We report for the first time a small series of compounds endowed in vitro with inhibitory properties for the human (h) expressed Carbonic Anhydrase (CAs, E.C. 4.2.1.1) enzymes of physiological interest (i.e. I, II, VA, IX and XII) and bearing the pyrazolo[1,5-a]pyrimidine (PP) scaffold at the tail section. Among the series reported, 1a-3a, 7a, 8a, 1b and 2b resulted effective ligands and with good selectivities for the hCAs II, IX or XII. In consideration of the nearly matching KI values of 7a for both the hCA II and IX (i.e. 26.4 and 23.0 nM respectively) we explored its binding mode within the CA IX mimic isoform by means of X-ray crystal experiments on the corresponding adduct.
Privileged scaffolds in medicinal chemistry: Studies on pyrazolo[1,5-a]pyrimidines on sulfonamide containing Carbonic Anhydrase inhibitors / Gumus A.; Bozdag M.; Angeli A.; Peat T.S.; Carta F.; Supuran C.T.; Selleri S.. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - ELETTRONICO. - 49:(2021), pp. 0-0. [10.1016/j.bmcl.2021.128309]
Privileged scaffolds in medicinal chemistry: Studies on pyrazolo[1,5-a]pyrimidines on sulfonamide containing Carbonic Anhydrase inhibitors
Bozdag M.;Angeli A.;Carta F.;Supuran C. T.;Selleri S.
2021
Abstract
We report for the first time a small series of compounds endowed in vitro with inhibitory properties for the human (h) expressed Carbonic Anhydrase (CAs, E.C. 4.2.1.1) enzymes of physiological interest (i.e. I, II, VA, IX and XII) and bearing the pyrazolo[1,5-a]pyrimidine (PP) scaffold at the tail section. Among the series reported, 1a-3a, 7a, 8a, 1b and 2b resulted effective ligands and with good selectivities for the hCAs II, IX or XII. In consideration of the nearly matching KI values of 7a for both the hCA II and IX (i.e. 26.4 and 23.0 nM respectively) we explored its binding mode within the CA IX mimic isoform by means of X-ray crystal experiments on the corresponding adduct.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.