Steroidal C-21 heteroaryl thioethers. Part 3: Pregn-4-eno-[3,2-c]pyrazole fused A ring modified steroids as selective glucocorticoid receptor modulators (dissociated steroids)
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- 作者：Purakkattle Biju ; purakkattle.biju@merck.com ; Hongwu Wang ; John Anthes ; Kevin McCormick ; Robert Aslanian ; Michael Berlin ; Rema Bitar ; Yeon-Hee Lim ; Yoon Joo Lee ; Daniel Prelusky ; Robbie Mcleod ; Yanlin Jia ; Xiomora Fernandez ; Gissela Lieber ; Johanna Jimenez ; Steve Eckel ; Aileen House ; Richard Chapman ; Jonathan Phillips
- 关键词：Selective glucocorticoid receptor modulators ; Dissociated steroids ; Prednisolone ; Transactivation ; Transrepression ; Pyrazole
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：1 May, 2012
- 年：2012
- 卷：22
- 期：9
- 页码：3291-3295
- 全文大小：1417 K
文摘
The introduction of A ring pyrazole modification to the hydrocortisone C-21 heteroaryl thioethers generated compounds with excellent transrepression potency (IL-8 inhibition) compared to their hydrocortisone analogs. However, the transcriptional transactivation activity of these compounds were considerably higher than the corresponding hydrocortisone analogs. Among all the compounds evaluated, a quinoxaline thioether modification demonstrated the best overall in vitro separation.