US 12,448,369 B2
Quinolinone amide compounds and uses thereof
Natalie Anne Hawryluk, Nederland, CO (US); Stephen Thomas Schlachter, Boulder, CO (US); Kevin Koch, Niwot, CO (US); Michael Joseph Luzzio, Groton, CT (US); Alan James Russell, Boulder, CO (US); Marc Justin Evanchik, Boulder, CO (US); Carlos Luis Del Rio, San Mateo, CA (US); and Kevin Hunt, Boulder, CO (US)
Assigned to Edgewise Therapeutics, Inc., Boulder, CO (US)
Filed by Edgewise Therapeutics, Inc., Boulder, CO (US)
Filed on Sep. 11, 2024, as Appl. No. 18/882,644.
Application 18/882,644 is a continuation of application No. PCT/US2024/021528, filed on Mar. 26, 2024.
Claims priority of provisional application 63/492,441, filed on Mar. 27, 2023.
Prior Publication US 2025/0026740 A1, Jan. 23, 2025
Int. Cl. C07D 405/12 (2006.01); A61K 31/4353 (2006.01); A61K 31/506 (2006.01); C07D 221/04 (2006.01); C07D 401/12 (2006.01)
CPC C07D 405/12 (2013.01) [A61K 31/4353 (2013.01); A61K 31/506 (2013.01); C07D 221/04 (2013.01); C07D 401/12 (2013.01)] 56 Claims
 
1. A compound represented by Formula (II-A):

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
X11 is selected from C(R17a) and N;
X12 is selected from C(R17b) and N;
X13 is selected from C(R17c) and N;
Y11 is selected from C(R17d) and N;
Y12 is selected from C(R17e) and N;
R11a, R11b, R11c and R11d are each independently selected from:
hydrogen, halogen, —NO2, —CN, —N3, —OR19a, —SR19a, —N(R19a)2, —C(O)R19a, —C(O)N(R19a)2, —N(R19a)C(O)R19a, —N(R19a)C(O)N(R19a)2, —OC(O)N(R19a)2, —N(R19a)C(O)OR19a, —C(O)OR19a, —OC(O)R19a, —S(O)R19a, and —S(O)2R19a;
C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19a, —SR19a, —N(R19a)2, —C(O)R19a, —C(O)N(R19a)2, —N(R19a)C(O)R19a, —C(O)OR19a, —OC(O)R19a, —N(R19a)C(O)N(R19a)2, —OC(O)N(R19a)2, —N(R19a)C(O)OR19a, —S(O)R19a, —S(O)2R19a, —NO2, ═O, ═S, ═N(R19a), —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R18a; and
C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19a, —SR19a, —N(R19a)2, —C(O)R19a, —C(O)N(R19a)2, —N(R19a)C(O)R19a, —N(R19a)C(O)N(R19a)2, —OC(O)N(R19a)2, —N(R19a)C(O)OR19a, —C(O)OR19a, —OC(O)R19a, —S(O)R19a, —S(O)2R19a, —NO2, ═O, ═S, ═N(R19a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R18a;
wherein when R11a, R11b, and R11c are each hydrogen; then R11d is not hydrogen;
wherein when R11b is —OCH3, then R11c is not —OMe;
R12 is selected from:
hydrogen, halogen, —NO2, —CN, —OR19b, —SR19b, —N(R19b)2, —C(O)R19b, —C(O)N(R19b)2, —N(R19b)C(O)R19b, —N(R19b)C(O)N(R19b)2, —OC(O)N(R19b)2, —N(R19b)C(O)OR19b, —C(O)OR19b, —OC(O)R19b, —S(O)R19b, and —S(O)2R19b;
C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19b, —SR19b, —N(R19b)2, —C(O)R19b, —C(O)N(R19b)2, —N(R19b)C(O)R19b, —C(O)OR19b, —OC(O)R19b, —N(R19b)C(O)N(R19b)2, —OC(O)N(R19b)2, —N(R19b)C(O)OR19b, —S(O)R19b, —S(O)2R19b, —NO2, ═O, ═S, ═N(R19b), —CN, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R18b; and
C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19b, —SR19b, —N(R19b)2, —C(O)R19b, —C(O)N(R19b)2, —N(R19b)C(O)R19b, —N(R19b)C(O)N(R19b)2, —OC(O)N(R19b)2, —N(R19b)C(O)OR19b, —C(O)OR19b, —OC(O)R19b, —S(O)R19b, —S(O)2R19b, —NO2, ═O, ═S, ═N(R19b), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R18b;
R13 is selected from:
hydrogen, halogen, —OR19c, —SR19c, —N(R19c)2, —NO2, and —CN;
C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR19c, —SR19c, —N(R19c)2, —NO2, and —CN; and
C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from —OR19c, —SR19c, —N(R19c)2, —C(O)R19c, —C(O)N(R19c)2, —N(R19c)C(O)R19c, —N(R19c)C(O)N(R19c)2, —OC(O)N(R19c)2, —N(R19c)C(O)OR19c, —C(O)OR19c, —OC(O)R19c, —S(O)R19c, —S(O)2R19c, —NO2, and —CN;
R14 is selected from:
hydrogen, halogen, —OR19d, —SR19d, —N(R19d)2, —NO2, and —CN;
C1-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, —OR19d, —SR19d, —N(R19d)2, —NO2, and —CN; and
C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19d, —SR19d, —N(R19d)2, —C(O)R19d, —C(O)N(R19d)2, —N(R19d)C(O)R19d, —N(R19d)C(O)N(R19d)2, —OC(O)N(R19d)2, —N(R19d)C(O)OR19d, —C(O)OR19d, —OC(O)R19d, —S(O)R19d, —S(O)2R19d, —NO2, ═O, ═S, ═N(R19d), and —CN;
R14′ is selected from:
hydrogen, halogen, —OR19d, —SR19d, —N(R19d)2, —NO2, and —CN; and
C1-6 alkyl which is optionally substituted with one or more substituents independently selected from halogen, —OR19d, —SR19d, —N(R19d)2, —NO2, and —CN; and
C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19d, —SR19d, —N(R19d)2, —C(O)R19d, —C(O)N(R19d)2, —N(R19d)C(O)R19d, —N(R19d)C(O)N(R19d)2, —OC(O)N(R19d)2, —N(R19d)C(O)OR19d, —C(O)OR19d, —OC(O)R19d, —S(O)R19d, —S(O)2R19d, —NO2, ═O, ═S, ═N(R19d), and —CN; or
R14 together with R14′ form a C3-10 carbocycle, or 3- to 10-membered heterocycle, wherein the C3-10 carbocycle or 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18c;
R15 is selected from:
hydrogen, halogen, —OR19e, —SR19e, —N(R19e)2—NO2, and —CN; and
C1-6 alkyl optionally substituted with one or more substituents independently selected from R18d; or
R15 together with R17a form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R15 together with R17b form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R15, R16, and R17b together form a bridged heterocycle, wherein the bridged heterocycle is optionally substituted with one or more substituents independently selected from R18f;
R16 is selected from:
hydrogen, halogen, —OR19f, —SR19f, —N(R19f)2, —NO2, and —CN; and
C1-6 alkyl optionally substituted with one or more substituents independently selected from R18e; or
R16 together with R17a form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R16 together with R17b form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R15, R16, and R17b together form a bridged heterocycle, wherein the bridged heterocycle is optionally substituted with one or more substituents independently selected from R18f;
R17a, R17b, R17c, R17d, and R17e are each independently selected from:
hydrogen, halogen, —OR19g, —SR19g, —N(R19g)2, —NO2, —CN, and —N3; and
C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from R18f; or
R15 together with R17a form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R15 together with R17b form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R16 together with R17a form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R16 together with R17b form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from R18f; or
R15, R16, and R17b together form a bridged heterocycle, wherein the bridged heterocycle is optionally substituted with one or more substituents independently selected from R18f;
each R18a, R18b, R18c, R18d, R18e, and R18f is independently selected from:
halogen, —OR19h, —SR19h, —N(R19h)2, —C(O)R19h, —C(O)N(R19h)2, —N(R19h)C(O)R19h, —N(R19h)C(O)N(R19h)2, OC(O)N(R19h)2, —N(R19h)C(O)OR19h, —C(O)OR19h, —OC(O)R19h, —S(O)R19h, —S(O)2R19h, —NO2, ═O, ═S, ═N(R19h), and —CN; and
C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR19h, —SR19h, —N(R19h)2, —C(O)R19h, —C(O)N(R19h)2, —N(R19h)C(O)R19h, —N(R19h)C(O)N(R19h)2, —OC(O)N(R19h)2, —N(R19h)C(O)OR19h, —C(O)OR19h, —OC(O)R19h, —S(O)R19h, —S(O)2R19h, —NO2, ═O, ═S, ═N(R19h), and —CN; and
each R19a, R19b, R19c, R19d, R19e, R19f, R19g, and R19h is independently selected from:
hydrogen;
C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, and 3- to 10-membered heterocycle; and
C3-10 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, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl.