2. Academic Validation
  3. Discovery of novel, potent, selective, and orally active human glucagon receptor antagonists containing a pyrazole core

Discovery of novel, potent, selective, and orally active human glucagon receptor antagonists containing a pyrazole core

  • Bioorg Med Chem Lett. 2011 Jan 1;21(1):76-81. doi: 10.1016/j.bmcl.2010.11.074.
Dong-Ming Shen 1,  Edward J Brady,  Mari R Candelore,  Qing Dallas-Yang,  Victor D-H Ding,  William P Feeney,  Guoquiang Jiang,  Margaret E McCann,  Steve Mock,  Sajjad A Qureshi,  Richard Saperstein,  Xiaolan Shen,  Xinchun Tong,  Laurie M Tota,  Michael J Wright,  Xiaodong Yang,  Song Zheng,  Kevin T Chapman,  Bei B Zhang,  James R Tata,  Emma R Parmee
Affiliations

Affiliation

  • 1 Department of Basic Chemistry, Merck Research Laboratories, PO Box 2000, RY50G-346, Rahway, NJ 07065, USA. [email protected]
PMID: 21147532 DOI: 10.1016/j.bmcl.2010.11.074
Abstract

A novel class of 1,3,5-pyrazoles has been discovered as potent human Glucagon Receptor antagonists. Notably, compound 26 is orally bioavailable in several preclinical species and shows selectivity towards cardiac ion channels, Other family B receptors such hGIP and hGLP1, and a large panel of Enzymes and additional receptors. When dosed orally, compound 26 is efficacious in suppressing glucagon induced plasma glucose excursion in rhesus monkey and transgenic murine pharmacodynamic models at 1 and 10 mpk, respectively.

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