Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists.
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.
Malleron
J L
JL
Département de Chimie Pharmaceutique, Centre de Recherches de Vitry Alfortville Rhône-Poulenc Rorer, Vitry-sur-Seine, France.
Comte
M T
MT
Gueremy
C
C
Peyronel
J F
JF
Truchon
A
A
Blanchard
J C
JC
Doble
A
A
Piot
O
O
Zundel
J L
JL
Huon
C
C
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
D003499:Cyclic S-Oxides; D009281:Naphthalenes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013844:Thiazoles; D016713:Ritanserin; C070475:fananserin; D008635:Mescaline