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New bis(pyrazolo[3,4-b]pyridines) and bis(thieno[2,3-b]pyridines) as potential acetylcholinesterase inhibitors: synthesis, in vitro and SwissADME prediction study

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Abstract

The bis(pyridine-2(1H)-thione) was prepared and taken as a key synthon of this study. The target bis(pyrazolo[3,4-b]pyridines) was prepared, in good yields, by the reaction of bis(pyridine-2(1H)-thione) with appropriate hydrazonyl chlorides to yield bis(hydrazonothioates) followed by their heating in ethanolic sodium ethoxide solution. Additionally, bis(pyridine-2(1H)-thione) reacted with different α-halogenated reagents to afford a new series of bis(thieno[2,3-b]pyridines), in good to excellent yields. In general, the tested series of bis(thieno[2,3-b]pyridines) demonstrated greater acetylcholinesterase inhibitory activity as well as DPPH antioxidant activity than the other series of (pyrazolo[3,4-b]pyridines). At a concentration of 100 μM, bis(thieno[2,3-b]pyridine-2-carbonitrile) showed the best acetylcholinesterase inhibitory activity with inhibition percentage of 83.2. In addition, the previous hybrid had the highest DPPH antioxidant activity, with an inhibition percentage of 82.6 when tested at a concentration of 25 μg/mL. Furthermore, SwissADME was used to predict the physicochemical properties, lipophilicity, and drug likeness of the new products.

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  1. Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt

    Ahmed A. M. Ahmed, Ahmed E. M. Mekky & Sherif M. H. Sanad

  2. Common First Year Deanship, Jouf University, Sakaka, Kingdom of Saudi Arabia

    Ahmed A. M. Ahmed

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Ahmed, A.A.M., Mekky, A.E.M. & Sanad, S.M.H. New bis(pyrazolo[3,4-b]pyridines) and bis(thieno[2,3-b]pyridines) as potential acetylcholinesterase inhibitors: synthesis, in vitro and SwissADME prediction study. J IRAN CHEM SOC 19, 4457–4471 (2022). https://doi.org/10.1007/s13738-022-02614-8

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