4-(Phenylsulfonyl) piperidines: novel, selective, and bioavailable 5-HT2A receptor antagonists

…, SKF Cheng, R Clarkson, D O'Connor…

文献索引：Fletcher, Stephen R.; Burkamp, Frank; Blurton, Peter; Cheng, Susan K. F.; Clarkson, Robert; O'Connor, Desmond; Spinks, Daniel; Tudge, Matthew; Van Niel, Monique B.; Patel, Smita; Chapman, Kerry; Marwood, Rose; Shepheard, Sara; Bentley, Graham; Cook, Gina P.; Bristow, Linda J.; Castro, Jose L.; Hutson, Peter H.; MacLeod, Angus M. Journal of Medicinal Chemistry, 2002 , vol. 45, # 2 p. 492 - 503

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被引用次数: 62

摘要

On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identifed as high-affinity, selective 5-HT2A 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 ...