2-Amino-5-sulfanyl-1,3,4-thiadiazoles: A new series of selective cyclooxygenase-2 inhibitors

Sharma, Rajesh; Sainy, Jitendra; Chaturvedi, Subhash

doi:10.2478/v10007-008-0011-6

Abstract

A new series of cyclooxygenase-2 inhibitors with 2-amino--5-sulfanyl-1,3,4-thiadiazole as the central scaffold unit has been synthesized. The newly synthesized compounds were characterized by analytical and spectral methods. Compounds were screened for cyclooxygenase inhibitory activity by the colorimetric COX (ovine) inhibitor screening assay, anti-inflammatory activity by the carrageenean induced rat paw oedema test and analgesic activity by the tail flick method. Some compounds exhibited significant biological activity.

References

M. C. Allison, A. G. Howastan, C. J. Torrance, F. D. Lee and R. N. Russell, Gastrointestinal damage associated with the use of nonsteroidal anti-inflammatory drugs, Engl. J. Med. 327 (1982) 749-754.10.1056/NEJM199209103271101
Search in Google Scholar
D. Bohl, H. Gaussmann, G. Vorberg, J. Sanch, R. Garcia-Barbal, J. F. Sarti and F. J. J. Harrison, A clinical trial comparing a new NSAID: Droxicam and proxicam in spinal osteoarthritis, Int. J. Clin. Pharmacol. Ther. Toxic. 28 (1990) 416-419.
Search in Google Scholar
R. S. Shelley and Y. Wei, Solutions of Aryl or Heteroaryl Substituted Alkanoic Acids in Lipophilic Solvents and Soft Gelatin Capsules Containing Such Solutions, Eur. Pat. Pub., 30 Nov. 1995, WO, 9531979, 1994.
Search in Google Scholar
K. Chegaev, L. Lazzarato, P. Tosco, C. Cena, E. Marini, B. Rolando, P. A. Carrupt, R. Fruttero and A. Gasco, NO-donor COX-2 inhibitors. New nitrooxy-substituted 1,5-diarylimidazoles endowed with COX-2 inhibitory and vasodilatory properties, J. Med. Chem. 50 (2007) 1449-1457; DOI: 10.1021/jm0607247.10.1021/jm0607247
Search in Google Scholar
M. Biava, G. C. Porretta, G. Poce, S. Supino, S. Forli, M. Rovini, A. Cappelli, F. Manetti, M. Botta, L. Sautebin, A. Rossi, C. Pergola, C. Ghelardini, E. Vivoli, F. Makovec, P. Anzellotti, P. Patrignani and M. Anzini, Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity, J. Med. Chem. 50 (2007) 5403-5411; DOI: 10.1021/jm0707525.10.1021/jm0707525
Search in Google Scholar
J. P. Waldo and R. C. Larock, The synthesis of highly substituted isoxazoles by electrophilic cyclization: An efficient synthesis of valdecoxib, J. Org. Chem. 72 (2007) 9643-9647; DOI: 10.1021/jo701942e.10.1021/jo701942e
Search in Google Scholar
J. R. Vane, Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs, Nature (New Biol.) 231 (1971) 232-235.10.1038/newbio231232a0
Search in Google Scholar
J. A. Mitchell, P. Akaraseenont, C. Themermann, R. J. Flower, J. R. Vane, Selectivity of non steroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase, Proc. Natl. Acd. Sci. USA. 90 (1993) 11693-11697.10.1073/pnas.90.24.11693
Search in Google Scholar
R. Sharma and S. C. Chaturvedi, Development of pharmacophoric models on 5,6-diarylimidaxo-[2,1-b]-thiazole for selective cyclooxygenase-2 inhibitors, Indian J. Pharm. Sci. 66 (2004) 758-772.
Search in Google Scholar
R. Sharma, S. C. Chaturvedi and A. K. Saxena, 3D-QSAR studies on novel terphenyls for selective inhibition of cyclooxygenase-2 enzyme, Indian J. Pharm. Sci. 66 (2004) 758-772.
Search in Google Scholar
F. Clerici and D. Pocar, Synthesis of 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives and evaluation of their antidepressant and anxiolytic activity, J. Med. Chem. 44 (2001) 931-936; DOI: 10.1021/jm001027w.10.1021/jm001027w
Search in Google Scholar
R. J. Kulmacz and W. E. M. Lands, Requirements for hydro peroxide by the cyclooxygenase and peroxidase activities of prostaglandin H synthase, Prostaglandins 25 (1983) 531-540.10.1016/0090-6980(83)90025-4
Search in Google Scholar
Colorimetric COX (ovine) inhibitor screening assay, Catalog No. 760111, Cayman Chemical, Ann Arbor (MI) 2005.
Search in Google Scholar
C. A. Winter, E. A. Risely and G. N. Nuss, Carrageenean-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs, Proc. Soc. Exp. Biol. 111 (1962) 544-547.10.3181/00379727-111-2784914001233
Search in Google Scholar
H. G. Vogel, Drug Discovery and Evaluation Pharmacological Assays, Springer, Frankfurt 2002, pp. 694.
Search in Google Scholar
R. R Ranatunge, M. Augustyniak, U. K. Bandarage, R. A. Earl, J. L. Ellis, D. S. Garvey, D. R. Janero, L. G. Letts, A. M. Martino, M. G Murty, S. K. Richardson, J. D. Schroeder, M. J. Shumway, S. W. Tam, A. M. Trocha and D. V. Young, Synthesis and selective cyclooxygenase-2 inhibitory activity of a series of novel, nitric oxide donor containing pyrazoles, J. Med. Chem. 47 (2004) 2180-2193; DOI: 10.1021/jm0302769.
Search in Google Scholar

2-Amino-5-sulfanyl-1,3,4-thiadiazoles: A new series of selective cyclooxygenase-2 inhibitors

Abstract

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