Thienopyrimidinone bis-aminopyrrolidine ureas as potent melanin-concentrating hormone receptor-1 (MCH-R1) antagonists.
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.
Zhang
Mingzhu
M
Department of Medicinal Chemistry, Pharmacology and Molecular Biology, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Tamiya
Junko
J
Nguyen
Linh
L
Rowbottom
Martin W
MW
Dyck
Brian
B
Vickers
Troy D
TD
Grey
Jonathan
J
Schwarz
David A
DA
Heise
Christopher E
CE
Haelewyn
Jason
J
Mistry
Monica S
MS
Goodfellow
Val S
VS
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*
D065690:Cytochrome P-450 CYP2D6 Inhibitors; C103263:MCHR1 protein, human; D011759:Pyrrolidines; D017481:Receptors, Somatostatin; D014508:Urea