Document Report Card

ID: ALA1125395

Journal: J Med Chem

Title: Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides.

Authors: Youssefyeh RD, Campbell HF, Klein S, Airey JE, Darkes P, Powers M, Schnapper M, Neuenschwander K, Fitzpatrick LR, Pendley CE.

Abstract: 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 Ki value of 0.19 nM and (b) blocking cisplatin-induced emesis in the ferret with an ED50 value determined to be 9 micrograms/kg po.

CiteXplore: 1312602

DOI: 10.1021/jm00083a014