ABSTRACT
Synthesis and evaluation of the activity of new 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT(2C) receptor agonists are described. Appropriately substituted, several analogs displayed selectivity against the other 5-HT(2) receptor subtypes of 1 order of magnitude or more. Selectivity was improved for several compounds versus the lead 1, increasing the therapeutic interest in this series of 5-HT(2C) receptor agonists.
Subject(s)
Eating/drug effects , Serotonin 5-HT2 Receptor Agonists , Serotonin Receptor Agonists/pharmacology , Animals , Indoles/chemical synthesis , Indoles/pharmacology , Injections, Subcutaneous , Pyrazines/chemical synthesis , Pyrazines/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Rats , Rats, Wistar , Serotonin Receptor Agonists/chemical synthesis , Structure-Activity RelationshipABSTRACT
A series of 1-(1-indolinyl)-2-propylamines was synthesised and evaluated as 5-HT(2C) receptor agonists for the treatment of obesity. The general methods of synthesis of the precursor indoles are described. The functional efficacy and radioligand binding data for all of the compounds at 5-HT(2) receptor subtypes are reported. A number of compounds were found to reduce food intake in rats after oral administration.
