Recent advances in the medicinal chemistry of carbonic anhydrase inhibitors.

Carbonic anhydrase (CA, EC 4.2.1.1) is an enzyme and a very omnipresent zinc metalloenzyme which catalyzed the reversible hydration and dehydration of carbon dioxide and bicarbonate; a reaction which plays a crucial role in many physiological and pathological processes. Carbonic anhydrase is present in human (h) with sixteen different isoforms ranging from hCA I-hCA XV. All these isoforms are widely distributed in different tissues/organs and are associated with a range of pivotal physiological activities. Due to their involvement in various physiological roles, inhibitors of different human isoforms of carbonic anhydrase have found clinical applications for the treatment of various diseases including glaucoma, retinopathy, hemolytic anemia, epilepsy, obesity, and cancer. However, clinically used inhibitors of CA (acetazolamide, brinzolamide, dorzolamide, etc.) are not selective causing the undesirable side effects. One of the major hurdles in the design and development of carbonic anhydrase inhibitors is the lack of balanced isoform selectivity which thrived to new chemotypes. In this review, we have compiled the recent strategies of various researchers related to the development of carbonic anhydrase inhibitors belonging to different structural classes like pyrimidine, pyrazoline, selenourea, isatin, indole, etc. This review also summarizes the structure-activity relationships, analysis of isoform selectivity including mechanistic and in silico studies to afford ideas and to provide focused direction for the design and development of novel isoform-selective carbonic anhydrase inhibitors with therapeutic implications.

Recent advancements in the development of bioactive pyrazoline derivatives.

Pyrazolines remain privileged heterocycles in drug discovery. 2-Pyrazoline scaffold has been proven as a ubiquitous motif which is present in a number of pharmacologically important drug molecules such as antipyrine, ramifenazone, ibipinabant, axitinib etc. They have been widely explored by the scientific community and are reported to possess wide spectrum of biological activities. For combating unprecedented diseases and worldwide increasing drug resistance, 2-pyrazoline has been tackled as a fascinating pharmacophore to generate new molecules with improved potency and lesser toxicity along with desired pharmacokinetic profile. This review aims to summarizes various recent advancements in the medicinal chemistry of pyrazoline based compounds with the following objectives: (1) To represent inclusive data on pyrazoline based marketed drugs as well as therapeutic candidates undergoing preclinical and clinical developments; (2) To discuss recent advances in the medicinal chemistry of pyrazoline derivatives with their numerous biological significances for the eradication of various diseases; (3) Summarizes structure-activity relationships (SAR) including in silico and mechanistic studies to afford ideas for the design and development of novel compounds with desired therapeutic implications.