Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1-methylethylamines. Improved therapeutics for obsessive compulsive disorder.
The syntheses of a series of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2- b]pyrrol-1-yl)-1-methylethylamines are reported. The binding affinities of the compounds at 5HT2C and 5HT2A receptors (79% homology in the transmembrane domain) were determined. The ligands displayed selectivity for 5HT2C receptors relative to 5HT2A receptors. Compounds were functionally characterized both in vitro and in vivo as 5HT2C receptor agonists. 5f, 5l, 5n, 5o, 5q, 14c, 14f, 14k, and 14m exhibited anticompulsive activity in an animal model of obsessive compulsive disorder.
Bös
M
M
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Jenck
F
F
Martin
J R
JR
Moreau
J L
JL
Sleight
A J
AJ
Wichmann
J
J
Widmer
U
U
D016475:3T3 Cells; D000818:Animals; D005021:Ethylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D010410:Penile Erection / Q000187:drug effects; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013894:Thirst / Q000187:drug effects
D005021:Ethylamines; D008024:Ligands; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin