Design and synthesis of novel hydantoin-containing melanin-concentrating hormone receptor antagonists.
We report here new chemical series acting as antagonists of melanin-concentrating hormone receptor 1 (MCHR-1). Synthesis and structure-activity relationships are described leading to the identification of compounds with optimized in vitro pharmacological and in vitro ADME profiles. In vivo activity has been demonstrated in animal models of food intake and depression.
Balavoine
Fabrice
F
Cerep, 19 avenue du Québec Courtaboeuf 1, 91951 Villebon sur Yvette, France. fabrice.balavoine@quantum-genomics.com <fabrice.balavoine@quantum-genomics.com>
Malabre
Patrice
P
Alleaume
Thierry
T
Rey
Astrid
A
Cherfils
Valérie
V
Jeanneton
Olivier
O
Seigneurin-Venin
Sophie
S
Revah
Frédéric
F
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D015195:Drug Design; D005247:Feeding Behavior / Q000187:drug effects; D006827:Hydantoins / Q000737:chemistry*; D007700:Kinetics; D008543:Melanins / Q000737:chemistry*; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D006827:Hydantoins; D008543:Melanins; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; C092274:melanin-concentrating hormone receptor