Compounds for the treatment of mycobacterial infections

Patent metadata

Field	Value
Publication number	US-10766872-B2
Application number	US-201715610545-A
Country	US
Kind code	B2
Filing date	May 31, 2017
Priority date	Sep 29, 2011
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

First claim

What is claimed is:

1. A compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is selected from the group consisting of phenyl, substituted phenyl, pyridinyl, and substituted pyridinyl;
R 3 is hydrogen, substituted C 1 -C 8 alkyl, or unsubstituted C 1 -C 8 alkyl;
R 4 is hydrogen, substituted C 1 -C 8 alkyl, or unsubstituted C 1 -C 8 alkyl;
R 2 is

R 6 and R 7 are each independently selected from the group consisting of hydrogen and unsubstituted C 1 -C 8 alkyl;
R 5 is selected from the group consisting of

R 100 and R 100 ′ are each independently hydrogen or unsubstituted C 1 -C 8 alkyl;
R 101 and R 102 are each independently hydrogen or unsubstituted C 1 -C 8 alkyl;
wherein the term “substituted” refers to the replacement of one or more hydrogen radicals in a given structure with the radical selected from halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxy, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, and aralkoxycarbonyl.

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

3. The compound according to claim 1 , wherein R 5 is selected from

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein R 3 is unsubstituted C 1 -C 8 alkyl, and R 4 is unsubstituted C 1 -C 8 alkyl.

5. The compound according to claim 1 selected from Table A or a pharmaceutically acceptable salt thereof:

TABLE A

No.
Structure

 1

  5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-4-phenyl-2H- chromen-2-one

 2

  5,7-dimethyl-4-phenyl-6-(4-(piperidin-1-ylmethyl)phenyl)-2H- chromen-2-one

 3

  6-(4-((cyclohexylamino)methyl)phenyl)-5,7-dimethyl-4-phenyl- 2H-chromen-2-one

 4

  5,7-dimethyl-6-(4-((hexylamino)methyl)phenyl)-4-phenyl-2H- chromen-2-one

 5

  5,7-dimethyl-6-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-4- phenyl-2H-chromen-2-one

 6

  4-(3-aminophenyl)-5,7-dimethyl-6-(4- (morpholinomethyl)phenyl)-2H-chromen-2-one hydrochloride

 7

  4-(4-aminophenyl)-5,7-dimethyl-6-(4- (morpholinomethyl)phenyl)-2H-chromen-2-one

 8

  5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-4-(3-nitrophenyl)- 2H-chromen-2-one

 9

  methyl 3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo- 2H-chromen-4-yl)benzoate

10

  N-(3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo-2H- chromen-4-yl)phenyl)acetamide

11

  N-(3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo-2H- chromen-4-yl)phenyl)methanesulfonamide

12

  ethyl (3-(5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2-oxo- 2H-chromen-4-yl)phenyl)carbamate

13

  5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-4-(pyridin-3-yl)- 2H-chromen-2-one

43

44

6. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

7. The compound of claim 3 , wherein R 5 is:

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 3 , wherein R 100 is hydrogen, or a pharmaceutically acceptable salt thereof.

9. The compound of claim 4 , wherein R 3 is unsubstituted C 1 -C 3 alkyl, and R 4 is unsubstituted C 1 -C 3 alkyl, or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 , wherein R 3 is methyl and R 4 is methyl, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 5 , or a pharmaceutically acceptable salt thereof.

Assignees

• Broad Inst Inc
• Massachusetts Gen Hospital
• The Board Inst Inc

Inventors

• Hung Deborah
• Stanley Sarah
• Kawate Tomohiko
• Iwase Noriakie
• Shimizu Motohisa

Classifications

• C07D311/18

  substituted otherwise than in position 3 or 7 · CPC title

• C07D405/04

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

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/37

  Coumarins, e.g. psoralen · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title