Heterocyclic derivatives and methods of use thereof

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is CH or N;
• R1 is hydrogen, a C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-14carbocyclyl, or a heterocyclyl,
• wherein R1 may be optionally substituted on carbon by one or more R6;
• and wherein if said hetercyclyl 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 R7;
• provided that R1 is not a substituted or unsubstituted phenyl;
• R2 is hydrogen or a C1-6alkyl;
• or
• R1 and R2, together with the nitrogen to which they are attached, form a heterocyclyl,
• wherein said heterocyclyl may be optionally substituted on carbon by one or more R8;
• wherein if said hetercyclyl 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 C6-14aryl or a heteroaryl;
• wherein R3 may be optionally substituted on carbon by one or more R14;
• and wherein if said heteraryl 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 heteroaryl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R15;
• provided that R3 is not an unsubstituted phenyl or an unsubstituted thiophenyl;
• R4, for each occurrence, is independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, C1-6alkanoyl, carbamoyl, N—C1-6alkylcarbamoyl, N—C1-6alkoxycarbamoyl, N,N—(C1-6alkyl)2carbamoyl, N—(SO2R′)carbamoyl, N—C1-6alkyl, C1-6alkyl-S(O)a—, R17R18N—S(O)1—, CH3-14carbocyclyl, and heterocyclyl;
• or two R4 taken together with the carbon atoms to which they are attached form a C3-14carbocyclyl or a heterocyclyl, wherein each R4 may be optionally substituted on carbon by one or more R16, wherein if either of said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R26;
• provided that ring B together with —(R4)n is not 3,4,5-trimethoxyphenyl;
• n is an integer from 1 to 5;
• a is 0, 1, or 2;
• R6, R8, and R14, for each occurrence, are each independently selected from the group consisting of hydroxy, halo, cyano, nitro, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, mercapto, C1-6alkoxy, C1-6alkylS(O)a wherein a is 0 to 2,—C(═N—OH)NH2, —C(O)NHNH2, phenoxy, carboxy, oxo, amino, N—C1-6alkylamino, N,N—(C1-6alkyl)2amino, C1-6alkoxycarbonyl, C1-6alkanoyl, C1-6alkanoyloxy, C1-6alkanoylamino, C1-6alkoxycarbonylamino, carbamoyl, N—C1-6alkylcarbamoyl, N—C1-6alkoxycarbamoyl, N,N‘3(C1-6alkyl)2carbamoyl, N—C1-6alkyl-N-alkoxycarbamoyl, N—(SO2R′)carbamoyl, N—C1-6alkyl-N—(SO2R′)carbamoyl, C1-6alkylsulphonylamino, sulphamoyl, N-(C1-6alkyl)sulphamoyl, N,N-(C1-6alkyl)2sulphamoyl, sulphamoylamino, N—(C1-6alkyl)sulphamoylamino, N,N—(C1-6alkyl)2sulphamoylamino, C3-14carbocyclyl-L- and heterocyclyl-L-;
• or two R14 taken together with the carbon atoms to which they are attached form a C3-14carbocyclyl or a heterocyclyl;
• wherein R6, R8, and R14 may be each independently optionally substituted on carbon by one or more R10;
• and wherein if said hetercyclyl 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 either of said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R11;
• R′ and R″, for each occurrence, are independently selected from the group consisting of C1-6alkyl, C6-14aryl and heterocyclyl, wherein R′ and R″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;
• R7, R9, R15 and R23, for each occurrence, are each independently selected from the group consisting of C1-6alkyl, C1-6alkoxycarbonyl, C1-6alkanoyl, carbamoyl, N—C1-6alkylcarbamoyl, N,N—(C1-6alkyl)2carbamoyl, C3-14carbocyclyl-C(O)—, heterocyclyl-C(O)—, (C1-6alkyl)3silyl, C1-6alkylS(O)a wherein a is 0 to 2, wherein R7, R9, and R15 may be each independently optionally substituted on carbon by one or more R12;
• and wherein if said hetercyclyl 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 R13;
• L, for each occurrence, is independent selected from a direct bond, —)—, —N(R25)—, —C(O)—, —N(R25)C(O)—, —C(O)N(R25)—, —S(O)s—, —SO2N(R25)— or —N(R25)SO2—;
• wherein R25, for each occurrence, is independently selected from hydrogen or C1-6alkyl and s is 0, 1 or 2;
• R10 and R12, for each occurrence, are independently selected from the group consisting of C1-6alkyl, phenyl, halo, cyano, nitro, oxo, carboxy, hydroxy, C1-6alkoxy, C1-6alkoxycarbonyl, amino, N—C1-6alkylamino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, C1-6alkylSO2NH—, carbamoyl, N—C1-6alkylcarbamoyl, N,N—(C1-6alkyl)2carbamoyl, N—C1-6alkyloxycarbamoyl, C1-6alkylS(O)a wherein a is 0 to 2, and heterocyclyl, wherein said R10 and R12 are independently optionally substituted on carbon by one or more C1-6alkyl and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R13′;
• R11, R13, R13′, and R26, for each occurrence, are each independently selected from the group consisting of C1-6alkyl, C1-6alkoxycarbonyl, C1-6alkanoyl, C3-6cycloalkanoyl, carbamoyl, C1-6alkanoyloxy, C1-6alkylS(O)a, arylS(O)a wherein a is 0 to 2, carboxy, sulphamoyl a wherein said R11, R13, R13′, and R26 are independently optionally substituted on carbon by one or more amino, C1-6alkyl, C1-6alkoxy or heterocyclyl;
• R16, for each occurrence, is independently, a halo, hydroxy, a C1-6alkyl, or a C1-6alkoxy;
• R17 and R18, for each occurrence, are independently hydrogen or a C1-6alkyl;
• or R17 and R18, together with the nitrogen to which they are attached form a heterocyclyl;
• R22, for each occurrence, is independently selected from the group consisting of halo, C1-6alkyl, S(O)aR″ wherein a is 0 to 2, C1-6alkanoyl, C1-6alkanoylamino and heterocyclyl wherein may be optionally substituted on carbon by one or more R24;
• R24 is selected from halo, C1-6alkanoylamino, and heterocyclyl;
• provided that —NR1R2 is not —NHCH3 or —N(CH3)2.