2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLE COMPOUNDS AND METHODS OF USE THEREOF
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.
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.