Quinolinone amide compounds and uses thereof

A compound represented by Formula (IV):

• or a salt thereof, wherein:
• RJ is a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from halogen, —OR410b, —SR410b, —N(R410b)2, —C(O)R410b, —C(O)N(R410b)2, —N(R410b)C(O)R410b, —N(R410b)C(O)N(R410b)2, —OC(O)N(R410b)2, —N(R410b)C(O)OR410b, —C(O)OR410b, —OC(O)R410b, —S(O)R410b, —S(O)2R410b, —NO2, ═O, ═S, ═N(R410b), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49a;
• X41 is selected from C(R41a) and N;
• X42 is selected from C(R41b) and N;
• X43 is selected from C(R41c) and N;
• X44 is selected from C(R41d) and N;
• wherein no more than two of X41, X42, X43, and X44 are N;
• R41a, R41b, R41c, and R41d are each independently selected from:
• hydrogen;
• halogen, —NO2, —N3, —CN, —OR410a, —SR410a, —N(R410a)2, —C(O)R410a, —C(O)N(R410)2, —N(R410a)C(O)R410a, —N(R410a)C(O)N(R410a)2, —OC(O)N(R410a)2, —N(R410a)C(O)OR410a, —C(O)OR410a, —OC(O)R410a, —S(O)R410a, and —S(O)2R410a;
• 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, —OR410a, —SR410a, —N(R410a)2, —C(O)R410a, —C(O)N(R410a)2, —N(R410a)C(O)R410a, —C(O)OR410a, —OC(O)R410a, —N(R410a)C(O)N(R410a)2, —OC(O)N(R410a)2, —N(R410a)C(O)OR410a, —S(O)R410a, —S(O)2R410a, —NO2, ═O, ═S, ═N(R410a), —N3, —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 R49a;
• 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, —OR410a, —SR410a, —N(R410a)2, —C(O)R410a, —C(O)N(R410a)2, —N(R410a)C(O)R410a, —N(R410a)C(O)N(R410a)2, —OC(O)N(R410a)2, —N(R410a)C(O)OR410a, —C(O)OR410a, —OC(O)R410a, —S(O)R410a, —S(O)2R410a, —NO2, ═O, ═S, ═N(R410a), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49a;
• wherein when X41 is C(H), X42 is C(H), and X43 is C(H);
• then R41d is not hydrogen;
• R43 is selected from:
• hydrogen, halogen, —OR410x, —SR410x, —N(R410x)2, —NO2, —CN, C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R47e;
• R4Z is selected from:
• —C(O)R410z, —C(O)N(R410z)2, —C(O)OR410z, and —CN;
• 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, —OR410z, —SR410zN(R410z)2, —C(O)R410z, —C(O)N(R410z)2, —N(R410z)C(O)R410z, —C(O)OR410z, —OC(O)R410z, —N(R410z)C(O)N(R410z)2, —OC(O)N(R410z)2, —N(R410z)C(O)OR410z, —S(O)R410z, —S(O)2R410z, —NO2, ═O, ═S, ═N(R410z), —N3, —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 R49z;
• 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, —OR410z, —SR410z, —N(R410z)2, —C(O)R410z, —C(O)N(R410z)2, —N(R410z)C(O)R410z, —N(R410z)C(O)N(R410z)2, —OC(O)N(R410z)2, —N(R410z)C(O)OR410z, —C(O)OR410z, —OC(O)R410z, —S(O)R410z, —S(O)2R410z, —NO2, ═O, ═S, ═N(R410z), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49z;
• R4C is selected from:
• hydrogen;
• —C(O)R410c, —C(O)N(R410c)2, —C(O)OR410c, and —CN;
• 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, —OR410c, —SR410c, —N(R410c)2, —C(O)R410c, —C(O)N(R410c)2, —N(R410c)C(O)R410c, —C(O)OR410c, —OC(O)R410c, —N(R410c)C(O)N(R410c)2, —OC(O)N(R410c)2, —N(R410c)C(O)OR410c, —S(O)R410c, —S(O)2R410c, —NO2, ═O, ═S, ═N(R410c), —N3, —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 R49e;
• 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, —OR410c, —SR410c, —N(R410c)2, —C(O)R410c, —C(O)N(R410c)2, —N(R410c)C(O)R410c, —N(R410c)C(O)N(R410c)2, —OC(O)N(R410c)2, —N(R410c)C(O)OR410c, —C(O)OR410c, —OC(O)R410c, —S(O)R410c, —S(O)2R410c, —NO2, ═O, ═S, ═N(R410c), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49c;
• R45 is selected from:
• hydrogen;
• halogen, —OR410d, SR410d, —N(R410d)2, C(O)R410d, —C(O)N(R410d)2, —N(R410d)C(O)R410d, —C(O)OR410d, —OC(O)R410d, —N(R410d)C(O)N(R410d)2, —OC(O)N(R410d)2, —N(R410d)C(O)OR410d, —S(O)R410d, S(O)2R410d, —NO2, —N3, and —CN;
• 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, —OR410d, —SR410d, —N(R410d)2, —C(O)R410d, —C(O)N(R410d)2, —N(R410d)C(O)R410d, —C(O)OR410d, —OC(O)R410d, —N(R410d)C(O)N(R410d)2, —OC(O)N(R410d)2, —N(R410d)C(O)OR410d, —S(O)R410d, —S(O)2R410d, —NO2, ═O, ═S, ═N(R410d), —N3, —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 R49d;
• 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, —OR410d, —SR410d, —N(R410d)2, —C(O)R410d, —C(O)N(R410d)2, —N(R410d)C(O)R410d, —N(R410d)C(O)N(R410d)2, —OC(O)N(R410d)2, —N(R410d)C(O)OR410d, —C(O)OR410d, —OC(O)R410d, —S(O)R410d, —S(O)2R410d, —NO2, ═O, ═S, ═N(R410d), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49d;
• or
• R45 together with R46 form a 3- to 10-membered heterocycle or C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C3-10 carbocycle is optionally substituted with one or more R49d;
• R46 is selected from:
• hydrogen;
• halogen, —OR410c, —SR410e, —N(R410e)2, —C(O)R410e, —C(O)N(R410e)2, —N(R410e)C(O)R410e, —C(O)OR410e, —OC(O)R410e, —N(R410e)C(O)N(R410e)2, —OC(O)N(R410e)2, —N(R410e)C(O)OR410e, —S(O)R410e, —S(O)2R410e, —NO2, —N3, and —CN;
• 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, —OR410e, —SR410e, N(R410e)2, —C(O)R410e, —C(O)N(R410e)2, —N(R410e)C(O)R410e, C(O)OR410e, —OC(O)R410e, —N(R410e)C(O)N(R410e)2, —OC(O)N(R410c)2, —N(R410e)C(O)OR410e, —S(O)R410e, S(O)2R410e, —NO2, ═O, ═S, ═N(R410e), —N3, —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 R49e;
• 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, —OR410e, —SR410e, —N(R410e)2, —C(O)R410e, —C(O)N(R410e)2, —N(R410e)C(O)R410e, —N(R410e)C(O)N(R410e)2, —OC(O)N(R410e)2, —N(R410e)C(O)OR410e, C(O)OR410e, —OC(O)R410e, S(O)R410e, —S(O)2R410e, —NO2, ═O, ═S, ═N(R410e), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49;
• R47 is selected from:
• hydrogen;
• —C(O)R410f, —C(O)N(R410f)2, —C(O)OR410f, —S(O)R410f, and —S(O)2R410f;
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR410f, —SR410f, —N(R410f)2, —C(O)R410c, —C(O)N(R410f)2, —N(R410f)C(O)R410f, —C(O)OR410f, —OC(O)R410f, —N(R410f)C(O)N(R410f)2, —OC(O)N(R410f)2, —N(R410)C(O)OR410f, —S(O)R410f, —S(O)2R410e, —NO2, ═O, ═S, ═N(R410f), —N3, —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 R49f;
• 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, —OR410f, —SR410f, —N(R410f)2, —C(O)R410f, —C(O)N(R410f)2, —N(R410f)C(O)R410f, —N(R410f)C(O)N(R410f)2, —OC(O)N(R410f)2, —N(R410f)C(O)OR410f, —C(O)OR410f, —OC(O)R410f, —S(O)R410f, —S(O)2R410f, —NO2, ═O, ═S, ═N(R410f), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49f;
• each R47e is independently selected from:
• halogen, —OR410y, —SR410y, —N(R410y)2, —C(O)R410y, —C(O)N(R410y)2, —N(R410)C(O)R410y, —N(R410y)C(O)N(R410y)2, —OC(O)N(R410y)2, —N(R410y)C(O)OR410y, —C(O)OR410y, —OC(O)R410y, —S(O)R410y, —S(O)2R410e, —NO2, ═O, ═S, ═N(R410y), 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, —OR410y, —SR410y, —N(R410y)2, —C(O)R410y, —C(O)N(R410y)2, —N(R410y)C(O)R410y, —N(R410y)C(O)N(R410y)2, —OC(O)N(R410y)2, —N(R410y)C(O)OR410y, —C(O)OR410y, —OC(O)R410y, —S(O)R410y, —S(O)2R410y, —NO2, ═O, ═S, ═N(R410y), and —CN;
• R48 is selected from:
• hydrogen;
• —C(O)R410g, —C(O)N(R410g)2, —C(O)OR410g, —S(O)R410g, and —S(O)2R410g;
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR410g, —SR410g, —N(R410g)2, —C(O)R410g, —C(O)N(R410g)2, —N(R410g)C(O)R410g, —C(O)OR410g, —OC(O)R410g, —N(R410g)C(O)N(R410g)2, —OC(O)N(R410g)2, —N(R410g)C(O)OR410g, —S(O)R410g, —S(O)2R410f, —NO2, ═O, ═S, ═N(R410g), —N3, —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 R499;
• 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, —OR410g, —SR410g, —N(R410g)2, —C(O)R410g, —C(O)N(R410g)2, —N(R410g)C(O)R410g, —N(R410g)C(O)N(R410g)2, —OC(O)N(R410g)2, —N(R410g)C(O)OR410g, —C(O)OR410g, —OC(O)R410g, —S(O)R410g, —S(O)2R410g, —NO2, ═O, ═S, ═N(R410g), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R49h;
• each R49a is independently selected from:
• halogen, —OR410a, —SR410a, —N(R410a)2, —C(O)R410a, —C(O)N(R410a)2, —N(R410a)C(O)R410a, —N(R410a)C(O)N(R410a)2, —OC(O)N(R410a)2, —N(R410a)C(O)OR410a, —C(O)OR410a, —OC(O)R410a, —S(O)R410a, —S(O)2R410a, —NO2, ═O, ═S, ═N(R410a), —N3, 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, —OR410a, —SR410a, N(R410a)2, —C(O)R410a, —C(O)N(R410a)2, —N(R410a)C(O)R410a, —N(R410a)C(O)N(R410a)2, —OC(O)N(R410a)2, —N(R410a)C(O)OR410a, —C(O)OR410a, —OC(O)R410a, —S(O)R410a, —S(O)2R410a, —NO2, ═O, ═S, ═N(R410a), —N3, and —CN;
• each R49z is independently selected from:
• halogen, —OR410z, SR410z, —N(R410z)2, —C(O)R410z, —C(O)N(R410z)2, —N(R410z)C(O)R410z, —N(R410z)C(O)N(R410z)2, —OC(O)N(R410z)2, —N(R410z)C(O)OR410z, —C(O)OR410z, —OC(O)R410z, S(O)R410z, —S(O)2R410z, —NO2, ═O, ═S, ═N(R410z), —N3, 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, —OR410z, —SR410z, —N(R410z)2, —C(O)R410z, —C(O)N(R410z)2, —N(R410z)C(O)R410z, —N(R410z)C(O)N(R410z)2, —OC(O)N(R410z)2, —N(R410z)C(O)OR410z, —C(O)OR410z, —OC(O)R410z, —S(O)R410z, —S(O)2R410z, —NO2, ═O, ═S, ═N(R410z), —N3, and —CN;
• each R49c is independently selected from:
• halogen, —OR410c, —SR410c, —N(R410c)2, —C(O)R410c, —C(O)N(R410c)2, —N(R410c)C(O)R410c, —N(R410c)C(O)N(R410c)2, —OC(O)N(R410c)2, —N(R410c)C(O)OR410c, —C(O)OR410c, —OC(O)R410c, —S(O)R410c, —S(O)2R410c, —NO2, ═O, ═S, ═N(R410c), —N3, 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, —OR410c, —SR410c, —N(R410c)2, —C(O)R410c, —C(O)N(R410c)2, —N(R410c)C(O)R410c, —N(R410c)C(O)N(R410c)2° —OC(O)N(R410c)2, —N(R410c)C(O)OR410c, —C(O)OR410c, —OC(O)R410c, —S(O)R410c, —S(O)2R410c, —NO2, ═O, ═S, ═N(R410c), —N3, and —CN;
• each R49d is independently selected from:
• halogen, —OR410d, SR410d, —N(R410d)2, C(O)R410d, —C(O)N(R410d)2, —N(R410d)C(O)R410d, —N(R410d)C(O)N(R410d)2, —OC(O)N(R410d)2, —N(R410d)C(O)OR410d, C(O)OR410d, —OC(O)R410d, —S(O)R410d, —S(O)2R410d, —NO2, ═O, ═S, ═N(R410d), —N3, 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, —OR410d, —SR410d, —N(R410d)2, —C(O)R410d, —C(O)N(R410d)2, —N(R410d)C(O)R410d, —N(R410d)C(O)N(R410d)2, —OC(O)N(R410d)2, —N(R410d)C(O)OR410d, —C(O)OR410d, —OC(O)R410d, —S(O)R410d, —S(O)2R410d, —NO2, ═O, ═S, ═N(R410d), —N3, and —CN;
• each R49e is independently selected from:
• halogen, —OR410e, —SR410e, —N(R410e)2, —C(O)R410e, —C(O)N(R410e)2, —N(R410e)C(O)R410e, —N(R410e)C(O)N(R410e)2, —OC(O)N(R410e)2, —N(R410e)C(O)OR410e, —C(O)OR410e, —OC(O)R410e, S(O)R410e, —S(O)2R410e, —NO2, ═O, ═S, ═N(R410e), —N3, 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, —OR410c, —SR410e, —N(R410e)2, —C(O)R410e, —C(O)N(R410e)2, —N(R410e)C(O)R410e, —N(R410e)C(O)N(R410e)2, —OC(O)N(R410e)2, —N(R410e)C(O)OR410e, —C(O)OR410e, —OC(O)R410e, —S(O)R410c, —S(O)2R410c, —NO2, ═O, ═S, ═N(R410e), —N3, and —CN;
• each R49f is independently selected from:
• halogen, —OR410f, —SR410f, —N(R410f)2, —C(O)R410f, —C(O)N(R410f)2, —N(R410f)C(O)R410f, —N(R410f)C(O)N(R410f)2, —OC(O)N(R410f)2, —N(R410f)C(O)OR410f, —C(O)OR410f, —OC(O)R410f, —S(O)R410f, —S(O)2R410f, —NO2, ═O, ═S, ═N(R410f), —N3, 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, —OR410f, —SR410f, —N(R410f)2, —C(O)R410f, —C(O)N(R410f)2, —N(R410f)C(O)R410f, —N(R410f)C(O)N(R410f)2, —OC(O)N(R410f)2, —N(R410f)C(O)OR410f, —C(O)OR410f, —OC(O)R410f, —S(O)R410f, —S(O)2R410f, —NO2, ═O, ═S, ═N(R410f), —N3, and —CN;
• each R49g is independently selected from:
• halogen, —OR410g, —SR410g, —N(R410g)2, —C(O)R410g, —C(O)N(R410g)2, —N(R410g)C(O)R410g, —N(R410g)C(O)N(R410g)2, —OC(O)N(R410g)2, —N(R410g)C(O)OR410g, —C(O)OR410g, —OC(O)R410g, —S(O)R410g, —S(O)2R410g, —NO2, ═O, ═S, ═N(R410g), —N3, 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, —OR410g, —SR410g, —N(R410g)2, —C(O)R410g, —C(O)N(R410g)2, —N(R410g)C(O)R410g, —N(R410g)C(O)N(R4100)2, —OC(O)N(R410g)2, —N(R410g)C(O)OR410b, —C(O)OR410g, —OC(O)R410b, —S(O)R410g, —S(O)2R410g, —NO2, ═O, ═S, ═N(R410g), —N3, and —CN;
• and
• each R410a, R410b, R410c, R410d, R410e, R410f, R410g, R410x, R410y and R410z 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, 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.

A method of treating a cardiac disease or a related condition in an individual in need thereof, the method comprising administering a therapeutically effective amount of a compound of Formula (III):

• or a salt thereof, wherein:
• X1, X2, X3, and X4 are independently selected from C(R) and N wherein no more than two of X1, X2, X3, and X4 are N;
• each R is independently selected from:
• hydrogen, halogen, —NO2, —CN, —N3, —OR28, —SR28, —N(R28)2, —C(O)R28, —C(O)N(R28)2, —N(R28)C(O)R28, —N(R28)C(O)N(R28)2, —OC(O)N(R28)2, —N(R28)C(O)OR28, —C(O)OR28, —OC(O)R28, —S(O)R28, and —S(O)2R28;
• 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, —OR28, —SR28, —N(R28)2, —C(O)R28, —C(O)N(R28)2, —N(R28)C(O)R28, —C(O)OR28, —OC(O)R28, —N(R28)C(O)N(R28)2, —OC(O)N(R28)2, —N(R28)C(O)OR28, —S(O)R28, —S(O)2R28, —NO2, ═O, ═S, ═N(R28), —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 R27;
• 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, —OR28, —SR28, —N(R28)2, —C(O)R28, —C(O)N(R28)2, —N(R28)C(O)R28, —N(R28)C(O)N(R28)2, —OC(O)N(R28)2, —N(R28)C(O)OR28, —C(O)OR28, —OC(O)R28, —S(O)R28, —S(O)2R28, —NO2, ═O—, ═S, ═N(R28), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27;
• R21 is 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, —OR28a, —SR28a, —N(R28a)2, —C(O)R28a, —C(O)N(R28a)2, —N(R28a)C(O)R28a, —C(O)OR28a, —OC(O)R28a, —N(R28a)C(O)N(R28a)2, —OC(O)N(R28a)2, —N(R28a)C(O)OR28a, —S(O)R28a, —S(O)2R28a, —NO2, ═O, ═S, ═N(R28a), —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 R27a;
• 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, —OR28a, —SR28a, —N(R28a)2, —C(O)R28a, —C(O)N(R28a)2, —N(R28a)C(O)R28a, —N(R28a)C(O)N(R28a)2, —OC(O)N(R28a)2, —N(R28a)C(O)OR28a, —C(O)OR28a, —OC(O)R28a, —S(O)R28a, —S(O)2R28a, —NO2, ═O—, ═S, ═N(R28a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27a;
• R22 is 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, —OR28b, —SR28b, —C(O)R28b, —C(O)N(R28b)2, —N(R28b)C(O)R28b, —C(O)OR28b, —OC(O)R28b, —N(R28b)C(O)N(R28b)2, —OC(O)N(R28b)2, —N(R28b)C(O)OR28b, —S(O)R28b, —S(O)2R28b, —NO2, ═O, ═S, ═N(R28b), —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 R27b;
• 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, —OR28b, —SR28b, —N(R28b)2, —C(O)R28b, —C(O)N(R28b)2, —N(R28b)C(O)R28b, —N(R28b)C(O)N(R28b)2, —OC(O)N(R28b)2, —N(R28b)C(O)OR28b, —C(O)OR28b, —OC(O)R28b, —S(O)R28b, —S(O)2R28b, —NO2, ═O—, ═S, ═N(R28b), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27b;
• or
• R21 together with R22 form a C3-10 carbocycle, or 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR28a, —SR28a, —N(R28a)2, —C(O)R28a, —C(O)N(R28a)2, —N(R28a)C(O)R28a, —N(R28a)C(O)N(R28a)2, —OC(O)N(R28a)2, —N(R28a)C(O)OR28a, —C(O)OR28a, —OC(O)R28a, —S(O)R28a, —S(O)2R28a, —NO2, ═O—, ═S, ═N(R28a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27b;
• R23 is selected from:
• hydrogen, halogen, —OR28c, —SR28c, —N(R28c)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more one or more substituents independently selected from R27c;
• or
• R21 together with R23 form a 3- to 10-membered heterocycle, which is optionally substituted with one or more substituents independently selected from halogen, —OR28a, —SR28a, —N(R28a)2, —C(O)R28a, —C(O)N(R28a)2, —N(R28a)C(O)R28a, —N(R28a)C(O)N(R28a)2, —OC(O)N(R28a)2, —N(R28a)C(O)OR28a, —C(O)OR28a, —OC(O)R28a, —S(O)R28a, —S(O)2R28a, —NO2, ═O—, ═S, ═N(R28a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27c;
• or
• R22 together with R23 form a C3-10 carbocycle, or 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR28a, —SR28a, —N(R28a)2, —C(O)R28a, —C(O)N(R28a)2, —N(R28a)C(O)R28a, —N(R28a)C(O)N(R28a)2, —OC(O)N(R28a)2, —N(R28a)C(O)OR28a, —C(O)OR28a, —OC(O)R28a, —S(O)R28a, —S(O)2R28a, —NO2, ═O—, ═S, ═N(R28a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27c;
• or R21, R2, and R23 together form a bicyclic heterocycle which is optionally substituted with one or more substituents independently selected from halogen, —OR28a, —SR28a, —N(R28a)2, —C(O)R28a, —C(O)N(R28a)2, —N(R28a)C(O)R28a, —N(R28a)C(O)N(R28a)2, —OC(O)N(R28a)2, —N(R28a)C(O)OR28a, —C(O)OR28a, —OC(O)R28a, —S(O)R28a, —S(O)2R28a, —NO2, ═O—, ═S, ═N(R28a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R27c;
• R24 is selected from:
• hydrogen, halogen, —OR28d, —SR28d, —N(R28d)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR28d, —SR28d, —N(R28d)2, —NO2, and —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 R27d;
• R24′ is selected from:
• hydrogen, halogen, —OR28d, —SR28d, —N(R28d)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR28d, —SR28d, —N(R28d)2, —NO2, and —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 R27d;
• or R24 and R24′ together 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 R27d;
• R25 is selected from:
• hydrogen, halogen, —OR28e, —SR28e, —N(R28e)2, —NO2, —CN, C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are each optionally substituted with one or more R27e;
• R26 is selected from:
• hydrogen, halogen, —OR28f, —SR28f, —N(R28f)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more substituents independently selected from R27f;
• each R27, R27a, R27b, R27c, R27d, R27e, and R27f is independently selected from:
• halogen, —OR28g, —SR28g, —N(R28g)2, —C(O)R28g, —C(O)N(R28g)2, —N(R28g)C(O)R28g, —N(R28g)C(O)N(R28g)2, —OC(O)N(R28g)2, —N(R28g)C(O)OR28g, —C(O)OR28g, —OC(O)R28g, —S(O)R28g, —S(O)2R28g, —NO2, ═O, ═S, ═N(R28g), 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, —OR28g, —SR28g, —N(R28g)2, —C(O)R28g, —C(O)N(R28g)2, —N(R28g)C(O)R28g, —N(R28g)C(O)N(R28g)2, —OC(O)N(R28g)2, —N(R28g)C(O)OR28g, —C(O)OR28g, —OC(O)R28g, —S(O)R28g, —S(O)2R28g, —NO2, ═O, ═S, ═N(R28g), and —CN;
• each R28, R28a, R28b, R28c, R28d, R28e, R28f, and R28g is independently selected from:
• hydrogen and halogen;
• and
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 carbocycle, 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, 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, —SO2—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.

A compound represented by Formula (I):

• or a salt thereof, wherein:
• X1, X2, and X3 are independently selected from C(R), and N wherein at least one of X1, X2, and X3 is N and no more than two of X1, X2, and X3 are N;
• X4 is selected from C(R);
• each R is independently selected from:
• hydrogen, halogen, —NO2, —CN, —N3, —OR8, —SR8, —N(R8)2, —C(O)R8, —C(O)N(R8)2, —N(R8)C(O)R8, —N(R8)C(O)N(R8)2, —OC(O)N(R8)2, —N(R8)C(O)OR8, —C(O)OR8, —OC(O)R8, —S(O)R8, and —S(O)2R8;
• 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, —OR8, —SR8, —N(R8)2, —C(O)R8, —C(O)N(R8)2, —N(R8)C(O)R8, —C(O)OR8, —OC(O)R8, —N(R8)C(O)N(R8)2, —OC(O)N(R8)2, —N(R8)C(O)OR8, —S(O)R8, —S(O)2R8, —NO2, ═O, ═S, ═N(R8), —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 R7;
• 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, —OR8, —SR8, —N(R8)2, —C(O)R8, —C(O)N(R8)2, —N(R8)C(O)R8, —N(R8)C(O)N(R8)2, —OC(O)N(R8)2, —N(R8)C(O)OR8, —C(O)OR8, —OC(O)R8, —S(O)R8, —S(O)2R8, —NO2, ═O—, ═S, ═N(R8), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R7;
• R1 is 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, —OR8a, —SR8a, —N(R8a)2, —C(O)R8a, —C(O)N(R8a)2, —N(R8a)C(O)R8a, —C(O)OR8a, —OC(O)R8a, —N(R8a)C(O)N(R8a)2, —OC(O)N(R8a)2, —N(R8a)C(O)OR8a, —S(O)R8a, —S(O)2R8a, —NO2, ═O, ═S, ═N(R8a), —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 R7a;
• 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, —OR8a, —SR8a, —N(R8a)2, —C(O)R8a, —C(O)N(R8a)2, —N(R8a)C(O)R8a, —N(R8a)C(O)N(R8a)2, —OC(O)N(R8a)2, —N(R8a)C(O)OR8a, —C(O)OR8a, —OC(O)R8a, —S(O)R8a, —S(O)2R8a, —NO2, ═O—, ═S, ═N(R8a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R7a;
• or
• R1 together with R2 form a C3-10 carbocycle, or 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR8a, —SR8a, —N(R8a)2, —C(O)R8a, —C(O)N(R8a)2, —N(R8a)C(O)R8a, —N(R8a)C(O)N(R8a)2, —OC(O)N(R8a)2, —N(R8a)C(O)OR8a, —C(O)OR8a, —OC(O)R8a, —S(O)R8a, —S(O)2R8a, —NO2, ═O—, ═S, ═N(R8a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R7b;
• R2 is 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, —OR8b, —SR8b, —N(R8b)2, —C(O)R8b, —C(O)N(R8b)2, —N(R8b)C(O)R8b, —C(O)OR8b, —OC(O)R8b, —N(R8b)C(O)N(R8b)2, —OC(O)N(R8b)2, —N(R8b)C(O)OR8b, —S(O)R8b, —S(O)2R8b, —NO2, ═O, ═S, ═N(R8b), —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 R7b;
• 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, —OR8b, —SR8b, —N(R8b)2, —C(O)R8b, —C(O)N(R8b)2, —N(R8b)C(O)R8b, —N(R8b)C(O)N(R8b)2, —OC(O)N(R8b)2, —N(R8b)C(O)OR8b, —C(O)OR8b, —OC(O)R8b, —S(O)R8b, —S(O)2R8b, —NO2, ═O—, ═S, ═N(R8b), —CN, —N3, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R7b;
• or
• R1 together with R2 form a C3-10 carbocycle, or 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR8a, —SR8a, —N(R8a)2, —C(O)R8a, —C(O)N(R8a)2, —N(R8a)C(O)R8a, —N(R8a)C(O)N(R8a)2, —OC(O)N(R8a)2, —N(R8a)C(O)OR8a, —C(O)OR8a, —OC(O)R8a, —S(O)R8a, —S(O)2R8a, —NO2, ═O—, ═S, ═N(R8a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from Rb;
• R3 is selected from:
• hydrogen, halogen, —OR8c, —SR8c, —N(R8c)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more one or more substituents independently selected from R7c;
• R4 is selected from:
• hydrogen, halogen, —OR8d, —SR8d, —N(R8d)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR8d, —SR8d, —N(R8d)2, —NO2, and —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 R7d;
• R4′ is selected from:
• hydrogen, halogen, —OR8d, —SR8d, —N(R8d)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR8d, —SR8d, —N(R8d)2, —NO2, and —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 R7d;
• or R4 and R4′ together 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 R7d;
• R5 is selected from:
• hydrogen, halogen, —OR8e, —SR8e, —N(R8e)2, —NO2, —CN, C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein the C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R7e;
• R6 is selected from:
• hydrogen, halogen, —OR8f, —SR8f, —N(R8f)2, —NO2, and —CN;
• and
• C1-6 alkyl optionally substituted with one or more substituents independently selected from R7f;
• each R7, R7a, R7b, R7c, R7d, R7e, and R7f is independently selected from:
• halogen, —OR8g, —SR8g, —N(R8g)2, —C(O)R8g, —C(O)N(R8g)2, —N(R8g)C(O)R8g, —N(R8g)C(O)N(R8g)2, —OC(O)N(R8g)2, —N(R8g)C(O)OR8g, —C(O)OR8g, —OC(O)R8g, —S(O)R8g, —S(O)2R8g, —NO2, ═O, ═S, ═N(R8g), 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, —OR8g, —SR8g, —N(R8g)2, —C(O)R8g, —C(O)N(R8g)2, —N(R8g)C(O)R8g, —N(R8g)C(O)N(R8g)2, —OC(O)N(R8g)2, —N(R8g)C(O)OR8g, —C(O)OR8g, —OC(O)R8g, —S(O)R8g, —S(O)2R8g, —NO2, ═O, ═S, ═N(R8g), and —CN;
• and
• each R8, R8a, R8b, R8c, R8d, R8e, R8f, and R8g is independently selected from:
• hydrogen and halogen;
• and
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 carbocycle, 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, 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, —SO2—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.