2-Amino 1H-Imidazo Ring Systems and Methods

A compound of the following Formula II:

• wherein:
• R2 is selected from the group consisting of:
• —R4a,
• -Qa-R4a,
• —X2—R5a, and
• —X2—N(R8a)-Qa-R4a;
• R2′ is selected from the group consisting of hydrogen, C1-4 alkyl, hydroxyC1-24 alkylenyl, and alkoxyC2-4 alkylenyl;
• Qa is selected from the group consisting of a bond, —C(R6)—, —C(R6)—C(R6)—, —S(O)2—, —C(R6)—N(R8a)—W—, —S(O)2—N(R8a)—, and —C(R6)—O—;
• X2 is selected from the group consisting of C2-4 alkylene and C2-4 alkenylene;
• R4a is selected from the group consisting of hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, arylC1-4 alkylenyl, aryloxyC1-4 alkylenyl, C1-4 alkylarylenyl, heteroaryl, heteroarylC1-4 alkylenyl, heteroaryloxyC1-4 alkylenyl, C1-4 alkylheteroarylenyl, heterocyclyl and heterocyclylC1-4 alkylenyl wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, arylC1-4 alkylenyl, aryloxyC1-4 alkylenyl, C1-4 alkylarylenyl, heteroaryl, heteroarylC1-4 alkylenyl, heteroaryloxyC1-4 alkylenyl, C1-4 alkylheteroarylenyl, heterocyclyl, and heterocyclylC1-4 alkylenyl groups are unsubstituted or substituted by one or more substituents independently selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, C1-4 alkanoyl, C1-4 alkoxycarbonyl, hydroxyC1-4 alkyl, haloC1-4 alkyl, haloC1-4 alkoxy, halogen, nitro, hydroxy, mercapto, cyano, amino, C1-4 alkylamino, di(C1-4 alkyl)amino, and in the case of C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and heterocyclyl, oxo;
• R5a is selected from the group consisting of:
• R7a is C2-4 alkylene;
• R8a is selected from the group consisting of hydrogen and C1-4 alkyl;
• RA1 and RB1 are independently selected from the group consisting of:
• hydrogen,
• halogen,
• alkyl,
• alkenyl,
• alkoxy,
• alkylthio, and
• —N(R9)2;
• or RA1 and RB1 taken together form a fused benzene ring or a fused pyridine ring wherein the benzene ring or pyridine ring is unsubstituted or substituted by one R3 group, or substituted by one R3 group and one R group, or substituted by one or more R groups;
• or RA1 and RB1 taken together form a fused 5 to 7 membered saturated ring optionally containing one nitrogen atom wherein the ring is unsubstituted or substituted by one or more R groups;
• R is selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, and —N(R9)2;
• R1 is selected from the group consisting of:
• —R4,
• —X1—R4,
• —X1—Y1—R4,
• —X1—Y1—X1—Y1—R4, and
• —X1—R5;
• R3 is selected from the group consisting of:
• -Z-R4,
• -Z-X—R4,
• -Z-X—Y—R4, and
• -Z-X—R5;
• X and X1 are independently selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, heteroarylene, and heterocyclylene wherein the alkylene, alkenylene, and alkynylene groups can be optionally interrupted or terminated with arylene, heteroarylene, or heterocyclylene, and optionally interrupted by one or more —O— groups;
• Y and Y1 are independently selected from the group consisting of:
• Z is selected from the group consisting of a bond and —O—;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, aryl, aryloxy, arylalkyleneoxy, heteroaryl, heteroaryloxy, heteroarylalkyleneoxy, heterocyclyl, amino, alkylamino, dialkylamino, (dialkylamino)alkyleneoxy, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo;
• R5 is selected from the group consisting of:
• A is selected from the group consisting of —O—, —C(O)—, —S(O)0-2—, and —N(R4)—;
• Q is selected from the group consisting of a bond, —C(R6)—, —C(R6)—C(R6)—, —S(O)2—, —C(R6)—N(R8)—W—, —S(O)2—N(R8)—, —C(R6)—O—, —C(R6)—S—, and —C(R6)—N(OR9)—;
• V is selected from the group consisting of —C(R6)—, —O—C(R6)—, —N(R8)—C(R6)—, and —S(O)2—;
• W is selected from the group consisting of a bond, —C(O)—, and —S(O)2—;
• a and b are independently integers from 1 to 6 with the proviso that a+b is ≦7;
• R6 is selected from the group consisting of ═O and ═S;
• R7 is C2-7 alkylene;
• R8 is selected from the group consisting of hydrogen, alkyl, alkoxyalkylenyl, and arylalkylenyl;
• R9 is selected from the group consisting of hydrogen and alkyl;
• and
• R10 is C3-8 alkylene;
• or a pharmaceutically acceptable salt thereof.

A compound of the following Formula IV:

• wherein:
• R2 is selected from the group consisting of:
• —R4a,
• -Qa-R4a,
• —X2—R5a, and
• —X2—N(R8a)-Qa-R4a;
• R2′ is selected from the group consisting of hydrogen, C1-4 alkyl, hydroxyC2-4 alkylenyl, and alkoxyC2-4 alkylenyl;
• Qa is selected from the group consisting of a bond, —C(R6)—, —C(R6)—C(R6)—, —S(O)2—, —C(R6)—N(R8a)—W—, —S(O)2—N(R8a)—, and —C(R6)—O—;
• X2 is selected from the group consisting of C2-4 alkylene and C2-4 alkenylene;
• R4a is selected from the group consisting of hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, arylC1-4 alkylenyl, aryloxyC1-4 alkylenyl, C1-4 alkylarylenyl, heteroaryl, heteroarylC1-4 alkylenyl, heteroaryloxyC1-4 alkylenyl, C1-4 alkylheteroarylenyl, heterocyclyl, and heterocyclylC1-4 alkylenyl wherein the C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, arylC1-4 alkylenyl, aryloxyC1-4 alkylenyl, C1-4 alkylarylenyl, heteroaryl, heteroarylC1-4 alkylenyl, heteroaryloxyC1-4 alkylenyl, C1-4 alkylheteroarylenyl, heterocycyl, and heterocyclylC1-4 alkylenyl groups are unsubstituted or substituted by one or more substituents independently selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, C1-4alkanoyl, C1-4alkoxycarbonyl, hydroxyC1-4alkyl, haloC1-4alkyl, haloC1-4 alkoxy, halogen, nitro, hydroxy, mercapto, cyano, amino, C1-4 alkylamino, di(C1-4 alkyl)amino, and in the case of C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and heterocyclyl, oxo;
• R5a is selected from the group consisting of:
• R7a is C2-4 alkylene;
• R8a is selected from the group consisting of hydrogen and C1-4 alkyl;
• R is selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, and —N(R9)2;
• R1 is selected from the group consisting of:
• —R4,
• —X1—R4,
• —X1—Y1—R4,
• —X1—Y1—X1—Y—R4, and
• —X1—R5;
• R3 is selected from the group consisting of:
• -Z-R4,
• -Z-X—R4,
• -Z-X—Y—R4, and
• -Z-X—R5;
• X and X1 are independently selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, heteroarylene, and heterocyclylene wherein the alkylene, alkenylene, and alkynylene groups can be optionally interrupted or terminated with arylene, heteroarylene, or heterocyclylene, and optionally interrupted by one or more —O— groups;
• Y and Y1 are independently selected from the group consisting of:
• Z is selected from the group consisting of a bond and —O—;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, aryl, aryloxy, arylalkyleneoxy, heteroaryl, heteroaryloxy, heteroarylalkyleneoxy, heterocyclyl, amino, alkylamino, dialkylamino, (dialkylamino)alkyleneoxy, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo;
• R5 is selected from the group consisting of:
• A is selected from the group consisting of —O—, —C(O)—, —S(O)0-2—, and —N(R4)—;
• Q is selected from the group consisting of a bond, —C(R6)—, —C(R6)—C(R6)—, —S(O)2—, —C(R6)—N(R8)—W—, —S(O)2—N(R8)—, —C(R6)—O—, —C(R6)—S—, and —C(R6)—N(OR9)—;
• V is selected from the group consisting of —C(R6)—, —O—C(R6)—, —N(R8)—C(R6)—, and —S(O)2—;
• NV is selected from the group consisting of a bond, —C(O)—, and —S(O)2—;
• a and b are independently integers from 1 to 6 with the proviso that a+b is ≦7;
• n is an integer from 0 to 4;
• m is 0 or 1, with the proviso that when m is 1, n is 0 or 1;
• R6 is selected from the group consisting of ═O and ═S;
• R7 is C2-7 alkylene;
• R8 is selected from the group consisting of hydrogen, alkyl, alkoxyalkylenyl, and arylalkylenyl;
• R9 is selected from the group consisting of hydrogen and alkyl;
• and
• R10 is C3-8 alkylene;
• or a pharmaceutically acceptable salt thereof.