title: Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity.
abstract: We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3'-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM K(i).
authors.affiliation: Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galiano
authors.forename: Javier
authors.initials: J
authors.lastname: Ceras
authors.forename: Nuria
authors.initials: N
authors.lastname: Cirauqui
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez
authors.forename: Laura
authors.initials: L
authors.lastname: Juanenea
authors.forename: Gildardo
authors.initials: G
authors.lastname: Rivera
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C521399:1-(3'-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-(2-(1-(4-methylbenzyl)-4-piperidinyl)ethyl)urea; D019440:Anti-Obesity Agents; D001713:Biphenyl Compounds; C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin; D014508:Urea