Synthesis and biological evaluation of thieno[2,3-d]pyrimidine derivatives for anti-inflammatory, analgesic and ulcerogenic activity

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Synthesis and biological evaluation of thieno[2,3-d]pyrimidine derivatives for anti-inflammatory, analgesic and ulcerogenic activity

5-Methyl-6-phenyl-2-thioxothieno[2,3-d]pyrimidone derivative (2) reacted with hydrazonoyl chloride derivatives to afford triazolothienopyrimidones 4a-f. Also, acetone-1-(2-amino-5-isopropyl-thiophene-3-carbonitrile) (3) reacted with functional and bifunctional groups to yield the corresponding compounds 5-11. The new products showed anti-inflammatory, analgesic, and ulcerogenic activities comparable to that of indomethacin and acetylsalicylic acid, respectively.

D. J. Brown, Pyrimidines and Their Benzo Derivatives, in Comprehensive Heterocyclic Chemistry (Ed. A. R. Katritzky and C. W. Rees), Vol. 3, Pergamon Press, Oxford 1984, p. 443.

B. Roth and C. Cheng, Diaminopyrimidines, in Progress in Medicinal Chemistry (Eds. G. B. Ellis and G. E. West), Vol. 19, Elsevier Biomedical Press, New York 1982, p. 267.

M. S. A. E.-A. El-Gaby, S. G. Abdel-Hamide, M. M. Ghorab and S. M. El-Sayed, Synthesis and anticancer activity in vitro of some new pyrimidines, Acta Pharm.49 (1999) 149-158.

C. R. Petrie, H. B. Cottam, P. A. Mckernan, R. K. Robins and G. R. Revankar, Synthesis and biological activity of 6-azacadeguomycin and certain 2,4,6-trisubstituted pyrazolo[3,4-d]-pyrimidine ribonucleosides, J. Med. Chem.28 (1985) 1010-1016.

M. N. Nasr and M. M. Gineinah, Pyrido[2,3-d]pyrimidines and pyrimido[5',4':5,6]-pyrido[2,3-d] pyrimidines as new antiviral agents: Synthesis and biological activity, Arch. Pharm.335 (2002) 289-295; DOI: 10.1002/1521-4184(200208)335:6 289.

P. G. Baraldi, M. G. Pavani, M. Nunez, P. Brigidi, B. Vitali, R. Gambari and R. Romagnoli, Antimicrobial and antitumor activity of N-heteroimine-1,2,3-diathiazoles and their transformation in triazolo-, imidazo- and pyrazolopyrimidines, Bioorg. Med. Chem.10 (2002) 449-456; DOI: 10.1016/S0968-0896(01)00294-2.

S. M. Sondhi, M. Johar, S. Rajvanshi, S. G. Dastidar, R. Shukla, R. Raghubir and J. W. Lown, Anticancer, anti-inflammatory and analgesic activity evaluation of heterocyclic compounds synthesized by the reaction of 4-isothiocyanato-4-methylpentan-2-one with substituted o-phenylenediamines, o-diaminopyridine and (un)substituted o-diamino-pyrimidines, Australian J. Chem.54 (2001) 69-74; DOI: 10.1071/CH00141.

A. Z. M. S. Chowdhury, M. M. Matin and M. N. Anwar, Synthesis and antimicrobial activities of fused pyrimidines: Benzothieno[2,3-d]imidazol[1,2-c]pyrimidine, Chittagong Univ. Stud. Part II21 (1997) 79-83; ref Chem. Abstr.130 (1999) 237530p.

A. M. Abdel-Fattah, A. S. Aly, F. A. Gad, M. E. A. Zaki and A. B. A. El-Gazzar, A facile synthesis of isooxazolo[5,4:4',5']thiazolo[3,2-a]thienopyrimidines, a new ring system, Phosphorus Sulfur141 (1998) 263-281; DOI: 10.1080/10426509808033738.

A. M. Abdel-Fattah, A. S. Aly, F. A. Gad, N. A. Hassan and A. B. A. El-Gazzar, Synthesis and reaction of polynuclear heterocycles, with a new ring system, Phosphorus Sulfur163 (2000) 1-27; DOI: 10.1080/10426500008046607.

A. K. Gewald, E. Schinke and H. Bottcher, 2-Amino-thiophene aus methylenaktiven Nitrilen, Carbonylverbindungen und Schwefel, Chem. Ber.99 (1966) 94-100.

P. Wolkoff, T. S. Nemeth and S. M. Gibson, Reaction of hydrazonyl halides with derivatives of thiourea and thiosemicarbazide; A new source of C-amino- and C-hydrazino-1,2,4-triazoles, Can. J. Chem.53 (1975) 3211-3215.

A. F. Hegarty, M. Cashoman, J. B. Aylward and F. L. Scott, Ortho-group participation in azocarbonium ion and 1,3-dipolar ion formation, J. Chem. Soc. B57 (1971) 1879-1883.

Guide to the Care and Use of Experimental Animals, Vol. 1, 2nd ed. (Eds. E. D. Olfert, B. M. Cross and A. A. McWilliam), Canadian Council of Animal Care, Ottawa 1993.

C. A. Winter, E. A. Risley and G. W. Nuss, Carrageenin-induced edema in hind paw of the rats as an assay anti-inflammatory drugs, Proc. Soc. Exp. Biol. Med.III (1962) 544-547.

J. Miño, V. Moscatelli, O. Hnatyszyn, S. Gorzalczany, C. Acevedo and G. Ferraro, J. Pharmacol. Res.50 (2004) 59-63; DOI: 10.1016/j.phrs.2003.12.016.

H. D. J. Collier, L. C. Dinnin, C. A. Johnson and C. Schneider., The abdominal response and its suppression by analgestic drugs in the mouse Br. J. Pharmacol. Chemother.32 (1968) 295-310.

R. K. Goel, A. Chakrabarthi and A. K. Sanyal, Planta Med.29 (1985) 85-88.

H. Shay, S. A. Komarav, S. E. Fels, D. Meraza, M. Gruenstein and H. Siplet, Gastroenterology5 (1994) 43-61.

A. K. Ganguly and O. P. Bhatnagar, Can. J. Physiol. Pharmacol.51 (1973) 748-750.

A. M. Abdel-Fattah, A. S. Aly, F. Abdel-Motti, N. A. Hassan and H. A. Aly, Synthesis and reaction of some thienopyrimidine derivatives and some of photooxidation, Egyptian J. Chem.38 (1995) 627-633.

A. S. Aly, A. B. A. El-Gazzar and H. A. R. Hussien, Synthesis and reactions of polynuclear heterocycles: Azolothienopyrimidines and thienothiazolopyrimidines, Phosphorus Sulfur181 (2006) 2771-2784; DOI: 10.1080/10426500600865293.

A. B. A. El-Gazzar, H. A. R. Hussien and A. S. Aly, Synthesis of some derivatives derived from 1,2,3,4-tetrahydrocyclo-hepteno[4,5]thieno[2,3-d]pyrimidine, Phosphorus Sulfur182 (2007) 35-56; DOI: 10.1080/10426500600864536.

B. Cacciari and G. Spalluto, Facile and versatile route to the synthesis of fused 2-pyridones: Useful intermediates for polycyclic systems, Synthetic Commun.36 (2006) 1177-1183; DOI: 10.1080/00397910500514063.

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