Guanidine derivatives for the treatment of hepatitis C

Patent metadata

Field	Value
Publication number	US-9655902-B2
Application number	US-201414762542-A
Country	US
Kind code	B2
Filing date	Jan 23, 2014
Priority date	Jan 25, 2013
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

Compounds of Formula I, including pharmaceutically acceptable salts thereof, are set forth, in addition to compositions and methods of using these compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

First claim

What is claimed is:

1. A compound of Formula I,

wherein:
a, b and c are each nitrogen;
R 1 is selected from alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl, hydroxycycloalkyl, alkoxycycloalkyl, halocycloalkyl, cycloalkenyl, indanyl, alkylcarbonyl, and benzyl, wherein the benzyl moiety is substituted with 0-3 substituents selected from halo, alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, cyano, haloalkyl, alkoxy, and haloalkoxy;
R 2 is selected from alkyl, cycloalkyl, ((Ar 1 )alkyl, (Ar 1 )cycloalkyl, ((Ar 1 )cycloalkyl)alkyl, ((Ar 1 )alkyl)cycloalkyl, and (((Ar 1 )alkyl)cycloalkyl)alkyl;
Ar 1 is phenyl substituted with 0-3 substituents selected from halo, hydroxy, cyano, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, alkoxy, and haloalkoxy;
R 3 is hydrogen, alkyl or cycloalkyl;
R 4 is selected from hydrogen, halogen, alkyl, alkoxyl, alkylamino and alkylthio;
Y is

X is CONR 11 ;
R 11 is hydrogen or alkyl;
R 5 is alkyl, substituted with 0-4 substituents selected from the group of halo, alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, hydroxy, alkoxy, benzyloxy, CO 2 R 13 , and CON(R 14 )(R 15 );
R 13 is hydrogen or alkyl;
R 14 is hydrogen or alkyl;
R 15 is hydrogen or alkyl;
or R 14 and R 15 taken together with the nitrogen to which they are attached is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is substituted with 0-2 substituents selected from alkyl, alkylcarbonyl, and alkoxycarbonyl;
R 16 is hydrogen, alkyl, cycloalkyl, alkylcarbonyl, or alkoxycarbonyl;
R 17 is hydrogen or alkyl;
or R 16 and R 17 taken together with the nitrogen to which they are attached is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is substituted with 0-2 substituents selected from alkyl, alkylcarbonyl, and alkoxycarbonyl;
R 6 is hydrogen, alkyl, cycloalkyl, CN or CON(R 16 )(R 17 );
R 7 is hydrogen, alkyl, cycloalkyl, CN or CON(R 16 )(R 17 );
R 8 is hydrogen, alkyl, cycloalkyl, CN or CON(R 16 )(R 17 ); and
R 9 is hydrogen, alkyl, cycloalkyl, CN or CON(R 16 )(R 17 );
or a pharmaceutically acceptable salt thereof.

2. A compound selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

3. A compound selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

4. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

5. A method of treating hepatitis C infection comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

Assignees

• Bristol Myers Squibb Co

Inventors

• Wang Tao
• Zhang Zhongxing
• Han Ying
• Yin Zhiwei
• Scola Paul Michael

Classifications

• A61P31/14

  for RNA viruses · CPC title

• C07D251/52

  with an oxygen or sulfur atom attached to the third ring carbon atom · CPC title

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title

• C07D403/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/53 Primary

  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 title