6-Alkynyl Pyridine

Patent metadata

Field	Value
Publication number	US-9278978-B2
Application number	US-201414463692-A
Country	US
Kind code	B2
Filing date	Aug 20, 2014
Priority date	Aug 23, 2013
Publication date	Mar 8, 2016
Grant date	Mar 8, 2016

Abstract

This invention relates to 6-alkynyl-pyridine 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 5 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 —C 1-3 alkyl, —C 1-3 haloalkyl or —H;
R 2 is —C 1-3 alkyl or —H;
R 2a is —C 1-3 alkyl or —H;
R 3 is phenyl or 5-12 membered heteroaryl, each of which is optionally substituted with one or more independently selected R 6 groups, or
R 3 is 8-12 membered aromatic heterocyclyl, optionally substituted with one or more moieties independently selected from the group consisting of ═O and R 6 ;
R 4 is phenyl or 5-12 membered heteroaryl, each of which is optionally substituted with one or more independently selected R 7 groups, or
R 4 is 8-12 membered aromatic heterocyclyl, optionally substituted with one or more moieties independently selected from the group consisting of ═O and R 7 ;
R 5 is —H, halogen, —O—C 1-3 alkyl or 5-6 membered heteroaryl;
R 6 is halogen, —C 1-3 alkyl, —O—C 1-3 alkyl, cyano, or 5-6 membered heteroaryl, wherein the heteroaryl group is optionally substituted with —C 1-3 alkyl, —O—C 1-3 alkyl or halogen; and
R 7 is halogen, —C 1-3 alkyl, —C 1-3 haloalkyl and —O—C 1-3 alkyl or cyano;
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 to claim 1 , wherein R 3 is phenyl,

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

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

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

7. A compound according to claim 1 , wherein R 3 is phenyl,

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

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

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

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

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

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

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

11. A compound according to claim 1 , wherein R 5 is —H, —Cl, —O—CH 3 or pyrimidinyl.

12. A compound according to claim 11 , wherein R 5 is —H.

13. A compound according to claim 1 , wherein R 3 is substituted with ═O or R 6 , wherein R 6 is —F, —CH 3 , —O—CH 3 , or

which imidazole is optionally substituted with —CH 3 .

14. A compound according to claim 1 , wherein R 4 is substituted with ═O or R 7 , wherein R 7 is —F, —CH 3 or —O—CH 3 .

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

EX

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Structure
Ex #
Structure

 1

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 5

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 9

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11

12

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Assignees

• Reiser Ulrich
• Madden James
• Boehringer Ingelheim Int

Inventors

• Reiser Ulrich
• Madden James

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

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

• A61P31/10

  Antimycotics · CPC title

• A61P29/00

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