Indolinone analogues

Patent metadata

Field	Value
Publication number	US-9102684-B2
Application number	US-201414225484-A
Country	US
Kind code	B2
Filing date	Mar 26, 2014
Priority date	Mar 27, 2013
Publication date	Aug 11, 2015
Grant date	Aug 11, 2015

Abstract

The present invention encompasses compounds of general formula (I)

wherein the groups R 1 to R 4 , A 1 and A 2 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein,
A 1 is selected from —C═O and —NR 5 ;
A 2 is selected from —O—, —C═O and —NR 6 ;
R 1 is —H, —OH or —C 1-3 alkyl;
R 2 is selected from phenyl, —C 5-8 cycloalkyl, 5-6 membered heteroaryl, 6 to 9 membered heterocycle optionally and independently substituted with one or more R 7 ;
R 3 is —H, —C 1-3 alkyl or —O—C 1-3 alkyl;
R 4 is —H or —C 1-3 alkyl;
R 5 is —H, —C 1-3 alkyl or 6 membered heteroaryl;
R 6 is —C 1-3 alkyl, optionally substituted with —N(—C 1-3 alkyl) 2 , or R 6 is 6 membered heterocycle;
or R 1 and R 6 taken together form a 5-6 membered heterocycloalkyl;
R 7 is selected from halogen, —O—C 1-3 alkyl, —C 1-3 alkyl, which —C 1-3 alkyl can be optionally substituted with morpholine;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein A 1 is —C═O and A 2 is NR 6 , wherein R 6 is —CH 3 , —CH(CH 3 ) 2 , —(CH 2 ) 2 —N(CH 3 ) 2 , —(CH 2 ) 3 —N(CH 3 ) 2 —N-methyl-piperidinyl.

3. The compound according to claim 1 wherein A 1 is NR 5 and A 2 is —C═O, wherein R 5 is —H, —CH 3 or pyridyl.

4. The compound according to claim 1 wherein A 1 is NR 5 and A 2 is —O—.

5. The compound according to claim 1 , wherein R 1 is —H, —OH, —CH 3 .

6. The compound according to claim 1 , wherein R 2 is phenyl, optionally substituted with one or more independently selected halogen, —CH 3 , —O—CH 3 and —CH 2 -morpholine.

7. The compound according to claim 1 , wherein R 2 is cyclopentyl, cyclohexyl or spiro[3.5]nonane.

8. The compound according to claim 1 , wherein R 2 is thiophenyl or pyridyl, optionally substituted with —CH 3 or tetrahydrofuran.

9. The compound according to claim 1 , wherein R 3 is —CH 3 or —OCH 3 .

10. The compound according to claim 1 , wherein R 4 is —H or —CH 3 .

11. The compound according to claim 1 , wherein R 5 is —H, —CH 3 or pyridyl.

12. The compound according claim 1 , wherein A 1 is —C═O and A 2 is NR 6 , R 6 and R 1 taken together form a oxazolidine or [1,3]oxazine.

13. A compound selected from

EX#
Structure

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Assignees

• Engelhardt Harald
• Gianni Davide
• Mantoulidis Andreas
• Smethurst Christian
• Boehringer Ingelheim Int

Inventors

• Engelhardt Harald
• Gianni Davide
• Mantoulidis Andreas
• Smethurst Christian

Classifications

• C07D413/14

  containing three or more hetero rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D413/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P43/00

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

• C07D498/04 Primary

  Ortho-condensed systems · CPC title