title: Synthesis and structure-activity relationships of spirohydantoin-derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1).
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA. mrowbottom@neurocrine.com
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
authors.forename: Troy D
authors.initials: TD
authors.lastname: Vickers
authors.forename: Junko
authors.initials: J
authors.lastname: Tamiya
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhang
authors.forename: Brian
authors.initials: B
authors.lastname: Dyck
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grey
authors.forename: David
authors.initials: D
authors.lastname: Schwarz
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Heise
authors.forename: Michael
authors.initials: M
authors.lastname: Hedrick
authors.forename: Jenny
authors.initials: J
authors.lastname: Wen
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Fisher
authors.forename: Anna
authors.initials: A
authors.lastname: Aparicio
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Val S
authors.initials: VS
authors.lastname: Goodfellow
mesh_terms: 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
chemical_list: D019440:Anti-Obesity Agents; D006827:Hydantoins; D011979:Receptors, Pituitary Hormone; D013141:Spiro Compounds; C092274:melanin-concentrating hormone receptor