title: Thienopyrimidinone bis-aminopyrrolidine ureas as potent melanin-concentrating hormone receptor-1 (MCH-R1) antagonists.
abstract: A series of thienopyrimidinone bis-aminopyrrolidine ureas were designed, synthesized, and evaluated for their ability to bind melanin-concentrating hormone receptor-1. These compounds exhibit potent binding affinity (K(i)=3 nM) and good in vitro metabolic stability.
authors.affiliation: Department of Medicinal Chemistry, Pharmacology and Molecular Biology, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhang
authors.forename: Junko
authors.initials: J
authors.lastname: Tamiya
authors.forename: Linh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
authors.forename: Brian
authors.initials: B
authors.lastname: Dyck
authors.forename: Troy D
authors.initials: TD
authors.lastname: Vickers
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grey
authors.forename: David A
authors.initials: DA
authors.lastname: Schwarz
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Heise
authors.forename: Jason
authors.initials: J
authors.lastname: Haelewyn
authors.forename: Monica S
authors.initials: MS
authors.lastname: Mistry
authors.forename: Val S
authors.initials: VS
authors.lastname: Goodfellow
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D011759:Pyrrolidines / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; C103263:MCHR1 protein, human; D011759:Pyrrolidines; D017481:Receptors, Somatostatin; D014508:Urea