Skip to main content
SpringerLink
Log in

Synthesis and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing an aminosulphonyl pharmacophore

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

A novel series of 2-pyrazoline derivatives 13a–l was synthesized via aldol condensation of 4-substituted acetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-hydrazinobenzenesulfonamide hydrochloride. The chemical structures of the target pyrazoline derivatives were proved by means of IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses data. All the synthesized compounds were evaluated for their cyclooxygenase selectivity, anti-inflammatory and ulcerogenic liability. While compounds 13e, 13h and 13i showed moderate COX-2 selectivity in vitro and good anti-inflammatory activity in vivo, compound 13i showed the highest anti-inflammatory activity that is very close in potency to the reference drug (celecoxib) with better gastric profile than celecoxib.

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

Fig. 1
Scheme 1

Similar content being viewed by others

References

  • Abdelazeem, A.H., S.A. Abdelatef, M.T. El-Saadi, H.A. Omar, S.I. Khan, C.R. McCurdy, and S.M. El-Moghazy. 2014. Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes; design, synthesis and biological evaluation as potential anti-inflammatory agents. European Journal of Pharmaceutical Sciences 62: 197–211.

    Article  CAS  PubMed  Google Scholar 

  • Abdellatif, K.R.A., M.A. Chowdhury, and E.E. Knaus. 2008a. Synthesis of new 1-[4-methane (amino) sulfonylphenyl)]-5-[4- (aminophenyl)]-3-trifluoromethyl-1H-pyrazoles. Journal of Heterocyclic Chemistry 45: 1707–1710.

    Article  CAS  Google Scholar 

  • Abdellatif, K.R.A., M.A. Chowdhury, C.A. Velázquez, Z. Huang, Y. Dong, D. Das, G. Yu, M.R. Suresh, and E.E. Knaus. 2010. Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. Bioorganic & Medicinal Chemistry Letters 20: 4544–4549.

    Article  CAS  Google Scholar 

  • Abdellatif, K.R.A., M.A. Chowdhury, Y. Dong, D. Das, G. Yu, C. Velázquez, M.R. Suresh, and E.E. Knaus. 2009. Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-carboxymethylphenyl)-1-(4-methanesulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its aminosulfonyl analog: Synthesis, biological evaluation and nitric oxide release studies. Bioorganic & medicinal chemistry 17: 5182–5188.

    Article  CAS  Google Scholar 

  • Abdellatif, K.R.A., M.A. Chowdhury, Y. Dong, and E.E. Knaus. 2008b. Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids: synthesis, nitric oxide release studies and anti-inflammatory activities. Bioorganic & medicinal chemistry 16: 6528–6534.

    Article  CAS  Google Scholar 

  • Abdellatif, K.R.A., M.A. Chowdhury, Y. Dong, C. Velázquez, D. Das, M.R. Suresh, and E.E. Knaus. 2008c. Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its methanesulfonyl analog: synthesis, biological evaluation and nitric oxide release studies. Bioorganic & Medicinal Chemistry 16: 9694–9698.

    Article  CAS  Google Scholar 

  • Ahlström, M.M., M. Redderström, I. Zamora, and K. Luthman. 2007. CYP2C9 structure–metabolism relationships: Optimizing the metabolic stability of COX-2 inhibitors. Journal of Medicinal Chemistry 50: 4444–4452.

    Article  PubMed  Google Scholar 

  • Ahn, J.H., H.M. Kim, S.H. Jung, S.K. Kang, K.R. Kim, S.D. Rhee, S.D. Yang, H.G. Cheon, and S.S. Kim. 2004. Synthesis and DP-IV inhibition of cyano-pyrazoline derivatives as potent anti-diabetic agents. Bioorganic & Medicinal Chemistry Letters 14: 4461–4465.

    Article  CAS  Google Scholar 

  • Al-Hourani, B.J., S.K. Sharma, J.Y. Mane, J. Tuszynski, V. Baracos, T. Kniess, M. Suresh, J. Pietzsch, and F. Wuest. 2011. Synthesis and evaluation of 1,5-diaryl-substituted tetrazoles as novel selective cyclooxygenase-2 (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters 21: 1823–1826.

    Article  CAS  Google Scholar 

  • Amutha, P., and S. Nagarajan. 2012. Synthesis and antimicrobial activities of new 4,6-diaryl-4,5-dihydro-3-hydroxy-2H-indazoles. Journal of Heterocyclic Chemistry 49: 428–432.

    Article  CAS  Google Scholar 

  • Bano, S., K. Javed, S. Ahmad, I.G. Rathish, S. Singh, and M.S. Alam. 2011. Synthesis and biological evaluation of some new 2-pyrazolines bearing benzene sulfonamide moiety as potential anti-inflammatory and anti-cancer agents. European Journal of Medicinal Chemistry 46: 5763–5768.

    Article  CAS  PubMed  Google Scholar 

  • Bashir, R., S. Ovais, S. Yaseen, H. Hamid, M.S. Alam, M. Samim, S. Singh, and K. Javed. 2011. Synthesis of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents. Bioorganic & Medicinal Chemistry Letters 21: 4301–4305.

    Article  CAS  Google Scholar 

  • Chandra, T., N. Garg, S. Lata, K.K. Saxena, and A. Kumar. 2010. Synthesis of substituted acridinyl pyrazoline derivatives and their evaluation for anti-inflammatory activity. European Journal of Medicinal Chemistry 45: 1772–1776.

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury, M.A., K.R.A. Abdellatif, Y. Dong, D. Das, M.R. Suresh, and E.E. Knaus. 2008a. Synthesis of celecoxib analogs that possess a N-hydroxypyrid-2(1H)one 5-lipoxygenase pharmacophore: biological evaluation as dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity. Bioorganic & Medicinal Chemistry Letters 18: 6138–6141.

    Article  CAS  Google Scholar 

  • Chowdhury, M.A., K.R.A. Abdellatif, Y. Dong, and E.E. Knaus. 2008b. Synthesis of new 4-[2-(4-methyl(amino)sulfonylphenyl)-5-trifluoromethyl-2H-pyrazol-3-yl]-1,2,3,6-tetrahydropyridines: A search for novel nitric oxide donor anti-inflammatory agents. Bioorganic & Medicinal Chemistry 16: 8882–8888.

    Article  CAS  Google Scholar 

  • Dogné, J.M., C.T. Supuran, and D. Pratico. 2005. Adverse cardiovascular effects of the coxibs. Journal of Medicinal Chemistry 48: 2251–2257.

    Article  PubMed  Google Scholar 

  • Fioravanti, R., A. Bolasco, F. Manna, F. Rossi, F. Orallo, F. Ortuso, S. Alcaro, and R. Cirilli. 2010. Synthesis and biological evaluation of N-substituted-3,5-diphenyl-2-pyrazoline derivatives as cyclooxygenase (COX-2) inhibitors. European Journal of Medicinal Chemistry 45: 6135–6138.

    Article  CAS  PubMed  Google Scholar 

  • Fun, H.K., S. Chantrapromma, P.S. Patil, E.D. D’Silva, and S.M. Dharmaprakash. 2008. (E)-3-(4-methyl-phen-yl)-1-(4-nitro-phenyl)prop-2-en-1-one. Acta Crystallographica Section E, Structure Reports Online 64: o954–o955.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gupta, R.A., and S.G. Kaskhedikar. 2012. Synthesis, antitubercular activity, and QSAR analysis of substituted nitroaryl analogs: Chalcone, pyrazole, isoxazole, and pyrimidines. Medicinal Chemistry Research 22: 3863–3880.

    Article  Google Scholar 

  • Habeeb, A.G., P.N.P. Rao, and E.E. Knaus. 2001. Design and synthesis of celecoxib and rofecoxib analogues as selective cyclooxygenase-2 (COX-2) Inhibitors: Replacement of sulfonamide and methylsulfonyl pharmacophores by an azido bioisostere. Journal of Medicinal Chemistry 44: 3039–3042.

    Article  CAS  PubMed  Google Scholar 

  • Hassan, G.S., S.M. Abou-Seri, G. Kamel, and M.M. Ali. 2014. Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents. European Journal of Medicinal Chemistry 76: 482–493.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, M., B.Younglove, L. Lee, R. LeBlanc, H.H. Jr., P. Hills, H. Mackay, T. Brown, S.L. Mooberry, and M. Lee. 2007. Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4. Bioorganic & medicinal chemistry letters 17: 5897–901.

  • Khode, S., V. Maddi, P. Aragade, M. Palkar, P.K. Ronad, S. Mamledesai, A.H.M. Thippeswamy, and D. Satyanarayana. 2009. Synthesis and pharmacological evaluation of a novel series of 5-(substituted)aryl-3-(3-coumarinyl)-1-phenyl-2-pyrazolines as novel anti-inflammatory and analgesic agents. European Journal of Medicinal Chemistry 44: 1682–1688.

    Article  CAS  PubMed  Google Scholar 

  • Lange, J.H.M., H.H.V. Stuivenberg, W. Veerman, H.C. Wals, B. Stork, H.K.A.C. Coolen, A.C. McCreary, T.J.P. Adolfs, and C.G. Kruse. 2005. Novel 3,4-diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity. Bioorganic & Medicinal Chemistry Letters 15: 4794–4798.

    Article  CAS  Google Scholar 

  • Ovais, S., R. Bashir, S. Yaseen, P. Rathore, M. Samim, and K. Javed. 2012. Synthesis and pharmacological evaluation of some novel 2-pyrazolines bearing benzenesulfonamide as anti-inflammatory and blood glucose lowering agents. Medicinal Chemistry Research 22: 1378–1385.

    Article  Google Scholar 

  • Ovais, S., S. Yaseen, R. Bashir, P. Rathore, M. Samim, S. Singh, V. Nair, and K. Javed. 2013. Synthesis and anti-inflammatory activity of celecoxib like compounds. Journal of Enzyme Inhibition and Medicinal Chemistry 28: 1105–1112.

    Article  CAS  PubMed  Google Scholar 

  • Rathish, I.G., K. Javed, S. Ahmad, S. Bano, M.S. Alam, K.K. Pillai, S. Singh, and V. Bagchi. 2009. Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide. Bioorganic & Medicinal Chemistry Letters 19: 255–258.

    Article  CAS  Google Scholar 

  • Romagnoli, R., P.G. Baraldi, M.D. Carrion, O. Cruz-Lopez, C.L. Cara, J. Balzarini, E. Hamel, A. Canella, E. Fabbri, R. Gambari, G. Basso, and G. Viola. 2009. Hybrid alpha-bromoacryloylamido chalcones. Design, synthesis and biological evaluation. Bioorganic & Medicinal Chemistry Letters 19: 2022–2028.

    Article  CAS  Google Scholar 

  • Rostom, S.A.F. 2006. Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some derived thiazole ring systems. Bioorganic & Medicinal Chemistry 14: 6475–6485.

    Article  CAS  Google Scholar 

  • Sahu, S.K., M. Banerjee, A. Samantray, C. Behera, and M.A. Azam. 2008. Synthesis, analgesic, anti-inflammatory and antimicrobial activities of some novel pyrazoline derivatives. Tropical Journal of Pharmaceutical Research 7: 961–968.

    Article  Google Scholar 

  • Scheen, A.J. 2004. Withdrawal of rofecoxib (Vioxx): what about cardiovascular safety of COX-2 selective non-steroidal anti-inflammatory drugs. Revue Medicale de Liege 59: 565–569.

    CAS  PubMed  Google Scholar 

  • Turner, R.A. 1965. Screening method in pharmacology. Anti-inflammatory agent 13, 158. New York: Academic Press.

    Google Scholar 

  • Zarghi, A., L. Najafnia, B. Daraee, O.G. Dadrass, and M. Hedayati. 2007. Synthesis of 2,3-diaryl-1,3-thiazolidine-4-one derivatives as selective cyclooxygenase (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters 17: 5634–5637.

    Article  CAS  Google Scholar 

  • Zarghi, A., T. Zebardast, B. Daraie, and M. Hedayati. 2009. Design and synthesis of new 1,3-benzthiazinan-4-one derivatives as selective cyclooxygenase (COX-2) inhibitors. Bioorganic & Medicinal Chemistry 17: 5369–5373.

  • Zebardast, T., A. Zarghi, B. Daraie, M. Hedayati, and O.G. Dadrass. 2009. Design and synthesis of 3-alkyl-2-aryl-1,3-thiazinan-4-one derivatives as selective cyclooxygenase (COX-2) inhibitors. Bioorganic & Medicinal Chemistry Letters 19: 3162–3165.

    Article  CAS  Google Scholar 

  • Zheng, C.J., S.M. Jiang, Z.H. Chen, B.J. Ye, and H.R. Piao. 2011. Synthesis and anti-bacterial activity of some heterocyclic chalcone derivatives bearing thiofuran, furan, and quinoline moieties. Archiv der Pharmazie 344: 689–695.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62514, Egypt

    Khaled R. A. Abdellatif, Mohamed A. Abdelgawad, Heba A. H. Elshemy & Shahinda S. R. Alsayed

  2. Department of Pharmacology, Faculty of Veterinary, Cairo University, Cairo, Egypt

    Gehan Kamel

Authors
  1. Khaled R. A. Abdellatif
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohamed A. Abdelgawad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heba A. H. Elshemy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahinda S. R. Alsayed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gehan Kamel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khaled R. A. Abdellatif.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdellatif, K.R.A., Abdelgawad, M.A., Elshemy, H.A.H. et al. Synthesis and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing an aminosulphonyl pharmacophore. Arch. Pharm. Res. 38, 1932–1942 (2015). https://doi.org/10.1007/s12272-015-0606-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-015-0606-7

Keywords

Search

Navigation