Lipophilic, aminohydrolase-activated prodrugs

• US 5,459,256 A
• Filed: 04/10/1991
• Issued: 10/17/1995
• Est. Priority Date: 04/17/1987
• Status: Expired due to Term

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America), United States As Represented By The Secretary Department of Health and Human Services
• Original Assignee: The United States of America As Represented By The Secretary of Agriculture
• Inventors: Ford, Harry Jr., Tomaszewski, Joseph E., Kelley, James A., Marquez, Victor E., Mitsuya, Hiroaki, Barchi, Joseph J. Jr., Johns, David G., Driscoll, John S., Tseng, Christopher K-H.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Wilson, James O.
• Application Number:
  US07/683,432
• Time in Patent Office: 1,651 Days
• Field of Search: 536/24, 536/27, 536/27.21, 536/27.6-27.63, 536/27.7, 536/27.8, 536/27.81, 536/27.14, 536/27.61, 536/27.62
• US Class Current: 536/27.14
• CPC Class Codes: C07H 19/16 Purine radicals

Abstract

The present invention relates, in general, to prodrugs. In particular, the present invention relates to lipophilic, aminohydrolase-activated, anti-viral nucleoside prodrug compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds.

Claims

1. A compound of the formula:

##STR10## wherein A is F;

B is H;

Y is H or NH₂ ; and

X is selected from the group consisting of halogen, NHR or OR, wherein

R is C_1-8 alkyl, straight chain or branched chain, and NROR, wherein R

is H or C_1-8 alkyl, straight chain or branched chain.

2. The compound according to claim 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is Cl.

3. The compound according to claim 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NH(CH₃).

4. The compound according to claim 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is O(CH₃).

5. The compound according to claim, 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NHOH.

6. The compound according to claim 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NHOCH₃.

7. The compound according to claim 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is N(CH₃)OH.

8. The compound according to claim 1, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is selected from the group consisting of halogen, NHR, or OR, wherein R is C_1-4 alkyl, and NROR, wherein R is H or C_1-4 alkyl.

9. The compound according to claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is Cl.

10. The compound according to claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NH(CH₃).

11. The compound according to claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is O(CH₃).

12. The compound according to claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NHOH.

13. The compound according to claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NHOCH₃.

14. The compound according to claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is N(CH₃)OH.

15. The compound according to claim 1 or claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is NH(C₂ H₅).

16. The compound according to claim 1 or claim 8, wherein A is F;

B is H;

Y is H or NH₂ ; and

X is O(C₂ H₅).

17. A composition comprising the compound according to claim 1, and an acceptable carrier, diluent, or excipient.

18. The composition according to claim 15, wherein in the compound of the composition, A is F;

B is H;

Y is H or NH₂ and X is Cl.