Naphthosultam Derivatives: A New Class of Potent and Selective 5-HT2 Antagonists

J Med Chem. 1991 Aug;34(8):2477-83. doi: 10.1021/jm00112a025.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Chemical Phenomena
  • Chemistry
  • Cyclic S-Oxides / chemical synthesis*
  • Cyclic S-Oxides / metabolism
  • Cyclic S-Oxides / pharmacology
  • Male
  • Mescaline / pharmacology
  • Mice
  • Molecular Structure
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / metabolism
  • Naphthalenes / pharmacology
  • Piperidines / metabolism
  • Piperidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / metabolism
  • Ritanserin
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / metabolism
  • Serotonin Antagonists / pharmacology
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / metabolism

Substances

  • Cyclic S-Oxides
  • Naphthalenes
  • Piperidines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Thiazoles
  • Ritanserin
  • fananserin
  • Mescaline