4-[N-(substituted 4-pyrimidinyl)amino]benzenesulfonamides as inhibitors of carbonic anhydrase isozymes I, II, VII, and XIII

Bioorg Med Chem. 2010 Nov 1;18(21):7413-21. doi: 10.1016/j.bmc.2010.09.011. Epub 2010 Sep 8.

Abstract

A series of 4-[N-(substituted 4-pyrimidinyl)amino]benzenesulfonamides were designed and synthesised. Their binding potencies as inhibitors of selected recombinant human carbonic anhydrase (hCA) isozymes I, II, VII, and XIII were measured using isothermal titration calorimetry and the thermal shift assay. To determine the structural features of inhibitor binding, the crystal structures of several compounds in complex with hCA II were determined. Several compounds exhibited selectivity towards isozymes I, II, and XIII, and some were potent inhibitors of hCA VII.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Calorimetry
  • Carbonic Anhydrase I / antagonists & inhibitors
  • Carbonic Anhydrase I / genetics
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase II / genetics
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / metabolism
  • Crystallography, X-Ray
  • Humans
  • Protein Structure, Tertiary
  • Pyrimidines / chemistry
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology

Substances

  • Carbonic Anhydrase Inhibitors
  • Pyrimidines
  • Recombinant Proteins
  • Sulfonamides
  • benzenesulfonamide
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • CA13 protein, human
  • Carbonic Anhydrases
  • carbonic anhydrase VI
  • pyrimidine