Medicinal Chemistry Research

, Volume 23, Issue 2, pp 948–957 | Cite as

Synthesis of new thiazolo[3,2-b][1,2,4]triazole-6(5H)-one derivatives as potent analgesic and anti-inflammatory agents

  • Mohammad Javad Assarzadeh
  • Ali Almasirad
  • Abbas Shafiee
  • Mansur Nassiri Koopaei
  • Mohammad Abdollahi
Original Research


A series of thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones were synthesized and evaluated for their analgesic and anti-inflammatory activities. The structures of these compounds were supported by FT-IR, 1HNMR, and Mass spectra. All of the final compounds showed potent analgesic activity and the best compound 9d was 2.4 times more potent than mefenamic acid as the reference drug. In addition, most of them showed comparable or better anti-inflammatory activity in comparison with mefenamic acid and indomethacin. Moreover, compounds 9d, 9e, 9g, 9h, 9i, 9k, 9n, and 9o did not exhibit any significant ulcerogenic activity.


Analgesic agents Anti-inflammatory activity Thiazolo-triazole Ulcerogenic activity 


  1. Abu-Hashem AA, Gouda MA (2011) Synthesis, anti-inflammatory and analgesic evaluation of certain new 3a,4,9,9a-tetrahydro-4,9-benzenobenz[f]isoindole-1,3-diones. Arch Pharm Chem Life Sci 344:543–551CrossRefGoogle Scholar
  2. Aktay G, Tozkoparan B, Ertan M (2005) Protective effects of thiazolo[3,2-b]-1,2,4-triazoles on ethanol-induced oxidative stres in mouse brain and liver. Arch Pharm Res 28(4):438–442CrossRefPubMedGoogle Scholar
  3. Almasirad A, Sheikhha M, Hosseini R, Tabatabai SA, Shafiee A (2004) Synthesis and morphine enhancement avtivity of N-[5-(2-phenoxyphenyl)-1,3,4-oxadiazole-2-yl]-N′-phenylurea derivatives. Arch Pharm Chem Life Sci 337:193–200CrossRefGoogle Scholar
  4. Almasirad A, Hosseini R, Jalalizadeh H, Rahimimoghaddam Z, Abaeian N, Janafrooz M, Abbaspour M, Ziaee V, Dalvandi A, Shafiee A (2006) Synthesis and analgesic activity of 2-phenoxybenzoic acid and N-phenylanthranilic acid hydrazides. Biol Pharm Bull 29(6):1180–1185CrossRefPubMedGoogle Scholar
  5. Almasirad A, Vousooghi N, Tabatabai SA, Kebriaeezadeh A, Shafiee A (2007) Synthesis, anti convulsant and muscle relaxant activities of 1,3,4-oxadiazole,1,3,4-thiadiazole and 1,2,4-triazole. Acta Chim Slov 54:317–324Google Scholar
  6. Berk B, Aktay G, Yesilada E, Ertan M (2001) Synthesis and pharmacological activities of some new 2-[1-(6-methoxy-2-naphtyl)ethyl]-6(substituted)benzylidene-thiazolo[3,2-b]-1,2,4-triazolole-5(6H)-one derivatives. Pharmazie 56(8):613–616PubMedGoogle Scholar
  7. Calıskan B, Yılmaz A, Evren I, Menevse S, Uludag O, Banoglu E (2013) Synthesis and evaluation of analgesic, anti-inflammatory, and anticancer activities of new pyrazole-3(5)-carboxylic acid derivatives. Med Chem Res 22:782–793CrossRefGoogle Scholar
  8. Cioli V, Silvestrini B, Dordoni F (1967) Evaluation of potential of gastric ulceration after administration of certain drugs. Exp Mol Pathol 6:68–75CrossRefPubMedGoogle Scholar
  9. Doğdaş E, Tozkoparan B, Kaynak FB, Eriksson L, Küpeli E, Yeşilada E, Ertan M (2007) Design and synthesis of some new thiazolo [3,2-b]-1,2,4-triazole-5(6H)-ones substituted with flurbiprofen as anti-inflammatory and analgesic agents. Arzneimittel-Forschung-Drug Res 57(4):196–202Google Scholar
  10. Lesyk R, Vladzimirska O, Holota S, Zaprutko L, Gzella A (2007) New 5-substituted thiazolo[3,2-b][1,2,4]triazol-6-ones: synthesis and anticancer evaluation. Eur J Med Chem 42(5):641–648CrossRefPubMedGoogle Scholar
  11. Moradi A, Navidpour L, Amini M, Sadeghian H, Shadnia H, Firouzi O, Miri R, Ebrahimi SES, Abdollahi M, Zahmatkesh MH, Shafiee A (2010) Design and synthesis of 2-phenoxynicotinic acid hydrazides as anti-inflammatory and analgesic agents. Arch Pharm Chem Life Sci 9:509–518CrossRefGoogle Scholar
  12. Pignatello R, Mazzone S, Panico AM, Mazzone G, Pennisi G, Castana Matera M, Blandino G (1991) Synthesis and biological evaluation of thiazolo-triazole derivatives. Eur J Med Chem 42(5):641–648Google Scholar
  13. Rineh A, Mahmoodi N, Abdollahi M, Foroumadi A, Sorkhi M, Shafiee A (2007) Synthesis, analgesic and anti-inflammatory activity of 4-(2-phenoxyphenyl)semicarbazones. Arch Pharm Chem Life Sci 340:409–415CrossRefGoogle Scholar
  14. Schoen RT, Vender RJ (1989) Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Am J Med 86(4):449–458CrossRefPubMedGoogle Scholar
  15. Shafiee A, Jalilian AR, Tabatabaiee-Yazdi M (1998) Syntheses, antibacterial and antifungal activities of substituted-thiazolo-1,3,4-thiadiazoles, 1,3,4-oxadiazoles and 1,2,4-triazoles. Iran J Chem Chem Eng 17:14–20Google Scholar
  16. Smith CJ, Zhang Y, Koboldt CM, Muhammad J, Zweifel BS, Shaffer A, Talley JJ, Masferrer JL, Seibert K, Isakson PC (1998) Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci USA 95(22):13313–13318PubMedCentralCrossRefPubMedGoogle Scholar
  17. Tiryaki D, Sukuroglu M, Dogruer DS, Akkol E, Ozgen S, Sahin MF (2012) Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities. Med Chem Res. doi:10.1007/s00044-012-0253-1 Google Scholar
  18. Tozkoparan B, Kilcigil GA, Ertan R, Ertan M, Kelicen P, Demirdamar S (1999) Synthesis and evaluation of anti-inflammatory activity of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their michael addition products. Arzneimittel-Forschung-Drug Res 49(12):1006–1011Google Scholar
  19. Tozkoparan B, Gökhan N, Aktay G, Yesilada E, Ertan M (2000) 6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones substituted with ibuprofen: synthesis, characterization and evaluation of anti-inflammatory activity. Eur J Med Chem 35(8):743–750CrossRefPubMedGoogle Scholar
  20. Tozkoparan B, Aytac SP, Gürsoy S, Aktay G (2012) Design and synthesis of some thiazolotriazolyl esters as anti-inflammatory and analgesic agents. Med Chem Res 21:192–201CrossRefGoogle Scholar
  21. Uzgören-Baran A, Cahide Tel B, Sarıgöl D, Inci Öztürk E, Kazkayası I, Okay G, Ertand M, Tozkoparan B (2012) Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: Novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance. Eur J Med Chem 57:398–406CrossRefPubMedGoogle Scholar
  22. Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR (1999) Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA 96(13):7563–7568PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Mohammad Javad Assarzadeh
    • 1
  • Ali Almasirad
    • 1
  • Abbas Shafiee
    • 2
  • Mansur Nassiri Koopaei
    • 1
  • Mohammad Abdollahi
    • 3
  1. 1.Department of Medicinal Chemistry, Pharmaceutical Sciences BranchIslamic Azad UniversityTehranIran
  2. 2.Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran
  3. 3.Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran

Personalised recommendations