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Published on: August 16, 2018
Discovery of novel, potent, selective, and orally active human glucagon receptor antagonists containing a pyrazole
Dong-Ming Shen1, Edward J Brady, Mari R Candelore
1Department of Basic Chemistry, Merck Research Laboratories, PO Box 2000, RY50G-346, Rahway, NJ 07065, USA. dongming.shen@merck.com
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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