Substituted pyridazinones for use in the treatment of neuromuscular diseases

A method of treating a disease, the method comprising administering to a subject in need thereof a compound or salt of Formula (III):

• or a salt thereof, wherein:
• each Y is independently selected from C(R3), N, and 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 —NR4—, R1 is additionally selected from hydrogen, 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, —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;
• each R3, R5, and R6 is 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;
• each R7 and R8 is 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 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;
• R30 and R31 are independently selected from R10 or R30 and R31 come together to form a C3-7 carbocycle, or 3- to 7-membered heterocycle, wherein C3-7 carbocycle and 3- to 7-membered heterocycle are optionally substituted with one or more substituents independently selected from R9;
• n is 0, 1, or 2;
• p is 0, 1, or 2;
• and
• q is 0, 1, 2, 3, 4, or 5,
• wherein the disease is selected from Congenital muscular dystrophies, Emery-Dreifuss muscular dystrophy, Congenital myopathies, distal myopathies, endocrine myopathies, inflammatory myopathies, myofibrillar myopathies, scapuloperoneal myopathy, and cardiomyopathies;
• wherein the Congenital muscular dystrophies are selected from Bethlem CMD, Fukuyama CMD, Muscle-eye-brain diseases, Rigid spine syndromes, Ullrich CMD, and Walker-Warburg syndromes;
• and
• wherein the metabolic myopathy is selected from acid maltase deficiency, carnitine deficiency, carnitine palmitoyltransferase deficiency, debrancher enzyme deficiency, lactate dehydrogenase deficiency, myoadenylate deaminase deficiency, phosphofructokinase deficiency, phosphoglycerate kinase deficiency, and phosphoglycerate mutase deficiency.