Granted Patent B2

US 12,600,721 · App. 18/546,943 · Granted Apr 14, 2026

Inventors: Anjali Pandey (Fremont, CA); Gregory Dietsch (Snohomish, WA); Bhaskar Chaudhuri (San Jose, CA); Seetharaman Manojveer (Karnataka, IN); Mahesh Thakkar (Karnataka, IN); Athisayamani Jeyaraj Duraiswamy (Karnataka, IN); Sukesh Kalva (Karnataka, IN)

Assignee: SUDO BIOSCIENCES LIMITED

C07D471/04A61K31/444A61K31/4985A61K31/501A61K31/5025A61K31/519C07D471/14

Abstract

Claims (129)

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

Ring A is an unsubstituted or substituted 6-membered heterocyclic ring wherein A 1 and A 2 are independently N or C, wherein if Ring A is substituted then Ring A is substituted with p instances of R 8 ;

each R 8 is independently hydrogen, halogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 deuteroalkyl, unsubstituted or substituted C 2 -C 6 alkenyl, unsubstituted or substituted C 2 -C 6 alkynyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted C 1 -C 6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —N(R 16 ) 2 , —NR 16 C(═O)R 17 , —SR 16 , —S(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ; wherein if R 8 is attached to a nitrogen atom, then R 8 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 deuteroalkyl, unsubstituted or substituted C 2 -C 6 alkenyl, unsubstituted or substituted C 2 -C 6 alkynyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted C 1 -C 6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —S(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ; or two R 8 attached to the same carbon atom are taken together to form ═O, ═S, or ═NH;

Z is —NR 10 —, —O—, —S—, —S(═O)—, or —SO 2 —;

R 10 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 fluoroalkyl, C 3 -C 6 cycloalkyl, or monocyclic heterocycle;

X 1 , X 2 , and X 3 are each independently CR 11 or N;

each R 11 is independently hydrogen, halogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, unsubstituted or substituted C 2 -C 6 alkynyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted C 1 -C 6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —N(R 16 ) 2 , —NR 16 C(═O)R 17 , —SR 16 , —S(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ;

B 1 is N or CR 12a ;

B 2 is N or CR 12b ;

R 12a and R 12b are each independently hydrogen, halogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, unsubstituted or substituted C 2 -C 6 alkynyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted C 1 -C 6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —N(R 16 ) 2 , —NR 16 C(═O)R 17 , —SR 16 , —S(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ;

R 1 is hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl;

R 2 is a Ring B that is an unsubstituted or substituted heterocycle or unsubstituted or substituted carbocycle, wherein if Ring B is substituted then Ring B is substituted with q instances of R 13 ;

each R 13 is independently halogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 2 -C 6 alkenyl, unsubstituted or substituted C 2 -C 6 alkynyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted C 1 -C 6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —N(R 16 ) 2 , —NR 16 C(═O)R 17 , —SR 16 , —S(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ;

or two R 13 groups on adjacent atoms of Ring B are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic carbocycle or an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle;

or R 2 is —C(═O)R 14 , —C(═O)NR 14 R 15 , or —C(═O)OR 14 ,

R 14 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl unsubstituted or substituted C 2 -C 6 alkenyl, unsubstituted or substituted C 2 -C 6 alkynyl, unsubstituted or substituted C 1 -C 6 heteroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, or unsubstituted or substituted bicyclic heterocycle;

R 15 is hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl;

or R 14 and R 15 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 4- to 6-membered monocyclic heterocycle;

or R 1 and R 15 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle;

W is —NR 3 — or —O—;

R 3 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 fluoroalkyl, C 3 -C 6 cycloalkyl, or monocyclic heterocycle;

R 4 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 fluoroalkyl, C 3 -C 6 cycloalkyl, or monocyclic heterocycle;

or R 3 and R 4 are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle;

or R 3 and R 12a are taken together with the intervening atoms to which they are attached to form a substituted or unsubstituted 5- or 6-membered heterocycle;

R 5 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 3 -C 6 cycloalkyl, or monocyclic heterocycle;

each R 6 and R 7 is independently hydrogen, deuterium, halogen, C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 fluoroalkyl, C 3 -C 6 cycloalkyl, or monocyclic heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —N(R 16 ) 2 , —NR 16 C(═O)R 17 , —SR 16 , —S(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ;

or one R 6 and one R 7 attached to the same carbon atom are taken together with the carbon atom to which they are attached to form C═O or C 3 -C 4 cycloalkyl;

each R 16 is independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;

or two R 16 on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle; and

each R 17 is independently substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;

wherein each substituted alkyl, substituted fluoroalkyl, substituted deuteroalkyl, substituted alkoxy, substituted fluoroalkoxy, substituted heteroalkyl, substituted carbocycle, and substituted heterocycle is substituted with one or more R s groups independently selected from the group consisting of deuterium, halogen, C 1 -C 6 alkyl, monocyclic carbocycle, monocyclic heterocycle, —CN, —CH 2 CN, —OR 18 , —CH 2 OR 18 , —CO 2 R 18 , —CH 2 CO 2 R 18 , —C(═O)N(R 18 ) 2 , —CH 2 C(═O)N(R 18 ) 2 , —N(R 18 ) 2 , —CH 2 N(R 18 ) 2 , —NR 18 C(═O)R 18 , —CH 2 NR 18 C(═O)R 18 , —NR 18 SO 2 R 19 , —CH 2 NR 18 SO 2 R 19 , —SR 18 , —CH 2 SR 18 , —S(═O)R 19 , —CH 2 S(═O)R 19 , —SO 2 R 19 , —CH 2 SO 2 R 19 , —SO 2 N(R 18 ) 2 , or —CH 2 SO 2 N(R 18 ) 2 ;

each R 18 is independently selected from hydrogen, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl;

or two R 18 groups are taken together with the N atom to which they are attached to form a N-containing heterocycle;

each R 19 is independently selected from C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl, and 6-membered heteroaryl;

n is 1, 2, or 3;

p is 0, 1, 2, 3, or 4; and

q is 0, 1, 2, 3, or 4.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

R 1 is hydrogen or C 1 -C 4 alkyl;

W is —NR 3 —;

R 3 is hydrogen, C 1 -C 4 alkyl, or C 1 -C 4 deuteroalkyl;

R 4 is hydrogen, C 1 -C 4 alkyl, or C 1 -C 4 deuteroalkyl; and

R 5 is hydrogen or C 1 -C 4 alkyl.

3 . The compound of claim 1 having a structure of Formula (II):

or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

X 1 is CR 11 , X 2 is CR 11 , and X 3 is CR 11 ;

or X 1 is CR 11 , X 2 is CR 11 , and X 3 is N;

or X 1 is CR 11 X 2 is N, and X 3 is CR 11 ;

or X 1 is N, X 2 is CR 11 , and X 3 is CR 11 ; and

each R 11 is independently hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, —CN, —OH, —OR 17 , or —N(R 16 ) 2 .

4 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

X 1 is CR 11 , X 2 is CR 11 , and X 3 is CR 11 ; and

each R 11 is independently hydrogen or fluoro.

5 . The compound of claim 1 having a structure of Formula (IV):

or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein Ring A is an unsubstituted or substituted 6-membered heteroaryl ring wherein A 1 and A 2 are independently N or C, wherein if Ring A is substituted then Ring A is substituted with p instances of R 8 .

6 . The compound of claim 1 having a structure of Formula (VIb) or Formula (VIc):

or a pharmaceutically acceptable salt, tautomer, or solvate thereof.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein each R 8 is independently hydrogen, halogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 deuteroalkyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , or —C(═O)N(R 16 ) 2 ; wherein if R 8 is attached to a nitrogen atom, then R 8 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 deuteroalkyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —C(═O)R 16 , —CO 2 R 16 , or —C(═O)N(R 16 ) 2 .

8 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

each R 6 and R 7 is independently hydrogen, deuterium, halogen, C 1 -C 4 alkyl, or C 1 -C 4 deuteroalkyl;

Z is —NR 10 — or —O—; and

R 10 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 deuteroalkyl, or cyclopropyl.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

R 2 is

 and q is 0, 1, 2, 3, or 4; and

each R 13 is independently halogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 fluoroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR 17 , —C(═O)R 16 , —CO 2 R 16 , —C(═O)N(R 16 ) 2 , —N(R 16 ) 2 , —NR 16 C(═O)R 17 , —SO 2 R 17 , or —SO 2 N(R 16 ) 2 ;

or R 2 is —C(═O)R 14 , —C(═O)NR 14 R 15 , or —C(═O)OR 14 ;

R 14 is unsubstituted or substituted C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl, unsubstituted or substituted C 3 -C 6 cycloalkyl, or unsubstituted or substituted 4- to 6-membered heterocycloalkyl; wherein the substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, or substituted heterocycloalkyl is substituted with one or more R s groups independently selected from the group consisting of deuterium, halogen, C 1 -C 6 alkyl, —CN, —OR 18 , and —N(R 18 ) 2 ; and

R 15 is hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl;

or R 14 and R 15 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 4- to 6-membered monocyclic heterocycle.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein R 2 is —C(═O)R 14 , and R 14 is unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 3 -C 4 cycloalkyl, or unsubstituted or substituted 4-membered heterocycloalkyl; wherein the substituted alkyl, substituted cycloalkyl, or substituted heterocycloalkyl is substituted with one or more R s groups independently selected from the group consisting of deuterium, halogen, —CN, —NH 2 , —OH, —NH (CH 3 ), —N(CH 3 ) 2 , —CH 3 , —CH 2 CH 3 , —OCH 3 , —OCHF 2 , and —OCF 3 .

11 . The compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:

B 1 is CR 12a , and B 2 is CR 12b ;

or B 1 is N; and B 2 is CR 12b ;

or B 1 is CR 12a , and B 2 is N;

or B 1 is N; and B 2 is N; and

R 12a and R 12b are each independently hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, or —CN.

12 . A compound selected from:

1: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)pyridazine-3-carboxamide;

2: 6-((5-fluoropyridin-2-yl)amino)-N-(methyl-d3)-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)pyridazine-3-carboxamide; and

3: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino) nicotinamide;

4: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrimido[5,4-c]quinolin-7-yl)amino)nicotinamide;

5: 6-(cyclopropanecarboxamido)-4-((3-fluoro-6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)-N-(methyl-d3)nicotinamide;

6: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrimido[5,4-c]quinolin-7-yl)amino)pyridazine-3-carboxamide;

7: 6-(cyclopropanecarboxamido)-4-((3-fluoro-6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

8: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrazino[2,3-c]quinolin-7-yl)amino)nicotinamide;

9: 6-(cyclopropanecarboxamido)-4-((2,6-dimethyl-1-oxo-1,2,5,6-tetrahydrobenzo[c] [2,6]naphthyridin-7-yl)amino)-N-(methyl-d3)nicotinamide;

10: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrazino[2,3-c]quinolin-7-yl)amino)pyridazine-3-carboxamide;

11: 6-(cyclopropanecarboxamido)-4-((2,6-dimethyl-1-oxo-1,2,5,6-tetrahydrobenzo[c][2,6]naphthyridin-7-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

12: 4-((3-cyano-6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)-6-(cyclopropanecarboxamido)-N-(methyl-d3)nicotinamide;

13: 4-((3-cyano-6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)-6-(cyclopropanecarboxamido)-N-(methyl-d3)pyridazine-3-carboxamide;

14: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrazino[2,3-c][1,7]naphthyridin-7-yl)amino)nicotinamide;

15: 6-(cyclopropanecarboxamido)-N-methyl-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)nicotinamide;

16: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrazino[2,3-c]quinolin-7-yl)amino)pyridazine-3-carboxamide;

17: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-(methyl-d3)-5,6-dihydropyrazino[2,3-c]quinolin-7-yl)amino)nicotinamide;

18: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-(methyl-d3)-5,6-dihydropyrazino[2,3-c]quinolin-7-yl)amino)pyridazine-3-carboxamide;

19: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydropyrido [3,4-h][1,6]naphthyridin-7-yl)amino)nicotinamide;

20: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)nicotinamide;

21: 6-(cyclopropanecarboxamido)-4-((3-fluoro-6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

22: 6-(cyclopropanecarboxamido)-4-((3-fluoro-6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)-N-(methyl-d3)nicotinamide;

23: 6-(cyclopropanecarboxamido)-4-((2,6-dimethyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

24: 6-(cyclopropanecarboxamido)-4-((2,6-dimethyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)-N-(methyl-d3)nicotinamide;

25: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-2-(trifluoromethyl)-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)nicotinamide;

26: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-2-(trifluoromethyl)-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl-5,5-d2)amino)pyridazine-3-carboxamide;

27: 6-(cyclopropanecarboxamido)-4-((2,6-dimethyl-1-oxo-1,2,5,6-tetrahydropyridazino[4,5-c]quinolin-7-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

28: 6-(cyclopropanecarboxamido)-4-((2,6-dimethyl-1-oxo-1,2,5,6-tetrahydropyridazino[4,5-c]quinolin-7-yl)amino)-N-(methyl-d3)nicotinamide;

29: 6-(cyclopropanecarboxamido)-N-methyl-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)pyridazine-3-carboxamide;

30: 6-(cyclopropanecarboxamido)-N-methyl-4-((6-methyl-5,6-dihydropyrazino[2,3-c]quinolin-7-yl)amino)nicotinamide;

31: 6-(cyclopropanecarboxamido)-4-((10-fluoro-5-methyl-5,6-dihydrophenanthridin-4-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

32: (R)-6-(cyclopropanecarboxamido)-4-((5,6-dimethyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide; and

33: (S)-6-(cyclopropanecarboxamido)-4-((5,6-dimethyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)-N-(methyl-d3)pyridazine-3-carboxamide;

or a pharmaceutically acceptable salt, tautomer, or solvate thereof.

13 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, and a pharmaceutically acceptable excipient.

14 . A method of treating a TYK2-mediated disease or condition in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof.

15 . The method of claim 14 , wherein the TYK2-mediated disease or condition is an inflammatory disease or condition or autoimmune disease or condition; or wherein the TYK2-mediated disease or condition is selected from rheumatoid arthritis, multiple sclerosis, psoriasis, psoriatic arthritis, lupus, systemic lupus erythematosus, Sjögren's syndrome, ankylosing spondylitis, vitiligo, atopic dermatitis, scleroderma, alopecia, hidradenitis suppurativa, uveitis, dry eye, intestinal bowel disease, Crohn's disease, ulcerative colitis, celiac disease, Bechet's disease, type 1 diabetes, systemic sclerosis, and idiopathic pulmonary fibrosis.

16 . A compound selected from:

3: 6-(cyclopropanecarboxamido)-N-(methyl-d3)-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)nicotinamide;

15: 6-(cyclopropanecarboxamido)-N-methyl-4-((6-methyl-5,6-dihydrobenzo[h][1,6]naphthyridin-7-yl)amino)nicotinamide;

34: 6-(cyclopropanecarboxamido)-4-((2,5-dimethyl-4,5-dihydro-2H-pyrazolo[4,3-c]quinolin-6-yl)amino)-N-methylpyridazine-3-carboxamide;

35: 4-((2,5-dimethyl-4,5-dihydro-2H-pyrazolo[4,3-c]quinolin-6-yl)amino)-6-((5-fluoropyridin-2-yl)amino)-N-methylnicotinamide;

36: 4-((2,5-dimethyl-4,5-dihydro-2H-pyrazolo[4,3-c]quinolin-6-yl)amino)-6-((2,6-dimethylpyrimidin-4-yl)amino)-N-methylnicotinamide;

37: 6-(cyclopropanecarboxamido)-4-((2,5-dimethyl-4,5-dihydro-2H-[1,2,3]triazolo[4,5-c]quinolin-6-yl)amino)-N-methylnicotinamide; and

38: 6-(cyclopropanecarboxamido)-4-((2,5-dimethyl-4,5-dihydropyrazolo[1,5-a]quinoxalin-6-yl)amino)-N-methylpyridazine-3-carboxamide;

or a pharmaceutically acceptable salt, tautomer, or solvate thereof.

17 . A pharmaceutical composition comprising the compound of claim 16 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, and a pharmaceutically acceptable excipient.

18 . A method of treating a TYK2-mediated disease or condition in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 16 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof.

19 . A method of treating a disease or condition of the eye in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, preferably wherein the disease or condition of the eye is selected from Sjogren's syndrome, uveitis, and dry eye, or a combination thereof.

20 . A method of treating a disease or condition of the eye in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 16 , or a pharmaceutically acceptable salt, tautomer, or solvate thereof, preferably wherein the disease or condition of the eye is selected from Sjogren's syndrome, uveitis, and dry eye, or a combination thereof.

Assignments (3)

Continuity (3)

References Cited (384)