1,1-Diphenyl-3-dialkylamino-1-silacyclopentane Derivatives: A New Class of Potent and Selective 5-HT2A Antagonists.

Abstract A new series of 1,1-diphenyl-3-dialkylamino-1-silacyclopentanes was synthesized, and most compounds demonstrated moderate to high affinity for the 5-HT2A receptor. A member of this series, compound 1p displays potent antagonist activity after oral administration against both mescaline and DOI-induced head-twitches in mice and rats, with a long duration of action. The dextrorotatory isomer (+)-1p is highly more potent than the levorotatory isomer (−)-1p in in vitro and in in vivo assays.