Pyrazole/pyrazoline as an excellent pharmacophore in the design of carbonic anhydrase inhibitors (2018-2022)

Carbonic anhydrase (CA) is a metalloenzyme that catalyzes the interconversion between carbon dioxide and water and dissociated ions of carbonic acid. In addition, CA performs various other functions in animals and plants, depending on the part of the living being. CAs have been found in almost all organisms. Besides, CAs are associated with several diseases, such as glaucoma, obesity, epilepsy, cancer, and so on. CAs are also involved in tumor cell growth and angiogenesis. Thus, inhibition of CA may be an attractive way of control of such diseases. Hence, CA inhibitors have been designed and developed to cure CA-associated diseases. Some examples of approved CA inhibitors are dorzolamide, methazolamide, brinzolamide, and dichlorphenamide. Furthermore, various heterocyclic scaffolds were utilized for the design of CA inhibitors. Among those, pyrazole/pyrazoline derivatives have exhibited greater potency toward CA inhibition. Hence, research that took place in the field of drug design and discovery of CA inhibition has been systematically reviewed and collated. Alongside, the structure-activity relationship has been described, followed by a description of the most potent molecules and their structural features.