Accelerated skin wound healing by selective 11 beta-Hydroxylase (CYP11B1) inhibitors

作者：Emmerich Juliette; van Koppen Chris J; Burkhart Jens L; Engeli Roger T; Hu Qingzhong; Odermatt Alex; Hartmann Rolf W^*

来源：European Journal of Medicinal Chemistry, 2018, 143: 591-597.

DOI：10.1016/j.ejmech.2017.11.018

• 11 beta-hydroxylase (CYP11B1) inhibitors
• 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)
• Wound healing
• Topical application
• Chronic wounds

Previous studies have shown that inhibition of cortisol biosynthesis in skin leads to accelerated wound healing. Here, pyridylmethyl pyridine type 11 beta-hydroxylase (CYP11B1) inhibitors were optimized for topical application to avoid systemic side effects. The resulting very potent, non-toxic CYP11B1 inhibitor 14 (IC50 = 0.8 nM) exhibited good selectivity over 11 beta-HSD1, CYP17A1 and CYP19A1. The compound showed high stability toward human plasma (t(1/2)= > 150 min, as a substitute for wound fluid) and low stability toward HLS9 (t(1/2) = 19 min) for rapid metabolic clearance after absorption. Compound 14 was able to accelerate wound healing in human skin.

• 出版日期2018-1-1