Bridged heterocyclic compounds and methods of use

摘要

This disclosure relates to new compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new bridged heterocyclic [4,3-b]indole compounds. Pharmaceutical compositions are also provided. 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.

主权项

1. A compound of the formula (E):or a salt thereof, wherein:
R1 is H, hydroxyl, unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8 perhaloalkoxy, alkoxy, aryloxy, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy; R2 is H, hydroxyl, alkoxy or substituted or unsubstituted C1-C8 alkyl; each R3a and R3b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, nitro, hydroxyl, alkoxy, amino, substituted amino, cycloalkyl, acylamino or acyloxy or R3a and R3b are taken together to form a cycloalkyl moiety or a carbonyl moiety; each X7, X8, X9 and X10 is independently N or CR4; m and q are independently 0 or 1; p is 1 or 2; n is 1; each R4 is independently H, hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, C1-C8 alkoxy, aryloxy, carboxyl, thiol, carbonylalkoxy, 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 R8a, R8b, R8c, R8d , R8e and R8f , where present, is independently H, hydroxyl, C1-C8 alkyl, carboxy, carbonylalkoxy, is taken together with the carbon to which it is attached and a geminal R8(a-f) to form a cycloalkyl moiety or a carbonyl moiety, is taken together with a geminal R8(a-f) to form a methylene or a substituted methylene, or is taken together with a vicinal R8(a-f) and the carbon atoms to which they are attached to form a substituted or unsubstituted C3-C 8 cycloalkyl, substituted or unsubstituted C3-C 8 cycloalkenyl or substituted or unsubstituted heterocyclyl moiety; R10 is H, hydroxyl, alkoxy or a substituted or unsubstituted C1-C8 alkyl; and Q is aminoacyl group, wherein the aminoacyl is —NRaC(O)Rb where each Ra and Rb group is independently selected from the group consisting of H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic or substituted heterocyclic.