Substituted chromones and quinolones as potent melanin-concentrating hormone receptor 1 antagonists.
A series of substituted chromones were designed, synthesized, and evaluated for their ability to bind melanin-concentrating hormone receptor 1. Compounds with subnanomolar binding affinity and 66% oral bioavailability in rats were discovered.
Dyck
Brian
B
Department of Medicinal Chemistry, Neurocrine Biosciences Inc., San Diego, CA 92130, USA. bdyck@neurocrine.com
Zhao
Liren
L
Tamiya
Junko
J
Pontillo
Joseph
J
Hudson
Sarah
S
Ching
Brett
B
Heise
Christopher E
CE
Wen
Jenny
J
Norton
Christi
C
Madan
Ajay
A
Schwarz
David
D
Wade
Warren
W
Goodfellow
Val S
VS
D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008543:Melanins / Q000737:chemistry*; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013997:Time Factors
D002867:Chromones; D008543:Melanins; D015363:Quinolones; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor