2. Academic Validation
  3. Discovery of potent α1L-adrenoceptor agonists: Design and synthesis of bicyclic derivatives

Discovery of potent α1L-adrenoceptor agonists: Design and synthesis of bicyclic derivatives

  • Bioorg Med Chem Lett. 2015 Aug 15;25(16):3368-72. doi: 10.1016/j.bmcl.2015.05.049.
Shinya Suzuki 1,  Tsubasa Okano 2,  Rie Horiuchi 3,  Nana Hareyama 4,  Kazutoshi Amikura 5,  Naoyoshi Yamamoto 6,  Yoshitaka Yoshizawa 7,  Mai Yagi 8,  Kanako Serizawa 9,  Ryoji Hayashi 10
Affiliations

Affiliations

  • 1 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Shinya_Suzuki@nts.toray.co.jp.
  • 2 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Tsubasa_Okano@nts.toray.co.jp.
  • 3 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Rie_Horiuchi@nts.toray.co.jp.
  • 4 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Nana_Hareyama@nts.toray.co.jp.
  • 5 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Kazutoshi_Amikura@nts.toray.co.jp.
  • 6 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Naoyoshi_Yamamoto@nts.toray.co.jp.
  • 7 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Yoshitaka_Yoshizawa@nts.toray.co.jp.
  • 8 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Mai_Yagi@nts.toray.co.jp.
  • 9 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Kanako_Serizawa@nts.toray.co.jp.
  • 10 Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Ryoji_Hayashi2@nts.toray.co.jp.
PMID: 26087939 DOI: 10.1016/j.bmcl.2015.05.049
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.

Keywords

Adrenoceptor agonist; Drug discovery; Stress urinary incontinence.

Figures