Potent 11尾-Hydroxylase Inhibitors with Inverse Metabolic Stability in Human Plasma and Hepatic S9 Fractions To Promote Wound Healing

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• 作者：Weixing Zhu ; Qingzhong Hu ; Nina Hanke ; Chris J. van Koppen ; Rolf W. Hartmann
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：September 25, 2014
• 年：2014
• 卷：57
• 期：18
• 页码：7811-7817
• 全文大小：336K
• ISSN：1520-4804

文摘

Topical application of CYP11B1 inhibitors to reduce cutaneous cortisol is a novel strategy to promote healing of chronic wounds. Pyridyl substituted arylsulfonyltetrahydroquinolines were designed and synthesized resulting in a strong inhibitor 34 (IC₅₀ = 5 nM). It showed no inhibition of CYP17 and CYP19 and no mutagenic effects. It exhibited inverse metabolic stability in plasma (t_1/2 鈮?150 min), which is similar to wound fluid in composition, and in liver S9 fractions (t_1/2 = 16 min).