| Autor: |
Yang Yu, Gary G. Chicchi, Frederick Wong, Janet S. Kerr, Sharon Tong, Zhe Feng, Guillermo Fernandez, Edward C. Sherer, Kwei-Lan Tsao, Qing Shao, Bei B. Zhang, Yun-Ping Zhou, Pierre Morissette, Shuwen He, Shrenik K. Shah, Vijay Bhasker G. Reddy, Liangqin Guo, Ravi P. Nargund, Margaret Wu, Cai Li, Zhixiong Ye, Alexander Pasternak, George J. Eiermann, Patricia R. Bunting, Hongbo Qi, Michele Pachanski, Stan Mitelman, Maria E. Trujillo, Quang Truong, Maria Madiera, Andrew D. Howard, Donald Nelson, Qingmei Hong, Zhong Lai, Yue Feng, Bindhu V. Karanam, Jian Liu, Koppara Samuel, Wu Du, William K. Hagmann, Tianying Jian, Dorina Trusca, Sylvia Volksdorf, Peter H. Dobbelaar |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
ACS medicinal chemistry letters. 6(5) |
| ISSN: |
1948-5875 |
| Popis: |
The imidazolyl-tetrahydro-β-carboline class of sstr3 antagonists have demonstrated efficacy in a murine model of glucose excursion and may have potential as a treatment for type 2 diabetes. The first candidate in this class caused unacceptable QTc interval prolongation in oral, telemetrized cardiovascular (CV) dogs. Herein, we describe our efforts to identify an acceptable candidate without CV effects. These efforts resulted in the identification of (1R,3R)-3-(4-(5-fluoropyridin-2-yl)-1H-imidazol-2-yl)-1-(1-ethyl-pyrazol-4-yl)-1-(3-methyl-1,3,4-oxadiazol-3H-2-one-5-yl)-2,3,4,9-tetrahydro-1H-β-carboline (17e, MK-1421). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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