5-Fluorouracil derivatives, and their pharmaceutical compositions

• US 4,349,552 A
• Filed: 01/14/1980
• Issued: 09/14/1982
• Est. Priority Date: 10/30/1978
• Status: Expired due to Term

• Current Assignee: Fujisawa Pharmaceutical Co (Astellas Pharma Incorporated)
• Original Assignee: Fujisawa Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Inventors: Tozuka, Zenzaburo, Takaya, Takao
• Primary Examiner(s): RIZZO, NICHOLAS
• Application Number:
  US06/111,643
• Time in Patent Office: 974 Days
• Field of Search: 544/313, 544/311
• US Class Current: 514/274
• CPC Class Codes: C07C 265/00 Derivatives of isocyanic acid
• CPC Class Codes: C07D 239/553 with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
• CPC Class Codes: C07D 317/70 condensed with ring systems containing two or more relevant rings
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

A compound of the formula: ##STR1## wherein R is a bridged alicyclic group selected from the group consisting of norbornyl, norbornenyl, bicyclo[2,2,2]-heptyl and adamantyl optionally substituted by at least one substituent selected from the group consisting of lower alkyl, carboxy, lower alkoxycarbonyl, alkylidenedioxy, N,N-di(lower)alkylcarbamoyl, amino, loweralkoxycarbonylamino and halogen. The present compound is useful in the therapeutic treatment of cancer in human beings and animals.

Claims

1. A compound of the formula:

##STR8## wherein R is a bridged alicyclic group selected from the group consisting of norbornyl, norbornenyl, bicyclo[2,2,2]-octyl, bicyclo[2,2,2]-2-octenyl, bicyclo[3,1,1]-heptyl and adamantyl optionally substituted by at least one substituent selected from the group consisting of lower alkyl, carboxy, lower alkoxycarbonyl, alkylidenedioxy, N,N-di(lower)-alkylcarbamoyl, amino, lower alkoxycarbonylamino and halogen.

2. The compound of claim 1, wherein R is said unsubstituted bridged alicyclic group.

3. The compound of claim 2, wherein R is norbornyl.

4. The compound of claim 3, wherein R is 2-norbornyl.

5. The compound of claim 2, wherein R is adamantyl.

6. The compound of claim 5, wherein R is 1-adamantyl.

7. The compound of claim 1, wherein said bridged alicyclic group is substituted by at least one of said substituents.

8. The compound of claim 7, wherein R is carboxynorbornyl.

9. The compound of claim 8, wherein R is 3-carboxy-2-norbornyl.

10. The compound of claim 8, wherein R is (lower)alkoxycarbonylnorbornyl.

11. The compound of claim 10, wherein R is methoxycarbonylnorbornyl.

12. The compound of claim 11, wherein R is 3-methoxycarbonyl-2-norbornyl.

13. The compound of claim 10, wherein R is ethoxycarbonylnorbornyl.

14. The compound of claim 13, wherein R is 3-ethoxycarbonyl-2-norbornyl.

15. The compound of claim 10, wherein R is isopropoxycarbonylnorbornyl.

16. The compound of claim 15, wherein R is 3-isopropoxycarbonyl-2-norbornyl.

17. The compound of claim 10, wherein R is 3-tert-butoxycarbonyl-2-norbornyl.

18. The compound of claim 7, wherein R is norbornyl which is substituted by (lower) alkoxycarbonyl and alkylidenedioxy.

19. The compound of claim 18, wherein R is norbornyl substituted by ethoxycarbonyl and isopropylidenedioxy.

20. The compound of claim 19, wherein R is 3-ethoxycarbonyl-5,6-isopropylidenedioxy-2-norbornyl.

21. The compound of claim 7, wherein R is N,N-di(lower)alkylcarbamoylnorbornyl.

22. The compound of claim 21, wherein R is 3-(N,N-diisopropylcarbamoyl)-2-norbornyl.

23. The compound of claim 7, wherein R is aminonorbornyl.

24. The compound of claim 23, wherein R is 3-amino-2-norbornyl.

25. The compound of claim 7, wherein R is 3-(lower)alkoxycarbonylamino-2-norbornyl.

26. The compound of claim 7, wherein R is carboxynorbornenyl.

27. The compound of claim 26, wherein R is 3-carboxy-5-norbornen-2-yl.

28. The compound of claim 7, wherein R is (lower)alkoxycarbonylnorbornenyl.

29. The compound of claim 28, wherein R is 3-methoxycarbonyl-5-norbornen-2-yl.

30. The compound of claim 28, wherein R is 3-ethoxycarbonyl-5-norbornen-2-yl.

31. The compound of claim 28, wherein R is 3-isopropoxycarbonyl-5-norbornen-2-yl.

32. The compound of claim 28, wherein R is 3-tert-butoxycarbonyl-5-norbornen-2-yl.

33. The compound of claim 7, wherein R is bicyclo[3,1,1]heptyl substituted by at least one lower alkyl group.

34. The compound of claim 33, wherein R is pinanyl.

35. The compound of claim 34, wherein R is 3-pinanyl.

36. The compound of claim 7, wherein R is (lower)alkoxycarbonylbicyclo[2,2,2]-octyl.

37. The compound of the claim 36, wherein R is 3-ethoxycarbonylbicyclo[2,2,2]oct-2-yl.

38. A pharmaceutical composition for the therapeutic treatment of cancer in mammals, comprising:

a therapeutically effective amount of the compound of claim 1 in association with a pharmaceutically acceptable, substantially nontoxic carrier or excipient.

39. A method for treating cancer which comprises administering a compound of the claim 1 to mammals.