Gabaergic receptor subtype selective ligands and their uses
Described herein are α3 or α2 or α2/α3 GABAergic receptor subtype selective ligands, pharmaceutical compositions, and methods of use of such ligands and compositions in treatment of anxiety disorders, epilepsy and schizophrenia with reduced sedative and ataxic side effects. In embodiments, such as α3 or α2 or α2/α3 GABAergic receptor subtype selective ligands lack ester linkages and may be thus relatively insensitive to hydrolysis by esterases.
1. A compound of formula (I):
or a salt thereof, wherein:
R is —H or —Si(Me) 3 ;
X is CH, CF, CCl or N; and
R′ is selected from the group consisting of —CHF 2 , —CH 2 CF 2 CH 3 , —CF 2 CHF 2 ,CF 2 CF 2 CH 3 , —CH 2 OCH 3 , —CF 2 CH 2 OCH 3 , —CF 2 OCH 2 CH 3 , —CH 2 OCH 2 CH 3 , —CH 2 OH, —CH 2 SCH 3 , —CF 2 CH 2 CH 3 , —CH 2 OCH 2 OCH 3 , —COCH 2 CH 3 , —C(CF 2 )OCH 2 CH 3 , —CH(CF 3 )OCH 2 CH 3 , —CH(CF 3 )NHCH 2 CH 3 ,
—CHO and —CH 2 CF 2 CH 3 , or
R′ is selected from the group consisting of:
wherein each R1 is independently selected from the group consisting of —CH 3 , —CH 2 CH 3 and —CH(CH 3 ) 2 .
2. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 , and a pharmaceutically acceptable carrier.
3. A method of treating a disorder selected from an anxiety disorder, epilepsy and schizophrenia in a subject in need of treatment, comprising administering to the subject an effective amount of a compound of formula (I) according to claim 1 .