title: Potent 11β-hydroxylase inhibitors with inverse metabolic stability in human plasma and hepatic S9 fractions to promote wound healing.
abstract: 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 (t1/2 ≫ 150 min), which is similar to wound fluid in composition, and in liver S9 fractions (t1/2 = 16 min).
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) , Campus C2-3, D-66123 Saarbrücken, Germany.
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhu
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Hu
authors.forename: Nina
authors.initials: N
authors.lastname: Hanke
authors.forename: Chris J
authors.initials: CJ
authors.lastname: van Koppen
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D008099:Liver / Q000378:metabolism*; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D047072:Aromatase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D001141:Aromatase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase