Prodrugs of phosphonate nucleotide analogues

• US 7,390,791 B2
• Filed: 03/11/2004
• Issued: 06/24/2008
• Est. Priority Date: 07/21/2000
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Rohloff, John C., Becker, Mark W., Lee, William A., He, Gong-Xin, Cihlar, Tomas, Sparacino, Mark L., Kernan, Michael R., Chapman, Harlan H., Prisbe, Ernest J., Eisenberg, Eugene J.
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): SRIVASTAVA, KAILASH C
• Application Number:
  US10/798,692
• Publication Number:
  US 20050009043A1
• Time in Patent Office: 1,566 Days
• Field of Search: 435/4, 435/7.1, 435/9.1, 514/44, 514/7, 514/81, 514/85
• US Class Current: 514/44.00R
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/18 Testing for antimicrobial activity of a material
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

A novel method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a)

having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided.

Claims

1. A diastereomerically enriched compound having the structure (3)

2. The compound of claim 1 containing less than 20% by weight of the diastereomer (4).

3. The compound of claim 1 containing less than 5% by weight of the diastereomer (4).

11. A composition comprising a compound of any of claims 1-8 or 2-10 and a pharmaceutically effective excipient.

12. The composition of claim 11 wherein the excipient is a gel.

13. The composition of claim 11 which is suitable for topical administration.

4. A diastereomerically enriched compound having the structure (5a)

5. The compound of claim 4 containing less than 20% by weight of the diastereomer (5b).

6. The compound of claim 4 containing less than 5% by weight of the diastereomer (5b).

7. A diastereomerically enriched compound of structure (6)

8. A diastereomerically enriched compound of structure (7)

9. The compound of claim 8 containing less than 20% by weight of the diastereomer (7a).

10. The compound of claim 8 containing less than 5% by weight of the diastereomer (7a).