# US 2014/0194422 A1 · Piperazine derivatives, compositions, and uses related thereto

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- Number: US 2014/0194422 A1
- Document ID: US20140194422A1
- Status: Published application
- Kind: A1
- Application number: 14/123,877
- Filed: 2012-06-12
- Published: 2014-07-10
- Earliest claimed: 2011-06-13
- Assignees: Emory University
- Inventors: Thota Ganesh; Aiming Sun; Susane M. Smith; John David Lambeth
- Web page: https://patentgrep.com/patent/US20140194422A1

## CPC

- C07D 307/14: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- C07D 209/18: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 211/58: attached in position 4
- C07D 239/42: One nitrogen atom (nitro radicals C07D239/30)
- C07D 239/90: with acyclic radicals attached in position 2 or 3
- C07D 241/08: with oxygen atoms directly attached to ring carbon atoms
- C07D 241/50: with hetero atoms directly attached to ring nitrogen atoms
- C07D 295/185: from aliphatic carboxylic acids
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

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

## Claims

### Claim 1

A pharmaceutical composition comprising a compound comprising Formula I,
or pharmaceutically acceptable salt or prodrug thereof, wherein;
Z is S, SO, SO2, C═O, C═S, C═N—OR8;
R1 and R2 are each, the same or different, alkyl, carbocyclyl, aryl, or heterocyclyl, wherein R1 and R2 are optionally substituted with one or more, the same or different, R10;
R8 is hydrogen or alkyl optionally substituted with one or more, the same or different, R10;
X3, X4, X5, and X6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X3, X4, X5, and X6 are each optionally substituted with one or more, the same or different, X10; or
X3 and R1 and the attached atoms form a polycyclic heterocyclyl optionally substituted with one or more, the same or different, R10;
R10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R11;
R11 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R12;
R12 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R13;
R13 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl;
X10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X10 is optionally substituted with one or more, the same or different, X11; and
X11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein Z is C═O.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein R1 is alkyl substituted with amino wherein the amino is substituted with an aryl group optionally substituted with one or more alkoxy.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein R1 is a heterocyclyl optionally substituted with one or more R10;

### Claim 5 (depends on 3)

The pharmaceutical composition of claim 3, wherein the heterocyclyl is indolyl, quinolinyl, or imidazolyl.

### Claim 6 (depends on 1)

A compound of formula I as in claim 1, selected from the group consisting of
2-((4-acetylphenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(4-methoxyphenyl)-3-methylpiperazin-1-yl)ethanone;
2-((4-isopropylphenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(4-ethoxyphenyl)piperazin-1-yl)ethanone;
2-((3,4-difluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;
2-((3-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(3-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(2-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(4-fluorophenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(2-fluorophenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(pyridin-4-yl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone;
4-(4-(2-((4-acetylphenyl)amino)acetyl)piperazin-1-yl)benzonitrile;
2-((2-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-fluorophenyl)amino)-1-(4-(4-methoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(3,4-dimethoxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(2-hydroxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(3-hydroxyphenyl)piperazin-1-yl)ethanone;
2-((4-acetylphenyl)amino)-1-(4-(2-aminophenyl)piperazin-1-yl)ethanone; and
2-((4-acetylphenyl)amino)-1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone or salts thereof.

### Claim 7 (depends on 1)

The composition of claim 1, wherein Formula I has Formula IE,
or pharmaceutically acceptable salt or prodrug thereof, wherein;
A is N or CR9;
R9 is hydrogen, amino, or alkyl optionally substituted with one or more, the same or different, R10;
Y1, Y2, Y3, Y4, and Y5 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein Y1, Y2, Y3, Y4, and Y5 are each optionally substituted with one or more, the same or different, Y10;
R3, R4, R5, and R6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R3, R4, R5, and R6 are each optionally substituted with one or more, the same or different, R10;
X1, X3, X4, X5, and X6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X1, X3, X4, X5, and X6 are each optionally substituted with one or more, the same or different, X10; or
R10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R11;
R11 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R12;
R12 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R13;
R13 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl;
X10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X10 is optionally substituted with one or more, the same or different, X11;
X11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl
Y10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein Y10 is optionally substituted with one or more, the same or different, Y11; and
Y11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

### Claim 8 (depends on 7)

The compound of claim 7 wherein, R5 is hydrogen, halogen, hydroxy, nitro, alkyl, alkoxy, alkylsulfonyl, alkoxycarbonyl, alkylcarbamoyl, alkanoyl, carboxy, or carbamoyl optionally substituted with one or more, the same or different, R10.

### Claim 9 (depends on 1)

A compound of formula I as in claim 1, selected from the group consisting of:
1-(2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone;
(5-methoxy-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-fluoro-1H-benzo[d]imidazol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5,6-dimethoxy-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(6-fluoro-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-fluoro-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
1-(2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-3-methyl-1H-indol-5-yl)ethanone;
(5-hydroxy-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-fluoro-3-methyl-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-ethyl-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(5-bromo-1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
N-(5-methoxy-2-(4-(4-methoxyphenyl)piperazine-1-carbonyl)-1H-indol-3-yl)acetamide;
(4-(4-methoxyphenyl)piperazin-1-yl)(5-nitro-1H-indol-2-yl)methanone;
indolin-2-yl(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(1H-indol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
(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;
(5-methoxy-1H-benzo[d]imidazol-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
methyl 1-(5-fluoro-1H-benzo[d]imidazole-2-carbonyl)-4-(4-methoxyphenyl)piperazine-2-carboxylate;
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;
(4-(4-ethoxyphenyl)piperazin-1-yl)(5-fluoro-1H-benzo[d]imidazol-2-yl)methanone;
1-(2-(4-(3-fluoro-4-methoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone;
1-(2-(4-(4-isopropoxyphenyl)piperazine-1-carbonyl)-1H-indol-5-yl)ethanone; and
(5-fluoro-1H-benzo[d]imidazol-2-yl)(4-(4-isopropoxyphenyl)piperazin-1-yl)methanone or salt thereof.

### Claim 10 (depends on 1)

The composition of claim 1, wherein Formula I has Formula IF,
or pharmaceutically acceptable salt or prodrug thereof, wherein;
Y1, Y2, Y3, Y4, Y5 and Y6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein Y1, Y2, Y3, Y4, Y5 and Y6 are each optionally substituted with one or more, the same or different, Y10;
R3, R4, R5, and R6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R3, R4, R5, and R6 are each optionally substituted with one or more, the same or different, R10;
X3, X4, X5, and X6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X3, X4, X5, and X6 are each optionally substituted with one or more, the same or different, X10; or
R10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R11;
R11 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R12;
R12 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R13;
R13 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl;
X10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X10 is optionally substituted with one or more, the same or different, X11;
X11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl;
Y10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein Y10 is optionally substituted with one or more, the same or different, Y11; and
Y11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

### Claim 11 (depends on 1)

A compound of formula I as in claim 1, selected from the group consisting of:
(6-fluoro-4-hydroxyquinolin-3-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone;
1-(4-hydroxy-3-(4-(4-methoxyphenyl)piperazine-1-carbonyl)quinolin-7-yl)ethanone; and
(8-fluoro-4-hydroxyquinolin-3-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone or salts thereof.

### Claim 12

A pharmaceutical composition comprising a compound comprising Formula II,
or pharmaceutically acceptable salt or prodrug thereof, wherein;
Z is S, SO, SO2, C═O, C═S, C═N—OR8, C═NHR8, —(CH2)m—;
n is 1 to 10;
m is 1 to 10;
J and G are a bicyclic carbocyclyl, aryl, or heterocyclyl optionally substituted with one or more, the same or different, R5;
R5 is the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R5 is optionally substituted with one or more, the same or different, R10;
R8 is hydrogen, cyano, or alkyl optionally substituted with one or more, the same or different, R10;
R9 is alkyl, amino, alkylamino, dialkylamino, carbocyclyl, aryl, or heterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R10;
X4, X5, and X6 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X4, X5, and X6 are each optionally substituted with one or more, the same or different, X10;
Y1, Y2, Y3, Y4, and Y5 are each, the same or different, hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein Y1, Y2, Y3, Y4, and Y5 are each optionally substituted with one or more, the same or different, Y10;
R10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R11;
R11 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R12;
R12 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R13;
R13 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl;
X10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein X10 is optionally substituted with one or more, the same or different, X11;
X11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl
Y10 is hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein Y10 is optionally substituted with one or more, the same or different, Y11; and
Y11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

### Claim 13 (depends on 12)

The compound of Formula II as in claim 12, 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.

### Claim 14 (depends on 1)

A method of treating or preventing a Nox related disease or condition comprising administering a pharmaceutical composition in claim 1 to a subject in need thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the Nox related disease or condition is liver failure, traumatic brain injury (TBI), neuropathic pain, hypertension, ischemia/reperfusion injury, stroke, myocardial infarction, diabetes, atherosclerosis, Alzheimer's disease, chronic obstructive pulmonary disease, various cancers, acute respiratory distress syndrome, acute lung inflammation, Parkinson's disease, pulmonary fibrosis, liver fibrosis, cardiac hypertrophy, diabetic nephropathy, diabetic neuropathy, scar formation, skin aging and damage, and psoriasis.

### Claim 16 (depends on 1)

The use of a compound as described in claim 1 in the production of a medicament for the treatment of a Nox related disease or condition.

### Claim 17 (depends on 1)

A method of preventing aging, sunburn, or scar formation comprising administering a composition comprising a compound in claim 1 to a subject in need thereof.

### Claim 18 (depends on 1)

A method of preventing tissue injury comprising administering a composition comprising a compound in claim 1 to subject before, during or after and organ transplant.

### Claim 19 (depends on 1)

An aqueous biological storage medium comprising a compound in claim 1.

### Claim 20 (depends on 19)

The biological storage medium of claim 19, further comprising a salt, an amino acid, a saccharide, a vitamin, or adenosine triphosphate.