Synthesis of a new class of camptothecin derivatives, the long-chain fatty acid esters of 10-hydroxycamptothecin, as a potent prodrug candidate, and their in vitro metabolic conversion by carboxylesterases

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 5, 1998, Pages 415-418

  Takayama, Hiromitsu ^a   Watanabe, Akihito ^a   Hosokawa, Masakiyo ^a   Chiba, Kan ^a   Satoh, Tetsuo ^a   Aimi, Norio ^a  

^a CHIBA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; CAMPTOTHECIN; CAMPTOTHECIN DERIVATIVE; CARBOXYLESTERASE; FATTY ACID ESTER; IRINOTECAN; PRODRUG; TOPOTECAN;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG METABOLISM; DRUG SYNTHESIS; IN VITRO STUDY; LIVER MICROSOME; NONHUMAN;

ANIMALS; CAMPTOTHECIN; CARBOXYLIC ESTER HYDROLASES; ESTERS; FATTY ACIDS; HUMANS; PRODRUGS; RATS; SWINE;

EID: 0032478250     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00039-0     Document Type: Article

References (19)

1. 1. (a) Kingsburry, W. D.; Boehrn, J. C.; Jakas, D. R.; Holden, K. G.; Hecht, S. M., Gallagher, G., Caranfa, M J. McCabe, F. L.; Faucette, L. F.; Johnson, R. K.; Hertzberg, R. P. J. Med. Chem. 1991, 34, 98-107.
2. (b) Creemers, G. J., Gerrits, C. J. H.; Eckardt, J. R.; Schellens, J. H. M.; Burris, H. A.; Planting, A. S. T.; Rodriguez, G. I., Loos, W. J.; Hudson, I.; Broom, C.; Verweij, J.; Von Hoff, D. D. J. Clin. OncoL 1997, 75, 1087-1093. See also
3. 2. (a) Sawada, S.; Matsuoka, S.; Nokata, K.; Nagata, H.; Furuta, T.; Yokokura, T.; Miyasaka, T. Chem. Pharm.Bull. 1991, 39, 3183-3188.
4. (b) Shirao, K.; Shimada, Y.; Kondo, H.; Saito, D.; Yamao, T.; Ono, H.; Yokoyama, T.; Fukuda, H.; Oka, M.; Watanabe, Y.; Ohtsu, A.; Boku, N.; Fujii, T.; Oda, Y.; Muro, K.; Yoshida, S. J. Clin. Oncol. 1997, 15, 921-927. See also
5. Drugs Fut. 1995, 20, 307-310 and references cited therein.
6. 3.(a) Satoh, T.; Hosokawa, M.; Atsumi, R.; Suzuki, W.; Hakusui, H.; Nagai, E. Biol. Pharm. Bull. 1994, 17, 662-664.
7. (b) Laurent, P.R.; Bowles, M.R.; Robert, J.; Pond, S.M; Biochem. Pharmacol. 1996, 52, 1103-1111.
8. (c) Slatter, J.G.; Su, P.; Sams, J.P.; Schaaf, L.J.; Wienkers, C. Drug Metab. Dispos. 1997, 25, 1157-1164.
9. (d) Satoh, T.; Hosokawa, M. Ann. Rev. Pharmacol. Toxicol. 1998, vol 39, in press.
10. 4. (a) Rao Vishnuvajjala, B.; Garzon-Aburbeh, A. Water Soluble Prodrugs of Camptothecin. U.S. Patent 4, 943, 579, 1990.
11. (b) Wall, M. E.; Wani, M. C.; Nicholas, A. W.; Manikumar, G.; Tele, C.; Moore, L.; Truesdale A.; Leitner, P. and Besterman, J. M. Plant Antitumor Agents. 30. Synthesis and Structure Activity of Novel Camptothecin Analogs. J. Med. Chem. 1993, 36, 2689-2700.
12. (c) Greenwald, R. B.; Pendri, A.; Conover, C.; Gilbert, C.; Yang, R.; Xia, J. J. Med. Chem. 1996, 39, 1938-1940.
13. 5. (a) Kitajima, M.; Masumoto, S.; Takayama, H.; Aimi, N. Tetrahedron Lett. 1997, 38, 4255-4258.
14. (b) Kitajima, M.; Nakamura, M.; Takayama, H.; Saito, K.; Stöckigt, J.; Aimi, N. Tetrahedron Lett. 1997, 38, 8997-9000.
15. 6. Burke, T. G. and Mi, Z. J. Med. Chem. 1993, 36, 2580-2582.
16. 7. Mason, F. A. J. Chem. Soc. 1925, 1195-1199.
17. 8. (a) Ejima, A.; Terasawa, H.; Sugimori, M.; Tagawa, H. Tetrahedron Lett. 1989, 30, 2639-2640.
18. (b) Ejima, A.; Terasawa, H.; Sugimori, M.; Tagawa, H. J. Chem. Soc. Perkin Trans, 1 1990, 27-31.
19. 3) δ: 8.33 (1H, s), 8.24 (1H, d, J=9.2 Hz), 7.68 (1H, d, J=2.6 Hz), 7.66 (1H, s), 7.57 (1H, dd, J=9.1 and 2.6 Hz), 5.75, 5.31 (2H, ABq, J=16.2 Hz), 5.30 (2H, s), 3.74 (1H, br), 2.65 (2H, t, J=7.5 Hz), 1.96-1.84 (2H, m), 1.81 (2H, quint, J=7.4 Hz), 1.46-1.26 (32H, m), 1.05 (3H, t, J=7.5 Hz), 0.88 (3H, t, J=7.0 Hz).