|
|||||
|
|
Discovery of novel, potent, and orally active spiro-urea human glucagon receptor antagonists |
|
| Authors: | Shen Dong-Ming Zhang Fengqi Brady Edward J Candelore Mari Rios Dallas-Yang Qing Ding Victor D-H Dragovic Jasminka Feeney William P Jiang Guoquiang McCann Peggy E Mock Steve Qureshi Sajjad A Saperstein Richard Shen Xiaolan Tamvakopoulos Constantin Tong Xinchun Tota Laurie M Wright Michael J Yang Xiaodong Zheng Song Chapman Kevin T Zhang Bei B Tata James R Parmee Emma R |
| Institution: | Department of Basic Chemistry, Merck Research Laboratories, PO Box 2000, RY50G-146, Rahway, NJ 07065, USA. dongming_shen@merck.com |
| Abstract: | A novel class of spiro-ureas has been discovered as potent human glucagon receptor antagonists in both binding and functional assays. Preliminary studies have revealed that compound 15 is an orally active human glucagon receptor antagonist in a transgenic murine pharmacodynamic model at 10 and 30 mpk. Compound 15 is orally bioavailable in several preclinical species and shows selectivity toward cardiac ion channels and other family B receptors, such as hGIP1 and hGLP. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |