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:
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2. A compound of the formula (A-2):
wherein:
R 1 is unsubstituted C 1 -C 8 alkyl;
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;
q is 0;
each R 8c , R 8d and R 8f is independently H, hydroxyl, C 1 -C 8 alkyl, C 1 -C 8 perhaloalkyl, carboxy or carbonylalkoxy;
R 8e is independently hydroxyl, C 1 -C 8 alkyl, C 1 -C 8 perhaloalkyl, carboxy or carbonylalkoxy; and
Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkenyl, substituted or a unsubstituted heterocyclyl, unsubstituted amino, substituted amino, alkoxy, aminoacyl, acyloxy, carbonylalkoxy, aminocarbonylalkoxy or acylamino;
or a salt thereof.
3. A compound of the formula (A-2):
or a salt thereof, wherein:
each X 8 and X 9 is independently CR 4 where R 4 is H, halo or methyl,
each X 7 and X 10 is CH,
R 1 is methyl,
q is 0 or 1,
each R 8a and R 8b is H when present,
each R 8c and R 8d is H,
each R 8e and R 8f is independently H, hydroxy or methyl, and
Q is selected from the group consisting of:
4. A compound of the formula (B):
or a salt thereof, wherein:
R 1 is methyl;
each R 2 , R 3a , R 3b and R 10 is H;
p is 1;
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, carbonylalkoxy, 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 8c , R 8d , R 8e and R 8f is independently H, hydroxyl, unsubstituted C 1 -C 4 alkyl or is taken together with the carbon to which it is attached and a geminal R 8 to form a cycloalkyl moiety; and
Q is substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl, provided that Q is other than phenyl.
5. The compound of claim 2 , or a salt thereof, wherein R 8c , R 8d , R 8e and R 8f are taken together with the carbon atoms to which they are attached form a moiety selected from the group consisting of:
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof.
7. The compound of claim 2 , or a pharmaceutically acceptable salt thereof.
8. The compound of claim 3 , or a pharmaceutically acceptable salt thereof.
9. The compound of claim 4 , or a pharmaceutically acceptable salt thereof.
10. The compound of claim 5 , or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising a compound according to any one of claims 1 , 2 , 3 , 4 and 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.