PYRROLE CARBOXAMIDES AS POTENTIAL CARBONIC ANHYDRASE INHIBITORS

by Marketwala, Nishrin Ismailbhai

Carbonic anhydrases (CAs) are metalloenzymes that catalyze the reversible interconversion of CO2 and bicarbonate. We recently initiated a screen of a broad range of indoles and pyrroles possessing acyl-, carboxyl-, amido-, sulfonyl-, sulfamyl- and oxime- functionalities as potential inhibitors of á-CA II isozyme. As slight inhibition was observed in the case of 2-carboxamido-1-(phenylsulfonyl)pyrrole, and aware that pyrrole carboxamide derived sulfonamides had been previously demonstrated to possess CA inhibition, we sought to prepare a series of 1-(phenylsulfonyl)pyrrole-2-carboxamides but lacking a sulfonamide moiety to ascertain if the activity in our case might be due to a hitherto unrecognized pyrrole pharmacophore. To this end, we examined synthetic routes to such derivatives and found optimal results when employing a microwave-assisted, polymer-supported amidation reaction of 1-(phenylsulfonyl)pyrrole-2-carboxylic acid. Additionally, we examined the microwave-assisted Beckmann rearrangement of the oximes of acyl-1-(phenylsulfonyl)pyrroles and observed optimal results using montmorillonite as catalyst under solventless conditions.