Inhibitors of protein phosphatase-1 and uses thereof

Patent metadata

Field	Value
Publication number	US-9447047-B2
Application number	US-201314421757-A
Country	US
Kind code	B2
Filing date	Mar 14, 2013
Priority date	Aug 14, 2012
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

Inhibitors of protein phosphatase-1 (PP-1) and their use in a method for the treatment or prevention of viral infections caused by HIV or ebola virus are disclosed. Inhibitors of protein phosphatase-1 in effective amounts have been shown to slow down viral replication upon contacting ebola virus or cells containing the ebola virus.

First claim

What is claimed is:

1. A method for treating a subject infected with or at risk of infection with Ebola, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (I) comprising:

wherein n is 1 or 2;
Ar is phenyl or thienyl, and is optionally substituted;
each R 1 is independently R 6 , C(O)R 6 , C(O)—OR 6 , or C(O) N(R 6 ) 2 ;
R 2 is H or optionally substituted C1-C6 alkyl, or a group of formula —C(O)NH—R 1 ;
R 3 is independently at each occurrence selected from halo, NO 2 , CN, R, OR, NR 2 ;
S(O) q R, COOR, and CONR 2 , where each R is independently H, C1-C4 alkyl, or C1-C4 haloalkyl;
m is 0-4;
R 4 is R 6 , halo, =0, COOR 6 , CON(R 6 ) 2 , S(O) q R 6 , N(R 6 ) 2 , or OR 6 ;
p is 0-2;
each q is independently 0-2;
Z is O or NR 5 ;
R 5 is R 6 or C(O)R 6 ; and
R 6 is independently at each occurrence selected from H, C1-C6 alkyl, C5-C6 aryl, and (C5-C6-aryl)-C1-C6 alkyl, where each alkyl and aryl is optionally substituted;
provided that n is 2 when Z is O and Ar represents para-halophenyl;
or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , comprising a pharmaceutically acceptable salt of a compound of formula I.

3. The method of claim 1 , wherein Z is O.

4. The method of claim 1 , wherein n is 1.

5. The method of claim 1 , wherein n is 2.

6. The method of claim 1 , wherein R 2 is H or C1-C4 alkyl.

7. The method of claim 1 , wherein Ar is optionally substituted phenyl.

8. The method of claim 1 , wherein Ar is optionally substituted 2-thienyl.

9. The method of claim 1 , wherein Ar is optionally substituted 3-thienyl.

10. A method to inhibit replication of Ebola virus, comprising contacting the Ebola virus or a cell containing the Ebola virus with a compound of formula (I).

11. A method for treating a subject infected with or at risk of infection with Ebola, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound selected from the group consisting of

and pharmaceutically acceptable salts of these compounds.

12. A method for inhibiting replication of Ebola virus, comprising contacting the Ebola virus or a cell containing the Ebola virus with a compound selected from the group consisting of

and pharmaceutically acceptable salts of these compounds.

Assignees

• Nekhai Sergei
• Bukreyev Alexander
• Univ Howard
• Univ Texas

Inventors

• Nekhai Sergei
• Bukreyev Alexander

Classifications

• C07D219/04 Primary

  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 carbon atoms of the ring system · CPC title

• C07D417/12

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

• C07D221/16

  containing carbocyclic rings other than six-membered · CPC title

• C07D409/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P31/14

  for RNA viruses · CPC title