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A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line

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Abstract

Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160 µM concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure–activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable.

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Acknowledgements

Authors thank The Scientific And Technological Research Council Of Turkey (TÜBİTAK- 119Z011) for financial support.

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Authors and Affiliations

  1. Pharmaceutical Chemistry Section, Van Yuzuncu Yil University, 65080, Van, Turkey

    Meltem Tan Uygun, Karina Amudi & Nurettin Menges

  2. SAFF Chemical Reagent RδD Laboratory, VAN-TEKNOKENT, 65080, Van, Turkey

    Meltem Tan Uygun, Karina Amudi & Nurettin Menges

  3. Department of Medical Biology, Faculty of Medicine, Ufuk University, 06520, Ankara, Turkey

    İrem Doğan Turaçlı

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  1. Meltem Tan Uygun
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  2. Karina Amudi
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  3. İrem Doğan Turaçlı
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  4. Nurettin Menges
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Correspondence to Nurettin Menges.

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Uygun, M.T., Amudi, K., Turaçlı, İ.D. et al. A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line. Mol Divers 26, 113–124 (2022). https://doi.org/10.1007/s11030-020-10161-8

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  • DOI: https://doi.org/10.1007/s11030-020-10161-8

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