Discovery of a Novel Glucagon Receptor Antagonist N-[(4-{(1 S)-1-[3-(3, 5-Dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1 H-pyrazol-1-yl] ethyl} phenyl) carbonyl]-β- …

…, R Liang, C Miller, Q Dallas-Yang, G Jiang…

文献索引：Xiong, Yusheng; Guo, Jian; Candelore, Mari R.; Liang, Rui; Miller, Corey; Dallas-Yang, Qing; Jiang, Guoqiang; McCann, Peggy E.; Qureshi, Sajjad A.; Tong, Xinchun; Xu, Shiyao Sherrie; Shang, Jackie; Vincent, Stella H.; Tota, Laurie M.; Wright, Michael J.; Yang, Xiaodong; Zhang, Bei B.; Tata, James R.; Parmee, Emma R. Journal of Medicinal Chemistry, 2012 , vol. 55, # 13 p. 6137 - 6148

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被引用次数: 34

摘要

A potent, selective glucagon receptor antagonist 9m, N-[(4-{(1 S)-1-[3-(3, 5-dichlorophenyl)- 5-(6-methoxynaphthalen-2-yl)-1 H-pyrazol-1-yl] ethyl} phenyl) carbonyl]-β-alanine, was discovered by optimization of a previously identified lead. Compound 9m is a reversible and competitive antagonist with high binding affinity (IC50 of 6.6 nM) and functional cAMP activity (IC50 of 15.7 nM). It is selective for glucagon receptor relative to other family B ...