2-Amino-3-cyanopyridine derivatives as carbonic anhydrase inhibitors


Ayvaz S., ÇANKAYA M., ATASEVER A., Altuntas A.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.28, no.2, pp.305-310, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 2
  • Publication Date: 2013
  • Doi Number: 10.3109/14756366.2011.639016
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.305-310
  • Keywords: 2-amino-3-cyanopyridines, 4-furyl, 4-thienyl, carbonic anhydrase, enzyme inhibition, ISOFORM-IX, SULFONAMIDES, THIOXOLONE, CHEMOTYPES, COUMARINS, MECHANISM
  • Gazi University Affiliated: Yes

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that catalyze the hydration of CO 2 to bicarbonate and protons. Inhibition of CAs has been clinically exploited for the treatment of various classes of diseases for decades, but investigating new classes of inhibitors continues to be important. We have synthesized a series of 2-amino-3-cyano-4-heteroaryl (5a-l) compounds and characterized the structures by NMR, IR and elemental analyses. We tested the ability of these compounds to inhibit two metalloenzyme human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and hCA II. Compounds 5d and 5b showed the best inhibition activity against hCA I (IC50: 33 and 34 mu M, respectively), and compound 5d showed the best activity against hCA II (IC50: 56 mu M).