SULFINYLAMINOBENZAMIDE AND SULFONYLAMINOBENZAMIDE DERIVATIVES
Provided is a compound of Formula (I): wherein the variable groups are defined herein.
1 . A compound of Formula I:
or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, wherein:
Q is selected from the group consisting of —S(O) 2 —, —S(O)—, —S(O)(NH)—, —S(O)(NR 8 )—.
R 1 is selected from a group consisting of: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —NR 13 R 13 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are optionally further substituted with one or more R 11 groups;
R 11 is selected from a group consisting of: hydroxyl, oxo, halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R 14 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —SH, —S(O) 0-2 R 14 , —S(O) 1-2 NR 13 R 13 , —SF 5 , —NO 2 , —NR 13 R 13 , —NR 13 SO 2 R 14 , —OS(O) 2 R 14 , —C(O)OR 14 , —C(O)R 14 , —NR 13 C(O)OR 14 , —NR 13 C(O)NR 13 R 13 , —NR 13 S(O) 2 NR 13 R 13 , and —C(O)NR 13 R 13 , wherein each C 16 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are optionally substituted with one or more R 9 groups;
each R 9 is independently selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 16 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR 13 R 13 , —NR 13 C(O)OR 14 , —OS(O) 2 R 14 —C(O)OR 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —S(O) 0-2 R 14 , —S(O) 1-2 NR 13 R 13 , —C(O)NR 13 R 13 , —NR 13 SO 2 R 14 , —C(O)R 14 , —NR 13 C(O)NR 13 R 13 , —NR 13 S(O) 2 NR 13 R 13 , SF 5 and —NO 2 , wherein
each of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with one or more R 16 groups;
each R 13 is independently selected from the group consisting of —H, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 15 groups.
each R 14 is independently selected from the group consisting of: C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 15 groups.
each R 15 is independently selected from —H, halo, —CN, —OH, oxo, —NO 2 , —SF 5 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R 16 , —S(O)(NR 8 )R 16 , —S(O)(NH)NR 16 R 16 , —S(O)(NR 8 )NR 16 R 16 , —S(O) 0-2 R 16 , —S(O) 2 NH 2 , —NH 2 , —S(O) 2 NR 16 R 16 , C(O)R 16 , —C(O)NR 16 R 16 and C(O)OR 16 , wherein 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are optionally substituted with one or more R 16 groups.
each R 16 is independently selected from halo, —CN, —OH, —NH 2 , oxo, —NO 2 , —SF 5 , C 1-3 alkyl, C 1-3 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, thiohaloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH 2 and —S(O) 2 NH 2 .
R 2 is selected from a group consisting of: —H, —CN, —F, —Cl, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 heteroalkyl, C 1 . 3 alkoxy and C 1-3 haloalkoxy;
each R 3 and R 4 is independently selected from a group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —SH, —NR 13 R 13 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , —NR 13 C(O)OR 14 , tri-C 1-4 alkylsilyl, —C(O)R 14 , —C(O)OR 14 , —C(O)NR 13 R 13 , and —NO 2 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are optionally further substituted with one or more R 9 groups;
R 5 is selected from a group consisting of: —H, —CN, —F, —Cl, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 heteroalkyl, C 1-3 alkoxy and C 1-3 haloalkoxy;
wherein R 2 and R 3 , or R 3 and R 4 , or R 4 and R 5 can optionally join, together with the atoms to which they are attached, to form a 5-6 membered cycloalkyl, a 5-6 membered heterocyclyl, phenyl, or a 5-6 membered heteroaryl, each such cyclic groups respectively fused to the phenyl to which they are attached, and each optionally substituted with one or more R 9 groups;
R 6 is selected from the group consisting of: 5-10 membered carbobicyclic ring, 8-10 membered tricyclic ring, 6-12 membered heterobicyclic ring, and 8-12 membered polycyclic ring, wherein the 5-10 membered carbobicyclic ring, the 8-10 membered tricyclic ring, the 8-12 membered polycyclic ring, or the 6-12 membered heterobicyclic ring may be fused, bridged or spiro, and wherein the 5-10 membered carbobicyclic ring, the 8-10 membered tricyclic ring, the 6-12 membered heterobicyclic and the 8-12 membered polycyclic ring are substituted with one or more R 7 ;
R 7 is selected from the group consisting of: —H, halo, —CN, oxo, —OH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O) 0-2 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —SH, —NR 13 R 13 , —P(O)R 14 R 14 , —C(O)OH, —C(O)OR 14 , —C(O)NR 13 R 13 , —S(O) 2 NR 13 R 13 , —C(O)R 14 , 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl; wherein each of said 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-12 membered cycloalkyl are optionally substituted with one or more R 15 ; and n is 1, 2, or 3;
R 8 is C 1-6 alkyl, —C(O)R 14 , 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, —C(O)OR 14 , —C(O)NR 13 R 13 , and —SO 2 R 14 , wherein each of C 1-6 alkyl, —C(O)R 14 , 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, —S(O) 1-2 R 14 , —S(O) 2 NR 13 R 13 , —NO 2 , —SF 5 , C 1-6 haloalkyl, C 16 haloalkoxy, C 1-6 hydroxyalkyl, —NR 13 R 13 , —C(O)OR 14 , C 1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with one or more R 16 , 4-12 membered heterocyclyl optionally substituted with one or more R 16 , 6-10 membered aryl optionally substituted with one or more R 16 , 5-10 membered heteroaryl optionally substituted with one or more R 16 ;
subject to the provisos that:
(i) when R 6 is a C 8-12 carbobicyclic ring, and both R 3 and R 7 are H,
then R 4 is selected from the group consisting of: C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl, 7-12 membered monocyclic heterocyclyl, —SF 5 , —NR 13 R 13 , —NR 13 C(O)OR 14 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , tri-C 1-4 alkylsilyl, —C(O)R 14 , —C(O)OR 14 , —C(O)NR 13 R 13 , —S(O) 0-2 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —SH and —NO 2 , wherein C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl and 7-12 membered monocyclic heterocyclyl are optionally substituted with one or more R 9 ; 5-6 membered heterocyclyl is optionally substituted with R 17 ; and 8-10 membered bicyclic heterocyclyl is optionally substituted with one or more R 18 .
(ii) when R 6 is an 8-10 membered heterobicyclic ring, R 3 is H and R 7 is —H, halo, cyano, oxo, —OH, C 1-4 alkoxy, C 1-4 alkyl or C 1-4 haloalkyl,
then R 4 is selected from the group consisting of: C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl, 7-12 membered monocyclic heterocyclyl, —SF 5 , —NR 13 R 13 , —NR 13 C(O)OR 14 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , tri-C 1-4 alkylsilyl, —C(O)R 14 , —C(O)OR 14 , —C(O)NR 13 R 13 , —S(O) 0-2 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —SH, and —NO 2 , wherein C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl and 7-12 membered monocyclic heterocyclyl are optionally substituted with one or more R 9 ; 5-6 membered heterocyclyl is optionally substituted with R 17 , and 8-10 membered bicyclic heterocyclyl is optionally substituted with one or more R 18 .
(iii) when R 6 is a C 6 -C 7 carbobicyclic ring, and R 7 is H or methyl,
then R 3 is selected from the group consisting of: halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —SH, —NR 13 R 13 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , —NR 13 C(O)OR 14 , tri-C 1-4 alkylsilyl, —C(O)R 14 , —C(O)OR 14 , —C(O)NR 13 R 13 , and —NO 2 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are optionally further substituted with one or more R 9 groups;
wherein R 17 is selected from —OH, oxo, —CN, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O) 0-2 R 14 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , —NR 13 C(O)OR 14 , —C(O)R 14 , —C(O)OR 14 and —C(O)NR 13 R 13 .
and wherein R 18 is selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O) 0-2 R 14 , —NR 13 R 13 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , —NR 13 C(O)OR 14 , —C(O)R 14 , —C(O)OR 14 and —C(O)NR 13 R 13 .
2 . The compound of claim 1 , wherein R 6 is selected from the group consisting of: 5-10 membered carbobicyclic ring, 6-12 membered heterobicyclic ring, and 8-10 membered tricyclic ring, wherein the 5-10 membered carbobicyclic ring, 8-10 membered tricyclic ring, or the 6-12 membered heterobicyclic ring may be fused, bridged or spiro, and wherein the 5-10 membered carbobicyclic ring, the 6-12 membered heterobicyclic ring and the 8-10 membered tricyclic ring are substituted with one or more R 7
3 . The compound of claim 2 , wherein R 6 is selected from the group consisting of: 5-10 membered carbobicyclic ring, 8-10 membered tricyclic ring, and 6-12 membered heterobicyclic ring, wherein the 5-10 membered carbobicyclic ring, the 8-10 membered tricyclic ring, or the 6-12 membered heterobicyclic ring are bridged, and wherein the 5-10 membered carbobicyclic ring, the 8-10 membered tricyclic ring, and the 6-12 membered heterobicyclic are substituted with one or more R 7 .
4 . The compound of claim 3 , wherein R 6 is selected from the group consisting of: 5-10 membered carbobicyclic ring, and 6-12 membered heterobicyclic ring, wherein the 5-10 membered carbobicyclic ring, or the 6-12 membered heterobicyclic ring are bridged, and wherein the 5-10 membered carbobicyclic ring, and the 6-12 membered heterobicyclic are substituted with one R 7 .
5 . The compound of any of claim 1 wherein Q is selected from the group consisting of —S(O) 2 —, —S(O)—, and —S(O)(NR 8 )—.
6 . The compound of claim 1 , wherein R 1 is selected from the group consisting of: C 1-6 alkyl, —NR 13 R 13 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are further substituted with one or more R 11 groups.
7 . The compound of claim 1 , wherein R 2 is selected from the group consisting of: —H, —CN, —F, methyl, methoxy and C 1 haloalkoxy
8 . The compound of claim 7 , wherein R 2 is selected from the group consisting of: —H and —F.
9 . The compound of claim 1 , wherein R 4 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —SF 5 , —S(O) 0-2 R 14 , —S(O)(NH)R 14 , —S(O)(NR 8 )R 14 , —S(O)(NH)NR 13 R 13 , —S(O)(NR 8 )NR 13 R 13 , —NR 13 R 13 , —NR 13 SO 2 R 14 , —NR 13 S(O) 2 NR 13 R 13 , —NR 13 C(O)NR 13 R 13 , —NR 13 C(O)OR 14 , —C(O)R 14 , —C(O)OR 14 , —C(O)NR 13 R 13 , —NO 2 , wherein C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, are further substituted with one or more R 9 groups.
10 . The compound of claim 9 , wherein R 4 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, —S(O) 0-2 R 14 , —C(O)R 14 , —SF 5 , —NO 2 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 14 is selected from the group consisting of C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, are optionally substituted with one or more R 16 groups, and R 16 is independently selected from halo, —CN, —OH.
11 . The compound of claim 10 , wherein R 4 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, —SR 14 , —SF 5 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 14 is selected from the group consisting of C 1-3 haloalkyl.
12 . The compound of claim 1 , wherein R 3 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, 6-10 membered aryl, 4-12 membered heterocyclyl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —S(O) 0-2 R 14 , —NO 2 , and —SF 5 , wherein said C 1-6 alkyl, 6-10 membered aryl, 4-12 membered heterocyclyl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl are optionally further substituted with one or more R 9 groups.
13 . The compound of claim 12 , wherein R 3 selected from the group consisting of: —H, —F, —Cl, —OH, —CN, C 1-6 alkyl, 4-12 membered heterocyclyl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —SR 14 , and —SF 5 , wherein said C 1-6 alkyl, C 1-6 alkoxy, C 3-12 cycloalkyl, 4-12 membered heterocyclyl, and 5-10 membered heteroaryl are optionally substituted with one or more R 16 , and R 14 is C 1-3 haloalkyl.
14 . The compound of claim 1 , wherein R 5 is selected from the group consisting of: —H, —F and methyl.
15 . A compound of Formula II:
or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, wherein:
wherein x, y, and z are independently 1, 2, 3, or 4,
Q is selected from the group consisting of —S(O) 2 —, —S(O)—, —S(O)(NH)—, —S(O)(NR 28 )—;
R 21 is selected from a group consisting of: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —NR 33 R 33 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are optionally further substituted with one or more R 31 groups;
R 31 is selected from the group consisting of: hydroxyl, oxo, halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R 34 R 34 , —S(O)(NH)R 34 , —S(O)(NR 28 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —SH, —S(O) 0-2 R 34 , —S(O) 1-2 NR 33 R 33 , —SF 5 , —NO 2 , —NR 33 R 33 , —NR 33 SO 2 R 34 , —OS(O) 2 R 34 , —C(O)OR 34 , —C(O)R 34 , —NR 33 C(O)OR 34 , —NR 33 C(O)NR 33 R 33 , —NR 33 S(O) 2 NR 33 R 33 , and —C(O)NR 33 R 33 , wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally substituted with one or more R 29 groups;
each R 29 is independently selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR 33 R 33 , —NR 33 C(O)OR 34 , —OS(O) 2 R 34 —C(O)OR 34 , —S(O)(NH)R 34 , —S(O)(NR 8 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —S(O) 0-2 R 34 , —S(O) 1-2 NR 33 R 33 , —C(O)NR 33 R 33 , —NR 33 SO 2 R 34 , —C(O)R 34 , —NR 33 C(O)NR 33 R 33 , —NR 33 S(O) 2 NR 33 R 33 , —SF 5 , —NO 2 , wherein each of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl is optionally substituted with one or more R 36 ;
each R 33 is independently selected from the group consisting of —H, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 35 groups;
each R 34 is independently selected from the group consisting of: C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 35 groups;
each R 35 is independently selected from —H, halo, —CN, —OH, oxo, —NO 2 , —SF 5 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R 36 , —S(O)(NR 28 )R 36 , —S(O)(NH)NR 36 R 36 , —S(O)(NR 28 )NR 36 R 36 , —S(O) 0-2 R 36 , —S(O) 2 NH 2 , —NH 2 , —S(O) 2 NR 36 R 36 , C(O)R 36 , —C(O)NR 36 R 36 and C(O)OR 36 , wherein 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally substituted with one or more R 36 groups;
each R 36 is independently selected from halo, —CN, —OH, —NH 2 , oxo, —NO 2 , —SF 5 , C 1-3 alkyl, C 1-3 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, thiohaloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH 2 and —S(O) 2 NH 2 ;
R 22 is selected from a group consisting of: —H, —CN, —F, —Cl, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 heteroalkyl, C 1-3 alkoxy and C 1-3 haloalkoxy;
each R 23 and R 24 is independently selected from a group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 2 -6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 34 , —S(O)(NH)R 34 , —S(O)(NR 28 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —SH, —NR 33 R 33 , —NR 33 SO 2 R 34 , —NR 33 S(O) 2 NR 33 R 33 , —NR 33 C(O)NR 33 R 33 , —NR 33 C(O)OR 34 , tri-C 1-4 alkylsilyl, —C(O)R 34 , —C(O)OR 34 , —C(O)NR 33 R 33 , —NO 2 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally further substituted with one or more R 29 groups;
wherein R 22 and R 23 , or R 23 and R 24 can optionally join, together with the atoms to which they are attached, to form a 5-6 membered cycloalkyl, a 5-6 membered heterocyclyl, phenyl, or a 5-6 membered heteroaryl, each such cyclic groups respectively fused to the phenyl to which they are attached, and each optionally substituted with one or more R 29 groups;
R 27 is selected from the group consisting of: —H, halo, —CN, oxo, —OH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O) 0-2 R 34 , —S(O)(NH)R 34 , —S(O)(NR 28 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —NR 33 R 33 , —P(O)R 34 R 34 , —C(O)OH, —C(O)OR 34 , —C(O)NR 33 R 33 , —S(O) 2 NR 33 R 33 , —C(O)R 34 , 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl; wherein each of said 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-12 membered cycloalkyl are optionally substituted with one or more R 35 ;
R 28 is C 1-6 alkyl, —C(O)R 34 , 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, —C(O)OR 34 , —C(O)NR 33 R 33 , —SO 2 R 34 , wherein each of C 1-6 alkyl, C 1-6 alkylcarbonyl, 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, —S(O) 1-2 R 34 , —S(O) 2 NR 33 R 33 , —NO 2 , —SF 5 , C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, —NR 33 R 33 , —C(O)OR 34 , C 1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with one or more R 36 , 4-12 membered heterocyclyl optionally substituted with one or more R 36 , 6-10 membered aryl optionally substituted with one or more R 36 , 5-10 membered heteroaryl optionally substituted with one or more R 36 ;
subject to the provisos that:
(i) when x+y+z is 6 to 10, and both R 23 and R 27 are H, then R 24 is selected from the group consisting of: C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl, 7-12 membered monocyclic heterocyclyl, —SF 5 , —NR 33 R 33 , —NR 33 C(O)OR 34 , —NR 33 SO 2 R 34 , —NR 33 S(O) 2 NR 33 R 33 , —NR 33 C(O)NR 33 R 33 , tri-C 1-4 alkylsilyl, —C(O)R 34 , —C(O)OR 34 , —C(O)NR 33 R 33 , —S(O) 0-2 R 34 , —S(O)(NH)R 34 , —S(O)(NR 28 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —SH and —NO 2 , wherein C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl and 7-12 membered monocyclic heterocyclyl are optionally substituted with one or more R 29 ; 5-6 membered heterocyclyl is optionally substituted with R 37 ; and 8-10 membered bicyclic heterocyclyl is optionally substituted with one or more R 38 ; and
(ii) when x+y+z is 4 or 5, and R 27 is —H or methyl, R 23 is selected from the group consisting of: halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 34 , —S(O)(NH)R 34 , —S(O)(NR 28 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —SH, —NR 33 R 33 , —NR 33 SO 2 R 34 , —NR 33 S(O) 2 NR 33 R 33 , —NR 33 C(O)NR 33 R 33 , —NR 33 C(O)OR 34 , tri-C 1-4 alkylsilyl, —C(O)R 34 , —C(O)OR 34 , —C(O)NR 33 R 33 , —NO 2 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally further substituted with one or more R 29 groups;
wherein R 37 is selected from —OH, oxo, —CN, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O) 0-2 R 34 , —NR 33 SO 2 R 34 , —NR 33 S(O) 2 NR 33 R 33 , —NR 33 C(O)NR 33 R 33 . —NR 33 C(O)OR 34 , —C(O)R 34 , —C(O)OR 34 and —C(O)NR 33 R 33 ;
and wherein R 38 is selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O) 0-2 R 34 , —NR 33 R 33 , —NR 33 SO 2 R 34 , —NR 33 S(O) 2 NR 33 R 33 , —NR 33 C(O)NR 33 R 33 , —NR 33 C(O)OR 34 , —C(O)R 34 , —C(O)OR 34 and —C(O)NR 33 R 33 .
16 . The compound of claim 15 wherein Q is selected from the group consisting of —S(O) 2 —, —S(O)—, and —S(O)(NR 28 )—.
17 . The compound of claim 15 , wherein R 21 is selected from a group consisting of: C 1-6 alkyl, —NR 33 R 33 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are further substituted with one or more R 31 groups.
18 . The compound of claim 15 , wherein R 22 is selected from the group consisting of: —H, —CN, —F, methyl, C 1 haloalkyl, C 1-3 heteroalkyl, methoxy and C 1 haloalkoxy.
19 . The compound of claim 18 , wherein R 22 is selected from the group consisting of: —H, —CN, —F, - and methyl.
20 . The compound of claim 16 , wherein R 24 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —SF 5 , —S(O) 0-2 R 34 , —S(O)(NH)R 34 , —S(O)(NR 28 )R 34 , —S(O)(NH)NR 33 R 33 , —S(O)(NR 28 )NR 33 R 33 , —NR 33 R 33 , —NR 33 SO 2 R 34 , —NR 33 S(O) 2 NR 33 R 33 , —NR 33 C(O)NR 33 R 33 , —NR 33 C(O)OR 34 , —C(O)R 34 , —C(O)OR 34 , —C(O)NR 33 R 33 , —NO 2 , wherein C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, are further substituted with one or more R 29 groups.
21 . The compound of claim 20 , wherein R 24 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, S(O) 0-2 R 34 , —C(O)R 34 , —NO 2 , —SF 5 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 34 is selected from the group consisting of C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, are optionally substituted with one or more R 36 groups, and R 36 is independently selected from halo, —CN and —OH.
22 . The compound of claim 21 , wherein R 24 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, —SR 34 , —SF 5 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 34 is selected from the group consisting of C 1-3 haloalkyl.
23 . The compound of claim 16 , wherein R 23 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, 3-12 membered cycloalkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —S(O) 0-2 R 34 , —NO 2 and —SF 5 , wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, and 3-12 membered cycloalkyl are optionally further substituted with one or more R 36 groups.
24 . The compound of claim 23 , wherein R 23 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —SR 34 , and —SF 5 , wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl are further substituted with one or more R 36 groups, and R 34 is C 1-3 haloalkyl
25 . A compound of Formula III:
or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, wherein:
Q is selected from the group consisting of —S(O) 2 —, —S(O)—, —S(O)(NH)—, —S(O)(NR 48 )—.
R 41 is selected from a group consisting of: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —NR 53 R 53 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are optionally further substituted with one or more R 51 groups;
R 51 is selected from the group consisting of: hydroxyl, oxo, halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R 54 R 54 , —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —S(O) 0-2 R 54 , —S(O) 1-2 NR 53 R 53 , —SF 5 , —NO 2 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —OS(O) 2 R 54 , —C(O)OR 54 , —C(O)R 54 , —NR 53 C(O)OR 54 , —NR 53 C(O)NR 53 R 53 , —NR 53 S(O) 2 NR 53 R 53 , and —C(O)NR 53 R 53 , wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally substituted with one or more R 49 groups;
each R 49 is independently selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR 53 R 53 , —NR 53 C(O)OR 54 , —OS(O) 2 R 54 —C(O)OR 54 , —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —S(O) 0-2 R 54 , —S(O) 1-2 NR 53 R 53 , —C(O)NR 53 R 53 , —NR 53 SO 2 R 54 , —C(O)R 54 , —NR 53 C(O)NR 53 R 53 , —NR 53 S(O) 2 NR 53 R 53 , —SF 5 , —NO 2 , wherein each of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl is optionally substituted with R 56 ;
each R 53 is independently selected from the group consisting of —H, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 55 groups;
Each R 54 is independently selected from the group consisting of: C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 55 groups;
each R 55 is independently selected from —H, halo, —CN, —OH, oxo, —NO 2 , —SF 5 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R 56 , —S(O)(NR 48 )R 56 , —S(O)(NH)NR 56 R 56 , —S(O)(NR 48 )NR 56 R 56 , —S(O) 0-2 R 56 , —S(O) 2 NH 2 , —NH 2 , —S(O) 2 NR 56 R 56 , C(O)R 56 , —C(O)NR 56 R 56 and C(O)OR 56 , wherein 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally substituted with one or more R 56 groups;
each R 56 is independently selected from halo, —CN, —OH, —NH 2 , oxo, —NO 2 , —SF 5 , C 1-3 alkyl, C 1-3 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, thiohaloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH 2 and —S(O) 2 NH 2 ;
R 42 is selected from a group consisting of: —H, —CN, —F, —Cl, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 heteroalkyl, C 1-3 alkoxy and C 1-3 haloalkoxy;
each R 43 and R 44 is independently selected from a group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 54 , —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —SH, —S(O) 1-2 NR 53 R 53 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —NR 53 S(O) 2 NR 53 R 353 , —NR 53 C(O)NR 53 R 53 , —NR 53 C(O)OR 54 , tri-C 1-4 alkylsilyl, —C(O)R 54 , —C(O)OR 54 , —C(O)NR 53 R 53 , —NO 2 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally further substituted with one or more R 49 groups;
wherein R 42 and R 43 , or R 43 and R 44 can optionally join, together with the atoms to which they are attached, to form a 5-6 membered cycloalkyl, a 5-6 membered heterocyclyl, phenyl, or a 5-6 membered heteroaryl, each such cyclic groups respectively fused to the phenyl to which they are attached, and each optionally substituted with one or more R 49 groups;
R 47 is selected from the group consisting of: —H, halo, —CN, —OH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 16 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O) 0-2 R 54 , —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —SH, —NR 53 R 53 , —P(O)R 54 R 54 , —C(O)OH, —C(O)OR 54 , —C(O)NR 53 R 53 , —S(O) 2 NR 53 R 53 , —C(O)R 54 , 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl; wherein each of said 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-12 membered cycloalkyl are optionally substituted with one or more R 55 ;
R 48 is C 1-6 alkyl, —C(O)R 54 , 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, C(O)OR 4 , C(O)NR 53 R 53 , and SO 2 R 54 , wherein each of C 1-6 alkyl, C 1-6 alkylcarbonyl, 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, —S(O) 1-2 R 54 , —S(O) 2 NR 53 R 53 , —NO 2 , —SF 5 , C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, —NR 53 R 53 , —C(O)OR 4 , C 1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with R 56 , 4-12 membered heterocyclyl optionally substituted with one or more R 56 , 6-10 membered aryl optionally substituted with one or more R 56 , and 5-10 membered heteroaryl optionally substituted with one or more R 56 ;
subject to the proviso that:
when both R 43 and R 47 are H, then R 44 is selected from the group consisting of: C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl, 7-12 membered monocyclic heterocyclyl, —SF 5 , —NR 53 R 53 , —NR 53 C(O)OR 54 , —NR 53 SO 2 R 54 , —NR 53 S(O) 2 NR 53 R 53 , —NR 53 C(O)NR 53 R 53 , tri-C 1-4 alkylsilyl, —C(O)R 54 , —C(O)OR 54 , —C(O)NR 53 R 53 , —S(O) 0-2 R 54 , —S(O)(NH)R 54 , —S(O)(NR 8 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 8 )NR 53 R 53 , —SH and —NO 2 , wherein C 7-12 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl and 7-12 membered monocyclic heterocyclyl are optionally substituted with one or more R 49 ; 5-6 membered heterocyclyl is optionally substituted with R 57 ; and 8-10 membered bicyclic heterocyclyl is optionally substituted with one or more R 58 ;
wherein R 57 is selected from —OH, oxo, —CN, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O) 0-2 R 54 , —NR 53 SO 2 R 54 , —NR 53 S(O) 2 NR 53 R 53 , —NR 53 C(O)NR 53 R 53 , —NR 53 C(O)OR 54 , —C(O)R 54 , —C(O)OR 54 and —C(O)NR 53 R 53 .
and wherein R 58 is selected from C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O) 0-2 R 54 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —NR 53 S(O) 2 NR 53 R 53 , —NR 53 C(O)NR 53 R 53 . —NR 53 C(O)OR 54 , —C(O)R 54 , —C(O)OR 54 and —C(O)NR 53 R 53 .
26 . The compound of claim 25 , wherein R 47 is selected from the group consisting of —H, halo, —CN, —OH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O) 0-2 R 54 , —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —NR 53 R 53 , —C(O)OH, —C(O)OR 54 , —C(O)NR 53 R 53 , —S(O) 2 NR 53 R 53 , —C(O)R 54 , 6-10 membered aryl, 5-10 membered heteroaryl, and 4-12 membered heterocyclyl; wherein each of said 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-12 membered cycloalkyl are optionally substituted with one or more R 55 .
27 . The compound of claim 25 , wherein R 47 is selected from the group consisting of —H, halo, —CN, —OH, C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, —S(O) 0-2 R 54 , —C(O)OH, —C(O)OR 54 , —C(O)NR 53 R 53 , —S(O) 2 NR 53 R 53 , —C(O)R 54 , 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl; wherein each of said 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-6 membered cycloalkyl are optionally substituted with one or more R 56 .
28 . The compound of claim 25 , wherein R 47 is selected from the group consisting of —H, halo, —CN, —OH, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, and 6-10 membered aryl, wherein each of said 6-10 membered aryl, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, and C 1-6 heteroalkyl are optionally substituted with one or more R 56 , wherein R 56 is selected from halo, —CN, —NO 2 , —SF 5 , C 1-3 alkyl, C 1-3 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, thiohaloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl;
29 . The compound of claim 25 wherein Q is selected from the group consisting of —S(O) 2 —, —S(O)—, and —S(O)(NR 48 )—.
30 . The compound of claim 25 , wherein R 41 is selected from the group consisting of: C 1-6 alkyl, —NR 53 R 53 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are further optionally substituted with one or more R 51 groups.
31 . The compound of claim 25 , wherein R 51 is selected from the group consisting of: hydroxyl, oxo, halo, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —S(O) 0-2 R 54 , —S(O) 1-2 NR 53 R 53 , —SF 5 , —NO 2 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —C(O)OR 54 , —C(O)R 54 , —NR 53 C(O)OR 54 , —and —C(O)NR 53 R 53 , wherein each C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are optionally substituted with one or more R 49 groups;
32 . The compound of claim 25 , wherein each R 49 is independently selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-3 alkyl, C 1-3 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, —NR 53 R 53 , —C(O)OR 54 , —S(O) 0-2 R 54 , —S(O) 1-2 NR 53 R 53 , —C(O)NR 53 R 53 , —NR 53 SO 2 R 54 , —C(O)R 54 , —SF 5 , and —NO 2 , wherein each of C 1-3 alkyl, C 1-3 alkoxy, 3-6 membered cycloalkyl, is optionally substituted with —CN, one or more halo, or C 1-6 heteroalkyl.
33 . The compound of claim 25 , wherein R 42 is selected from the group consisting of: —H, —CN, —F, methyl, C 1 haloalkyl, C 1-3 heteroalkyl, methoxy and C 1 haloalkoxy.
34 . The compound of claim 25 , wherein R 42 is selected from the group consisting of: —H and —F.
35 . The compound of claim 25 wherein R 44 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —SF 5 , —S(O) 0-2 R 5 4, —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —NR 53 S(O) 2 NR 53 R 53 , —NR 53 C(O)NR 53 R 53 , —NR 53 C(O)OR 54 , —C(O)R 54 , —C(O)OR 54 , —C(O)NR 53 R 53 , —NO 2 , wherein C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl are further substituted with one or more R 49 groups.
36 . The compound of claim 25 , wherein R 44 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, —S(O) 0-2 R 54 , —NO 2 , —SF 5 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 54 is selected from the group consisting of C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, are optionally substituted with one or more R 55 groups, and R 55 is independently selected from halo, —CN, —OH, oxo.
37 . The compound of claim 25 , wherein R 4 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, —SR 54 , —SF 5 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 54 is C 1-3 haloalkyl.
38 . The compound of claim 25 , wherein R 43 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-12 cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 54 , —S(O)(NH)R 54 , —S(O)(NR 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —NR 53 S(O) 2 NR 53 R 53 . —NR 53 C(O)NR 53 R 53 , —NR 53 C(O)OR 54 , —C(O)R 54 , —C(O)OR 54 , —C(O)NR 53 R 53 , and —NO 2 , wherein C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-12 cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are further substituted with one or more R 49 groups.
39 . The compound of claim 25 , wherein R 49 is selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-3 alkyl, C 1-3 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, —NR 53 R 53 , —C(O)OR 54 , —S(O) 0-2 R 54 , —S(O) 1-2 NR 53 R 53 , —C(O)NR 53 R 53 , —C(O)R 54 , wherein each of C 1-3 alkyl, C 1-3 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-6 membered cycloalkyl is optionally substituted with —CN or one or more halo.
40 . The compound of claim 25 , wherein R 43 is selected from the group consisting of: —H, halo, —CN, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 4-6 membered heterocyclyl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 54 , and —NO 2 , wherein C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 4-6 membered heterocyclyl, and 5-10 membered heteroaryl are further substituted with one or more R 49 groups.
41 . The compound of claim 40 , wherein R 49 is selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, —C(O)OR 54 , —S(O) 0-2 R 54 , —S(O) 1-2 NR 53 R 53 , —C(O)R 54 , wherein each of C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, and 3-6 membered cycloalkyl is optionally substituted with —CN or one or more halo.
42 . A compound of Formula IV:
or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, wherein:
Q is selected from the group consisting of —S(O) 2 —, —S(O)—, —S(O)(NH)—, —S(O)(NR 68 )—;
R 61 is selected from a group consisting of: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —NR 73 R 73 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are optionally further substituted with one or more R 71 groups;
R 71 is selected from the group consisting of: hydroxyl, oxo, halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R 74 R 74 , —S(O)(NH)R 74 , —S(O)(NR 68 )R 74 , —S(O)(NH)NR 73 R 73 , —S(O)(NR 68 )NR 73 R 73 , —SH, —S(O) 0-2 R 74 , —S(O) 1-2 NR 73 R 73 , —SF 5 , —NO 2 , —NR 73 R 73 , —NR 73 SO 2 R 74 , —OS(O) 2 R 74 , —C(O)OR 74 , —C(O)R 74 , —NR 73 C(O)OR 74 , —NR 73 C(O)NR 73 R 73 , —NR 73 S(O) 2 NR 73 R 73 , and —C(O)NR 73 R 73 , wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally substituted with one or more R 69 groups;
each R 69 is independently selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR 73 R 73 , —NR 73 C(O)OR 74 , —OS(O) 2 R 74 —C(O)OR 74 , —S(O)(NH)R 74 , —S(O)(NR 68 )R 74 , —S(O)(NH)NR 73 R 73 , —S(O)(NR 68 )NR 73 R 73 , —SH, —S(O) 0-2 R 74 , —S(O) 1-2 NR 73 R 73 , —C(O)NR 73 R 73 , —NR 73 SO 2 R 74 , —C(O)R 74 , —NR 73 C(O)NR 73 R 73 , —NR 73 S(O) 2 NR 73 R 73 , —SF 5 , —NO 2 , wherein each of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl is optionally substituted with one or more R 76 groups;
each R 73 is independently selected from the group consisting of —H, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 75 groups;
Each R 74 is independently selected from the group consisting of: C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with one or more R 75 groups;
each R 75 is independently selected from —H, halo, —CN, —OH, oxo, —NO 2 , —SF 5 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R 66 , —S(O)(NR 68 )R 66 , —S(O)(NH)NR 66 R 66 , —S(O)(NR 68 )NR 66 R 66 , —SH, —S(O) 0-2 R 66 , —S(O) 2 NH 2 , —NH 2 , —S(O) 2 NR 66 R 66 , C(O)R 66 , —C(O)NR6 66 R 66 and C(O)OR 66 , wherein 3-6 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally substituted with one or more R 76 groups;
each R 76 is independently selected from halo, —CN, —OH, —NH 2 , oxo, —NO 2 , —SF 5 , C 1-3 alkyl, C 1-3 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, thioalkyl, thiohaloalkyl, thiocycloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH 2 and —S(O) 2 NH 2 ;
R 62 is selected from a group consisting of: —H, —CN, —F, —Cl, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 heteroalkyl, C 1-3 alkoxy and C 1-3 haloalkoxy;
each R 63 and R 64 is independently selected from a group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 74 , —S(O)(NH)R 74 , —S(O)(NR 68 )R 74 , —S(O)(NH)NR 73 R 73 , —S(O)(NR 68 )NR 73 R 73 , —SH, —NR 73 R 73 , —NR 73 SO 2 R 74 , —NR 73 S(O) 2 NR 73 R 73 , —NR 73 C(O)NR 73 R 73 , —NR 73 C(O)OR 74 , tri-C 1-4 alkylsilyl, —C(O)R 74 , —C(O)OR 74 , —C(O)NR 73 R 73 and —NO 2 , wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl are optionally further substituted with one or more R 69 groups;
wherein R 62 and R 63 , or R 63 and R 64 can optionally join, together with the atoms to which they are attached, to form a 5-6 membered cycloalkyl, a 5-6 membered heterocyclyl, phenyl, or a 5-6 membered heteroaryl, each such cyclic groups respectively fused to the phenyl to which they are attached, and each optionally substituted with one or more R 69 groups;
R 67 is selected from the group consisting of: —H, halo, —CN, —OH, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 16 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O) 0-2 R 74 , —S(O)(NH)R 74 , —S(O)(NR 68 )R 74 , —S(O)(NH)NR 73 R 73 , —S(O)(NR 68 )NR 73 R 73 , —SH, —NR 73 R 73 , —P(O)R 74 R 74 , —C(O)OH, —C(O)OR 74 , —C(O)NR 73 R 73 , —S(O) 2 NR 73 R 73 , —C(O)R 74 , 6-10 membered aryl, 5-10 membered heteroaryl and 4-12 membered heterocyclyl; wherein each of said 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, tri-C 1-4 alkylsilyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-12 membered cycloalkyl are optionally substituted with one or more R 75 .
R 68 is C 1-6 alkyl, —C(O)R 74 , 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, —C(O)OR 74 , —C(O)NR 73 R 73 , —SO 2 R 74 , wherein each of C 1-6 alkyl, C 1-6 alkylcarbonyl, 3-12 membered cycloalkyl, C 1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, —S(O) 1-2 R 74 , —S(O) 2 NR 73 R 73 , —NO 2 , —SF 5 , C 1-6 haloalkyl, C 16 haloalkoxy, C 1-6 hydroxyalkyl, NR 73 R 73 , —C(O)OR 74 , C 1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with R 76 , 4-12 membered heterocyclyl optionally substituted with one or more R 76 , 6-10 membered aryl optionally substituted with one or more R 76 , and 5-10 membered heteroaryl optionally substituted with one or more R 76 ;
43 . The compound of claim 42 wherein Q is selected from the group consisting of —S(O) 2 —, —S(O)—, and —S(O)(NR 68 )—.
44 . The compound of claim 42 , wherein R 61 is selected from the group consisting of: C 1-6 alkyl, —NR 73 R 73 , 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C 1-6 alkyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl are further substituted with one or more R 71 groups.
45 . The compound of claim 42 , wherein R 62 is selected from the group consisting of: —H, —CN, —F, methyl, C 1 haloalkyl, C 1-3 heteroalkyl, methoxy and C 1 haloalkoxy.
46 . The compound of claim 45 , wherein R 62 is selected from the group consisting of: —H, and —F.
47 . The compound of claim 42 , wherein R 64 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, —SF 5 , —S(O) 0-2 R 74 , —S(O)(NH)R 74 , —S(O)(NR 68 )R 74 , —S(O)(NH)NR 73 R 73 , —S(O)(NR 68 )NR 73 R 73 , —NR 73 R 73 , —NR 73 SO 2 R 74 , —NR 73 S(O) 2 NR 73 R 73 , —NR 73 C(O)NR 73 R 73 , —NR 73 C(O)OR 74 , —C(O)R 74 , —C(O)OR 74 , —C(O)NR 73 R 73 , —NO 2 , wherein C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl are further substituted with one or more R 69 groups.
48 . The compound of claim 47 , wherein R 64 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, —S(O) 0-2 R 74 , —SF 5 , —NO 2 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alky or C 1-6 alkoxy is optionally substituted with one or more —F. and R 74 is selected from the group consisting of C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, are optionally substituted with one or more R 75 groups, and R 75 is independently selected from halo, —CN, —OH, oxo.
49 . The compound of claim 48 , wherein R 64 is selected from the group consisting of: —H, —F, —Cl, —OH, —CN, SR 74 , —SF 5 , C 1-6 alkyl, and C 1-6 alkoxy, and wherein said C 1-6 alkyl or C 1-6 alkoxy is optionally substituted with one or more —F, and R 74 is C 1-3 haloalkyl.
50 . The compound of claim 42 , wherein R 63 is selected from the group consisting of: —H, halo, —OH, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-12 cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 74 , —S(O)(NH)R 74 , —S(O)(NR 68 )R 74 , —S(O)(NH)NR 73 R 73 , —S(O)(NR 48 )NR 73 R 73 , —NR 73 R 73 , —NR 73 SO 2 R 74 , —NR 73 S(O) 2 NR 73 R 73 . —NR 73 C(O)NR 73 R 73 , —NR 73 C(O)OR 74 , —C(O)R 74 , —C(O)OR 74 , —C(O)NR 73 R 73 , and —NO 2 , wherein C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, C 3-12 cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are further substituted with one or more R 69 groups.
51 . The compound of claim 42 , wherein R 69 is selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-3 alkyl, C 1-3 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, —NR 73 R 73 , —C(O)OR 74 , —S(O) 0-2 R 74 , —S(O) 1-2 NR 73 R 73 , —C(O)NR 73 R 73 , —C(O)R 74 , wherein each of C 1-3 alkyl, C 1-3 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-6 membered cycloalkyl is optionally substituted with —CN or one or more halo.
52 . The compound of claim 50 , wherein R 63 is selected from the group consisting of: —H, halo, —CN, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 4-6 membered heterocyclyl, 5-10 membered heteroaryl, —SF 5 , —S(O) 0-2 R 74 , and —NO 2 , wherein C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, C 3-6 cycloalkyl, 4-6 membered heterocyclyl, and 5-10 membered heteroaryl are further substituted with one or more R 69 groups.
53 . The compound of claim 51 , wherein R 69 is selected from the group consisting of: —H, oxo, —OH, —CN, halo, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, 3-6 membered cycloalkyl, —C(O)OR 74 , —S(O) 0-2 R 74 , —S(O) 1-2 NR 73 R 73 , —C(O)R 74 , wherein each of C 1-3 alkyl, C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 1-6 heteroalkyl, and 3-6 membered cycloalkyl is optionally substituted with —CN or one or more halo.
54 . A compound selected from the group consisting of:
55 . A compound selected from the group consisting of:
56 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, together with a pharmaceutically acceptable excipient.
57 . A pharmaceutical composition comprising a compound of claim 15 , or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, together with a pharmaceutically acceptable excipient.
58 . A pharmaceutical composition comprising a compound of claim 25 , or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, together with a pharmaceutically acceptable excipient.
59 . A pharmaceutical composition comprising a compound of claim 42 , or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, together with a pharmaceutically acceptable excipient.
60 . A pharmaceutical composition comprising a compound of claim 54 , or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, together with a pharmaceutically acceptable excipient.
61 . A pharmaceutical composition comprising a compound of claim 55 , or a pharmaceutically acceptable salt, stereoisomer, mixtures of stereoisomers, tautomer, or deuterated analogs thereof, together with a pharmaceutically acceptable excipient.
62 . A method of treating NAFLD, NASH, ASH or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a composition of claim 56 .
63 . A method of treating NAFLD, NASH, ASH or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a composition of claim 57 .
64 . A method of treating NAFLD, NASH, ASH or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a composition of claim 58 .
65 . A method of treating NAFLD, NASH, ASH or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a composition of claim 59 .
66 . A method of treating NAFLD, NASH, ASH or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a composition of claim 60 .
67 . A method of treating NAFLD, NASH, ASH or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a composition of claim 61 .