Heterocyclic urea derivatives and methods of use thereof

A compound of formula (IA):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is CH;
• X1 is N;
• X2 is CR24;
• R1 is ethyl;
• R2 is hydrogen
• R3 is trifluouromethyl or phenyl;
• R5 is selected from —OH, ethoxy, 2-hydroxyethoxy, 3-hydroxypropoxy, 2-(phosphonooxy)ethoxy, 3-(phosphonooxy)propoxy, and 2-{[bis(benzyloxy)phosphoryl]oxy}ethoxy;
• R6 is selected from hydrogen, C1-6alkyl, C3-14carbocyclyl-L and heterocyclyl-L-;
• wherein said C1-6alkl, C3-14carbocyclyl-L-, or heterocyclyl-L- are optionally substituted with one or more R16;
• and wherein if said heterocyclyl contains an ═N— or a —S— moiety that nitrogen may be optionally substituted by one oxo group and that sulfur may be optionally substituted by one or two oxo groups;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R17;
• R16 is a substituent on carbon which, for each occurrence, is independently selected from halo, nitro, cyano, hydroxy, 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, 1 or 2, C1-6alkoxycarbonyl, C1-6alkoxycarbonylamino, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, C3-6carbocyclyl, heterocyclyl and —OP(═O)(ORa)2, wherein Ra, for each occurrence is independently H or a C1 -6alkyl;
• wherein said carbamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkoxy, C1-6alkanoyl, C1-6alkanoyloxy, N—(C1-6alky)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, 1 or 2, C1-6alkoxcarbonyl, C1-6alkoxy carbonylamino, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkysulphonylamino, C3-6carbocyclyl and heterocyclyl independently of each other may be optionally substituted on one or more carbon by one or more R19;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R20;
• and wherein if said heterocyclyl contains an ═N— or a —S— moiety that nitrogen may be optionally substituted by one oxo group and that sulfur may be optionally substituted by one or two oxo groups;
• R17 and R20, for each occurrence, are independently selected from C1-6alkyl, C3-6cycloalkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• wherein said C1-6alkyl C3-6cycloalky, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N, N—(C1-6alkyl)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsuphonyl independently of each other may be optionally substituted on carbon by one or more R23;
• R19 and R23, for each occurrence, are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, phenyl, morpholinyl, piperazinyl, piperidinyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6alkyl, C1-6alkoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, dipropylamino, 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 and N-methyl-N-ethylsulphamoyl;
• R24 is selected from hydrogen, halo, nitro, cyano, hydroxy, amino, mercapto, heterocyclyl, C1-6alkyl, C2-6alkenyl, C2-6alkenyl, C1-6alkoxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, and C1-6alkylsulfanyl;
• wherein said heterocyclyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, N—C1-6alkyl)amino, N,N—(C1-6alkyl)2amino and C1-6alkylsulfanyl may be optionally substituted on one or more carbon by one or more R25;
• wherein if said heterocyclyl contains an —NH—moiety that nitrogen may be optionally substituted by C1-6 alkyl;
• R25 is a substituent on carbon which, for each occurrence, is independently selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, 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, 1 or 2, C1-6alkoxycarbonyl, C1-6alkoxycarbonylamino, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, C3-6carbocyclyl and heterocyclyl;
• wherein said carbamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C-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, 1 or 2, C1-6alkoxycarbonyl, C1-6alkoxycarbonylamino N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, C3-6carbocyclyl and heterocyclyl may be optionally substituted on one or more carbon by one or more R26;
• and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R27;
• and wherein if said heterocyclyl contains an ═N— or a —S— moiety that nitrogen may be optionally substituted by one oxo group and that sulfur may be optionally substituted by one or two oxo groups;
• R26 and R28, for each occurrence, are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1 -6alkyl, C1-6alkoxy, 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 and N-methyl-N-ethylsulphamoyl;
• R27, for each occurrence, is independently selected from C1-6alkyl, C3-6cycloalkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• wherein said C1-6alkyl, C3-6cycloakyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl may be optionally substituted on carbon by one or more R28;
• and
• L is a direct bond or a C1-6alkylene.