Skip to main content

Advertisement

SpringerLink
Log in

Synthesis, antihistaminic action and theoretical studies of (4-methoxybenzyl)(1,4,5,6-tetrahydropirimidin-2-yl)amine hydroiodide

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

In this study, (4-methoxybenzyl)(1,4,5,6-tetrahydropyrimidin-2-yl)amine hydroiodide (2) was synthesized by reaction of 2-methylmercapto-1,4,5,6-tetrahydropyrimidine hydroiodide (1) and 4-methoxybenzylamine. The synthesized compound was tested for its in vitro H1-antihistaminic activity on guinea pig trachea. A promising bronchorelaxant effect of 2 was observed in histamine-contracted guinea pig tracheal chain via H1 receptor antagonism. In addition, the molecular geometry and gauge including atomic orbital (GIAO) 1H chemical shift values of the title compound in the ground state were calculated using the density functional method (DFT/UB3LYP) and Hartree–Fock (HF) approach using 6–311G+(d), 6–311G+(d,p), LANL2DZ, DGDZVP, and DGDZVP2 basis sets and compared with the experimental data. According to the experimental and theoretical results, HF/6–311G+(d) showed a better fit to experimental values in evaluating 1H-nuclear magnetic resonance (NMR) chemical shift values. Theoretical studies supported our findings, revealing the N12 atom as the most nucleophilic. In addition, other structures of the compound such as the aromatic ring and OCH3 group increased this property.

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
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. K.S. Atwal, S. Moreland, Bioorg. Med. Chem. Lett. I, 291 (1991)

    Article  Google Scholar 

  2. W.M. Moore, R.K. Webber, K.F. Fok, G.M. Jerome, J.R. Connor, P.T. Manning, P.S. Wyatt, T.P. Misko, F.S. Tjoeng, M.G. Currie, J. Med. Chem. 39, 669 (1996)

    Article  CAS  Google Scholar 

  3. S.M. Sondhi, N. Singh, M. Johar, A. Kumar, Bioorg. Med. Chem. 13, 158 (2005)

    Google Scholar 

  4. M. Ishikawa, D. Kubota, M. Yamamoto, C. Kuroda, M. Iguchi, A. Koyanagi, S. Murakami, K. Ajito, Bioorg. Med. Chem. 14, 2109 (2006)

    Article  CAS  Google Scholar 

  5. D. Kubota, M. Ishikawa, M. Ishikawa, N. Yahata, S. Murakami, K. Fujishima, M. Kitakaze, K. Ajito, Bioorg. Med. Chem. 14, 2089–2108 (2006)

    Article  CAS  Google Scholar 

  6. Y. Shao, Y. Ding, Z. Li Jia, X. Lu, Z. Ke, W. Xu, G. Lu, Bioorg. Med. Chem. 17, 4274 (2009)

    Article  CAS  Google Scholar 

  7. V.B. Kadu, A.G. Doshi, Res. J. Chem. Environ. 2, 69 (1998)

    CAS  Google Scholar 

  8. I.W. Althaus, K.C. Chou, R.J. Lemay, K.M. Fraks, M.R. Diebel, F.Z. Kezdy, L. Resnick, M.E. Buss, K.M. Downey, D.L. Romero, R.L. Thomas, P.A. Aristoff, W.G. Tarpley, Biochem. Pharmacol. 51, 743 (1996)

    Article  CAS  Google Scholar 

  9. A. Hirabayashi, H. Mukaiyama, H. Kobayashi, H. Shiohara, S. Nakayama, M. Ozawa, E. Tsuji, K. Miyazawa, K. Misawa, H. Ohnota, M. Isaji, Bioorg. Med. Chem. 16, 9247 (2008)

    Article  CAS  Google Scholar 

  10. D.T. Connor, D.T. Sorenson, W.A. Cetenko, J.J. Kerbleski, F. Tinney, J. Med. Chem. 27, 528 (1984)

    Article  CAS  Google Scholar 

  11. K. Gyires, S. Furst, I. Miklya, I. Budavari, J. Knoll, Drugs Exp. Clin. Res. 11, 493 (1985)

    CAS  Google Scholar 

  12. S.C. Kuo, S.Y. Tsai, H.T. Li, C.H. Wu, K. Ishii, H. Nakamura, Chem. Pharm. Bull. 36, 4403 (1988)

    Article  CAS  Google Scholar 

  13. G. Roma, M. Di Braccio, G. Leoncini, B. Aprile, Farmaco 48, 1225 (1993)

    CAS  Google Scholar 

  14. G. Wagner, Prantz J. Pharmazie 48, 250 (1993)

    CAS  Google Scholar 

  15. G. Hou, D. Gravier, F. Casadebaig, J.P. Dupin, H. Bernard, M. Biosseau, Pharmazie 50, 719 (1995)

    CAS  Google Scholar 

  16. G. Leoncini, G. Signorello, G. Roma, M. Di Braccio, Biochem. Pharmacol. 53, 1667 (1997)

    Article  CAS  Google Scholar 

  17. E.A. Kowaluk, J. Mikusa, C.T. Wismer, C.Z. Zhu, E. Schweitzer, J.L. Lynch, J. Pharmacol. Exp. Ther. 295, 1165 (2000)

    CAS  Google Scholar 

  18. Y. Hamasaki, M. Zaitu, K. Tsuji, M. Miyazaki, R. Hayasaki, E. Muro, Int. J. Immunopharmacol. 22, 483 (2000)

    Article  CAS  Google Scholar 

  19. P. Molina, E. Aller, A. Lorenzo, P. Lopez-Cremades, I. Rioja, A. Ubeda et al., J. Med. Chem. 44, 1011 (2001)

    Article  CAS  Google Scholar 

  20. B.N. Suhagia, M.T. Chhabria, A.G. Makwana, J. Enzyme Inhib. Med. Chem. 21, 681 (2006)

    Article  CAS  Google Scholar 

  21. F.E. Simons, K.J. Simons, N. Engl. J. Med. 330, 1663 (1994)

    Article  CAS  Google Scholar 

  22. K.J. Simons, M.S. Benedetti, F.E.R. Simons, M. Gillard, E. Baltes, J. Allergy Clin. Immunol. 119, 1551 (2007)

    Article  CAS  Google Scholar 

  23. A.A. Carr, D.R. Meyer, Arzneimittelforschung 32, 1157 (1982)

    CAS  Google Scholar 

  24. R.J. Hopp, A. Bewtra, N.M. Nair, R.G. Townley, J. Allergy Clin. Immunol. 76, 609 (1985)

    Article  CAS  Google Scholar 

  25. N. Chairungsrilerd, K. Furukawa, T. Ohta, S. Nozoe, Y. Ohizumi, Eur. J. Pharmacol. 314, 351 (1996)

    Article  CAS  Google Scholar 

  26. C. Jamorski, M.E. Casida, D.R. Salahub, J. Phys. Chem. 104, 5134 (1996)

    Article  CAS  Google Scholar 

  27. R. Bauerschmitt, R. Alrichs, Chem. Phys. Lett. 256, 454 (1996)

    Article  Google Scholar 

  28. R. Bauerschmitt, M. Häser, O. Treutler, R. Alrichs, Chem. Phys. Lett. 264, 573 (1997)

    Article  Google Scholar 

  29. N. Tokay, Z. Seferoğlu, C. Öğretir, N. Ertan, Arkivoc 15, 9 (2008)

    Article  Google Scholar 

  30. A. Zarrouk, B. Hammouti, H. Zarrok, R. Salghi, M. Bouachrine, F. Bentiss,S.S. Al-Deyab, Res. Chem. Intermed. (2012). doi:10.1007/s11164-012-0548-3

  31. F. Della Sala, A. Georling, J. Chem. Phys. 115, 5718 (2001)

    Article  CAS  Google Scholar 

  32. W. Hieringer et al., Chem. Phys. Lett. 383, 115–121 (2004)

    Article  CAS  Google Scholar 

  33. G. Rauhut, S. Puyear, K. Wolinski, P. Pulay, J. Phys. Chem. 100, 6310 (1996)

    Article  CAS  Google Scholar 

  34. K. Sztanke, K. Pasternak, A. Sidor-Wojtowicz, J. Truchlinska, K. Jozwiak Bioorg, Med. Chem. 14, 3635 (2006)

    Article  CAS  Google Scholar 

  35. J. Chang-Fong, K. Benamour, B. Szymoski, F. Thamasson, J. Morand, M. Cussac, Chem. Pharm. Bull. 48, 729 (2000)

    Article  CAS  Google Scholar 

  36. M.S. Youssouf, P. Kaiser, G.D. Singh, S. Singh, S. Bani, V.K. Gupta, N.K. Satti, K.A. Suri, R.K. Johri, Int. Immunopharmacol. 8, 1049 (2008)

    Article  CAS  Google Scholar 

  37. M.S. Ashenager, T. Grgela, Y. Aragane, A. Kawada, J. Investig. Allergol. Clin. Immunol. 17, 20 (2007)

    CAS  Google Scholar 

  38. S.T. Holgate, Clin. Exp. Allergy 29, 80 (1999)

    Google Scholar 

  39. B. Zweiman, M.E. Rothenberg, J. Allergy Clin. Immunol. 113, 1009 (2004)

    Google Scholar 

Download references

Acknowledgments

We are indebted to the Adiyaman University Research Foundation (FEFBAP2010/004) for financial support of this work. The authors would like to thank Assist. Prof. Dr. Halil Berber from Anadolu University, Faculty of Science, Department of Chemistry for providing Gaussian 09W software (Gaussian 09, rev. B.01, version EM64T/Linux).

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science and Arts, Adiyaman University, 02040, Adiyaman, Turkey

    Murat Genc

  2. Department of Chemistry, Faculty of Science and Art, University of Bitlis Eren, 13800, Bitlis, Turkey

    Engin Yılmaz

  3. Department of Pharmacology, Faculty of Medicine, University of Firat, 23119, Elazig, Turkey

    Selcuk Ilhan

  4. Department of Chemistry, Faculty of Science, University of Firat, 23119, Elazig, Turkey

    Zuhal Karagoz

Authors
  1. Murat Genc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Engin Yılmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Selcuk Ilhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zuhal Karagoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Murat Genc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Genc, M., Yılmaz, E., Ilhan, S. et al. Synthesis, antihistaminic action and theoretical studies of (4-methoxybenzyl)(1,4,5,6-tetrahydropirimidin-2-yl)amine hydroiodide. Res Chem Intermed 39, 3011–3021 (2013). https://doi.org/10.1007/s11164-012-0813-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-012-0813-5

Keywords

Search

Navigation