2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole compounds and methods of use thereof

Abstract

This disclosure relates to new tricyclic compounds that may be used to modulate a histamine receptor in an individual. Compounds are described, including new 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole compounds. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

What is claimed is: 
     
         1 . A compound of the Formula (E): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8  perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; 
 each R 2a  and R 2b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R 2a  and R 2b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each R 3a  and R 3b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano hydroxyl, alkoxy, nitro or R 3a  and R 3b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each X 7 , X 8 , X 9  and X 10  is independently N or CR 4 ; 
 m and q are independently 0 or 1; 
 n is 0 or 1; 
 each R 4  is independently H, hydroxyl, nitro, cyano, halo, C 1 -C 8  perhaloalkyl, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8  perhaloalkoxy, C 1 -C 8  alkoxy, aryloxy, carboxyl, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl; 
 each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f)  to form a cycloalkyl moiety; 
 each R 10a  and R 10b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, hydroxyl, alkoxyl or R 10a  and R 10b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; and 
 Q is acyclic or cyclic acylamino, carbonylalkoxy, acyloxy, aminoacyl, aminocarbonylalkoxy, substituted or unsubstituted lactam or substituted or unsubstituted cycloalkyl; 
 provided that: (ia) Q is substituted or unsubstituted cycloalkyl or a lactam moiety when each of m, n and q is 0 and (ib) m, n and q are 0 when Q is a substituted or unsubstituted cycloalkyl or a lactam moiety, (ii) Q is cyclic acylamino only when each of m, n and q is 1, (iii) when Q is carbonylalkoxy, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is other than cycloalkyl and substituted alkyl; (iv) the compound is other than a compound in Table 1, and (v) the compound is other than 5-cyclohexyl-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole and 5-cyclopentyl-2,3,4,5-tetrahydro-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1H-pyrido[4,3-b]indol-1-one; 
 or a salt thereof. 
 
     
     
         2 . The compound of  claim 1  wherein the compound is selected from the group consisting of compounds 1-73, or a salt thereof. 
     
     
         3 . The compound of  claim 1  wherein each X 7 , X 8  and X 10  is CH, X 9  is N or CR 4  where R 4  is chloro, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is acyclic acylamino, aminoacyl or carbonylalkoxy. 
     
     
         4 . The compound of  claim 1  wherein each X 7 , X 8  and X 10  is CH, X 9  is CR 4  where R 4  is methyl, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is acyclic acylamino or aminoacyl. 
     
     
         5 . The compound of  claim 1  wherein each X 7 , X 8  and X 10  is CH, X 9  is N or CR 4  where R 4  is chloro or methyl, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is acylamino of the formula —C(O)NHR′ where R′ is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl or unsubstituted or substituted heterocyclyl. 
     
     
         6 . The compound of  claim 1  wherein each X 7 , X 8  and X 10  is CH, X 9  is N or CR 4  where R 4  is methyl, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is of the formula —NHC(O)R′ where R′ is alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, alkoxy or substituted alkoxy. 
     
     
         7 . A compound of the formula (Vc): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is methyl; 
 m and q are independently 0 or 1; 
 each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f)  to form a cycloalkyl moiety; and 
 Q is acyclic or cyclic acylamino, carbonylalkoxy, acyloxy, aminoacyl or aminocarbonylalkoxy; 
 or a salt thereof. 
 
     
     
         8 . The compound of  claim 7  wherein Q is acyclic acylamino, carbonylalkoxy or aminoacyl. 
     
     
         9 . The compound of  claim 7  wherein at least one of m and q is 1. 
     
     
         10 . A compound of the formula (Vf): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is methyl; 
 R 4  is chloro or methyl; 
 m and q are independently 0 or 1; 
 each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f)  to form a cycloalkyl moiety; and 
 Q is acyclic or cyclic acylamino, carbonylalkoxy, acyloxy, aminoacyl or aminocarbonylalkoxy; 
 provided that when R 4  is methyl, Q is acyclic or cyclic acylamino, acyloxy, aminoacyl or aminocarbonylalkoxy; 
 or a salt thereof. 
 
     
     
         11 . The compound of  claim 10  wherein R 1  is methyl and R 4  is chloro. 
     
     
         12 . The compound of  claim 10  wherein R 1  and R 4  are methyl and Q is acyclic acylamino, acyloxy, aminoacyl or aminocarbonylalkoxy. 
     
     
         13 . A compound of the formula (F): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8  perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; 
 each R 2a  and R 2b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R 2a  and R 2b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each R 3a  and R 3b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano hydroxyl, alkoxy, nitro or R 3a  and R 3b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each R 10a  and R 10b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, hydroxyl, alkoxyl or R 10a  and R 10b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; and or a salt thereof, 
 each X 7 , X 8 , X 9  and X 10  is independently N or CR 4 ; 
 each R 4  is independently H, hydroxyl, nitro, cyano, halo, C 1 -C 8  perhaloalkyl, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8  perhaloalkoxy, C 1 -C 8  alkoxy, aryloxy, carboxyl, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl; and 
 Q is substituted cycloalkyl or a lactam moiety: 
 or a salt thereof. 
 
     
     
         14 . The compound of  claim 13  wherein Q is a moiety selected from the structures: 
       
         
           
           
               
               
           
         
       
     
     
         15 . A compound of the formula (G): 
       
         
           
           
               
               
           
         
         or a salt thereof, 
       
       wherein:
 R 1a  is alkyl; 
 R 4a  is selected from alkyl, aryl, and substituted aryl; 
 R 5  is alkyl; and 
 R 8g  is selected from alkyl, substituted alkyl and aralkyl. 
 
     
     
         16 . The compound of  claim 15  wherein R 8g  is alkyl. 
     
     
         17 . The compound of any of  claims 1 - 16  wherein the compound modulates at least one of the following receptors: adrenergic receptor (e.g., α 1D , α 2A  and/or α 2B ), serotonin receptor (e.g., 5-HT 2A , 5-HT 2B , 5-HT 6  and/or 5-HT 7 ), dopamine receptor (e.g., D 2L ) and histamine receptor (e.g., H 1 , H 2  and/or H 3 ). 
     
     
         18 . A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of the formula (E): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8  perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; 
 each R 2a  and R 2b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R 2a  and R 2b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each R 3a  and R 3b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano hydroxyl, alkoxy, nitro or R 3a  and R 3b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each X 7 , X 8 , X 9  and X 10  is independently N or CR 4 ; 
 m and q are independently 0 or 1; 
 n is 0 or 1; 
 each R 4  is independently H, hydroxyl, nitro, cyano, halo, C 1 -C 8  perhaloalkyl, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8  perhaloalkoxy, C 1 -C 8  alkoxy, aryloxy, carboxyl, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl; 
 each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f)  to form a cycloalkyl moiety; 
 each R 10a  and R 10b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, hydroxyl, alkoxyl or R 10a  and R 10b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; and 
 Q is acyclic or cyclic acylamino, carbonylalkoxy, acyloxy, aminoacyl, aminocarbonylalkoxy, substituted or unsubstituted lactam or substituted or unsubstituted cycloalkyl; 
 provided that: (ia) Q is substituted or unsubstituted cycloalkyl or a lactam moiety when each of m, n and q is 0 and (ib) m, n and q are 0 when Q is a substituted or unsubstituted cycloalkyl or a lactam moiety, (ii) Q is cyclic acylamino only when each of m, n and q is 1, (iii) when Q is carbonylalkoxy, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is other than cycloalkyl and substituted alkyl; 
 or a salt thereof. 
 
     
     
         19 . The method of  claim 18 , further provided that (iv) the compound is other than a compound in Table 1, and (v) the compound is other than 5-cyclohexyl-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole and 5-cyclopentyl-2,3,4,5-tetrahydro-2-[(4-methyl-1H-imidazol-5-yl)methyl]-1H-pyrido[4,3-b]indol-1-one. 
     
     
         20 . The method of  claim 18  wherein the compound is selected from the group consisting of compounds I-73, CD1 and CD57, or a salt thereof. 
     
     
         21 . The method of  claim 20  wherein the compound is selected from the group consisting of compounds I-73 or a salt thereof. 
     
     
         22 . The method of  claim 18  wherein each X 7 , X 8  and X 10  is CH, X 9  is N or CR 4  where R 4  is chloro, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is acyclic acylamino, aminoacyl or carbonylalkoxy. 
     
     
         23 . The method of  claim 18  wherein each X 7 , X 8  and X 10  is CH, X 9  is CR 4  where R 4  is methyl, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is acyclic acylamino or aminoacyl. 
     
     
         24 . The method of  claim 18  wherein each X 7 , X 8  and X 10  is CH, X 9  is N or CR 4  where R 4  is chloro or methyl, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is acylamino of the formula —C(O)NHR′ where R′ is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl or unsubstituted or substituted heterocyclyl. 
     
     
         25 . The method of  claim 18  wherein each X 7 , X 8  and X 10  is CH, X 9  is N or CR 4  where R 4  is methyl, R 1  is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a  and R 10b  is H, each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is H when present and Q is of the formula —NHC(O)R′ where R′ is alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, alkoxy or substituted alkoxy. 
     
     
         26 . A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of the formula (Vc): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8  perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; 
 m and q are independently 0 or 1; 
 each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f)  to form a cycloalkyl moiety; and 
 Q is acyclic or cyclic acylamino, carbonylalkoxy, acyloxy, aminoacyl or aminocarbonylalkoxy; 
 or a salt thereof. 
 
     
     
         27 . The method of  claim 26  wherein R 1  is methyl. 
     
     
         28 . The method of  claim 26  wherein at least one of m and q is 1. 
     
     
         29 . A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of the formula (Vf): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8  perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; 
 each R 4  is independently H, hydroxyl, nitro, cyano, halo, C 1 -C 8  perhaloalkyl, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8  perhaloalkoxy, C 1 -C 8  alkoxy, aryloxy, carboxyl, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl; 
 m and q are independently 0 or 1; 
 each R 8a , R 8b , R 8c , R 8d , R 8e  and R 8f  is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f)  to form a cycloalkyl moiety; and 
 Q is acyclic or cyclic acylamino, carbonylalkoxy, acyloxy, aminoacyl or aminocarbonylalkoxy; 
 or a salt thereof. 
 
     
     
         30 . The method of  claim 29  wherein R 1  is methyl and R 4  is chloro. 
     
     
         31 . The method of  claim 29  wherein R 1  and R 4  are methyl and Q is acyclic acylamino, acyloxy, aminoacyl or aminocarbonylalkoxy. 
     
     
         32 . A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of the formula (F): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8  perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; 
 each R 2a  and R 2b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R 2a  and R 2b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each R 3a  and R 3b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, cyano hydroxyl, alkoxy, nitro or R 3a  and R 3b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; 
 each R 10a  and R 10b  is independently H, substituted or unsubstituted C 1 -C 8  alkyl, halo, hydroxyl, alkoxyl or R 10a  and R 10b  are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; and or a salt thereof, 
 each X 7 , X 8 , X 9  and X 10  is independently N or CR 4 ; 
 each R 4  is independently H, hydroxyl, nitro, cyano, halo, C 1 -C 8  perhaloalkyl, substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 2 -C 8  alkenyl, substituted or unsubstituted C 2 -C 8  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8  perhaloalkoxy, C 1 -C 8  alkoxy, aryloxy, carboxyl, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl; and 
 Q is substituted or unsubstituted cycloalkyl or a lactam moiety: 
 or a salt thereof. 
 
     
     
         33 . The method of  claim 32  wherein Q is a moiety selected from the structures: 
       
         
           
           
               
               
           
         
       
     
     
         34 . A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of the formula (G): 
       
         
           
           
               
               
           
         
         or a salt thereof, 
       
       wherein:
 R 1a  is alkyl; 
 R 4a  is selected from alkyl, aryl, and substituted aryl; 
 R 5  is alkyl; and 
 R 8g  is selected from alkyl, substituted alkyl and aralkyl. 
 
     
     
         35 . A pharmaceutical composition comprising a compound according to any of  claims 1  to  16  and a pharmaceutically acceptable carrier. 
     
     
         36 . A kit comprising a compound according to any of  claims 1  to  16  and instructions for use in the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder.