Diaminocyclohexane compounds and uses thereof

A compound of formula Ib

• wherein
• X is CH2, O, or NH;
• B is absent or is (CH2)m—;
• R is H or (C1-C6)alkyl;
• R1 is (C6)aryl or 5- to 8-membered cycloalkyl or 5- to 8-membered heteroaryl, said heteroaryl containing 1-4 heteroatoms selected from N, O, and S, wherein the cycloalkyl, aryl and heteroaryl may be optionally substituted with one or more R3;
• R2 is (C6)aryl or 5- to 8-membered heteroaryl, said heteroaryl containing 1-4 heteroatoms selected from N, O, and S, wherein both the aryl and heteroaryl may be optionally substituted with one or more R4, wherein R2 is connected to ring A through the nitrogen atom;
• R3 is independently one or more halogen, —OH, —CN, —NO2, —COOH, —CO2(C1-C6)alkyl, —CF3, —OCHF2, —OCF3, —(C1-C6)-alkyl, —(C1-C6)-alkyloxy, —CONR9R10, —O(C═O)NR9R10, —NR9R10, —(C1-C6)-alkylCOOH, —(C1-C6)-alkyl-CO2(C1-C6)-alkyl, —(C1-C6)-alkylOH, —(C1-C6)-alkylCONR9R10, —(C6-10)aryl, a 5- to 8-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S;
• and a 5- to 10-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S;
• wherein any alkyl, aryl, heteroaryl, and heterocyclyl may be optionally substituted with one or more substituents selected from the group consisting of:
• halo, —OH, cyano, nitro, —CF3, —OCF3, —OCF2, (C1-C6)-alkyl, (C2-C6)-alkynyl, (C1-C6)-alkyloxy, —COOH, —CO2(C1-C6)-alkyl, —CONR9R10, —NR9R10, —O(C═O)—(C1-C6)-alkyl, —O(C═O)NR9R10;
• —(C1-C6)-alkylCOOH, —(C1-C6)-alkylOH, —(C1-C6)-alkylCONR9R10, —(C1-C6)-alkyl-CO2(C1-C6)-alkyl, (C6-C10)aryl, a 5- to 8-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S, a 5- to 10-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S;
• or R3 and another R3 can optionally be taken together with the carbon atom that they are attached to form a —(C4-C8)cycloalkyl, —(C6)aryl, a 5- to 8-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S, or a 5- to 8-membered heteroaryl ring, which contains 1-4 heteroatoms selected from N, O, and S, that may be optionally substituted with one or more substituents selected from the group consisting of:
• halo, —OH, cyano, nitro, —CF3, —OCF3, —OCF2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C1-C6)-alkyloxy, —COOH, —CO2(C1-C6)-alkyl, —CONR9R10, —NR9R10, —O(C═O)—(C1-C6)-alkyl, —O(C═O)NR9R10;
• —(C1-C6)-alkylCOOH, —(C1-C6)-alkylOH, —(C1-C6)-alkylCONR9R10, —(C1-C6)-alkyl-CO2(C1-C6)-alkyl, (C6-10)aryl, a 5- to 8-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S, a 5- to 10-membered heterocyclo, which contains 1-4 heteroatoms selected from N, O, and S;
• halo(C1-C6)alkyl, and halo(C1-C6)alkyloxy;
• R4 is halogen, —OH, CF3, —OCF2, —CN, —NO2, —COOH, (C1-C6)-alkyl, alkyloxy, —CO(C1-C6)-alkyl, —CO2(C1-C6)-alkyl, —CONR9R10, —NR9R10, or a 5- to 10-membered heteroaryl containing 1-4 heteroatoms selected from N, O, and S, optionally substituted with one or more R5;
• R5 is halogen, —OH, —CF3, —OCF2, —OCF3, —CN, —NO2, —(C1-C6)alkyl, or —(C1-C6)alkyloxy;
• R6 is halogen, —OH, (C1-C6)-alkyl or (C3-C6)-cycloalkyl;
• R9 and R10, at each occurrence, are independently hydrogen or (C1-C8)-alkyl, wherein the alkyl may be optionally substituted with one or more R11's;
• or R9 and R10 are taken together with the nitrogen to which both are attached to form a 3- to 8-membered ring, which may optionally contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R11's;
• R11 is halo, —OH, cyano, (C1-C6)-alkyl;
• m is 1, 2, to 3;
• n is 1, 2 or 3;
• or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

A compound of formula Ic

• wherein
• X is CH2, O, or NH;
• B is absent or is —(CH2)m—;
• R is H or (C1-C6)alkyl;
• R1 is (C6)aryl or 5- to 8-membered cycloalkyl or 5- to 8-membered heteroaryl, said heteroaryl containing 1-4 heteroatoms selected from N, O, and S, wherein the cycloalkyl, aryl and heteroaryl may be optionally substituted with one or more R3;
• R2 is (C6)aryl or 5- to 8-membered heteroaryl, said heteroaryl containing 1-4 heteroatoms selected from N, O, and S, wherein both the aryl and heteroaryl may be optionally substituted with one or more R4, wherein R2 is connected to ring A through the nitrogen atom;
• R3 is independently one or more halogen, —OH, —CN, —NO2, —COOH, —CO2(C1-C6)alkyl, —CF3, —OCHF2, —OCF3, —(C1-C6)-alkyl, —(C1-C6)-alkyloxy, —CON R9R10, —O(C═O)NR9R10, —NR9R10, —(C1-C6)-alkylCOOH, —(C1-C6)-alkyl-CO2(C1-C6)-alkyl, —(C1-C6)-alkylOH, —(C1-C6)-alkylCON R9R10, —(C6-10)aryl, a 5- to 8-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S;
• and a 5- to 10-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S;
• wherein any alkyl, aryl, heteroaryl, and heterocyclyl may be optionally substituted with one or more substituents selected from the group consisting of:
• halo, —OH, cyano, nitro, —CF3, —OCF3, —OCF2, (C1-C6)-alkyl, (C2-C6)-alkynyl, (C1-C6)-alkyloxy, —COOH, —CO2(C1-C6)-alkyl, —CONR9R10, —NR9R10, —O(C═O)—(C1-C6)-alkyl, —O(C═O)NR9R10;
• —(C1-C6)-alkylCOOH, —(C1-C6)-alkylOH, —(C1-C6)-alkylCONR9R10, —(C1-C6)-alkyl-CO2(C1-C6)-alkyl, (C6-10)aryl, a 5- to 8-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S, a 5- to 10-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S;
• or R3 and another R3 can optionally be taken together with the carbon atom that they are attached to form a —(C4-C8)cycloalkyl, —(C6)aryl, a 5- to 8-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S, or a 5- to 8-membered heteroaryl ring, which contains 1-4 heteroatoms selected from N, O, and S, that may be optionally substituted with one or more substituents selected from the group consisting of:
• halo, —OH, cyano, nitro, —CF3, —OCF3, —OCF2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C1-C6)-alkyloxy, —COOH, —CO2(C1-C6)-alkyl, —CONR9R10, —NR9R10, —O(C═O)—(C1-C6)-alkyl, —O(C═O)NR9R10;
• —(C1-C6)-alkylCOOH, —(C1-C6)-alkylOH, —(C1-C6)-alkylCONR9R10, —(C1-C6)-alkyl-CO2(C1-C6)-alkyl, (C6-10)aryl, a 5- to 8-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S, a 5- to 10-membered heterocyclo, which contains 1-4 heteroatoms selected from N, O, and S;
• halo(C1-C6)alkyl, and halo(C1-C6)alkyloxy;
• R4 is halogen, —OH, CF3, —OCF2, —OCF3, —CN, —NO2, —COOH, (C1-C6)-alkyl, (C1-C6)-alkyloxy, —CO(C1-C6)-alkyl, —CO2(C1-C6)-alkyl, —CONR9R10, —NR9R10, or a 5- to 10-membered heteroaryl containing 1-4 heteroatoms selected from N, O, and S, optionally substituted with one or more R5;
• R5 is halogen, —OH, —CF3, —OCF2, —OCF3, —CN, —NO2, —(C1-C6)alkyl, or —(C1-C6)alkyloxy;
• R6 is halogen, —OH, (C1-C6)-alkyl or (C3-C6)-cycloalkyl;
• R9 and R10, at each occurrence, are independently hydrogen or (C1-C8)-alkyl, wherein the alkyl may be optionally substituted with one or more R11's;
• or R9 and R10 are taken together with the nitrogen to which both are attached to form a 3- to 8-membered ring, which may optionally contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R11's;
• R11 is halo, —OH, cyano, (C1-C6)-alkyl;
• m is 1, 2, to 3;
• n is 1, 2 or 3;
• or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.