Anti-viral 7-deaza L-nucleosides

• US 20030153744A1
• Filed: 12/20/2002
• Published: 08/14/2003
• Est. Priority Date: 12/21/2001
• Status: Abandoned Application

• Current Assignee: Migenix Inc. (Global Gaming Technologies Corp.)
• Original Assignee: Micrologix Biotech Incorporated
• Inventors: Mekouar, Khalid, Iyer, Radhakrishnan P., Deziel, Robert, Mounir, Samir
• Application Number:
  US10/326,573
• Publication Number:
  US 20030153744A1
• Time in Patent Office: Days
• US Class Current: 536/27.2
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07H 19/044 Pyrrole radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/23 Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22

Abstract

The present invention comprises 7-deaza L-nucleosides having unexpectedly high inhibitory activity against the hepatitis B virus. The invention further comprises pharmaceutical compositions comprising such compounds as well as methods of treating mammals, particularly humans, infected with HBV and other viral infections.

Claims

1. A compound of formula (I):

2. The compound according to claim 1, wherein:

a) R¹ is —

NH₂, R² and R³ are independently —

H, methyl, —

F, or C₁-C₄-alkyl, and R₄ is —

H;

b) R₁ is —

NH₂, R² is —

H, R³ is —

H, and R⁴ is —

C₁-C₄-alkyl;

c) R¹ is —

NHZR⁵;

d) R¹ is —

NH₂, R² and R³ together with the carbons to which they are attached form a 5-membered ring, and R⁴ is —

H;

e) R¹ is —

H or C₁-C₄-alkyl, R² is —

H R³ is —

H, and R⁴ is H;

or

f) R¹ is —

NH₂, R² and R³ are —

H are independently —

H or C₁-C₄-alkyl, and R⁴ is —

NHZR⁵.

3. The compound according to claim 1, wherein:

a) R⁶ is —

H, R⁷ is —

H, and R⁸ is —

OH, and R⁹ is —

H;

b) R⁶ is —

H, R⁷ is —

OH, and R⁸ is —

OH, and R⁹ is —

H;

c) R⁶ is —

H, R⁷ is C₁-C₄-alkyloxy, R⁸ is —

OH, and R⁹ is —

H;

d) R⁶ is —

H, R⁷ is —

NHZR⁵, R⁸ is —

OH, and R⁹ is —

H;

e) R⁶ is —

H, R⁷ is —

F, and R⁸ is —

OH;

f) R⁶ is —

OH or F, R⁷ is —

H, and R⁸ is —

H or —

OH;

or

g) R⁶, R⁷, and R⁸ are —

H, and R⁹ is —

OH or —

F.

4. The compound according to claim 1 having structure (II):

5. A pharmaceutical composition comprising a compound according to any one of claims 1-4 and a pharmaceutically acceptable carrier.

6. A method of treating a mammal infected with HBV, the method comprising administering to the mammal an effective amount of a composition according to claim 5.

7. The method according to claim 6, wherein the mammal is a human.