The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis

Bioorg Med Chem Lett. 2017 May 1;27(9):2023-2028. doi: 10.1016/j.bmcl.2017.02.078. Epub 2017 Mar 9.

Abstract

A series of potent, competitive and highly selective kynurenine monooxygenase inhibitors have been discovered via a substrate-based approach for the treatment of acute pancreatitis. The lead compound demonstrated good cellular potency and clear pharmacodynamic activity in vivo.

Keywords: Kynurenine; Monooxygenase; Pancreatitis; Substrate; Tryptophan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacokinetics
  • Benzoxazoles / pharmacology
  • Drug Discovery
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • HEK293 Cells
  • Humans
  • Indazoles / chemistry
  • Indazoles / pharmacokinetics
  • Indazoles / pharmacology
  • Kynurenine / metabolism
  • Kynurenine 3-Monooxygenase / antagonists & inhibitors*
  • Kynurenine 3-Monooxygenase / metabolism
  • Pancreatitis / drug therapy*
  • Pancreatitis / enzymology
  • Pancreatitis / metabolism
  • Rats
  • Tryptophan / metabolism

Substances

  • Benzoxazoles
  • Enzyme Inhibitors
  • Indazoles
  • Kynurenine
  • benzoxazolone
  • Tryptophan
  • Kynurenine 3-Monooxygenase