Derivatives of camptothecin and methods of treating cancer using these derivatives

• US 5,731,316 A
• Filed: 01/30/1996
• Issued: 03/24/1998
• Est. Priority Date: 01/30/1996
• Status: Expired due to Term

• Current Assignee: The Christus Stehlin Foundation for Cancer Research
• Original Assignee: The Stehlin Foundation For Cancer Research
• Inventors: Cao, Zhisong, Giovanella, Beppino C.
• Primary Examiner(s): Daus, Donald G.
• Application Number:
  US08/594,235
• Time in Patent Office: 784 Days
• Field of Search: 514/283, 514/279, 546/41, 546/48
• US Class Current: 514/283
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings

Abstract

Derivatives of camptothecin are disclosed and are represented by the general formula: ##STR1## wherein when R₂ is H, R₁ is a C₂ -C₁₅ alkyl group, a C₂ -C₁₅ alkenyl group or an epoxy group; and when R₂ is a nitro group, R₁ is a C₁ -C₁₅ alkyl group, a C₁ -C₁₅ alkenyl group or an epoxy group. Processes for making these derivatives and for using them in cancer treatment are also disclosed.

Claims

1. A compound of formula (I):

##STR7## wherein R₁ is a C₁ -C₁₅ alkyl group, a C₂ -C₁₅ alkenyl group or a C₂ -C₁₅ epoxidized alkenyl group and R₂ is NO₂.

2. A compound of claim 1, wherein R₁ is a linear C₁ -C₁₅ alkyl group.

3. A compound of claim 1, wherein R₁ is a linear C₂ -C₁₅ alkenyl group.

4. A compound of claim 1, wherein R₁ is a C₂ -C₁₅ epoxidized alkenyl group.

5. A compound of claim 1, wherein R₁ is methyl.

6. A compound of claim 1, wherein R₁ is propyl.

7. A compound of claim 1, wherein R₁ is a C₃ alkyl group.

8. A compound of claim 1, wherein R₁ is a C₄ alkyl group.

9. A compound of claim 1, wherein R₁ is ethyl.

10. A method for treating a malignant tumor in a patient comprising administering a composition comprising an effective amount of the compound of claim 1 wherein said malignant tumor is susceptible to treatment with 20(s)-camptothecin.

11. The method of claim 10, wherein R₁ is a C₁ -C₁₅ alkyl group.

12. The method of claim 10, wherein R₁ is a linear C₂ -C₁₅ alkenyl group.

13. The method of claim 10, wherein R₁ is an epoxidized alkenyl group.

14. The method of claim 10, wherein R₁ is a C₁ alkyl group.

15. The method of claim 10, wherein R₁ is a C₃ alkyl group.

16. The method of claim 10, wherein R₁ is a C₄ alkyl group.

17. The method of claim 10, wherein R₁ is ethyl.