5-Aza-7-deazapurine derivatives for treating Flaviviridae

• US 20060040944A1
• Filed: 06/23/2005
• Published: 02/23/2006
• Est. Priority Date: 06/23/2004
• Status: Abandoned Application

• Current Assignee: Centre National De La Recherche Scientifique, Idenix Pharmaceuticals (Merck & Co., Inc.), Universite Montpellier II, University of Calgary
• Original Assignee: Centre National De La Recherche Scientifique, Idenix Pharmaceuticals (Merck & Co., Inc.), Universite Montpellier II, University of Calgary
• Inventors: Gosselin, Gilles, Dukhan, David, Leroy, Frederic, Storer, Richard, La Colla, Paolo, Seela, Frank
• Application Number:
  US11/166,498
• Publication Number:
  US 20060040944A1
• Time in Patent Office: Days
• US Class Current: 514/243
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA 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: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

This invention is directed to a method for treating a host, especially a human, infected with hepatitis C, flavivirus and/or pestivirus, comprising administering to that host an effective amount of an anti-flavivirus or anti-pestivirus, biologically active compound has a 5-aza-7-deazapurine moiety. The 5-aza-7-deazapurine moiety may be substituted or unsubstituted, and may comprise a nucleoside analogue, or a salt or prodrug thereof. The compound of the present invention may be administered alone or in combination with another anti-hepatitis C, anti-flavivirus and/or anti-pestivirus agent.

Claims

1. A method of treating a host infected with a flavivirus or pestivirus, comprising administering an effective amount of a biologically active compound to a host in need thereof, wherein the biologically active compound has the structure of Formulae (i), (ii), (iii), (iv), (v) or (vi):

2. The method of claim 1 wherein substituent R is selected from the group consisting H;

C_1-10 cyclic or acyclic, branched or unbranched alkyl, alkenyl, alkynyl;

acyl;

aryl;

aralkyl;

3-7 membered carbocycle or heterocycle;

3. The method of claim 1 wherein the host is a mammal.

4. The method of claim 3 wherein the mammal is a human.

5. The method of claim 1, wherein the compound has a structure of Formula (i) or (ii);

A and B are H;

V is N;

Z is O; and

Y is NR′

R″

;

or NR.

6. The method of claim 5, wherein R is H;

C_1-10 cyclic or acyclic, branched or unbranched alkyl, optionally substituted with amino, carboxamido carboxylate or alkylamino;

a 3-7 membered carbocycle or heterocycle;

or a functional group that dissociates to provide the base where R is H, selected from the following structures;

7. The method of claim 6, wherein each R′

and R″

independently is H;

C_1-10 cyclic or acyclic, branched or unbranched alkyl, alkenyl, or alkynyl.

8. The method of claim 7, wherein R′

″

is R′

″

is H, OH, SH, halo, optionally substituted C_1-4 alkyl, optionally substituted C_2-4 alkenyl or C_2-4 alkynyl, where the optional substitutions on alkyl, alkenyl and/or alkynyl may be one or more halogen, hydroxy, amino, alkoxy, or alkylthio groups.

9. The method of claim 1 wherein the compound of Formula (i) or (ii) has the structure:

10. The method of claim 1 wherein the compound of Formula (i) or (ii) has the structure:

11. A pharmaceutical composition comprising a compound of Formula (i) or (ii) having the structure:

12. A pharmaceutical composition comprising a compound of Formula (i) or (ii) having the structure: