Piperazine derivatives, compositions, and uses related thereto

Patent metadata

Field	Value
Publication number	US-9428478-B2
Application number	US-201214123877-A
Country	US
Kind code	B2
Filing date	Jun 12, 2012
Priority date	Jun 13, 2011
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

Abstract

The disclosure relates to piperazine derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidase.

First claim

What is claimed:

1. A pharmaceutical composition comprising a compound of Formula IE,

or pharmaceutically acceptable salt thereof, wherein;
A is CR 9 ;
R 9 is hydrogen, or alkyl;
Y 3 is methoxy, ethoxy, trifluoromethoxy, isopropoxy, or alkoxy;
Y 1 , Y 2 , Y 4 and Y 5 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, or aryl;
R 3 , R 4 , and R 6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, or aryl;
R 5 is alkylsulfonyl, alkoxycarbonyl, alkylcarbamoyl, alkanoyl, carboxy, or carbamoyl;
X 1 is hydrogen;
X 3 , X 4 , X 5 , and X 6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, or aryl.

2. The composition of claim 1 wherein the compound is selected from the group consisting of:
1-(2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone;
1-(2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-3-methyl-1H-indol-5-yl)ethanone;
(4-(4-methoxyphenyl)piperazin-1-yl)(5-(methylsulfonyl)-1H-indol-2-yl)methanone;
methyl 2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-1H-indole-5-carboxylate;
2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-N-methyl-1H-indole-5-carboxamide;
2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-1H-indole-5-carboxamide;
2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-1H-indole-5-carboxylic acid;
1-(2-(4-(4-ethoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone;
1-(2-(4-(3-fluoro-4-methoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone; and
1-(2-(4-(4-isopropoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone;
or salt thereof.

3. A pharmaceutical composition comprising a compound comprising Formula IIB,

or pharmaceutically acceptable salt thereof, wherein;
n is 1 or 2;
R 3 , R 4 , R 5 , and R 6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, or aryl;
R 9 is amino, alkylamino, dialkylamino, piperidinyl, piperazinyl, or morpholinyl wherein R 9 is optionally substituted with alkyl or dialkylamino;
X 1 , X 4 , X 5 , and X 6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, or aryl;
Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, or aryl.

4. A pharmaceutical composition comprising a compound selected from the group consisting of:
(3-(((2-(diethylamino)ethyl)amino)methyl)-5-fluoro-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-fluoro-3-(morpholinomethyl)-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-fluoro-3-(((1-methylpiperidin-4-yl)amino)methyl)-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(3-((4-ethylpiperazin-1-yl)methyl)-5-fluoro-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone; and
(3-((diethylamino)methyl)-5-fluoro-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone
or salts thereof.

Assignees

• Ganesh Thota
• Sun Aiming
• Smith Susane M
• Lambeth John David
• Univ Emory

Inventors

• Ganesh Thota
• Sun Aiming
• Smith Susane M
• Lambeth John David

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07D211/58

  attached in position 4 · CPC title

• C07D295/185

  from aliphatic carboxylic acids · CPC title

• C07D307/14 Primary

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title