Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2260–2271 | Cite as

Pharmacological screening of some newly synthesized triazoles for H1 receptor antagonist activity

Original Research


The present work deals with the pharmacological screening of some newly synthesized triazoles. A series of 1,2,4-triazoles have been synthesized using benzoic acid or 4-chloro benzoic acid as the starting materials. The synthesized compounds were characterized by physical and spectral analysis viz., Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, Gas Chromatography-Mass Spectrometry and elemental analysis Carbon, Hydrogen and Nitrogen analysis in order to confirm the structure. Acute toxicity studies were carried out in accordance with the Organization for Economic Co-operation and Development guideline 425. The compounds were not found to be lethal even at a dose level of 2000 mg/kg. Pharmacological evaluation was done following three intact animal experiments and one experiment on the isolated tissue. Results of the study indicated that the compound 7bi and 7bj protected up to 60% against histamine-induced dyspnea. Antihistaminic nature of the test compounds 7bi, 7bj, 7ai, and 7bk were also confirmed by the loss of catalepsy after the administration of clonidine (1%, s.c.). During experiments on isolated tissue, suppression of dose-response curve of histamine indicates a noteworthy denouement in favor of the said effect.


Triazoles Amines Antihistaminic H1 antagonist 



The authors are thankful to the GLA University administration for providing research facilities for the present work. The authors wish to thank SAIF-CIL Panjab University, Chandigarh for spectral studies.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1928_MOESM1_ESM.docx (2.4 mb)
Supplementary Information


  1. Al-Masoudi IA, Al-Soud YA, Al-Salihi NJ, Al-Masoudi NA (2006) 1,2,4-Triazoles: synthetic approaches and pharmacological importance. Chem Heterocycl Compd 42:1377–1403CrossRefGoogle Scholar
  2. Alagarsamy V, Giridhar R, Yadav MR (2006) Synthesis and pharmacological investigation of novel 1-substituted-4-(4-substituted phenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as a new class of H1-antihistamine agents. J Pharm Pharmacol 58:1249–1255CrossRefPubMedGoogle Scholar
  3. Asif M (2014) A mini review on antimalarial activities of biologically active substituted triazoles derivatives. Int J Adv Res Chem Sci 1:22–28Google Scholar
  4. Bekircan O, Kahveci B, Kucuk M (2006) Synthesis and anticancer evaluation of some new unsymmetrical 3,5-diaryl-4H-1,2,4-triazole derivatives. Turk J Chem 30:29–40Google Scholar
  5. Bhat AR, Bhat GV, Shenoy GG (2001) Synthesis and in-vitro antimicrobial activity of new 1,2,4-triazoles. J Pharm Pharmacol 53:267–272CrossRefPubMedGoogle Scholar
  6. Blank B, Nichols DM, Vaidya PD (1972) Synthesis of 1,2,4-triazoles as potential hypoglycemic agents. J Med Chem 15:694–696CrossRefPubMedGoogle Scholar
  7. Cansiz A, Koparir M, Demirdag A (2004) Synthesis of some new 4,5-substituted-4H-1,2,4-triazole-3-thiol derivatives. Molecules 9:204–212CrossRefPubMedGoogle Scholar
  8. Cetin A, Gecibesler IH (2015) Evaluation as antioxidant agents of 1,2,4-triazole derivatives: effects of essential functional groups. J Appl Pharm Sci 5:120–126CrossRefGoogle Scholar
  9. Chernyshev VM, Chernysheva AV, Taranushich VA (2006) Synthesis of esters and amides of 5-amino-1,2,4-triazole-3-carboxylic and 5-amino-1,2,4-triazol-3-ylacetic acids. Russ J Appl Chem 79:783–786CrossRefGoogle Scholar
  10. DeRuiter J (2001) Histamine H1-receptor antagonists: antihistaminic agents. Princ Drug Action 2:1–20Google Scholar
  11. Donoso AO, Broitman ST (1979) Effects of a histamine synthesis inhibitor and antihistamines on the sexual behavior of female rats. Psychopharmacology 66:251–255CrossRefPubMedGoogle Scholar
  12. Ghochikyan TV, Samvelyan MA, Galstyan AS, Grigoryan SV (2016) Synthesis of some s-derivatives of 1,2,4-triazoles. Chem Biol 2:8–12Google Scholar
  13. Godhani DR, Jogel AA, Sanghani AM, Mehta JP (2015) Synthesis and biological screening of 1,2,4-triazole derivatives. Indian J Chem 54B:556–564Google Scholar
  14. Gupta D, Jain DK (2015) Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives. J Adv Pharm Technol Res 6:141–146CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hou YP, Sun J, Pang ZH, Lv PC, Li DD, Yan L, Zhang HJ, Zheng EX, Zhao J, Zhu HL (2011) Synthesis and antitumor activity of 1,2,4-triazoles having 1,4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors. Bioorg Med Chem 19:5948–5954CrossRefPubMedGoogle Scholar
  16. Hussain S, Sharma J, Amir M (2008) Synthesis and antimicrobial activities of 1,2,4-triazole and 1,3,4,-thiadiazole derivatives of 5-amino-2-hydroxybenzoic acid. E-J Chem 5:963–968CrossRefGoogle Scholar
  17. Jadhav S, Rai M, Durrani A, Bembalkar SR (2010) Synthesis and characterization of substituted 1,2,4-triazole and its derivatives. Asian J Chem 26:725–728Google Scholar
  18. Kamboj VK, Verma PK, Dhanda A, Ranjan S (2015) 1,2,4-Triazole derivatives as potential scaffold for anticonvulsant activity. Cent Nerv Syst Agents Med Chem 15:17–22CrossRefPubMedGoogle Scholar
  19. Kane JM, Dudley MW, Sorensen SM, Miller FP (1988) 2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents. J Med Chem 31:1253–1258CrossRefPubMedGoogle Scholar
  20. Kochikyan TV, Samvelyan MA, Arutyunyan VS, Avetisyan AA, Tamazyan RA, Aivazyan AG (2010) Synthesis of 1,2,4-triazole-3-thiols and their S-substituted derivatives. Russ J Org Chem 46:551–555CrossRefGoogle Scholar
  21. Li X, Li XQ, Liu HM, Zhou XZ, Shao ZH (2012) Synthesis and evaluation of antitumor activities of novel chiral 1,2,4-triazole schiff bases bearing γ-butenolide moiety. Org Med Chem Lett 2:26CrossRefPubMedPubMedCentralGoogle Scholar
  22. Lin Y, Wang Y, Sima LF, Wang DH, Chen LG, Li L (2012) Design, synthesis and antihistamine evaluations of several N-hydroxyalkyl desloratadine analogues. Med Chem 8:1126–1132PubMedGoogle Scholar
  23. Mange YJ, Isloor AM, Malladi S, Isloor S, Fun HK (2013) Synthesis and antimicrobial activities of some novel 1,2,4-triazole derivatives. Arab J Chem 6:177–181CrossRefGoogle Scholar
  24. Martins P, Jesus J, Santos S, Raposo LR, Rodrigues CR, Baptista PV, Fernandes AR (2015) Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine’s tool box. Molecules 20:16852–16891CrossRefPubMedGoogle Scholar
  25. Ozdemir A, Turan-Zitouni G, Kaplancikli ZA, Chevallet P (2007) Synthesis of some 4-arylidenamino-4H-1,2,4-triazole-3-thiols and their antituberculosis activity. J Enzyme Inhib Med Chem 22:511–516CrossRefPubMedGoogle Scholar
  26. Patil BS, Krishnamurthy G, Lokesh MR, Shashikumar ND, Bhojyanaik HS, Latthe PR, Ghate M (2013) Synthesis of some novel 1,2,4-triazole and 1,3,4-oxadiazole derivatives of biological interest. Med Chem Res 22:3341–3349CrossRefGoogle Scholar
  27. Pattan S, Gadhave P, Tambe V, Dengale S, Thakur D, Hiremath SV, Shete RV, Deotarse P (2012) Synthesis and evaluation of some novel 1,2,4-triazole derivatives for antimicrobial, antitubercular and anti-inflammatory activities. Indian J Chem 51B:297–301Google Scholar
  28. Romagnoli R, Baraldi PG, Lopez OC, Cara CL, Carrion MD, Brancale A, Hamel E, Chen L, Bortolozzi R, Basso G, Viola G (2010) Synthesis and antitumor activity of 1,5-disubstituted 1,2,4-triazoles as cis-restricted combretastatin analogues. J Med Chem 53:4248–4258CrossRefPubMedPubMedCentralGoogle Scholar
  29. Sadek B, Alisch R, Buschauer A, Elz S (2013) Synthesis and dual histamine H1 and H2 receptor antagonist activity of cyanoguanidine derivatives. Molecules 18:14186–14202CrossRefPubMedGoogle Scholar
  30. Saini MS, Kumar A, Dwivedi J, Singh R (2013) A review: biological significances of heterocyclic compounds. Int J Pharma Sci Res 4:66–77CrossRefGoogle Scholar
  31. Shaker RM (2006) The chemistry of mercapto- and thione- substituted 1,2,4-triazoles and their utility in heterocyclic synthesis. Arkivoc 9:59–112Google Scholar
  32. Taur DJ, Patil RY (2011) Antihistaminic activity of Abrus precatorius using clonidine induced catalepsy in mice. Orient Pharm Exp Med 12:11–14CrossRefGoogle Scholar
  33. Upmanyu N, Gupta JK, Shah K, Mishra P (2011a) Synthesis of new 1,2,4-triazoles as anti-inflammatory and anti-nociceptive agents. Pharm Chem J 45:433–439CrossRefGoogle Scholar
  34. Upmanyu N, Gupta JK, Shah K, Mishra P (2011b) Anti-inflammatory and antinociceptive evaluation of newly synthesized 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles. J Pharm Bioallied Sci 3:259–265CrossRefPubMedPubMedCentralGoogle Scholar
  35. Upmanyu N, Kumar S, Kharya MD, Shah K, Mishra P (2011c) Synthesis and anti-microbial evaluation of some novel 1,2,4-triazole derivatives. Acta Pol Pharm – Drug Res 68:213–221Google Scholar
  36. Upmanyu N, Kumar S, Porwal P, Shah K, Mishra P (2012) Synthesis and evaluation of 4-(substituted)-acetylamino-3-mercapto-5-(4-substituted) phenyl-1,2,4-triazole derivatives as antimicrobial agents. Med Chem Res 21:1967–1976CrossRefGoogle Scholar
  37. Uygun Y, Bayrak H, Ozkan H (2013) Synthesis and biological activities of methylenebis-4H-1,2,4-triazole derivatives. Turk J Chem 37:812–823CrossRefGoogle Scholar
  38. Viswanatha GL, Priyadarshini BJ, Krishnadas N, Janardhanan S, Rangappa S, Hanumanthappa S (2012) Synthesis and antihistaminic activity of 3H-benzo [4,5] thieno [2,3-d][1,2,3] triazin-4-ones. Saudi Pharm J 20:45–52CrossRefPubMedGoogle Scholar
  39. Zamani K, Faghihi K (2003) Synthesis of some new substituted 1,2,4-triazole and 1,3,4-thiadiazole and their derivatives. Turk J Chem 27:119–125Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Institute of Pharmaceutical ResearchGLA UniversityMathuraIndia

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