Identification of a novel series of benzimidazoles as potent and selective antagonists of the human melanocortin-4 receptor.
A novel series of benzimidazoles was identified and optimized, leading to the discovery of potent and selective antagonists of the human melanocortin-4 receptor. In addition, compound 5i was shown to cross the blood-brain barrier after intravenous dosing in rats.
Poitout
Lydie
L
Department of Medicinal Chemistry, Ipsen Research Laboratories, Institut Henri Beaufour, 5 Avenue du Canada, 91966 Les Ulis Cedex, France. lydie.poitout@ipsen.com
Brault
Valérie
V
Sackur
Carole
C
Bernetière
Sonia
S
Camara
José
J
Plas
Pascale
P
Roubert
Pierre
P
D000818:Animals; D019540:Area Under Curve; D001562:Benzimidazoles / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D044105:Receptor, Melanocortin, Type 4