Compounds for the treatment of mycobacterial infections

Patent metadata

Field	Value
Publication number	US-RE48105-E
Application number	US-201816103823-A
Country	US
Kind code	E1
Filing date	Aug 14, 2018
Priority date	Sep 29, 2011
Publication date	Jul 21, 2020
Grant date	Jul 21, 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 Ia 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 or unsubstituted C 1 -C 8 alkyl;
R 4 is hydrogen or unsubstituted C 1 -C 8 alkyl;
R 2 is:

each R 6 , R 7 , R 10 and R 11 is independently selected from the group consisting of hydrogen and unsubstituted C 1 -C 8 alkyl;
m is 0;
R 5 is selected from the group consisting of:

R 100 is hydrogen or unsubstituted C 1 -C 8 alkyl; and
R 100 ′ is hydrogen or unsubstituted C 1 -C 8 alkyl;
wherein the substituted phenyl and the substituted pyridinyl are each independently substituted with one or more substituents independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl,-alkoxy alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl,-alkoxycarbonyl alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxy, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, and sulfonyl.

2. The compound of claim 1 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 of any of thereof.

3. The compound of claim 1 , wherein R 5 is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein R 3 is unsubstituted C 1 -C 8 alkyl, and R 4 is unsubstituted C 1 -C 8 alkyl, or a pharmaceutically acceptable salt thereof.

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

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

7. A compound selected from the table below, 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-l-ylmethyl)phenyl)-2H-

chromen-2-one

 3

6-(4-((cyclohexylamino )methyl)phenyl)-5,7-dimethyl-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-

Assignees

• Broad Inst Inc
• Massachusetts Gen Hospital

Inventors

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

Classifications

• 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

• C07D311/18

  substituted otherwise than in position 3 or 7 · CPC title

• C07D311/16 Primary

  substituted in position 7 · CPC title