Pyridone derivatives and uses thereof in the treatment of tuberculosis

Patent metadata

Field	Value
Publication number	US-9546138-B2
Application number	US-201314648217-A
Country	US
Kind code	B2
Filing date	Dec 12, 2013
Priority date	Dec 13, 2012
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

A compound of Formula (I) is provided that has been shown to be useful for treating a disease, disorder or syndrome that is mediated by the inhibition of mycolic acid biosynthesis through inhibition of M. tuberculosis Enoyl Acyl Carrier Protein Reductase enzyme (InhA):

wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein.

First claim

What is claimed is:

1. A compound of Formula (I)

wherein
R 1 is H, methyl or ethyl;
R 2 is phenyl, wherein said phenyl is optionally substituted with one or more substituents independently selected from fluoro or chloro; provided that when said substituent is chloro, said chloro is on the meta or ortho position of said phenyl and the number of chloro substituent is not more than one;
R 3 is a structural formula selected from the group consisting of

where R 100 and R 200 are each independently selected from the group consisting of H, (C 1 -C 6 )alkyl, and cycloalkyl;
R 4 is H or —C(═O)NH 2 ;
R 5 is selected from the group consisting of (C 1 -C 6 )alkyl, cycloalkyl, and phenyl, optionally substituted with one or more independent R 300 substituents; and
R 300 is selected from the group consisting of H, (C 1 -C 6 )alkyl, cycloalkyl, hydroxy, amino and F;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is H.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is phenyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is (Ia).

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is (IC), and R 100 and R 200 are both H.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is H.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is (C 1 -C 6 )alkyl or phenyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is cycloalkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is cyclohexane.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is cyclohexane which is substituted with one or more substituents independently selected from (C 1 -C 6 )alkyl, cycloalkyl or F.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is cyclohexane which is substituted with one or more substituents independently selected from methyl, cyclopropane or F.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is cyclohexane which is substituted with two methyl substitutents.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound has the following structure

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound has the following structure

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound has the following structure

17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

Assignees

• Kondreddi Ravinder Reddy
• Ma Ngai Ling
• Peukert Stefan
• Rao Srinivasa P S
• Ujjini Manjunatha
• Novartis Ag

Inventors

• Kondreddi Ravinder Reddy
• Ma Ngai Ling
• Peukert Stefan
• Rao Srinivasa P S
• Ujjini Manjunatha

Classifications

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D401/04 Primary

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