Substituted indazole derivatives active as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9029356-B2
Application number	US-201414212256-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Jul 20, 2007
Publication date	May 12, 2015
Grant date	May 12, 2015

Abstract

Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.

First claim

The invention claimed is:

1. A compound of formula (Ia),

wherein:
R is aryl substituted with one or more halogen;
R1, R2 and R3 are hydrogen;
Ar is aryl substituted with one or more NR5R6; and
R5 and R6 are independently selected from hydrogen and optionally substituted heterocyclyl, or R5 and R6, taken together with the nitrogen atom to which they are bonded, form an optionally substituted heterocyclyl group;
or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein:
R is phenyl substituted with one or more halogen; and
Ar is phenyl substituted with one or more NR5R6, wherein R5 and R6 are as defined in claim 3 ;
or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2 , wherein R is phenyl substituted with one or more fluoro, or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 2 , wherein:
Ar is phenyl substituted with NH(heterocyclyl) and NR5R6; and
R5 and R6, together with the nitrogen atom to which they are bonded, form an optionally substituted heterocyclyl group;
or a pharmaceutically acceptable salt thereof.

5. A compound according to 4 , wherein R is phenyl substituted with one or more fluoro, or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 5 , wherein R is difluorophenyl, or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 6 , wherein R is 3,5-difluorophenyl, or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 4 , wherein
R is phenyl substituted with one or more fluoro; and
Ar is phenyl substituted with NH(tetrahydropyran-4-yl) and NR5R6, wherein NR5R6 form an optionally substituted piperazin-1-yl group;
or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 1 , wherein:
R is difluorophenyl; and
Ar is phenyl substituted with NH(tetrahydropyran-4-yl) and NR5R6, wherein NR5R6 form an optionally substituted piperazin- 1 -yl group;
or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 9 , wherein said NR5R6 form a piperazin- 1-yl group that is substituted with C 1 -C 6 alkyl, or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 10 , wherein said NR5R6 form a 4-(C 1 -C 6 alkyl)-piperazin-1-yl group, or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 9 , wherein R is 3,5-difluorophenyl, or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 10 , wherein R is 3,5-difluorophenyl, or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 11 , wherein R is 3,5-difluorophenyl, or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, carrier or diluent.

Assignees

• Nerviano Medical Services S R L
• Nerviano Medical Sciences Srl

Inventors

• Lombardi Borgia Andrea
• Menichincheri Maria
• Orsini Paolo
• Panzeri Achille
• Perrone Ettore
• Vanotti Ermes
• Nesi Marcella
• Marchionni Chiara

Classifications

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title