Compounds for the treatment of mycobacterial infections

Patent metadata

Field	Value
Publication number	US-9682064-B2
Application number	US-201615215895-A
Country	US
Kind code	B2
Filing date	Jul 21, 2016
Priority date	Sep 29, 2011
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

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 method of treating bacterial infection in a patient in need thereof comprising the step of administering to the patient an effective amount of 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 selected from hydrogen substituted C 1 -C 8 , and 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

and
R 100 and R 100 ′ are each independently hydrogen, unsubstituted C 1 -C 8 alkyl, or substituted C 1 -C 8 alkyl.

2. The method according to claim 1 , wherein, R 1 is substituted phenyl or unsubstituted phenyl.

3. The method according to claim 1 , wherein said Compound of Formula I is selected from the group consisting of:
4-(3-aminophenyl)-5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2H-chromen-2-one; and,
4-phenyl-5,7-dimethyl-6-(4-(morpholinomethyl)phenyl)-2H-chromen-2-one; or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein R 5 is:

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

6. The method of claim 5 , wherein R 3 and R 4 are each methyl.

7. The method according to claim 1 , wherein said compound of Formula I is 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

8. The method of claim 1 , wherein said bacterial infection is mycobacterial infection.

9. The method of claim 8 , wherein the patient is suffering from tuberculosis.

Assignees

• Broad Inst Inc
• Massachusetts Gen Hospital

Inventors

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

Classifications

• A61K31/5377

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

• A61K31/37 Primary

  Coumarins, e.g. psoralen · CPC title

• A61K31/453

  containing a six-membered ring with oxygen as a ring hetero atom · CPC title

• A61K31/496

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

• C07D405/04

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