Bis-amido pyridines

Patent metadata

Field	Value
Publication number	US-9249151-B2
Application number	US-201414463690-A
Country	US
Kind code	B2
Filing date	Aug 20, 2014
Priority date	Aug 23, 2013
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

Abstract

This invention relates to bis-amido pyridines of general formula (I)

their use as SMAC mimetics, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer.

The groups R 1 to R 4 have the meanings given in the claims and in the specification.

First claim

The invention claimed is:

1. A compound of the formula (I)

wherein,
R 1 is —CH 3 , —CH 2 CH 3 , —C 1-3 haloalkyl or —H;
R 2 is —H or —C 1-3 alkyl;
R 2a is —H or —C 1-3 alkyl;
R 3 is benzyl, phenyl or 5-12 membered heteroaryl, each of which groups is optionally substituted with one or more independently selected R 5 groups, or
R 3 is 8-12 membered aromatic heterocyclyl, which is optionally substituted with one or more moieties independently selected from the group consisting of ═O and R 5 ;
R 4 is —H, halogen, phenyl, naphthyl or 5-12 membered heteroaryl, each of which groups is optionally substituted with one or more independently selected R 6 groups, or
R 4 is 8-12 membered aromatic heterocyclyl, which heterocyclyl is optionally substituted with one or more moieties independently selected from the group consisting of ═O and R 6 ;
R 5 is halogen, —CN, —C 1-3 alkyl or —O—C 1-5 alkyl; and
R 6 is halogen, —CN, —NH 2 , —C 1-3 alkyl, —C 1-3 haloalkyl or —O—C 1-3 alkyl;
or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein R 1 is —CH 3 or —CH 2 CH 3 .

3. A compound according to claim 1 , wherein R 2 is —CH 3 or —CH 2 CH 3 .

4. A compound according to claim 1 , wherein R 2a is —H.

5. A compound according claim 1 , wherein R 3 is 5-12 membered heteroaryl, optionally substituted with one or more independently selected R 5 groups.

6. A compound according to claim 1 , wherein R 3 is pyridyl, pyrimidinyl,

each of which groups is optionally substituted as defined in claim 1 .

7. A compound according to claim 6 , wherein R 3 is pyridyl or

each of which group is optionally substituted as defined in claim 1 .

8. A compound according to claim 1 , wherein R 4 is 5-12 membered heteroaryl, optionally substituted with one or more independently selected R 6 groups.

9. A compound according to claim 1 , wherein R 4 is —Cl, pyridyl, pyrimidinyl,

each of which group is optionally substituted with one or more substituents as defined in claim 1 .

10. A compound according to claim 1 , wherein R 4 is pyridyl,

each of which groups is optionally substituted as defined in claim 1 .

11. A compound according to claim 1 , wherein R 4 is

each of which groups is optionally and independently substituted as defined in claim 1 .

12. A compound according to claim 1 , wherein R 5 —CN, —F, —Cl, —CH 3 or —O—CH 3 .

13. A compound according to claim 1 , wherein R 4 is substituted with one or more substituents selected from ═O and R 6 , wherein R 6 is —CN, —F, —Cl, —NH 2 , —CH 3 or —O—CH 3 .

14. A compound according to claim 1 selected from the group consisting of

EX #
Structure

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Assignees

• Reiser Ulrich
• Boehringer Ingelheim Int

Inventors

• Reiser Ulrich

Classifications

• A61P43/00

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

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P35/02

  specific for leukemia · CPC title