Bridged heterocyclic compounds and methods of use
View Patent ↗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.
1. A compound, or a salt thereof, wherein the compound is selected from the group consisting of compounds:
Compound #
Structure
115
116
117
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
163
164
165
2. A compound of the formula (F-1):
wherein:
R 1 is H, hydroxyl, 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, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;
each R 2 and R 10 is independently H, hydroxyl, alkoxyl or substituted or unsubstituted C 1 -C 8 alkyl;
each R 3a and R 3b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano, nitro, hydroxyl, alkoxy, amino, substituted amino, cycloalkyl, acylamino or acyloxy or R 3a and R 3b are taken together to form a cycloalkyl or a carbonyl moiety;
p is 1 or 2;
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, 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;
R 11 and R 12 are independently H, C 1 -C 8 alkyl, C 1 -C 8 perhaloalkyl, carboxy, carbonylalkoxy, or taken together with the carbon atoms to which they are attached to form a substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkenyl or substituted or unsubstituted heterocyclyl moiety or are taken together to form a bond, thereby providing an acetylenyl moiety; indicates the presence of either an E or Z double bond configuration when R 11 and R 12 are independently H or C 1 -C 8 alkyl; and
Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or an unsubstituted heterocyclyl, unsubstituted amino, substituted amino, alkoxy, aminoacyl, acyloxy, carbonylalkoxy, aminocarbonylalkoxy, acylamino, carboxy, alkynyl or cyano;
or a salt thereof.
3. The compound of claim 2 , or a salt thereof, wherein R 1 is methyl, each R 2 , R 3a , R 3b and R 10 is H, p is 1, X 9 is CR 4 where R 4 is halo or methyl, each X 7 , X 8 and X 10 is CH, R 11 is H, R 12 is methyl and Q is substituted phenyl.
4. The compound of claim 2 , wherein the compound is of the formula (F-2):
or a salt thereof.
5. The compound of claim 4 , or a salt thereof, wherein R 1 is methyl, each R 2 , R 3a , R 3b and R 10 is H, p is 1, X 9 is CR 4 where R 4 is halo or methyl, each X 7 , X 8 and X 10 is CH and Q is substituted pyridyl.
6. The compound of claim 2 , or a salt thereof, wherein R 11 is H and Q is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.
7. The compound of claim 6 , or a salt thereof, wherein R 12 is H or methyl.
8. The compound of claim 7 , or a salt thereof, wherein R 1 is methyl, p is 1, and X 9 is CR 4 where R 4 is halo or methyl.
9. A pharmaceutical composition comprising a compound according to any one of claims 1 , 2 - 5 and 6 - 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
10. A kit comprising a compound according to any one of claims 1 , 2 - 5 and 6 - 8 or salt thereof and instructions for using said compound or salt thereof.