본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.33 no.6, 2010년, pp.797 - 805   SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Synthesis and Anti-Hepatitis B Activity of New Substituted Uracil and Thiouracil Glycosides

Abdel-Aal, Mohammed T.    (Chemistry Department, Faculty of Science, Menoufia University  );
  • 초록

    A number of N- and S-substituted uracil and thiouracil glycosides were synthesized by coupling reaction of 5,6-dibenzyle pyrimidine derivatives with the corresponding acetobromosugar. The synthesized compounds were tested for their antiviral activity against hepatitis B virus. Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds which showed moderate to high antiviral activities.


  • 주제어

    Pyrimidines .   Glycosides .   Thioglycosides .   Antiviral activity.  

  • 참고문헌 (52)

    1. Abbot, J., Goodgame, D. M. L., and Jeeves, I., Complexes of pyrimidine-2-thione with some bivalent metal halides of the first transition series. J. Chem. Soc. Dalton Trans. I, 880-884 (1978). 
    2. Abdel-Aal, M. T., El-Sayed, W. A., Abdel Al-Aleem, A. H., and El-Ashry, E. S. H., Synthesis of some functionalized arylaminomethyl-1,2,4-triazoles, 1,3,4-oxa- and thiadiazoles. Pharmazie, 58, 788-792 (2003). 
    3. Abdel-Aal, M. T., El-Sayed, W. A., and El-Ashry, E. S. H., Synthesis and antiviral evaluation of some sugar arylglycinoylhydrazones and their oxadiazoline derivatives. Arch. Pharm. (Weinheim), 339, 656-663 (2006). 
    4. Abdel-Aal, M. T., El-Sayed, W. A., El-Kosy, S. M., and El- Ashry, E. S. H., Synthesis and Antiviral Evaluation of Novel 5-(N-Aryl-aminomethyl-1,3,4-oxadiazol-2-yl)hydrazines and their Sugars, 1,2,4-triazoles, tetrazoles and pyrazolyl Derivatives. Arch. Pharm. (Weinheim), 341, 307-313 (2008). 
    5. Agarwal, A., Srivastava, K., Purib, S. K., and Chauhana, P. M. S., Synthesis of 2,4,6-trisubstituted pyrimidines as antimalarial agents. Bioorg. Med. Chem., 13, 4645-4650 (2005). 
    6. Atwal, K., Preparation of 2-amino dihydropyrimidin-5- carboxylates as cardiovascular agents. U.S. Patent, 4769371, Sept. 6, 1988. 
    7. Blanc-Muesser, M., Vigne, L., Driguez, H., Lehmann, J., Steck, J., and Urbahns, K., Spacer-modified disaccharide and pseudo-trisaccharide methyl glycosides that mimic maltotriose, as competitive inhibitors for pancreatic alphaamylase: a demonstration of the "clustering effect". Carbohydr. Res., 224, 59-71 (1992). 
    8. Brajeswar, P. and Walter, K., S-, N-, and O-glycosyl derivatives of 2-acetamido-2-deoxyglucose with hydrophobic aglycons as potential chemotherapeutic agents and Nacetyl- $\beta$-glucosaminidase inhibitors. Carbohydr. Res., 126, 27-43 (1984). 
    9. Capdeville, R., Buchdunger, E., Zimmermann, J., and Matter, A., Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discov, 1, 493-502 (2002). 
    10. Chang L. C. W., Spanjersberg R. F., Jvon Frijtag Drabbe Kunzel, K., Mulder-Krieger, T., van den Hout, G., Beukers, M. W.; Brussee, J., and IJzerman, A. P., 2,4,6-Trisubstituted Pyrimidines as a New Class of Selective Adenosine A1 Receptor Antagonists. J. Med. Chem., 47, 6529-6540 (2004). 
    11. Chu, M. Y. W., Naguib, F. N. M., Iltzsch, M. H., El Kouni, M. H., Chu, S. H., Cha, S., and Calabresi, P., Potentiation of 5-Fluoro-2'-deoxyuridine Antineoplastic Activity by the Uridine Phosphorylase Inhibitors Benzylacyclouridine and Benzyloxybenzylacyclouridine. Cancer Res., 44, 1852-1856 (1984). 
    12. Defaye, J. and Gelas, J., In Atta-ur-Rahman (Ed.). Studies in Natural Products Chemistry. Elsevier, Amsterdam, 8E, pp. 315-357, (1991). 
    13. Diana, G. D., Carabateas, P. M., Johnson, R. E., Williams, G. L., Pancic, F., and Collins, J. C., Antiviral Activity of Some 0-Diketones. 4. Benzyl Diketones. In Vitro Activity against Both RNA and DNA Viruses. J. Med. Chem., 21, 889-894 (1978). 
    14. Diana, G. D., Salvador, C. J., Zalay, E. S., Johnson, R. E., Collins, J. C., Johnson, D., Hinshaw, W. B., Lorenz, R. R., Thielking, W. H., and Pancic, F., Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem., 20, 750756 (1977). 
    15. Ding, J., Das, K., Moereels, H., Koyuans, L., Andries, K., Janssen, P. A. J., Hughes, S. H., and Arnold, E., Structure of HIV-1 RT/TIBO R 86183 in the binding of diverse nonnucleoside inhibitors. Nat. Struct. Biol., 2, 407-415 (1995). 
    16. El Ashry, E. S. H., Awad, L. F., and Atta, I. A., Synthesis and role of glycosylthio heterocycles in carbohydrate chemistry. Tetrahedron, 62, 2943-2998 (2006). 
    17. El Ashry, E. S. H., Awad, L. F., Abdel-Hamid, H., and Atta, I. A., Synthesis of interglycosidically S-linked 1-thio-oligosaccharides under microwave irradiation. J. Carbohydr. Chem., 24, 745-753 (2005). 
    18. El Ashry, E. S. H., Rashed, N., and Shobier, A. H., Glycosidase inhibitors and their chemotherapeutic value, Part1. Pharmazie, 55, 251-262 (2000a). 
    19. El Ashry, E. S. H., Rashed, N., and Shobier, A. H., Glycosidase inhibitors and their chemotherapeutic value, Part 2. Pharmazie, 55, 331-348 (2000b). 
    20. El Ashry, E. S. H., Rashed, N., Awad, L F., Ramadan, E., Abdel-Mageed, S. M., and Rezki, N., Novel Regioselective Hydroxyl-Alkylation of 4,5-Diphenylimidazole-2-Thione and A Competitive Intramolecular Ring Closure of the SHydroxyalkyl- Imidazoles to Imidazo[2,1-b]Thiazines and Thiazoles. Role of Catalyst, Microwave Irradiation, and Solid Support. Nucleosides Nucleotides Nucleic Acids, 26, 423-435 (2007a). 
    21. El-Brollosy, N. R., Jorgensen, P. T., Daha, B., Boel, A. M., Pederson, E. B., Nielsen, C., Synthesis of Novel N-1 (Allyloxymethyl) Analogues of 6-Benzyl-1-(ethoxymethyl)- 5-isopropyluracil (MKC-442, Emivirine) with Improved Activity Against HIV-1 and Its Mutants. J. Med. Chem., 45, 5721-5726 (2002). 
    22. El-Sayed, W. A., Fathi, N. M., Gad, W. A., and El-Ashry, E. S. H., Synthesis, and Antiviral Evaluation Of Some 5-NArylaminomethyl- 2-glycosylsulphanyl-1,3,4-oxadiazoles and their analogues against Hepatitis A and Herpes simplex viruses. J. Carbohydr. Chem., 27, 357-372 (2008). 
    23. El-Sayed, W. A., Rashad, A. E., Awad, S. M., and Ali, M. M., Synthesis and in vitro Antitumor Activity of Some New Substituted Thiopyrimidines Through Radical Balance Regulation. Nucleosides Nucleotides Nucleic Acids, 28, 261-274 (2009). 
    24. Fouad, T., Nielsen, C., Brunn, L., and Pederson, E. B., Use of standardization cell culture assay to assess activities of some potent anti-HIV nucleoside analogues against hepatitis B virus replication. Sc. J. Az. Med. Fac. (GIRLS), 19, 1173-1187 (1998). 
    25. Gadhachanda, V. R., Wu, B., Wang, Z., Kuhen, K. L., Caldwell, J., Zondler, H., Walter, H., Havenhand, M., and He, Y., 4- Aminopyrimidines as novel HIV-1 inhibitors. Bioorg. Med. Chem. Lett., 17, 260-265 (2007). 
    26. Hawthorne, M. F., Die Rolle der Chemie in der Entwicklung einer Krebstherapie durch die Bor-Neutroneneinfangreaktion. Angew. Chem. Weinheim Bergstr. Ger., 105, 997-1033 (1993). 
    27. Hegab, M. I., Hassan, N. A., Rashad, A. E., Fahmy, A. A., and Abdel-Megeid, F. M. E., Synthesis, Reactions, and Antimicrobial Activity of Some Fused Thieno[2,3-d]pyrimidine Derivatives. Phosphorus Sulfur Silicon Relat. Elem., 182, 1535-1556 (2007). 
    28. Holland, J. F., Guthrie, R., Sheeke, P., and Tieckelman, H., Inhibition of Tumor Growth in Mice by a Series of 2- Substituted Thiopyrimidines. Cancer Res., 18, 776-780 (1958). 
    29. Holy, A., Phosphonylmethyl Analogs of Nucleotides and Their Derivatives: Chemistry and Biology. Nucleosides Nucleotides Nucleic Acids, 6, 147-155 (1987). 
    30. Kelley, J. L., Linn, J. A., Davis, R. G., and Selway, J. W. T., 6-(3-Fluoroanilino)-9-(substituted-benzyl)-2-trifluoromethyl- 9H-purines with antirhinovirus activity. Eur. J. Med. Chem., 25, 623-628 (1990). 
    31. Kim, J., Kim, K., Lee, H. S., Park, K.-S., Park, S. Y., Kang, S.-Y., Lee, S. J., Park, H. S., Kim, D.-E., and Chong, Y., Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues. Bioorg. Med. Chem. Lett., 18, 4661-4665 (2008). 
    32. Korba, B. E. and Gerin, J. L., Use of a standardized cell culture assay to assess activities of nucleoside analogs against hepatitis B virus replication. Antiviral Res., 19, 55-70 (1992). 
    33. Kuhn, C. S., Lehmann, J., and Steck, J., Syntheses and properties of some photolabile $\beta$-thioglycosides. Potential photoaffinity reagents for $\beta$-glycoside hydrolases. Tetrahedron, 46, 3129-3134 (1990). 
    34. Larson, A., Alenius, S., Johnsson, N. G., and Oberg, B., Antiherpetic activity and mechanism of action of 9-(4-hydroxybutyl) guanine. Antiviral Res., 3, 77-86 (1983). 
    35. Lin, T. -S. and Liu, M. -C., Synthesis of 1-[[2-hydroxy-1-(hydroxymethyl) ethoxy]methyl]-5-benzyluracil and its amino analog new potent uridine phosphorylase inhibitors with high water solubility. J. Med. Chem., 28, 971-973 (1985). 
    36. Malik, V., Singh, P., and Kumar, S., Unique. Chlorine effect in regioselective one-pot synthesis of 1-alkyl-/allyl-3-(ochlorobenzyl) uracils: anti-HIV activity of selected uracil derivatives. Tetrahedron, 62, 5944-5951 (2006). 
    37. Matloobi, M. and Kappe, C. O., Microwave-Assisted Solutionand Solid-Phase Synthesis of 2-Amino-4-arylpyrimidine Derivatives. J. Comb. Chem., 9, 275-284 (2007). 
    38. Mereyala, H. B. and Gurijala, V. R., Use of 2-pyridyl-2-acetamido- 3,4,6-tri-O-acetyl-2-deoxy-1-thio-$\beta$-D-gluco-pyranoside as a glycosyl donor and methyl iodide as an activator for the synthesis of 1,2-trans-linked saccharides. Carbohydr. Res., 242, 277-280 (1993). 
    39. Niedzwicki, J. G., Chu, S. H., el koni, M. H., Row, E. C., and Cha, S., 5-Benzylacyclouridine and 5-benzyloxybenzylacyclouridine, potent inhibitors of uridine phosphorylase. Biochem. Pharmacol., 31, 1857-1861 (1982). 
    40. Nisho, M., Hirota, M., and Umerzawa, Y., The CH-p interactions; Wiley-VCH: New York, NY, (1988). 
    41. Nugent, R. A., Schlachter, S. T., Murphy, M. I., Cleek, G. J., Poel, T. J., Wishka, D. G., Graber, D. R., Yagi, Y., Kaiser, B. J., Olmsted, R. A., Kopta, L. A., Swaney, S. M., Poppe, S. M., Morris, J., Tarpley, W. G., and Thomas, R. C., Pyrimidine Thioethers: A Novel Class of HIV-1 Reverse Transcriptase Inhibitors with Activity Against BHAPResistant HIV. J. Med. Chem., 41, 3793-3803 (1998). 
    42. Ozeki, K., Ichikawa, T., Hiroyuki, T., Tanimury, K., Sato, M., and Yaginuna, H., Studies on Antiallergy Agents. III. Synthesis of 2-Anilino-1, 6-dihydro-6-oxo-5-pyrimidinecarboxylic Acids and Related Compounds. Chem. Pharm. Bull., 37, 1780-1787 (1989). 
    43. Park, K. S., El Kouni, M. H., Krenitsky, T. A., Chu, S. H., and Cha, S., Inhibition of uridine phosphorylase from Escherichia coli by benzylacyclouridines. Biochem. Pharmacol. 35, 3853-3855 (1986). 
    44. Pontikis, R., Benhida, R., Aubertin, A.-M., Grierson, D. S., and Monheret, C., Synthesis and Anti-HIV Activity of Novel N-1 Side Chain-Modified Analogs of 1-[(2-Hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT)C. J. Med. Chem., 40, 1845-1854 (1997). 
    45. Rashad, A. E., Hegab, M. I., Abdel-Megeid, R. E., Micky, J. A., and Abdel-Megeid, F. M. E., Synthesis and antiviral evaluation of some new pyrazole and fused pyrazolopyrimidine derivatives. Bioorg. Med. Chem., 16, 7102-7106 (2008). 
    46. Scheurer, P. G. and Smith, F., Synthesis of Acetobromo Sugars. J. Am. Chem. Soc., 76, 3224-3225 (1954). 
    47. Sells, M. A., Chen, M. L., and Acs, G., Production of hepatitis B virus particles in HepG2 cells transfected with cloned hepatitis B virus DNA. Proc. Natl. Acad. Sci. U.S.A., 84, 1005-1009 (1987). 
    48. Smerdon, S. J., Jager, J., Wang, J., Kohlstaedt, L. A., Chirino, A. J., Frieduan, J. M., Rice, P. A., and Steitz, T. A., Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U.S.A., 91, 3911-3915 (1994). 
    49. Spence, R. A., Kati,W. M., Anderson, K. S., and Johnson, K. A., Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science, 267, 988-993 (1995). 
    50. Zaki, M. E., Soliman, H. A., Hiekal, O. A., and Rashad, A. E., Pyrazolopyranopyrimidines as a Class of Anti-Inflammatory Agents. Z. Naturforsch. C, 61, 1-5 (2006). 
    51. El Ashry, E. S. H., Kassem, A. A., Abdel-Hamid, H., Louis, F. F., Khattab, Sh. A. N., and Aouad, M. R., Novel Regioselective Formation of S- and N-Hydroxyl-Alkyls of 5-(3- Chlorobenzo[b]Thien-2-yl)-3-Sulfanyl-4H-1,2,4-Triazole and A Facile Synthesis of Triazolo-Thiazoles and Thiazolo- Triazoles. Role of Catalyst and Microwave. Nucleosides Nucleotides Nucleic Acids, 26, 437-451 (2007b). 
    52. Tanaka, H., Takashima, H., Ubasawa, M., Sekiya, K., Inouye, N., Baba, M., Shigeta, S., Walker, R. T., De Clercq, E., and Miyasaka, T., Synthesis and Antiviral Activity of 6-Benzyl Analogs of 1-[(2-Hydroxyethoxy)methyl]-5- (phenylthio)thymine (HEPT) as Potent and Selective Anti- HIV-1 Agents. J. Med. Chem., 38, 2860-2865 (1995). 

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기