3′-C-Branched 2′-Deoxy-5-methyluridines: Synthesis, Enzyme Inhibition, and Antiviral Properties

Journal of Medicinal Chemistry

Volumn 35, Issue 24, 1992, Pages 4567-4575

  Fedorov, Ivan I ^a   Kazmina, Ema M ^a   Novicov, Nicolai A ^a   Gurskaya, Galina V ^b   Bochkarev, Alex V ^b   Jasko, Maxim V ^b   Victorova, Lyubov S ^b   Kukhanova, Marina K ^b   Krayevsky, Alexander A ^b   Balzarini, Jan ^c   De Clercq, Erik ^c  

^a I M SECHENOV FIRST MOSCOW STATE MEDICAL UNIVERSITY   (Russian Federation)

^b ENGELHARDT INSTITUTE OF MOLECULAR BIOLOGY   (Russian Federation)

^c REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

2' DEOXYNUCLEOSIDE; 2',3' DIDEOXY 3' METHYLIDENETHYMIDINE; 3' METHYLTHYMIDINE; 3' METHYLTHYMIDINE 5' PHOSPHITE; DEOXYURIDINE DERIVATIVE; DNA POLYMERASE; NUCLEOSIDE DERIVATIVE; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG; VIRUS ENZYME;

ANTIVIRAL ACTIVITY; ARTICLE; AUTORADIOGRAPHY; CARBON NUCLEAR MAGNETIC RESONANCE; CIRCULAR DICHROISM; COMPETITIVE INHIBITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA SYNTHESIS; DRUG CONFORMATION; DRUG SYNTHESIS; ENZYME INHIBITION; GLYCOSYLATION; HUMAN; HUMAN CELL; METHYLATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANTIVIRAL AGENTS; BASE SEQUENCE; CHEMISTRY, PHYSICAL; CIRCULAR DICHROISM; CRYSTALLIZATION; DEOXYRIBOSE; DEOXYURIDINE; DNA-DIRECTED DNA POLYMERASE; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR CONFORMATION; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MYELOBLASTOSIS VIRUS, AVIAN; REVERSE TRANSCRIPTASE INHIBITORS; SPECTROPHOTOMETRY, ULTRAVIOLET; URIDINE; X-RAY DIFFRACTION;

EID: 0027075004     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00102a009     Document Type: Article

References (33)

1. De Clercq, E. New acquisitions in the development of anti-HIV agents. Antiviral Res. 1989,12, 1-20.
2. Michailov, S. N. Substrate properties of C′-methylnucleoside and C′-methyl-2′-deoxynucleoside 5′-triphosphates in RNA and DNA synthesis reactions catalysed by RNA and DNA polymerases. Nucleosides Nucleotides 1988, 5-6, 679-682.
3. Aivazashvilli, V. A.; Mikhailov, S. N.; Padiukova, N. Sh.; Karpeysky, M. Ja.; Beabealashvilli, R. Sh. Bioorg. Chem. (Moscow) 1986, 12, 708-710.
4. Webb, T. R. The direct conversion of 5′-0-trityl-3′-keto-2′-deoxythymidine to l-(2′-deoxy-3′-methyl)-/3-D-xylothymine. Tetrahedron Lett. 1988, 29, 3769-3772.
5. Kawana, M.; Takeuchi, K.; Ohba, T.; Kuzuchara, H. The deoxygenations of tosylated adenosine derivatives with Grignard reagents. Nucleic Acids Res. 1986, Symp. Series No. 17, 343-346.
6. Koole, L. H.; Moody, H. M.; Buck, H. M.; Grouiller, A.; Essadiq, H.; Vial, J.-M.; Chattopadhyaya, J. Synthesis and conformation of l-(3′-C-methyl-2′-deoxy-/S-D-xylofuranosyl)-uracil and 9-(3′-C-methyl-2′-deoxy-(S-D-xylofuranosyl)-adenine. Recl. Trav. Chim. Pays-Bas 1988, 107, 343-346.
7. Kawana, M.; Koresawa, T.; Kuzuhara, H. The use of Grignard reagents in carbohydrate synthesis. The synthesis of branched-chain deoxy sugars and their anomerizations. Bull. Chem. Soc. Jpn. 1983, 56, 1095-1100.
8. Mikhailov, S. N.; Fomichova, M. V. Unequivocal synthesis of 1-(3′-C-methyl-β-D-erythro-pentofuranosyl)uracil. Bioorg. Khim. 1990, 16, 699-707.
9. Vorbruggen, H. Methods of nucleoside synthesis. In Nucleoside Analogues. Chemistry, Biology and Medical Applications; Walker, R. T., De Clercq, E., Eckstein, F., Eds.; NATO Advanced Study Institute Series, Series A: Life Sciences; Plenum Press: New York, 1979; vol. 26, pp 35-69.
10. Hoffe, G.; Steglish, W.; Vorbruggen, H. Angew. Chem. 1978, 90, 602-615.
11. Rosenthal, A.; Mikhailov, S. N. Branched-chain nucleosides. Synthesis of 3′-C-ethyl (and 3′-C-butyl)uridine. Carbohydr. Res. 1980, 79, 224-235.
12. Matsuda, A.; Okajiama, H.; Ueda, T. Deoxygenation of the allyl alcohol system in 3′-deoxy-3′-methylidene-5-methyluridine derivatives. Nucleic Acids Res. 1988, Symp. Series No. 20,15-16.
13. Sharma, M.; Bobek, M. Synthesis of 2′,3′-dideoxy-3′-methylene pyrimidine nucleosides as potential anti-AIDS agents. Tetrahedron Lett. 1990, 31, 5839-5842.
14. Czemecky, S.; Ezzitouni, A.; Krausz, P. Synthesis of 3′-deoxy-2′,3′-didehydrothymidine, a potential anti-HIV agent. Synthesis 1990, 651-653.
15. Matsuda, A.; Okajima, H.; Ueda, T. Synthesis of 2′,3′-dideoxy-3′-methylidenethymidine and 2′,3′-didehydro-2′,3′-dideoxy-3′-M methylthymidine: deoxygenation of the allylic alcohol system in 3′-deoxy-3′-methylidene-5-methyluridine. Heterocycles 1989, 29, 25-38.
16. Kawaguchi, T.; Fukushima, S.; Ohmura, M.; Mishima, M.; Nakano, M. Enzymatic and chemical stability of 2′,3′-dideoxy-2′,3′-didehydropyrimidine nucleosides: potential anti-acquired immunodeficiency syndrome agents. Chem. Pharm. Bull. 1989, 37, 1944-1946.
17. Ludvig, I. A new route to nucleoside 5′-triphosphates. Acta Biochim. Biophys. Acad. Sci. Hung. 1981, 16, 131-133.
18. Dyatkina, N. B.; von Janta-Lipinsky, M.; Minassyan, Sh.; Kukhanova, M. K.; Krayevsky, A. A.; Chidgeavadze, Z. G.; Beabealashvilli, R. Sh. A new terminator of DNA biosynthesis supposedly modelling the conformational state of the substrate in the DNA synthesising complex. Bioorg. Khim. 1987,13,1366-1374.
19. Tarussova, N. B.; Khorlin, A. A.; Krayevsky, A. A.; Korneyeva, M. N.; Nosik, D. N.; Kruglov, N. V.; Galegov, G. A.; Beabealashvilli, R. Sh. Inhibition of HIV reproduction in cell culture by 5′-phosphonates of 3′-azido-2′,3/-dideoxynucleosides. Mol. Biol. 1989,23, 1716-1723.
20. Karamov, E. V.; Lukashov, V. V.; Tarussova, N. B.; Kornilayeva, G. V.; Rodova, M. A.; Kukhanova, M. K.; Krayevsky, A. A. Inhibition of human immunodeficiency virus production in cell culture by S′-phosphites of 3′-azido-2′,3′-dideoxynucleosides. Mol. Biol. 1990, 24, 1100-1108.
21. Bochkarev, A. V.; Gurskaya, G. V.; Zdanov, A. S.; Kazmina, E. M.; Fedorov, I.I. The molecular and crystal structure of l-(3′-C-methyl-2′-deoxy-β-D-ribofuranosyl)thymine. Bioorg. Khim. 1991,17, 1094-1100.
22. Young, B. V.; Tollin, P.; Wilson, H. R. The crystal and molecular structure of thymidine. Acta Crystallogr. 1969, B25, 1423-1431.
23. Gurskaya, G. V.; Javadova, G. M.; Mikhailov, S. N. X-ray crystallographic studies of nucleoside analogs. II. The crystal structure of l-(3′-C-methyl-β-D-ribofuranosyl)cytoeine. Crystallogr. Struct. Commun. 1982, 11, 1263-1258.
24. Balzarini, J.; Naesens, L.; Herdewijn, P.; Rosenberg, I.; Holy, A.; Pauwels, R.; Baba, M.; Johns, D. G.; De Clercq, E. 2′,3′-Didehydro-2′,3′-dideoxy-5-chlorocytidine is a selective antiretrovirus agent. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 332-336.
25. Ferrin, I. J.; Mildvan, A. S. Nuclear Overhauser effect studies of the conformations and binding site environments of deoxynucleoeide triphosphate substrates bound to DNA polymerase I and its large fragment. Biochemistry 1985, 24, 6904-6913.
26. Fenin, I. J.; Mildvan, A. S. Studies of conformations and interactions of substrates and ribonucleotide templates bound to the large fragment of DNA polymerase I. Biochemistry 1986, 25, 5131-5146.
27. Dyatkina, N.; Minassyan, Sh.; Kukhanova, M.; Krayevsky, A.; von Janta-Lipinsky, M.; Chidgeavadze, Z.; Beabealashvilli, E. Properties of 2′,3′-dideoxy-2′,3′-didehydrothymidine 5′-triphosphate in terminating DNA synthesis catalyzed by several different DNA polymerases. FEBS Lett. 1987, 219, 151-155.
28. Krayevsky, A.; Kukhanova, M. Physicochemical aspects of functioning of DNA polymerases. Sov. Sci. Rev. Physicochem. Biol. 1990, 9, 179-242.
29. Krayevsky, A. A.; Kukhanova, M. K.; Atrazhev, A. M.; Dyatkina, N. B.; Papchikhin, A. V.; Chidgeavadze, Z. G.; Beabealashvilli, E. Sh. Selective inhibitors of DNA chain elongation catalyzed by DNA polymerases. Nucleosides Nucleotides 1988, 7, 613-617.
30. Chidgeavadze, Z. G.; Beabealashvilli, R. Sh.; Krayevsky, A. A.; Kukhanova, M. K. Nucleoside 5′-triphosphates with modified sugars as substrates for DNA polymerases. Biochim. Biophys. Acta 1986, 868, 145-152.
31. Krayevsky, A.; Kukhanova, M.; Atrazev, A. M.; Chidgeavadze, Z. G.; Beabealashvilli, R. Sh. Substrate inhibitors for DNA biosynthesis. Mol. Biol. 1987, 21, 33-38.
32. Krayev, A. S. A starter complication of techniques for cloning into M13 and DNA sequencing with terminators. Mol. Biol. 1987, 21, 1164-1197.
33. Beabealashvilli, R. Sh.; Scamrov, A. V.; Kutateladze, T. V.; Mazo, A. M.; Krayevsky, A. A.; Kukhanova, M. K. Nucleoside 5′-triphosphates modified at sugar residues as substrates for calf thymus terminal deoxynucleotidyl transferase and for AMV reverse transcriptase. Biochim. Biophys. Acta 1986, 868, 136-144.