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US 2008/0167347 A1Published application
Ctgf Expression Inhibitor
AssigneeShiongi & Co., Ltd.
InventorsKaoru Seno, Toshihiro Shinosaki, Satoshi Hata, Isamu Yamada, Hiroki Sato, Mikayo Hayashi
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Abstract
A CTGF expression inhibitor comprising a compound of the formula I: a pharmaceutically acceptable salt or solvate thereof as an active ingredient, (wherein Y is hydroxy or a group of the formula: —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl), and R1 to R9 are each independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy or the like).
Claims29
A CTGF expression inhibitor comprising a compound of the formula I:
- a pharmaceutically acceptable salt or solvate thereof as an active ingredient,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is hydrogen, halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or
- a group of the formula:
- —O—R2′ (wherein R2′ is optionally substituted alkyl, alkylsulfonyl, cycloalkyl, optionally substituted nonaromatic heterocycle or heteroaryl), or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3 is hydrogen, halogen, cyano, optionally substituted sulfamoyl, optionally substituted carbamoyl, optionally substituted amino, nitro, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle or
- a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5 is hydrogen, carbamoyl, cyano, nitro, halogen, optionally substituted alkyl, alkenyl, alkoxycarbonyl amino, alkoxy, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, optionally substituted amino, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle,
- a group of the formula:
- —X′—R5″ (wherein X′ is —C≡C—, and R5′ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle, optionally substituted alkyl, alkoxy, hydroxy or hydrogen) or
- a group of the formula:
- —X″—R5″ (wherein X″ is —O-Z-, —S-Z-, —C(═O)—, —SO-Z-, —SO2-Z-, —NRSO2—, —NRC(═O)—, —SO2NR—, —C(═O)NR—, —CR(OH)—, —SO2O— or —NR—, R5″ is optionally substituted aryl, optionally substituted heteroaryl or optionally substituted nonaromatic heterocycle, R is hydrogen or alkyl, and Z is a bond or alkylene), and R6, R7, R8 and R9 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halogen, optionally substituted alkoxy, cyano, nitro, optionally substituted amino, optionally substituted aryl or nonaromatic heterocycle).
14 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is hydrogen, halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, optionally substituted alkoxy, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl, or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3is a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5 is hydrogen, carbamoyl, cyano, nitro, halogen, alkyl, alkenyl, alkoxycarbonylamino, alkoxy, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle,
- a group of the formula:
- —X′—R5′ (wherein X′ is —C≡C—, and R5′ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle, optionally substituted alkyl, alkoxy, hydroxy or hydrogen) or
- a group of the formula:
- —X″—R5″ (wherein X″ is —O-Z-, —S-Z-, —C(═O)—, —SO-Z-, —SO2-Z-, —NRSO2—, —NRC(═O)—, —SO2NR—, —C(═O)NR—, —CR(OH)—, —SO2O— or —NR—, R5″ is optionally substituted aryl, optionally substituted heteroaryl or optionally substituted nonaromatic heterocycle, R is hydrogen or alkyl, and Z is a bond or alkylene),
- R6 is hydrogen, alkyl or halogen,
- R7 is hydrogen, optionally substituted alkoxy, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl,
- R8 is hydrogen, nitro, optionally substituted amino, halogen, optionally substituted alkyl, alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, cyano or haloalkoxy, and
- R9 is hydrogen, alkyl, halogen or optionally substituted aryl).
15 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is hydrogen, halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, optionally substituted alkoxy, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl, or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3 is hydrogen, halogen, cyano, optionally substituted sulfamoyl, optionally substituted carbamoyl, optionally substituted amino, nitro, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle or
- a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5is a group of the formula:
- —X′—R5′ (wherein X′ is —C≡C—, and R5′ is substituted aryl or optionally substituted alkyl),
- R6 is hydrogen, alkyl or halogen,
- R7 is hydrogen, optionally substituted alkoxy, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl,
- R8 is hydrogen, nitro, optionally substituted amino, halogen, optionally substituted alkyl, alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, cyano or haloalkoxy, and
- R9 hydrogen, alkyl, halogen or optionally substituted aryl).
13 more elements
A compound ofthe formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is hydrogen, halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, optionally substituted alkoxy, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl, or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3 is substituted aryl or optionally substituted heteroaryl,
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5 is hydrogen, carbamoyl, cyano, nitro, halogen, alkyl, alkenyl, alkoxycarbonylamino, alkoxy, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle,
- a group of the formula:
- —X′—R5′ (wherein X′ is —C≡C—, and R5′ is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle, optionally substituted alkyl, alkoxy, hydroxy or hydrogen) or
- a group of the formula:
- —X″—R5″ (wherein X″ is —O-Z-, —S-Z-, —C(═O)—, —SO-Z-, —SO2-Z-, —NRSO2—, —NRC(═O)—, —SO2NR—, —C(═O)NR—, —CR(OH)—, —SO2O— or —NR—, R5″ is optionally substituted aryl, optionally substituted heteroaryl or optionally substituted nonaromatic heterocycle, R is hydrogen or alkyl, and Z is a bond or alkylene),
- R6 is hydrogen, alkyl or halogen,
- R7 is hydrogen, optionally substituted alkoxy, halogen, cyano, nitro, alkyl, haloalkyl, optionally substituted alkenyl or optionally substituted alkynyl,
- R8 is hydrogen, nitro, optionally substituted amino, halogen, optionally substituted alkyl, alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, cyano or haloalkoxy, and
- R9 is hydrogen, alkyl, halogen or optionally substituted aryl, provided that, one of R7 and R8 is not hydrogen).
14 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is hydrogen, halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or
- a group of the formula:
- —O‘R (wherein R2′ is optionally substituted alkyl, alkylsulfonyl, cycloalkyl, optionally substituted nonaromatic heterocycle or heteroaryl), or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3 is hydrogen, halogen, cyano, optionally substituted sulfamoyl, optionally substituted carbamoyl, optionally substituted amino, nitro, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle or
- a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5 is substituted aryl,
- R6 is hydrogen, alkyl or halogen,
- R7 is hydrogen, optionally substituted alkoxy, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl,
- R8 is hydrogen, nitro, optionally substituted amino, halogen, optionally substituted alkyl, alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, cyano or haloalkoxy, and
- R9 is hydrogen, alkyl, halogen or optionally substituted aryl).
14 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl or
- a group of the formula:
- —O—R2′ (wherein R2′ is optionally substituted alkyl, alkylsulfonyl, cycloalkyl, optionally substituted nonaromatic heterocycle or heteroaryl), or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3 is hydrogen, halogen, cyano, optionally substituted sulfamoyl, optionally substituted carbamoyl, optionally substituted amino, nitro, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle or
- a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5is optionally substituted nonaromatic heterocycle,
- R6 is hydrogen, alkyl or halogen,
- R7 is hydrogen, optionally substituted alkoxy, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl,
- R8 is halogen or haloalkyl, and
- R9 is hydrogen, alkyl, halogen or optionally substituted aryl).
14 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is hydrogen, halogen, nitro, optionally substituted amino, cyano, optionally substituted alkyl, optionally substituted carbamoyl, optionally substituted alkoxy, hydroxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl, or
- R1 and R2 can be taken together with the neighboring carbon atom to form an optionally substituted 5 or 6-membered ring optionally containing heteroatom(s),
- R3 is hydrogen, halogen, cyano, optionally substituted sulfamoyl, optionally substituted carbamoyl, optionally substituted amino, nitro, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle or
- a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5is optionally substituted nonaromatic heterocycle,
- R6 is hydrogen, alkyl or halogen,
- R7 is hydrogen, optionally substituted alkoxy, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl,
- R8 is halogen or haloalkyl, and
- R9 is hydrogen, alkyl, halogen or optionally substituted aryl).
12 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy or a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl or optionally substituted alkyl),
- R1 is hydrogen, optionally substituted alkyl, optionally substituted amino, nitro, optionally substituted alkoxy, halogen, optionally substituted alkenyl or optionally substituted alkynyl,
- R2 is halogen,
- R3 is hydrogen, halogen, cyano, optionally substituted sulfamoyl, optionally substituted carbamoyl, optionally substituted amino, nitro, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nonaromatic heterocycle or
- a group of the formula:
- —C≡C—R3′ (wherein R3′ is hydrogen, optionally substituted aryl, optionally substituted heteroaryl, hydroxy or optionally substituted alkyl),
- R4 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkylthio,
- R5is a group of the formula:
- —X″—R5′ (wherein X″ is —C(═O)—, —NHSO2—, —NHC(═O)—, —CH(OH)— or —NR—, R5″ is substituted aryl, and R is hydrogen or alkyl),
- R6 is hydrogen, alkyl or halogen,
- R7 is haloalkyl or haloalkoxy,
- R8 is hydrogen, nitro, optionally substituted amino, halogen, optionally substituted alkyl, alkoxy, optionally substituted alkenyl, optionally substituted alkynyl, cyano or haloalkoxy, and
- R9 is hydrogen, alkyl, halogen or optionally substituted aryl).
12 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is hydroxy,
- R1 is hydrogen,
- R2 is a group of the formula:
- —O—R2′ (wherein R2′ is optionally substituted nonaromatic heterocycle),
- R3 is hydrogen,
- R4 is hydrogen,
- R5 is halogen, aryl or optionally substituted heteroaryl,
- R6 is hydrogen,
- R7 is hydrogen,
- R8 is haloalkyl, and
- R9 is hydrogen).
9 more elements
A compound of the formula II:
- a pharmaceutically acceptable salt or solvate thereof,
- (wherein Y is a group of the formula:
- —NH—SO2—Y′ (wherein Y′ is optionally substituted aryl),
- R1 is hydrogen,
- R2 is hydrogen, halogen, nitro, cyano, optionally substituted carbamoyl or a group of the formula:
- —O—R2′ (wherein R2′ is optionally substituted alkyl),
- R3 is hydrogen, halogen, nitro, cyano, optionally substituted aryl or nonaromatic heterocycle,
- R4 is hydrogen,
- R5 is hydrogen, halogen, optionally substituted alkyl, alkoxy, optionally substituted amino or optionally substituted nonaromatic heterocycle,
- R6 is hydrogen, optionally substituted alkyl or halogen,
- R7 is hydrogen, halogen or optionally substituted nonaromatic heterocycle,
- R8 is hydrogen, halogen, haloalkyl or haloalkoxy, and
- R9 is hydrogen).
10 more elements
Dependencies are inferred from the claim text.