Abstract
Agonists of the 5-HT(2C) receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT(2B) receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT(2C) agonists with no detectable agonism of the 5-HT(2B) receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing.
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Administration, Oral
-
Animals
-
Anti-Obesity Agents / administration & dosage
-
Anti-Obesity Agents / chemistry*
-
Anti-Obesity Agents / metabolism
-
Eating / drug effects
-
Eating / physiology
-
Humans
-
Male
-
Obesity / drug therapy*
-
Obesity / metabolism
-
Protein Binding / physiology
-
Quinazolinones / administration & dosage
-
Quinazolinones / chemistry*
-
Rats
-
Rats, Sprague-Dawley
-
Receptor, Serotonin, 5-HT2C / metabolism
-
Serotonin 5-HT2 Receptor Agonists*
-
Serotonin Receptor Agonists / administration & dosage
-
Serotonin Receptor Agonists / chemistry*
-
Serotonin Receptor Agonists / metabolism
Substances
-
Anti-Obesity Agents
-
Quinazolinones
-
Receptor, Serotonin, 5-HT2C
-
Serotonin 5-HT2 Receptor Agonists
-
Serotonin Receptor Agonists