A novel series of glucagon receptor antagonists with reduced molecular weight and lipophilicity.

Abstract

A novel series of glucagon receptor antagonists has been discovered. These pyrazole ethers and aminopyrazoles have lower molecular weight and increased polarity such that the molecules fall into better drug-like property space. This work has culminated in compounds 44 and 50 that were shown to have good pharmacokinetic attributes in dog, in contrast to rats, in which clearance was high; and compound 49, which demonstrated a dose-dependent reduction in glucose excursion in a rat glucagon challenge experiment.

DOI: 10.1016/j.bmcl.2011.10.113

Cite this paper

@article{Filipski2012ANS, title={A novel series of glucagon receptor antagonists with reduced molecular weight and lipophilicity.}, author={Kevin J Filipski and Jianwei Bian and David C Ebner and Esther C Y Lee and Jian-Cheng Li and Matthew F Sammons and Stephen W. Wright and Benjamin D. Stevens and Mary Didiuk and Meihua Tu and Christian Perreault and Janice A. Brown and Karen A Atkinson and Beijing Tan and Christopher T Salatto and John Litchfield and Jeffrey A. Pfefferkorn and Angel Guzman-Perez}, journal={Bioorganic & medicinal chemistry letters}, year={2012}, volume={22 1}, pages={415-20} }