Abstract
Reaction of 6-chloro-9-benzyl-8-(methylthio)purine3 with primary amines afforded, the corresponding 6-(substitutedamino)purines4a-g. The latter products when methylated with methyl iodide yielded smoothly N3-methyl purinium iodide salts5a-f rather than the probable N1-and N7-derivatives. 9-Benzyl-3-methyl-6-(methylimino)-8-(methylthio)purine8 was obtained upon treating the purinium iodide5a with alkali. Most of the synthesized compounds were screened for their antitumor activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References Cited
Bharat, T. and Brumo, R., N6-Disubstituted adenosines: Synthesis and structure-activity relationships.J. Med. Chem., 32(8), 1667–1673 (1989).
Dutta, S. P., Tritsch, G. L., Cox, C. and Chheda, G. B., Synthesis and biological activities of some N6-(nitro-and amino-benzyl)adenosines.J. Med. Chem., 18 (8), 780–783 (1975).
El-Bayouki, Kh. A. M., Hammad, M., Osman, S. and Basyouni, W. M., Synthesis and quaternization of 5-amino-1-arylimidazole-4-carboxamides and their related imidazo-pyrazines.Oriental J. Chem., 2 45–50 (1986).
El-Bayouki, Kh. A. M., El-Sayed, A. S. and Basyouni, W. M., Ethyl chloroformate/DMF in organic synthesis (I): A novel reagent for ring closure of 5-amino-1-aryl-4-imidazole carboxamides to their hypoxanthine derivatives.Gazzetta Chimica Italiana, 119, 163–165 (1989).
El-Bayouki, Kh. A. M., Basyouni, W. M. and El-Sayed, M. M., Molluscicidal activity of newly synthesised triazolo- and tetrazolothiazolopyrimidines and related derivatives.Egypt. J. Bilharziasis, 12, 45–58 (1990).
El-Merzabani, M. M., El-Aaser, A. A., Attia, M. A., El-Duweini, A. K. and Ghazal, A. M., Screening system for Egyptien plants with potential antitumor activity.J. Med. Plant. Res. (Planta Medica), 36, 150–155 (1979).
Fleysher, M. M., Bloch, A., Hakala, M. T. and Nicol, C. A., Synthesis and biological activity of some new N6-substituted purine nucleosides.J. Med. Chem., 12, 1056–1061 (1969).
Johannsen, F., Jargensen, A., El-Bayouki, Kh. A. M. and Pedersen, E., Phosphorus pentaoxide in organic organic synthesis XXVI: Preparation and alkylation of furo(2,3-d) pyrimidin-4-amines.Chemica Scripta, 26, 337–342 (1986).
Kelly, J. L. and Soroka, F. E., 9-(2-Fluorobenzyl)-6-(methylamino)-9H-purine hydrochloride: Synthesis and anticonvulsant activity.J. Med. Chem., 29, 1133–1134 (1986).
Kiyoto, I., Hajime, K. and Kiyoshi, I., 7-Hydroxyguanine compounds and their use as antitumor agents.European Patent Applied EP, 204,251 (1985);C.A. 106. 156161 (1987).
Kozalka, G., Krentsky, T., Rideout, J. and Burns, C., Preparation of 9-β-2′-3′-dideoxyribofuranosylpurines for treatment and prophylaxix of human immunodeficiency virus infection.European Patent, EP 286,425 (1987);C.A., 111, 23910 (1989).
Marsico, J. and Goldman, L., Site of alkylation of N6,N6-di-alkyl-9-substituted adenosines: Synthesis and alkaline degradation of 6-diethylamino-3,9-dimethylpurinium iodide.J. Org. Chem., 30, 3597–3600 (1965).
McGee, D. P. C., Martin, J. C., Smee, D. F., Matthews, T. R. and Verheyden, J. P. H., Synthesis and antiherbes simplex virus activity of 9-[(1,3-dihydroxy-2-propylthio)methyl]guanine.J. Med. Chem., 28(9), 1242–1245 (1985).
McLimans, W. F., Davis, E. V., Golve, F. I. and Rake, G. W., The submerged culture of mammalien cells: The spinner culture.J. Immunol., 79, 428–433 (1957).
Moharram, H. and Osman, A., Reactions of purine derivatives with phosphorus pentaoxide and triethylamine and their antitumor effects.Arch. Pharm. Res., 12(1), 1–4 (1989).
Neiman, Z. and Bergman, F., Benzylation of 6-alkylthiopurines in aprotic solvents.Isracel J. Chem., 5, 243–245 (1967).
Saito, T., Inous, I. and Fuji, T., Purines XLI: An alemative synthesis and the chemical behaviour of 7,9-dialkyladeninium salts.Chem. Pharm. Bull., 38(6), 1536–1547 (1990).
Sen, A. and Sibbos, R., Synthesis of compounds related to 4(5)-aminoimidazole-5(4)-carboxamides: Part II.Ind. J. Chem., 14B, 222–225 (1976).
Shaw, E., A new synthesis of the purines adenine, hypoxanthine, xanthine and isoguanine.J. Biol. Chem.,185, 439–447 (1950).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
El-Bayouki, K.A.M., Basyouni, W.M., El-Din, S.M. et al. Synthesis and quartermization of 6-(substitutedamino)-purines with antitumor activity screening. Arch. Pharm. Res. 17, 60–65 (1994). https://doi.org/10.1007/BF02974224
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02974224