Pyrazolylcarboxamide compounds and their use in therapy

A compound represented by Formula II:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• A1 is a 6 membered heteroaryl containing 1 or 2 nitrogen atoms, wherein the heteroaryl is substituted with m occurrences of R5 and n occurrences of R6;
• R1 is hydrogen or C1-4 alkyl;
• R2 is C1-6 alkyl, C1-6 haloalkyl, C1-6 deuteroalkyl, C1-6 hydroxyalkyl, or C3-7 cycloalkyl;
• R3 represents independently for each occurrence halo, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl, or C3-7 cycloalkyl;
• R4 and R7 are independently hydrogen, C1-6 alkyl, or C3-7 cycloalkyl, or R4 and R7 are taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclic ring containing 1 nitrogen atom;
• R5 is a 5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein the heteroaryl is substituted with q occurrences of R8;
• R6 represents independently for each occurrence halo, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxyl, C3-7 cycloalkyl, cyano, —O—C3-7 cycloalkyl, or —N(R4)(R7);
• R8 represents independently for each occurrence halo, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl, or C3-7 cycloalkyl;
• X is a C1-7 bivalent straight or branched saturated hydrocarbon chain wherein 1 or 2 methylene units of the chain are independently and optionally replaced with O;
• and
• m, n, and q are independently 0, 1, or 2.

A compound represented by Formula III:

• or a pharmaceutically acceptable salt thereof, wherein:
• A1 is phenyl or a 6 membered heteroaryl containing 1 or 2 nitrogen atoms, wherein the phenyl and heteroaryl are substituted with m occurrences of R5 and n occurrences of R6;
• A2 is a 5-7 membered partially unsaturated ring containing 0, 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, or a 5-7 membered partially unsaturated oxo-substituted ring containing 0, 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur;
• A3 represents independently for each occurrence a 4-6 membered saturated heterocyclyl containing 1 or 2 heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein the heterocyclyl is substituted with y occurrences of R12;
• R1 is hydrogen or C1-4 alkyl;
• R2 is C1-6 alkyl, C1-6 haloalkyl, C1-6 deuteroalkyl, C1-6 hydroxyalkyl, C3-7 cycloalkyl, —(C1-6 alkylene)-N(R8)(R9), —(C1-6 alkylene)-C1-6 alkoxyl, or a 3-5 membered saturated heterocyclyl containing 1 or 2 heteroatoms independently selected from oxygen and nitrogen;
• or R2 and R1 are taken together with their intervening atoms to form a 5-7 membered ring containing 2 nitrogen atoms;
• or R2 and one occurrence of R7 are taken together with their intervening atoms to form a 5-7 membered ring containing 1 nitrogen atom;
• R3 is C1-6 haloalkyl, C1-6 alkyl, or hydrogen;
• R4 is phenyl, a 5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, a 9-10 membered bicyclic heteroaryl containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, a 3-10 membered monocyclic or bicyclic saturated or partially unsaturated heterocyclyl containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur,
• wherein the phenyl, heteroaryl,
• are substituted with t occurrences of R7;
• R5 is a 5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein the heteroaryl is substituted with q occurrences of R12;
• R6 represents independently for each occurrence halo, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxyl, C3-7 cycloalkyl, cyano, —O—C3-7 cycloalkyl, —N(R9)(R10), —(C0-4 alkylene)-C(O)R8, —C(O)N(R9)(R10), —N(R)C(O)R11, or —SO2R11;
• R7 represents independently for each occurrence halo, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxyl, C3-7 cycloalkyl, cyano, —O—C3-7 cycloalkyl, —(C0-4 alkylene)-CN, —(C1-4 alkylene)-(C1-6 alkoxyl), C2-4 alkynyl, —N(R9)(R10), —(C0-4 alkylene)-C(O)R8, —C(O)N(R9)(R10), —N(R9)C(O)R11, —SO2R11, or —O-A3;
• R8 is —OH, —O—(C1-6 alkyl), —O—C3-7 cycloalkyl, or A3;
• R9 and R10 are independently hydrogen, C1-6 alkyl, or C3-7 cycloalkyl, or R9 and R10 are taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclic ring containing 1 nitrogen atom, wherein the heterocyclic ring is substituted with 0 or 1 groups independently selected from hydroxyl, halo, and C1-6 alkyl;
• R11 represents independently for each occurrence C1-6 alkyl or (C0-5 alkylene)-C3-7 cycloalkyl;
• R12 represents independently for each occurrence halo, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl, or C3-7 cycloalkyl;
• X is a bond, C1-5 alkylene, C3-5 cycloalkylene, C2-4 alkenylene, —(C0-2 alkylene)-O—(C0-2 alkylene), —(C0-2 alkylene)-N(R9)—(C0-2 alkylene), or —C(O)—;
• and
• m, n, q, t, and y are independently 0, 1, or 2;
• provided that R2 and R3 are not simultaneously C1-4 alkyl.