IP Library › Granted Patent US 12,559,464

Granted Patent B2

US 12,559,464 · App. 18/882,652 · Granted Feb 24, 2026

Quinazolinone dione compounds and uses thereof

Inventors: Natalie Anne Hawryluk (Nederland, CO); Stephen Thomas Schlachter (Boulder, CO); Kevin Koch (Niwot, CO); Michael Joseph Luzzio (Groton, CT); Michael Mark Duvall (Vancouver, WA); Alan James Russell (Boulder, CO); Marc Justin Evanchik (Boulder, CO); Kevin Hunt (Boulder, CO)

Assignee: EDGEWISE THERAPEUTICS, INC.

C07D239/96 A61K31/517 A61K31/519 A61K31/5377 C07D401/06 C07D401/12 C07D403/12 C07D405/12 C07D409/12 C07D413/12 C07D417/12 C07D471/04 C07D487/04 C07D491/048

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Quick Facts

Patent No.: US 12,559,464
App. No.: 18/882,652
Granted: Feb 24, 2026
Kind: B2

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Abstract

Provided are quinazolinone dione compounds for treating cardiac indications such as hypertrophic cardiomyopathy and diastolic dysfunction.

Claims (146)

1 . A compound represented by Formula (Ia):

or a salt thereof, wherein:

X 1 is selected from C(R 1a ), N, and N + (—O − );

X 2 is selected from C(R 1b ), N, and N + (—O − );

X 3 is selected from C(R 1c ), N, and N + (—O − );

X 4 is selected from C(R 1d ), N, and N + (—O − );

wherein no more than two of X 1 , X 2 , X 3 , and X 4 are N or N + (—O − );

U is absent or selected from —O − ;

Y 2 is selected from C(R 9bB ), N, and N + (—O − );

Y 4 is selected from C(R 9bD ), N, and N + (—O − );

Y 5 is selected from C(R 9bE ), N, and N + (—O − );

wherein no more than two of Y 2 , Y 4 , and Y 5 are N or N + (—O − );

R 1a , R 1b , and R 1c are each independently selected from:

hydrogen;

halogen, —NO 2 , —N 3 , —CN, —OR 10a , —SR 10a , —N(R 10a ) 2 , —C(O)R 10a , —C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —C(O)OR 10a , —OC(O)R 10a , —S(O)R 10a , and —S(O) 2 R 10a ;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10a , —SR 10a , —N(R 10a ) 2 , —C(O)R 10a , —C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —C(O)OR 10a , —OC(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —S(O)R 10a , —S(O) 2 R 10a , —NO 2 , ═O, ═S, ═N(R 10a ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9a ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10a , —SR 10a , —N(R 10a ) 2 , —C(O)R 10a , —C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —C(O)OR 10a , —OC(O)R 10a , —S(O)R 10a , —S(O) 2 R 10a , —NO 2 , ═O, ═S, ═N(R 10a ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9a ;

R 1d is selected from:

hydrogen;

NO 2 , —N 3 , —CN, —OR 10a , —SR 10a —N(R 10a ) 2 , —C(O)R 10a -C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —C(O)OR 10a , —OC(O)R 10a , —S(O)R 10a , and —S(O) 2 R 10a ;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10a , —SR 10a N(R 10a ) 2 , —C(O)R 10a , —C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —C(O)OR 10a , —OC(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —S(O)R 10a , —S(O) 2 R 10a , —NO 2 , —O, ═S, —N(R 10a ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9a ; and

R Z is selected from:

CN, —C(O)R 10z , —C(O)N(R 10z ) 2 , and —C(O)OR 10z ;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10z —SR 10z , —N(R 10z ) 2 , —C(O)R 10z , —C(O)N(R 10z ) 2 , -N(R 10z )C(O)R 10z , —C(O)OR 10z , —OC(O)R 10z , —N(R 10z )C(O)N(R 10z ) 2 , —OC(O)N(R 10z ) 2 , —N(R 10z )C(O)OR 10z , —S(O)R 10z , —S(O) 2 R 10z , —NO 2 , ═O, ═S, ═N(R 10z ), —N 3 , —CN, C 3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9z ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10z , —SR 10z , —N(R 10z ) 2 , —C(O)R 10z , —C(O)N(R 10z ) 2 , —N(R 10z )C(O)R 10z , —N(R 10z )C(O)N(R 10z ) 2 , —OC(O)N(R 10z ) 2 , —N(R 10z )C(O)OR 10z , —C(O)OR 10z , —OC(O)R 10z , —S(O)R 10z , —S(O) 2 R 10z , —NO 2 , ═O, ═S, ═N(R 10z ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein the C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9z ;

R C is selected from:

hydrogen;

CN, —C(O)R 10c , —C(O)N(R 10c ) 2 , and —C(O)OR 10c ;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10c , —SR 10c , —N(R 10c ) 2 , —C(O)R 10c , —C(O)N(R 10c ) 2 , —N(R 10c )C(O)R 10c , —C(O)OR 10c , —OC(O)R 10c , —N(R 10c )C(O)N(R 10c ) 2 , —OC(O)N(R 10c ) 2 , —N(R 10c )C(O)OR 10c , —S(O)R 10c , —S(O) 2 R 10c , —NO 2 , ═O, ═S, ═N(R 10c ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9c ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10c , —SR 10c , —N(R 10c ) 2 , —C(O)R 10c , —C(O)N(R 10c ) 2 , —N(R 10c )C(O)R 10c , —N(R 10c )C(O)N(R 10c ) 2 , —OC(O)N(R 10c ) 2 , —N(R 10c )C(O)OR 10c , —C(O)OR 10c , —OC(O)R 10c , —S(O)R 10c , —S(O) 2 R 10c , —NO 2 , ═O, ═S, ═N(R 10c ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein the C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9c ; or

R Z together with R C form a 3- to 10-membered heterocycle or C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents independently selected from R 9c ;

R 5 is selected from:

hydrogen;

halogen, —OR 10d , —SR 10d , —N(R 10d ) 2 , —C(O)R 10d , —C(O)N(R 10d ) 2 , —N(R 10d )C(O)R 10d , —C(O)OR 10d , —OC(O)R 10d , —N(R 10d )C(O)N(R 10d ) 2 , —OC(O)N(R 10d ) 2 , —N(R 10d )C(O)OR 10d , —S(O)R 10d , —S(O) 2 R 10d , —NO 2 , —N 3 , and —CN;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10d , —SR 10d , N(R 10d ) 2 , —C(O)R 10d , —C(O)N(R 10d ) 2 , —N(R 10d )C(O)R 10d , —C(O)OR 10d , —OC(O)R 10d , —N(R 10d )C(O)N(R 10d ) 2 , —OC(O)N(R 10d ) 2 , —N(R 10d )C(O)OR 10d , —S(O)R 10d , —S(O) 2 R 10d , —NO 2 , -O, ═S, ═N(R 10d ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9d ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10d , —SR 10d , —N(R 10d ) 2 , —C(O)R 10d , —C(O)N(R 10d ) 2 , —N(R 10d )C(O)R 10d , —N(R 10d )C(O)N(R 10d ) 2 , —OC(O)N(R 10d ) 2 , —N(R 10d )C(O)OR 10d , —C(O)OR 10d , —OC(O)R 10d , —S(O)R 10d , —S(O) 2 R 10d , —NO 2 , ═O, ═S, ═N(R 10d ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9d ; or

R 5 together with R 6 form a 3- to 10-membered heterocycle or C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents independently selected from R 9d ;

R 6 is selected from:

hydrogen;

halogen, —OR 10e , —SR 10e , —N(R 10e ) 2 , —C(O)R 10e , —C(O)N(R 10e ) 2 , —N(R 10e )C(O)R 10e , —C(O)OR 10e , —OC(O)R 10e , —N(R 10e )C(O)N(R 10e ) 2 , —OC(O)N(R 10e ) 2 , —N(R 10e )C(O)OR 10e , —S(O)R 10e , —S(O) 2 R 10e , —NO 2 , —N 3 , and —CN;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10e , —SR 10e , —N(R 10e ) 2 , —C(O)R 10e , —C(O)N(R 10e ) 2 , —N(R 10e )C(O)R 10e , —C(O)OR 10e , —OC(O)R 10e , —N(R 10e )C(O)N(R 10e ) 2 , —OC(O)N(R 10e ) 2 , —N(R 10e )C(O)OR 10e , —S(O)R 10e , —S(O) 2 R 10e , —NO 2 , -O, ═S, ═N(R 10e ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9e ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10e , —SR 10e , —N(R 10e ) 2 , —C(O)R 10e , —C(O)N(R 10e ) 2 , —N(R 10e )C(O)R 10e , —N(R 10e )C(O)N(R 10e ) 2 , —OC(O)N(R 10e ) 2 , —N(R 10e )C(O)OR 10e , —C(O)OR 10e , —OC(O)R 10e , —S(O)R 10e , —S(O) 2 R 10e , —NO 2 , ═O, ═S, ═N(R 10e ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein the C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9e ; or

R 6 together with R 5 form a 3- to 10-membered heterocycle or C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents independently selected from R 9e ;

R 7 is selected from:

hydrogen;

C(O)R 10f , —C(O)N(R 10f ) 2 , —C(O)OR 10f , —S(O)R 10f , and —S(O) 2 R 10f , C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR 10f , —SR 10f , —N(R 10f ) 2 , —C(O)R 10f , —C(O)N(R 10f ) 2 , —N(R 10f )C(O)R 10f , —C(O)OR 10f , —OC(O)R 10f , —N(R 10f )C(O)N(R 10f ) 2 , —OC(O)N(R 10f ) 2 , —N(R 10f )C(O)OR 10f , —S(O)R 10f , —S(O) 2 R 10f , —NO 2 , ═O, ═S, ═N(R 10f ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9f ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10f , —SR 10f , —N(R 10f ) 2 , —C(O)R 10f , —C(O)N(R 10f ) 2 , —N(R 10f )C(O)R 10f , —N(R 10f )C(O)N(R 10f ) 2 , —OC(O)N(R 10f ) 2 , —N(R 10f )C(O)OR 10f , —C(O)OR 10f , —OC(O)R 10f , —S(O)R 10f , —S(O) 2 R 10f , —NO 2 , ═O, ═S, —N(R 10f ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein the C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9f ;

R 8 is selected from:

hydrogen;

C(O)R 10g , —C(O)N(R 10g ) 2 , —C(O)OR 10g , —S(O)R 10g , and —S(O) 2 R 10g ;

C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR 10g , —SR 10g , —N(R 10g ) 2 , —C(O)R 10g , —C(O)N(R 10g ) 2 , —N(R 10g )C(O)R 10g , —C(O)OR 10g , —OC(O)R 10g , —N(R 10g )C(O)N(R 10g ) 2 , —OC(O)N(R 10g ) 2 , —N(R 10g )C(O)OR 10g , —S(O)R 10g , —S(O) 2 R 10g , —NO 2 , ═O, ═S, ═N(R 10g ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R 9g ; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10g , —SR 10g , —N(R 10g ) 2 , —C(O)R 10g , —C(O)N(R 10g ) 2 , —N(R 10g )C(O)R 10g , —N(R 10g )C(O)N(R 10g ) 2 , —OC(O)N(R 10g ) 2 , —N(R 10g )C(O)OR 10g , —C(O)OR 10g , —OC(O)R 10g , —S(O)R 10g , —S(O) 2 R 10g , —NO 2 , ═O, ═S, ═N(R 10g ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein the C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R 9g ;

each R 9a is independently selected from:

halogen, —OR 10a , —SR 10a , —N(R 10a ) 2 , —C(O)R 10a , —C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —C(O)OR 10a , —OC(O)R 10a , —S(O)R 10a , —S(O) 2 R 10a , —NO 2 , -O, ═S, ═N(R 10a ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10a , —SR 10a , —N(R 10a ) 2 , —C(O)R 10a , —C(O)N(R 10a ) 2 , —N(R 10a )C(O)R 10a , —N(R 10a )C(O)N(R 10a ) 2 , —OC(O)N(R 10a ) 2 , —N(R 10a )C(O)OR 10a , —C(O)OR 10a , —OC(O)R 10a , —S(O)R 10a , —S(O) 2 R 10a , —NO 2 , ═O, ═S, ═N(R 10a ), —N 3 , and —CN;

R 9bB , R 9bD , and R 9bE are each independently selected from:

hydrogen;

halogen, —NO 2 , —N 3 , —CN, —OR 10b , —SR 10b , —N(R 10b ) 2 , —C(O)R 10b , —C(O)N(R 10b ) 2 , —N(R 10b )C(O)R 10b , —N(R 10b )C(O)N(R 10b ) 2 , —OC(O)N(R 10b ) 2 , —N(R 10b )C(O)OR 10b , —C(O)OR 10b , —OC(O)R 10b , —S(O)R 10b , and —S(O) 2 R 10b ;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10b , —SR 10b , —N(R 10b ) 2 , —C(O)R 10b , —C(O)N(R 10b ) 2 , —N(R 10b )C(O)R 10b , —C(O)OR 10b , —OC(O)R 10b , —N(R 10b )C(O)N(R 10b ) 2 , —OC(O)N(R 10b ) 2 , —N(R 10b )C(O)OR 10b , —S(O)R 10b , —S(O) 2 R 10b , —NO 2 , ═O, ═S, =N(R 10b ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10b , —SR 10b , —N(R 10b ) 2 , —C(O)R 10b , —C(O)N(R 10b ) 2 , —N(R 10b )C(O)R 10b , —N(R 10b )C(O)N(R 10b ) 2 , —OC(O)N(R 10b ) 2 , —N(R 10b )C(O)OR 10b , —C(O)OR 10b , —OC(O)R 10b , —S(O)R 10b , —S(O) 2 R 10b , —NO 2 , ═O, ═S, ═N(R 10b ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

R 9bC is selected from:

halogen, —NO 2 , —N 3 , —CN, —OR 10b , —SR 10b , —N(R 10b ) 2 , —C(O)R 10b , —C(O)N(R 10b ) 2 , —N(R 10b )C(O)R 10b , —N(R 10b )C(O)N(R 10b ) 2 , —OC(O)N(R 10b ) 2 , —N(R 10b )C(O)OR 10b , C(O)OR 10b , —OC(O)R 10b , —S(O)R 10b , and —S(O) 2 R 10b ;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10b , —SR 10b , —N(R 10b ) 2 , —C(O)R 10b , C(O)N(R 10b ) 2 , —N(R 10b )C(O)R 10b , C(O)OR 10b , —OC(O)R 10b , —N(R 10b )C(O)N(R 10b ) 2 , —OC(O)N(R 10b ) 2 , —N(R 10b )C(O)OR 10b , —S(O)R 10b , —S(O) 2 R 10b , —NO 2 , ═O, ═S, ═N(R 10b ), —N 3 , —CN, C 3-10 carbocycle and 3- to 10-membered heterocycle; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10b , —SR 10b , —N(R 10b ) 2 , —C(O)R 10b , C(O)N(R 10b ) 2 , —N(R 10b )C(O)R 10b , —N(R 10b )C(O)N(R 10b ) 2 , —OC(O)N(R 10b ) 2 , —N(R 10b )C(O)OR 10b , —C(O)OR 10b , —OC(O)R 10b , —S(O)R 10b , —S(O) 2 R 10b , —NO 2 , —O, ═S, ═N(R 10b ), —N 3 , —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

each R 9z is independently selected from:

halogen, —OR 10z , —SR 10z , —N(R 10z ) 2 , —C(O)R 10z , —C(O)N(R 10z ) 2 , —N(R 10z )C(O)R 10z , —N(R 10z )C(O)N(R 10z ) 2 , —OC(O)N(R 10z ) 2 , —N(R 10z )C(O)OR 10z , —C(O)OR 10z , —OC(O)R 10z , —S(O)R 10z , —S(O) 2 R 10z , —NO 2 , ═O, ═S, ═N(R 10z ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10z , —SR 10z , —N(R 10z ) 2 , —C(O)R 10z , —C(O)N(R 10z ) 2 , —N(R 10z )C(O)R 10z , —N(R 10z )C(O)N(R 10z ) 2 , —OC(O)N(R 10z ) 2 , —N(R 10z )C(O)OR 10z , —C(O)OR 10z , —OC(O)R 10z , —S(O)R 10z , —S(O) 2 R 10z , —NO 2 , ═O, ═S, ═N(R 10z ), —N 3 , and —CN;

each R 9c is independently selected from:

halogen, —OR 10c , —SR 10c , —N(R 10c ) 2 , —C(O)R 10c , —C(O)N(R 10c ) 2 , —N(R 10c )C(O)R 10c , —N(R 10c )C(O)N(R 10c ) 2 , —OC(O)N(R 10c ) 2 , —N(R 10c )C(O)OR 10c , —C(O)OR 10c , —OC(O)R 10c , —S(O)R 10c , —S(O) 2 R 10c , —NO 2 , ═O, ═S, ═N(R 10c ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10c , —SR 10c , —N(R 10c ) 2 , —C(O)R 10c , —C(O)N(R 10c ) 2 , —N(R 10c )C(O)R 10c , —N(R 10c )C(O)N(R 10c ) 2 , —OC(O)N(R 10c ) 2 , —N(R 10c )C(O)OR 10c , —C(O)OR 10c , —OC(O)R 10c , —S(O)R 10c , —S(O) 2 R 10c , —NO 2 , ═O, ═S, ═N(R 10c ), —N 3 , and —CN;

each R 9d is independently selected from:

halogen, —OR 10d , —SR 10d , —N(R 10d ) 2 , —C(O)R 10d , —C(O)N(R 10d ) 2 , —N(R 10d )C(O)R 10d , —N(R 10d )C(O)N(R 10d ) 2 , —OC(O)N(R 10d ) 2 , —N(R 10d )C(O)OR 10d , —C(O)OR 10d , —OC(O)R 10d , —S(O)R 10d , —S(O) 2 R 10d , —NO 2 , ═O, ═S, ═N(R 10d ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10d , —SR 10d , —N(R 10d ) 2 , —C(O)R 10d , —C(O)N(R 10d ) 2 , —N(R 10d )C(O)R 10d , —N(R 10d )C(O)N(R 10d ) 2 , —OC(O)N(R 10d ) 2 , —N(R 10d )C(O)OR 10d , —C(O)OR 10d , —OC(O)R 10d , —S(O)R 10d , —S(O) 2 R 10d , —NO 2 , ═O, ═S, ═N(R 10d ), —N 3 , and —CN;

each R 9e is independently selected from:

halogen, —OR 10e , —SR 10e , —N(R 10e ) 2 , —C(O)R 10e , —C(O)N(R 10e ) 2 , —N(R 10e )C(O)R 10e , —N(R 10e )C(O)N(R 10e ) 2 , —OC(O)N(R 10e ) 2 , —N(R 10e )C(O)OR 10e , —C(O)OR 10e , —OC(O)R 10e , —S(O)R 10e , —S(O) 2 R 10e , —NO 2 , ═O, ═S, ═N(R 10e ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10e , —SR 10e , —N(R 10e ) 2 , —C(O)R 10e , —C(O)N(R 10e ) 2 , —N(R 10e )C(O)R 10e , —N(R 10e )C(O)N(R 10e ) 2 , —OC(O)N(R 10e ) 2 , —N(R 10e )C(O)OR 10e , —C(O)OR 10e , —OC(O)R 10e , —S(O)R 10e , —S(O) 2 R 10e , —NO 2 , ═O, ═S, ═N(R 10e ), —N 3 , and —CN;

each R 9f is independently selected from:

halogen, —OR 10f , —SR 10f , —N(R 10f ) 2 , —C(O)R 10f , —C(O)N(R 10f ) 2 , —N(R 10f )C(O)R 10f , —N(R 10f )C(O)N(R 10f ) 2 , —OC(O)N(R 10f ) 2 , —N(R 10f )C(O)OR 10f , —C(O)OR 10f , —OC(O)R 10f , —S(O)R 10f , —S(O) 2 R 10f , —NO 2 , ═O, ═S, ═N(R 10f ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10f , —SR 10f , —N(R 10f ) 2 , —C(O)R 10f , —C(O)N(R 10f ) 2 , —N(R 10f )C(O)R 10f , —N(R 10f )C(O)N(R 10f ) 2 , —OC(O)N(R 10f ) 2 , —N(R 10f )C(O)OR 10f , —C(O)OR 10f , —OC(O)R 10f , —S(O)R 10f , —S(O) 2 R 10f , —NO 2 , ═O, ═S, ═N(R 10f ), —N 3 , and —CN;

each R 9g is independently selected from:

halogen, —OR 10g , —SR 10g , —N(R 10g ) 2 , —C(O)R 10g , —C(O)N(R 10g ) 2 , —N(R 10g )C(O)R 10g , —N(R 10g )C(O)N(R 10g ) 2 , —OC(O)N(R 10g ) 2 , —N(R 10g )C(O)OR 10g , —C(O)OR 10g , —OC(O)R 10g , —S(O)R 10g , —S(O) 2 R 10g , —NO 2 , ═O, ═S, ═N(R 10g ), —N 3 , and —CN; and

C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR 10g , —SR 10g , —N(R 10g ) 2 , —C(O)R 10g , —C(O)N(R 10g ) 2 , —N(R 10g )C(O)R 10g , —N(R 10g )C(O)N(R 10g ) 2 , —OC(O)N(R 10g ) 2 , —N(R 10g )C(O)OR 10g , —C(O)OR 10g , —OC(O)R 10g , —S(O)R 10g , —S(O) 2 R 10g , —NO 2 , ═O, ═S, ═N(R 10g ), —N 3 , and —CN; and

each R 10a , R 10b , R 10z , R 10c , R 10d , R 10e , R 10f , and R 10g is independently selected from: hydrogen;

C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO 2 , —NH 2 , =O, =S, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , —NH(C 1-6 alkyl), C 3-10 carbocycle, and 3- to 10-membered heterocycle; and

C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO 2 , —NH 2 , ═O, ═S, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —N(C 1-6 alkyl) 2 , —NH(C 1-6 alkyl), C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 carbocycle, 3- to 10-membered heterocycle, and C 1-6 haloalkyl.

2 . The compound or salt of claim 1 , wherein:

X 1 is selected from C(R 1a );

X 2 is selected from C(R 1b );

X 3 is selected from C(R 1c );

X 4 is selected from (R 1d ); and

no more than one of Y 2 , Y 4 , and Y 5 is N or N + (O − ).

3 . The compound or salt of claim 1 , wherein

X 1 is selected from C(H), C(F), and C(CN), and C(CH 3 );

X 2 is selected from N, C(H), C(F), C(CH 3 ), and C(CN);

X 3 is C(H); and

X 4 is CH).

4 . The compound or salt of claim 1 , wherein R 1a , R 1b , and R 1c are each independently selected from:

hydrogen;

halogen, —NO 2 , —CN, —OR 10a , —SR 10a , and —N(R 10a ) 2 ; and

C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR 10a , —SR 10a , —N(R 10a ) 2 , —NO 2 , ═O, and —CN.

5 . The compound or salt of claim 1 , wherein R 1a , R 1b , and R 1c are each independently selected from: hydrogen, halogen, —CN, and C 1-6 alkyl.

6 . The compound or salt of claim 1 , wherein R Z is selected from C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and —OH.

7 . The compound or salt of claim 1 , wherein R Z is selected from —CH 3 , and R C is selected from hydrogen.

8 . The compound or salt of claim 1 , wherein R 5 together with R 6 form a cyclopropyl.

9 . The compound or salt of claim 1 , wherein R 5 is hydrogen, and R 6 is hydrogen.

10 . The compound or salt of claim 1 , wherein R 7 is hydrogen.

11 . The compound or salt of claim 1 , wherein R 7 is hydrogen, and R 8 is hydrogen.

12 . The compound or salt of claim 1 , wherein:

Y 2 is selected from C(H), C(F), C(CH 3 ), and N;

R 9bC is selected from —CN, C—F, C—Cl, and C—OH;

Y 4 is selected from C(H), C(F), C(CH 3 ), and N; and

Y 5 is selected from N, C(H), C(F), and C(CH 3 ).

13 . The compound or salt of claim 1 , wherein R 9bC is selected from C—CN.

14 . The compound or salt of claim 1 , wherein:

Y 2 is C(R 9bB ), Y 4 is C(R 9bD ), and Y 5 is C(R 9bE ); or

Y 2 is C(R 9bB ), Y 4 is C(R 9bD ), and Y 5 is N; or

Y 2 is N, Y 4 is C(R 9bD ), and Y 5 is C(R 9bE ).

15 . The compound or salt of claim 1 , wherein R 9bB , R 9bD , and R 9bE are each independently selected from: hydrogen; halogen, —CN, —OR 10b , —SR 10b , and —N(R 10b ) 2 ; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR 10b , —SR 10b , —N(R 10b ) 2 , ═O, and —CN.

16 . The compound or salt of claim 1 , wherein R 9bB , R 9bD , and R 9bE are each independently selected from: hydrogen, fluoro, —CN, —OH, and C 1 alkyl.

17 . The compound or salt of claim 1 , wherein each R 9a , R 9z , R 9c , R 9e , R 9f , and R 9g is independently selected from: fluoro and —CN; and each R 10a , R 10b , R 10z , R 10c , R 10d , R 10e , R 10f , and R 10g is independently selected from: hydrogen and C 1-6 alkyl.

18 . The compound or salt of claim 1 , wherein:

R 8 is hydrogen.

19 . The compound or salt of claim 1 , wherein R 1d is selected from:

hydrogen;

NO 2 , —CN, —OR 10a , —SR 10a , and —N(R 10a ) 2 ; and

C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR 10a , —SR 10a , —N(R 10a ) 2 , —NO 2 , ═O, and —CN.

20 . The compound or salt of claim 1 , wherein R 1d is selected from: hydrogen, —CN, and C 1-6 alkyl.

21 . The compound or salt of claim 1 , wherein U is absent.

22 . The compound of claim 1 , wherein the compound is

or a salt thereof.

23 . The compound of claim 1 , wherein the compound is

or a salt thereof.

24 . The compound of claim 1 , wherein the compound is

or a salt thereof.

25 . The compound of claim 1 , wherein the compound is

or a salt thereof.

26 . The compound of claim 1 , wherein the compound is

or a salt thereof.

27 . The compound of claim 1 , wherein the compound is

or a salt thereof.

28 . The compound of claim 1 , wherein the compound is

or a salt thereof.

29 . The compound of claim 1 , wherein the compound is

or a salt thereof.

30 . A pharmaceutical composition comprising the compound or salt of claim 1 and a pharmaceutically acceptable excipient.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2025

From: HUNT, KEVIN

To: EDGEWISE THERAPEUTICS, INC.

Reel/Frame 070718/0277 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 6, 2025

From: HAWRYLUK, NATALIE ANNE; SCHLACHTER, STEPHEN THOMAS; KOCH, KEVIN; LUZZIO, MICHAEL JOSEPH; DUVALL, MICHAEL MARK; RUSSELL, ALAN JAMES; EVANCHIK, MARC JUSTIN

To: EDGEWISE THERAPEUTICS, INC.

Reel/Frame 070431/0689 →

Continuity (4)

Continuation PCTUS2024021537 · Mar 26, 2024

Provisional Application 63513844 · Jul 14, 2023

Provisional Application 63492439 · Mar 27, 2023

Related Publication 20250026726A1 · Jan 23, 2025

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Database Registry, Chemical Abstracts Service (Jun. 23, 2020), Database accession No. 2432461-84-0, XP093279900. [cited by applicant]

Database Registry, Chemical Abstracts Service (Aug. 31, 2020), Database accession No. 2468117-82-8, XP093279897. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Sep. 23, 2021), Database accession No. 2699886-11-6, XP093277387. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Oct. 14, 2021), Database accession No. 2712289-98-8, XP093277386. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Oct. 15, 2021), Database accession No. 2712788-51-5, XP093277508. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Oct. 17, 2021), Database accession No. 2713664-04-9, XP093277384. [cited by applicant]

Database Registry, Chemical Abstracts Service (Jul. 26, 2022), Database accession No. 2797160-72-4, XP093279894. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Sep. 1, 2022), Database accession No. 2816805-43-1, X P093277382. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Jun. 23, 2023), Database accession No. 2935080-68-3, XP093277525. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Aug. 29, 2023), Database accession No. 2966899-34-1, XP093277520. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Aug. 31, 2023), Database accession No. 2968160-16-7, XP093277515. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Oct. 18, 2023), Database accession No. 2990803-91-1, XP093277379. [cited by applicant]

Database Registry, Chemical Abstracts Service; (Dec. 1, 2023), Database accession No. 3009361-40-1, XP093277454. [cited by applicant]

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Ukrainets I. V. et al. 4-Hydroxyquinolin-2-ones. 45. Synthesis, Structure, and Biological Activity of N-Substituted 1H-4-Hydroxy-2-oxoquinoline-3-acetic Acid Amides. Chemistry of Heterocyclic Compounds XP093278700, 36(1… [cited by applicant]