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US 7,622,482 B2Granted
Chemical compounds
AssigneeAstraZeneca AB
InventorsYongxin Han, Michelle Lamb, Peter Mohr, Bin Wang, Tao Wang, Dingwei Yu
Life of this patent
Estimating the term…
Abstract
This invention relates to novel compounds having the formula (I): and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.
Claims13
A compound of formula (I):
- wherein:
- R1 and R2 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl or heterocyclyl;
- wherein R1 and R2 independently of each other may be optionally substituted on carbon by one or more R7;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R8;
- X1, X2 and X3 are independently ═N— or ═CR9—;
- R3 and R9 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl-R10— or heterocyclyl-R11;
- wherein R3 and R9 independently of each other may be optionally substituted on carbon by one or more R12;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R13;
- R4 and R5 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl or heterocyclyl;
- wherein R4 and R5 independently of each other may be optionally substituted on carbon by one or more R14;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R15;
- A is a direct bond or C1-2alkylene;
- wherein said C1-2alkylene may be optionally substituted by one or more
- Ring C is carbocyclyl or heterocyclyl;
- wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R17;
- R6 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl or heterocyclyl;
- wherein R6 may be optionally substituted on carbon by one or more R18;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R19;
- n is 0, 1, 2 or 3;
- wherein the values of R6 may be the same or different;
- R7, R12, R14, R16 and R18 and are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl-R20— or heterocyclyl-R21—;
- wherein R7, R12, R14, R16 and R18 independently of each other may be optionally substituted on carbon by one or more R22;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R23;
- R8, R13, R15, R17, R19 and R23 are independently selected from C1-6alkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
- wherein R8, R13, R15, R17, R19 and R23 independently of each other may be optionally substituted on carbon by on or more
- R22 and R24 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl or heterocyclyl;
- wherein R22 and R24 independently of each other may be optionally substituted on carbon by one or more R25;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R26;
- R10, R11, R20 and R21 are independently selected from a direct bond, —O—, —N(R27)—, —C(O)—, —N(R28)C(O)—, —C(O)N(R29)—, —S(O)—, —SO2N(R30)— or —N(R31)SO2—;
- wherein R27, R28R29, R30 and R31 are independently selected from hydrogen or C1-6alkyl and s is 0-2;
- R25 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, 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, methylsulphinyl, ethylsulphinyl, mesyl, ethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulphamoyl, N-ethylsulphamoyl, N,N-dimethylsulphamoyl, N,N-diethylsulphamoyl or N-methyl-N-ethylsulphamoyl;
- and
- R26 is selected from C1-6alkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
- or a pharmaceutically acceptable salt thereof.
31 more elements
A compound of formula (I):
- wherein:
- R1 is selected from methyl, t-butyl, isopropoxy or cyclopropyl;
- R2 is hydrogen;
- X1, X2 and X3 are independently ═N— or ═CR9—;
- R3 and R2 are independently selected from hydrogen, fluoro, chloro, hydroxy and methyl;
- R4 and R5 are independently selected from hydrogen, methyl or hydroxymethyl;
- A is a direct bond;
- Ring C is phenyl;
- R6 is fluoro;
- and
- n is 1;
- or a pharmaceutically acceptable salt thereof.
9 more elements
A compound of formula (I):
- selected from:
- (S)—N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-(1-(4-fluorophenyl)ethyl)-3H-imidazo[4,5-b]pyridin-5-amine;
- (R)-2-(5-(5-cyclopropyl-1H-pyrazol-3-ylamino)-3H-imidazo[4,5-b]pyridin-3-yl)-2-(4-fluorophenyl)ethanol;
- (S)-6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-(1-(4-fluorophenyl)ethyl)-3H-imidazo[4,5-b]pyridin-5-amine;
- (R)-2-(6-chloro-5-(5-cyclopropyl-1H-pyrazol-3-ylamino)-3H-imidazo[4,5-b]pyridin-3-yl)-2-(4-fluorophenyl)ethanol;
- (R)-2-(6-chloro-5-(5-methyl-1H-pyrazol-3-ylamino)-3H-imidazo[4,5-b]pyridin-3-yl)-2-(4-fluorophenyl)ethanol;
- (S)-6-fluoro-3-(1-(4-fluorophenyl)ethyl)-N-(5-methyl-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine;
- (R)-2-(5-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)-2-(4-fluorophenyl)ethanol;
- (S)—N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-fluoro-3-(1-(4-fluorophenyl)ethyl)-3H-imidazo[4,5-b]pyridin-5-amine;
- (S)-6-fluoro-3-(1-(4-fluorophenyl)ethyl)-N-(5-isopropoxy-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine;
- and
- (S)-6-chloro-3-(1-(4-fluorophenyl)ethyl)-N-(5-isopropoxy-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine;
- or a pharmaceutically acceptable salt thereof.
10 more elements
Dependencies are inferred from the claim text.