Synthesis of 2-amino-3-cyanopyridine derivatives and investigation of their carbonic anhydrase inhibition effects

The conversion of carbon dioxide (CO2) and bicarbonate (HCO3 −) to each other is very important for living metabolism. Carbonic anhydrase (CA, E.C.4.2.1.1), a metalloenzyme familly, catalyzes the interconversion of these ions (CO2 and HCO3 −) and are very common in living organisms. In this study, a series of novel 2-amino-3-cyanopyridines supported with some functional groups was synthesized and tested as potential inhibition effects against both cytosolic human CA I and II isoenzymes (hCA I and II) using by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. The structural elucidations of novel 2-amino-3-cyanopyridines were achieved by NMR, IR, and elemental analyses. Ki values of the novel synthesized compounds were found in range of 2.84–112.44 μM against hCA I and 2.56–31.17 μM against hCA II isoenzyme. While compound 7d showed the best inhibition activity against hCA I (Ki: 2.84 μM), the compound 7b demonstrated the best inhibition profile against hCA II isoenzyme (Ki: 2.56 μM). © 2017 Wiley Periodicals, Inc.