Bulletin of the Korean Chemical Society

  • 제18권7호
  • /
  • Pages.711-714
  • /
  • 1997
  • /
  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
권호 표지
DOI QR코드

DOI QR Code

Synthesis and Antitumor Activity of 2',3'-Didehydro-3'-Didehydro-3'-deoxy-thymidine and Its Derivative

  • 발행 : 1997.07.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

In an effort to enhance the lipophilicities, thereby, the penetration into the cell membrane and to increase the antitumor activities of modified derivatives of 2',3'-didehydro-3'-deoxythymidine (d4T, 1), derivatives of 1 were designed and synthesized. Starting from thymidine, 1, 2',3'-didehydro-3'-deoxythymidine-5'-phosphate, disodium salt (d4T-p, 7), and two nicotinate esters of 1; 2',3'-didehydro-3'-deoxy-5'-O-(3-pyridinylcarbonyl)thymidine (d4T-NA, 5) and 2',3'-didehydro-3'-deoxy-5'-phosphoryl-O-(3-pyridinylcarbonyl)thymidine (d4T-p-NA, 8) were synthesized. The lipophilicities of the synthesized compounds were measured by P-values and antitumor activities of those were estimated against mouse leukemia P388, murine mammary carcinoma FM3A, and human histiocytic lymphoma U937 tumor cells in vitro. Although the lipophilicities of the nicotinate esters, 5 and 8 were increased 2.75- and 9.71-fold relative to that of 1 and 7, respectively, the synthesized compounds, 1, 5, 7, and 8 were found to be inactive against P388 and FM3A cells except weak antitumor activity against U937 cell.

키워드

참고문헌

  1. J. Med. Chem. v.30 Kim, C.;Marquez, V. E.;Mitsuya, H.;Driscoll, J. S.
  2. J. Med. Chem. v.32 Muzammil, M. M.;John, E.;Starrett, Jr.;John, C. M.
  3. Proc. Natl. Acad. Sci. U.S.A. v.74 Sanger, F.;Nicklen, S.;Coulson, A. R.
  4. J. Org. Chem. v.53 Hiroshi, S.;Yasuo, I.;Hideyuki, S.;Kenzo, Y.;Naohiko, Y.
  5. Tetrahedron Lett v.29 Farina, V.;Benigni, D. A.
  6. J. Am. Chem. Soc. v.108 Saito, I.;Ikehara, H.;Kasatani, R.;Watanabe, M.;Matsuura, T.
  7. J. Org. Chem. v.31 Horwitz, J.;Chua, J.;Da Rooge, M. A.;Novel, M.;Klundt, I. L.
  8. Tetrahedron Lett v.50 Yoshikawa, M.;Kato, T.;Tanenishi, T.
  9. J. Med. Chem. v.16 Hong, C. I.;Chheda, G. B.
  10. J. Med. Chem. v.22 no.11 Hong, C. I.;Nechaev, A.;West, C. R.
  11. J. Med. Chem. v.23 Hong, C. I.;Nechaev, A.;Kiristis, A. J.;Buchheit, D. J.;West, C. R.
  12. J. Biol. Chem. v.262 Zimmerman, T. P.;Mahony, W. B.;Prus, K. L.
  13. J. Med. Chem. v.33 Palomino, E.;Meltsner, B. R.;Kessel, D.;Morwitz, J. P.
  14. Immunol. Method v.65 Mosmann, T.
  15. Microscale Organic Laboratory Mayo, D. W.;Pike, R. M.;Butcher, S. S.
  16. J. Biol. Chem. v.243 Kessel, D.
  17. Purification of Laboratory Chemicals(3rd Ed) Perrin, D. D.;Armarego, W. L. F.
  18. Introduction to Chromatography Bobbitt, J. M.;Schqarting, A. E.;Gritter, R. J.
  19. J. Med. Chem. v.33 Chu, C. K.;Bhadti, V. S.;Doshi, K. J.;Etse, J. T.;Gallo, J. M.;Boudinot, F. D.;Schinazi, R. F.