首页 | 本学科首页   官方微博 | 高级检索  
     


Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake
Authors:Derong Ding  Justin R. Nickell  Agripina G. Deaciuc  Narsimha Reddy Penthala  Linda P. Dwoskin  Peter A. Crooks
Affiliation:1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA;2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Abstract:Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a15c and 22a22c) potently inhibited [3H]dopamine (DA) uptake into isolated synaptic vesicles (Ki ? 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (Ki = 24 nM), and was twofold more potent that either lobelane (2a, Ki = 45 nM) or norlobelane (2b, Ki = 43 nM). The trans-methylenedioxy analog, 15c (Ki = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis- and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse.
Keywords:Lobelane  Azetidine analogs  Methamphetamine abuse  VMAT2
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号