Uracil derivatives and antitumor effect potentiator and antitumor agent containing the same

• US 6,294,535 B1
• Filed: 12/09/1999
• Issued: 09/25/2001
• Est. Priority Date: 03/29/1995
• Status: Expired due to Term

• Current Assignee: Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: Sato, Tsutomu, Yamashita, Junichi, Tada, Yukio, Kazuno, Hideki, Asao, Tetsuji, Suzuki, Norihiko, Fukushima, Masakazu, Yano, Shingo, Emura, Tomohiro
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): TRUONG, TAMTHOM NGO
• Application Number:
  US09/457,668
• Time in Patent Office: 656 Days
• Field of Search: 514/235.8, 544/123, 544/310, 544/311, 544/313
• US Class Current: 514/235.8
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 239/54 as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• 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 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention relates to novel uracil derivatives having excellent inhibiting effects on human derived thymidine phosphorylates and anti-tumor activity. The pharmaceutical compositions, anti-tumor potentiators and antitumor agents containing such novel compounds, and a process for their preparation and use are described. The novel uracil derivative compounds are represented by the general formula (1′):

Claims

1. A pharmaceutical composition comprising:

a uracil derivative represented by the following formula (1);

 

wherein R¹ is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and

R² represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group;

or a salt thereof; and

a pharmaceutically acceptable carrier.

2. The uracil derivative of claim 1, wherein R¹ is chlorine or iodine.

3. The uracil derivative of claim 1, wherein R¹ is cyano.

4. The uracil derivative of claim 1, wherein R¹ is a lower alkyl group.

5. The uracil derivative of claim 1, wherein R² is an amino group with one or both of the hydrogen atoms on the nitrogen atom substituted by a lower alkyl group.

6. method for potentiating an antitumor effect of an antitumor agent containing a 2′

deoxypyrmidine nucleoside, which comprises administering to a patient an effective amount of an uracil derivative represented by the following formula (1);

 

wherein R¹ is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and

R² represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group;

or a salt thereof.

7. The uracil derivative of claim 6, wherein R¹ is chlorine or iodine.

8. The uracil derivative of claim 6, wherein R¹ is cyano.

9. The uracil derivative of claim 6, wherein R¹ is a lower alkyl group.

10. The uracil derivative of claim 6, wherein R² is an amino group with one or both of the hydrogen atoms on the nitrogen atom substituted by a lower alkyl group.

11. A therapeutic method for treating cancer, which comprises administering to a patient in need of treatment an effective amount of a uracil derivative represented by the following formula (1):

 

wherein R¹ is selected from the group consisting of chlorine, bromine, iodine, cyano and a lower alkyl group; and

R² represents an amino group, one or both of the hydrogen atoms on the nitrogen atom of which may each be substituted by a lower alkyl group;

or a salt thereof; and

a 2′

-deoxypyrimidine nucleoside.

12. The uracil derivative of claim 11, wherein R¹ is chlorine or iodine.

13. The uracil derivative of claim 11, wherein R¹ is cyano.

14. The uracil derivative of claim 11, wherein R¹ is a lower alkyl group.

15. The uracil derivative of claim 11, wherein R² is an amino group with one or both of the hydrogen atoms on the nitrogen atom substituted by a lower alkyl group.