(Hetero)aryl substituted thiazol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators

J Enzyme Inhib Med Chem. 2019 Dec;34(1):224-229. doi: 10.1080/14756366.2018.1543292.

Abstract

Using histamine as lead molecule, a library of (hetero)aryl substituted thiazol-2,4-yl derivatives incorporating pyridine as proton shuttling moiety were obtained and investigated as activators of human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I, II, VII and XIV. Some derivatives displayed good activating and selectivity profiles. This study provides an interesting opportunity to study the thiazole scaffold for the design of CA activators (CAAs), possibly acting on the central nervous system and targeting pathologies involving memory and learning impairments.

Keywords: Thiazole scaffold; carbonic anhydrase activators; drug design; isozymes; synthesis.

MeSH terms

  • Carbonic Anhydrase I / metabolism*
  • Carbonic Anhydrase II / metabolism*
  • Carbonic Anhydrases / metabolism*
  • Enzyme Activators / chemistry
  • Enzyme Activators / pharmacology*
  • Humans
  • Molecular Structure
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Enzyme Activators
  • Thiazoles
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Carbonic Anhydrases
  • carbonic anhydrase VI
  • carbonic anhydrase XIV