Nitrogen-containing bicyclic heteroaryl compounds and methods of use

A compound of Formula I:

• or stereoisomer, tautomer, solvate, pharmaceutically acceptable salt, derivative or prodrug thereof, wherein
• Z is
• Z′ is a 5- or 6-membered aromatic ring of carbon atoms optionally comprising 1-3 heteroatoms selected from N, O and S, such that Z′ and Z taken together form a fused 8-, 9- or 10-membered heteroaryl or heterocyclic ring;
• R1 is
• wherein
• each of A1, A1a, A2, A3 and A4 is, independently, CR6 or N;
• X is CR6R6, C(O), NR6, O or S(O)p wherein p is 0, 1, or 2;
• R4 is halo, haloalkyl, NO2, CN, R7, NR7R7, NR7R8, OR7, SR7, OR8, SR8, C(O)R7, OC(O)R7, COOR7, C(O)R8, OC(O)R8, COOR8, C(O)NR7R7, C(S)NR7R7, NR7C(O)R7, NR7C(S)R7, NR7C(O)NR7R7, NR7C(S)NR7R7, NR7(COOR7), OC(O)NR7R7, C(O)NR7R8, C(S)NR7R8, NR7C(O)R8, NR7C(S)R8, NR7C(O)NR7R8, NR7C(S)NR7R8, NR7(COOR8), OC(O)NR7R8, S(O)2R7, S(O)2NR7R7, NR7S(O)2NR7R7, NR7S(O)2R7, S(O)2R8, S(O)2NR7R8, NR7S(O)2NR7R8 or NR7S(O)2R8;
• alternatively, R4 taken together with the R6 of A1a when A1a is CR6, form a 5- or 6-membered ring of carbon atoms optionally comprising 1-3 heteroatoms selected from N, O and S, and optionally substituted with 1-3 substituents of NR7R7, NR7R8, OR7, SR7, OR8, SR8, C(O)R7, C(O)R8, C(O)NR7R7, NR7C(O)R7, NR7C(O)NR7R7, NR7(COOR7), C(O)NR7R8, NR7C(O)R8, NR7C(O)NR7R8, NR7(COOR8), S(O)2R7, S(O)2NR7R7, NR7S(O)2NR7R7, NR7S(O)2R7, S(O)2R8, S(O)2 NR7R8, NR7S(O)2NR7R8 NR7S(O)2R8 or R9;
• R5 is H, halo, haloalkyl, NO2, CN, OR7, SR7, NR7R7, NR7R8, C(O)R7, COOR7, C(O)NR7R7, C(O)NR7R8, NR7C(O)NR7R7, NR7C(O)NR7R8, OC(O)NR7R8, S(O)2R7, S(O)2NR7R7, S(O)2NR7R8, NR7S(O)2R7, NR7S(O)2R8, 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 one or more substituents of R8 or R9;
• each R6 is, independently, H, halo, haloalkyl, NO2, CN, NR7R7, NR7R8, OR7, SR7, C(O)R7, OC(O)R7, COOR7, C(O)NR7R7, C(O)NR7R8, NR7C(O)R7, NR7C(O)R8, NR8C(O)NR7R8, NR7 (COOR7), OC(O)NR7R8, S(O)2R7, S(O)2NR7R8, NR7S(O)2NR7R8, NR7S(O)2R7, NR7S(O)2R7, 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 one or more substituents of R8 or R9;
• R2 is halo, haloalkyl, NO2, CN, NR7R7, NR7R8, OR7,
• SR7, C(O)R7, OC(O)R7, COOR7, C(O)NR7R7, C(O)NR7R8, NR7C(O)R7, NR7C(O)R8, NR8C(O)NR7R8, NR7(COOR7), OC(O)NR7R8, S(O)2R7, S(O)2NR7R8, NR7S(O)2NR7R8, NR7S(O)2R7, NR7S(O)2R7, 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 one or more substituents of R8 or R9;
• R3 is NR10R10, NR10R11, OR10, SR10, OR11, SR11, C(O)R10, C(S)R10, C(NCN)R10, C(O)R11, C(S)R11, C(NCN)R11, C(O)C(O)R10, OC(O)R10, COOR10, C(O)SR10, C(O)C(O)R11, OC(O)R11, COOR11, C(O)SR11, C(O)NR10R10, C(S)NR10R10, C(O)NR10R11, C(S)NR10R11, OC(O)NR10R11, NR10C(O)R10, NR10C(O)R10, NR10C(S)R10, NR10C(S)R11, NR10C(O)NR10R10, NR10C(O)NR10R11, NR10C(S)NR10R10, NR10C(S)NR10R11, NR10(COOR10), NR10(COOR11), NR10C(O)C(O)R10, NR10C(O)C(O)R11, NR10C(O)C(O)NR10R11, S(O)2R10, S(O)2R11, S(O)2NR10R10, S(O)2NR10R11, NR10S(O)2NR10R11, NR10S(O)2R10 or NR10S(O)2R11;
• R7 is H, 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 one or more substituents of NR8R9, NR9R9, OR8, SR8, OR9, SR9, C(O)R8, OC(O)R8, COOR8, C(O)R9, OC(O)R9, COOR9, C(O)NR8R9, C(O)NR9R9, NR9C(O)R8, NR9C(O)R9, NR9C(O)NR8R9, NR9C(O)NR9R9, NR9(COOR8), NR9(COOR9), OC(O)NR8R9, OC(O)NR9R9, S(O)2R8, S(O)2NR8R9, S(O)2R9, S(O)2NR9R9, NR9S(O)2NR8R9, NR9S(O)2NR9R9, NR9S(O)2R8, NR9S(O)2R9 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 each ring of 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;
• alternatively, R7 and R8 taken together form a saturated or partially or fully 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 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, 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, 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, methylamine, dimethylamine, ethylamine, diethylamine, propylamine, isopropylamine, dipropylamine, diisopropylamine, benzyl or phenyl;
• R10 is H, 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 one or more 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)NR11R11R12, 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-alkoxyl 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)R15C(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, NR4S(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 each ring of 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;
• 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, isopropylamino, benzyl or phenyl;
• R17 is H, halo, haloalkyl, CN, OH, NO2, NH2, acetyl, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, cyclopropyl, butyl, isobutyl, sec-butyl, tert-butyl, methylamine, dimethylamine, ethylamine, diethylamine, propylamine, isopropylamine, dipropylamine, diisopropylamine, butylamine, benzyl or phenyl;
• and
• n is 0, 1, 2 or 3,
• provided that (1) when Z and Z′ taken together form a fused ring of
• wherein n is 0 and R3 is NHR11, then (a) R1 is not phenyl, naphthyl or a mono- or bicyclic heteroaryl comprising 1, 2 or 3 nitrogen atoms and optionally substituted with C1-6-alkyl, C1-6-alkoxyl or C1-6-haloalkyl, and (b) R11 is not a benzimidazole, benzothiazole, isoquinoline, quinoline or an optionally substituted phenyl ring.