Azabicyclic-substituted fused heteroaryl compounds for the treatment of disease

Abstract

The invention provides compounds of Formula I: wherein Azabicyclo is These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful in pharmaceuticals in which α7 is known to be involved.

1 . A compound of the Formula I:  
     
       
         
         
             
             
         
       
     
     wherein Azabicyclo is  
     
       
         
         
             
             
         
       
     
     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 R 3 , R 6 , and R 15 ; 
 X is O, or S;  
 R 0  is H, lower alkyl, substituted lower alkyl, or halogenated lower alkyl;  
 Each R 1  is H, alkyl, cycloalkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl;  
 Each R 2  is alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, aryl, F, Cl, Br, I, or R 2  is absent provided that k 2 , k 5 , or k 6  is 0;  
 R 2-3  is H, alkyl, substituted alkyl, halogenated alkyl, F, Cl, Br, or I;  
 k 2  is 0 or 1;  
 k 5  and k 6  are independently 0, 1, or 2;  
 A---A′---A″ is N(R 4 )—C(R 3 )═C(R 3 ), N═C(R 3 )—C(R 5 ) 2 , C(R 3 )═C(R 3 )—N(R 4 ), C(R 3 ) 2 —N(R 4 )—C(R 3 ) 2 , C(R 15 ) 2 —C(R 3 )═N, N(R 4 )—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —C(R 3 ) 2 —N(R 4 ), O—C(R 3 )═C(R 3 ), O—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —O—C(R 3 ) 2 , C(R 3 )═C(R 3 )—O, C(R 3 ) 2 —C(R 3 ) 2 —O, S—C(R 3 )═C(R 3 ), S—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —S—C(R 3 ) 2 , C(R 3 )═C(R 3 )—S, or C(R 3 ) 2 —C(R 3 ) 2 —S;  
 Each R 3  is independently a bond to the core molecule provided that only one R 3  and no R 6  or R 15  is also said bond, H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, —CN, —NO 2 , F, Br, Cl, I, —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —S(O) 2 R 19 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7 , or R 9 ;  
 J, L, M, and Q are N or C(R 6 ) provided that only one of J, L, M, or Q, is N and the others are C(R 6 ), 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(R 6 ), provided that when the molecule is attached to the phenyl moiety at Y, G is CH;  
 R 4  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , or R 9 ;  
 Each R 5  is independently H, lower alkyl, or lower alkenyl;  
 Each R 6  is independently H, F, Br, I, Cl, —CN, —CF 3 , —OR 5 , —SR 5 , —N(R 5 ) 2 , or a bond to the core molecule provided that only one Rr and no R 3  or R 15  is said bond;  
 V is selected from O, S, or N(R 4 );  
 R 7  is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms independently selected from the group consisting of ═N—, —N(R 17 )—, —O—, and —S—, and having 0-1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I, or R 7  is 9-membered fused-ring moieties having a 6-membered ring fused to a 5-membered ring including the formula  
                     
 wherein G 1  is O, S or NR 17 ,  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 18 ), provided that both G 2  and G 3  are not simultaneously O, simultaneously S, or simultaneously O and S, or  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 17 ), each 9-membered fused-ring moiety having 0-1 substituent selected from R 18  and further having 0-3 substituent(s) independently selected from F, Cl, Br, or I, wherein the R 7  moiety attaches to other substituents as defined in formula I at any position on either ring as valency allows;  
 Each R 8  is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , R 9 , phenyl, or substituted phenyl;  
 R 9  is 6-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms selected from ═N— and having 0-1 substituent selected from R 18  and 0-3 substituent(s) independently selected from F, Cl, Br, or I, or R 9  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 R 18  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 R 10  is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with I substituent selected from R 13 , cycloalkyl substituted with 1 substituent selected from R 13 , heterocycloalkyl substituted with 1 substituent selected from R 13 , halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;  
 Each R 11  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;  
 R 12  is —NO 2 , —CN, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 ;  
 R 13  is —CN, —CF 3 , —NO 2 , —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 ;  
 Each R 14  is H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —S(O) 2 R 19 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7  or R 9 ;  
 Each R 15  is independently alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —CO 2 R 19 , aryl, R 7 , R 9 , or a bond to the core molecule provided that only one R 15  and no R 6  or R 3  is said bond;  
 Each R 16  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, F, Cl, Br, I, —NO 2 , —CN, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , 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, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —NO 2 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 , and further provided that the fused-ring moiety has 0-3 substituent(s) selected from F, Cl, Br, or I;  
 R 17  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, phenyl, —SO 2 R 9 , or phenyl having 1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I;  
 R 18  is alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 , S(O) 2 R 11 , —NO 2 , alkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , cycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , or heterocycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 ;  
 R 19  is H, alkyl, cycloalkyl, substituted alkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl;  
 or pharmaceutically acceptable salt, racemic mixture, and pure enantiomer thereof.  
 
   
   
       2 - 53 . (canceled)  
   
   
       54 . A compound of Formula I:  
     
       
         
         
             
             
         
       
     
     wherein Azabicyclo is  
     
       
         
         
             
             
         
       
     
     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 R 3 , R 6 , and R 15 ; 
 X is O;  
 Each R 1  is H, alkyl, or cycloalkyl.  
 Each R 2  is alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, aryl, F, Cl, Br, I, or R 2  is absent provided that k 2 , k 5 , or k 6  is 0;  
 k 2  is 0 or 1;  
 k 5  and k 6  are independently 0, 1, or 2;  
 A---A′---A″ is N(R 4 )—C(R 3 )═C(R 3 ), N═C(R 3 )—C(R 15 ) 2 , C(R 3 )═C(R 3 )—N(R 4 ), C(R 3 ) 2 —N(R 4 )—C(R 3 ) 2 , C(R 15 ) 2 —C(R 3 )═N, N(R 4 )—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —C(R 3 ) 2 —N(R 4 ), O—C(R 3 )═C(R 3 ), O—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —O—C(R 3 ) 2 , C(R 3 )═C(R 3 )—O, C(R 3 ) 2 —C(R 3 ) 2 —O, S—C(R 3 )═C(R 3 ), S—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —S—C(R 3 ) 2 , C(R 3 )═C(R 3 )—S, or C(R 3 ) 2 —C(R 3 ) 2 —S;  
 Each R 3  is independently a bond to the core molecule provided that only one R 3  and no R 6  or R 15  is also said bond, H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, —CN, —NO 2 , F, Br, Cl, I, —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —S(O) 2 R 19 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7 , or R 9 ;  
 J, L, M, and Q are N or C(R 6 ) provided that only one of J, L, M, or Q, is N and the others are C(R 6 ), 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;  
 R 4  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , or R 9 ;  
 Each R 5  is independently lower alkyl or lower alkenyl;  
 Each R 6  is independently H, F, Br, I, Cl, —CN, —CF 3 , —OR 5 , —SR 5 , —N(R 5 ) 2 , or a bond to the core molecule provided that only one R 6  and no R 3  or R 15  is said bond;  
 R 7  is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms independently selected from the group consisting of ═N—, —N(R 17 )—, —O—, and —S—, and having 0-1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I, or R 7  is 9-membered fused-ring moieties having a 6-membered ring fused to a 5-membered ring of the formula:  
                     
 wherein G 1  is O, S or NR 17 ,  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 18 ), provided that both G 2  and G 3  are not simultaneously O, simultaneously S, or simultaneously O and S, or  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 17 ), each 9-membered fused-ring moiety having 0-1 substituent selected from R 18  and further having 0-3 substituent(s) independently selected from F, Cl, Br, or I, wherein the R 7  moiety attaches to other substituents as defined in formula I at any position on either ring as valency allows;  
 Each R 8  is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , R 9 , phenyl, or substituted phenyl;  
 R 9  is 6-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms selected from ═N— and having 0-1 substituent selected from R 18  and 0-3 substituent(s) independently selected from F, Cl, Br, or I, or R 9  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 R 18  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 R 10  is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with 1 substituent selected from R 13 , cycloalkyl substituted with 1 substituent selected from R 13 , heterocycloalkyl substituted with 1 substituent selected from R 13 , halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;  
 Each R 11  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;  
 R 13  is —CN, —CF 3 , —NO 2 , —OR 11 , —SR 11 , —NR 11 R 11 —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 ;  
 Each R 14  is H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —S(O) 2 R 9 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7  or R 19 ;  
 Each R 15  is independently alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —CO 2 R 19 , aryl, R 7 , R 9 , or a bond to the core molecule provided that only one R 15  and no R 6  or R 3  is said bond;  
 Each R 16  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, F, Cl, Br, I, —NO 2 , —CN, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 1 , 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, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —NO 2 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 , and further provided that the fused-ring moiety has 0-3 substituent(s) selected from F, Cl, Br, or I;  
 R 17  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, phenyl, —SO 2 R 19 , or phenyl having 1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I;  
 R 8  is alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , —NO 2 , alkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , cycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , or heterocycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 ;  
 R 19  is H, alkyl, cycloalkyl, substituted alkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl;  
 or a pharmaceutically acceptable salt, racemic mixture, or pure enantiomer thereof.  
 
   
   
       55 . The compound according to  claim 54 , wherein A---A′---A″ is N(R 4 )—C(R 3 )═C(R 3 ), N═C(R 3 )—C(R 15 ) 2 , C(R 3 )═C(R 3 )—N(R 4 ), C(R 3 ) 2 —N(R 4 )—C(R 3 ) 2 , C(R 15 ) 2 —C(R 3 )═N, N(R 4 )—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —C(R 3 ) 2 —N(R 4 ), O—C(R 3 )═C(R 3 ), O—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —O—C(R 3 ) 2 , C(R 3 )═C(R 3 )—O, C(R 3 ) 2 —C(R 3 ) 2 —O, S—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —S—C(R 3 ) 2 , or C(R 3 ) 2 —C(R 3 ) 2 —S;  
   
   
       56 . The compound of  claim 54 , wherein (a) is thieno[2,3-b]pyridin-2-yl, thieno[2,3-b]pyridin-5-yl, thieno[2,3-b]pyridin-6-yl, thieno[3,2-b]pyridin-2-yl, thieno[3,2-b]pyridin-5-yl, thieno[3,2-b]pyridin-6-yl, thieno[2,3-c]pyridin-2-yl, thieno[2,3-c]pyridin-5-yl, thieno[3,2-c]pyridin-2-yl, thieno[3,2-c]pyridin-6-yl, furo[3,2-c]pyridin-2-yl, furo[3,2-c]pyridin-6-yl, furo[2,3-b]pyridin-2-yl, furo[2,3-c]pyridin-2-yl, furo[2,3-c]pyridin-5-yl, 2,3-dihydrofuro[2,3-c]pyridin-5-yl, or 1H-pyrrolo[2,3-c]pyridin-5-yl, 
 optionally substituted on up to 4 different carbon atoms as valency allows and as allowed by the definition of W with F, Br, Cl, I, —CN, —NO 2 , —CF 3 , —OR 5 , —OR 19 , —SR 5 , —SR 19 , —N(R 5 ) 2 , —N(R 10 ) 2 , —C(O)R 19 , —CO 2 R 19 , —C(O)N(R 10 ) 2 , —S(O) 2 R 19 , alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, aryl, R 7 , R 9 ,    and further optionally substituted on a nitrogen as allowed by the definition of W with alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , or R 9 ,    provided that one carbon is used to bond W to the core molecule.    
   
   
       57 . The compound of  claim 56 , wherein the optional substituents are selected from F, Br, Cl, I, —CN, —CF 3 , —OR 5 , —SR 5 , —N(R 5 ) 2 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 10 ) 2 , —S(O) 2 R 5 , lower alkyl, lower substituted alkyl, or lower alkynyl, 
 where R 10  is H, lower halogenated alkyl, or lower alkyl optionally substituted with —CN, —CF 3 , —NO 2 , —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 , wherein R 11  is H, lower alkyl, lower halogenated alkyl, or lower substituted alkyl.    
   
   
       58 . The compound of  claim 57 , wherein each k 5  and k 6  is independently 0 or 1.  
   
   
       59 . The compound of  claim 58 , wherein R 2  is alkyl, halogenated alkyl, substituted alkyl, or is absent provided that k 2 , k 5 , or k 6  is 0.  
   
   
       60 . The compound of  claim 59 , wherein R 1  is H or lower alkyl, and wherein R 2  is lower alkyl or is absent provided that k 2 , k 5 , or k 6  is 0.  
   
   
       61 . A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and a carrier, wherein formula I is:  
     
       
         
         
             
             
         
       
     
     wherein Azabicyclo is  
     
       
         
         
             
             
         
       
     
     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 R 3 , R 6 , and R 15 ; 
 X is O;  
 Each R 1  is H, alkyl, or cycloalkyl.  
 Each R 2  is alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, aryl, F, Cl, Br, I, or R 2  is absent provided that k 2 , k 5 , or k 6  is 0;  
 k 2  is 0 or 1;  
 k 5  and k 6  are independently 0, 1, or 2;  
 A---A′---A″ is N(R 4 )—C(R 3 )═C(R 3 ), N═C(R 3 )—C(R 15 ) 2 , C(R 3 )═C(R 3 )—N(R 4 ), C(R 3 ) 2 —N(R 4 )—C(R 3 ) 2 , C(R 15 ) 2 —C(R 3 )═N, N(R 4 )—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —C(R 3 ) 2 —N(R 4 ), O—C(R 3 )═C(R 3 ), O—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —O—C(R 3 ) 2 , C(R 3 )═C(R 3 )—O, C(R 3 ) 2 —C(R 3 ) 2 —O, S—C(R 3 )═C(R 3 ), S—C(R 3 ) 2 —C(R 3 ) 2 , C(R 3 ) 2 —S—C(R 3 ) 2 , C(R 3 )═C(R 3 )—S, or C(R 3 ) 2 —C(R 3 ) 2 —S;  
 Each R 3  is independently a bond to the core molecule provided that only one R 3  and no R 6  or R 15  is also said bond, H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, —CN, —NO 2 , F, Br, Cl, I, —OR 9 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 9 , —S(O) 2 R 19 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7 , or R 9 ;  
 J, L, M, and Q are N or C(R 6 ) provided that only one of J, L, M, or Q, is N and the others are C(R 6 ), 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;  
 R 4  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , or R 9 );  
 Each R 5  is independently lower alkyl or lower alkenyl;  
 Each R 6  is independently H, F, Br, I, Cl, —CN, —CF 3 , —OR 5 , —SR 5 , —N(R 5 ) 2 , or a bond to the core molecule provided that only one R 6  and no R 3  or R 15  is said bond;  
 R 7  is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms independently selected from the group consisting of ═N—, —N(R 17 )—, —O—, and —S—, and having 0-1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I, or R 7  is 9-membered fused-ring moieties having a 6-membered ring fused to a 5-membered ring of the formula:  
                     
 wherein G 1  is O, S or NR 17 ,  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 18 ), provided that both G 2  and G 3  are not simultaneously 0, simultaneously S, or simultaneously O and S, or  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 17 ), each 9-membered fused-ring moiety having 0-1 substituent selected from R 18  and further having 0-3 substituent(s) independently selected from F, Cl, Br, or I, wherein the R 7  moiety attaches to other substituents as defined in formula I at any position on either ring as valency allows;  
 Each R 8  is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , R 9 , phenyl, or substituted phenyl;  
 R 9  is 6-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms selected from ═N— and having 0-1 substituent selected from R 18  and 0-3 substituent(s) independently selected from F, Cl, Br, or I, or R 9  is I O-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 R 18  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 R 10  is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with 1 substituent selected from R 13 , cycloalkyl substituted with 1 substituent selected from R 13 , heterocycloalkyl substituted with 1 substituent selected from R 13 , halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;  
 Each R 11  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;  
 R 13  is —CN, —CF 3 , —NO 2 , —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 ;  
 Each R 14  is H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 9 , —S(O) 2 R 19 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7  or R 9 ;  
 Each R 15  is independently alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —CO 2 R 19 , aryl, R 7 , R 9 , or a bond to the core molecule provided that only one R 15  and no R 6  or R 3  is said bond;  
 Each R 16  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, F, Cl, Br, I, —NO 2 , —CN, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , 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, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —NO 2 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 , and further provided that the fused-ring moiety has 0-3 substituent(s) selected from F, Cl, Br, or I;  
 R 17  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, phenyl, —SO 2 R 8 , or phenyl having 1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I;  
 R 18  is alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , —NO 2 , alkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , cycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , or heterocycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 ;  
 R 19  is H, alkyl, cycloalkyl, substituted alkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl.  
 
   
   
       62 . A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and a carrier, wherein formula I is:  
     
       
         
         
             
             
         
       
     
     wherein Azabicyclo is  
     
       
         
         
             
             
         
       
     
     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 R 6 ; 
 X is O;  
 Each R 1  is H, alkyl, or cycloalkyl.  
 Each R 2  is alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, aryl, F, Cl, Br, I, or R 2  is absent provided that k 2 , k 5 , or k 6  is 0;  
 k 2  is 0 or 1;  
 k 5  and k 6  are independently 0, 1, or 2;  
 J, L, M, and Q are N or C(R 6 ) provided that only one of J, L, M, or Q, is N and the others are C(R 6 ), 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;  
 R 4  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , or R 9 ;  
 Each R 5  is independently H, lower alkyl, or lower alkenyl;  
 Each R 6  is independently H, F, Br, I, Cl, —CN, —CF 3 , —OR 5 , —SR 5 , —N(R 5 ) 2 , or a bond to the core molecule provided that only one R 6  is said bond;  
 V is selected from O, S, or N(R 4 );  
 R 7  is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms independently selected from the group consisting of ═N—, —N(R 17 )—, —O—, and —S—, and having 0-1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I, or R 7  is 9-membered fused-ring moieties having a 6-membered ring fused to a 5-membered ring of the formulas:  
                     
 wherein G 1  is O, S or NR 17 ,  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 18 ), provided that both G 2  and G 3  are not simultaneously O, simultaneously S, or simultaneously O and S, or  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 17 ), each 9-membered fused-ring moiety having 0-1 substituent selected from R 18  and further having 0-3 substituent(s) independently selected from F, Cl, Br, or I, wherein the R 7  moiety attaches to other substituents as defined in formula I at any position on either ring as valency allows;  
 Each R 8  is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , R 9 , phenyl, or substituted phenyl;  
 R 9  is 6-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms selected from ═N— and having 0-1 substituent selected from R 18  and 0-3 substituent(s) independently selected from F, Cl, Br, or I, or R 9  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 R 18  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 R 10  is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with 1 substituent selected from R 13 , cycloalkyl substituted with 1 substituent selected from R 13 , heterocycloalkyl substituted with 1 substituent selected from R 13 , halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;  
 Each R 11  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;  
 R 13  is —CN, —CF 3 , —NO 2 , —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 ;  
 Each R 14  is H, alkyl, substituted alkyl, halogenated alkyl, alkenyl, substituted alkenyl, halogenated alkenyl, alkynyl, substituted alkynyl, halogenated alkynyl, F, Br, Cl, I, —CN, —NO 2 , —OR 19 , —C(O)N(R 10 ) 2 , —N(R 10 ) 2 , —SR 19 , —S(O) 2 R 19 , —C(O)R 19 , —CO 2 R 19 , aryl, R 7  or R 9 ;  
 Each R 16  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, F, Cl, Br, I, —NO 2 , —CN, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , 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, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —NO 2 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11  S(O) 2 R 11 , and further provided that the fused-ring moiety has 0-3 substituent(s) selected from F, Cl, Br, or I;  
 R 17  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, phenyl, —SO 2 R 8 , or phenyl having 1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I;  
 R 18  is alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , —NO 2 , alkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , cycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , or heterocycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 ;  
 R 19  is H, alkyl, cycloalkyl, substituted alkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl.  
 
   
   
       63 . A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and a carrier, wherein formula I is:  
     
       
         
         
             
             
         
       
     
     wherein Azabicyclo is  
     
       
         
         
             
             
         
       
     
     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 R 6 ; 
 X is O;  
 Each R 1  is H, alkyl, or cycloalkyl.  
 Each R 2  is alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, aryl, F, Cl, Br, I, or R 2  is absent provided that k 2 , k 5 , or k 6  is 0;  
 k 2  is 0 or 1;  
 k 5  and k 6  are independently 0, 1, or 2;  
 J, L, M, and Q are N or C(R 6 ) provided that only one of J, L, M, or Q, is N and the others are C(R 6 ), 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(R 6 ), provided that when the molecule is attached to the phenyl moiety at Y, G is CH;  
 R 4  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , or R 9 ;  
 Each R 5  is independently H, lower alkyl, or lower alkenyl;  
 Each R 6  is independently H, F, Br, 1, Cl, —CN, —CF 3 , —OR 5 , —SR 5 , —N(R 5 ) 2 , or a bond to the core molecule provided that only one R 1  is said bond;  
 V is selected from O, S, or N(R 4 );  
 R 7  is 5-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms independently selected from the group consisting of ═N—, —N(R 17 )—, —O—, and —S—, and having 0-1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I, or R 7  is 9-membered fused-ring moieties having a 6-membered ring fused to a 5-membered ring of the formulas  
                     
 wherein G 1  is O, S or NR 17 ,  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 18 ), provided that both G 2  and G 3  are not simultaneously O, simultaneously S, or simultaneously O and S, or  
                     
 wherein G is C(R 16 ) or N, and each G 2  and G 3  are independently selected from C(R 16 ) 2 , C(R 16 ), O, S, N, and N(R 17 ), each 9-membered fused-ring moiety having 0-1 substituent selected from R 18  and further having 0-3 substituent(s) independently selected from F, Cl, Br, or I, wherein the R 7  moiety attaches to other substituents as defined in formula I at any position on either ring as valency allows;  
 Each R 8  is independently H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, heterocycloalkyl, halogenated heterocycloalkyl, substituted heterocycloalkyl, R 7 , R 9 , phenyl, or substituted phenyl;  
 R 9  is 6-membered heteroaromatic mono-cyclic moieties containing within the ring 1-3 heteroatoms selected from ═N— and having 0-1 substituent selected from R 18  and 0-3 substituent(s) independently selected from F, Cl, Br, or I, or R 9  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 R 18  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 R 10  is independently H, alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted with 1 substituent selected from R 13 , cycloalkyl substituted with 1 substituent selected from R 13 , heterocycloalkyl substituted with 1 substituent selected from R 13 , halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, phenyl, or substituted phenyl;  
 Each R 11  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, or halogenated heterocycloalkyl;  
 R 13  is —CN, —CF 3 , —NO 2 , —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 1 ;  
 Each R 16  is independently H, alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, F, Cl, Br, I, —NO 2 , —CN, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , 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, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —NO 2 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , or —NR 11 S(O) 2 R 11 , and further provided that the fused-ring moiety has 0-3 substituent(s) selected from F, Cl, Br, or I;  
 R 17  is H, alkyl, halogenated alkyl, substituted alkyl, cycloalkyl, halogenated cycloalkyl, substituted cycloalkyl, phenyl, —SO 2 R 8 , or phenyl having 1 substituent selected from R 18  and further having 0-3 substituents independently selected from F, Cl, Br, or I;  
 R 18  is alkyl, cycloalkyl, heterocycloalkyl, halogenated alkyl, halogenated cycloalkyl, halogenated heterocycloalkyl, —OR 11 , —SR 11 , —NR 11 R 11 , —C(O)R 11 , —C(O)NR 11 R 11 , —CN, —NR 11 C(O)R 11 , —S(O) 2 NR 11 R 11 , —NR 11 S(O) 2 R 11 , —NO 2 , alkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , cycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 , or heterocycloalkyl substituted with 1-4 substituent(s) independently selected from F, Cl, Br, I, or R 13 ;  
 R 19  is H, alkyl, cycloalkyl, substituted alkyl, halogenated alkyl, substituted phenyl, or substituted naphthyl.