Inhibitors of cytomegalovirus

Patent metadata

Field	Value
Publication number	US-9334249-B2
Application number	US-201314440087-A
Country	US
Kind code	B2
Filing date	Oct 31, 2013
Priority date	Nov 3, 2012
Publication date	May 10, 2016
Grant date	May 10, 2016

Abstract

Compounds of Formula (I) wherein n, R 1 , R 1A , R 2 , R 4 and Z are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.

First claim

The invention claimed is:

1. A compound of Formula (I) or racemate, enantiomer, diastereomer or tautomer thereof:

wherein
R 1 is S;
R 1A is CH;
Ring Z is benzothiazole optionally mono-, di- or tri-substituted with Z 1 ;
Z 1 is each independently selected from the group consisting of (C 1-6 )alkyl, —(C 1-6 )alkyl-(C 3-7 )cycloalkyl and —O—(C 1-6 )alkyl;

R 2 is

(wherein the site of attachment to the Z ring is indicated with * and the site of attachment to the phenyl ring is indicated with Φ);
R 2A is H or (C 1-6 )alkyl;
R 3 is absent, (C 3-7 )cycloalkyl or (C 1-6 )alkyl optionally mono-, di- or tri-substituted with R 3A ;
R 3A is each independently selected from the group consisting of halo, OH, —O—(C 1-6 )alkyl, —C(═O)OH, —C(═O)NH 2 , N(H)—C(═O)—O—(C 1-6 )alkyl, —(C 3-7 )cycloalkyl-C(═O)OH, —O-aryl and —O—(C 1-6 )alkyl-aryl;

R 4 is halo, (C 1-6 )haloalkyl, —CN, OH, —O—(C 1-6 )alkyl or (C 1-6 )alkyl,
wherein each said alkyl is optionally mono- or di-substituted with OH, C(═O)OH or aryl;

n is 0, 1, 2 or 3;

or a salt thereof.

2. The compound according to claim 1 , having the formula:

wherein Z 4 is S;
or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein
R 2 is

wherein the site of attachment to the Z ring is indicated with * and the site of attachment to the phenyl ring is indicated with Φ;
R 2A is H or (C 1-6 )alkyl;
R 3 is absent or (C 1-6 )alkyl optionally mono-, di- or tri-substituted with R 3A ;
R 3A is each independently selected from the group consisting of OH, —O—(C 1-6 )alkyl, —O-aryl and —O—(C 1-6 )alkyl-aryl;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein
R 2 is

wherein the site of attachment to the Z ring is indicated with * and the site of attachment to the phenyl ring is indicated with Φ;
R 3 is absent or (C 1-6 )alkyl optionally mono-, di- or tri-substituted with R 3A ;
R 3A is each independently selected from the group consisting of OH, —O—(C 1-6 )alkyl, —O-aryl and —O—(C 1-6 )alkyl-aryl;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , wherein R 4 is halo, (C 1-6 )haloalkyl, —CN or (C 1-6 )alkyl;
or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 6 , wherein R 4 is halo or (C 1-6 )haloalkyl;
or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 , wherein n is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 8 , wherein n is 1 or 2;
or a pharmaceutically acceptable salt thereof.

10. A method for the treatment of CMV disease and/or infection comprising administering a therapeutically effective amount of a compound according to claim 1 to a patient in need thereof.

11. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Boehringer Ingelheim Int

Inventors

• Fader Lee
• Parisien Mathieu
• Thibeault Carl
• Morency Louis
• Duplessis Martin
• James Clint
• Morin Sébastien
• Gillard James

Classifications

• C07D417/12

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

• C07D277/56 Primary

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title

• C07D413/12

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

• A61P31/22

  for herpes viruses · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title