2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives

• US 5,977,325 A
• Filed: 06/03/1998
• Issued: 11/02/1999
• Est. Priority Date: 11/15/1988
• Status: Expired due to Fees

• Current Assignee: Aventis Incorporated (Sanofi )
• Original Assignee: Merrell Pharmaceuticals Incorporated (Dow, Inc.)
• Inventors: Edwards, Michael L., Matthews, Donald P., McCarthy, James R.
• Primary Examiner(s): Knode, Marian C.
• Assistant Examiner(s): Crane, L. Eric
• Application Number:
  US09/089,839
• Time in Patent Office: 517 Days
• Field of Search: 514/45, 514/49, 514/50, 514/262, 514/274, 536/4.1, 536/27.8, 536/27.81, 536/28.5, 536/28.51, 536/28.52, 536/28.53, 536/28.54, 536/28.55, 544/242, 544/276
• US Class Current: 536/4.1
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals

Abstract

This invention relates to certain novel 2'"'"'-halomethylidene, 2'"'"'-ethenylidene and 2'"'"'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease states.

Claims

1. A compound of the formula ##STR10## wherein V is oxy, methylene, or thio,

A₁ and A₂ are each independently hydrogen or a --C.tbd.CR group, wherein R is hydrogen or C₁ -C₄ alkyl, with the proviso that where A₁ is hydrogen A₂ is a --C.tbd.CR group,

and where A₁ is a --C.tbd.CR group A₂ is hydrogen,

B is a radical of the formula ##STR11## wherein Y₁ is nitrogen, a CH group, a CCl group, a CBr group or a CNH₂ group;

Y₂ and Y₃ are each independently nitrogen or a CH group;

Y₄ is hydrogen, C₁ -C₄ alkyl, C₁ -C₄ alkoxy or halogen;

Y₅ is amino or C₁ -C₄ alkoxy; and

Z is hydrogen, halogen, or NH₂ ;

or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 wherein R is hydrogen.

3. A compound of claim 1 wherein V is oxy.

4. A compound of claim 1 wherein Z is hydrogen.

5. A compound of claim 1 wherein Y₁ is a CH group.

6. A compound of claim 1 wherein Y₂ is nitrogen.

7. A compound of claim 1 wherein Y₃ is nitrogen.

8. A compound of claim 1 wherein Z is hydrogen.

9. A compound of claim 1 wherein Y₂ is a CH group.

10. A compound of claim 1 wherein the compound is 2'"'"'-deoxy-2'"'"'(R or S)-ethynyl-cytidine.

11. A compound of claim 1 wherein the compound is 2'"'"'-deoxy-2'"'"'(R or S)-ethynyl-uridine.

12. A compound of claim 1 wherein the compound is 2'"'"'-deoxy-2'"'"'(R or S)-ethynyl-guanosine.

13. A composition comprising a compound of claim 3 in admixture or otherwise in association with one or more acceptable carriers or excipients.