Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis B

Patent metadata

Field	Value
Publication number	US-10995064-B2
Application number	US-201715681309-A
Country	US
Kind code	B2
Filing date	Aug 18, 2017
Priority date	Aug 28, 2012
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

First claim

The invention claimed is:

1. A compound of Formula (I)

or a stereoisomer or tautomeric form thereof, wherein:
B is a monocyclic 5 membered aromatic ring containing two or more heteroatoms each independently selected from the group consisting of S and N, said 5 membered aromatic ring optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, C 1 -C 3 alkyl, CFH 2 , CF 2 H and CF 3 ;
R 1 is hydrogen or C 1 -C 3 alkyl;
R 2 is C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkyl-R 5 , C(═O)—R 5 , CFH 2 , CF 2 H, CF 3 , a dihydroindenyl or tetrahydronaphthalenyl moiety optionally substituted with OH, or a 3-7 membered saturated ring optionally containing one or more heteroatoms each independently selected from the group consisting of O, S and N, said 3-7 membered saturated ring, C 1 -C 6 alkyl-R 5 or C 1 -C 6 alkyl optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, C 1 -C 4 alkyloxy, C 1 -C 4 alkyloxycarbonyl, oxo, C(═O)—C 1 -C 3 alkyl, C 1 -C 4 alkyl, OH, CN, CFH 2 , CF 2 H and CF 3 ;
each R 4 is independently selected from the group consisting of hydrogen, halo, C 1 -C 4 alkyloxy, C 1 -C 4 alkenyl, OH, CN, CFH 2 , CF 2 H, CF 3 , HC═C and a 3-5 membered saturated ring optionally containing one or more heteroatoms each independently selected from the group consisting of O and N, said C 1 -C 4 alkyl optionally substituted with OH; and
R 5 is selected from the group consisting of C 1 -C 6 alkyl, CFH 2 , CF 2 H, CF 3 , phenyl, pyridyl and a 3-7 membered saturated ring optionally containing one or more heteroatoms each independently selected from the group consisting of O, S and N, said 3-7 membered saturated ring optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, C 1 -C 4 alkyloxy, C 1 -C 4 alkyloxycarbonyl, oxo, C(═O)—C 1 -C 3 alkyl, OH, CN, CFH 2 , CF 2 H and CF 3 ;
or a pharmaceutically acceptable salt or a solvate thereof.

2. The compound of claim 1 , wherein R 1 is hydrogen.

3. The compound of claim 1 , wherein R 2 is a 4-7 membered saturated ring optionally containing one or more heteroatoms each independently selected from the group consisting of O, S and N, said 4-7 membered saturated ring optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, C 1 -C 4 alkyloxy, C 1 -C 4 alkyloxycarbonyl, C(═O)—C 1 -C 3 alkyl, C 1 -C 4 alkyl, OH, CN, CFH 2 , CF 2 H and CF 3 .

4. The compound of claim 1 , wherein R 2 is C 4 -C 6 cycloalkyl.

5. The compound of claim 1 , wherein B is imidazolyl or thiazolyl, each optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, C 1 -C 3 alkyl, CFH 2 , CF 2 H and CF 3 .

6. A compound of claim 1 , wherein the compound is selected from the group consisting of

or pharmaceutically acceptable salts thereof.

7. A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier.

8. A product containing (a) at least one compound of claim 1 , and (b) an HBV inhibitor, as a combined preparation for simultaneous, separate or sequential use in the treatment of HBV infection.

9. A method of treating an HBV infection in a subject in need thereof, comprising administering to said subject an effective amount of at least one compound of claim 1 .

10. A method of treating an HBV infection in a subject in need thereof, comprising administering to said subject the pharmaceutical composition of claim 7 .

Assignees

• Janssen Sciences Ireland Uc

Inventors

• Vandyck Koen
• Last Stefaan Julien
• Rombouts Geert
• Verschueren Wim Gaston
• Raboisson Pierre Jean-Marie Bernard

Classifications

• C07D231/14

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D213/04

  having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom · CPC title

• C07C311/15 Primary

  Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings · CPC title

• A61K31/381

  having five-membered rings · CPC title

• A61K31/335

  having oxygen as the only ring hetero atom, e.g. fungichromin · CPC title