Nucleotide and oligonucleotide prodrugs

• US 8,076,303 B2
• Filed: 12/12/2006
• Issued: 12/13/2011
• Est. Priority Date: 12/13/2005
• Status: Expired due to Fees

• Current Assignee: Spring Bank Pharmaceuticals, Inc.
• Original Assignee: Spring Bank Pharmaceuticals, Inc.
• Inventors: Iyer, Radhakrishnan P., Padmanabhan, Seetharamaiyer
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US11/637,520
• Publication Number:
  US 20070149462A1
• Time in Patent Office: 1,827 Days
• Field of Search: None
• US Class Current: 514/43
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 31/7084 Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07J 17/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton cardanolide, bufanolide C07J19/00
• CPC Class Codes: C07J 43/003 not condensed

Abstract

The present invention discloses compounds of formula (I):

which exhibit antiviral properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of anti-HBV treatment. The invention also relates to methods of treating a HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Claims

1. A pronucleotide of formula (I):

2. A pronucleotide according to claim 1, represented by the formula (II):

3. A pronucleotide according to claim 1, represented by the formula (III):

4. A pronucleotide according to claim 1, represented by the formula (IV):

5. A compound of claim 4 having the Formula A1, selected from compounds 1-8 of table 1:

6. A pronucleotide according to claim 1, represented by the formula (V):

7. A compound of claim 6 having the Formula B1, selected from compounds 9-16 of Table 2:

9. A method for treating HBV in a subject in need of such treatment comprising, administering to said subject a therapeutically effective amount of a compound according to claim 1.

10. A method for treating HBV in a subject in need of such treatment comprising, administering to said subject a therapeutically effective amount of a compound according to claim 1, in combination with other agents.

11. A method for treating HBV in a subject infected with resistant strains of HBV in need of such treatment comprising, administering to said subject a therapeutically effective amount of a compound according to claim 1, alone or in combination with other agents.

12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier or excipient.

13. A method for treating HBV in a subject in need of such treatment comprising, administering to said subject a therapeutically effective amount of a pharmaceutical composition of claim 7.

8. A pronucleotide represented by the formula (VI):