Sulfinylaminobenzamide and sulfonylaminobenzamide derivatives

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:
• R21 is selected from the group consisting of:
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —NR33R33, 6-10 membered aryl, 5-10 membered heteroaryl, C3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C3-12 cycloalkyl, and 4-12 membered heterocyclyl is optionally further substituted with one or more R3 groups;
• R31 is selected from the group consisting of:
• hydroxyl, oxo, halo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R34R34, —S(O)(NH)R34, —S(O)(NR28)R34, —S(O)(NH)NR33R33, —S(O)(NR28)NR33R33, —SH, —S(O)0-2R34, —S(O)1-2NR33R33, —SF5, —NO2, —NR33R33, —NR33SO2R34, —OS(O)2R34, —C(O)OR34, —C(O)R34, —NR33C(O)OR34, —NR33C(O)NR33R33, —NR33S(O)2NR33R33, and —C(O)NR33R33, wherein each of the C1-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6 hydroxyalkyl, C1-6 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 R29 groups;
• each R29 is independently selected from the group consisting of:
• —H, oxo, —OH, —CN, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR33R33, —NR33C(O)OR34, —OS(O)2R34, —C(O)OR34, —S(O)(NH)R34, —S(O)(NR8)R34, —S(O)(NH)NR33R33, —S(O)(NR28)NR33R33, —S(O)0-2R34, —S(O)1-2NR33R33, —C(O)NR33R33, —NR33SO2R34, —C(O)R34, —NR33C(O)NR33R33, —NR33S(O)2NR33R33, —SF5, and —NO2, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R36;
• each R33 is independently selected from the group consisting of —H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, C3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 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 R35 groups;
• each R34 is independently selected from the group consisting of:
• C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, C3-6cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 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 R35 groups;
• each R35 is independently selected from the group consisting of —H, halo, —CN, —OH, oxo, —NO2, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R36, —S(O)(NR28)R26, —S(O)(NH)NR36R36, —S(O)(NR28)NR36R36, —S(O)0-2R36, —S(O)2NH2, —NH2, —S(O)2NR36R36, C(O)R36, —C(O)NR36R36 and C(O)OR36, 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 R36 groups;
• each R36 is independently selected from halo, —CN, —OH, —NH2, oxo, —NO2, —SF5, C1-3 alkyl, C1-3 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, thiohaloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH2 and —S(O)2NH2;
• R22 is selected from the group consisting of:
• —H, —CN, —F, —Cl, C1-3 alkyl, C1-3 haloalkyl, C1-3 heteroalkyl, C1-3 alkoxy and C1-3 haloalkoxy;
• each R23 and R24 is independently selected from the group consisting of:
• —H, halo, —OH, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF5, —S(O)0-2R34, —S(O)(NH)R34, —S(O)(NR28)R34, —S(O)(NH)NR33R33, —S(O)(NR28)NR33R33, —SH, —NR33R33, —NR33SO2R34, —NR33S(O)2NR33R33, —NR33C(O)NR33R33, —NR33C(O)OR34, tri-C1-4 alkylsilyl, —C(O)R34, —C(O)OR34, —C(O)NR33R33, and —NO2, wherein said C1-6, alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R29 groups;
• wherein R22 and R23, or R23 and R24 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 R29 groups;
• R27 is selected from the group consisting of:
• —H, halo, —CN, oxo, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, tri-C1-4 alkylsilyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O)0-2R34, —S(O)(NH)R34, —S(O)(NR28)R34, —S(O)(NH)NR33R33, —S(O)(NR28)NR33R33, —NR33R33, —P(O)R34R34, —C(O)OH, —C(O)OR34, —C(O)NR33R33, —S(O)2NR33R33, —C(O)R34, 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, tri-C1-4 alkylsilyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, and 3-12 membered cycloalkyl is optionally substituted with one or more R35;
• R28 is selected from the group consisting of:
• C1-6 alkyl, —C(O)R34, 3-12 membered cycloalkyl, C1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, —C(O)OR34, —C(O)NR33R33, and —SO2R34, wherein each of the C1-6 alkyl, 3-12 membered cycloalkyl, C1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C1-6alkyl, C1-6alkoxy, —S(O)1-2R34, —S(O)2NR33R33, —NO2, —SF5, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —NR33R33, —C(O)OR34, C1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with one or more R36, 4-12 membered heterocyclyl optionally substituted with one or more R36, 6-10 membered aryl optionally substituted with one or more R36, or 5-10 membered heteroaryl optionally substituted with one or more R36:
• subject to the provisos that:
• (i) when x+y+z is 6 to 10, and both R23 and R27 are H, then R24 is selected from the group consisting of:
• C7-12 cycloalkyl, C2-6 alkenyl, C1-6 alkynyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl, 7-12 membered monocyclic heterocyclyl, —SF5, —NR33R33, —NR33C(O)OR34, —NR33SO2R34, —NR33S(O)2NR33R33, —NR33C(O)NR33R33, tri-C1-4 alkylsilyl, —C(O)R34, —C(O)OR34, —C(O)NR33R33, —S(O)0-2R34, —S(O)(NH)R34, —S(O)(NR28)R34, —S(O)(NH)NR33R33, —S(O)(NR28)NR33R33, —SH and —NO2, wherein each of the C7-12 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl and 7-12 membered monocyclic heterocyclyl is optionally substituted with one or more R29;
• 5-6 membered heterocyclyl optionally substituted with R37;
• and 8-10 membered bicyclic heterocyclyl optionally substituted with one or more R38;
• and
• (ii) when x+y+z is 4 or 5, and R27 is —H or methyl, R23 is selected from the group consisting of:
• halo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF5, —S(O)0-2R34, —S(O)(NH)R34, —S(O)(NR28)R34, —S(O)(NH)NR33R33, —S(O)(NR)NR33R33, —SH, —NR33R33, —NR33SO2R34, —NR33S(O)2NR33R33, —NR33C(O)NR33R33, —NR33C(O)OR34, tri-C1-4 alkylsilyl, —C(O)R34, —C(O)OR34, —C(O)NR33R33, and —NO2, wherein each of the C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R29 groups;
• wherein R37 is selected from the group consisting of —OH, oxo, —CN, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)0-2R34, —NR33SO2R34, —NR33S(O)2NR33R33, —NR33C(O)NR33R33, —NR33C(O)OR34, —C(O)R34, —C(O)OR34 and —C(O)NR33R33;
• and wherein R38 is selected from the group consisting of C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)0-2R34, —NR33R33, —NR33SO2R34, —NR33S(O)2NR33R33, —NR33C(O)NR33R33, —NR33C(O)OR34, —C(O)R34, —C(O)OR34 and —C(O)NR33R33.

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—;
• R41 is selected from the group consisting of:
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —NR53R53, 6-10 membered aryl, 5-10 membered heteroaryl, C3-12 cycloalkyl, and 4-12 membered heterocyclyl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C3-12 cycloalkyl, and 4-12 membered heterocyclyl is optionally further substituted with one or more R51 groups;
• R51 is selected from the group consisting of:
• hydroxyl, oxo, halo, —CN, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R54R54, —S(O)(NH)R54, —S(O)(NR48)R54, —S(O)(NH)NR53R53, —S(O)(NR48)NR53R53, —S(O)0-2R54, —S(O)1-2NR53R53, —SF5, —NO2, —NR53R53, —NR53SO2R54, —OS(O)2R54, —C(O)OR54, —C(O)R54, —NR53C(O)OR54, —NR53C(O)NR53R53, —NR53S(O)2NR53R53, and —C(O)NR53R53, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R49 groups;
• each R49 is independently selected from the group consisting of:
• —H, oxo, —OH, —CN, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR53R53, —NR53C(O)OR54, —OS(O)2R54, —C(O)OR54, —S(O)(NH)R54, —S(O)(NR48)R54, —S(O)(NH)NR53R53, —S(O)(NR48)NR53R53, —S(O)0-2R54, —S(O)1-2NR53R53, —C(O)NR53R53, —NR53SO2R54, —C(O)R54, —NR53C(O)NR53R53, —NR53S(O)2NR53R53, —SF5, and —NO2, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with R56:
• each R53 is independently selected from the group consisting of —H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, C3-6cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 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 R55 groups;
• each R54 is independently selected from the group consisting of:
• C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, C3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 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 R55 groups;
• each R55 is independently selected from —H, halo, —CN, —OH, oxo, —NO2, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R56, —S(O)(NR48)R56, —S(O)(NH)NR56R56, —S(O)(NR48)NR56R56, —S(O)0-2R56, —S(O)2NH2, —NH2, —S(O)2NR56R56, C(O)R56, —C(O)NR56R56 and C(O)OR56, 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 R56 groups;
• each R51 is independently selected from the group consisting of halo, —CN, —OH, —NH2, oxo, —NO2, —SF5, C1-3 alkyl, C1-3 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, thiohaloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH2 and —S(O)2NH2;
• R42 is selected from the group consisting of:
• —H, —CN, —F, —Cl, C1-3 alkyl, C1-3 haloalkyl, C1-3 heteroalkyl, C1-3 alkoxy and C1-3 haloalkoxy;
• each R43 and R44 is independently selected from the group consisting of:
• —H, halo, —OH, —CN, C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF5—, —S(O)0-2R54, —S(O)(NH)R54, —S(O)(NR48)R54, —S(O)(NH)NR53R53, —S(O)(NR48)NR53R53, —SH, —S(O)1-2NR53R53, —NR53R53, —NR53SO2R54, —NR53S(O)2NR53R353, —NR53C(O)NR53R53, —NR53C(O)OR54, tri-C1-4 alkylsilyl, —C(O)R54, —C(O)OR54, —C(O)NR53R53, and —NO2, wherein said C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R49 groups;
• wherein R42 and R43, or R43 and R44 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 R49 groups;
• R47 is selected from the group consisting of:
• —H, halo, —CN, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, tri-C1-4 alkylsilyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, —S(O)0-2R54, —S(O)(NH)R54, —S(O)(NR48)R54, —S(O)(NH)NR53R53, —S(O)(NR48)NR53R53, —SH, —NR53R53, —P(O)R54R54, —C(O)OH, —C(O)OR54, —C(O)NR53R53, —S(O)2NR53R53, —C(O)R54, 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, tri-C1-4 alkylsilyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, and 3-12 membered cycloalkyl is optionally substituted with one or more R55;
• R48 is selected from the group consisting of:
• C1-6 alkyl, —C(O)R54, 3-12 membered cycloalkyl, C1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, C(O)OR54, C(O)NR53R53, and SO2R54, wherein each of C1-6 alkyl, 3-12 membered cycloalkyl, C1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C1-6alkyl, C1-6alkoxy, —S(O)1-2R54, —S(O)2NR53R53, —NO2, —SF5, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —NR53R53, —C(O)OR54, C1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with R56, 4-12 membered heterocyclyl optionally substituted with one or more R56, 6-10 membered aryl optionally substituted with one or more R56, or 5-10 membered heteroaryl optionally substituted with one or more R56:
• subject to the proviso that:
• when both R43 and R47 are H, then R44 is selected from the group consisting of:
• C7-12 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl, 7-12 membered monocyclic heterocyclyl, —SF5, —NR53R53, —NR53C(O)OR54, —NR53SO2R54, —NR53S(O)2NR53R53, —NR53C(O)NR53R53, tri-C1-4 alkylsilyl, —C(O)R54, —C(O)OR54, —C(O)NR53R53, —S(O)0-2R54, —S(O)(NH)R54, —S(O)(NR48)R54, —S(O)(NH)NR53R53, —S(O)(NR48)NR53R53, —SH and —NO2, wherein each of the C7-12 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 4-membered heterocyclyl, 7-membered heterocyclyl and 7-12 membered monocyclic heterocyclyl are optionally substituted with one or more R49;
• 5-6 membered heterocyclyl optionally substituted with R57;
• and 8-10 membered bicyclic heterocyclyl optionally substituted with one or more R58;
• wherein R57 is selected from the group consisting of:
• —OH, oxo, —CN, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)0-2R54, —NR53SO2R54, —NR53S(O)2NR53R53, —NR53C(O)NR53R53, —NR53C(O)OR54, —C(O)R54, —C(O)OR54 and —C(O)NR53R53,
• and wherein R58 is selected from the group consisting of:
• C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)0-2R54, —NR53R53, —NR53SO2R54, —NR53S(O)2NR53R53, —NR53C(O)NR53R53, —NR53C(O)OR54, —C(O)R54, —C(O)OR54 and —C(O)NR53R53.

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—;
• R61 is selected from the group consisting of:
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —NR73R73, 6-10 membered aryl, 5-10 membered heteroaryl, C3-12cycloalkyl, and 4-12 membered heterocyclyl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 6-10 membered aryl, 5-10 membered heteroaryl, C3-12 cycloalkyl, and 4-12 membered heterocyclyl is optionally further substituted with one or more R71 groups;
• R71 is selected from the group consisting of:
• hydroxyl, oxo, halo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —P(O)R74R74, —S(O)(NH)R74, —S(O)(NR68)R74, —S(O)(NH)NR73R73, —S(O)(NR68)NR73R73, —SH, —S(O)0-2R74, —S(O)1-2NR73R73, —SF5, —NO2, —NR73R73, —NR73SO2R74, —OS(O)2R74, —C(O)OR74, —C(O)R74, —NR73C(O)OR74, —NR73C(O)NR73R73, —NR73S(O)2NR73R73, and —C(O)NR73R73, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R69 groups;
• each R69 is independently selected from the group consisting of:
• —H, oxo, —OH, —CN, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —NR73R73, —NR73C(O)OR74, —OS(O)2R74, —C(O)OR74, —S(O)(NH)R74, —S(O)(NR68)R74, —S(O)(NH)NR73R73, —S(O)(NR68)NR73R73, —SH, —S(O)0-2R74, —S(O)1-2NR73R73, —C(O)NR73R73, —NR73SO2R74, —C(O)R73, —NR73C(O)NR73R73, —NR73S(O)2NR73R73, —SF5, and —NO2, wherein each of the C1-6 alkyl, C1-6alkoxy, C1-6 hydroxyalkyl, C1-6 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 R76 groups;
• each R73 is independently selected from the group consisting of —H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, C3-6cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 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 R75 groups;
• each R74 is independently selected from the group consisting of:
• C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 heteroalkyl, C3-6 cycloalkyl, 6-10 membered aryl, 4-12 membered heterocyclyl and 5-10 membered heteroaryl, wherein the C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 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 R75 groups;
• each R75 is independently selected from —H, halo, —CN, —OH, oxo, —NO2, —SF5, C1-6 alkyl, C1-6haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —S(O)(NH)R76, S(O)(NR68)R76, —S(O)(NH)NR76R76, —S(O)(NR68)NR76R76, —SH, —S(O)0-2R76, —S(O)2NH2, —NH2, —S(O)2NR76R76, —C(O)R76, —C(O)NR76R76 and —C(O)OR76, 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 R76 groups;
• each R76 is independently selected from halo, —CN, —OH, —NH2, oxo, —NO2, —SF5, C1-3 alkyl, C1-3 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, thioalkyl, thiohaloalkyl, thiocycloalkyl, sulfonylalkyl, sulfonylhaloalkyl, sulfonylcycloalkyl, 3-6 membered cycloalkyl, —C(O)NH2 and —S(O)2NH2;
• R62 is selected from the group consisting of:
• —H, —CN, —F, —Cl, C1-3 alkyl, C1-3 haloalkyl, C1-3 heteroalkyl, C1-3 alkoxy and C1-3 haloalkoxy;
• each R63 and R64 is independently selected from the group consisting of:
• —H, halo, —OH, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, 3-12 membered cycloalkyl, 4-12 membered heterocyclyl, 6-10 membered aryl, 5-10 membered heteroaryl, —SF5, —S(O)0-2R74, —S(O)(NH)R74, —S(O)(NR68)R74, —S(O)(NH)NR73R73, —S(O)(NR68)NR73R73, —SH, —NR73R73, —NR73SO2R74, —NR73S(O)2NR73R73, —NR73C(O)NR73R73, —NR73C(O)OR74, tri-C1-4 alkylsilyl, —C(O)R74, —C(O)OR74, —C(O)NR73R73 and —NO2, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 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 R69 groups;
• wherein R62 and R63, or R63 and R64 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 R69 groups;
• R67 is selected from the group consisting of:
• —H, halo, —CN, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, tri-C1-4 alkylsilyl, C1-6alkoxy, C1-6 hydroxyalkyl, C1-6heteroalkyl, 3-12 membered cycloalkyl, —S(O)0-2R74, —S(O)(NH)R74, —S(O)(NR68)R74, —S(O)(NH)NR73R73, —S(O)(NR68)NR73R73, —SH, —NR73R73, —P(O)R74R74, —C(O)OH, —C(O)OR74, —C(O)NR73R73, —S(O)2NR73R73, —C(O)R74, 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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, tri-C1-4 alkylsilyl, C1-6 alkoxy, C1-6 hydroxyalkyl, C1-6 heteroalkyl, and 3-12 membered cycloalkyl is optionally substituted with one or more R75;
• R68 is selected from the group consisting of C1-6 alkyl, —C(O)R74, 3-12 membered cycloalkyl, C1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, 4-12 membered heterocyclyl, —C(O)OR74, —C(O)NR73R73, and —SO2R74, wherein each of the C1-6 alkyl, 3-12 membered cycloalkyl, C1-6 heteroalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-12 membered heterocyclyl is optionally substituted with halo, —CN, oxo, hydroxyl, C1-6alkyl, C1-6alkoxy, —S(O)1-2R74, —S(O)2NR73R73, —NO2, —SF5, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —NR73R73, —C(O)OR74, C1-6 heteroalkyl, 3-6 membered cycloalkyl optionally substituted with R76, 4-12 membered heterocyclyl optionally substituted with one or more R76, 6-10 membered aryl optionally substituted with one or more R76, and 5-10 membered heteroaryl optionally substituted with one or more R76.