Synthesis and biological effects of some 5-heterocyclicmethyl-2′-deoxyuridines
Tóm tắt
The synthesis of 5-heterocyclicmethyl-2′-deoxyuridines (4a-f) has been accomplished by displacement reaction of 5-(bromomethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine with heterocyclic compounds, followed by removal of acetyl protecting group with methanolic ammonia. The compounds synthesized were evaluated the inhibitory effects on L1210 cell proliferation and antiviral activities against Herpes simplex virus type 1 (HSV-1). None of the compounds exhibited sufficient biological activities.
Tài liệu tham khảo
De Clereq, E.: Pyrimidine nucleoside analogues as antiviral agents. In targets for the design of Antiviral Agents, De Clercq, E. and Walker, R.T., Eds., Plenum Publishing Corp., New York, p. 203 (1984).
Balzarini, J., De Clercq, E., Mertes, M.P., Shugar, D. and Torrence, P.F.: 5-substituted 2′-deoxyuridines: Correlation between inhibition of Tumor cell growth and inhibition of Thymidine kinase and Thymidylate synthetase.Biochem. Pharm. 31, 3673 (1982).
Shiau, G.T., Schinazi, R.F., Chen, M.S. and Prusoff, W.H.: Synthesis and biological Activities of 5-(hydroxymethyl, azidomethyl, or aminomethyl)-2′-deoxyuridine and related 5′-substituted Analogues.J. Med. Chem. 23, 127 (1980).
Bärwolff, D. and Langen, P.:Nucleic Acid Chemistry, L.B. Townsend and R.S. Tipson Eds., John Wliey and Sons, New York, p. 359 (1979).
Kampf, A., Pillar, C.J., Woodford, W.J. and Mertes, M.P.: Synthesis of 5-substituted 2′-deoxyuridines.J. Med. Chem. 19, 909 (1976).
Edelman, M.S., Barfknecht, R.L., Huet-Rose, R., Boguslawski, S. and Mertes, M.P.: Thymidylate Synthetase Inhibitors. Synthesis of N-substituted 5-amino-methyl-2′-deoxyuridine 5′-phosphate,J. Med. Chem. 20, 669 (1977).
Park, J.S., Cheng, C.T.-C. and Mertes, M.P.: 5-[(4-methyl-1,2,3,4-tetrahydroquinoxalyl) methyl]-2′-deoxyuridine 5′-phosphate: An analogue of a proposed intermediate in Thymidylate synthetase Catalysis.J. Med. Chem. 22, 1134 (1979).
Srinivasan, A., Amarnath, V., Broom, A.D., Zou, F.C. and Cheng, T.-C.: A potent Multisubstrate Analogue Inhibitor of Human Thymidylate Synthetase.J. Med. Chem. 27, 1710 (1984).
Wilson, R.S. and Mertes, M.P.: A Chemical Model for Thymidylate Synthetase Catalysis.Biochem.12, 2879 (1973).
Beltz, R.E. and Visser, D.W.: Growth Inhibition ofEscherichia coli by New Thymidine Analogs.J. Am. Chem. Soc. 77, 736 (1955).
Hiremath, S.P. and Hosmane, R.S.: Applications of Nuclear Magnetic Resonance Spectroscopy to Heterocyclic Chemistry: Indole and Its Derivatives. InAdvances in Heterocyclic Heterocyclic Chemistry, Katritzky, A.R. and Boulton, A.J. Eds.,11, 383 (1970).
Alan Jones, R.: Physicochemical properties ofPyrroles. In Advances in Heterocyclic Chemistry, Katritzky, A.R. and Boulton, A.J. Eds.,5, 277 (1973).