4.5 Article

Privileged scaffolds in medicinal chemistry: Studies on pyrazolo[1,5-a]pyrimidines on sulfonamide containing Carbonic Anhydrase inhibitors

Journal

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 49, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2021.128309

Keywords

Pyrazolopyrimidines; Carbonic Anhydrase inhibitors; Privilege scaffolds; X-ray crystallography

Funding

  1. TUBITAK (The Scientific and Technological Research Council of Turkey)
  2. Fon-dazione Cassa di Risparmio di Firenze [ECR2018.1001]

Ask authors/readers for more resources

In this study, a small series of compounds with inhibitory properties for human Carbonic Anhydrase enzymes were reported for the first time. Some of these compounds showed good selectivity for specific CAs, and one compound exhibited nearly matching K-I values for both hCA II and IX. X-ray crystal experiments were used to explore the binding mode of this compound within the CA IX mimic isoform.
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 K-I 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available