title: Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists.
abstract: A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (Ki = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha 1 (Ki = 38 nM) and D2 (Ki greater than 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats.
authors.affiliation: Département de Chimie Pharmaceutique, Centre de Recherches de Vitry Alfortville Rhône-Poulenc Rorer, Vitry-sur-Seine, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Malleron
authors.forename: M T
authors.initials: MT
authors.lastname: Comte
authors.forename: C
authors.initials: C
authors.lastname: Gueremy
authors.forename: J F
authors.initials: JF
authors.lastname: Peyronel
authors.forename: A
authors.initials: A
authors.lastname: Truchon
authors.forename: J C
authors.initials: JC
authors.lastname: Blanchard
authors.forename: A
authors.initials: A
authors.lastname: Doble
authors.forename: O
authors.initials: O
authors.lastname: Piot
authors.forename: J L
authors.initials: JL
authors.lastname: Zundel
authors.forename: C
authors.initials: C
authors.lastname: Huon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008635:Mescaline / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D003499:Cyclic S-Oxides; D009281:Naphthalenes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013844:Thiazoles; D016713:Ritanserin; C070475:fananserin; D008635:Mescaline