Dissemin is shutting down on January 1st, 2025

Published in

American Chemical Society, Journal of Medicinal Chemistry, 21(58), p. 8564-8572, 2015

DOI: 10.1021/acs.jmedchem.5b01144

Links

Tools

Export citation

Search in Google Scholar

Discovery of 1,1'-Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors

This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Orange circle
Postprint: archiving restricted
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

New 1,1′-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1–21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1′-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.