4-(Phenylsulfonyl)piperidines: Novel, Selective, and Bioavailable 5-HT2AReceptor Antagonists
Citations Over Time
Abstract
On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identified as high-affinity, selective 5-HT(2A) receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound.
Related Papers
- → Effect of retinol on iron bioavailability from Iranian bread in a Caco-2 cell culture model(2006)20 cited
- → Dissolution Systems for Chloramphenicol Tablet Bioavailability(1979)15 cited
- → Study of the bioavailability of different formulations of 8‐methoxypsoralen in the dog(1988)4 cited
- → Prediction of Bioavailability(2003)2 cited
- → ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ(2024)