Heteroaryl-substituted alkyne compounds and method of use

A compound of Formula I:

• or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein
• A1 is CR3;
• A2 is CR4 or N;
• A3 is CR5 or N;
• A4 is CR6 or N;
• provided that only one of A2, A3 and A4 is N;
• R1 and R3 taken together with the atoms to which they are attached form an imidazole fused ring optionally substituted independently with 1-3 substituents of R8 or R9;
• R2 is
• wherein
• R3a is COOR10, COOR11, C(O)SR10, C(O)SR11, C(O)NR10R10, C(O)NR10R11, NR10R11, NR10C(O)R10, NR10C(O)R11, S(O)2NR10R10, S(O)2NR10R11, NR10S(O)2NR10R11, NR10S(O)2R10 or NR10S(O)2R11;
• each of R3b, R3c and R3d, independently, is H, F, Cl, Br, I, CF3, CF2CF3 OCF3 OCF2CF3, CN, NO2 NH2, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, acetylenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, OH, methoxyl, ethoxyl, propoxyl, SH, thiomethyl or thioethyl;
• R4 is H, halo, haloalkyl, NO2, CN, NR7R7, OR7;
• SR7, C(O)R7, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl or C3-10-cycloalkyl, each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl and C3-10-cycloalkyl optionally comprising 1-4 heteroatoms selected from N, O and S and optionally substituted with 1-5 substituents of R9;
• R5 is H, halo, haloalkyl, NO2, CN, NR7R7, OR7;
• SR7, C(O)R7, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl or C3-10-cycloalkyl, each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl and C3-10-cycloalkyl optionally comprising 1-4 heteroatoms selected from N, O and S and optionally substituted with 1-5 substituents of R9;
• R6 is H, halo, haloalkyl, NO2, CN, SR7, OR7, C(O)R7, COOR7, OC(O)R7, NR7R7, NR7R8, C(O)NR7R7, C(O)NR7R8, NR7C(O)R7, NR7C(O)NR7R8, S(O)NR7R8, S(O)2NR7R8 , NR7S(O)NR7R8, NR7S(O)2NR7R8, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl or C4-10-cycloalkenyl, each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl and C4-10-cycloalkenyl optionally comprising 1-4 heteroatoms selected from N, O and S and optionally substituted with 1-5 substituents of R8 or R9;
• R7 is R8 or R9;
• R8 is a partially or fully saturated or unsaturated 5-8 membered monocyclic, 6-12 membered bicyclic, or 7-14 membered tricyclic ring system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, and wherein said ring system is optionally substituted independently with 1-5 substituents of R9, oxo, NR9R9, OR9;
• SR9, C(O)R9 or a partially or fully saturated or unsaturated 5-6 membered ring of carbon atoms optionally including 1-3 heteroatoms selected from O, N, or S, and optionally substituted independently with 1-5 substituents of R9;
• R9 is H, halo, haloalkyl, CN, OH, NO2, NH2, acetyl, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl, C1-10-thioalkoxyl or a saturated or partially or fully unsaturated 5-8 membered monocyclic or a 6-12 membered bicyclic, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, wherein each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl, C1-10-thioalkoxyl and ring of said ring system is optionally substituted independently with 1-5 substituents of halo, haloalkyl, CN, NO2, NH2, OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, methylamino, dimethylamino, ethylamino, diethylamino, propylamino, isopropylamino, dipropylamino, diisopropylamino, benzyl or phenyl;
• R10 is H, halo, haloalkyl, CN, NO2, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl or C4-10-cycloalkenyl, each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl and C4-10-cycloalkenyl optionally comprising 1-4 heteroatoms selected from N, O and S and optionally substituted with 1-5 substituents of R11, R12 or R16, NR11R12, NR12R12, OR11, SR11, OR12, SR12, C(O)R11, OC(O)R11, COOR11, C(O)R12, OC(O)R12, COOR12, C(O)NR11R12, NR12C(O)R11, C(O)NR12R12, NR12C(O)R12, NR12C(O)NR11R12, NR12C(O)NR12R12, NR12(COOR11), NR12(COOR12), OC(O)NR11R12, OC(O)NR12R12, S(O)2R11, S(O)2R12, S(O)2NR11R12, S(O)2NR12R12, NR12S(O)2NR11R12, NR12S(O)2NR12R12, NR12S(O)2R11, NR12S(O)2R12, NR12S(O)2R11 or NR12S(O)2R12;
• R11 is a partially or fully saturated or unsaturated 5-8 membered monocyclic, 6-12 membered bicyclic, or 7-14 membered tricyclic ring system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, and wherein each ring of said ring system is optionally substituted independently with 1-5 substituents of R12, R13, R14 or R16;
• alternatively, R10 and R11 taken together form a partially or fully saturated or unsaturated 5-6 membered ring of carbon atoms optionally including 1-3 heteroatoms selected from O, N, or S, and the ring optionally substituted independently with 1-5 substituents of R12, R13, R14 or R16;
• R12 is H, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-allcoxyl or C1-10-thioalkyl, each of which is optionally substituted independently with 1-5 substituents of R13, R14, R15 or R16;
• R13 is NR14R15, NR15R15, OR14;
• SR14, OR15;
• SR15, C(O)R14, OC(O)R14, COOR14, C(O)R15, OC(O)R15, COOR15, C(O)NR14R15, C(O)NR15R15, NR14C(O)R14, NR15C(O)R14, NR14C(O)R15, NR15C(O)R15, NR15C(O)NR14R15, NR15C(O)NR15R15, NR15(COOR14), NR15(COOR15), OC(O)NR14R15, OC(O)NR15R15, S(O)2R14, S(O)2R15, S(O)2NR14R15, S(O)2NR15R15, NR14S(O)2NR14R15, NR15S(O)2NR15R15, NR14S(O)2R14 or NR15S(O)2R15;
• R14 is a partially or fully saturated or unsaturated 5-8 membered or a saturated or partially or fully unsaturated 5-8 membered monocyclic, 6-12 membered bicyclic, or 7-14 membered tricyclic ring system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic, said heteroatoms selected from O, N, or S, and wherein said ring system is optionally substituted independently with 1-5 substituents of R15 or R16;
• R15 is H or C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl or C1-10-thioalkoxyl, each of which is optionally substituted independently with 1-5 substituents of R16;
• and
• R16 is H halo, haloalkyl, CN, OH, NO2, NH2, OH, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, methylamino, dimethylamino, ethylamino, diethylamino, isopropylamino, oxo, acetyl, benzyl, phenyl, cyclopropyl, cyclobutyl or a partially or fully saturated or unsaturated 5-8 membered monocyclic or 6-12 membered bicyclic ring system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, and optionally substituted independently with 1-5 substituents of halo, haloalkyl, CN, NO2, NH2, OH, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, methylamino, dimethylamino, ethylamino, diethylamino, propylamino, isopropylamino, dipropylamino, diisopropylamino, benzyl or phenyl,
• provided that the compound is not 1-piperazinecarboxylic acid, 4-[-4-[[4-fluoro-3-[2-(3H-imidazo4,5-b]pyridin-6-yl)ethynyllbenzoyl]amino]-2-(trifluoromethyl)phenyl]-, 1,1-dimethylethyl ester or 1-piperazinecarboxylic acid, 4-[4-[[3-[2-(3H-imidazo[4,5b]pyridin-6-yl)ethynyl]benzoyl]amino]-2-(trifluoromethyl)phenyl]-, 1,1-dimethylethyl ester.