Antiviral pyridopyrazinedione compounds

Patent metadata

Field	Value
Publication number	US-12466821-B2
Application number	US-202117352734-A
Country	US
Kind code	B2
Filing date	Jun 21, 2021
Priority date	Sep 12, 2018
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

The invention provides compounds of Formula (I)

as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections, particularly infections caused by herpesviruses.

First claim

The invention claimed is:

1 . A compound of Formula (IV):

wherein:
R 11 is H or C 1 -C 6 alkyl optionally substituted up to three times with Z;
R 3 represents up to two (0-2) optional substituents on the ring to which -L-W is directly attached, each of which is independently selected from halo, CN, C 1-3 alkoxy, C 1-3 alkyl, COOR′, and C(O)NR′R′;
R 4 is H, halo, or C 1-3 alkyl;
R 5 is selected from H, halo, CN, C 1-3 alkoxy, —NR′R′, C 1-3 alkyl substituted up to three times with Z 5 , C 2-4 alkenyl substituted up to three times with Z 5 , C 2-4 alkynyl substituted up to three times with Z 5 , and a ring selected from a 3-6 membered cycloalkyl ring, a 4-6 membered heterocyclic ring containing one or two heteroatoms selected from N, O and S as ring members, and a 5-6 membered heteroaryl ring containing up to four heteroatoms selected from N, O and S as ring members, where the 3-6 membered cycloalkyl ring, 4-6 membered heterocyclic ring, or 5-6 membered heteroaryl ring is optionally substituted with 1-2 Z 5 ;
L is a C 1 -C 4 straight chain or branched alkylene linker;
W is H, —OH, —OR, —C(O)NR′R′, —COOR′, —NR′R′, —NR′COOR, —NR′C(O)R, —SO 2 R, —SO 2 NR′R′, —NR′SO 2 R, —P(O)(OR′) 2 , or an optionally substituted ring selected from 3-6 membered cycloalkyl, phenyl, 5-6-membered heterocyclyl containing one or two N, O or S heteroatoms as ring members, and 5-membered heteroaryl containing up to 4 heteroatoms selected from N, O and S as ring members that is optionally fused to phenyl,
wherein the optional substituents for said optionally substituted ring are 1-3 groups selected independently from C 1-3 alkyl, oxo, halo, C 1-3 haloalkyl, -L 2 -OH, -L 2 -OR, -L 2 -OC(O)—NR′R′, -L 2 -SO 2 R, -L 2 -SO 2 NR′R′, -L 2 -SO 2 NR′—C(O)R, -L 2 -C(O)—NR′—SO 2 R, -L 2 -SOR, -L 2 -S(═O)(═NR′)R, -L 2 -NR′SO 2 NR′R′, -L 2 -NR′SO 2 R, -L 2 -NR′R′, -L 2 -NR′C(O)R′, -L 2 -NR′COOR, -L 2 -C(O)NR′R′, and -L 2 -COOR′;
R at each occurrence is selected independently from C 1-4 alkyl, 3-6 membered cycloalkyl, phenyl, 5-6 membered heteroaryl containing up to 4 heteroatoms selected from N, O and S as ring members, and 4-6 membered heterocyclyl containing one or two heteroatoms selected from N, O and S as ring members,
wherein each R is optionally substituted with one or two groups independently selected from C 1-4 alkyl, C 1-2 haloalkyl, oxo, -L 3 -CN, -L 3 -halo, -L 3 -C 1-3 alkoxy, -L 3 -OH, -L 3 -OC(O)—NR′R′, -L 3 -SO 2 R′, -L 3 -SO 2 NR′R′, -L 3 -SO 2 NR′—C(O)R′, -L 3 -C(O)—NR′—SO 2 R′, -L 3 -SOR′, -L 3 -S(═O)(═NR′)R′, -L 3 -NR′SO 2 NR′R′, -L 3 -NR′SO 2 R′, -L 3 -NR′R′, -L 3 -NR′C(O)R′, -L 3 -NR′COOR′, -L 3 -C(O)NR′R′, and -L 3 -COOR′, -L 3 -(5-6-membered heterocyclyl containing one or two N, O or S heteroatoms as ring members), -L 3 -C 3-5 cycloalkyl, and -L 3 -(5-6 membered heteroaryl ring having up to four heteroatoms comprising 1-4 nitrogen atoms, 0-1 oxygen atoms, and 0-1 sulfur atoms as ring members), where the C 1-4 alkyl, 5-6-membered heterocyclyl, C 3-5 cycloalkyl and 5-6 membered heteroaryl ring are each optionally further substituted with up to three groups independently selected from halo, C 1-3 alkyl, C 1-3 haloalkyl, -L 4 -OR′, -L 4 -CN, and -L 4 -N(R′) 2 ;

R′ at each occurrence is independently selected from H, C 1-4 alkyl optionally substituted with halo, —OH, amino, or C 1-2 alkoxy, and C 3-6 alkyl optionally substituted with halo, —OH, amino, or C 1-2 alkoxy;
or two R′ taken together with a nitrogen atom to which both are directly attached can form a 4-6 membered ring optionally containing an additional N, O or S as a ring member and optionally substituted with one to three groups selected from C 1-2 alkyl, C 1-2 alkoxy, oxo, and hydroxy;
each L 2 and L 3 and L 4 is independently a bond or a straight chain or branched C 1-3 alkylene;

Z and Z 5 are independently selected at each occurrence from halo, hydroxy, CN, C 1-3 alkoxy, C 1-3 alkyl, and C 3-5 cycloalkyl,
and two Z groups, or two Z 5 groups, taken together with a carbon atom to which both are directly attached can form a 3-5 membered cycloalkyl ring or a 4-6 membered heterocyclic ring containing O, N or S as a ring member and optionally substituted by up to two groups selected from oxo and C 1-3 alkyl;
or a salt thereof.

2 . The compound of claim 1 , wherein R 11 is H or C 1 -C 6 alkyl.

3 . The compound of claim 1 , wherein R 3 is absent.

4 . The compound of claim 1 , wherein R 4 and R 5 are each H.

5 . The compound according to claim 1 , wherein:
W is —SO 2 R, —SO 2 NR′R′, —NR′SO 2 R, or an optionally substituted C 1 -C 3 alkyl, or an optionally substituted 3-6 membered cycloalkyl;
wherein the optional substituents for said optionally substituted C 1 -C 3 alkyl and optionally substituted cycloalkyl are 1-3 groups independently selected from C 1-3 alkyl, oxo, halo, C 1-3 alkoxy, OH, —SO 2 R, —SO 2 NR′R′, —NR′SO 2 NR′R′, —NR′SO 2 R, —NR′R′, —OR, —NR′COOR, —C(O)NR′R′, and COOR′,
R at each occurrence is independently selected from C 1-4 alkyl, 3-6 membered cycloalkyl, phenyl, 5-6 membered heteroaryl containing up to 4 heteroatoms selected from N, O and S as ring members, and 4-6 membered heterocyclyl containing one or two heteroatoms selected from N, O and S as ring members,
wherein each R is optionally substituted with one or two groups selected from C 1-3 alkyl, oxo, CN, halo, C 1-3 alkoxy, OH, and C 3-5 cycloalkyl;

R′ at each occurrence is independently selected from H and C 1-4 alkyl optionally substituted with halo, —OH or C 1-2 alkoxy;
or two R′ taken together with a nitrogen atom to which both are directly attached can form a 4-6 membered ring optionally containing an additional N, O or S as a ring member and optionally substituted with one or two groups selected from C 1-2 alkyl, C 1-2 alkoxy, oxo, and hydroxy.

6 . The compound according to claim 1 , wherein
the group W-L- is selected from the group consisting of:

7 . The compound according to claim 1 , wherein L is CH 2 .

8 . The compound according to claim 1 , wherein R at each occurrence is selected independently from methyl, ethyl, isopropyl and cyclopropyl.

9 . The compound according to claim 1 , wherein R′ at each occurrence is selected independently from H and methyl.

10 . The compound of claim 1 , selected from the group consisting of:

6-(dimethoxymethyl)-2-oxo-1,2-dihydropyridine-3- carboxylic acid;

2-((1-((1- ((benzyloxy)methyl)cyclopropyl)sulfonyl)cyclopropyl) methyl)-1,6-dioxo-2,3,4,6-tetrahydro-1H-pyrido[1,2- alpyrazine-7-carboxylic acid;

2-((1-((1- (hydroxymethyl)cyclopropyl)sulfonyl)cyc

Assignees

• Novartis Ag

Inventors

• Becker Christopher
• Li Xiaolin
• Lu Peichao
• Rajapaksa Naomi Samadara
• Tully David Charles
• Wang Xiaojing Michael
• Zhao Qian

Classifications

• A61P31/22

  for herpes viruses · CPC title

• A61P31/12 Primary

  Antivirals · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title