Solid-phase synthesis and structure-activity relationships of novel biarylethers as melanin-concentrating hormone receptor-1 antagonists.
Melanin-concentrating hormone (MCH) is a cyclic 19 amino acid orexigenic neuropeptide. The action of MCH on feeding is thought to involve the activation of its respective G protein-coupled receptor MCH-R1. Consequently, antagonists that block MCH regulated MCH-R1 activity may provide a viable approach to the treatment of diet-induced obesity. This communication reports the discovery of a novel MCH-R1 receptor antagonist, the biarylether 7, identified through high throughput screening. The solid-phase synthesis and structure-activity relationship of related analogs is described.
Ma
Vu
V
Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. vma@amgen.com
Bannon
Anthony W
AW
Baumgartner
Jamie
J
Hale
Clarence
C
Hsieh
Faye
F
Hulme
Christopher
C
Rorrer
Kirk
K
Salon
John
J
van Staden
Carlo
C
Tempest
Paul
P
D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009765:Obesity / Q000188:drug therapy; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004987:Ethers; C103263:MCHR1 protein, human; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; C092274:melanin-concentrating hormone receptor