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Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor |
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| Authors: | Duffy Joseph L Kirk Brian A Konteatis Zenon Campbell Elizabeth L Liang Rui Brady Edward J Candelore Mari Rios Ding Victor D H Jiang Guoqiang Liu Frank Qureshi Sajjad A Saperstein Richard Szalkowski Deborah Tong Sharon Tota Lauri M Xie Dan Yang Xiaodong Zafian Peter Zheng Song Chapman Kevin T Zhang Bei B Tata James R |
| Institution: | Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. joseph_duffy@merck.com |
| Abstract: | A novel class of antagonists of the human glucagon receptor (hGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice). |
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