title: Discovery of 1,3-disubstituted-1H-pyrrole derivatives as potent melanin-concentrating hormone receptor 1 (MCH-R1) antagonists.
abstract: A series of 1,3-disubstituted-1H-pyrrole-based antagonists of the human Melanin-Concentrating Hormone Receptor 1 (h-MCH-R1) are reported. High-throughput screening of the AstraZeneca compound collection yielded 1, a hit with moderate affinity towards MCH-R1. Subsequent structural manipulations and SAR analysis served to rationalize potency requirements, and 12 was identified as a novel, functional MCH-R1 antagonist with favorable pharmacokinetic properties.
authors.affiliation: Medicinal Chemistry, AstraZeneca R&D Mölndal, Pepparedsleden 1, SE-431 83, Mölndal, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Berglund
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Egner
authors.forename: Henrik
authors.initials: H
authors.lastname: Gradén
authors.forename: Joakim
authors.initials: J
authors.lastname: Gradén
authors.forename: David G A
authors.initials: DG
authors.lastname: Morgan
authors.forename: Tord
authors.initials: T
authors.lastname: Inghardt
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giordanetto
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004355:Drug Stability; D006801:Humans; D051379:Mice; D011758:Pyrroles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; C103263:MCHR1 protein, human; D011758:Pyrroles; D017481:Receptors, Somatostatin