Novel amidrazone derivatives: Design, synthesis and activity evaluation

Bioorg Med Chem. 2018 Jul 23;26(12):3158-3165. doi: 10.1016/j.bmc.2018.04.042. Epub 2018 Apr 21.

Abstract

A series of new 6-styryl-naphthalene-2-amidrazone derivatives were synthesized and evaluated as potential ASIC1a inhibitors. Among them, compound 5e showed the most activity to inhibit [Ca2+]i. elevation in acid-induced articular chondrocytes. Together with the important role of ASIC1a in the pathogenesis of tissue acidification diseases including rheumatoid arthritis, these results might provide a meaningful hint or inspiration in developing drugs targeting at tissue acidification diseases.

Keywords: ASIC activity; Amidrazone; Articular chondrocytes; [Ca(2+)](i).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / chemistry
  • Acid Sensing Ion Channels / metabolism
  • Animals
  • Calcium / metabolism
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry*
  • Carboxylic Acids / pharmacology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Drug Design*
  • Naphthalenes / chemistry
  • Rats
  • Sodium Channel Agonists / chemical synthesis*
  • Sodium Channel Agonists / chemistry
  • Sodium Channel Agonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Acid Sensing Ion Channels
  • Carboxylic Acids
  • Naphthalenes
  • Sodium Channel Agonists
  • naphthalene
  • Calcium