1,3‐dipolar cycloaddition reactions of the compound obtaining from cyclopentadiene‐PTAD and biological activities of adducts formed selectively

• Published in: Journal of heterocyclic chemistry 2022-05, Vol.59 (5), p.864-878
• Main Authors: Yavari, Mirali Akbar, Taslimi, Parham, Bayrak, Cetin, Taskin‐Tok, Tugba, Menzek, Abdullah
• Format: Article
• Language: English
• Subjects: Adducts; Benzaldehyde; Biological activity; Biological effects; Chemical synthesis; Cycloaddition; Cyclopentadiene; Dichloromethane; Enzymes; Glucosidase; Imines; Molecular docking; Oximes; Reagents; Sodium hypochlorite
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4426

After known adduct (4) was synthesized by cycloaddition reaction of cyclopentadiene with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione, seven new isoxazoline derivatives were synthesized from reactions of 4 with corresponding oximes prepared from benzaldehyde derivatives in the existence of the aqueous NaOCl in CH2Cl2 at 0°C—RT via nitrile oxides. Four new pyrazoline derivatives were also synthesized from reactions of 4 with corresponding prepared reagents via nitrile imines. Selectively, each of all isoxazole and pyrazoline derivatives was synthesized by 1,3‐dipolar cycloaddition reactions of compound 4 with the corresponding reagents. Based on the results of their biological activity analyses, Ki values for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha‐glucosidase (α‐Gly) enzymes were obtained in this range 32.15 ± 5.73–107.44 ± 19.52 22.57 ± 4.30–186.07 ± 23.51, and 69.08 ± 8.54–528.07 ± 38.46 nM, respectively. Besides that, these compounds were subjected to molecular docking to describe the interaction against AChE, BChE, and α‐Gly enzymes in which important interactions were visualized and evaluated with residues of the binding region in each target enzyme. After known adduct (4) was synthesized by cycloaddition reaction of cyclopentadiene with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione, new seven isoxazoline and four pyrazoline derivatives were selectively synthesized from reactions of 4 with nitrile oxides and nitrile imines. Based on the results of their biological activity analyses, Ki values for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha‐glucosidase (α‐Gly) enzymes were obtained in this range 32.15 ± 5.73–107.44 ± 19.52 22.57 ± 4.30–186.07 ± 23.51, and 69.08 ± 8.54–528.07 ± 38.46 nM, respectively