ABSTRACT
A series of 1-(1-pyrrolo(iso)quinolinyl)-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 the compounds at 5-HT(2) receptor subtypes are reported. The analogue which showed the highest 5-HT(2C) binding affinity (27, 1.6nM) was found to be successful in reducing food intake in rats.
Subject(s)
Eating/drug effects , Isoquinolines/pharmacology , Quinolines/pharmacology , Serotonin 5-HT2 Receptor Agonists , Serotonin Receptor Agonists/pharmacology , Animals , Anti-Obesity Agents/pharmacology , Disease Models, Animal , Isoquinolines/chemistry , Pyrroles/chemistry , Quinolines/chemistry , Radioligand Assay , RatsABSTRACT
We describe a concise and convergent synthesis of (rac)-5-methoxy-6-azatricyclco[7.3.1.0(2,7)]trideca-2(7),3,5,11-tetraen-13-ol, which has the basic ring system of huperzine A, a potent inhibitor of acetylcholinesterase. We also describe the synthesis of the novel system 5-methoxy-6-azatricyclo[7.2.2.0(2,7)]trideca-2(7),3,5-trien-10-one and a series of related systems.
