Therapeutic hydroxyquinolones

Patent metadata

Field	Value
Publication number	US-9701638-B2
Application number	US-201314441797-A
Country	US
Kind code	B2
Filing date	Nov 8, 2013
Priority date	Nov 9, 2012
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

The invention provides compounds of formula (I) and salts thereof wherein R 4 -R 8 have any of the meanings defined in the specification, as well as pharmaceutical compositions comprising the compounds or salts and methods for their use in therapy. The compounds have useful antiviral properties.

First claim

What is claimed is:

1. A compound of formula (I):

wherein:
R 4 is:
(C 4 -C 10 )alkanoyl;
(C 1 -C 10 )alkyl that is substituted with one or more groups independently selected from cyano, halo, nitro, hydroxy, oxo, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy, heterocycleoxy-, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , and —CONR e R f ; wherein each heterocycle of R m is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, oxo, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —COOR g , and —CONR e R f ; wherein each aryl and heteroaryl of R m is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, carboxy, aryl, heteroaryl, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , —COOR g , and —CONR e R f ; wherein each each R g is independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, (C 3 -C 12 )carbocycle, aryl, and heteroaryl; or
(C 1 -C 10 )alkanoyl that is substituted with one or more groups independently selected from cyano, halo, nitro, hydroxy, oxo, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy, heterocycleoxy-, —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , and —CONR e R f ; wherein each heterocycle of R m is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, oxo, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —COOR g , and —CONR e R f ; wherein each aryl and heteroaryl of R m is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, carboxy, aryl, heteroaryl, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , —COOR g , and —CONR e R f ; wherein each each R g is independently selected from hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, (C 3 -C 12 )carbocycle, aryl, and heteroaryl;
R 5 is H, halo, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, —NR e R f , —COOR g , cyano, nitro, aryl, heteroaryl, or (C 1 -C 10 )alkanoyl, wherein each (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, and (C 1 -C 10 )alkanoyl are optionally substituted with one or more groups independently selected from R m ; and wherein each aryl and heteroaryl is optionally substituted with one or more groups independently selected from R n ;
R 6 is H, halo, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 carbocycle, —NR e R f , —COOR g , cyano, nitro, aryl, heteroaryl, or (C 1 -C 6 )alkanoyl, wherein each (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, and (C 1 -C 10 )alkanoyl are optionally substituted with one or more groups independently selected from R m ; and wherein each aryl and heteroaryl is optionally substituted with one or more groups independently selected from R n ;
R 7 is H, halo, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, —NR e R f , —COOR g , cyano, nitro, aryl, heteroaryl, or (C 1 -C 10 )alkanoyl, wherein each (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, and (C 1 -C 10 )alkanoyl are optionally substituted with one or more groups independently selected from R m ; and wherein each aryl and heteroaryl is optionally substituted with one or more groups independently selected from R n ;
R 8 is H, halo, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, —NR e R f , —COOR g , cyano, nitro, aryl or (C 1 -C 10 )alkanoyl, (C 1 -C 10 )alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )alkoxy, (C 3 -C 12 )carbocycle, and (C 1 -C 10 )alkanoyl are optionally substituted with one or more groups independently selected from R m ; and wherein each aryl is optionally substituted with one or more groups independently selected from R n ;
each R e and R f is independently selected from hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, (C 3 -C 12 )carbocycle, aryl, and heteroaryl; or R e and R f together with the nitrogen to which they are attached form a aziridino, azetidino, morpholino, piperazino, pyrrolidino or piperidino;
each R g is independently selected from hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, (C 3 -C 12 )carbocycle, aryl, and heteroaryl;
each R m is independently selected from cyano, halo, nitro, hydroxy, oxo, aryl, heteroaryl, heterocycle, aryloxy, heteroaryloxy, heterocycleoxy-, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , —COOR g , and —CONR e R f ; wherein each heterocycle of R m is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, oxo, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —COOR g , and —CONR e R f ; wherein each aryl and heteroaryl of R m is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, carboxy, aryl, heteroaryl, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , —COOR g , and —CONR e R f ;
each R n independently selected from C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, aryl, heteroaryl, heterocycle, cyano, halo, nitro, hydroxy, carboxy, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —S(O) n NR e R f , —COOR g , and —CONR e R f ; wherein each (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, heterocycle, and (C 3 -C 12 )carbocycle of R n is optionally substituted with one or more groups independently selected from cyano, halo, nitro, hydroxy, carboxy, heteroaryl, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —COOR g , and —CONR e R f ; wherein each aryl and heteroaryl of R n is optionally substituted with one or more groups independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 12 )carbocycle, cyano, halo, nitro, hydroxy, aryl, heteroaryl, aryloxy, heteroaryloxy, heterocycleoxy, —NR e R f , —S(O) n R g , —N(R y )S(O) n R g , —COOR g , —S(O) n NR e R f , and —CONR e R f ;
each R y is independently selected from hydrogen and (C 1 -C 6 )alkyl; and
n is 0, 1, or 2;
or a salt thereof.

2. A compound of formula (I):

Assignees

• Univ Rutgers

Inventors

• Lavoie Edmond J
• Bauman Joseph David
• Sagong Hye Yeon
• Arnold Eddy
• Parhi Ajit
• Das Kalyan
• Vijayan Suyambu Kesava
• Patel Disha

Classifications

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61P31/18

  for HIV · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D215/227

  only one oxygen atom which is attached in position 2 · CPC title