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Design, Synthesis of New Pyrazolo[3,4-d]Pyrimidine Derivatives and In Vitro Evaluation of Antiproliferative Activity against Leukemia Cell Lines

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Abstract

A series of new pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and evaluated against leukemia cell lines. All the compounds showed good in vitro anti-proliferative activities and some of them were 8–10 times more potent than BTK inhibitor ibrutinib. The IC50 values of promising compounds (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-2-bromoprop-2-en-1-one (IIc), (R,Z)-4-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-4-oxobut-2-enenitrile (IIk), (R,E)-4-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl) piperidin-1-yl)-4-oxobut-2-enenitrile (III) were observed in the range of 0.84–2.9 μM against L1210, K562 and HL-60 cell lines.

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REFERENCES

  1. Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., and Bray, F., CA Cancer J. Clin., 2021, caac.21660. https://doi.org/10.3322/caac.21660

  2. Martin, G.S., Cancer Cell, 2003, vol. 4, pp. 167–174. https://doi.org/10.1016/s1535-6108(03)00216-2

    Article  CAS  PubMed  Google Scholar 

  3. Hanahan, D. and Weinberg, R.A., Cell, 2011, vol. 144, pp. 646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  4. Santos, R., Ursu, O., Gaulton, A., Bento, A.P., Donadi, R.S., Bologa, C.G., Karlsson, A., Al-Lazikani, B., Hersey, A., and Oprea, T.I., Nat. Rev. Drug Discov., 2016, vol. 16, pp. 19–34. https://doi.org/10.1038/nrd.2016.230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fedorov, O., Müller, S., and Knapp, S., Nat. Chem. Biol., 2010, vol. 6, pp. 166–169. https://doi.org/10.1038/nchembio.297

    Article  CAS  PubMed  Google Scholar 

  6. Das, D. and Hong, J., Mini-Rev. Med. Chem., 2020, vol. 20, pp. 1732–1753. https://doi.org/10.2174/1389557520666200513121524

    Article  CAS  PubMed  Google Scholar 

  7. Das, D., Wang, J., and Hong, J., ChemMedChem, 2021, cmdc.202100166. https://doi.org/10.1002/cmdc.202100166

  8. Swinney, D.C., Curr. Opin. Drug Discov. Dev., 2009, vol. 12, pp. 31–9.

    CAS  Google Scholar 

  9. Mah, R., Thomas, J.R., and Shafer, C.M., Bioorg. Med. Chem. Lett., 2014, vol. 24, pp. 33–39. https://doi.org/10.1016/j.bmcl.2013.10.003

    Article  CAS  PubMed  Google Scholar 

  10. Das, D., Xie, L., Wang, J., Xu, X., Zhang, Z., Shi, J., Le, X., and Hong, J., Bioorg. Med. Chem. Lett., 2019, vol. 29, pp. 591–596. https://doi.org/10.1016/j.bmcl.2018.12.056

    Article  CAS  PubMed  Google Scholar 

  11. Das, D., Xie, L., Wang, J., Shi, J., and Hong, J., Bioorg. Chem., 2020, vol. 99, 103790. https://doi.org/10.1016/j.bioorg.2020.103790

    Article  CAS  PubMed  Google Scholar 

  12. Das, D., Wang, J., Li, Y., Shi, J., and Hong, J., Bioorg. Med. Chem. Lett., 2019, vol. 29, pp. 1514–1517. https://doi.org/10.1016/j.bmcl.2019.04.012

    Article  CAS  PubMed  Google Scholar 

  13. Cherukupalli, S., Hampannavar, G.A., Chinnam, S., Chandrasekaran, B., Sayyad, N., Kayamba, F., Reddy Aleti, R., and Karpoormath, R., Bioorg. Med. Chem., 2018, vol. 26, pp. 309–339. https://doi.org/10.1016/j.bmc.2017.10.012

    Article  CAS  PubMed  Google Scholar 

  14. Abdellatif, K.R.A. and Bakr, R.B., Bioorg. Chem., 2018, vol. 78, pp. 341–357. https://doi.org/10.1016/j.bioorg.2018.03.032

    Article  CAS  PubMed  Google Scholar 

  15. Radi, M., Dreassi, E., Brullo, C., Crespan, E., Tintori, C., Bernardo, V., Valoti, M., Zamperini, C., Daigl, H., and Musumeci, F., J. Med. Chem., 2011, vol. 54, pp. 2610–2626. https://doi.org/10.1021/jm1012819

    Article  CAS  PubMed  Google Scholar 

  16. Trivedi, A.R., Dholariya, B.H., Vakhariya, C.P., Dodiya, D.K., Ram, H.K., Kataria, V.B., Siddiqui, A.B., and Shah, V.H., Med. Chem. Res., 2012, vol. 21, pp.1887–1891. https://doi.org/10.1007/s00044-011-9712-3

    Article  CAS  Google Scholar 

  17. Bouton, J., Ferreira de Almeida Fiuza, L., Cardoso Santos, C., Mazzarella, M.A., Soeiro, M. de N.C., Maes, L., Karalic, I., Caljon, G., and Van Calenbergh, S., J. Med. Chem., 2021, vol. 64, pp. 4206–4238. https://doi.org/10.1021/acs.jmedchem.1c00135

    Article  CAS  PubMed  Google Scholar 

  18. Lamie, P.F., El-Kalaawy, A.M., Abdel Latif, N.S., Rashed, L.A., and Philoppes, J.N.P., Eur. J. Med. Chem., 2021, vol. 214, 113222. https://doi.org/10.1016/j.ejmech.2021.113222

    Article  CAS  PubMed  Google Scholar 

  19. Ismail, N.S.M., Ali, E.M.H., Ibrahim, D.A., Serya, R.A.T., and Abou El Ella, D.A., Future J. Pharm. Sci., 2016, vol. 2, pp. 20–30. https://doi.org/10.1016/j.fjps.2016.02.002

    Article  Google Scholar 

  20. Baillache, D.J. and Unciti-Broceta, A., RSC Med. Chem., 2020, vol. 11, pp. 1112–1135. https://doi.org/10.1039/D0MD00227E

    Article  CAS  Google Scholar 

  21. Rashad, A.E., Mahmoud, A.E., and Ali, M.M., Eur. J. Med. Chem., 2011, vol. 46, pp. 1019–1026. https://doi.org/10.1016/j.ejmech.2011.01.013

    Article  CAS  PubMed  Google Scholar 

  22. Lee, C.-S., Rattu, M.A., and Kim, S.S., J. Oncol. Pharm. Pract., 2016, vol. 22, pp. 92–104. https://doi.org/10.1177/1078155214561281

    Article  CAS  PubMed  Google Scholar 

  23. Davids, M.S. and Brown, J.R., Future Oncol., 2014, vol. 10, pp. 957–967. https://doi.org/10.2217/fon.14.51

    Article  CAS  PubMed  Google Scholar 

  24. Wang, M.L., Rule, S., Martin, P., Goy, A., Auer, R., Kahl, B.S., Jurczak, W., Advani, R.H., Romaguera, J.E., and Williams, M.E., N. Engl. J. Med., 2013, vol. 369, pp. 507–516. https://doi.org/10.1056/NEJMoa1306220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Treon, S.P., Tripsas, C.K., Meid, K., Warren, D., Varma, G., Green, R., Argyropoulos, K.V., Yang, G., Cao, Y., and Xu, L., N. Engl. J. Med., 2015, vol. 372, pp. 1430–1440. https://doi.org/10.1056/NEJMoa1501548

    Article  CAS  PubMed  Google Scholar 

  26. Gao, W., Wang, M., Wang, L., Lu, H., Wu, S., Dai, B., Ou, Z., Zhang, L., Heymach, J.V., and Gold, K.A. JNCI, J. Natl. Cancer Inst., 2014, vol. 106, dju204. https://doi.org/10.1093/jnci/dju204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Grabinski, N. and Ewald, F. Invest. New Drugs, 2014, vol. 32, pp. 1096–1104. https://doi.org/10.1007/s10637-014-0141-2

    Article  CAS  PubMed  Google Scholar 

  28. Shakeel, F., Iqbal, M., and Ezzeldin, E., J. Pharm. Pharmacol., 2016, vol. 68, pp. 772–780. https://doi.org/10.1111/jphp.12550

    Article  CAS  PubMed  Google Scholar 

  29. Bender, A.T., Gardberg, A., Pereira, A., Johnson, T., Wu, Y., Grenningloh, R., Head, J., Morandi, F., Haselmayer, P., and Liu-Bujalski, L., Mol. Pharmacol., 2017, vol. 91, pp. 208–219. https://doi.org/10.1124/mol.116.107037

    Article  CAS  PubMed  Google Scholar 

  30. Fletcher, S., Org. Chem. Front., 2015, vol. 2, pp. 739–752. https://doi.org/10.1039/C5QO00016E

    Article  CAS  Google Scholar 

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ACKNOWLEDGMENTS

The authors are thankful to Shanghai Medicilon Inc. for providing biological assay services.

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Authors and Affiliations

  1. Discovery Chemistry Research, Arromax Pharmatech Co. Ltd. Sangtiandao Science Innovation Park, 215123, Suzhou, P.R. China

    Debasis Das, Lingzhi Xie, Jingbing Wang, Dandan Qiao & Jian Hong

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  1. Debasis Das
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  2. Lingzhi Xie
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Correspondence to Debasis Das or Jian Hong.

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Debasis Das, Xie, L., Wang, J. et al. Design, Synthesis of New Pyrazolo[3,4-d]Pyrimidine Derivatives and In Vitro Evaluation of Antiproliferative Activity against Leukemia Cell Lines. Russ J Bioorg Chem 48, 153–162 (2022). https://doi.org/10.1134/S1068162022010046

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