# US 12,006,306 B2 · Substituted pyridazines as TYK2 inhibitors

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- Number: US 12,006,306 B2
- Document ID: US12006306B2
- Status: Granted
- Kind: B2
- Application number: 17/243,508
- Filed: 2021-04-28
- Published: 2023-01-26
- Granted: 2024-06-11
- Earliest claimed: 2018-10-22
- Assignees: Alumis Inc.
- Applicants: Alumis Inc.
- Inventors: Bohan Jin; Qing Dong; Gene Hung; Stephen W. Kaldor
- Web page: https://patentgrep.com/patent/US12006306B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61P 37/00: Drugs for immunological or allergic disorders
- C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- 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, for example, substituted pyridazines, that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

## Claims

### Claim 1

A compound of Formula (XII):
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
Rx is H, D, halogen, CN, NO2, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, NRbC(O)Ra, NRbC(O)NRcRd, NRbC(O)ORb, NHS(O)2Ra, ORb, OC(O)Ra, OC(O)NRcRd, OC(O)ORb, SRb, S(O)Ra, S(O)2Ra, or S(O)2NRcRd;
R5 is halogen, CN, NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(NCN)R7, C(NCN)NR9R10, C(NCN)OR8, C(O)R7, C(O)NR9R10, C(O)OR8, NR9R10, NR8C(NCN)R7, NR8S(NOH)R7, NR8C(NCN)NR9R10, NR8C(NCN)OR8, NR8C(O)R7, NR8C(O)NR9R10, NR8C(O)OR8, NR8S(O)R7, NR8S(NR8)(O)R7, NR8S(O)2R7, OR8, OC(NCN)R7, OC(NCN)NR9R10, OC(NCN)OR8, OC(O)R7, OC(O)NR9R10, OC(O)OR8, SR8, S(O)R7, S(O)2R7, S(O)2NR9R10, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, =0, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
wherein the cycloalkyl or heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, ═O, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O;
wherein each cycloalkyl and heterocycloalkyl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O; and
wherein each aryl and heteroaryl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, and ORb;
R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
wherein the cycloalkyl or heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; and
wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, and OCH3;
R8 is H, CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
wherein the cycloalkyl or heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; and
wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, and OCH3;
R9 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, ═O, cycloalkyl, and heterocycloalkyl;
wherein the cycloalkyl or heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 hydroxydeuteroalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, ═O, cycloalkyl, and heterocycloalkyl; and
wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 hydroxydeuteroalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, cycloalkyl, and heterocycloalkyl;
R10 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, ═O, cycloalkyl, and heterocycloalkyl;
wherein the cycloalkyl or heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 hydroxydeuteroalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, ═O, cycloalkyl, and heterocycloalkyl; and
wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 hydroxydeuteroalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, cycloalkyl, and heterocycloalkyl; or
R8 and R9, taken together with the atoms to which they are attached, form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; or
R9 and R10, taken together with the nitrogen atom to which they are attached, form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
R16 is C(O)R11;
R11 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more R11a substituents independently selected from the group consisting of D, halogen, CN, NO2, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, NRbC(O)Ra, NRbC(O)NRcRd, NRbC(O)ORb, NHS(O)2Ra, ORb, OC(O)Ra, OC(O)NRcRd, OC(O)ORb, SRb, S(O)Ra, S(O)2Ra, and S(O)2NRcRd; and
wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with one or more R11a substituents independently selected from the group consisting of D, halogen, CN, NO2, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, NRbC(O)Ra, NRbC(O)NRcRd, NRbC(O)ORb, NHS(O)2Ra, ORb, OC(O)Ra, OC(O)NRcRd, OC(O)ORb, SRb, S(O)Ra, S(O)2Ra, and S(O)2NRcRd;
R3 is H, C1-C6 alkyl, C1-C6 deuteroalkyl, or C1-C6 haloalkyl;
R4 is H, D, halogen, CN, NO2, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, NRbC(O)Ra, NRbC(O)NRcRd, NRbC(O)ORb, NHS(O)2Ra, ORb, OC(O)Ra, OC(O)NRcRd, OC(O)ORb, P(O)RbRb, SRb, S(O)Ra, S(O)2Ra, or S(O)2NRcRd;
Ring B is phenyl or a 5- to 10-membered heteroaryl;
L is a bond;
Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with one or more independently selected RA substituents;
each RA is independently D, halogen, CN, NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, NRbC(O)Ra, NRbC(O)NRcRd, NRbC(O)ORb, NHS(O)2Ra, ORb, OC(O)Ra, OC(O)NRcRd, OC(O)ORb, SRb, S(O)Ra, S(O)2Ra, S(O)2NRcRd, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O;
wherein each cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O; and
wherein each aryl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, and ORb; or
two geminal RA, taken together with the carbon atom to which they are attached, form —C(O)—;
each Ra is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
wherein each cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; and
wherein each aryl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, and OCH3;
each Rb is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
wherein each cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; and
wherein each aryl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, and OCH3;
each Rc is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
wherein each cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; and
wherein each aryl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, and OCH3; and
each Rd is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O;
wherein each cycloalkyl and heterocycloalkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O; and
wherein each aryl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, and OCH3; or
any Rc and Rd, taken together with the nitrogen atom to which they are attached, independently forms a heterocycloalkyl, wherein each heterocycloalkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Rx is H.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R5 is NR8C(O)NR9R10 or heterocycloalkyl;
wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, ═O, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O;
wherein each cycloalkyl and heterocycloalkyl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O; and
wherein each aryl and heteroaryl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, and ORb.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R5 is NR8C(O)NR9R10.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R5 is heterocycloalkyl;
wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C1-C6 hydroxyalkyl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C2-C6 alkenyl, C2-C6 alkynyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, ═O, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
wherein each C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O;
wherein each cycloalkyl and heterocycloalkyl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, and ═O; and
wherein each aryl and heteroaryl substituent is optionally and independently substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, and ORb.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R9 and R10, taken together with the nitrogen atom to which they are attached, form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R5 is NR8C(O)R7 or NR8C(O)NR9R10;
R7 is cycloalkyl;
R8 is H; and
R9 and R10, taken together with the nitrogen atom to which they are attached, form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C(O)CH3, C(O)OH, C(O)OCH3, NH2, OH, OCH3, and ═O.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R11 is C1-C6 alkyl or cycloalkyl, wherein the C1-C6 alkyl is optionally substituted with one or more independently selected R11a substituents; and
each R11a is an independently selected halogen substituent.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R3 is H.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R4 is H, D, halogen, CN, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, C(O)Ra, C(O)NRcRd, C(O)ORb, NRcRd, ORb, or OC(O)NRcRd.

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R4 is H or ORb; and
Rb is C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of D and halogen.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Ring B is a bicyclic 5- to 10-membered heteroaryl.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Ring A is heterocycloalkyl or heteroaryl;
wherein the heterocycloalkyl or heteroaryl is 3- to 6-membered; and
wherein the heterocycloalkyl or heteroaryl is optionally substituted with one or more independently selected RA substituents.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Ring A is heterocycloalkyl or heteroaryl;
wherein the heterocycloalkyl or heteroaryl is 5-membered; and
wherein the heterocycloalkyl or heteroaryl is optionally substituted with one or more independently selected RA substituents.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each RA is independently D, halogen, or C1-C6 alkyl, wherein each C1-C6 alkyl is optionally and independently substituted with one or more substituents independently selected from the group consisting of D and halogen.

### Claim 16 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.