title: Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 2.
abstract: The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki = 1 nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA. shudson@neurocrine.com
authors.forename: Sarah
authors.initials: S
authors.lastname: Hudson
authors.forename: Mehrak
authors.initials: M
authors.lastname: Kiankarimi
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
authors.forename: Troy D
authors.initials: TD
authors.lastname: Vickers
authors.forename: Dongpei
authors.initials: D
authors.lastname: Wu
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: Brett
authors.initials: B
authors.lastname: Ching
authors.forename: Wesley
authors.initials: W
authors.lastname: Dwight
authors.forename: Val S
authors.initials: VS
authors.lastname: Goodfellow
authors.forename: David
authors.initials: D
authors.lastname: Schwarz
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Heise
authors.forename: Ajay
authors.initials: A
authors.lastname: Madan
authors.forename: Jenny
authors.initials: J
authors.lastname: Wen
authors.forename: William
authors.initials: W
authors.lastname: Ban
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Warren S
authors.initials: WS
authors.lastname: Wade
mesh_terms: D000818:Animals; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C491208:MCHR1 protein, rat; D011759:Pyrrolidines; D017481:Receptors, Somatostatin; C514080:bis-aminopyrrolidine urea; D014508:Urea