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

Patent metadata

Field	Value
Publication number	US-2016002155-A1
Application number	US-201414771448-A
Country	US
Kind code	A1
Filing date	Feb 27, 2014
Priority date	Feb 28, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

Inhibitors of HBV replication of Formula (I)

including stereochemically isomeric forms, salts, hydrates and solvates thereof, wherein R 1 , R 2 , R 3 and R 4 have the meaning as defined herein.
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

1 . A compound of Formula (I)

or a stereoisomer or tautomeric form thereof, wherein:
R 1 represents hydrogen;
R 2 represents C 1 -C 8 alkyl substituted with one or more R 5 ,
R 3 represents Hydrogen or methyl;
R 4 represents methyl;
Each R 5 is independently selected from the group consisting of —C≡CH, —CN, —OH, oxo, C 1 -C 4 alkyloxy, —C(═O)O—R 6 , —C(═O)N(R 6 ) 2 , —N(R 6 ) 2 , —NR 9 C(═O)—R 6 , —NR 9 C(═O)O—R 6 and SO 2 R 9 ;
Each R 6 independently represents hydrogen or C 1 -C 3 alkyl;
R 9 represents hydrogen or C 1 -C 3 alkyl;
or a pharmaceutically acceptable salt or a solvate thereof.

2 . The compound according to claim 1 , wherein the C 1 -C 8 alkyl group as defined in R 2 represents a branched C 2 -C 6 alkyl.

3 . A compound according to claim 1 of Formula (Ib)

wherein:
R 7 is selected from the group consisting of —C≡CH, —CN, —C(═O)O—R 6 , —C(═O)N(R 6 ) 2 and C 1 -C 4 alkyl optionally substituted with one or more substituents selected from the group consisting of —C≡CH, —CN, —OH, C 1 -C 4 alkyloxy, —C(═O)O—R 6 , —C(═O)N(R 6 ) 2 , —N(R 6 ) 2 , —NHC(═O)—R 6 and —NHC(═O)O—R 6 ;
Each R 6 independently represents hydrogen or C 1 -C 3 alkyl; and wherein
Each R 8 independently represents hydrogen or C 1 -C 2 alkyl optionally substituted with OH.

4 . A compound according to claim 3 , wherein R 7 is selected from the group consisting of C 1 -C 4 alkyl optionally substituted with —C≡CH, —CN, —OH, C 1 -C 4 alkyloxy, —C(═O)O—R 6 , —C(═O)N(R 6 ) 2 , —N(R 6 ) 2 , —NHC(═O)—R 6 and —NHC(═O)O—R 6 .

5 . A compound according to claim 1 , wherein at least one R 5 is —OH.

6 . A compound according to claim 3 , wherein at least one R 8 is C 1 -C 2 alkyl substituted with OH.

7 . A method of treating an HBV infection, comprising administering a therapeutically effective amount of at least one compound according to claim 1 .

8 . A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.

9 . (canceled)

10 . The pharmaceutical composition of claim 8 , further comprising a second HBV inhibitor.

11 . A method of treating an HBV infection, comprising administering the pharmaceutical composition of claim 8 .

12 . A method of treating an HBV infection, comprising administering the pharmaceutical composition of claim 10 .

Assignees

• Janssen Sciences Ireland Uc

Inventors

• Vandyck Koen
• Last Stefaan Julien
• Raboisson Pierre Jean-Marie Bernard

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P31/20

  for DNA viruses · CPC title

• C07C311/19

  to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups · CPC title

• C07C311/37 Primary

  having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C311/17

  to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms · CPC title