Discovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes.

@article{Xiong2012DiscoveryOA,
  title={Discovery of a novel glucagon receptor antagonist N-[(4-\{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl\}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes.},
  author={Yusheng Xiong and Jian Guo and Mari Rios Candelore and Rui Liang and Corey E. Miller and Qing Dallas-yang and Guoqiang Jiang and Peggy E McCann and Sajjad A. Qureshi and Xinchun Tong and Shiyao Sherrie Xu and Jackie Shang and Stella H. Vincent and Laurie M. Tota and Michael J. Wright and Xiaodong Yang and Bei B. Zhang and James R Tata and Emma R. Parmee},
  journal={Journal of medicinal chemistry},
  year={2012},
  volume={55 13},
  pages={
          6137-48
        }
}
A potent, selective glucagon receptor antagonist 9m, N-[(4-{(1S)-1-[3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-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 (IC(50) of 6.6 nM) and functional cAMP activity (IC(50) of 15.7 nM). It is selective for glucagon receptor relative to other family B GPCRs, showing IC(50) values of 1020 nM for GIPR… CONTINUE READING
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