Pyridazinone compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-10364226-B2
Application number	US-201415021073-A
Country	US
Kind code	B2
Filing date	Sep 10, 2014
Priority date	Sep 12, 2013
Publication date	Jul 30, 2019
Grant date	Jul 30, 2019

Abstract

Disclosed herein are pyridazinone compounds, pharmaceutical compositions that include one or more pyridazinone compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection, with a pyridazinone compounds. Examples of an orthomyxovirus viral infection includes an influenza infection.

First claim

What is claimed is:

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:
G 1 is selected from the group consisting of

and R 5 ;
G 2 is hydrogen, halogen, —CN, an optionally substituted C 1-6 alkyl, an optionally substituted aryl, an optionally substituted heteroaryl, —CH 2 OH, —CH(Y 1 )(OH) or —C(O)Y 1 ;
G 3 is selected from the group consisting of hydrogen, —C(O)Y 2 , —C(O)O—Y 2 , —(CH 2 )—OC(O)Y 2 , —(CH 2 )—OC(O)OY 2 , —(CHCH 3 )—OC(O)Y 2 and —(CHCH 3 )—OC(O)OY 2 ;
Y 1 and Y 2 are independently an optionally substituted C 1-6 alkyl or an optionally substituted aryl;
R 1 is selected from the group consisting of OR 6 , NH 2 , an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted mono-substituted amine, an optionally substituted di-substituted amine, an optionally substituted heterocyclyl, an optionally substituted N-sulfonamido and an optionally substituted alkoxyamine,
or R 1 is R 10 ;
R 2 is hydrogen, C 1-6 alkyl, an optionally substituted C 3-6 cycloalkyl, an optionally substituted aryl, an optionally substituted aryl(C 1-6 alkyl) or an optionally substituted C-amido;
R 3 is hydrogen or C 1-6 alkyl;
or R 2 and R 3 are taken together with the carbon to which they are attached to form an optionally substituted C 3-6 cycloalkyl or an optionally substituted 5 to 6 membered heterocyclyl,
or R 2 and R 3 are taken together to form ═O;

R 4 is selected from the group consisting of an optionally substituted aryl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl;
or R 4 is A 1 R A4 R B4 , wherein A 1 is CH or N; and R A4 and R B4 are each independently an optionally substituted phenyl;
R 5 is selected from the group consisting of an optionally substituted aryl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl;
R 6 is selected from the group consisting of hydrogen, C 1-6 alkyl, —C(O)R 7 and —C(O)NR 8 R 9 ;
R 7 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocyclyl, aryl(C 1-6 alkyl), heteroaryl(C 1-6 alkyl) and heterocyclyl(C 1-6 alkyl); and
R 8 and R 9 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocyclyl, aryl(C 1-6 alkyl), heteroaryl(C 1-6 alkyl) and heterocyclyl(C 1-6 alkyl);
or R 8 and R 9 are taken together with the nitrogen to which they are attached to form an optionally substituted heterocyclyl;
wherein when R 1 is R 10 , then the compound of Formula (I) has the structure of Formula (Ih) or (Ij),

wherein the ring containing R 10 , L 1 , and R 4 is an 11- to 20-membered ring, and the ring containing R 10 , L 1 , and R 5 is an 11- to 20-membered ring;
R 10 is optionally substituted —CH 2 —, optionally substituted —CH═CH—, O (oxygen), S (sulfur) or NR 11 ;
R 11 is hydrogen or C 1-6 alkyl;
L 1 is -L 2 - or -L 3 -L 4 -L 5 -;
L 2 is selected from the group consisting of an optionally substituted alkylene, an optionally substituted alkenylene, an optionally substituted heteroalkylene and an optionally substituted heteroalkenylene,
L 3 is an optionally substituted C 1-6 alkylene,
L 4 is an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, O (oxygen), S (sulfur) or NR 11 ; and
L 5 is an optionally substituted C 1 . 6 alkylene or an optionally substituted heteroalkylene, and

Z 1 and Z 2 are independently 0, 1, 2, 3 or 4.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof,
wherein:
G 2 is hydrogen or C 1-6 alkyl;
G 3 is selected from the group consisting of hydrogen, —C(O)Y 2 , —C(O)O—Y 2 , —(CH 2 )—OC(O)Y 2 , —(CH 2 )—OC(O)OY 2 , —(CHCH 3 )—OC(O)Y 2 and —(CHCH 3 )—OC(O)OY 2 ;
Y 2 is C 1-6 alkyl;
R 1 is selected from the group consisting of OR 6 , NH 2 , an optionally substituted mono-substituted amine, an optionally substituted di-substituted amine, an optionally substituted heterocyclyl and an optionally substituted N-sulfonamido, said an optionally substituted mono-substituted amine, an optionally substituted di-substituted amine, an optionally substituted heterocyclyl and an optionally substituted N-sulfonamido are each optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), (heterocyclyl)alkyl, hydroxy, alkoxy, acyl, cyano, halogen, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, an amino, a mono-substituted amino group and a di-substituted amino;
R 2 is hydrogen or C 1-6 alkyl;
R 3 is hydrogen or C 1-6 alkyl;
or R 2 and R 3 are taken together with the carbon to which they are attached to form an optionally substituted C 3-6 cycloalkyl or an optionally substituted 5 to 6 membered heterocyclyl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof,
wherein:
G 1 is

and
R 2 and R 3 are taken together with the carbon to which they are attached to form an optionally substituted piperidino or an optionally substituted pyrrolidino.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the structure of Formula (Ih) or Formula (Ij), or a pharmaceutically acceptable salt thereof:

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein L 2 is an optionally substituted alkylene or an optionally substituted alkenylene.

6. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein L 2 is an optionally substituted heteroalkylene or an optionally substituted heteroalkenylene.

7. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein L 2 is an optionally substituted —(CH 2 ) 3 —O—, an optionally substituted —(CH 2 ) 4 —O—, an optionally substituted —(CH 2 ) 5 —O—, an optionally substituted —(CH 2 ) 3 —S—, an optionally substituted —(CH 2 ) 4 —S—, an optionally substituted —(CH 2 ) 5 —S—, an optionally substituted —(CH 2 ) 3 —NH—, an optionally substituted —(CH 2 ) 4 —NH—, an optionally substituted —(CH 2 ) 5 —NH—, an optionally substituted —(CH 2 )(CH═CH)(CH 2 )—O—, an optionally substituted —(CH 2 ) 2 (CH═CH)(CH 2 )—O—, an optionally substituted —(CH 2 )(CH═CH)(CH 2 ) 2 —O—, an optionally substituted —(CH 2 ) 2 (CH═CH)(CH 2 ) 2 —O—, an optionally substituted —(CH 2 ) 2 (CH═CH)(CH 2 )—S—, an optionally substituted —(CH 2 )(CH═CH)(CH 2 ) 2 —S—, an optionally substituted —(CH 2 ) 2 (CH═CH)(CH 2 ) 2 —S an optionally substituted —(CH 2 ) 2 (CH═CH)(CH 2 )—NH—, an optionally substituted —(CH 2 )(CH

Assignees

• Alios Biopharma Inc

Inventors

• Beigelman Leonid
• Hendricks Robert Than
• Stoycheva Antitsa Dimitrova
• Deval Jerome
• Stevens Sarah Katherine

Classifications

• C07D498/22

  in which the condensed system contains four or more hetero rings · CPC title

• C07D498/18

  Bridged systems · CPC title

• C07D498/10

  Spiro-condensed systems · CPC title

• C07D498/08

  Bridged systems · CPC title

• C07D487/22

  in which the condensed system contains four or more hetero rings · CPC title