Heterocyclic urea derivatives and methods of use thereof

A compound of formula (I′):

• or a pharmaceutically acceptable salt thereof, wherein:
• Ring A is attached to one of the carbon atoms indicated by “*”;
• X is N, CH or CR4;
• R1 is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl or C3-6cycloalkyl;
• wherein R1 may be optionally substituted on carbon by one or more R7;
• R2 is selected from hydrogen or C1-6alkyl;
• wherein said C1-6alkyl may be optionally substituted by one or more groups independently selected from halo, cyano, hydroxy, nitro and amino;
• or R1 and R2 together with the nitrogen to which they are attached form a heterocyclyl;
• wherein said heterocyclyl may be optionally substituted on one or more carbon atoms with one or more R8;
• 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 R9;
• R3 is a C3-14carbocyclyl or a heterocyclyl;
• wherein the carbocyclyl or heterocyclyl may be optionally substituted on one or more carbon atoms by one or more R10;
• 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 R11;
• R4 and R15, for each occurrence, are independently selected from the group consisting of halo, nitro, cyano, hydroxy, amino, mercapto, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, and C1-6alkylsulfanyl;
• wherein R4 and R15 independently of each other may be optionally substituted on one or more carbon by one or more one or more R12;
• R5′ is —OH, a C1-6alkoxy, C3-14cycloalkoxy, or —NRaRb;
• wherein the C1-6alkoxy group may be optionally substituted on one or more carbon atoms with one or more, independently selected R14;
• and wherein Ra and Rb are each independently, hydrogen, a C1-6alkyl, or a C3-14carbocycle, or Ra and Rb, together with the nitrogen to which they are attached form a heterocycle, wherein Ra and Rb may be optionally substituted on one or more carbon atoms with one or more, independently selected R14;
• 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 R22;
• R6′, for each occurrence, is independently selected from the group consisting of hydrogen, C1-6alkyl, C1-6alkylsulfanyl, carboxy, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C3-14carbocyclyl-L-, and heterocyclyl-L-;
• wherein R6 is optionally substituted on one or more carbon atoms 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′;
• R13 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, amino, mercapto, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, and C1-6alkylsulfanyl;
• wherein R13 may be optionally substituted on one or more carbon by one or more one or more R16;
• or
• R6′ and R13 together with the intervening ring atoms may form a fused heterocyclyl, wherein the fused heterocyclyl may be optionally substituted on one or more carbon atoms with one or more independently selected R16;
• and wherein if said fused 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 fused heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R17′;
• m is 0 or 1;
• p is 0, 1, or 2;
• L, for each occurrence, is independently a direct bond or a C1-6alkylene;
• R7,R8, R10, R12, R14 and R16 are substituents on carbon which, for each occurrence, are 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 or heterocyclyl;
• wherein R7, R8, R10, R12, R14 and R16 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;
• R9, R11, 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)2carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• wherein R9, R11, and R20 independently of each other may be optionally substituted on carbon by one or more R23;
• R17′, 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)carbamoyl, benzyl, benzyloxycarbonyl, benzoyl, phenylsulphonyl, C3-14carbocyclyl-L-, and heterocyclyl-L-;
• wherein each R17′, independently, 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;
• 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;
• R22, for each occurrence is independently selected from C1-6alkyl, C3-6cycloalkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N,N—(C1-6alkyl)2sulfamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl;
• wherein R22 for each occurrence may be independently 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, 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 or N-methyl-N-ethylsulphamoyl;
• R24, for each occurrence, are independently selected from halo, nitro, cyano, hydroxy, oxo, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C1-6 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 or N-methyl-N-ethylsulphamoyl;
• and
• R25, for each occurrence is independently selected from a C1-6alkyl, provided that the compound is not one of the following compounds: