Journal of Medicinal Chemistry p. 7410 - 7424 (2017)
Update date:2022-08-15
Topics:
Nguyen, Thuy
German, Nadezhda
Decker, Ann M.
Langston, Tiffany L.
Gamage, Thomas F.
Farquhar, Charlotte E.
Li, Jun-Xu
Wiley, Jenny L.
Thomas, Brian F.
Zhang, Yanan
Allosteric modulators of the cannabinoid CB1 receptor have recently been reported as an alternative approach to modulate the CB1 receptor for therapeutic benefits. In this study, we report the design and synthesis of a series of diarylureas derived from PSNCBAM-1 (2). Similar to 2, these diarylureas dose-dependently inhibited CP55,940-induced intracellular calcium mobilization and [35S]GTP-γ-S binding while enhancing [3H]CP55,940 binding to the CB1 receptor. Structure-activity relationship studies revealed that the pyridinyl ring of 2 could be replaced by other aromatic rings and the pyrrolidinyl ring is not required for CB1 allosteric modulation. 34 (RTICBM-74) had similar potencies as 2 in all in vitro assays but showed significantly improved metabolic stability to rat liver microsomes. More importantly, 34 was more effective than 2 in attenuating the reinstatement of extinguished cocaine-seeking behavior in rats, demonstrating the potential of this diarylurea series as promising candidates for the development of relapse treatment of cocaine addiction.
View MoreChangzhou Anyi Biochem Co., Ltd.(expird)
Contact:+86-519-88836158
Address:no,51 caoda
HAINAN JINYING IMPORT AND EXPORT CO. LTD
Contact:+86-898-32875423
Address:A SECTION 19TH FL, TIMES SQUARE, NO.2 GUO MAO AVENUE HAIKOU, HAINAN, P. R. OF CHINA
Changzhou Ansciep Chemical Co.,Ltd.
Contact:+86 519 8630 5871
Address:A-710 Boan International, 8 East Guangdian Road,Wujin,Changzhou
Contact:86-28-61993785
Address:No.70-13-21, North Section, Erhuan
Contact:86-532-68629711 13780605697
Address:NO 220 YANAN 3 ROAD,(POST ADMINISTRATION BUILDING),QINGDAO,CHINA
Doi:10.1016/j.tetlet.2004.09.034
(2004)Doi:10.1039/c4ob01948b
(2015)Doi:10.1021/jo00340a046
(1982)Doi:10.1002/ejoc.200700338
(2007)Doi:10.1248/cpb.30.51
(1982)Doi:10.1021/j100290a063
(1987)