title: Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists.
abstract: We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.
authors.affiliation: Lead Generation, Computational Chemistry, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. fabrizio.giordanetto@astrazeneca.com
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giordanetto
authors.forename: Olle
authors.initials: O
authors.lastname: Karlsson
authors.forename: Jan
authors.initials: J
authors.lastname: Lindberg
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Larsson
authors.forename: Anna
authors.initials: A
authors.lastname: Linusson
authors.forename: Emma
authors.initials: E
authors.lastname: Evertsson
authors.forename: David G A
authors.initials: DG
authors.lastname: Morgan
authors.forename: Tord
authors.initials: T
authors.lastname: Inghardt
mesh_terms: D003510:Cyclohexanes / Q000737:chemistry*; D003517:Cyclopentanes / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*
chemical_list: D003510:Cyclohexanes; D003517:Cyclopentanes; D003959:Diamines; C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin; C506365:Cyclohexane