Sulfide alkyl compounds for HBV treatment

Patent metadata

Field	Value
Publication number	US-9597332-B2
Application number	US-201514957020-A
Country	US
Kind code	B2
Filing date	Dec 2, 2015
Priority date	Dec 2, 2014
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.

First claim

The invention claimed is:

1. A compound of Formula IIIa:

or a pharmaceutically acceptable salt, solvate, or N-oxide thereof;
wherein
each R 1 is halo;
R 2 is halo;
R 3 is halo;
and R 4 is C 3-7 -cycloalkyl or (C 1-6 -alkyl)-(C 3-7 -cycloalkyl), each of which may be independently substituted with C(O)OH; or
R 4 is (C 3-7 -cycloalkyl)-C(O)R 5 , and R 5 is C 3-7 -heterocycloalkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or N-oxide thereof, wherein R 5 is morpholinyl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or N-oxide thereof, wherein the compound is selected from the group consisting of:

4. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt, solvate, or N-oxide thereof, further comprising at least one pharmaceutically acceptable carrier.

5. A method of treating an HBV infection in an individual having an HBV infection, comprising administering to the individual a therapeutically effective amount of a compound according to claim 1 .

6. The method of claim 5 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of an HBV vaccine, HBV polymerase inhibitor, interferon, pegylated interferon, viral entry inhibitor, viral maturation inhibitor, BAY 41-4109, reverse transcriptase inhibitor, a TLR-agonist, AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide), and AT-130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide), and a combination thereof.

7. The method of claim 6 , wherein the pegylated interferon is pegylated interferon alpha (IFN-α), pegylated interferon lambda (IFN-λ), or pegylated interferon gamma (IFN-γ).

8. The method of claim 6 , wherein the reverse transcriptase inhibitor is at least one of Zidovudine, Didanosine, Zalcitabine, ddA, Stavudine, Lamivudine, Abacavir, Emtricitabine, Entecavir, Apricitabine, Atevirapine, ribavirin, acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir, Tenofovir, Adefovir, cidofovir, Efavirenz, Nevirapine, Delavirdine, or Etravirine.

9. The method of claim 6 , wherein the TLR-agonist is selected from the group consisting of SM360320 (9-benzyl-8-hydroxy-2-(2-methoxy-ethoxy)adenine) and AZD 8848 (methyl [3-({[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl][3-(4-morpholinyl)propyl]amino}methyl)phenyl]acetate).

Assignees

• Novira Therapeutics Inc

Inventors

• Chen Austin
• Bravo Yalda
• Stock Nicholas
• Pedram Bijan
• Jacintho Jason
• Clark Ryan C

Classifications

• A61K31/5375 Primary

  1,4-Oxazines, e.g. morpholine · CPC title

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• C07D305/06

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring atoms · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• C07C2101/14

  Chemistry & Metallurgy · mapped topic