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US 2008/0176872 A1Published application
Chemical Compounds
AssigneeAstraZeneca AB
InventorsMichelle Lamb, Tao Wang, Dingwei Yu, Peter Mohr, Bin Wang
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.
Claims28
A compound of formula (I):
- wherein:
- R1 and R2 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-16alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2-amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2-carbamoyl, 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 R8;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R9;
- X1, X2 and X3 are independently ═N— or ═CR10—;
- R3 and R10 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)2-amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2-carbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl-R11— or heterocyclyl-R12—;
- wherein R3 and R10 independently of each other may be optionally substituted on carbon by one or more R13;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R14;
- R4 is hydrogen or optionally substituted C1-6alkyl;
- wherein said optional substituents are selected from one or more R15;
- R5 and R6 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)2-amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2-carbamoyl, 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 R5 and R6 independently of each other may be optionally substituted on carbon by one or more R16;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R17;
- A is a direct bond or C1-2alkylene;
- wherein said C1-2alkylene may be optionally substituted by one or more R18;
- 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 R19;
- R7 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)2-carbamoyl, 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 R7 may be optionally substituted on carbon by one or more R20;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21;
- n is 0, 1, 2 or 3;
- wherein the values of R7 may be the same or different;
- R8, R13, R15, R16, R18 and R20 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)2-amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2-carbamoyl, C1-6alkylS(O)3 wherein a is 0 to 2, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl-R22— or heterocyclyl-R23—;
- wherein R8, R13, R15, R16, R18 and R20 independently of each other may be optionally substituted on carbon by one or more R24;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R25;
- R9, R14, R17, R19, R21 and R25 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 R9, R14, R17, R19, R21 and R25 independently of each other may be optionally substituted on carbon by on or more R26;
- R24 and R26 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)2-amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2-carbamoyl, 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 R24 and R26 independently of each other may be optionally substituted on carbon by one or more R27;
- and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R28;
- R11, R12, R22 and R23 are independently selected from a direct bond, —O—, —N(R29)—, —C(O)—, —N(R30)C(O)—, —C(O)N(R31)—, —S(O)s—, —SO2N(R32)— or —N(R33)SO2—;
- wherein R29, R30, R31, R32 and R33 are independently selected from hydrogen or C1-6alkyl and s is 0-2;
- R27 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
- R28 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.
33 more elements
A compound of formula (I):
- wherein:
- R1 is selected from methyl, isopropoxy and cyclopropyl;
- R2 is hydrogen;
- X1, X2 and X3 are independently ═N— or ═CR10—;
- R3 is selected from hydrogen, cyano, carbamoyl, methyl, hydroxymethyl and methoxycarbonyl;
- R10 is selected from hydrogen, fluoro, chloro, cyano, carbamoyl, methyl, aminomethyl and acetylaminomethyl;
- R4 is hydrogen;
- R5 is selected from hydrogen, methyl, ethyl or hydroxymethyl;
- R6 is selected from hydrogen or hydroxymethyl;
- A is a direct bond, methylene or hydroxymethylene;
- Ring C is phenyl, pyrid-2-yl, 1,3-benzodioxol-5-yl or 1H-indol-3-yl;
- R7 is trifluoromethyl and fluoro;
- and
- n is 0, 1 or 2;
- wherein the values of R7 may be the same or different;
- or a pharmaceutically acceptable salt thereof.
13 more elements
A compound of formula (I):
- selected from:
- (2R)-2-[9-(5-cyclopropyl-1H-pyrazol-3-yl)-6-methyl-9H-purin-2-ylamino]-2-(4-fluorophenyl)ethanol;
- (2R)-2-{[9-(5-cyclopropyl-1H-pyrazol-3-yl)-9H-purin-2-yl]amino}-2-(4-fluorophenyl)ethanol;
- N—((S)-1-(4-fluorophenyl)ethyl)-9-(5-isopropoxy-1H-pyrazol-3-yl)-9H-purin-2-amine;
- 3-(5-cyclopropyl-1H-pyrazol-3-yl)-N—[(S)-1-(4-fluorophenyl)ethyl]-3H-imidazo[4,5-b]pyridin-5-amine;
- 3-(5-isopropoxy-1H-pyrazol-3-yl)-N—((S)-1-(pyridin-2-yl)ethyl)-3H-imidazo[4,5-b]pyridin-5-amine;
- N—((S)-1-(4-fluorophenyl)ethyl)-3-(5-isopropoxy-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine;
- (2R)-2-(4-fluorophenyl)-2-(3-(5-isopropoxy-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-ylamino)ethanol;
- 6-chloro-N—((S)-1-(4-fluorophenyl)ethyl)-3-(5-isopropoxy-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine;
- 3-(5-cyclopropyl-1H-pyrazol-3-yl)-N—[(S)-1-(4-fluorophenyl)ethyl]-3H-benzo[d]imidazol-5-amine;
- and
- N-((1-(5-cyclopropyl-1H-pyrazol-3-yl)-6-((S)-1-(4-fluorophenyl)ethylamino)-1H-benzo[d]imidazol-5-yl)methyl)acetamide;
- or a pharmaceutically acceptable salt thereof.
10 more elements
Dependencies are inferred from the claim text.