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An Efficient Synthesis and Reactions of 5-Acetyl-6-Methyl-4-(1,3-Diphenyl-1H-Pyrazol-4-yl)-3,4-Dihydropyrmidin-2(1H)-Thione as Potential Antimicrobial and Anti-Inflammatory Agents

Russian Journal of Bioorganic Chemistry volume 47, pages 561–571 (2021)Cite this article

Abstract

The synthesis of 5-acetyl-6-methyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)-3,4-dihydropyrmidin-2(1H)-thione was achieved by one-pot three-component synthesis using CaCl2 in refluxing EtOH. The starting compound was utilized to synthesize a new series of 5-pyrazolyl; isoxazolyl; pyrimidinyl derivatives via the synthesized chalcone. Also, fused isoxazolo [5,4-d]pyrimidine and pyrazolo[3,4-d]pyrimidine were obtained by the treatment of 5-acetyl derivative with hydroxyl amine and/ or hydrazine hydrate. Also, the thiosemicarbazide derivative was prepared and utilized to synthesize other new thiazole derivatives. The structures of all compounds have been established on the basis of their analytical and spectral data. All compounds was also evaluated for their antibacterial and antifungal activity against various strains of bacteria and fungi. Also, the anti-inflammatory activity of some of synthesized compounds was evaluated using the carrageenan induced paw oedema test in rats using indomethacin as the reference drug.

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REFERENCES

  1. Kappe, C.O., Eur. J. Med. Chem., 2000, vol. 35, pp. 1043–1052. https://doi.org/10.1016/S0223-5234(00)01189-2

  2. Chitra, S., Devanathan, D., and Pandiarajan, K., Eur. J. Med. Chem.,2010, vol. 45, pp. 367–371. https://doi.org/10.1016/j.ejmech.2009.09.018

    CAS  Article  PubMed  Google Scholar 

  3. Biginelli, P., Grazz. Chim. Ital., 1893, vol. 23, pp. 360–416.

    Google Scholar 

  4. Kappe, C. O., Acc. Chem. Res., 2000, vol. 33, pp. 879–888. https://doi.org/10.1021/ar000048h

    CAS  Article  PubMed  Google Scholar 

  5. Zhu, J. and Bienayme, H., Multicomponent Reactions, Weinheim, Germany: Wiley-Vch, 2005.

    Book  Google Scholar 

  6. Domling, A., Chem. Rev., 2006, vol. 106, pp. 17–89 https://doi.org/10.1021/cr0505728

    CAS  Article  PubMed  Google Scholar 

  7. Tejedor, D. and Garcia-Tellado, F., Chem. Soc. Rev., 2007, vol. 36, pp. 484–491. https://doi.org/10.1039/B608164A

    CAS  Article  PubMed  Google Scholar 

  8. Muller, T.J.J., Beilstein J. Org. Chem., 2011, vol. 7, pp. 960–961. https://doi.org/10.3762/bjoc.7.107

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Atwal, K.S., Rovnyak, G.C., Kimball, S.D., Floyd, D.M., Moreland, S., Swanson, B.N., Gougoutas, J.Z., Schawtrz, J., and Malley, M.F., J. Med. Chem., 1990, vol. 33, pp. 2629–2635. https://doi.org/10.1021/jm00171a044t

    CAS  Article  PubMed  Google Scholar 

  10. Rovnyak, G.C., Kimball, S.D., Beyer, B., Cucinotta, G., Dimarco, J.D., Gougoutas, J.Z., Hedberg, A., Malley, M.F., Macarthy, J.P., Zhang, R., and Moreland, S., J. Med. Chem., 1995, vol. 38, pp. 119–129. https://doi.org/10.1021/jm0001a017

    CAS  Article  PubMed  Google Scholar 

  11. Santosh, N.M., Sandeep, S.S., Rupali, D.E., Jaiprakash, N.S., and Devanand, S., Bioorg. Med. Chem., 2010, vol. 20, pp. 4424–4426. https://doi.org/10.1016/j.bmcl.2010.06.058

    CAS  Article  Google Scholar 

  12. Grover, G.J. Dzwonczyk, S., McMullen, D.M., Normandin, D.E., Parham, C.S., Sleph, P.G., and Moreland, S., Cardiovasc. Pharmacol., 1995, vol. 26, pp. 289–294. https://doi.org/10.1097/00005344-199508000-00015

    CAS  Article  Google Scholar 

  13. Lewis, R.W., Mabry, J., Polisar, J.G., Eagen, K.P., Ganem, B., and Hess, G.P., Biochemistry, 2010, vol. 49, pp. 4841–4851. https://doi.org/10.1021/bi100119t

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Chikhale, R.V., Bhole, R.P., Khedekar, P.B., and Brusari, K.P., Eur. J. Med. Chem., 2009, vol. 44, pp. 3645–3653. https://doi.org/10.1016/j.ejmech.2009.02.021

    CAS  Article  PubMed  Google Scholar 

  15. Nofal, M.Z., Fahmy, H.H., Zerea, E.S., and Eleraky, W., Acta Pol. Pharm., 2011, vol. 68, pp. 507–517. ISSN 0001-6837

  16. Boukis, A.C., Llevot, A., and Meie, M.A.R., Macromol. Rapid Commun., 2016, vol. 37, pp. 643–649. https://doi.org/10.1002/marc.201500717

    CAS  Article  PubMed  Google Scholar 

  17. Zhao, Y., Yu, Y., Zhang, Y., Wang, X., Yang, B., Zhang, Y., Zhang, Q., Fu, C., Weia, Y., and Tao, L., Polym. Chem., 2015, vol. 6, pp. 4940–4945. https://doi.org/10.1021/acsmacrolett.5b00428

    CAS  Article  Google Scholar 

  18. Patil, S.R., Choudhary, A.S., Patil, V.S., and Sekar, N., Fibers Polym., 2015, vol. 16, pp. 2349–2358. https://doi.org/10.1007/s12221-015-5233-x

  19. Abdel-Mohsen, Sh.A., and Hussein, E.M., Russ. J. Bioorg. Chem., 2014, vol. 40, pp. 343–349. https://doi.org/10.1134/S1068162014030029

    CAS  Article  Google Scholar 

  20. Abdel-Mohsen, S.A., and El-Emary, T.I., Arkivoc, 2016, vol. IV, pp. 184–192. https://doi.org/10.3998/ark.5550190.poo9.602

    Article  Google Scholar 

  21. Abdel-Mohsen, S.A. and El-Ossaily, Y.A., Heterocycl. Commun., 2015, vol. 21, pp. 207–210. https://doi.org/10.1515/hc-2015-00331

    CAS  Article  Google Scholar 

  22. Gangadasu, B., Narender, P., China Rajn, B., and Jayathirtha Rao, V., Ind. J. Chem., 2006, vol. 45B, pp. 1259–1263.

    CAS  Google Scholar 

  23. Kappe, C.O., J. Org. Chem., 1997, vol. 62, pp. 7201–7204. https://doi.org/10.1021/jo971010u

    CAS  Article  PubMed  Google Scholar 

  24. El-Hamouly, W.S., El-Khamry, A.A., and Abbas, E.M.H., Ind. J. Chem. 2006, vol. 45B, pp. 2091–2098.

    CAS  Google Scholar 

  25. Kwon-Chung, K.J. and Bennett, J.W. Medical Mycology, Philadelphia: Lea and Febiger, 1992, pp. 81–102.

  26. Winter, C.A., Risley, E.A., and Nus, G.N., Proc. Soc. Exp. Biol., 1962, vol. 111, pp. 544–547.

    CAS  Article  Google Scholar 

  27. Karema, N.M.H., Sayed, K.R., Sameh, A.R., and Maher, A.E., Synth. Commun., 2020, vol. 50, pp. 1159–1175. https://doi.org./10.1080/00397911.2020.1720739

    Article  Google Scholar 

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ACKNOWLEDGMENTS

The authors are grateful to Prof. Dr. Ahmed Moharem. professor of Botany and Microbiology department and the director of Mycology center and collogues of Faculty of Medicine, Assiut Univeristy for their kind help in performing the pharmacological screening.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Assiut University 71516, Assiut, Egypt

    Talaat I. El-Emary, Shawkat A. Abdel-Mohsen & Shereen A. Mohamed

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  1. Talaat I. El-Emary
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  2. Shawkat A. Abdel-Mohsen
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  3. Shereen A. Mohamed
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Correspondence to Shawkat A. Abdel-Mohsen.

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This article does not contain any studies involving human participants performed by any of the authors and does not contain any studies involving animals performed by any of the author.

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Talaat I. El-Emary, Abdel-Mohsen, S.A. & Mohamed, S.A. An Efficient Synthesis and Reactions of 5-Acetyl-6-Methyl-4-(1,3-Diphenyl-1H-Pyrazol-4-yl)-3,4-Dihydropyrmidin-2(1H)-Thione as Potential Antimicrobial and Anti-Inflammatory Agents. Russ J Bioorg Chem 47, 561–571 (2021). https://doi.org/10.1134/S1068162021020102

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  • DOI: https://doi.org/10.1134/S1068162021020102

Keywords:

  • one pot reaction
  • DHPMs
  • chalcone
  • azole
  • thiazole
  • biological activity