Hasegawa Futoshi, Niidome Kazumi, Migihashi Chiaki, Murata Makoto, Negoro Toshiyuki, Matsumoto Takafumi, Kato Kaori, Fujii Akihito
Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
Bioorg Med Chem Lett. 2014 Sep 1;24(17):4266-70. doi: 10.1016/j.bmcl.2014.07.025. Epub 2014 Jul 24.
Furan-2-carbohydrazides were found as orally active glucagon receptor antagonists. Starting from the hit compound 5, we successfully determined the structure activity relationships of a series of derivatives obtained by modifying the acidity of the phenol. We identified the ortho-nitrophenol as a good scaffold for glucagon receptor inhibitory activity. Our efforts have led to the discovery of compound 7l as a potent glucagon receptor antagonist with good bioavailability and satisfactory long half-life.
呋喃 - 2 - 碳酰肼被发现是口服活性胰高血糖素受体拮抗剂。从先导化合物5开始，我们成功确定了通过改变苯酚酸度得到的一系列衍生物的构效关系。我们确定邻硝基苯酚是具有胰高血糖素受体抑制活性的良好骨架。我们的努力导致发现化合物7l是一种有效的胰高血糖素受体拮抗剂，具有良好的生物利用度和令人满意的长半衰期。
