the group consisting of (C 1 -C 4 )alkyl,

wherein said (C 1 -C 4 )alkyl is substituted with 0, 1 or 2 groups selected from the group consisting of

(C 1 -C 4 )alkylamino,

(C 1 -C 4 )acyloxy,

(C 1 -C 4 )alkoxy,

and

(C 2 -C 4 )alkoxy substituted with 0, 1 or 2

 (C 1 -C 4 )alkoxy groups;

or a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 , wherein

Ar is selected from the group consisting of

X is CH;

R 1 is selected from the group consisting of

and

wherein

R 1-3 is H or (C 1 -C 4 )alkyl,

R 1-5 and R 1-6 are selected from the group consisting of

H,

indan-5-yl,

phenyl substituted with 0, 1, or 2 groups independently selected from the group consisting of (C 1 -C 4 )alkyl, halo, nitro, (C 1 -C 4 )alkoxy and cyano,

5- or 6-membered heteroaryl substituted with 0, 1 or 2 groups selected from the group consisting of

cyano,

halo,

nitro,

(C 1 -C 4 )alkyl,

wherein said (C 1 -C 4 )alkyl is optionally substituted with 0, 1, or 2 groups selected from

(C 1 -C 4 )alkylamino,

(C 1 -C 4 )acyloxy,

(C 1 -C 4 )alkoxy,

and

(C 2 -C 4 )alkoxy substituted with up to 0, 1 or 2 (C 1 -C 4 )alkoxy groups;

(C 3 -C 6 )cycloalkyl substituted with 0, 1 or 2 groups selected from the group consisting of (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, cyano, and halo;

and

(C 1 -C 6 )alkyl,

wherein said (C 1 -C 6 )alkyl is independently substituted with 0 or 1 group selected from the group consisting of

NH 2 ,

(C 1 -C 4 )alkoxy,

(C 2 -C 4 )alkoxy independently substituted with 0, 1, 2 or 3 (C 1 -C 4 )alkoxy and OH groups,

and

independently optionally substituted with fluorine up to the perfluoro level,

carboxyl,

(C 1 -C 4 )alkoxycarbonyl

(C 1 -C 4 )alkylamino,

aminocarbonyl,

(C 1 -C 4 )alkylsulfonyl,

phenyl substituted with 0, 1, or 2 groups independently selected from the group consisting of (C 1 -C 4 )alkyl, halo, nitro, (C 1 -C 4 )alkoxy and cyano,

5- or 6-membered heteroaryl independently substituted with 0, 1, 2 or 3 groups selected from the group consisting of (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, cyano, halo, and nitro

and

heterocyclyl is independently substituted with 0, 1, 2 or 3 groups selected from the group consisting of (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, cyano, and halo,

and

wherein said (C 1 -C 6 )alkyl is independently substituted with 0, 1 or 2 OH or halo groups,

and

wherein said (C 1 -C 6 )alkyl is independently optionally substituted with F up to the perfluoro level;

and

R 1-3 and R 1-5 , and R 1-3 and R 1-6 , when attached to the same nitrogen atom, may form, together with the N atom to which they are attached, a 5- or 6-membered saturated heterocyclic ring selected from pyrrolidinyl, morpholinyl, thiomorpholinyl and piperizinyl optionally substituted on N with (C 1 -C 4 )alkyl;

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 , wherein

Ar is

X is CH;

R 1 is selected from

and

wherein

R 1-3 is H,

R 1-5 is (C 1 -C 6 )alkyl,

wherein said (C 1 -C 6 )alkyl is independently substituted with 0 or 1 group selected from

(C 1 -C 4 )alkoxy,

(C 2 -C 4 )alkoxy independently substituted with 0, 1, or 2 (C 1 -C 4 )alkoxy and OH groups,

and

independently optionally substituted with fluorine up to the perfluoro level,

and

wherein said (C 1 -C 6 )alkyl is independently substituted with 0, 1 or 2 OH or halo groups,

and

wherein said (C 1 -C 6 )alkyl is independently optionally substituted with F up to the perfluoro level;

R 1-6 is selected from the group

H,

and

(C 1 -C 6 )alkyl,

wherein said (C 1 -C 6 )alkyl is independently substituted with 0 or 1 group selected from

(C 1 -C 4 )alkoxy,

(C 2 -C 4 )alkoxy independently substituted with 0, 1, 2 or 3 (C 1 -C 4 )alkoxy and OH groups,

 and

 independently optionally substituted with fluorine up to the perfluoro level,

and

wherein said (C 1 -C 6 )alkyl is independently substituted with 0, 1 or 2 OH or halo groups,

and

wherein said (C 1 -C 6 )alkyl is independently optionally substituted with F up to the perfluoro level;

or a pharmaceutically acceptable salt thereof.

4 . A compound of claim 1 for the treatment or prevention of disorders.

5 . A pharmaceutical composition comprising the compound of claim 1 .

6 . The pharmaceutical composition of claim 5 , additionally comprising at least one pharmaceutically acceptable carrier or excipient.

7 . A pharmaceutical composition of claim 5 for the treatment or prevention of cancer.

8 . A process for preparing the pharmaceutical composition of claim 6 , comprising combining at least one compound according to claim 1 with at least one pharmaceutically acceptable carrier or excipient and bringing the resulting combination into a form suitable for said pharmaceutical composition.

9 . A use of a compound of claim 1 for manufacturing a pharmaceutical composition for the treatment or prevention of a disease.

10 . The use of claim 9 , wherein the disease is cancer.

11 . A method of treating a disease or condition in a mammal, comprising administering to a mammal in need thereof an effective amount of a compound of claim 1 .

12 . The method of claim 11 , wherein the disease or condition is cancer.