Metabolically stable alkoxyalkyl esters of antiviral or antiproliferative phosphonates, nucleoside phosphonates and nucleoside phosphates

• US 7,749,983 B2
• Filed: 04/18/2007
• Issued: 07/06/2010
• Est. Priority Date: 05/03/2006
• Status: Active Grant

• Current Assignee: Chimerix Incorporated, US Department of Veterans Affairs (Government of the United States of America), Regents of the University of California (University of California)
• Original Assignee: Chimerix Incorporated, Regents of the University of California (University of California)
• Inventors: Riley, Timothy A., Painter, George R., Almond, Merrick R., Beadle, James R., Francom, Paula, Hostetler, Karl Y., Ruiz, Jacqueline
• Primary Examiner(s): Lewis; Patrick T
• Application Number:
  US11/736,614
• Publication Number:
  US 20080009462A1
• Time in Patent Office: 1,175 Days
• Field of Search: None
• US Class Current: 514/79
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07F 9/6512 having the nitrogen atoms in positions 1 and 3
• CPC Class Codes: C07F 9/6552 the oxygen atom being part of a six-membered ring
• 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
• CPC Class Codes: C07F 9/657172 the ring phosphorus atom and one oxygen atom being part of a (thio)phosphinic acid ester: (X = O, S)

Abstract

The present invention relates to phosphonate, nucleoside phosphonate or nucleoside phosphate compounds, compositions containing them, processes for obtaining them, and their use in treating a variety of medical disorders, in particular viral infections, cancers and the like.

Claims

1. A nucleoside phosphonate selected from the group of compounds having the following structures:

2. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

3. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

4. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

5. The phosphonate of claim 4 wherein X is F.

6. The phosphonate of claim 1 wherein R is selected from the group of compounds having the following structure:

7. The phosphonate of claim 6 wherein X is F.

8. The phosphonate of claim 6 wherein R is selected from the group of compounds having the following structures:

9. The nucleoside phosphonate of claim 1 wherein R is selected to prevent or decrease metabolic degradation of the phosphonate.

10. The nucleoside phosphonate of claim 1 wherein said phosphonate is selected from a compound having the following structures:

11. The nucleoside phosphonate of claim 1 wherein said phosphonate is selected from a compound having the following structures:

13. The nucleoside phosphonate of claim 1 wherein said phosphonate is selected from an antiviral or an antineoplastic agent.

14. The nucleoside phosphonate of claim 13, wherein said antiviral agent is a derivative is adefovir, cidofovir, cyclic cidofovir, tenofovir, phosphonomethyoxyethylguanine or HPMPA.

15. A pharmaceutical composition comprising a nucleoside phosphonate according to claim 1 and a pharmaceutically acceptable carrier.

16. A method for treating a viral infection, said method comprising administering to a host in need thereof an effective amount of a phosphonate compound according to claim 1.

12. A nucleoside phosphonate selected from the group consisting of:

3-(12-methyltridecyloxy)propyl cyclic cidofovir, 3-(13-methyltetradecyloxy)propyl cyclic cidofovir, 3-(14-methylpentadecyloxy)propyl cyclic cidofovir, 2-(17-methyloctadecyloxy)ethyl cyclic cidofovir, 3-(15-methylhexadecyloxy)propyl cyclic cidofovir, 3-(15-methylhexadecyloxy)ethyl(S)-cyclic HPMPA, 3-(15-methylhexadecyloxy)propyl(S)-cyclic HPMPA, 2-(17-methyloctadecyloxy)ethyl-(S)-cyclic HPMPA, 3-(12-methyltridecyloxy)propyl cidofovir, 3-(13-methyltetradecyloxy)propyl cidofovir, 3-(14-methylpentadecyloxy)propyl cidofovir, 3-(15-methylhexadecyloxy)propyl cidofovir, sodium, 3-(15-methylhexadecyloxy)propyl cidofovir, ammonium, 2-(17-methyloctadecyloxy)ethyl cidofovir, 2-(15-methylhexadecyloxy)ethyl cidofovir, 3-(phytanyloxy)propyl cidofovir, 3-(15-methylhexadceyloxy)ethyl-(S)-HPMPA, 2-(17-methyloctadecyloxy)ethyl-(S)-HPMPA, 3-(hex-dec-15-enyloxy)propyl cidofovir, ammonium, 3-(15-fluorohexadecyloxy)propyl cidofovir, 3-(15-fluorohexadecyloxy)propyl cyclic cidofovir, 3-(15-fluorohexadceyloxy)propyl-(S)-HPMPA, 3-(15-fluorohexadceyloxy)propyl-(S)-cyclic HPMPA, 3-(16-fluorohexadecyloxy)propyl cidofovir, 3-(16-fluorohexadecyloxy)propyl cyclic cidofovir, 3-(16-fluorohexadceyloxy)propyl-(S)-HPMPA, 3-(16-fluorohexadceyloxy)propyl-(S)-cyclic HPMPA, and 11-(7,7,8,8,8-pentafluoro-octyloxy)-undecyl cidofovir, ammonium salt.