IP Library › Granted Patent US 6,958,348

Granted Patent B2

US 6,958,348 · App. 10/232,394 · Granted Oct 25, 2005

3-glyoxylamideindoles for treating cancer

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Quick Facts

Patent No.: US 6,958,348
App. No.: 10/232,394
Granted: Oct 25, 2005
Kind: B2

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Abstract

Disclosed is an anti-cancer compound represented by Structural Formula (I): The variables in Structural Formula (I) are described hereinbelow. Also disclosed is a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by Structural Formula (I) (preferably an effective amount). Also disclosed is a method of treating a subject with cancer by administering to the subject an effective amount of a compound represented by Structural Formula (I).

Claims (73)

1. A compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is substituted or unsubstituted and is optionally fused to an aryl group;

Z 1 and Z 2 are independently ═O, ═S, ═N—OR 9 or ═NR 9 ;

R 4 is —H, a substituted alkyl group or an unsubstituted alkyl group;

R 9 is —H or a substituted or unsubstituted alkyl group;

each R 15 is independently —Br, —Cl, —F, —R 18 , —OR 18 , —CN, —COOR 18 , —N(R 18 ) 2 , —CON(R 18 ) 2 , —NR 18 COR 19 , —NHCONH 2 or —SO 2 N(R 18 ) 2 ;

n is an integer from 1-4;

R 16 and R 17 are independently —H, an aliphatic group, a substituted aliphatic group, an unsubstituted non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic group, an unsubstituted carbocyclic aryl group, a substituted carbocyclic aryl group; a substituted or unsubstituted imidazolyl, a substituted or unsubstituted isoimidazolyl, a substituted or unsubstituted thienyl, a substituted or unsubstituted furanyl, a substituted or unsubstituted pyridyl, a substituted or unsubstituted pyranyl, a substituted or unsubstituted pyrrolyl, a substituted or unsubstituted pyrazinyl, a substituted or unsubstituted isothiazolyl, a substituted or unsubstituted oxazolyl, a substituted or unsubstituted isoxazolyl, a substituted or unsubstituted 1,2,3-triazolyl, a substituted or unsubstituted 1,2,4-triazolyl, a substituted or unsubstituted tetrazolyl, a substituted or unsubstituted benzothienyl, a substituted or unsubstituted benzofuranyl, a substituted or unsubstituted indolyl, a substituted or unsubstituted quinolinyl, a substituted or unsubstituted benzothiazolyl, a substituted or unsubstituted benzoisothiazolyl, a substituted or unsubstituted benzoxazolyl, a substituted or unsubstituted benzoisoxazolyl, a substituted or unsubstituted benzoimidazolyl, a substituted or unsubstituted quinolinyl, a substituted or unsubstituted isoquinolinyl or a substituted or unsubstituted isoindolyl; or —NR 16 R 17 , taken together, is a substituted or unsubstituted non-aromatic nitrogen-containing heterocyclic group or a substituted or unsubstituted nitrogen-containing heteroaryl group; and

R 18 and R 19 are independently —H, alkyl or substituted alkyl.

2. The compound of claim 1 wherein:

Ring A is substituted or unsubstituted;

Z 1 and Z 2 are ═O;

R 4 is —H;

each R 15 is independently —Cl, —F, —R 18 , —OR 18 , —CN, —NH 2 , —CONH 2 or —NHCOR 18 ;

n is 0 or 1;

R 16 is —H;

R 17 is a substituted or unsubstituted aryl group; and

R 18 is a C1-C4 alkyl group.

3. The compound of claim 2 wherein:

Ring A is substituted with zero, one or more groups selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN and —NH 2 ; and

R 17 is a substituted or unsubstituted phenyl, quinolinyl, or pyridyl group.

4. The compound of claim 3 wherein n is 0; and R 17 is pyridyl.

5. The compound of claim 4 wherein R 17 is 4-pyridyl.

6. A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of a compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is substituted or unsubstituted and is optionally fused to an aryl group;

Z 1 and Z 2 are independently ═O, ═S, ═N—OR 9 or ═NR 9 ;

R 4 is —H, a substituted alkyl group or an unsubstituted alkyl group;

R 9 is —H or a substituted or unsubstituted alkyl group;

each R 15 is independently —Br, —Cl, —F, —R 18 , —OR 18 , —CN, —COOR 18 , —N(R 18 ) 2 , —CON(R 18 ) 2 , —NR 18 COR 19 , —NHCONH 2 and —SO 2 N(R 18 ) 2 ;

n is an integer from 1-4;

R 18 and R 19 are independently —H, alkyl or substituted alkyl, wherein the cancer is human breast cancer, human myeloid leukemia, human uterine sarcoma, human prostate cancer, human leukemia, or a multidrug resistant strain thereof.

7. The method of claim 6 wherein:

Ring A is substituted or unsubstituted;

Z 1 and Z 2 are ═O;

R 4 is —H;

each R 15 is independently —Cl, —F, —R 18 , —OR 18 , —CN, —NH 2 , —CONH 2 or —NHCOR 18 ;

n is 0 or 1;

R 16 is —H;

R 17 is a substituted or unsubstituted aryl group; and

R 18 is a C1-C4 alkyl group.

8. The method of claim 7 wherein:

Ring A is substituted with zero, one or more groups selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN and —NH 2 ; and

R 17 is a substituted or unsubstituted phenyl, quinolinyl, or pyridyl group.

9. The method of claim 8 wherein n is 0; and R 17 is pyridyl.

10. The method of claim 9 wherein R 17 is 4-pyridyl.

11. The method of claim 6 wherein the cancer is multi-drug resistant.

12. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is substituted or unsubstituted and is optionally fused to an aryl group;

Z 1 and Z 2 are independently ═O, ═S, ═N—OR 9 or ═NR 9 ;

R 4 is —H, a substituted alkyl group or an unsubstituted alkyl group;

R 9 is —H or a substituted or unsubstituted alkyl group;

each R 15 is independently —Br, —Cl, —F, —R 18 , —OR 18 , —CN, —COOR 18 , —N(R 18 ) 2 , —CON(R 18 ) 2 , —NR 18 COR 19 , —NHCONH 2 or —SO 2 N(R 18 ) 2 ;

n is an integer from 1-4;

R 18 and R 19 are independently —H, alkyl or substituted alkyl.

13. The composition of claim 12 wherein:

Ring A is substituted or unsubstituted;

Z 1 and Z 2 are ═O;

R 4 is —H;

each R 15 is independently —Cl, —F, —R 18 , —OR 18 , —CN, —NH 2 , —CONH 2 or —NHCOR 18 ;

n is 0 or 1;

R 16 is —H;

R 17 is a substituted or unsubstituted aryl group; and

R 18 is a C1-C4 alkyl group.

14. The composition of claim 13 wherein:

Ring A is substituted with zero, one or more groups selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN and —NH 2 ; and

R 17 is a substituted or unsubstituted phenyl, quinolinyl, or pyridyl group.

15. The composition of claim 14 wherein n is 0; and R 17 is pyridyl.

16. The composition of claim 15 wherein R 17 is 4-pyridyl.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 14, 2003

From: KOYA, KEIZO; SUN, LIJUN; ONO, MITSUNORI; LIANG, GUIQING; JAMES, DAVID; LI, HAO; XIA, ZHI-QIANG

To: SYNTA PHARMACEUTICALS CORP.

Reel/Frame 013754/0894 →