US 12,466,821 B2
Antiviral pyridopyrazinedione compounds
Christopher Becker, Pleasant Hill, CA (US); Xiaolin Li, Alameda, CA (US); Peichao Lu, Pleasant Hill, CA (US); Naomi Samadara Rajapaksa, Fremont, CA (US); David Charles Tully, Danville, CA (US); Xiaojing Michael Wang, Livermore, CA (US); and Qian Zhao, Louisville, CO (US)
Assigned to Novartis AG, Basel (CH)
Filed by Novartis AG, Basel (CH)
Filed on Jun. 21, 2021, as Appl. No. 17/352,734.
Application 17/352,734 is a division of application No. 16/569,107, filed on Sep. 12, 2019, granted, now 11,072,610.
Claims priority of provisional application 62/730,361, filed on Sep. 12, 2018.
Prior Publication US 2023/0052629 A1, Feb. 16, 2023
Int. Cl. C07D 471/04 (2006.01); A61P 31/22 (2006.01); A61K 31/4985 (2006.01); A61P 31/12 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 31/22 (2018.01)] 10 Claims
 
1. A compound of Formula (IV):

OG Complex Work Unit Chemistry
wherein:
R11 is H or C1-C6 alkyl optionally substituted up to three times with Z;
R3 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, C1-3 alkoxy, C1-3 alkyl, COOR′, and C(O)NR′R′;
R4 is H, halo, or C1-3 alkyl;
R5 is selected from H, halo, CN, C1-3 alkoxy, —NR′R′, C1-3 alkyl substituted up to three times with Z5, C2-4 alkenyl substituted up to three times with Z5, C2-4 alkynyl substituted up to three times with Z5, 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 Z5;
L is a C1-C4 straight chain or branched alkylene linker;
W is H, —OH, —OR, —C(O)NR′R′, —COOR′, —NR′R′, —NR′COOR, —NR′C(O)R, —SO2R, —SO2NR′R′, —NR′SO2R, —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 C1-3 alkyl, oxo, halo, C1-3 haloalkyl, -L2-OH, -L2-OR, -L2-OC(O)—NR′R′, -L2-SO2R, -L2-SO2NR′R′, -L2-SO2NR′—C(O)R, -L2-C(O)—NR′—SO2R, -L2-SOR, -L2-S(═O)(═NR′)R, -L2-NR′SO2NR′R′, -L2-NR′SO2R, -L2-NR′R′, -L2-NR′C(O)R′, -L2-NR′COOR, -L2-C(O)NR′R′, and -L2-COOR′;
R at each occurrence is selected independently from C1-4 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 C1-4 alkyl, C1-2 haloalkyl, oxo, -L3-CN, -L3-halo, -L3-C1-3 alkoxy, -L3-OH, -L3-OC(O)—NR′R′, -L3-SO2R′, -L3-SO2NR′R′, -L3-SO2NR′—C(O)R′, -L3-C(O)—NR′—SO2R′, -L3-SOR′, -L3-S(═O)(═NR′)R′, -L3-NR′SO2NR′R′, -L3-NR′SO2R′, -L3-NR′R′, -L3-NR′C(O)R′, -L3-NR′COOR′, -L3-C(O)NR′R′, and -L3-COOR′, -L3-(5-6-membered heterocyclyl containing one or two N, O or S heteroatoms as ring members), -L3-C3-5 cycloalkyl, and -L3-(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 C1-4 alkyl, 5-6-membered heterocyclyl, C3-5 cycloalkyl and 5-6 membered heteroaryl ring are each optionally further substituted with up to three groups independently selected from halo, C1-3 alkyl, C1-3 haloalkyl, -L4-OR′, -L4-CN, and -L4-N(R′)2;
R′ at each occurrence is independently selected from H, C1-4 alkyl optionally substituted with halo, —OH, amino, or C1-2 alkoxy, and C3-6 alkyl optionally substituted with halo, —OH, amino, or C1-2 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 C1-2 alkyl, C1-2 alkoxy, oxo, and hydroxy;
each L2 and L3 and L4 is independently a bond or a straight chain or branched C1-3 alkylene;
Z and Z5 are independently selected at each occurrence from halo, hydroxy, CN, C1-3 alkoxy, C1-3 alkyl, and C3-5 cycloalkyl,
and two Z groups, or two Z5 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 C1-3 alkyl;
or a salt thereof.