Phosphonate-nucleotide ester derivatives

• US 6,037,335 A
• Filed: 10/02/1997
• Issued: 03/14/2000
• Est. Priority Date: 06/29/1993
• Status: Expired due to Fees

• Current Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Original Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Inventors: Takashima, Hideaki, Sekiya, Kouichi, Ubasawa, Masaru, Inoue, Naoko, Yabuuchi, Shingo
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US08/942,490
• Time in Patent Office: 894 Days
• Field of Search: 544/244, 514/81, 514/80
• US Class Current: 514/80
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C07F 9/65616 containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs

Abstract

Phosphonate-nucleotide ester compounds of the formula (I) have excellent antiviral activity and antineoplastic activity. Further, they can be orally administered. ##STR1## wherein ring A represents ##STR2## wherein R¹ and R² independently represent hydrogen, halogen, hydroxyl, mercapto, C₆ -C₁₀ arylthio or amino; R³ represents C₁ -C₄ alkyl or ethyl having one or more substituents selected from the group consisting of fluorine, C₁ -C₄ alkoxy, phenoxy, C₇ -C₁₀ phenylalkoxy and C₂ -C₅ acyloxy; R⁴ represents ethyl having one or more substituents selected from the group consisting of fluorine, C₁ -C₄ alkoxy, phenoxy, C₇ -C₁₀ phenylalkoxy and C₂ -C₅ acyloxy; X, Y and Z independently represent methyne or nitrogen atom; or a pharmaceutically acceptable salt thereof.

Claims

1. A phosphonate-nucleotide ester compound of the following formula (I):

##STR21## wherein ring A represents ##STR22## wherein R¹ represents halogen, hydroxyl, mercapto, tolylthio or amino;

R² represents hydrogen or amino;

R³ represents ethyl having one or more fluorine substituents;

R⁴ represents ethyl having one or more fluorine substituents;

X, Y and Z independently represent methyne or nitrogen atom;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, wherein R¹ is tolylthio.

3. The compound according to claim 1, wherein R² is amino.

4. The compound according to claim 1, wherein R³ is 2,2,2-trifluoroethyl.

5. The compound according to claim 1, wherein R⁴ is 2,2,2-trifluoroethyl.

6. The compound according to claim 1, wherein X and Z are nitrogen atoms, X and Y are nitrogen atoms, or X, Y and Z are nitrogen atoms.

7. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier.