Skip to main content

Advertisement

SpringerLink
Log in

Pyrimidino piperazinyl acetamides: innovative class of hybrid acetamide drugs as potent antimicrobial and antimycobacterial agents

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

A series of new 2-(4-methylpiperazin-1-yl)-N-(4,6-diarylpyrimidin-2-yl)acetamides (34 – 42) have been synthesized and tested for their in vitro antimicrobial and antimycobacterial properties. Compounds 34, 39 against S. aureus, 39 against β-H. Streptococcus, 42 against V. cholerae, 40 – 42 against E. coli, 38, 39 against K. pneumonia, and 37 – 41 against P. aeruginosa showed excellent antibacterial activity by inhibiting the growth of the respective organisms at a minimum inhibitory concentration of 6.25 μg/mL. Noteworthy compounds 40 against A. flavus, 34 against M. indicus, 40, 42 against R. arrhizus and M. gypseum also exhibited excellent antifungal activity by inhibiting the growth of these microorganisms, at a minimum inhibitory concentration of 6.25 μg/mL. Moreover, compounds 36, 38, and 40 – 42 showed promising antitubercular activity by inhibiting the growth of M. tuberculosis H 37 Rv and clinically isolated isoniazid-resistant M. tuberculosis strains.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1

Similar content being viewed by others

References

  1. K. Coleman, Recent Advances in the Treatment of Gram-Positive Infections, Drug Discov. Today Ther. Strateg., No. 1, 455 – 460 (2004).

  2. A. P. Johnson, D. M. Livermore, and G. S. Tillotson, J. Hosp. Infect., 49, S3 – S11 (2001).

    Article  PubMed  Google Scholar 

  3. S. Emami, A. Shafiee, and F. Foroumadi, Mini Rev. Med. Chem., 6, 375 – 386 (2006).

    Article  PubMed  CAS  Google Scholar 

  4. G. W. Kenner and A. Todd, Heterocyclic Compounds, R. C. Elderfield (Ed.), Wiley, New York (1957), p. 6.

    Google Scholar 

  5. D. J. Brown, The Chemistry of Heterocyclic Compounds, A. Weissberger (Ed.), Interscience, New York (1962), p. 16.

    Chapter  Google Scholar 

  6. J. P. D. van Veldhoven, L. C. W. Chang, J. K. von Frijtag, et al., Bioorg. Med. Chem., 16, 2741 – 2752 (2008).

    Article  PubMed  Google Scholar 

  7. T. V. Hughes, S. L. Emanuel, A. K. Beck, et al., Bioorg. Med. Chem. Lett., 17, 3266 – 3270 (2007).

    Article  PubMed  CAS  Google Scholar 

  8. M. T. Chhabria, H. G. Bhatt, H. G. Raval, and P. M. Oza, Bioorg. Med. Chem. Lett., 17, 1022 – 1024 (2007).

    Article  PubMed  CAS  Google Scholar 

  9. K. L. Sayle, J. F. Bentley, T. Boyle, et al., Bioorg. Med. Chem. Lett., 13, 3079 – 3082 (2003).

    Article  PubMed  CAS  Google Scholar 

  10. A. Pastor, R. Alajarin, J. J. Vaquero, et al., Tetrahedron, 50, 8085 – 8098 (1994).

    Article  CAS  Google Scholar 

  11. M. S. Youssouf, P Kaiser, G. D. Singh, et al., Int. Immunopharmacol., 8, 1049 – 1055 (2008).

    Article  PubMed  CAS  Google Scholar 

  12. C. Gasse, D. Douguet, V. Huteau, G. Marchal, H. Munier-Lehmann, and S. Pochet, Bioorg. Med. Chem., 16, 6075 – 6085 (2008).

    Article  PubMed  CAS  Google Scholar 

  13. G. Y. Domany, G. Barta-Szalai, E. Palori,, S. Szabo, I. Schoen, New 4-Arylaminopiperidines with Antihypoxic and Anticonvulsive Activity, Arzneimittelforschung, 44, 989 – 991 (1994); Chem. Abstr., 122, 17834f (1994).

    Google Scholar 

  14. K. E. Hamlin, A. W. Weston, F. E. Fischer, and R. J. Michaels, J. Am. Chem. Soc., 71, 2731 – 2734 (1949).

    Article  CAS  Google Scholar 

  15. M. Tugnait, E. M. Hawes, G. Mackay, et al., Drug. Metab. Dispos., 25, 524 – 527 (1997).

    PubMed  CAS  Google Scholar 

  16. H. Altintas, O. Ates, A. Kocabalkanli, et al., Indian J. Chem., 44B, 585 – 590 (2005).

    CAS  Google Scholar 

  17. J. Jianjing, S. S. Kulkarni, S. M. Husbands, et al., J. Med. Chem., 46, 2589 – 2598 (2003).

    Article  Google Scholar 

  18. J. C. Agarwal, C. Nath, M. Sharma, et al., Arch. Pharm., 316, 690 – 694 (1983).

    Article  CAS  Google Scholar 

  19. A. M. Creighton, K. Hellmann, and S. Whitecross, Nature, 222, 384 – 385 (1969).

    Article  PubMed  CAS  Google Scholar 

  20. S. Akhondzadeh, M. M Hosseini, A. Ghoreishi, et al., Progr. Neuro-Psychopharmacol. Biol. Psychiatry, 32, 1879 – 1883 (2008).

    Article  CAS  Google Scholar 

  21. K. Nagaiah, A. S. Rao, S. J. Kulkarni, et al., J. Catal., 147, 349 – 351 (1994).

    Article  CAS  Google Scholar 

  22. J. C. Pecknold, P. Familamiri, H. Chang, et al., Progr. Neuro-Psychopharmacol. Biol. Psychiatry, 9, 639 – 642 (1985).

    Article  CAS  Google Scholar 

  23. H. Lal, P. L. Prather, and S. M. Rezazadeh, Alcohol, 8, 467 – 471 (1991).

    Article  PubMed  CAS  Google Scholar 

  24. V. Kumar, A. K. Abbas, N. Fausto, and R. Mitchell, Robbins’ Basic Pathology, 8th Ed., Elsevier, Saunders (2007), pp. 516 – 522.

    Google Scholar 

  25. K. J. Ryan and C. G. Ray, in Sherris’ Medical Microbiology, 4th Ed., McGraw Hill, 2004.

  26. M. Pereira, S. Tripathy, V. Inamdar, et al., Indian J. Med. Res., 121, 235 – 239 (2005).

    PubMed  CAS  Google Scholar 

  27. K. Takayama, C. Wang, and G. S. Besra, Clin. Microbiol. Rev., 18, 81 – 101 (2005).

    Article  PubMed  CAS  Google Scholar 

  28. C. E. Barry, R. E. Lee, K. Mdluli, et al., Progr. Lipid Res., 37, 143 – 179 (1998).

    Article  CAS  Google Scholar 

  29. M. Zhang, J. Yue, Y. P. Yang, et al, J. Clin. Microbiol., 43, 5477 – 5482 (2005).

    Article  PubMed  CAS  Google Scholar 

  30. M. V. N. De Souza, Mini-Rev. Med. Chem., 5, 1009 – 1017 (2005).

    Article  PubMed  Google Scholar 

  31. V. Kanagarajan, J. Thanusu, and M. Gopalakrishnan, Eur. J. Med. Chem., 45, 1583 – 1589 (2010).

    Article  PubMed  CAS  Google Scholar 

  32. V. Kanagarajan and M. Gopalakrishnan, Eur. Rev. Med. Pharm. Sci., 14, 513 – 520 (2010).

    CAS  Google Scholar 

  33. J. Thanusu, V. Kanagarajan, and M. Gopalakrishnan, Bioorg. Med. Chem. Lett., 20, 713 – 717 (2010).

    Article  PubMed  CAS  Google Scholar 

  34. J. Thanusu, V. Kanagarajan, and M. Gopalakrishnan, J. Enzyme Inhib. Med. Chem., 25, 756 – 764 (2010).

    CAS  Google Scholar 

  35. J. Thanusu, V. Kanagarajan, S. Nagini, and M. Gopalakrishnan, J. Enzyme Inhib. Med. Chem., 25, 836 – 843 (2010).

    CAS  Google Scholar 

  36. M. Gopalakrishnan, J. Thanusu, V. Kanagarajan, and R. Govindaraju, Med. Chem. Res., 18, 341 – 350 (2009).

    Article  CAS  Google Scholar 

  37. Bioorganic and Medicinal Chemistry of Fluorine, J. P. Begue and D. Bonnet-Delpon (Eds.), John Wiley & Sons, Hoboken, NJ (2008).

  38. C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, Drug Deliv. Rev., 23, 3 – 25 (1997).

    Article  CAS  Google Scholar 

  39. S. Purser, P. R. Moore, S. Swallow, and V. Gouverneur, Chem. Soc. Rev., 37, 320 – 330 (2008).

    Article  PubMed  CAS  Google Scholar 

  40. W. Guthrie and X. P. Wang, Can. J. Chem., 69, 339 – 340 (1991).

    Article  CAS  Google Scholar 

  41. B. G. Metchock, F. S. Nolte, and R. J. Wallace Jr., Mycobacterium, in: P. R. Murray, E. J. Baron, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (Eds.), Manual of Clinical Microbiology, 7th ed., ASM Press, Washington, DC (1999), pp. 399 – 437.

    Google Scholar 

  42. M. H. Dhar, M. M. Dhar, B. N. Dhawan, et al., Indian J. Exp. Biol., 6, 232 – 247 (1968).

    PubMed  CAS  Google Scholar 

  43. P. M. Sivakumar, S. Prabu Seenivasan, V. Kumar, and M. Doble, Bioorg. Med. Chem. Lett., 17, 1695 – 1700 (2007).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors are thankful to NMR Research Centre (Indian Institute of Science, Bangalore) for recording spectra. One of the authors (V. K.) is grateful to Energetics Research Institute (Nanyang Technological University, Singapore, Republic of Singapore) for the award of Postdoctoral Research Fellowship and Council of Scientific and Industrial Research (CSIR, New Delhi, Republic of India) for providing financial support in the form of CSIR-Senior Research Fellowship (SRF) in Organic Chemistry.

Author information

Authors and Affiliations

  1. Energetics Research Institute, Nanyang Technological University, Singapore, 639798, Republic of Singapore

    V. Kanagarajan

  2. Synthetic Organic Chemistry Laboratory, Department of Chemistry, Annamalai University, Annamalainagar, Tamil Nadu, 608002, India

    V. Kanagarajan & M. Gopalakrishnan

Authors
  1. V. Kanagarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Gopalakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Gopalakrishnan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanagarajan, V., Gopalakrishnan, M. Pyrimidino piperazinyl acetamides: innovative class of hybrid acetamide drugs as potent antimicrobial and antimycobacterial agents. Pharm Chem J 46, 26–34 (2012). https://doi.org/10.1007/s11094-012-0729-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-012-0729-9

Keywords

Search

Navigation