Novel sulfamides as potential carbonic anhydrase isoenzymes inhibitors

Bioorg Med Chem. 2013 Mar 15;21(6):1379-85. doi: 10.1016/j.bmc.2013.01.019. Epub 2013 Jan 22.

Abstract

Sulfamides represent an important class of biologically active compounds. A series of novel sulfamides were synthesized from 1-aminoindanes, 1-aminotetralin, 2-aminoindanes and 2-aminotetralin via the reactions of free amines, benzyl alcohol and chlorosulfonyl isocyanate (CSI) followed by hydrogenolysis of the obtained sulfamoylcarbamates. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the new sulfamides have been investigated. The human (h) isozymes hCA I and hCA II have been investigated in this study by using an esterase assay with 4-nitrophenyl acetate as substrate. The new sulfamides showed inhibition constants in the micro-submicromolar range, with one compound (N-(indane-1-yl)sulfamide) showing a Ki of 0.45μM against hCA I and of 1.07μM against hCA II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase I / chemistry
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / metabolism
  • Erythrocytes / enzymology
  • Humans
  • Kinetics
  • Nitrophenols / chemistry
  • Nitrophenols / metabolism
  • Protein Binding
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism

Substances

  • Carbonic Anhydrase Inhibitors
  • Nitrophenols
  • Sulfonamides
  • 4-nitrophenyl acetate
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II