Sulfamoylbenzamide derivatives as antiviral agents against HBV infection

Patent metadata

Field	Value
Publication number	US-9399619-B2
Application number	US-201214130140-A
Country	US
Kind code	B2
Filing date	Jun 29, 2012
Priority date	Jul 1, 2011
Publication date	Jul 26, 2016
Grant date	Jul 26, 2016

Abstract

Pharmaceutical compositions of the invention comprise sulfamoylbenzamide derivative useful as pregenomic RNA encapsidation inhibitors, useful for the treatment of Hepatitis B virus (HBV) infection.

First claim

What is claimed is:

1. A method for treating Hepatitis B virus (HBV) infection and related conditions, said method comprising administering to a subject in need of such treatment a therapeutically effective amount of at least one compound having formula (I):

wherein
R 1 is hydrogen;
R 2 is selected from a group consisting of hydrogen, methyl, trifluoromethyl, fluorine, and chlorine;
R 3 is selected from a group consisting of hydrogen, methyl, fluorine, and chlorine;
R 4 is selected from a group consisting of hydrogen, fluorine, chlorine, and methyl;
R 5 is selected from a group consisting of hydrogen and chlorine;
R 7 is selected from a group consisting of hydrogen, chlorine, fluorine, and bromine;
R 9 is selected from a group consisting of hydrogen, methyl, fluorine, and chlorine;
R x is selected from the group consisting of: NH 2 ,

or a pharmaceutically acceptable salt form thereof.

2. The method of claim 1 , wherein the at least one compound is selected from the group consisting of
2-Chloro-5-sulfamoyl-N-3-methylphenyl-benzamide;
4-Fluoro-3-sulfamoyl-N-(3-trifluoromethyl-phenyl)-benzamide;
N-(2-Chloro-5-trifluoromethyl-phenyl)-4-fluoro-3-sulfamoyl-benzamide;
N-Phenyl-3-sulfamoyl-benzamide;
5-sec-Butylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
3-Diethylsulfamoyl-N-phenyl-benzamide;
5-Diethylsulfarnoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzarnide;
2-Chloro-5-diethylsulfamoyl-N-m-tolyl-benzamide;
N-(4-Chloro-phenyl)-3-diethylsulfamoyl-benzamide;
5-Allylsulfamoyl-N(3,4-difluoro-phenyl)-2-fluoro-benzamide;
N-(3,4-Difluoro-phenyl)-5-dipropylsulfamoyl-2-fluoro-benzamide;
5-Cycloheptylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
5-Cycloheptylsulfamoyl-2-fluoro-N-p-tolyl-benzamide;
5-Cyclohexylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
2-Bromo-5-cyclohexylsulfamoyl-N-phenyl-benzamide;
4-Chloro-3-cyclohexylsulfamoyl-N-(4-fluoro-phenyl)-benzamide;
3-Cyclohexylsulfamoyl-4-methyl-N-phenyl-benzamide;
N-(3,4-Difluoro-phenyl)-4-fluoro-3-(2-methyl-cyclohexylsulfamoyl)-benzamide;
3-Cyclopentylsulfamoyl-N-phenyl-benzamide,
5-Cyclopentylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
5-Cyclopentylsulfamoyl-2-fluoro-N-(4-fluoro-phenyl)-benzamide;
5-Cyclopentylsulfamoyl-N-(3,5-dimethyl-phenyl)-2-fluoro-benzamide;
3-Cyclopentylsulfamoyl-4-fluoro-N-3-methylphenyl-benzamide;
5-Cyclopentylsulfamoyl-N-(3,5-dichloro-phenyl)-2-fluoro-benzamide;
3-[(Furan-2-ylmethyl)-sulfamoyl]-N-phenyl-benzamide;
N-(3-Chloro-4-fluoro-phenyl)-5-[(furan-2-ylmethyl)-sulfamoyl]-2-methyl-benzamide;
2-Fluoro-N-(3-fluoro-phenyl)-5-[(furan-2-ylmethyl)-sulfamoyl]-benzamide;
N-(3,5-Dichloro-phenyl)-2-fluoro-5-[(furan-2-ylmethyl)-sulfamoyl]-benzamide;
4-Fluoro-3-[(furan-2-ylmethyl)-sulfamoyl]-N-3-methylphenyl-benzamide;
5-[(4-Chloro-3-phenylcarbamoyl-benzenesulfonylamino)-methyl]-furan-2-carboxylic acid methyl ester;
N-(3-Chloro-phenyl)-5-(2-cyclohex-1-enyl-ethylsulfamoyl)-2-fluoro-benzamide;
5-(2-Cyclohex-1-enyl-ethylsulfamoyl)-N-(3,5-dimethyl-phenyl)-2-fluoro-benzamide;
5-(2-Cyclohex-1-enyl-ethylsulfamoyl)-N-(3,5-dimethyl-phenyl)-2-fluoro-benzamide;
N-(3-Chloro-phenyl)-4-fluoro-3-[(pyridin-3-ylmethyl)-sulfamoyl]-benzamide;
N-(3,4-Difluoro-phenyl)-2-fluoro-5-phenethylsulfamoyl-benzamide;
N-(3-Chloro-phenyl)-2-fluoro-5-phenethylsulfamoyl-benzamide;
5-Benzylsulfamoyl-N-(3-chloro-4-fluoro-phenyl)-2-fluoro-benzamide;
5-Benzylsulfamoyl-2-chloro-N-phenyl-benzamide;
N-(4-Chloro-phenyl)-5-[2-(3,4-dimethoxy-phenyl)-ethylsulfamoyl]-2-fluoro-benzamide;
5-(2-Chloro-benzylsulfamoyl)-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
3-(2-Chloro-benzylsulfamoyl)-N-(4-chloro-phenyl)-4-fluoro-benzamide;
2-Fluoro-5-(4-methoxy-phenylsulfamoyl)-N-3-methylphenyl-benzamide;
2-Fluoro-5-(4-fluoro-phenylsulfamoyl)-N-3-methylphenyl-benzamide;
N-(4-Chloro-phenyl)-3-(3-fluoro-phenylsulfamoyl)-benzamide;
N-(4-Chloro-phenyl)-3-2-methylphenylsulfamoyl-benzamide;
N-Phenyl-3-m-tolylsulfamoyl-benzamide;
N-Phenyl-3-o-tolylsulfamoyl-benzamide;
3-(Benzyl-ethyl-sulfamoyl)-N-(3,4-difluoro-phenyl)-4-fluoro-benzamide;
5-(Azepane-1-sulfonyl)-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
4-Methyl-N-phenyl-3-(piperidine-1-sulfonyl)-benzamide;
4-chloro-N-(4-fluorophenyl)-3-(piperidin-1-ylsulfonyl)benzamide;
4-Chloro-N-(3-fluoro-phenyl)-3-(morpholine-4-sulfonyl)-benzamide;
4-Chloro-N-phenyl-3-(thiomorpholine-4-sulfonyl)-benzamide;
or a pharmaceutically acceptable form thereof.

3. The method of claim 1 , wherein the at least one compound is administered in a composition further comprising at least one pharmaceutically acceptable excipient.

4. The method of claim 3 , wherein the at least one compound is selected from the group consisting of
2-Chloro-5-sulfamoyl-N-3-methylphenyl-benzamide;
4-Fluoro-3-sulfamoyl-N-(3-trifluoromethyl-phenyl)-benzamide;
N-(2-Chloro-5-trifluoromethyl-phenyl)-4-fluoro-3-sulfamoyl-benzamide;
N-Phenyl-3-sulfamoyl-benzamide;
5-sec-Butylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
3-Diethylsulfamoyl-N-phenyl-benzamide;
5-Diethylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzarnide;
2-Chloro-5-diethylsulfamoyl-N-m-tolyl-benzamide;
N-(4-Chloro-phenyl)-3-diethylsulfamoyl-benzamide;
5-Allylsulfamoyl-N(3,4-difluoro-phenyl)-2-fluoro-benzamide;
N-(3,4-Difluoro-phenyl)-5-dipropylsulfamoyl-2-fluoro-benzamide;
5-Cycloheptylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
5-Cycloheptylsulfamoyl-2-fluoro-N-p-tolyl-benzamide;
5-Cyclohexylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
2-Bromo-5-cyclohexylsulfamoyl-N-phenyl-benzamide;
4-Chloro-3-cyclohexylsulfamoyl-N-(4-fluoro-phenyl)-benzamide;
3-Cyclohexylsulfamoyl-4-methyl-N-phenyl-benzamide;
N-(3,4-Difluoro-phenyl)-4-fluoro-3-(2-methyl-cyclohexylsulfamoyl)-benzamide;
3-Cyclopentylsulfamoyl-N-phenyl-benzamide,
5-Cyclopentylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
5-Cyclopentylsulfamoyl-2-fluoro-N-(4-fluoro-phenyl)-benzamide;
5-Cyclopentylsulfamoyl-N-(3,5-dimethyl-phenyl)-2-fluoro-benzamide;
3-Cyclopentylsulfamoyl-4-fluoro-N-3-methylphenyl-benzamide;
5-Cyclopentylsulfamoyl-N-(3,5-dichloro-phenyl)-2-fluoro-benzamide;
3-[(Furan-2-ylmethyl)-sulfamoyl]-N-phenyl-benzamide;
N-(3-Chloro-4-fluoro-phenyl)-5-[(furan-2-ylmethyl)-sulfamoyl]-2-methyl-benzamide;
2-Fluoro-N-(3-fluoro-phenyl)-5-[(furan-2-ylmethyl)-sulfamoyl]-benzamide;
N-(3,5-Dichloro-phenyl)-2-fluoro-5-[(furan-2-ylmethyl)-sulfamoyl]-benzamide;
4-Fluoro-3-[(furan-2-ylmethyl)-sulfamoyl]-N-3-methylphenyl-benzamide;
5-[(4-Chloro-3-phenylcarbamoyl-benzenesulfonylamino)-methyl]-furan-2-carboxylic acid methyl ester;
N-(3-Chloro-phenyl)-5-(2-cyclohex-1-enyl-ethylsulfamoyl)-2-fluoro-benzamide;
5-(2-Cyclohex-1-enyl-ethylsulfamoyl)-N-(3,5-dimethyl-phenyl)-2-fluoro-benzamide;
5-(2-Cyclohex-1-enyl-ethylsulfamoyl)-N-(3,5-dimethyl-phenyl)-2-fluoro-benzamide;
N-(3-Chloro-phenyl)-4-fluoro-3-[(pyridin-3-ylmethyl)-sulfamoyl]-benzamide;
N-(3,4-Difluoro-phenyl)-2-fluoro-5-phenethylsulfamoyl-benzamide;
N-(3-Chloro-phenyl)-2-fluoro-5-phenethylsulfamoyl-benzamide;
5-Benzylsulfamoyl-N-(3-chloro-4-fluoro-phenyl)-2-fluoro-benzamide;
5-Benzylsulfamoyl-2-chloro-N-phenyl-benzamide;
N-(4-Chloro-phenyl)-5-[2-(3,4-dimethoxy-phenyl)-ethylsulfamoyl]-2-fluoro-benzamide;
5-(2-Chloro-benzylsulfamoyl)-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide;
3-(2-Chloro-benzylsulfamoyl)-N-(4-chloro-phenyl)-4-fluoro-benzamide;
2-Fluoro-5-(4-methoxy-phenylsulfamoyl)-N-

Assignees

• Guo Ju-Tao
• Xu Xiaodong
• Block Timothy M
• Baruch S Blumberg Inst
• Univ Drexel

Inventors

• Guo Ju-Tao
• Xu Xiaodong
• Block Timothy M

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• C07D281/14

  [b, e]-condensed · CPC title