Sulfinylaminobenzamide and sulfonylaminobenzamide derivatives

1. A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof, wherein:

Q is —S(O) 2 —;

R 1 is selected from the 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 of the 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 is 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)NR 13 R 13 , and —C(O)NR 13 R 13 , 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, and 5-10 membered heteroaryl is 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 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 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 the 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 the group consisting of —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 said 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 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 the 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 the 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 a 5-10 membered carbobicyclic ring, wherein the 5-10 membered carbobicyclic ring, may be fused, bridged or spiro, and wherein the 5-10 membered carbobicyclic ring, is 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, 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 is optionally substituted with one or more R 15 ; and n is 1, 2, or 3;

R 8 is selected from the group consisting 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, —C(O)OR 14 , —C(O)NR 13 R 13 , and —SO 2 R 14 , wherein each of the C 1-6 alkyl, —C(O)R 14 , 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 14 , —S(O) 2 NR 13 R 13 , —NO 2 , —SF 5 , C 1-6 haloalkyl, C 1-6 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 , or 5-10 membered heteroaryl optionally substituted with one or more R 16 ;

subject to the provisos that:

(i) when R 6 is a C 8-10 carbocyclic 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 each of the 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 is optionally substituted with one or more R 9 ; 5-6 membered heterocyclyl optionally substituted with R 17 ; and 8-10 membered bicyclic heterocyclyl optionally substituted with one or more R 18 ,

(ii) when R 6 is a C 6 -C 7 carbocyclic 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 each of the 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 is optionally further substituted with one or more R groups;

wherein R 17 is selected from the group consisting of —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 the group consisting of 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 method 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 is further substituted with one or more R 11 groups.

3. The method of claim 1 , wherein R 2 is selected from the group consisting of: —H, —CN, —F, methyl, methoxy and C 1 haloalkoxy.

4. The method of claim 3 , wherein R 2 is selected from the group consisting of: —H and —F.

5. The method 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 , and —NO 2 , wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, is further substituted with one or more R 9 groups.

6. The method of claim 5 , 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, and 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 15 groups, and R 15 is independently selected from the group consisting of halo, —CN, and —OH.

7. The method of claim 6 , 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 a C 1-3 haloalkyl.

8. The method 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 is optionally further substituted with one or more R 9 groups.

9. The method of claim 8 , 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 3-2 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 is optionally substituted with one or more R 9 , and R 14 is C 1-3 haloalkyl.

10. The method of claim 1 , wherein R 5 is selected from the group consisting of: —H, —F, and methyl.

11. A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a compound of Formula II:

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof, wherein:

x, y, and z are independently 1, 2, 3, or 4,

Q is S(O) 2 :

R 21 is selected from the 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 is optionally further substituted with one or more R 3 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 of the 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 is 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 , and —NO 2 , wherein each of the 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 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 the group consisting of —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 26 , —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 said 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 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 the 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 the 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 , and —NO 2 , wherein said 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 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, 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 is optionally substituted with one or more R 35 ;

R 28 is selected from the group consisting of: 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 , and —SO 2 R 34 , wherein each of the C 1-6 alkyl, 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 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 , or 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 1-6 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 each of the 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 is optionally substituted with one or more R 29 ; 5-6 membered heterocyclyl optionally substituted with R 37 ; and 8-10 membered bicyclic heterocyclyl 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)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 , and —NO 2 , wherein each of the 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 29 groups;

wherein R 37 is selected from the group consisting of —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 the group consisting of 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 .

12. The method of claim 11 , wherein R 21 is selected from a group consisting of: C 1-6 alkyl, —NR 13 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 is further substituted with one or more R 31 groups.

13. The method of claim 11 , 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.

14. The method of claim 13 , wherein R 22 is selected from the group consisting of: —H, —CN, —F, and methyl.

15. The method of claim 11 , 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 , and —NO 2 , wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, is further substituted with one or more R 29 groups.

16. The method of claim 15 , 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, and C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, is optionally substituted with one or more R 35 groups, and R 35 is independently selected from the group consisting of halo, —CN and —OH.

17. The method of claim 16 , 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 a C 1-6 haloalkyl.

18. A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a compound of Formula III:

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof, wherein:

Q is —S(O) 2 —;

R 41 is selected from the 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 is optionally further substituted with one or more R 51 groups;

R 51 is selected from the group consisting of: hydroxyl, oxo, halo, —CN, C 2-6 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, and 5-10 membered heteroaryl is 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 , and —NO 2 , wherein each of the 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 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 is 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 is 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 said 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 56 groups;

each R 51 is independently selected from the group consisting of 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 the 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 the 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 , and —NO 2 , wherein said 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 is optionally further substituted with one or more R 49 groups;

wherein R 42 and R 43 , or R 43 and R 44 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 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 , —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, 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 is optionally substituted with one or more R 55 ;

R 48 is selected from the group consisting of: 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 54 , C(O)NR 53 R 53 , and SO 2 R 54 , wherein each of C 1-6 alkyl, 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 54 , 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 , or 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 48 )R 54 , —S(O)(NH)NR 53 R 53 , —S(O)(NR 48 )NR 53 R 53 , —SH and —NO 2 , wherein each of the 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 optionally substituted with R 57 ; and 8-10 membered bicyclic heterocyclyl optionally substituted with one or more R 58 ;

wherein R 57 is selected from the group consisting of: —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 the group consisting of: 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 .

19. The method of claim 18 , 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 is optionally substituted with one or more R 55 .

20. The method of claim 18 , 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, 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 alkynyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, C 1-6 heteroalkyl, and 3-6 membered cycloalkyl is optionally substituted with one or more R 55 .

21. The method of claim 18 , wherein R 47 is selected from the group consisting of —H, halo, —CN, —OH, C 1-3 alkyl, C 1-3 alkoxy, C 1-6 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 is optionally substituted with one or more R 55 , wherein R 55 is selected from the group consisting of: halo, —CN, —NO 2 , —SF 5 , C 1-3 alkyl, C 1-3 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy.

22. The method of claim 18 , 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 is further optionally substituted with one or more R 51 groups.

23. The method of claim 18 , 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) 12 NR 53 R 53 , —SF 5 , —NO 2 , —NR 53 R 53 , —NR 53 SO 2 R 54 , —C(O)OR 14 , —C(O)R 54 , —NR 53 C(O)OR 14 , 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 is optionally substituted with one or more R 49 groups.

24. The method of claim 18 , 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 3 R 53 , —C(O)NR 53 R 53 , —NR 53 SO 2 R 54 , —C(O)R 14 , —SF 5 , and —NO 2 , wherein each of the C 1-3 alkyl, C 3 alkoxy, and 3-6 membered cycloalkyl, is optionally substituted with —CN, or one or more halo.

25. The method of claim 18 , 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.

26. The method of claim 18 , wherein R 42 is selected from the group consisting of: —H and —F.

27. The method of claim 18 , 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 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 each C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl is further substituted with one or more R 49 groups.

28. The method of claim 18 , wherein R 18 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, and C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, is optionally substituted with one or more R 55 groups, and R 55 is independently selected from halo, —CN, —OH, and oxo.

29. The method of claim 18 , wherein R 44 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.

30. The method of claim 18 , 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 54 , —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 the 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 is further substituted with one or more R 49 groups.

31. The method of claim 18 , 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 , and —C(O)R 54 , wherein each of the 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.

32. The method of claim 18 , 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 each of the 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 is further substituted with one or more R 4 groups.

33. The method of claim 32 , wherein R 41 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 , and —C(O)R 54 , wherein each of the 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.

34. A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof, an effective amount of a compound of Formula IV:

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof, wherein:

Q is —S(O) 2 —;

R 61 is selected from the 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 is 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 of the 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 is 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 73 , —NR 73 C(O)NR 73 R 73 , —NR 73 S(O) 2 NR 73 R 73 , —SF 5 , and —NO 2 , wherein each of the 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 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 is 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 is 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 76 , S(O)(NR 68 )R 76 , —S(O)(NH)NR 76 R 76 , —S(O)(NR 68 )NR 76 R 76 , —SH, —S(O) 0-2 R 76 , —S(O) 2 NH 2 , —NH 2 , —S(O) 2 NR 76 R 76 , —C(O)R 76 , —C(O)NR 76 R 76 and —C(O)OR 76 , wherein said 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 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 the 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 the 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 said 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 is 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 1-6 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 is optionally substituted with one or more R 75 ;

R 68 is selected from the group consisting of 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 , and —SO 2 R 74 , wherein each of the C 1-6 alkyl, 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 1-6 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 .

35. The method of claim 34 , 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 of the C 1-6 alkyl, 6-10 membered aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl is further substituted with one or more R 71 groups.

36. The method of claim 34 , 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.

37. The method of claim 36 , wherein R 62 is selected from the group consisting of: —H and —F.

38. The method of claim 34 , 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 , and —NO 2 , wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl is further substituted with one or more R 69 groups.

39. The method of claim 38 , 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 alkyl 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, and C 1-6 heteroalkyl, wherein the C 1-6 alkyl, C 1-6 hydroxyalkyl, and C 1-6 heteroalkyl, is optionally substituted with one or more R 75 groups, and R 76 is independently selected from the group consisting of: halo, —CN, —OH, and oxo.

40. The method of claim 39 , 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.

41. The method of claim 34 , 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 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 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 is further substituted with one or more R 69 groups.

42. The method of claim 34 , 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 , and —C(O)R 74 , wherein each of the 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.

43. The method of claim 41 , 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 said 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 is further substituted with one or more R 1 groups.

44. The method 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 1-3 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 , and —C(O)R 74 , wherein each of the 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.

45. The method of claim 1 , wherein the compound is selected from the group consisting of:

46. The method of claim 1 , wherein the compound is selected from the group consisting of:

47. The method of claim 1 , wherein the compound is selected from the group consisting of:

48. The method of claim 1 , wherein the compound is selected from the group consisting of:

49. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

50. The method of claim 1 , wherein the compound is