Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2602–2613 | Cite as

Heterocycles 39. Synthesis, characterization and evaluation of the anti-inflammatory activity of thiazolo[3,2-b][1,2,4]triazole derivatives bearing pyridin-3/4-yl moiety

Original Research
  • 72 Downloads

Abstract

A series of pyridin-3/4-yl-thiazolo[3,2-b][1,2,4]triazole derivatives (5ag, 6ag) were synthesised by Hantzsch condensation of 5-pyridin-3/4-yl-1,2,4-triazole-3-thiol and diverse α-halocarbonyl compounds. Different reaction conditions (pH, temperature, solvent) were investigated for the efficient obtention of the target compounds. Under reflux and acidic conditions, the Hantzsch condensation was a one-step reaction. At room temperature and under basic conditions, it was possible to isolate the iminothioether intermediates 3/4ag. These intermediates were cyclized in a subsequent step by treatment with concentrated sulphuric acid. The obtained compounds were evaluated for their anti-inflammatory activity. Three synthesised pyridyl-thiazolo[3,2-b][1,2,4]triazole derivatives (6c, 6d, 6f) were found to be good anti-inflammatory agents.

Graphical Abstract

Open image in new window

Keywords

Thiazolo[3,2-b][1,2,4]triazole Pyridine Anti-inflammatory activity 

Notes

Acknowledgements

This study was possible with the financial support of the European Social Fund, under the project POSDRU number 107/1.5/S/78702.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1959_MOESM1_ESM.doc (25 mb)
Supplementary Information

References

  1. Aggarwal R, Kumar S, Kaushik P, Kaushik D, Gupta GK (2013) Synthesis and pharmacological evaluation of some novel 2-(5-hydroxy-5-trifluoromethyl-4,5,-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles. Eur J Med Chem 62:508–514CrossRefPubMedGoogle Scholar
  2. Al-Omar MA, Abd El-Galil EA, Al-Salahi RA (2010) Anti-inflammatory, analgesic, anticonvulsant and antiparkinsonian activities of some pyridine derivatives using 2,6-disubstituted isonicotinic acid hydrazides. Arch Pharm Chem Life Sci 10:648–656CrossRefGoogle Scholar
  3. Arafa RK, Hegazy GH, Piazza GA, Abadi AH (2013) Synthesis and in vitro antiproliferative effect of novel quinoline-bases potential anticancer agents. Eur J Med Chem 63:826–832CrossRefPubMedGoogle Scholar
  4. Assarzadeh MJ, Almasirad A, Shafiee A, Koopaei MN, Abdollahi M (2014) Synthesisi of new thiazolo[3,2-b][1,2,4]triazole-6(5H)-one derivatives as potent analgezic and anti-inflammatory agents. Med Chem Res 23:948–957CrossRefGoogle Scholar
  5. Avanzo RE, Anesini C, Fascio ML, Errea MI, D’Accorso NB (2012) 1,2,4-Triazole D-ribose derivatives: design, synthesis and antitumoral evalation. Eur J Med Chem 47:104–110CrossRefPubMedGoogle Scholar
  6. Barbuceanu SF, Bancescu G, Draghici C, Barbuceanu F, Cretu OD, Apostol TV, Bancescu A (2012) Synthesis and antibacterial activity of some triazole, thiadiazole and oxadiazole derivatives. Rev Chem 63:362–366Google Scholar
  7. Barbuceanu SF, Almăjan GL, Samaret I, Drăghici C, Tarcomnicu AI, Bănescu G (2009) Synthesis, characterization and evaluation of antibacterial activity of some thiazolo[3,2-b][1,2,4]triazole incorporating diphenylsulfone moieties. Eur J Med Chem 44:4752–4757CrossRefPubMedGoogle Scholar
  8. Creanga AA, Bercean VN, Badea V, Patras AI, Cocarta AI, Tatu CA, Csunderlik C (2010) Comparative study of the synthesis of some 5(2-,3-,4-pyridil)substituted-4H-4-amino-3-mercapto-1,2,4-triazoles. Rev Chim 61:1169–1172Google Scholar
  9. Desai NC, Rajpara KM, Joshi VV (2013) Microwave induced synthesis of fluorobenzamides containing thiazole and thiazolidine as promising antimicrobial analogs. J Fluor Chem 145:102–111CrossRefGoogle Scholar
  10. Dulla B, Wan B, Franzblau SG, Kapavarapu R, Reiser O, Iqbal I, Pal M (2012) Construction and functionalization of fused pyridine ring leading to novel compounds as potentail antitubercular agents. Bioorg Med Chem Lett 22:4629–4635CrossRefPubMedGoogle Scholar
  11. El-Emam AA, Al-Tamimi AMS, Al-Omar MA, Alrashood KA, Habib EE (2013) Synthesis and antimicrobial activity of novel 5-(1-adamantyl)-2-aminomethyl-4-substituted-1,2,4-triazoline-3-thiones. Eur J Med Chem 68:96–102CrossRefPubMedGoogle Scholar
  12. El-Messery SM, Hassan GS, Al-Omary FAM, El-Subbagh IH (2012) Substituted thiazoles VI. Synthesis and antitumor activity of new 2-acetamido- and 2 or 3-propanamido-thiazole analogs. Eur J Med Chem 54:615–625CrossRefPubMedGoogle Scholar
  13. Feng L, Yang KW, Zhou LS, Xiao JM, Yang X, Zhai L, Zhang YL, Crowder MW (2012) N-Heterocyclic dicarboxylic acids: broad-spectrum inhibitors of metallo-b-lactamases with co-antibacterial effect against antibiotic-resistant bacteria. Bioorg Med Chem Lett 22:5185–5189CrossRefPubMedGoogle Scholar
  14. Franklin PX, Pillai AD, Rathod PD, Yerande S, Nivsarkar M, Padh H, Vasu KK, Sudarsanam V (2008) 2-Amino-5-thiazolyl motif: a novel scaffold for designing anti-inflammatory agents of diverse structures. Eur J Med Chem 43:129–134CrossRefPubMedGoogle Scholar
  15. Griesbacher T, Suttlif RL, Lembeck F (1994) Anti-inflammatory and analgesic activity of the bradykinin antagonist, ictibant (Hoe 140), against an extract from Phorphyromonas gingivalis. Br J Pharmacol 112:1004–1006CrossRefPubMedPubMedCentralGoogle Scholar
  16. Karegoudar P, Karthikeyan MS, Prasad DJ, Mahalinga M, Holla SB, Kumari NS (2008) Synthesis of some novel 2,4-disubstituted thiazoles as possible antimicrobial agents. Eur J Med Chem 43:261–267CrossRefPubMedGoogle Scholar
  17. Karthikeyan MS (2009) Synthesis, analgesic, anti-inflammatory and antimicrobial studies of 2,4-dichloro-5-fluorophenyl containing thiazolotriazoles. Eur J Med Chem 44:827–833CrossRefPubMedGoogle Scholar
  18. Khidre RE, Abu-Hashem AA, El-Shazly M (2011) Synthesis and anti-microbial activity of some 1-substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile derivatives. Eur J Med Chem 46:5057–5064CrossRefPubMedGoogle Scholar
  19. Kumar H, Javed SA, Khan SA, Amir M (2008) 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: synthesis and preliminary evaluation of biological properties. Eur J Med Chem 43:2688–2689CrossRefPubMedGoogle Scholar
  20. Liu H, Yi L, Wang XY, Wang B, He HY, Liu JY, Xiang ML, He J, Wu XH, Yang L (2013) Synthesis, preliminary structure–activity relationships, and in vitro biological evaluation of 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives as potential anti-inflammatory agents. Bioorg Med Chem Lett 23:2349–2352CrossRefPubMedGoogle Scholar
  21. Lu X, Zhang H, Li X, Chen G, Li QS, Luo Y, Ruan BF, Clen XW, Zhu HL (2011) Design, synthesis and biological evaluation of pyridine acyl sulfonamide derivatives as novel COX-2 inhibitors. Bioorg Med Chem 19:6827–6832CrossRefPubMedGoogle Scholar
  22. Lv PC, Wang KR, Yang Y, Mao WJ, Chen J, Xiong J, Zhu HL (2009) Design, synthesis and biological evaluation of novel thiazole derivatives as potent FabH inhibitors. Bioorg Med Chem Lett 19:6750–6754CrossRefPubMedGoogle Scholar
  23. Palage M, Zaharia V, Simiti I (1997) Heterocycles 77: quaternary ammonium salts and nitrones in the 2-aryl-thiazole-[3.2-b]-1,2,4-triazole. Correlations between chemical structure and biological activity. Farmacia 45(3):37–46Google Scholar
  24. Patel NB, Khan IH, Rajani SD (2010) Pharmacological evaluation and characterization of newly synthesized 1,2,4-triazoles. Eur J Med Chem 45:4293–4299CrossRefPubMedGoogle Scholar
  25. Plech T, Wujec M, Kosikowka U, Malm A, Rajtar B, Polz-Dacewicz M (2013) Synthesis and in vitro activity of 1,2,4-triazole-ciprofloxacin hybrids against drug-susceptible and drug-resistant bacteria. Eur J Med Chem 60:128–134CrossRefPubMedGoogle Scholar
  26. Prasanna DS, Kavitha CV, Vinaya K, Ranganatha SR, Raghavan SC, Rangappa KS (2010) Synthesis and identification of a new class of antileukemik agents containing 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole. Eur J Med Chem 45:5331–5336CrossRefPubMedGoogle Scholar
  27. PubChem (2004) Compound summary for CID 56692339. https://pubchem.ncbi.nlm.nih.gov/compound/56692339?from=summary#section=Top. Accessed 12 Sep 2015
  28. Romagnoli R, Baraldi PG, Salvador MK, Camacho ME, Preti D, Tabrizi AM, Bassetto M, Brancale A, Hamel E, Bortolozzi R, Basso G, Viola G (2012) Synthesis and biological evaluation of 2-substituted-4-(3’,4’,5’-trimetoxy-phenyl)-5-aryl thiazoles as anticancer agents. Bioorg Med Chem 20:7083–7094CrossRefPubMedPubMedCentralGoogle Scholar
  29. Shelke SH, Mhaske PC, Nandave M, Narkhade S, Walhekar MN, Bobade DV (2012) Synthesis and pharmacological evaluation of a novel series of 3-aryl-2-(2-substituted-4-methylthiazole-5-yl)thiazolidin-4-one as possible anti-inflammatory and antimicrobial agents. Bioorg Med Chem Lett 22:6373–6376CrossRefPubMedGoogle Scholar
  30. Short KM, Pham SM, Williams DC, Datta S (2011) Multisubstituted aromatic compounds as inhibitors of thrombin. Patent WO2011/126903Google Scholar
  31. Simiti I, Zaharia V, Coman M, Demian H (1991) Heterocycles 65. Synthesis and chemical characterization of some 2-aryl-6-ethoxycarbonyl-5-methyl-thiazolo[3,2-b]-1,2,4-triazoles. Arch Pharm (Weinheim) 324:49–51CrossRefGoogle Scholar
  32. Tozkoparan B, Ayatac SP, Gursoy S, Aktay G (2012) Design and synthesis of some thiazolotriazolyl esters as anti-inflammatory and analgezic agents. Med Chem Res 21:192–201CrossRefGoogle Scholar
  33. Winter CA, Risley EA, Nuss GW (1962) Carrageenin-induced edema in hind paw of the rat as an essay for anti-inflammatory drugs. Proc Soc Exp Biol Med 111:544–547CrossRefPubMedGoogle Scholar
  34. Zaharia D, Zaharia V, Matinca D, Simiti I (1999) L’obtention et l’evaluation de l’activite antimicrobienne de quelques 2-aryl-5-r-thiazolo [3,2-b]1,2,4-triazoles. Farmacia 47:51–60Google Scholar
  35. Zaharia V, Imre S, Palibroda N (2009) Heterocycles. Obtaining and physico-chemical characterization of some thiazolo and thiazolo [3,2-b][1,2,4]triazolic hydroxy-heterochalcones. Rev Chim 60:391–397Google Scholar
  36. Zaharia V, Silvestru A, Palibroda N, Mogoşan C (2011) Heterocycles 28. Synthesis and characterization of some bis and polyheterocyclic compounds with anti-inflammatory potential. Farmacia 59:624–635Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Organic Chemistry“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.Department of Pharmacology, Physiology and Physiopathology“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania
  3. 3.Department of Pharmaceutical Technology and Biopharmaceutics“Iuliu Haţieganu” University of Medicine and PharmacyCluj-NapocaRomania

Personalised recommendations