title: Synthesis and SAR of 1-alkyl-2-phenylethylamine derivatives designed from N,N-dipropyl-4-methoxy-3-(2-phenylethoxy)phenylethylamine to discover sigma(1) ligands.
abstract: The synthesis and structure-activity relationships (SAR) of 1-alkyl-2-phenylethylamine derivatives 5-8 designed from N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (1, NE-100) are presented. The SAR between compound 1 and 1-alkyl-2-phenylethylamine derivatives suggested that the alkyl group on the 1-position carbon of 2-[4-methoxy-3-(2-phenylethyl)phenyl]ethylamine derivatives played the role of one of the propyl groups on the aminic nitrogen of compound 1. (-)-N-Propyl-1-butyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylam ine hydrochloride ((-)-6d, NE-537) and (-)-N-propyl-1-(3-methybutyl)-2-[4-methoxy-3-(2-phenylethoxy )phenyl]e thylamine hydrochloride ((-)-6i, NE-535), typical compounds in this series, have potent and selective sigma(1) affinity.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Company Ltd., 1-403 Yoshino-cho, Ohmiya, Saitama 330-8530, Japan. S10968@ccm.taisho.co.jp
authors.forename: A
authors.initials: A
authors.lastname: Nakazato
authors.forename: T
authors.initials: T
authors.lastname: Kumagai
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Chaki
authors.forename: S
authors.initials: S
authors.lastname: Okuyama
authors.forename: K
authors.initials: K
authors.lastname: Tomisawa
mesh_terms: D000478:Alkylation; D000840:Anisoles / Q000737:chemistry* / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000737:chemistry* / Q000494:pharmacology*; D007536:Isomerism; D008024:Ligands; D010627:Phenethylamines; D011437:Propylamines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000840:Anisoles; D014150:Antipsychotic Agents; D008024:Ligands; D010627:Phenethylamines; D011437:Propylamines; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride