title: Optimization of piperazinebenzylamines with a N-(1-methoxy-2-propyl) side chain as potent and selective antagonists of the human melanocortin-4 receptor.
abstract: Piperazinebenzylamines bearing a small N-(1-methoxy-2-propyl) side chain were found to be potent and selective antagonists of the human melanocortin-4 (MC4) receptor. Compound 7b, having K(i) values of 6.9 and 2800 nM at the human MC4 and MC3 receptors, respectively, has moderate oral bioavailability in mice, which is improved relative to the arylethyl analogues.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Joe A
authors.initials: JA
authors.lastname: Tran
authors.forename: Melissa
authors.initials: M
authors.lastname: Arellano
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Jenny
authors.initials: J
authors.lastname: Wen
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Jodie
authors.initials: J
authors.lastname: Nelson
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Alan C
authors.initials: AC
authors.lastname: Foster
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002460:Cell Line; D006801:Humans; D051379:Mice; D010879:Piperazines / Q000737:chemistry; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*
chemical_list: D001596:Benzylamines; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4