US 12,240,833 B2
Pyridazinone compounds and uses thereof
Kevin Hunt, Boulder, CO (US); Kevin Koch, Boulder, CO (US); Alan Russell, Boulder, CO (US); Stephen Schlachter, Boulder, CO (US); Paul Winship, Cambridge (GB); Grace Uzoho, Cambridge (GB); and Chris Steele, Cambridge (GB)
Assigned to EDGEWISE THERAPEUTICS, INC., Boulder, CO (US)
Filed by Edgewise Therapeutics, Inc., Boulder, CO (US)
Filed on May 27, 2022, as Appl. No. 17/827,547.
Application 17/827,547 is a continuation of application No. 17/088,468, filed on Nov. 3, 2020, granted, now 11,390,606.
Application 17/088,468 is a continuation of application No. PCT/US2019/060148, filed on Nov. 6, 2019.
Claims priority of provisional application 62/756,552, filed on Nov. 6, 2018.
Prior Publication US 2023/0048816 A1, Feb. 16, 2023
Int. Cl. C07D 403/04 (2006.01); A61P 21/00 (2006.01); C07D 237/04 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 403/10 (2006.01); C07D 403/14 (2006.01); C07D 405/10 (2006.01); C07D 405/14 (2006.01); C07D 417/10 (2006.01)
CPC C07D 403/04 (2013.01) [A61P 21/00 (2018.01); C07D 237/04 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 403/10 (2013.01); C07D 403/14 (2013.01); C07D 405/10 (2013.01); C07D 405/14 (2013.01); C07D 417/10 (2013.01)] 28 Claims
 
1. A method of treating a neuromuscular condition, the method comprising administering to a patient in need thereof a compound represented by Formula (I):

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
each X is independently selected from C(R3), N, and N+(—O−) wherein at least one X is N or N+(—O−);
A is selected from —O—, —NR4—, —CR5R6—, —C(O)—, —S—, —S(O)—, and —S(O)2—;
R1 is selected from:
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, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —NO2, ═O, ═S, ═N(R10), —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 R9; 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, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —NO2, ═O, ═S, ═N(R10), and —CN; or
R1 together with R3 form a 5- to 10-membered heterocycle or C5-10 carbocycle, wherein the 5- to 10-membered heterocycle or C5-10 carbocycle is optionally substituted with one or more R9; or R1 together with R5 form a 3- to 10-membered heterocycle or saturated C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or saturated C3-10 carbocycle is optionally substituted with one or more R9; or R1 together with R4 form a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more R9; and
when A is —C(O)—, R1 is additionally selected from —N(R10)2 and —OR10; each R2 is independently selected from:
halogen, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —NO2, and —CN;
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, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —NO2, ═O, ═S, ═N(R10), and —CN; and
C3-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —NO2, ═O, ═S, ═N(R10), and —CN;
R3, R5, and R6 are each independently selected from:
hydrogen, halogen, —OR10, —SR10, —N(R10)2, —NO2, and —CN; and
C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10, —SR10, —N(R10)2, —NO2, and —CN; or
R3 together with R1 form a 5- to 10-membered heterocycle or C5-10 carbocycle, wherein the 5- to 10-membered heterocycle or C5-10 carbocycle is optionally substituted with one or more R9; or R5 together with R1 form a 3- to 10-membered heterocycle or saturated C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or saturated C3-10 carbocycle is optionally substituted with one or more R9;
R4 is independently selected from:
hydrogen; and
C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10, —SR10, —N(R10)2, —NO2, and —CN; or
R4 together with R1 form a 3- to 10-membered heterocycle, which is optionally substituted with one or more R9;
R7 and R8 are independently selected from:
halogen, —OR10, —SR10, —N(R10)2, —NO2, —CN, —CHF2, —CF3, —CH2F, and C2-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10, —SR10, —N(R10)2, —NO2, and —CN;
each R9 is independently selected from:
halogen, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10—S(O)2R10, —NO2, ═O, ═S, ═N(R10), 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, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —N(R10)C(O)N(R10)2, —OC(O)N(R10)2, —N(R10)C(O)OR10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —NO2, ═O, ═S, ═N(R10), and —CN;
each R10 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 haloalkyl;
n is 0, 1, or 2;
p is 0, 1, or 2; and
q is 1, 2, 3, 4, or 5, and when R1 is other than —CH3, q is further selected from 0.