Azabicyclic compounds for the treatment of disease

A compound of the Formula I:

• wherein Azabicyclo is
• X is O or S;
• R1 is H, alkyl, halogenated alkyl, cycloalkyl, substituted phenyl, or substituted naphthyl;
• R2 is H, F, Cl, Br, I, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, or aryl;
• k is 1 or 2;
• W is any positional isomer of pyridinyl, pyrimidinyl, naphthyl, quinolinyl, or isoquinolinyl, any of which is optionally substituted with 1–2 substituents independently selected from F, Cl, lower alkyl, lower halogenated alkyl, lower substituted alkyl, lower alkynyl, ——CN, ——NO2, ——OR10, ——SR10, ——N(R10)2, ——C(O)N(R10)2, or —C(O)R10, wherein each R10 is independently H, lower alkyl, or lower halogenated alkyl,
• wherein substituted alkyl is an alkyl moiety from 1–6 carbon atoms having 0–3 substituents independently selected from F, Cl, Br, or I and further having 1 substituent selected from R7, R9, ——OR10, ——SR10, ——NR10R10, ——C(O)R10, ——C(O)NR10R10, ——CN, ——NR10C(O)R10, ——S(O)2NR10R10, ——NR10S(O)2R10, ——NO2, phenyl, or phenyl having 1 substituent selected from R15 and further having 0–3 substituents independently selected from F, Cl, Br, or I;
• and
• wherein lower substituted alkyl is lower alkyl having 0–3 substituents independently selected from F, Cl, Br, or I, and further having 1 substituent selected from ——OR10, ——SR10, ——N(R10)2, ——C(O)R10, ——C(O)N(R10)2, ——CN, ——NR10C(O)R10, ——S(O)2N(R10)2, ——NR10S(O)2R10, ——NO2, or phenyl,
• wherein each R10 is independently H, lower alkyl, cycloalkyl, heterocycloalkyl, or phenyl,
• wherein any lower alkyl, cycloalkyl, heterocycloalkyl, or phenyl is optionally substituted with up to two halogens independently selected from F or Cl, and is further optionally substituted with one other substituent independently selected from ——OR11, ——SR11, ——N(R11)2, ——C(O)R11, ——C(O)N(R11)2, ——CN, ——CF3, ——NR11C(O)R11, ——S(O)2N(R11)2, ——NR11S(O)2R11, or ——NO2, and
• wherein each R11 is independently H, lower alkyl, lower cycloalkyl, heterocycloalkyl, lower halogenated alkyl, lower halogenated cycloalkyl, or halogenated heterocycloalkyl;
• and
• wherein substituted alkenyl is an unsaturated alkenyl moiety having from 2–6 carbon atoms and having 0–3 substituents independently selected from F, or Cl, and further having 1 substituent selected from R7, R9, ——OR10, ——SR10, ——NR10R10, ——C(O)R10, ——C(O)NR10R10, ——NR10C(O)R10, ——S(O)2NR10R10, —NR10S(O)2R10, —CN, phenyl, or phenyl having 1 substituent selected from R15, and further having 0–3 substituents independently selected from F, Cl, Br, or I, wherein each R10 is independently H, lower alkyl, cycloalkyl, heterocycloalkyl, or phenyl, wherein any lower alkyl, cycloalkyl, heterocycloalkyl, or phenyl is optionally substituted with up to two halogens independently selected from F or Cl, and is further optionally substituted with one other substituent independently selected from ——OR11, ——SR11, N(R11)2, ——C(O)R11, ——C(O)N(R11)2, ——CN, ——CF3, ——NR11C(O)R11, ——S(O)2N(R11)2, ——NR11S(O)2R11, or ——NO2, and wherein each R11 is independently H, lower alkyl, lower cycloalkyl, heterocycloalkyl, lower halogenated alkyl, lower halogenated cycloalkyl, or halogenated heterocycloalkyl;
• and
• wherein substituted alkynyl is an unsaturated alkynyl moiety having from 3–6 carbon atoms and having 0–3 substituents independently selected from F, or Cl, and further having 1 substituent selected from R7, R9, ——OR10, ——SR10, ——NR10R10, ——C(O)R10, ——C(O)NR10R10, ——NR10C(O)R10, ——S(O)2NR10R10, ——NR10S(O)2R10, ——CN, phenyl, or phenyl having 1 substituent selected from R15, and further having 0–3 substituents independently selected from F, Cl, Br, or I, wherein each R10 is independently H, lower alkyl, cycloalkyl, heterocycloalkyl, or phenyl, wherein any lower alkyl, cycloalkyl, heterocycloalkyl, or phenyl is optionally substituted with up to two halogens independently selected from F or Cl, and is further optionally substituted with one other substituent independently selected from ——OR11, ——SR11, ——N(R11)2, ——C(O)R11, ——C(O)N(R11)2, ——CN, CF3, ——NR11C(O)R11, ——S(O)2N(R11)2, ——NR11S(O)2R11, or ——NO2, and wherein each R11 is independently H, lower alkyl, lower cycloalkyl, heterocycloalkyl, lower halogenated alkyl, lower halogenated cycloalkyl, or halogenated heterocycloalkyl;
• and
• wherein substituted cycloalkyl is a cyclic moiety having from 3–6 carbon atoms and having 0–3 substituents independently selected from F, or Cl, and further having 1 substituent selected from ——OR10, ——SR10, ——NR10R10, ——C(O)R10, ——CN, ——C(O)NR10R10, ——NR10C(O)R10, ——S(O)2NR10R10, ——NR10S(O)2R10, ——NO2, phenyl, or phenyl having 1 substituent selected from R15, and further having 0–3 substituents independently selected from F, Cl, Br, or I;
• and
• wherein substituted heterocycloalkyl is a cyclic moiety having from 4–7 atoms with 1–2 atoms within the ring being ——S——, ——N(R19)——, or ——O—— and having 0–3 substituents independently selected from ——F, or ——Cl, and further having 1 substituent selected from R7, R9, ——OR10, ——SR10, ——NR10R10, ——C(O)R10, ——C(O)NR10R10, ——CN, ——NR10C(O)R10, ——NO2, ——S(O)2NR10R10, ——NR10S(O)2R10, phenyl, or phenyl having 1 substituent selected from R15 and further having 0–3 substituents independently selected from F, Cl, Br, or I;
• R7 is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1–3 heteroatoms independently selected from —O—, ═N—, —N(R14)—, and —S—, and having 0–1 substituent selected from R15 and 0–3 substituents independently selected from F, Cl, Br, or I,
• or R7 is a 9-membered fused-ring moiety having a 6-membered ring fused to a 5-membered ring and having the formula
• wherein each A is independently CR18 or N, provided that only up to one A is N, E1 and E2 are independently selected from CR18, O, S, or NR14, and G is CR18, provided that R18 or R14 of E1, E2, and G can be a bond when ———forms a double bond and further provided that only one R18 or R14 can be a bond for bonding R7 to a moiety to which it is attached;
• Each R8 is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, phenyl, or phenyl substituted with 0–4 substituents independently selected from F, Cl, Br, I, or R15;
• 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 R12 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—, each 10-membered fused-ring moiety having 0–1 substituent selected from R12 and 0–3 substituent(s) independently selected from F, Cl, Br, or I and having a bond for bonding R9 to a moiety to which it is attached where valency allows;
• Each R10 is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with 1 substituent selected from R13, cycloalkyl substituted with 1 substituent selected from R13, heterocycloalkyl substituted with 1 substituent selected from R13, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;
• Each R11 is independently H, alkyl, cycloalkyl, heterocyclo-alkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;
• R12 is —OR11—SR11, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, —NR11R11—C(O)R11, —NO2, —C(O)NR11R11, —CN, —NR11C(O)R11, —S(O)2NR11R11, or —NR11S(O)2R11;
• R13 is —OR11, —SR11, —NR11R11, —C(O)R11, —SOR11, —SO2R11, —C(O)NR11R11, —CN, —CF3, —NR11C(O)R11, —S(O)2NR11R11, —NR11S(O)2R11, or —NO2;
• Each R14 is independently H, alkyl, halogenated alkyl, limited substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, or substituted heterocycloalkyl;
• R15 is alkyl, substituted alkyl, halogenated alkyl, —OR11, —CN, —NO2, —NR10R10;
• Each R18 is independently selected from H, 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)2NR11R11, or —NR11S(O)2R11, F, CI, Br, or I, or a bond directly or indirectly attached to W, provided that there is only one said bond to W 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)2NR11R11, or —NR11S(O)2R11, and further provided that the fused-ring moiety has 0–3 substituent(s) selected from F, Cl, Br, or I;
• or a pharmaceutically acceptable salt, racemic mixture, or pure enantiomer thereof.