The present invention relates to novel anthracycline compounds and further to the use of the novel anthracycline compounds, that is, the use thereof as antitumor agents.
Daunomycin (U.S. Pat. No. 3,616,242) and adriamycin (U.S. Pat. No. 3,590,028) are known as anthracycline type compounds. These compounds are extensively used in clinical stages. However, they are known to have serious side effects such as cardiotoxicity, impairment of bone marrow and the like, and thus their uses remain only unsatisfactory.
On the other hand, preparation of novel and miscellaneous analogous compounds by methods including fermentation, semi-synthesis, microbial transformation and the like have been attempted, and there have already been reported several compounds such as 4'-epiadriamycin (Japan Science Society Press, Tokyo/University Park Press, Baltimore, 292-312, 1978), 4-demethoxyadriamycin (Cancer Treat. Rep., 60: 829, 1976), and THP-adriamycin (J. Antibiotics 32: 1082, 1979).
For the purpose of providing a useful anthracycline derivative, we have also proposed morpholino derivatives of 13-deoxocarminomycin, 13-deoxo-10-hydroxycarminomycin and 13-deoxo-11-deoxycarminomycin (referred to hereinafter as R20 substances) represented by the formula (I) (Japanese Patent Application Laid-Open Nos. 167696/86 and 16495/87): ##STR3## (1) 13-deoxocarminomycin (referred to hereinafter as R20X), R.sup.a : OH, R.sup.b : H,
(2) 13-deoxo-10-hydroxycarminomycin (referred to hereinafter as R20X2), R.sup.a : OH, R.sup.b : OH, and PA0 (3) 13-deoxo-11-deoxycarminomycin (referred to hereinafter as R20Y5), R.sup.a : H, R.sup.b : H. PA0 1. N-trifluoroacetyl-13-deoxocarminomycin, PA0 2. N-carboxymethoxyacetyl-13-deoxocarminomycin, PA0 3. N-ethyl-13-deoxocarminomycin, PA0 4. N,N-diethyl-13-deoxocarminomycin, PA0 5. N-benzyl-13-deoxocarminomycin, PA0 6. N-allyl-13-deoxocarminomycin, PA0 7. N,N-diallyl-13-deoxocarminomycin, PA0 8. N-(2"-hydroxypropyl)-13-deoxocarminomycin, PA0 9. N-[(2"S)-2",3"-dihydroxypropyl]-13-deoxocarminomycin, PA0 10. N-[(2"R)-2",3"-dihydroxypropyl]-13-deoxocarminomycin, PA0 11. N-(1"-hydroxy-2"-propyl)-13-deoxocarminomycin, PA0 12. A, B N-(1",1"-dimethoxy-2"-propyl)-13-deoxocarminomycin, PA0 13. N-carboxymethyl-13-deoxocarminomycin, PA0 14. N-cyclopentyl-13-deoxocarminomycin, PA0 15. N-(4"-tetrahydropyranyl)-13-deoxocarminomycin, PA0 16. N-(4"-piperidinyl)-13-deoxocarminomycin, PA0 17. N-(1"-trifluoroacetyl-4"-piperidinyl)-13-deoxocarminomycin, PA0 18. N-(1"-trifluoroacetyl-4"-piperidinyl)-13-deoxo-10-hydroxycarminomycin, PA0 19. N-(2",3"-diethylidenedioxypropyl)-13-deoxocarminomycin, PA0 20. N-(2",3"-dipropylidenedioxypropyl)-13-deoxocarminomycin, PA0 21. N-(2",3"-cyclopentylidenedioxypropyl)-13-deoxocarminomycin, PA0 22. N-(2",3"-cycloheptylidenedioxypropyl)-13-deoxocarminomycin, PA0 23. 3'-deamino-3'-(1"-piperidino)-13-deoxocarminomycin, PA0 24. 3'-deamino-3'-(1"-acetyl-4"-piperazinyl)-13-deoxocarminomycin, PA0 25. 3'-deamino-3'-(1"-acetyl-4"-piperazinyl)-13-deoxo-10-hydroxycarminomycin, PA0 26. 3'-deamino-3'-[(2"R)-2"-acetamido-4"-morpholino]-13-deoxocarminomycin, PA0 27. 3'-deamino-3'-[(2"R)-2"-acetamido-4"-morpholino]-13-deoxo-10-hydroxycarmin omycin, PA0 28. A, B 3'-deamino-3'-(6"-hydroxy-2"-methoxy-4"-perhydroxazepinyl)-13-deoxocarmino mycin, PA0 29. A, B 4'-O-tetrahydropyranyl-13-deoxocarminomycin, PA0 30. A, B 3'-deamino-3'-(4"-morpholino)-4'-O-tetrahydropyranyl-13-deoxocarminomycin, PA0 31. N-[18"-(18"-deoxojosamycinyl)]-13-deoxocarminomycin, PA0 32. 3'-deamino-3'-(4"-morpholino)-13-deoxo-10-oxocarminomycin,