In:
Future Medicinal Chemistry, Future Science Ltd, Vol. 1, No. 5 ( 2009-08), p. 947-967
Abstract:
Background: Since the cannabinoid receptor 1 (CB1) antagonist SR141716 (rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. Discussion: In the present study, biarylpyrazole analogues based on a sulfur-containing pyrazole core coupled with 1,3,4-oxadiazole and 1,3,4-thiadiazole were synthesized and assayed for rat CB1 receptor binding affinity. Results: The structure–activity relationship studies to optimize pyrazole substituents as well as 1,3,4-oxadiazole or 1,3,4-thiadiazole rings led to four novel CB1 antagonists with IC 50 values of approximately 1 nM for the rat CB1 receptor binding. Among these derivatives, we identified trifluoromethylcyclobutyl analogues 19e and 19l as promising precandidates for the development as anti-obesity agents.
Type of Medium:
Online Resource
ISSN:
1756-8919
,
1756-8927
Language:
English
Publisher:
Future Science Ltd
Publication Date:
2009
SSG:
15,3
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