- Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides
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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.
- Youssefyeh,Campbell,Klein,Airey,Darkes,Powers,Schnapper,Neuenschwander,Fitzpatrick,Pendley,Martin
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- Conformational and Steric Modifications of the Pyran Ring of the Potassium-Channel Activator Cromakalim
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The syntheses of analogues of the novel smooth muscle relaxant cromakalim, in which the C-2 methyl groups have been successively replaced by hydrogen, are described and the relative stereochemistry of the two corresponding, isomeric monomethyl compounds,
- Buckle, Derek R.,Eggleston, Drake S.,Houge-Frydrych, Catherina S. V.,Pinto, Ivan L.,Readshaw, Simon A.,et al.
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p. 2763 - 2772
(2007/10/02)
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- Quinuclidyl benzoxepins as 5-HT3 antagonists
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Certain specific substituted 9-N-(1-azabicyclo-[2.2.2.]octan-3-yl)carboxamido-2,3,4,5-tetrahydro-1-benzoxepins and their valuable use as 5-HT3 antagonists having CNS and gastric prokinetic acticity and void of any significant D2 receptor binding properties are disclosed. Methods for their preparation also are described.
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