title: Indolylpiperidine derivatives as potent and selective α1B adrenoceptor antagonists.
abstract: A series of novel indolylpiperidine derivatives were synthesized, and their pharmacological profiles were assessed at rat α1A and α1B adrenoceptors through in vitro binding studies. Compound 12 (2-(3-(4-(6-fluoro-1H-indol-3-yl)piperidin-1-yl)propyl)-1,2,3,4-tetrahydroisoquinoline) was a potent α1B adrenoceptor antagonist (Ki=0.61 nM) and was about 40-fold more selective for the α1B adrenoceptor than for the α1A adrenoceptor. In addition, useful structure-activity relationship information was acquired for further improving selectivity for the α1B adrenoceptor.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Ryoji_Hayashi2@nts.toray.co.jp.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Ohmori
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Moriwaki
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kumagai
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Isogaya
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; C000607830:Indolylpiperidine; D010880:Piperidines; D018340:Receptors, Adrenergic, alpha-1
keywords: 1,2,3,4-Tetrahydroisoquinoline; 4-(Indol-3-yl)piperidine; Adrenoceptor; α(1B)