2-Pyrazoline core is a very interesting five-membered heterocycle, which has been explored in recent years due to its vast applications as the core structure of bioactive and industrial agents. Based on literature studies, versatile synthetic approaches have been employed for the preparation of 2pyrazolines, among them the reaction between hydrazines and α,β-unsaturated enones as the most used method. In this review article, different methods for the synthesis of 2-pyrazolines using hydrazine derivatives were classified and presented.Initially, numerous catalytic methods for the preparation of 2pyrazolines from hydrazines and α,β-unsaturated enones are reviewed and various aspects of these methods discussed including catalyst efficiency, catalyst recovery, green chemistry, cost-effectiveness, scope of the method, enantioselectivity, and yield. In addition, reactions between hydrazines and other reagents in multicomponent and two-component reactions, developed recently, are discussed. Finally, some of the important applications of 2-pyrazolines are summarized.

A new series of 1,3,5‐trisubstituted 2‐pyrazolines for the inhibition of cyclooxygenase‐2 (COX‐2) were synthesized. The designed structures include a COX‐2 pharmacophore SO2CH3 at the para‐position of the phenyl ring located at C‐5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX‐1/COX‐2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT‐29. The lead compound (4‐chlorophenyl){5‐[4‐(methanesulfonyl)phenyl]‐3‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl}methanone (16) showed significant COX‐2 inhibition (IC50=0.05±0.01 μM), and antiproliferative activity (IC50=5.46±4.71 μM). Molecular docking studies showed that new pyrazoline‐based compounds interact via multiple hydrophobic and hydrogen‐bond interactions with key binding site residues of the COX‐2 enzyme.

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