title: Bis(aminopyrrolidine)-derived ureas (APUs) as potent MCH1 receptor antagonists.
abstract: Ureas derived from two substituted 3-aminopyrrolidine subunits were prepared as constrained analogs of a linear lead compound and tested as antagonists of the MCH(1) receptor. The series was optimized for substitution and stereochemistry to generate a functional antagonist with a K(i) of 3.3 nM and IC(50) of 12 nM (GTPgammaS).
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grey
authors.forename: Brian
authors.initials: B
authors.lastname: Dyck
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
authors.forename: Junko
authors.initials: J
authors.lastname: Tamiya
authors.forename: Troy D
authors.initials: TD
authors.lastname: Vickers
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhang
authors.forename: Liren
authors.initials: L
authors.lastname: Zhao
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Heise
authors.forename: David
authors.initials: D
authors.lastname: Schwarz
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Val S
authors.initials: VS
authors.lastname: Goodfellow
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011759:Pyrrolidines; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; D014508:Urea