Suzuki Shinya, Okano Tsubasa, Horiuchi Rie, Hareyama Nana, Amikura Kazutoshi, Yamamoto Naoyoshi, Yoshizawa Yoshitaka, Yagi Mai, Serizawa Kanako, Hayashi Ryoji
Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Bioorg Med Chem Lett. 2015 Aug 15;25(16):3368-72. doi: 10.1016/j.bmcl.2015.05.049. Epub 2015 May 31.
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.
我们旨在开发一种新型强效α(1L)-肾上腺素能受体激动剂，因为这类激动剂有可能成为治疗压力性尿失禁的候选药物。我们采用基于配体的药物设计方法，并评估了所设计化合物的α(1L)-肾上腺素能受体激动剂活性。其中，四氢喹啉衍生物50表现出最强的活性（去甲肾上腺素半数最大效应浓度的比值为0.0028），并能有效诱导大鼠膀胱颈收缩。
