# US 12,600,721 B2 · TYK2 inhibitors and uses thereof

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- Number: US 12,600,721 B2
- Document ID: US12600721B2
- Status: Granted
- Kind: B2
- Application number: 18/546,943
- Filed: 2022-02-16
- Published: 2024-06-20
- Granted: 2026-04-14
- Earliest claimed: 2021-02-19
- Assignees: Sudo Biosciences Limited
- Applicants: Sudo Biosciences Limited
- Inventors: Anjali Pandey; Gregory Dietsch; Bhaskar Chaudhuri; Seetharaman Manojveer; Mahesh Thakkar; Athisayamani Jeyaraj Duraiswamy; Sukesh Kalva
- Web page: https://patentgrep.com/patent/US12600721B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]}
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/5025: ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- C07D 221/04: Ortho- or peri-condensed ring systems
- C07D 471/14: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Described herein are compounds that are TYK2 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of TYK2 activity.

## Claims

### Claim 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 A1 and A2 are independently N or C, wherein if Ring A is substituted then Ring A is substituted with p instances of R8;
each R8 is independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2; wherein if R8 is attached to a nitrogen atom, then R8 is hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —S(═O)R17, —SO2R17, or —SO2N(R16)2; or two R8 attached to the same carbon atom are taken together to form ═O, ═S, or ═NH;
Z is —NR10—, —O—, —S—, —S(═O)—, or —SO2—;
R10 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
X1, X2, and X3 are each independently CR11 or N;
each R11 is independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
B1 is N or CR12a;
B2 is N or CR12b;
R12a and R12b are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
R1 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;
R2 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 R13;
each R13 is independently halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
or two R13 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 R2 is —C(═O)R14, —C(═O)NR14R15, or —C(═O)OR14,
R14 is hydrogen, unsubstituted or substituted C1-C6 alkyl, C1-C6 deuteroalkyl unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, or unsubstituted or substituted bicyclic heterocycle;
R15 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;
or R14 and R15 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 R1 and R15 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 —NR3— or —O—;
R3 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
R4 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
or R3 and R4 are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle;
or R3 and R12a are taken together with the intervening atoms to which they are attached to form a substituted or unsubstituted 5- or 6-membered heterocycle;
R5 is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
each R6 and R7 is independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
or one R6 and one R7 attached to the same carbon atom are taken together with the carbon atom to which they are attached to form C═O or C3-C4 cycloalkyl;
each R16 is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;
or two R16 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 R17 is independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 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 Rs groups independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, —CN, —CH2CN, —OR18, —CH2OR18, —CO2R18, —CH2CO2R18, —C(═O)N(R18)2, —CH2C(═O)N(R18)2, —N(R18)2, —CH2N(R18)2, —NR18C(═O)R18, —CH2NR18C(═O)R18, —NR18SO2R19, —CH2NR18SO2R19, —SR18, —CH2SR18, —S(═O)R19, —CH2S(═O)R19, —SO2R19, —CH2SO2R19, —SO2N(R18)2, or —CH2SO2N(R18)2;
each R18 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl;
or two R18 groups are taken together with the N atom to which they are attached to form a N-containing heterocycle;
each R19 is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 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.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
R1 is hydrogen or C1-C4 alkyl;
W is —NR3—;
R3 is hydrogen, C1-C4 alkyl, or C1-C4 deuteroalkyl;
R4 is hydrogen, C1-C4 alkyl, or C1-C4 deuteroalkyl; and
R5 is hydrogen or C1-C4 alkyl.

### Claim 3 (depends on 1)

The compound of claim 1 having a structure of Formula (II):
or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
X1 is CR11, X2 is CR11, and X3 is CR11;
or X1 is CR11, X2 is CR11, and X3 is N;
or X1 is CR11 X2 is N, and X3 is CR11;
or X1 is N, X2 is CR11, and X3 is CR11; and
each R11 is independently hydrogen, halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, —CN, —OH, —OR17, or —N(R16)2.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
X1 is CR11, X2 is CR11, and X3 is CR11; and
each R11 is independently hydrogen or fluoro.

### Claim 5 (depends on 1)

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 A1 and A2 are independently N or C, wherein if Ring A is substituted then Ring A is substituted with p instances of R8.

### Claim 6 (depends on 1)

The compound of claim 1 having a structure of Formula (VIb) or Formula (VIc):
or a pharmaceutically acceptable salt, tautomer, or solvate thereof.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein each R8 is independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, or —C(═O)N(R16)2; wherein if R8 is attached to a nitrogen atom, then R8 is hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —C(═O)R16, —CO2R16, or —C(═O)N(R16)2.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
each R6 and R7 is independently hydrogen, deuterium, halogen, C1-C4 alkyl, or C1-C4 deuteroalkyl;
Z is —NR10— or —O—; and
R10 is hydrogen, C1-C4 alkyl, C1-C4 deuteroalkyl, or cyclopropyl.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
R2 is
and q is 0, 1, 2, 3, or 4; and
each R13 is independently halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SO2R17, or —SO2N(R16)2;
or R2 is —C(═O)R14, —C(═O)NR14R15, or —C(═O)OR14;
R14 is unsubstituted or substituted C1-C6 alkyl, C1-C6 deuteroalkyl, unsubstituted or substituted C3-C6 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 Rs groups independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, —CN, —OR18, and —N(R18)2; and
R15 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;
or R14 and R15 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 4- to 6-membered monocyclic heterocycle.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein R2 is —C(═O)R14, and R14 is unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C3-C4 cycloalkyl, or unsubstituted or substituted 4-membered heterocycloalkyl; wherein the substituted alkyl, substituted cycloalkyl, or substituted heterocycloalkyl is substituted with one or more Rs groups independently selected from the group consisting of deuterium, halogen, —CN, —NH2, —OH, —NH (CH3), —N(CH3)2, —CH3, —CH2CH3, —OCH3, —OCHF2, and —OCF3.

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
B1 is CR12a, and B2 is CR12b;
or B1 is N; and B2 is CR12b;
or B1 is CR12a, and B2 is N;
or B1 is N; and B2 is N; and
R12a and R12b are each independently hydrogen, halogen, C1-C4 alkyl, C1-C4 fluoroalkyl, or —CN.

### Claim 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.

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 1)

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.

### Claim 15 (depends on 14)

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.

### Claim 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.

### Claim 17 (depends on 16)

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

### Claim 18 (depends on 16)

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.

### Claim 19 (depends on 1)

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.

### Claim 20 (depends on 16)

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.