Synthesis and structure-activity relationships of spirohydantoin-derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1).
The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1.
Rowbottom
Martin W
MW
Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA. mrowbottom@neurocrine.com
Vickers
Troy D
TD
Tamiya
Junko
J
Zhang
Mingzhu
M
Dyck
Brian
B
Grey
Jonathan
J
Schwarz
David
D
Heise
Christopher E
CE
Hedrick
Michael
M
Wen
Jenny
J
Tang
Hui
H
Wang
Hua
H
Fisher
Andrew
A
Aparicio
Anna
A
Saunders
John
J
Goodfellow
Val S
VS
D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D011485:Protein Binding; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D006827:Hydantoins; D011979:Receptors, Pituitary Hormone; D013141:Spiro Compounds; C092274:melanin-concentrating hormone receptor