Identification of 1, 4-Dihydrothieno [3', 2':5, 6]thiopyrano[4, 3-c] pyrazole derivatives as human 5-Lipo-oxygenase inhibitors

Chem Biol Drug Des. 2014 Dec;84(6):642-7. doi: 10.1111/cbdd.12356. Epub 2014 Jun 21.

Abstract

A series of novel 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]-pyrazole-3-carboxamide derivatives were synthesized and evaluated for their inhibitory activity to human 5-lipo-oxygenase (5-LOX). Compound 7c was found to exhibit significant inhibition to human 5-LOX with IC50 value of 5.7 ± 0.9 μm. Compound 7c was further studied using molecular docking in order to delineate its structure-activity relationship and to gain insight into the design of effective 5-LOX inhibitors.

Keywords: bioassay; cross-reactivity; human 5-lipo-oxygenase inhibitors; molecular docking; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / chemistry*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Binding Sites
  • Heterocyclic Compounds, 3-Ring / chemical synthesis
  • Heterocyclic Compounds, 3-Ring / chemistry*
  • Heterocyclic Compounds, 3-Ring / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Lipoxygenase Inhibitors / chemistry*
  • Lipoxygenase Inhibitors / metabolism
  • Molecular Docking Simulation
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Protein Structure, Tertiary
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism
  • Structure-Activity Relationship

Substances

  • 1-(7-bromo-1,4-dihydrothieno(3',2'-5,6)thiopyrano(4,3-c)pyrazole-3-carbonyl)-4-(2-fluorophenyl)piperazine
  • Heterocyclic Compounds, 3-Ring
  • Lipoxygenase Inhibitors
  • Piperazines
  • Pyrazoles
  • pyrazole
  • Arachidonate 5-Lipoxygenase