Skip to main content
SpringerLink
Log in

A novel approach to the synthesis of 1,2,3-triazoles and their SAR studies

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A series of biologically active 4-acetyl-2-aryl-5-methyl-1-vinyl-2,3-dihydro-1H-1,2,3-triazole derivatives has been synthesized. The compounds were synthesized in excellent yields (80–85%) and the structures were established on the basis of corresponding IR, 1H NMR, and elemental analysis data. The purity has been ascertained on the basis of chromatographic resolution using acetic acid-toluene (4:6 v/v) as binary eluent. All the compounds (4a–l) have been tested for their antifungal activity against a representative panel of fungal microbes. These synthesized compounds exhibited significant activities against A. niger, C. albicans, C. azyma, and A. flavus. For all the tests conducted, voriconazole was used as the control drug. The hydrophobic parameter (log P) also has been quantized for correlation of structure with biological activity, and a critical evaluation of structure-activity relationship (SAR) has been performed.

Graphical Abstract

The paper delineates the novel synthesis of substituted highly significant triazoles. A large number of various substituted 1,2,3-triazole derivatives have been synthesized in a facile manner. Further, All the compounds have been tested for their antimicrobial activity against a representative panel of fungi with the aim to search for new chemical entities, which can be envisaged as the potent antifungal agents.

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

Similar content being viewed by others

References

  • Amantini D, Fringuelli F, Piermatti O, Pizzo F, Zunino E, Vaccaro L (2005) J Org Chem 70:6526–6529. doi:10.1021/jo0507845

    Article  CAS  PubMed  Google Scholar 

  • Angell Y, Burgess K (2005) Ring closure to β-turn mimics via copper-catalyzed azide/alkyne cycloadditions. J Org Chem 70:9595–9598. doi:10.1021/jo0516180

    Article  CAS  PubMed  Google Scholar 

  • Angelo NG, Arora PS (2005) Nonpeptidic foldamers from amino acids: synthesis and characterization of 1,3-substituted triazole oligomers. J Am Chem Soc 127:17134–17135. doi:10.1021/ja056406z

    Article  CAS  PubMed  Google Scholar 

  • Aucagne V, Leigh DA (2006) Chemoselective formation of successive triazole linkages in one pot: “click–click” chemistry. Org Lett 8:4505–4507. doi:10.1021/ol061657d

    Article  CAS  PubMed  Google Scholar 

  • Barluenga J, Valdés C, Beltrán G, Escribano M, Aznar F (2006) Developments in Pd catalysis: synthesis of 1H–1,2,3-triazoles from sodium azide and alkenyl bromides. Angew Chem Int Ed 45:6893–6896. doi:10.1002/anie.200601045

    Article  CAS  Google Scholar 

  • Barral K, Moorhouse AD, Moses JE (2007) Efficient conversion of aromatic amines into azides: a one-pot synthesis of triazole linkages. Org Lett 9:1809–1811. doi:10.1021/ol070527h

    Article  CAS  PubMed  Google Scholar 

  • Bock VD, Perciaccante R, Jansen TP, Hiemstra H, Maarseveen JH (2006) Click chemistry as a route to cyclic tetrapeptide analogues: synthesis of cyclo-[pro-val-ψ(triazole)-pro-tyr]. Org Lett 8:919–922. doi:10.1021/ol053095o

    Article  CAS  PubMed  Google Scholar 

  • Chuprakov S, Chernyak N, Dudnik AS, Gevorgyan V (2007) Direct Pd-catalyzed arylation of 1,2,3-triazoles. Org Lett 9:2333–2336. doi:10.1021/ol070697u

    Article  CAS  PubMed  Google Scholar 

  • Czollner L, Sxilagli G, Lango J, Janaky J (1990) Synthesis of new 1, 5-diphenyl-3–1H-1,2,4-triazoles substituted with H-, alkyl, or carboxyl groups at C-3. Arch Pharm 323:225–231. doi:10.1002/ardp.19903230409

    Article  CAS  Google Scholar 

  • Er-Rhaimini A, Mornet R (1992) Synthesis and photochemical degradation of N-arylmethyl derivatives of the herbicide 3-amino-1, 2, 4-triazole. J Heterocycl Chem 29:1561–1566. doi:10.1002/jhet.5570290632

    Article  CAS  Google Scholar 

  • Horne WS, Stout CD, Ghadiri MR (2003) A heterocyclic peptide nanotube. J Am Chem Soc 125:9372–9376. doi:10.1021/ja034358h

    Article  CAS  PubMed  Google Scholar 

  • Horne WS, Yadav MK, Stout CD, Ghadiri MR (2004) Heterocyclic peptide backbone modifications in an α-helical coiled coil. J Am Chem Soc 126:15366–15367. doi:10.1021/ja0450408

    Article  CAS  PubMed  Google Scholar 

  • Jain R, Pandey P (1987) 70. Polarographic investigation on some coupled products of aromatic amines with β-diketones. Bull Electrochem 3:177–180

    CAS  Google Scholar 

  • Kamijo S, Jin T, Huo Z, Yamamoto Y (2003) Synthesis of triazoles from nonactivated terminal alkynes via the three-component coupling reaction using a pd(0)–cu(i) bimetallic catalyst. J Am Chem Soc 125:7786–7787. doi:10.1021/ja034191s

    Article  CAS  PubMed  Google Scholar 

  • Kupchinsky S, Espinosa JE, Johnson K, Stradman B, Brooks N, Hartley JA, Lee M (1998) Design, synthesis and DNA binding properties of a series of 4,5-bis(substituted)-1,2,3-triazole derivatives of imidazole- and pyrrole-containing analogs of distamycin. Heterocycl Commun 4:415–422

    CAS  Google Scholar 

  • Lipshutz BH, Taft BR (2006) Heterogeneous copper-in-charcoal-catalyzed click chemistry. Angew Chem Int Ed 45:8235–8238. doi:10.1002/anie.200603726

    Article  CAS  Google Scholar 

  • Montagnat OD, Lessene G, Hughes AB (2006) Synthesis of azide-alkyne fragments for ‘click’ chemical applications; formation of oligomers from orthogonally protected trialkylsilyl-propargyl azides and propargyl alcohols. Tetrahedron Lett 47:6971–6974. doi:10.1016/j.tetlet.2006.07.131

    Article  CAS  Google Scholar 

  • Moreno-Manas M, Arredondo Y, Pleixats R, Teixido M, Haga MM, Palacin C, Castello JM, Oritiz JA (1992) New triazole antifungal agents derived from mercaptomethylisoxazoles. J Heterocycl Chem 29:1557–1560. doi:10.1002/jhet.5570290631

    Article  CAS  Google Scholar 

  • Orbai AS, Moneim MA (2001) Synthesis and physicochemical studies of some antimicrobial active triazole metal complexes. Pol J Chem 74:1675–1683

    Google Scholar 

  • Paul A, Bittermann H, Gmeiner P (2006) Triazolopeptides: chirospecific synthesis and cis/trans prolyl ratios of structural isomers. Tetrahedron 62:8919–8927. doi:10.1016/j.tet.2006.07.007

    Article  CAS  Google Scholar 

  • Punna S, Kuzelka J, Wang Q, Finn MG (2005) Head-to-tail peptide cyclodimerization by copper-catalyzed azide-alkyne cycloaddition. Angew Chem Int Ed 44:2215–2220. doi:10.1002/anie.200461656

    Article  CAS  Google Scholar 

  • Rodionov VO, Presolski SI, Gardinier S, Lim YH, Finn MG (2007) Benzimidazole and related ligands for Cu-catalyzed azide–alkyne cycloaddition. J Am Chem Soc 129:12696–12704. doi:10.1021/ja072678l

    Article  CAS  PubMed  Google Scholar 

  • Roice M, Johannsen I, Meldal M (2004) High capacity poly(ethylene glycol) based amino polymers for peptide and organic synthesis. QSAR Comb Sci 23:662–673. doi:10.1002/qsar.200420021

    Article  CAS  Google Scholar 

  • Sharma P, Kumar A, Sharma S, Rane N (2005) Studies on synthesis and evaluation of quantitative structure–activity relationship of 5-[(3′-chloro-4′,4′-disubstituted-2-oxoazetidinyl)(N-nitro)amino]-6-hydroxy-3-alkyl/aryl[1,3]azaphospholo[1,5-a]pyridin-1-yl-phosphorus dichlorides. Bioorg Med Chem Lett 15:937–943. doi:10.1016/j.bmcl.2004.12.050

    Article  CAS  PubMed  Google Scholar 

  • Sharma P, Kumar A, Gurram V, Rane N (2006a) Studies on synthesis and evaluation of quantitative structure–activity relationship of 10-methyl-6-oxo-5-arylazo-6,7-dihydro-5H-[1,3]azaphospholo[1,5-d][1,4]benzodiazepin-2-phospha-3-ethoxycarbonyl-1-phosphorus dichlorides. Bioorg Med Chem Lett 16:2484–2491. doi:10.1016/j.bmcl.2006.01.080

    Article  PubMed  Google Scholar 

  • Sharma P, Kumar A, Sharma M (2006b) Synthesis and QSAR studies on 5-[2-(2-methylprop1-enyl)-1H benzimidazol-1yl]-4,6-diphenyl-pyrimidin-2-(5H)-thione derivatives as antibacterial agents. Eur J Med Chem 41:833–840. doi:10.1016/j.ejmech.2006.03.022

    Article  CAS  PubMed  Google Scholar 

  • Sharma P, Rane N, Pandey P (2006c) Synthesis and evaluation of antimicrobial activity of novel hydrazino and N-benzylidinehydrazino- substituted 4, 8-dihydro-1H, 3H-pyrimido[4, 5-d]pyrimidin-2,7-dithiones. Archiv der pharma 339:572–578

    Article  CAS  Google Scholar 

  • Silvester MJ (1994) Recent advances in fluoroheterocyclic chemistry. Adv Heterocycl Chem 59:1–38. doi:10.1016/S0065-2725(08)60006-9

    Article  CAS  Google Scholar 

  • Skagerbeg B, Bonelli D, Clementi S, Cruciani G, Ebert C (1989) Principal properties for aromatic substituents. A multivariate approach for design in QSAR. Quant Struct-Act Relat 8:32–38. doi:10.1002/qsar.19890080105

    Article  Google Scholar 

  • Stewart JJP (1989) Optimization of parameters for semiempirical methods I. Method. J Comput Chem 10:209–220. doi:10.1002/jcc.540100208

    Article  CAS  Google Scholar 

  • Stewart JP (1990) MOPAC 6.0. QCPE 455, Indiana University, Bloomington (IN 47405)

  • Van Maarseveen JH, Horne WS, Ghadiri MR (2005) Efficient route to C2 symmetric heterocyclic backbone modified cyclic peptides. Org Lett 7:4503–4506. doi:10.1021/ol0518028

    Article  PubMed  Google Scholar 

  • Whiting M, Muldoon J, Lin YC, Silverman SM, Lindstom W, Olson AJ, Kolb HC, Finn MG, Sharpless KB, Elder JH, Fokin VV (2006) Inhibitors of HIV-1 protease by using in situ click chemistry. Angew Chem In Ed 45:1435–1439

    Article  CAS  Google Scholar 

  • Zhang Z, Fan E (2006) Solid phase synthesis of peptidotriazoles with multiple cycles of triazole formation. Tetrahedron Lett 47:665–669. doi:10.1016/j.tetlet.2005.11.111

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Central Drug Research Institute, Lucknow, India, for providing spectroanalytical facilities and to the Council of Scientific and Industrial Research (CSIR), New Delhi, for providing research fellowship to one of the authors (VS).

Author information

Authors and Affiliations

  1. School of Chemical Sciences, Devi Ahilya University, Takshashila Campus, Indore, MP, 452 001, India

    Pratibha Sharma, Ashok Kumar, Siya Upadhyay, Jitendra Singh & Vinita Sahu

Authors
  1. Pratibha Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashok Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siya Upadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jitendra Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vinita Sahu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pratibha Sharma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, P., Kumar, A., Upadhyay, S. et al. A novel approach to the synthesis of 1,2,3-triazoles and their SAR studies. Med Chem Res 19, 589–602 (2010). https://doi.org/10.1007/s00044-009-9215-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-009-9215-7

Keywords

Search

Navigation