Claims
- 1. A daunorubicin derivative of the formula ##STR8## wherein R.sub.1 represents a group of the formula ##STR9## in which (i) X.sub.1 and X.sub.2 both represent oxygen or both represent sulphur and the symbols R.sub.3 each represent alkyl of 1 through 4 carbon atoms, phenyl or phenyl-substituted in the para-position by methyl, methoxy or methylthio, or together form an alkylene radical of 2 through 4 carbon atoms, or (ii) one of X.sub.1 and X.sub.2 represents oxygen and the other represents sulphur and the symbols R.sub.3 together form an alkylene radical of 2 through 4 carbon atoms, and R.sub.4 represents hydrogen, alkyl of 1 through 4 carbon atoms or phenyl, and R.sub.2 represents hydrogen or trifluoroacetyl, or a non-toxic pharmaceutically acceptable acid addition salt of said derivative in which R.sub.2 represents hydrogen.
- 2. A daunorubicin derivative according to claim 1 wherein X.sub.1 and X.sub.2 both represent oxygen atoms or both represent sulphur atoms and the symbols R.sub.3 each represent alkyl of 1 through 4 carbon atoms, phenyl or--when X.sub.1 and X.sub.2 represent sulphur--together form an alkylene radical of 2 through 4 carbon atoms, and R.sub.4 represents hydrogen or a non-toxic pharmaceutically acceptable acid addition salt of said derivative in which R.sub.2 represents hydrogen.
- 3. A daunorubicin derivative according to claim 1 wherein X.sub.1 and X.sub.2 both represent oxygen or both represent sulphur and the symbols R.sub.3 each represent alkyl of 1 through 4 carbon atoms, phenyl or phenyl-substituted in the para-position by methoxy, or together form an alkylene radical of 2 or 3 carbon atoms, or one of the symbols X.sub.1 and X.sub.2 represents oxygen and the other represents sulphur and the symbols R.sub.3 together form an alkylene radical of 2 or 3 carbon atoms, and R.sub.4 represents hydrogen, methyl or phenyl, and non-toxic pharmaceutically acceptable acid addition salt of said derivative in which R.sub.2 represents hydrogen.
- 4. A daunorubicin derivative according to claim 1 wherein X.sub.1 and X.sub.2 both represent oxygen or both represent sulphur and the symbols R.sub.3 each represent alkyl of 1 through 4 carbon atoms, or phenyl or p-methoxyphenyl, or together form an alkylene radical of 2 or 3 carbon atoms, or one of X.sub.1 and X.sub.2 represents oxygen and the other represents sulphur and the symbols R.sub.3 together form an alkylene radical of 2 or 3 carbon atoms, R.sub.4 represents hydrogen, and R.sub.2 represents hydrogen, or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 5. A daunorubicin derivative according to claim 1 wherein X.sub.1 and X.sub.2 both represent oxygen or both represent sulphur and the symbols R.sub.3 each represent alkyl of 1 through 4 carbon atoms, phenyl or phenyl-substituted in the para-position by methyl, methoxy, or methylthio or together form an alkylene radical of 2 or 3 carbon atoms, or one of the symbols X.sub.1 and X.sub.2 represents oxygen and the other represents sulphur and the symbols R.sub.3 together form an alkylene radical of 2 or 3 carbon atoms, and R.sub.4 represents hydrogen, methyl or phenyl, or a nontoxic pharmaceutically acceptable acid addition salt of said derivative in which R.sub.2 represents hydrogen.
- 6. A daunorubicin derivative according to claim 1 wherein X.sub.1 and X.sub.2 both represent oxygen or both represent sulphur and the symbols R.sub.3 each represent alkyl of 1 through 4 carbon atoms, or phenyl, p-methylphenyl, p-methoxyphenyl, or p-methylthiophenyl or together form an alkylene radical of 2 or 3 carbon atoms, or one of X.sub.1 and X.sub.2 represents oxygen and the other represents sulphur and the symbols R.sub.3 together form an alkylene radical of 2 or 3 carbon atoms, R.sub.4 represents hydrogen, and R.sub.2 represents hydrogen or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 7. The daunorubicin derivative according to claim 1 which is 14-(2,2-diethoxy-acetoxy)daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 8. The daunorubicin derivative according to claim 1 which is 14-(2,2-dibutoxy-acetoxy)daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 9. The daunorubicin derivative according to claim 1 which is 14-(2,2-diphenoxy-acetoxy)daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 10. The daunorubicin derivative according to claim 1 which is 14[2,2-bis(4-methoxyphenoxy)acetoxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 11. The daunorubicin derivative according to claim 1 which is 14-(2,2-diethylthio-acetoxy)daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 12. The daunorubicin derivative according to claim 1 which is 14-(2,2-diphenylthio-acetoxy)daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 13. The daunorubicin derivative according to claim 1 which is 14[(1,3-dioxolan-2-yl)carbonyloxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 14. The daunorubicin derivative according to claim 1 which is 14-[(1,3-dithiolan-2-yl)carbonyloxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 15. The daunorubicin derivative according to claim 1 which is 14-[(1,3-dithian-2-yl)carbonyloxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 16. The daunorubicin derivative according to claim 1 which is 14-[(1,3-oxathiolan-2-yl)carbonyloxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 17. The daunorubicin derivative according to claim 1 which is 14-[2,2-bis(4-methylphenoxy)acetoxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 18. The daunorubicin derivative according to claim 1 which is 14-[2,2-bis(4-methylthiophenoxy)acetoxy]daunorubicin or a non-toxic pharmaceutically acceptable acid addition salt thereof.
- 19. A pharmaceutical composition for parenteral administration which comprises a therapeutically effective amount of a daunorubicin derivative of the formula specified in claim 1 or a nontoxic pharmaceutically acceptable acid addition salt of a said derivative in which R.sub.2 represents hydrogen, in association with a sterile compatible injectable pharmaceutical carrier.
- 20. The pharmaceutical composition of claim 19 wherein said daunorubicin derivative is present in an amount from about 1 to about 5 mg/kg of body weight of the subject to whom said derivative is administered.
Priority Claims (3)
Number |
Date |
Country |
Kind |
75 34450 |
Nov 1975 |
FRX |
|
76 28977 |
Sep 1976 |
FRX |
|
76 28978 |
Sep 1976 |
FRX |
|
Parent Case Info
This application is a continuation-in-part of copending application Ser. No. 740,769, filed Nov. 10, 1976, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4031211 |
Patelli et al. |
Jun 1977 |
|
Non-Patent Literature Citations (4)
Entry |
American Druggist, May 19, 1969, (Pharm. & Med. Science, pp. 33-34). _ |
Journ. Med. Chem., 1974, vol. 17, No. 3, pp. 335-337. _ |
Experientia 26, 4, pp. 389-390 (1970). _ |
Merck Index, 9th Edition, 1976, No. 3428. _ |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
740769 |
Nov 1976 |
|