Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease

A compound of the Formula I:

• 70
• wherein Azabicyclo is
• 71 72
• provided that the bond between the —C(═X)— group and the W group may be attached at any available carbon atom within the W group as provided in R3, R6, and R15;
• X is O, or S;
• R0 is H, lower alkyl, substituted lower alkyl, or halogenated lower alkyl;
• Each R1 is H, alkyl, cycloalkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl;
• Each R2 is alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, aryl, F, Cl, Br, I, or R2 is absent provided that k2, k5, or k6 is 0;
• R2-3 is H, alkyl, substituted alkyl, halogenated alky, F, Cl, Br, or I;
• k2 is 0 or 1;
• k5 and k6 are independently 0, 1, or 2;
• A-A′-A″ is N(R4)—C(R3)═C(R3), N═C(R3)—C(R15)2, C(R3)═C(R3)—N(R4), C(R3)2—N(R4)—C(R3)2, C(R15)2—C(R3)═N,N(R4)—C(R3)2—C(R3)2, C(R3)2—C(R3)2—N(R4), O—C(R3)═C(R3), O—C(R3)2—C(R3)2, C(R3)2—O—C(R3)2, C(R3)═C(R3)—O, C(R3)2—C(R3)2—O, S—C(R3)═C(R3), S—C(R3)2—C(R3)2, C(R3)2—S—C(R3)2, C(R3)—C(R3)—S, or C(R3)2—C(R3)2—S;
• Each R3 is independently a bond to the core molecule provided that only one R3 and no R6 or R15 is also said bond, H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, —CN, —NO2, F, Br, Cl, I, —OR19, —C(O)N(R10)2, —N(R10)2, —SR19, —S(O)2R19, —C(O)R19, —CO2R19, aryl, R7, or R9;
• J, L, M, and Q are N or C(R6) provided that only one of J, L, M, or Q, is N and the others are C(R6), further provided that when the core molecule is attached to the pyridinyl moiety at M, Q is C(H), and further provided that there is only one attachment to the core molecule;
• G and Y are C(R6), provided that when the molecule is attached to the phenyl moiety at Y, G is CH;
• R4 is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R7, or R9;
• Each R5 is independently H, lower alkyl, or lower alkenyl;
• Each R6 is independently H, F, Br, I, Cl, —CN, —CF3, —OR5, —SR5, —N(R5)2, or a bond to the core molecule provided that only one R6 and no R3 or R15 is said bond;
• V is selected from O, S, or N(R4);
• R7 is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms independently selected from the group consisting of ═N—, —N(R17)—, —O—, and —S—, and having 0-1 substituent selected from R18 and further having 0-3 substituents independently selected from F, Cl, Br, or I, or R7 is 9-membered fused-ring moieties having a 6-membered ring fused to a 5-membered ring including the formula
• 73
• wherein G1 is O, S or NR17,
• 74
• wherein G is C(R16) or N, and each G2 and G3 are independently selected from C(R16)2, C(R16), O, S, N, and N(R18), provided that both G2 and G3 are not simultaneously 0, simultaneously S, or simultaneously O and S, or
• 75
• wherein G is C(R16) or N, and each G2 and G3 are independently selected from C(R16)2, C(R16), O, S, N, and N(R17), each 9-membered fused-ring moiety having 0-1 substituent selected from R18 and further having 0-3 substituent(s) independently selected from F, Cl, Br, or I, wherein the R7 moiety attaches to other substituents as defined in formula I at any position on either ring as valency allows;
• Each R8 is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R7, R9, phenyl, or substituted phenyl;
• R9 is 6-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms selected from ═N— and having 0-1 substituent selected from R18 and 0-3 substituent(s) independently selected from F, Cl, Br, or I, or R9 is 10-membered heteroaromatic bi-cyclic moieties containing within one or both rings 1-3 heteroatoms selected from ═N—, including, but not limited to, quinolinyl or isoquinolinyl, each 10-membered fused-ring moiety having 0-1 substituent selected from R18 and 0-3 substituent(s) independently selected from F, Cl, Br, or I, and having a bond directly or indirectly attached to the core molecule where valency allows;
• Each R10 is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with I substituent selected from R13, cycloalkyl substituted with 1 substituent selected from R13, heterocycloalkyl substituted with I substituent selected from R13, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;
• Each R11 is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;
• R12 is —NO2, —CN, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, —OR11, —SR11, —NR11R11, —C(O)R11, —C(O)NR R11, —NR11C(O)R11, —S(O)2NR11R11, or —NR11S(O)2R11;
• R13 is —CN, —CF3, —NO2, —OR11, —SR11, —NR11R11, —C(O)R11, —C(O)NR11R11, —NR11C(O)R11, —S(O)2NR11R11, or —NR11S(O)2R11;
• Each R14 is H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO2, —OR19, —C(O)N(R10)2, —N(R10)2, —SR19, —S(O)2R9, —C(O)R19, —CO2R19, aryl, R7 or R9;
• Each R15 is independently alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO2, —OR19, —C(O)N(R10)2, —N(R10)2, —SR19, —CO2R19, aryl, R7, R9, or a bond to the core molecule provided that only one R15 and no R6 or R3 is said bond;
• Each R16 is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, F, Cl, Br, I, —NO2, —CN, —OR11, —SR11, —NR11R11, —C(O)R11, —C(O)NR11R11, —NR11C(O)R11, —S(O)2NR11R11, —NR11S(O)2R11, or a bond directly or indirectly attached to the core molecule, provided that there is only one said bond to the core molecule within the 9-membered fused-ring moiety, further provided that the fused-ring moiety has 0-1 substituent selected from alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, —OR11, —SR11, —NR11R11, —C(O)R11, —NO2, —C(O)NR11R11, —CN, —NR11C(O)R11, —S(O)2NR11R1, or —NR11S(O)2R11, and further provided that the fused-ring moiety has 0-3 substituent(s) selected from F, Cl, Br, or I;
• R17 is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, phenyl, —SO2R8, or phenyl having 1 substituent selected from R18 and further having 0-3 substituents independently selected from F, Cl, Br, or I;
• R18 is alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, —OR11, —SR11, —NR11R11, —C(O)R11, —C(O)NR11R11, —CN, —NR11C(O)R11, —S(O)2NR11R11, —NR11S(O)2R11, —NO2, alkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R13, cycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R13, or heterocycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R13;
• R19 is H, alkyl, cycloalkyl, substituted alkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl;
• or pharmaceutically acceptable salt, racemic mixture, and pure enantiomer thereof.