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Research on Chemical Intermediates

, Volume 42, Issue 3, pp 2597–2617 | Cite as

Design, synthesis, and pharmacological studies of some new Mannich bases and S-alkylated analogs of pyrazole integrated 1,3,4-oxadiazole

  • Shivapura Viveka
  • Dinesha
  • Prasanna Shama
  • Gundibasappa Karikannar Nagaraja
  • Nagaraju Deepa
  • Marikunte Yanjarappa Sreenivasa
Article

Abstract

A facile and convenient synthesis of Mannich bases 5af and S-alkylated derivatives 6af and 7af has been carried out from the key intermediate 5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole-2(3H)-thione (4). Intermediate 4 was obtained from one-pot reaction of ethyl acetoacetate, phenylhydrazine, and N,N-dimethylformamide dimethyl acetal (DMF-DMA) followed by reaction with hydrazine hydrate and carbon disulfide. The structure of the newly synthesized compounds was established on the basis of elemental analysis, infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopic data. All synthesized compounds were screened for in vivo antiinflammatory, in vivo analgesic, and in vitro antimicrobial activity. From the activity studies, it was concluded that, among all the derivatives, compounds 5c, 5e, 5f, 6c, 7b, and 7c showed potent antiinflammatory activity, whereas 5b, 5c, 5e, 5f, 6c, 6f, 7b, 7c, and 7e exhibited good analgesic activity. Compounds 6a, 6c, 7b, 7c, and 7d showed maximum activity against the bacterial strains. Efforts were also made to establish structure–activity relationships among the tested compounds.

Keywords

Pyrazole Mannich bases S-alkylation Antimicrobial Antiinflammatory Analgesic activity 

Notes

Acknowledgments

The authors gratefully acknowledge UGC, SAP, and DST-PURSE for financial assistance. We are grateful to IISC Bangalore and USIC, Mangalore University for providing the spectral analysis.

References

  1. 1.
    S. Laufer, S. Luik, Methods Mol. Biol. 644, 91–116 (2010)CrossRefGoogle Scholar
  2. 2.
    M.F. Mahdi, H.N. Alsaad, Pharmaceuticals 5, 1080–1091 (2012)CrossRefGoogle Scholar
  3. 3.
    J.E.F. Reynolds, The extra pharmacopoeia, in Martindale, 30th edn., ed. by J.E.F. Reynold (Pharmaceutical Press, London, 1993), p. 1310Google Scholar
  4. 4.
    N.M. Davies, J.L. Wallace, J. Gastroenterol. 32, 127–133 (1997)CrossRefGoogle Scholar
  5. 5.
    M.M. Wolfe, D.R. Lichtenstein, G. Singh, N. Engl. J. Med. 340, 1888–1899 (1999)CrossRefGoogle Scholar
  6. 6.
    M.B. Kimmey, J. Rheumatol. 19, 68–73 (1992)Google Scholar
  7. 7.
    A. Hall, A. Billinton, S.H. Brown, N.M. Clayton, A. Chowdhury, G.M.P. Giblin, P. Goldsmith, T.G. Hayhow, D.N. Hurst, I.R. Kilford, A. Naylor, B. Passingham, L. Winyard, Bioorg. Med. Chem. Lett. 18, 3392–3399 (2008)CrossRefGoogle Scholar
  8. 8.
    M. Amir, H. Kumar, S.A. Khan, Bioorg. Med. Chem. Lett. 18, 918–922 (2008)CrossRefGoogle Scholar
  9. 9.
    R. Sridhar, P.T. Perumal, S. Etti, G. Shanmugam, M.N. Ponnuswamy, V.R. Prabavathy, N. Mathivanan, Bioorg. Med. Chem. Lett. 14, 6035–6040 (2004)CrossRefGoogle Scholar
  10. 10.
    R. Lin, G. Chiu, Y. Yu, P.J. Connolly, S. Li, Y. Lu, M. Adams, A.R. Fuentes-Pesquera, S.L. Emanuel, L.M. Greenberger, Bioorg. Med. Chem. Lett. 17, 4557–4561 (2007)CrossRefGoogle Scholar
  11. 11.
    P.G. Baraldi, S. Manfredini, R. Romagnoli, L. Stevanato, A.N. Zaid, R. Manservigi, Nucleosides Nucleotides 17, 2165–2173 (1998)CrossRefGoogle Scholar
  12. 12.
    P. Rathelot, N. Azas, H. El-Kashef, F. Delmas, C.D. Giorgio, P. Timon-David, J. Maldonado, P. Vanelle, Eur. J. Med. Chem. 37, 671–679 (2002)CrossRefGoogle Scholar
  13. 13.
    A.M. Isloor, B. Kalluraya, P. Shetty, Eur. J. Med. Chem. 44, 3784–3787 (2009)CrossRefGoogle Scholar
  14. 14.
    A.M. Bernard, M.T. Cocco, A. Maccioni, A. Plumitallo, Farmaco Ed. Sci. 40, 259–271 (1985)Google Scholar
  15. 15.
    A. Gürsoy, Ş. Demirayak, G. Çapan, K. Erol, K. Vural, Eur. J. Med. Chem. 35, 359–364 (2000)CrossRefGoogle Scholar
  16. 16.
    A.A. Bekhit, H.M.A. Ashour, Y.S.A. Ghany, A.E.A. Bekhit, A. Baraka, Eur. J. Med. Chem. 43, 456–463 (2008)CrossRefGoogle Scholar
  17. 17.
    C.R.W. Guimaraes, D.L. Boger, W.L. Jorgensen, J. Am. Chem. Soc. 127, 17377–17384 (2005)CrossRefGoogle Scholar
  18. 18.
    B. Rigo, D. Couturier, J. Heterocycl. Chem. 22, 287–288 (1985)CrossRefGoogle Scholar
  19. 19.
    A.A. El-Emam, O.A. Al-Deeb, M. Al-Omar, J. Lehmann, Bioorg. Med. Chem. 12, 5107–5113 (2004)CrossRefGoogle Scholar
  20. 20.
    M. Zareef, R. Iqbal, N.G. De Dominquez, J. Rodrigues, J.H. Zaidi, M. Arfan, C.T. Supuran, J. Enzyme Inhib. Med. Chem. 22, 301–308 (2007)CrossRefGoogle Scholar
  21. 21.
    M. Amir, K. Shikha, Eur. J. Med. Chem. 39, 535–545 (2004)CrossRefGoogle Scholar
  22. 22.
    D. Dewangan, A. Pandey, T. Sivakumar, R. Rajavel, R.D. Dubey, Int. J. ChemTech. Res. 3, 1397–1412 (2010)Google Scholar
  23. 23.
    S.V. Bhandari, K.G. Bothara, M.K. Raut, A.A. Patil, A.P. Sarkate, V.J. Mokale, Bioorg. Med. Chem. 16, 1822–1831 (2008)CrossRefGoogle Scholar
  24. 24.
    S. Bondock, S. Adel, H.A. Etman, F.A. Badria, Eur. J. Med. Chem. 48, 192–199 (2012)CrossRefGoogle Scholar
  25. 25.
    M.S.Y. Khan, R.M. Khan, S. Drabu, Indian J. Heterocycl. Chem. 11, 119–122 (2001)Google Scholar
  26. 26.
    H. Khalilullah, M.J. Ahsan, M. Hedaitullah, S. Khan, B. Ahmed, Mini Rev. Med. Chem. 12, 789–801 (2012)CrossRefGoogle Scholar
  27. 27.
    N.C. Desai, N. Bhatt, H. Somani, A. Trivedi, Eur. J. Med. Chem. 67, 54–59 (2013)CrossRefGoogle Scholar
  28. 28.
    T. Chandra, N. Garg, S. Lata, K.K. Saxena, A. Kumar, Eur. J. Med. Chem. 45, 1772–1776 (2010)CrossRefGoogle Scholar
  29. 29.
    K. Manjunatha, B. Poojary, P.L. Lobo, J. Fernandies, N.S. Kumari, Eur. J. Med. Chem. 45, 5225–5233 (2010)CrossRefGoogle Scholar
  30. 30.
    N.B. Patel, A.C. Purohit, D.P. Rajani, R. Moo-Puc, G. Rivera, Eur. J. Med. Chem. 62, 677–687 (2013)CrossRefGoogle Scholar
  31. 31.
    S. Viveka, Dinesha, S.S. Laxmeshwar, G.K. Nagaraja, Molbank 3, M776 (2012)CrossRefGoogle Scholar
  32. 32.
    S. Viveka, Dinesha, L.N. Madhu, G.K. Nagaraja, Monatsh. Chem. Chem. Mon. (2015). doi: 10.1007/s00706-015-1428-5 Google Scholar
  33. 33.
    C.S. Reddy, L.S. Rao, G.R. Kumar, A. Nagaraj, Chem. Pharm. Bull. 58, 1328–1331 (2010)CrossRefGoogle Scholar
  34. 34.
    P.M. Chandrika, T. Yakaiah, G. Gayatri, K.P. Kumar, B. Narsaiah, U.S.N. Murthy, A.R. Ram Rao, Eur. J. Med. Chem. 45, 78–84 (2010)CrossRefGoogle Scholar
  35. 35.
    M.M. Alam, A. Husain, S.M. Hasan, Suruchi, T. Anwer, Eur. J. Med. Chem. 44, 2636–2642 (2009)CrossRefGoogle Scholar
  36. 36.
    K.M. Amin, M.M. Hanna, H.E. Abo-Youssef, R.F. George, Eur. J. Med. Chem. 44, 4572–4584 (2009)CrossRefGoogle Scholar
  37. 37.
    C.A. Winter, E.A. Risley, G.W. Nuss, Proc. Soc. Exp. Biol. 111, 544–547 (1962)CrossRefGoogle Scholar
  38. 38.
    D.M. Kar, S.K. Sahu, P.K. Misro, Indian Drug. 40, 261–266 (2003)Google Scholar
  39. 39.
    R. Cruickshank, J.P. Duguid, B. Marmion, R.H.A. Swain, Medical Microbiology, 11th edn. (Churchill Livingstone, London, 1975), p. 190Google Scholar
  40. 40.
    O. Prakash, D.K. Aneja, P. Lohan, K. Hussain, S. Arora, C. Sharma, K.R. Aneja, Med. Chem. Res. 21, 2961–2968 (2012)CrossRefGoogle Scholar
  41. 41.
    S. Viveka, Dinesha, P. Shama, G.K. Nagaraja, S. Ballav, S. Kerkar, Eur. J. Med. Chem. 101, 442–451 (2015)Google Scholar
  42. 42.
    S. Viveka, G. Vasantha, Dinesha, S. Naveen, N.K. Lokanath, G.K. Nagaraja, Mol. Cryst. Liq. Cryst. (2015) (accepted)Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Shivapura Viveka
    • 1
  • Dinesha
    • 1
  • Prasanna Shama
    • 2
  • Gundibasappa Karikannar Nagaraja
    • 1
  • Nagaraju Deepa
    • 3
  • Marikunte Yanjarappa Sreenivasa
    • 3
  1. 1.Department of Studies in ChemistryMangalore UniversityMangaloreIndia
  2. 2.Department of PharmacologyN.G.S.M. Institute of Pharmaceutical SciencesMangaloreIndia
  3. 3.Department of MicrobiologyMysore UniversityMysoreIndia

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