Dimethyl-diphenyl-propanamide Derivatives As Nonsteroidal Dissociated Glucocorticoid Receptor Agonists
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- 作者：Bingwei V. Yang ; David S. Weinstein ; Lidia M. Doweyko ; Hua Gong ; Wayne Vaccaro ; Tram Huynh ; Hai-yun Xiao ; Arthur M. Doweyko ; Lorraine Mckay ; Deborah A. Holloway ; John E. Somerville ; Sium Habte ; Mark C
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：December 9, 2010
- 年：2010
- 卷：53
- 期：23
- 页码：8241-8251
- 全文大小：998K
- 年卷期：v.53,no.23(December 9, 2010)
- ISSN：1520-4804
文摘
A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed.