US 12,006,306 B2Granted

Substituted pyridazines as TYK2 inhibitors

AssigneeAlumis Inc.

InventorsBohan Jin, Qing Dong, Gene Hung, Stephen W. Kaldor

Life of this patent

Estimating the term…

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.

Claims16

Dependent claims

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.

72 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/243,508Filed 28 Apr 2021 · continuation
Priority: 22 Oct 2018
Published: US 2023/0023761 A126 Jan 2023
Granted: 11 Jun 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/501
Pyridazines; Hydrogenated pyridazines: not condensed and containing further heterocyclic rings
A61P 37/00
Drugs for immunological or allergic disorders

Family

Application62/749,003Us provisional application · filed 22 Oct 2018
Application62/756,942Us provisional application · filed 7 Nov 2018
Application62/839,459Us provisional application · filed 26 Apr 2019
Application62/875,449Us provisional application · filed 17 Jul 2019
Application62/893,721Us provisional application · filed 29 Aug 2019
Application62/907,354Us provisional application · filed 27 Sep 2019
PCT/US2019/057485Parent of this continuation · filed 22 Oct 2019
Application16/938,183Parent of this continuation · filed 24 Jul 2020
US 2023/0023761 A1Pre-grant publication · published 26 Jan 2023
US 11,053,219 B2Parent of this continuation
US 2020/0354338 A1Published application
US 12,006,306 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

Building an agent or pulling many patents? Use the API or MCP server instead of scraping pages. Get an API key

patentgrep

Loading patent…

Abstract

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.

72 more elements

Facts

Application

17/243,508Filed 28 Apr 2021 · continuation

Priority

22 Oct 2018

Published

US 2023/0023761 A126 Jan 2023

Granted

11 Jun 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/501
Pyridazines; Hydrogenated pyridazines: not condensed and containing further heterocyclic rings
A61P 37/00
Drugs for immunological or allergic disorders

Family

Application62/749,003Us provisional application · filed 22 Oct 2018

Application62/756,942Us provisional application · filed 7 Nov 2018

Application62/839,459Us provisional application · filed 26 Apr 2019

Application62/875,449Us provisional application · filed 17 Jul 2019

Application62/893,721Us provisional application · filed 29 Aug 2019

Application62/907,354Us provisional application · filed 27 Sep 2019

PCT/US2019/057485Parent of this continuation · filed 22 Oct 2019

Application16/938,183Parent of this continuation · filed 24 Jul 2020

US 2023/0023761 A1Pre-grant publication · published 26 Jan 2023

US 11,053,219 B2Parent of this continuation

US 2020/0354338 A1Published application

US 12,006,306 B2This patent

From the US filing history. Foreign family members aren’t listed.