Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists

  • Bioorg Med Chem Lett. 2014 Sep 1;24(17):4266-70. doi: 10.1016/j.bmcl.2014.07.025.
Futoshi Hasegawa  1 ,  Kazumi Niidome  2 ,  Chiaki Migihashi  2 ,  Makoto Murata  2 ,  Toshiyuki Negoro  2 ,  Takafumi Matsumoto  2 ,  Kaori Kato  2 ,  Akihito Fujii  2
Affiliations
  • 1. Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan. Electronic address: [email protected].
  • 2. Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
PMID: 25127101 DOI: 10.1016/j.bmcl.2014.07.025
Abstract

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.

Keywords
Furan-2-carbohydrazide; Glucagon; Glucagon receptor antagonist; Hyperglucagonemia; Type 2 diabetes.
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