| Autor: |
Duane, DeMong, Xing, Dai, Joyce, Hwa, Michael, Miller, Sue-Ing, Lin, Ling, Kang, Andrew, Stamford, William, Greenlee, Wensheng, Yu, Michael, Wong, Brian, Lavey, Joseph, Kozlowski, Guowei, Zhou, De-Yi, Yang, Bhuneshwari, Patel, Aileen, Soriano, Ying, Zhai, Christopher, Sondey, Hongtao, Zhang, Jean, Lachowicz, Diane, Grotz, Kathleen, Cox, Richard, Morrison, Teresa, Andreani, Yang, Cao, Mark, Liang, Tao, Meng, Paul, McNamara, Jesse, Wong, Prudence, Bradley, Kung-I, Feng, Jitendra, Belani, Ping, Chen, Peng, Dai, Jolicia, Gauuan, Peishan, Lin, He, Zhao |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Journal of medicinal chemistry. 57(6) |
| ISSN: |
1520-4804 |
| Popis: |
A novel series of spiroimidazolone-based antagonists of the human glucagon receptor (hGCGR) has been developed. Our efforts have led to compound 1, N-((2H-tetrazol-5-yl)methyl)-4-((R)-1-((5r,8R)-8-(tert-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822), a potent hGCGR antagonist with exceptional selectivity over the human glucagon-like peptide-1 receptor. Oral administration of 1 lowered 24 h nonfasting glucose levels in imprinting control region mice on a high fat diet with diet-induced obesity following single oral doses of 3 and 10 mg/kg. Furthermore, compound 1, when dosed orally, was found to decrease fasting blood glucose at 30 mg/kg in a streptozotocin-treated, diet-induced obesity mouse pharmacodynamic assay and blunt exogenous glucagon-stimulated glucose excursion in prediabetic mice. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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