title: Discovery of potent α1L-adrenoceptor agonists: Design and synthesis of bicyclic derivatives.
abstract: We aimed to create a novel and potent α(1L)-adrenoceptor agonist because such agonists are possible drug candidates for stress urinary incontinence. We used ligand-based drug design and evaluated the α(1L)-adrenoceptor agonist activity of the designed compounds. Among them, tetrahydroquinoline derivative 50 showed the most potent activity (ratio of noradrenaline half maximal effective concentration, 0.0028) and effectively induced contraction of rat bladder neck.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Shinya_Suzuki@nts.toray.co.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Tsubasa_Okano@nts.toray.co.jp.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Okano
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Rie_Horiuchi@nts.toray.co.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Horiuchi
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Nana_Hareyama@nts.toray.co.jp.
authors.forename: Nana
authors.initials: N
authors.lastname: Hareyama
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Kazutoshi_Amikura@nts.toray.co.jp.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Amikura
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Naoyoshi_Yamamoto@nts.toray.co.jp.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Yoshitaka_Yoshizawa@nts.toray.co.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshizawa
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Mai_Yagi@nts.toray.co.jp.
authors.forename: Mai
authors.initials: M
authors.lastname: Yagi
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Kanako_Serizawa@nts.toray.co.jp.
authors.forename: Kanako
authors.initials: K
authors.lastname: Serizawa
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
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D001743:Urinary Bladder / Q000187:drug effects
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011804:Quinolines; C542964:1,2,3,4-tetrahydroquinoline
keywords: Adrenoceptor agonist; Drug discovery; Stress urinary incontinence