Zeolite‐catalyzed synthesis of nicotinyl‐fused indolo‐pyrazoles and evaluation of their activities against Anopheles arabiensis and Lipoxygenase

Abstract

A series of nicotyl‐fused indolo‐pyrazoles (NFIPs) were synthesized by a one‐pot multicomponent reaction of aryl aldehydes, isoniazid, and indole in the presence of zeolite as a catalyst. Structures of all the synthesized compounds were established by IR, 1H‐NMR, 13C‐NMR, 2D‐NMR, TOF‐MS, and elemental analysis. The products were obtained in excellent yields and high purity. All 10 compounds were screened for larvicidal and insecticidal properties against Anopheles arabiensis and tested for their lipoxygenase inhibitory activity. Compounds (3‐(3‐hydroxy‐4‐methoxyphenyl)‐2,3‐dihydropyrazolo[4,3‐b]indol‐1(4H)‐yl)(pyridin‐4‐yl)methanone (4i) and (3‐(3‐bromo‐5‐hydroxy‐4‐methoxyphenyl)‐2,3‐dihydropyrazolo[4,3‐b]indol‐1(4H)‐yl)(pyridin‐4‐yl)methanone (4j) displayed highest larvae mortality at a 4 μg/ml dose in 24 h. Compounds (3‐(4‐methoxyphenyl)‐2,3‐dihydropyrazolo[4,3‐b]indol‐1(4H)‐yl)(pyridin‐4‐yl)methanone (4h) and (3‐(3‐hydroxy‐4‐methoxyphenyl)‐2,3‐dihydropyrazolo[4,3‐b]indol‐1(4H)‐yl)(pyridin‐4‐yl)methanone (4i) showed a significant knockdown activity after 24 h with 70% mortality. Furthermore, (3‐(4‐chlorophenyl)‐2,3‐dihydropyrazolo[4,3‐b]indol‐1(4H)‐yl)(pyridin‐4‐yl)methanone (4c) and (3‐(3‐bromo‐5‐hydroxy‐4‐methoxyphenyl)‐2,3‐dihydropyrazolo[4,3‐b]indol‐1(4H)‐yl)(pyridin‐4‐yl)methanone (4j) displayed promising lipoxygenase inhibitory activity with a mortality of 70% and 60%, respectively.