138605-34-2Relevant academic research and scientific papers
Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides
Youssefyeh,Campbell,Klein,Airey,Darkes,Powers,Schnapper,Neuenschwander,Fitzpatrick,Pendley,Martin
, p. 895 - 903 (2007/10/02)
This report describes the development of novel benzamides which are orally active, highly potent, specific antagonists of 5-HT3 receptors. Described in this first report are the structure-activity relationships that led to novel structures with improved potency and selectivity. From this series of compounds, (S)-28 was identified and selected for further evaluation as a 5- HT3 receptor antagonist. Compared with 5-HT3 antagonists such as GR 38032F, BRL 43694, and metoclopramide, (S)-28 was most active in (a) inhibiting binding to 5-HT3 receptor binding sites in rat entorhinal cortex with an K(i) value of 0.19 nM and (b) blocking cisplatin-induced emesis in the ferret with an ED50 value determined to be 9 μg/kg po.
