1, 4-dihydroquinazolinone compound and application thereof

Abstract

Dihydroquinazolinone and azadihydroquinazolinone compounds are provided for use in the treatment of cardiac indications, such as hypertrophic cardiomyopathy and diastolic dysfunction.

Description

[0001] Cross-reference

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 377,175, filed Sep. 26, 2022, which is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION

[0003] Hypertrophic cardiomyopathy (HCM) is a chronic progressive disease of the cardiac sarcomere. The etiology of HCM is multifactorial; a substantial portion of the affected population has at least one mutation in a gene encoding a cardiac sarcomeric protein. Regardless of the cause of HCM, in many cases, the formation of excessive myosin-actin cross-bridges during systole and diastole results in hyperdynamic contraction and impaired relaxation. Over time, this excessive stress leads to tissue remodeling, which histologically is characterized by myocyte hypertrophy, myofilament disarray, microvascular remodeling, and fibrosis. HCM can be genetic (e.g., inheritable) or non-genetic. HCM encompasses a group of highly penetrant, monogenic, autosomal dominant cardiomyopathies. This form of HCM can be caused by one or more of over 1000 known point mutations in any of the proteins that contribute to the functional unit of the myocardium, i.e., the sarcomere. It has been found that in the general population, approximately 1 in 500 individuals has left ventricular hypertrophy that cannot be explained by other known causes (e.g., hypertension or valvular disease), and it has been shown that, for example, many of these individuals are likely to have HCM once other heritable (e.g., lysosomal storage diseases), metabolic, or infiltrative causes have been excluded.

[0004] Medical therapies for HCM are limited, and many patients' symptoms are empirically addressed with β-blockers, non-dihydropyridine calcium channel blockers, and / or disopyramide. None of these agents are labeled for the indication of treating HCM, and there is essentially no rigorous clinical trial evidence to guide their use. In approximately 60% of patients with HCM, the left ventricular outflow tract becomes obstructed, impeding blood flow and creating a pressure gradient between the LV cavity and the aorta. For patients with severely hemodynamically significant outflow tract obstruction (gradient >50 mmHg), surgical myectomy or alcohol septal ablation can be employed to relieve the hemodynamic obstruction, despite the relatively high clinical morbidity and mortality. The present disclosure provides new therapeutic agents and methods to address the long-felt need for improving the treatment of HCM and related cardiac diseases. SUMMARY OF THE INVENTION

[0005] The present disclosure provides compounds and salts thereof for treating diseases. In certain aspects, the present disclosure provides compounds of Formulas (I), (II), and (III), pharmaceutical compositions thereof, and methods for treating diseases.

[0006] Compounds represented by Formula (I) are disclosed herein:

[0007]

[0008] or a salt thereof, wherein:

[0009] X 1 、X 2 、X 3 and X 4 are each independently selected from C(R 1 )、N and N + (-O - ), where at least one of X 1 、X 2 、X 3 or X 4 is N; and no more than two of X 1 、X 2 、X 3 and X 4 are N;

[0010] Each R 1 is independently selected from:

[0011] hydrogen;

[0012] halogen, -NO2, -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)2R 10a ;

[0013] 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 the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted by one or more R 9a ; and

[0014] C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 by one or more R 9a ;

[0015] R 2 is selected from:

[0016] C 1-6Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, where the C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9b ; and

[0017] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6Alkynyl, wherein C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted by one or more R 9b substituents;

[0018] R 3 and R 4 are each independently selected from:

[0019] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0020] optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN of C 1-6 alkyl; or

[0021] R 3 and R 4 together 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 by one or more R 9c substituents;

[0022] R 5 and R 6 are each independently selected from:

[0023] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN;

[0024] optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle of one or more substituents substituted C 1-6 alkyl, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0025] C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently with one or more substituents selected from the following: halogen, -OR 10c 、-SR 10c 、-N(R 10c )2、-NO2 and -CN; or

[0026] R 5 together with R 6 forms a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted with one or more R 9c substituents;

[0027] R 7 is selected from:

[0028] hydrogen, and C 10d alkyl optionally substituted independently with one or more substituents selected from halogen, -OR 10d 、-SR 10d )2、-NO2 and -CN; 1-6 alkyl;

[0029] R 8 is selected from:

[0030] hydrogen; and

[0031] C 10e alkyl optionally substituted independently with one or more substituents selected from halogen, -OR 10e 、-SR 10e )2、-NO2、-CN、C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein each C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic ring is optionally substituted independently with one or more substituents selected from the following: halogen, -OR 3-10 、-SR 10e 、-N(R 10e )2、-NO2 and -CN; 10e )2、-C(O)R

[0032] Each R 9a is independently selected from:

[0033] 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and

[0034] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN;

[0035] Each R 9b is independently selected from:

[0036] 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)OR10b 、 -OC(O)R 10b 、 -S(O)R 10b 、 -S(O)2R 10b 、 -NO2, =O, =S, =N(R 10b ) and -CN; and

[0037] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10b 、 -NO2, =O, =S, =N(R 10b ) and -CN;

[0038] Each R 9c is independently selected from:

[0039] 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)2R 10c 、 -NO2, =O, =S, =N(R 10c) and -CN; and

[0040] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0041] each R 10a , R 10b , R 10c , R 10d and R 10e is independently selected from: hydrogen;

[0042] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0043] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C1-6 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;

[0044] wherein if X 3 and X 1 are both N, then R 8 is selected from hydrogen, and optionally C 10 alkyl substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 ),2, -NO2, and -CN; and wherein if X 1-4 and X 4 are both N, then R 2 is selected from hydrogen, and optionally C 8 alkyl substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 ),2, -NO2, and -CN. The compound or salt according to claim 1, wherein X 1-4 , X 1 , X 2 , and X 3 and X 4 are each independently selected from C(R 1 ) and N.

[0045] There is disclosed herein a compound represented by formula (II):

[0046]

[0047] or a salt thereof, wherein:

[0048] n is 0, 1, 2, 3, or 4;

[0049] each R 1 is independently selected from:

[0050] halogen, -NO2, -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)2R 10a ; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently substituted by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, where C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted by one or more R 9a ; and

[0051] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally independently substituted by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, where C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted by one or more R 9a substituents;

[0052] R 2 is selected from:

[0053] halogen, -NO2, -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)2R 10b ; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10b 、 -NO2、 =O、 =S、 =N(R 10b )、 -CN、 C 3-10 carbocyclic rings and 3 - to 10 - membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3 - to 10 - membered heterocyclic rings are each optionally substituted by one or more R 9b ; and

[0054] C 3-10 carbocyclic rings and 3 - to 10 - membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10b 、 -NO2、 =O、 =S、 =N(R 10b )、 -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 by one or more R 9b ; or

[0055] R 2 and R 11 together form a 3 - to 10 - membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3 - to 10 - membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted by one or more R 9b’ ;

[0056] R 3 and R 4 are each independently selected from:

[0057] hydrogen, halogen, -OR 10c、-SR 10c 、-N(R 10c )2, -NO2 and -CN; and optionally independently selected from halogen, -OR 10c 、-SR 10c 、-N(R 10c )2, -NO2 and -CN substituted with one or more substituents C 1-6 Alkyl; or R 3 With R 4 Together they form a 3- to 10-membered heterocyclic ring or C 3-10 Carbocyclic ring, 3- to 10-membered heterocyclic ring or C 3-10 The carbocyclic ring is optionally substituted with one or more R 9c replace;

[0058] R 5 and R 6 Each independently selected from:

[0059] Hydrogen, halogen, -OR 10d 、-SR 10d 、-N(R 10d )2, -NO2 and -CN; and optionally independently selected from halogen, -OR 10d 、-SR 10d 、-N(R 10d )2, -NO2 and -CN substituted with one or more substituents C 1-6 Alkyl; or R 5 With R 6 Together they form a 3- to 10-membered heterocyclic ring or C 3-10 Carbocyclic ring, 3- to 10-membered heterocyclic ring or C 3-10 The carbocyclic ring is optionally substituted with one or more R 9d replace;

[0060] R 7 Selected from:

[0061] hydrogen, and optionally independently selected from halogen, -OR 10e 、-SR 10e 、-N(R 10e )2, -NO2 and -CN substituted with one or more substituents C 1-6 alkyl;

[0062] R 8 Selected from:

[0063] hydrogen, and optionally independently selected from halogen, -OR 10f 、-SR 10f 、-N(R 10f )2, -NO2 and -CN substituted with one or more substituents C 1-6 alkyl;

[0064] R 11 Selected from:

[0065] halogen, -NO2, -CN, -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 and -S(O)2R 10g ; and

[0066] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10g , -NO2, =S, =N(R 10g ), -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, where C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted by one or more R 9g ;

[0067] R 12 Selected from

[0068] Hydrogen;

[0069] Optionally independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h substituted by one or more substituents selected from the group consisting of: 1-6 alkyl; and

[0070] each optionally independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h substituted by one or more substituents selected from the group consisting of: 3-6 carbocyclic ring and 3- to 10-membered heterocyclic ring; or R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system;

[0071] Each R 9a is independently selected from:

[0072] 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN;

[0073] Each R 9b is independently selected from:

[0074] 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN;

[0075] Each R 9b’ is independently selected from:

[0076] 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10b 、 -NO2, =O, =S, =N(R 10b ) and -CN;

[0077] Each R 9c is independently selected from:

[0078] 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)2R 10c 、 -NO2, =O, =S, =N(R 10c ) and -CN; and

[0079] 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 the following: 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)2R 10c 、 -NO2, =O, =S, =N(R 10c ) and -CN;

[0080] Each R 9dIndependently selected from:

[0081] 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN; and

[0082] 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN;

[0083] Each R 9g is independently selected from:

[0084] halogen, -OR 10g , -SR 10g , -N(R 10g )2, -C(O)R10g ,-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)2R 10g ,-NO2, =O, =S, =N(R 10g ) and -CN; and

[0085] C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10g , -NO2, =O, =S, =N(R 10g ) and -CN;

[0086] Each R 10a , R 10b , R 10c , R 10d , R 10e , R 10f , R 10g , R 10h is independently selected from:

[0087] hydrogen;

[0088] C 1-6 alkyl, C 2-6Alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0089] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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.

[0090] Disclosed herein is a method of treating a cardiovascular disease or related condition, the method comprising administering to a subject in need a compound or salt of formula (III):

[0091]

[0092] or a salt thereof, wherein

[0093] X 1 、X 2 、X 3 and X 4 are each independently selected from C(R 1 )、N and N + (-O - );

[0094] Each R 1 is independently selected from:

[0095] Hydrogen;

[0096] Halogen, -NO2, -CN, -OR 10a 、-SR 10a 、-N(R 10a )2、-C(O)R 10a 、-C(O)N(R 10a )2、-N(R10a )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)2R 10a ;

[0097] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a 、 -NO2、 =O、 =S、 =N(R 10a )、 -CN、 C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, where the C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring are each optionally substituted by one or more R 9a ; and

[0098] C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 by one or more R 9a substituents;

[0099] R 2 is selected from:

[0100] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocycle and 3 - to 10 - membered heterocycle, wherein C 3-10 carbocycle and 3 - to 10 - membered heterocycle are each optionally substituted by one or more R 9b substituents; and

[0101] C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, where C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted by one or more R 9b ;

[0102] R 3 and R 4 are each independently selected from:

[0103] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0104] optionally substituted independently by one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN of C 1-6 alkyl; or

[0105] R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, where the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted by one or more R 9c ;

[0106] R 5and R 6 each independently selected from:

[0107] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN;

[0108] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, any one of which is optionally, each time it appears, independently substituted by one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted by one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0109] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted by one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or

[0110] R 5 together with R 6 forms a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted by one or more R 9c ;

[0111] R 7 is selected from:

[0112] hydrogen, and C 10d alkyl optionally substituted, each time it appears, independently by one or more substituents selected from halogen, -OR 10d , -SR 10d , -N(R 1-6 )2, -NO2 and -CN;

[0113] R 8 is selected from:

[0114] hydrogen; and

[0115] optionally substituted, each time it appears, independently by one or more substituents selected from halogen, -OR 10e, -SR 10e , -N(R 10e )2, -NO2, -CN, C 3-10 alkyl substituted by one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, where each C 1-6 alkyl, and where each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally independently substituted by one or more substituents selected from halogen, -OR 10e , -SR 10e , -N(R 10e )2, -NO2, and -CN;

[0116] Each R 9a is independently selected from:

[0117] 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and

[0118] C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, where each of which is optionally independently substituted by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), and -CN;

[0119] Each R 9b is independently selected from:

[0120] 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)2R 10b , -NO2, =O, =S, =N(R 10b ), and -CN; and

[0121] 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 the following: 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)2R 10b , -NO2, =O, =S, =N(R10b ) and -CN;

[0122] Each R 9c is independently selected from:

[0123] 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0124] 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 the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN;

[0125] Each R 10a , R 10b , R 10c , R10d , R 10e are independently selected from:

[0126] hydrogen; and

[0127] 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 the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0128] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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.

[0129] Incorporated by reference

[0130] All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. Detailed Description

[0131] In certain aspects, the present disclosure provides methods for treating heart diseases in an individual in need thereof, the methods comprising administering a therapeutically effective amount of a compound of formula (I), (II), or (III).

[0132] Diseases treated by the methods described herein include, but are not limited to, heart diseases. Heart diseases treated by the methods described herein include, but are not limited to, myocardial diseases (cardiomyopathies), hypertrophic cardiomyopathy (HCM), cardiac arrhythmias, aortic diseases, Marfan syndrome, coronary artery diseases, heart attacks, heart failure, rheumatic heart disease, peripheral vascular diseases, strokes, deep vein thrombosis, and pulmonary embolisms.

[0133] Cardiomyopathy is a heart disease in which the heart may become abnormally enlarged, thickened, and / or stiffened, and there may be few or no symptoms in the early stages. As the disease gets worse, symptoms can include, but are not limited to, shortness of breath, fatigue, irregular heartbeat, fainting, and episodes of heart failure. Types of cardiomyopathy include, but are not limited to, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and Takotsubo cardiomyopathy. Hypertrophic cardiomyopathy (HCM) can be genetic (e.g., inheritable) or non-genetic. HCM can be obstructive or non-obstructive. Inherited hypertrophic cardiomyopathy (HCM) includes a group of highly penetrant, single-gene, autosomal dominant cardiomyopathies. HCM can be caused by one or more of over 1000 known point mutations in any of the proteins that contribute to the functional units of the myocardium (i.e., sarcomeres).

[0134] In approximately two-thirds of HCM subjects, the path along which blood leaves the heart, called the left ventricular outflow tract (LVOT), becomes blocked by the enlarged and diseased myocardium, restricting blood flow from the heart to the rest of the body (obstructive HCM). In other subjects, the thickened myocardium does not block the LVOT, and their disease is driven by diastolic injury resulting from the enlarged and stiffened myocardium (non-obstructive HCM). In obstructive or non-obstructive HCM subjects, exertion can lead to fatigue or shortness of breath, impairing the subject's ability to participate in daily life activities. HCM has also been associated with an increased risk of atrial fibrillation, stroke, heart failure, and sudden cardiac death.

[0135] Currently available therapies for HCM vary in effectiveness in relieving symptoms, but generally show decreasing efficacy as the duration of the disease increases. Thus, patients empirically use β-blockers, non-dihydropyridine calcium channel blockers, and / or disopyramide to cope. In approximately 60% of HCM patients, the left ventricular outflow tract becomes blocked, impeding blood flow and creating a pressure gradient between the LV cavity and the aorta. For patients with severely hemodynamically obstructive outflow tracts (gradient >50 mmHg), surgical myectomy or alcohol septal ablation can be used to relieve the hemodynamic obstruction, despite the relatively high clinical morbidity and mortality. The present disclosure provides new therapeutic agents and methods to address the long-standing need to improve the treatment of HCM and related heart diseases.

[0136] The compounds of the present invention or pharmaceutically acceptable salts thereof can alter the natural history of HCM and other diseases, rather than merely alleviating symptoms. The mechanisms that confer clinical benefit to patients with HCM can extend to other forms of patients with shared similar pathophysiology of heart disease, with or without an apparent genetic influence. For example, by improving ventricular relaxation during diastole, effective treatment of HCM can also be effective in a broader population characterized by diastolic dysfunction. The compounds of the present invention or pharmaceutically acceptable salts thereof can specifically target the root cause of the disorder or act on other downstream pathways. Thus, the compounds of the present invention or pharmaceutically acceptable salts thereof can also benefit patients with heart failure with preserved ejection fraction, ischemic heart disease, angina, or restrictive cardiomyopathy. The compounds of the present invention or pharmaceutically acceptable salts thereof can also be combined with therapies (valve repair / replacement, effective antihypertensive therapy) aimed at correcting or alleviating the primary causes of volume or pressure overload, promoting beneficial ventricular remodeling in left ventricular hypertrophy caused by volume or pressure overload (e.g., chronic mitral regurgitation, chronic aortic stenosis, or chronic systemic hypertension). By reducing left ventricular filling pressure, the compound can reduce the risk of pulmonary edema and respiratory failure. Reducing or eliminating functional mitral regurgitation and / or lowering left atrial pressure can reduce the risk of paroxysmal or permanent atrial fibrillation and, concomitantly, the attendant risk of arterial thromboembolic complications, including but not limited to cerebral artery embolic stroke. Reducing or eliminating dynamic and / or static left ventricular outflow tract obstruction can reduce the likelihood of requiring (surgical or percutaneous) septal reduction therapy and the attendant risk of its short-term and long-term complications. The compound or pharmaceutically acceptable salt thereof can alleviate the severity of the chronic ischemic state associated with HCM and can thereby reduce the risk of sudden cardiac death (SCD) or its equivalent (frequent and / or repeated ICD shocks) and / or the need for potentially toxic antiarrhythmic drugs in patients with an implantable cardioverter defibrillator. The compound or pharmaceutically acceptable salt thereof can be valuable in reducing or eliminating the need for concomitant medications and their attendant potential toxicity, drug-drug interactions, and / or side effects. The compound or pharmaceutically acceptable salt thereof can alleviate interstitial myocardial fibrosis and / or slow the progression of left ventricular hypertrophy, arrest or reverse left ventricular hypertrophy.

[0137] Definitions

[0138] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0139] As used in this specification and claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0140] The term "C x-y " or "C x -C y " (e.g., when used with a chemical moiety such as an alkyl, alkenyl, or alkynyl group) means a group that includes a number of carbon atoms greater than or equal to x and less than or equal to y carbon atoms in the chemical moiety, depending on the following. The term "C x-y " or "C x -C y " is not intended to limit the number of carbon atoms that can be attached to the chemical moiety when the chemical moiety is substituted by a second chemical moiety. For example, the term "C 1-6 alkyl" or "C1 to C6 alkyl" refers to a saturated, substituted, or unsubstituted hydrocarbon group containing 1, 2, 3, 4, 5, or 6 carbon atoms, including straight-chain alkyl groups (e.g., linear alkyl groups) and branched alkyl groups, plus whatever number of carbon atoms may be present in any substituents of the C 1-6 alkyl. For example, if the C 1-6 alkyl is optionally substituted by a second chemical moiety containing two carbon atoms, it will be understood that the C 1-6 alkyl can contain 1 to 8 carbon atoms.

[0141] The terms "C x-y alkenyl" and "C x-y alkynyl" refer to substituted or unsubstituted unsaturated aliphatic groups that are similar to the above alkyl groups in length and possible substitution but contain at least one double bond or triple bond, respectively.

[0142] "Amino" refers to the -NH2 moiety.

[0143] "Cyano" refers to the -CN moiety.

[0144] "Nitro" refers to the -NO2 moiety.

[0145] "Oxa" refers to the -O- moiety.

[0146] "Oxo" refers to the =O moiety.

[0147] "Thio" refers to the =S moiety.

[0148] "Imino" refers to the =N-H moiety.

[0149] "Oximino" refers to the =N-OH moiety.

[0150] "Hydrazino" refers to the =N-NH2 moiety.

[0151] "Alkyl" refers to a completely saturated straight-chain (e.g., linear) or branched hydrocarbon moiety consisting only of carbon and hydrogen atoms. In certain embodiments, "alkyl" contains 1 to 15 carbon atoms (e.g., C1-C15 alkyl). In certain embodiments, the alkyl contains 1 to 13 carbon atoms (e.g., C1-C 13 alkyl). In certain embodiments, the alkyl contains 1 to 8 carbon atoms (e.g., C1-C8 alkyl). In certain embodiments, the alkyl contains 1 to 6 carbon atoms (e.g., C1-C6 alkyl). In other embodiments, the alkyl contains 1 to 5 carbon atoms (e.g., C1-C5 alkyl). In other embodiments, the alkyl contains 1 to 4 carbon atoms (e.g., C1-C4 alkyl). In other embodiments, the alkyl contains 1 to 3 carbon atoms (e.g., C1-C3 alkyl). In other embodiments, the alkyl contains 1 to 2 carbon atoms (e.g., C1-C2 alkyl). In other embodiments, the alkyl contains 1 carbon atom (e.g., C1 alkyl, e.g., methyl). In other embodiments, the alkyl contains 5 to 15 carbon atoms (e.g., C5-C 15 alkyl). In other embodiments, the alkyl contains 5 to 8 carbon atoms (e.g., C5-C8 alkyl). In other embodiments, the alkyl contains 2 to 5 carbon atoms (e.g., C2-C5 alkyl). In other embodiments, the alkyl contains 3 to 5 carbon atoms (e.g., C3-C5 alkyl). In other embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (2-propyl, isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl is attached to the remainder of the molecule by a single bond.

[0152] "Aminoalkyl" refers to a moiety in which a nitrogen atom is bonded in the form of –N(H)(alkyl) or N(alkyl)(alkyl), where when the moiety is N(alkyl)(alkyl), the two alkyl groups bonded to the nitrogen can be the same alkyl group or different alkyl groups.

[0153] "Alkoxy" refers to a moiety bonded through an oxygen atom of the formula –O-alkyl, where the alkyl is an alkyl chain as defined above.

[0154] "Alkenyl" refers to a straight-chain (e.g., linear) or branched hydrocarbon moiety consisting only of carbon and hydrogen atoms that contains at least one carbon-carbon double bond. In certain embodiments, the alkenyl contains 2 to 12 carbon atoms. In certain embodiments, the alkenyl contains 2 to 8 carbon atoms. In other embodiments, the alkenyl contains 2 to 4 carbon atoms. The alkenyl is attached to the remainder of the molecule by a single bond, e.g., vinyl (i.e., ethenyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, pent-1,4-dienyl, etc.

[0155] "Alkynyl" refers to a straight-chain (e.g., linear) or branched hydrocarbon moiety consisting solely of carbon and hydrogen atoms, which contains at least one carbon-carbon triple bond. In some embodiments, the alkynyl contains 2 to 12 carbon atoms. In some embodiments, the alkynyl optionally further contains at least one carbon-carbon double bond. In certain embodiments, the alkynyl contains 2 to 8 carbon atoms. In other embodiments, the alkynyl contains 2 to 6 carbon atoms. In other embodiments, the alkynyl contains 2 to 4 carbon atoms. The alkynyl is attached to the remainder of the molecule by a single bond, e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc.

[0156] "Alkylene" or "alkylene chain" refers to a linear (e.g., straight-chain) or branched divalent hydrocarbon moiety. The "alkylene" or "alkylene chain" can connect a part of a molecule to a second part. The "alkylene" or "alkylene chain" consists solely of carbon and hydrogen atoms (it can be specified that the alkylene is substituted by one or more substituents containing atoms other than hydrogen such as N, O, and S). The "alkylene" or "alkylene chain" may not contain unsaturation (although the attachment point of the alkylene to the remainder of the molecule). In certain embodiments, the "alkylene" or "alkylene chain" contains 1 to 12 carbon atoms, e.g., methylene, ethylene, propylene, n-butylene, etc. The alkylene chain can be attached to a part of the molecule by a single bond and attached to the second part by a single bond. The attachment point of the alkylene chain to the remainder of the molecule and the attachment point to the second part can be through one carbon atom in the alkylene chain, or can be through any two carbon atoms within the alkylene. In certain embodiments, the alkylene contains 1 to 8 carbon atoms (e.g., C1-C8 alkylene). In other embodiments, the alkylene contains 1 to 5 carbon atoms (e.g., C1-C5 alkylene). In other embodiments, the alkylene contains 1 to 4 carbon atoms (e.g., C1-C4 alkylene). In other embodiments, the alkylene contains 1 to 3 carbon atoms (e.g., C1-C3 alkylene). In other embodiments, the alkylene contains 1 to 2 carbon atoms (e.g., C1-C2 alkylene). In other embodiments, the alkylene contains 1 carbon atom (e.g., C1 alkylene). In other embodiments, the alkylene contains 5 to 8 carbon atoms (e.g., C5-C8 alkylene). In other embodiments, the alkylene contains 2 to 5 carbon atoms (e.g., C2-C5 alkylene). In other embodiments, the alkylene contains 3 to 5 carbon atoms (e.g., C3-C5 alkylene).

[0157] "Alkenylene" or "alkenylene chain" means a linear (e.g., straight-chain) or branched divalent hydrocarbon moiety. An "alkenylene" or "alkenylene chain" can connect a part of a molecule to a second part. An "alkenylene" or "alkenylene chain" consists only of carbon and hydrogen atoms (it may be specified that the alkenylene is substituted with one or more substituents containing atoms other than hydrogen such as N, O, and S). An "alkenylene" or "alkenylene chain" contains at least one carbon-carbon double bond. In certain embodiments, an "alkenylene" or "alkenylene chain" contains 2 to 12 carbon atoms. The alkenylene chain can be attached to a part of the molecule by a single bond and attached to the second part by a single bond. The attachment points of the alkenylene chain to the rest of the molecule and to the second part can be through one carbon atom in the alkenylene chain, or through any two carbon atoms within the alkenylene chain. In certain embodiments, the alkenylene contains 2 to 8 carbon atoms (e.g., C2-C8 alkenylene). In other embodiments, the alkenylene contains 2 to 5 carbon atoms (e.g., C2-C5 alkenylene). In other embodiments, the alkenylene contains 2 to 4 carbon atoms (e.g., C2-C4 alkenylene). In other embodiments, the alkenylene contains 2 to 3 carbon atoms (e.g., C2-C3 alkenylene). In other embodiments, the alkenylene contains 5 to 8 carbon atoms (e.g., C5-C8 alkenylene). In other embodiments, the alkenylene contains 2 to 5 carbon atoms (e.g., C2-C5 alkenylene). In other embodiments, the alkenylene contains 3 to 5 carbon atoms (e.g., C3-C5 alkenylene).

[0158] "Alkynylene" or "alkynylene chain" refers to a linear (e.g., straight-chain) or branched divalent hydrocarbon moiety. An "alkynylene" or "alkynylene chain" can connect a part of a molecule to a second part. An "alkynylene" or "alkynylene chain" consists only of carbon and hydrogen (it may be specified that the alkynylene is substituted with one or more substituents containing atoms other than hydrogen such as N, O, and S). An "alkynylene" or "alkynylene chain" contains at least one carbon-carbon triple bond. In certain embodiments, an "alkynylene" or "alkynylene chain" contains 2 to 12 carbon atoms. The alkynylene chain can be attached to a part of the molecule by a single bond and attached to the second part by a single bond. The attachment points of the alkynylene chain to the rest of the molecule and to the second part can be through one carbon atom in the alkynylene chain, or through any two carbon atoms within the alkynylene chain. In certain embodiments, the alkynylene contains 2 to 8 carbon atoms (e.g., C2-C8 alkynylene). In other embodiments, the alkynylene contains 2 to 5 carbon atoms (e.g., C2-C5 alkynylene). In other embodiments, the alkynylene contains 2 to 4 carbon atoms (e.g., C2-C4 alkynylene). In other embodiments, the alkynylene contains 2 to 3 carbon atoms (e.g., C2-C3 alkynylene). In other embodiments, the alkynylene contains two carbon atoms (e.g., C2 alkylene). In other embodiments, the alkynylene contains 5 to 8 carbon atoms (e.g., C5-C8 alkynylene). In other embodiments, the alkynylene contains 3 to 5 carbon atoms (e.g., C3-C5 alkynylene).

[0159] As used herein, the term "carbocyclic ring" refers to a saturated or unsaturated (e.g., aromatic or non-aromatic unsaturated) ring or ring system in which each atom of the ring is carbon. For example, the term "carbocyclic ring" includes monocyclic rings having 3 to 12 members (e.g., monocyclic rings having 3 to 10 members) and polycyclic ring systems having 4 to 20 members (e.g., 5- to 15-membered spiro polycyclic ring systems, 5- to 15-membered bridged polycyclic ring systems, or 4- to 15-membered fused polycyclic ring systems). For example, carbocyclic rings include bicyclic rings having 4 to 15 members (e.g., 5- to 15-membered spirobicyclic rings, 5- to 15-membered bridged bicyclic ring systems, or 4- to 15-membered fused bicyclic ring systems). For example, carbocyclic rings include tricyclic ring systems, which can be bridged, fused, spiro, or combinations thereof. For example, carbocyclic rings include tetracyclic ring systems, which can be bridged, fused, spiro, or combinations thereof. For example, carbocyclic rings include: ring systems that are both fused and bridged; ring systems that are both fused and spiro; ring systems that are both bridged and spiro; and ring systems that are both fused and bridged and also spiro. Each ring of a polycyclic carbocyclic ring can be selected from saturated and unsaturated (e.g., aromatic or non-aromatic unsaturated) rings. In an exemplary embodiment, an aromatic ring (e.g., phenyl) of a polycyclic carbocyclic ring can be fused to a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, cyclohexene, or phenyl). Polycyclic carbocyclic rings include any combination permitted by the valences of the saturated and unsaturated (e.g., aromatic or non-aromatic unsaturated) rings. For example, a polycyclic carbocyclic ring can be a spirobicyclic ring, such as spiro[2.2]pentane. For example, polycyclic carbocyclic rings include any combination of ring sizes, such as 2-2 spiro ring systems (e.g., spiro[2.2]pentane), 3-3 spiro ring systems, 4-4 spiro ring systems, 4-5 fused ring systems (e.g., bicyclo[4.5.0] fused ring systems), 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems (e.g., naphthalene), 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, naphthyl, trans-bicyclo[4.4.0]decane, cis-bicyclo[4.4.0]decane, spiro[3.4]octane, fluoranthene, and bicyclo[1.1.1]pentyl.

[0160] The term "aryl" refers to an aromatic monocyclic or polycyclic hydrocarbon ring system containing at least one cyclic delocalized (4n + 2)π - electron system that complies with Hückel's theory, where n is an integer greater than or equal to 0. In some embodiments, the aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen atoms and carbon atoms. In some embodiments, the aromatic monocyclic or polycyclic system contains 3 to 20 carbon atoms. In some embodiments, at least one of the rings in the polycyclic aromatic ring system is aromatic. In some embodiments, the aromatic monocyclic or polycyclic hydrocarbon ring system contains a cyclic delocalized (4n + 2)π - electron system that complies with Hückel's theory. In some embodiments, the ring system from which the aryl group is derived includes, but is not limited to, groups such as benzene, fluorene, indane, indene, anthracene, tetrahydronaphthalene, and naphthalene. In some embodiments, the aryl substituent is uncharged (e.g., neutral). In some embodiments, the aryl substituent has no net charge. In some embodiments, the aryl substituent has no net charge and is not zwitterionic. In some embodiments, none of the carbon atoms of the aryl substituent is charged. In some embodiments, none of the carbon atoms of the aryl substituent is charged. Alternatively, in some embodiments, the aryl substituent is positively charged or negatively charged or zwitterionic.

[0161] The term "cycloalkyl" refers to a saturated ring in which each atom of the ring is carbon. Cycloalkyl can include monocyclic and polycyclic rings, such as 3 - to 10 - membered monocyclic, 5 - to 12 - membered bicyclic, 5 - to 12 - membered spirobicyclic, and 5 - to 12 - membered bridged rings. In certain embodiments, cycloalkyl contains 3 to 10 carbon atoms. In other embodiments, cycloalkyl contains 3 to 7 carbon atoms. In other embodiments, cycloalkyl contains 5 to 7 carbon atoms. Cycloalkyl can be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyl include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl include, but are not limited to, adamantyl, spiropentane, norbornyl (i.e., bicyclo[2.2.1]heptanyl), decahydronaphthyl, 7,7 - dimethylbicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, spiropentane, etc.

[0162] The term "cycloalkenyl" refers to a saturated ring in which each atom of the ring is carbon and there is at least one double bond between two ring carbons. Cycloalkenyl can include monocyclic and polycyclic rings, such as 3 - to 10 - membered monocyclic and 4 - to 12 - membered bicyclic (e.g., 5 - to 12 - membered bridged bicyclic, fused 4 - to 12 - membered bicyclic, and spiro 5 - to 12 - membered bicyclic). In other embodiments, cycloalkenyl contains 5 to 7 carbon atoms. Cycloalkenyl can be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyl include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0163] The term "halo", "halogen" or "halide" means fluoro, chloro, bromo or iodo. In some embodiments, halo is fluoro, chloro or bromo. In some embodiments, halo is fluoro or chloro.

[0164] The term "haloalkyl" means an alkyl group as defined above substituted with one or more halogens, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-chloromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl portion of the haloalkyl is optionally further substituted as described herein.

[0165] As used herein, the term "heterocycle" refers to a saturated or unsaturated (e.g., aromatic or non-aromatic unsaturated) ring or ring system in which one or more heteroatoms are members of the ring or ring system. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. For example, heterocycles include 3- to 12-membered monocyclic rings (e.g., 3- to 10-membered monocyclic rings) and 4- to 20-membered polycyclic ring systems (e.g., 4- to 15-membered fused polycyclic systems, 5- to 15-membered spiro polycyclic systems, and 5- to 15-membered bridged polycyclic systems). For example, heterocycles include 4- to 20-membered bicyclic ring systems (e.g., 4- to 15-membered fused bicyclic systems, 5- to 15-membered spiro bicyclic systems, and 5- to 15-membered bridged bicyclic systems). For example, heterocycles include tricyclic ring systems, which can be bridged, fused, spiro, or combinations thereof. For example, heterocycles include tetracyclic ring systems, which can be bridged, fused, spiro, or combinations thereof. For example, heterocycles include: ring systems that are both fused and bridged; ring systems that are both fused and spiro; ring systems that are both bridged and spiro; and ring systems that are both fused and bridged and also spiro. Each ring of a polycyclic heterocycle can be selected from saturated and unsaturated (e.g., aromatic or non-aromatic unsaturated) rings. Polycyclic heterocycles include any combination permitted by the valences of saturated and unsaturated (e.g., aromatic or non-aromatic unsaturated) rings. In an exemplary embodiment, in a heterocycle, an aromatic ring, e.g., pyridyl or phenyl, can be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, morpholine, piperidine, or cyclohexene, provided that at least one atom in the resulting fused ring system is a heteroatom. Polycyclic heterocycles include any combination of ring sizes, such as 3-3 spiro ring systems, 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Bicyclic heterocycles further include spirobicycles, e.g., 5- to 12-membered spirobicycles, such as 2-oxa-6-aza-spiro[3.3]heptane. In some embodiments, the heterocycle contains multiple heteroatoms. In some embodiments, the heterocycle contains atoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocycle contains multiple atoms selected from nitrogen, oxygen, and sulfur. Non-limiting examples of heterocycles include pyridine, pyrrole, indole, carbazole, piperidine, oxazole, morpholine, thiophene, benzothiophene, furan, tetrahydrofuran, and pyran. Non-limiting examples of heterocycles include az yl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benz[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]diox group, benzoxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxanyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothienyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopentadieno[d]pyrimidinyl, 6,7-dihydro-5H-cyclopentadieno[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cycloheptatrieno[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothienyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocyclooctatetraeno[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocyclooctatetraeno[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocyclooctatetraeno[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolinyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinone, oxadiazolyl, 2-oxaazepinyl group, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cycloheptatrieno[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridinyl and thienyl (i.e., thienyl). In some embodiments, the heterocycle is attached to the molecule through a carbon atom. In some embodiments, the heterocycle is attached to the molecule through a nitrogen atom. In some embodiments, the heterocycle comprises a moiety selected from heteroaryl, heterocycloalkyl and heterocycloalkenyl. In some embodiments, the heterocycle is heteroaryl. In some embodiments, the heterocycle is heterocycloalkyl. In some embodiments, the heterocycle is heterocycloalkenyl.

[0166] In some embodiments, the heterocycle contains atoms selected from nitrogen and oxygen. In some embodiments, the heterocycle contains atoms selected from nitrogen and sulfur. In some embodiments, the heterocycle contains atoms selected from oxygen and sulfur. In some embodiments, the heterocycle contains atoms selected from nitrogen. In some embodiments, the heterocycle contains atoms selected from oxygen. In some embodiments, the heterocycle contains atoms selected from sulfur.

[0167] In some embodiments, the heterocycle contains 1 to 8 heteroatoms. In some embodiments, the heterocycle contains 1 to 5 heteroatoms. In some embodiments, the heterocycle contains 1 to 3 heteroatoms. In some embodiments, the heterocycle contains 1 to 2 heteroatoms. In some embodiments, the heterocycle is mono-substituted, di-substituted, tri-substituted, tetra-substituted or penta-substituted.

[0168] In a molecule (e.g., in a heterocycle), one or more nitrogen atoms, if present, may optionally be quaternized. In some embodiments, the heterocyclic substituent is positively charged. In some embodiments, the heterocyclic substituent is negatively charged. In some embodiments, the heterocyclic substituent is neutral. In some embodiments, the heterocyclic substituent is zwitterionic. Alternatively or additionally, in some embodiments, the heterocyclic substituent is not charged. In some embodiments, the heterocyclic substituent has no charge. In some embodiments, the heterocyclic substituent has no net charge. In some embodiments, the atoms within the heterocyclic substituent have no net charge. In some embodiments, the heterocyclic substituent has no net charge and is not zwitterionic.

[0169] The term "heteroaryl" refers to a moiety derived from an aromatic monocyclic or aromatic polycyclic ring system, wherein one or more heteroatoms are members of the ring system and the ring system contains at least one cyclic delocalized (4n+2)π-electron system that complies with Hückel's theory, where n is an integer greater than or equal to 0. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. In some embodiments, the heteroaryl contains one or more heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl contains multiple heteroatoms selected from nitrogen, oxygen, and sulfur. In certain embodiments, "heteroaryl" includes rings and ring systems containing 3 to 20 atoms. In some embodiments, "heteroaryl" includes rings and ring systems containing 2 to 17 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, a heteroaryl moiety is a monocyclic or polycyclic (e.g., bicyclic, tricyclic, or tetracyclic) ring system, wherein at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic delocalized (4n+2)π-electron system that complies with Hückel's theory. Heteroaryl includes fused, bridged, and spiro ring systems. The heteroatoms in the heteroaryl moiety are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the remainder of the molecule through any atom of the ring. Examples of heteroaryl include, but are not limited to, azetidinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxanyl yl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxanyl group, benzob[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxanyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothienyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benz[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopentadieno[d]pyrimidinyl, 6,7-dihydro-5H-cyclopentadieno[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cycloheptatrieno[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothienyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocyclooctatetraeno[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocyclooctatetraeno[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocyclooctatetraeno[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolinyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinone, oxadiazolyl, 2-oxaazepinyl Base, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridyl and thienyl (i.e., thiophenyl). In some embodiments, the heteroaryl substituent is positively charged or negatively charged. In some embodiments, the heteroaryl substituent is neutral. In some embodiments, the heteroaryl substituent is zwitterionic; alternatively or additionally, in some embodiments, the heteroaryl substituent is not charged. In some embodiments, the heteroaryl substituent has no charge. In some embodiments, the heteroaryl substituent has no net charge. In some embodiments, the heteroaryl substituent has no net charge and is not zwitterionic.

[0170] The term "heterocyclic" includes "heteroaryl" and "heterocycloalkyl". The term "carbocyclic" includes "aryl" and "cycloalkyl".

[0171] The term "heterocycloalkyl" refers to a saturated ring containing carbon atoms and at least one heteroatom. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycloalkyl can include monocyclic and polycyclic rings, such as 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, 5- to 12-membered spirobicyclic rings, or 5- to 12-membered bridged rings. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. Heterocycloalkyl is attached to the remainder of the molecule through any atom permitted by the valence of the heterocycloalkyl, such as any carbon or nitrogen atom of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thieno[1,3]dithianyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidinonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thioxomorpholinyl, 1-oxo-thiomorpholinyl, 2-oxa-6-azaspiro[3.3]heptane, and 1,1-dioxo-thiomorpholinyl. In some embodiments, heterocycloalkyl contains one heteroatom. In some embodiments, heterocycloalkyl contains one heteroatom selected from N, O, and S. In some embodiments, heterocycloalkyl contains multiple heteroatoms. In some embodiments, heterocycloalkyl contains multiple heteroatoms selected from N, O, and S.

[0172] The term "heterocycloalkenyl" refers to an unsaturated ring containing carbon atoms and at least one heteroatom and having at least one double bond between two ring carbons. Heterocycloalkenyl does not include heteroaryl rings. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycloalkenyl can include monocyclic and polycyclic rings, such as 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 5- to 12-membered bridged rings. In other embodiments, heterocycloalkenyl contains 5 to 7 ring atoms. Heterocycloalkenyl can be attached to the remainder of the molecule through a single bond. Examples of monocyclic cycloalkenyls include, for example, pyrroline (dihydropyrrole), pyrazoline (dihydropyrazole), imidazoline (dihydroimidazole), triazoline (dihydrotriazole), dihydrofuran, dihydrothiophene, oxazoline (dihydrooxazole), isoxazoline (dihydroisoxazole), thiazoline (dihydrothiazole), isothiazoline (dihydroisothiazole), oxadiazoline (dihydrooxadiazole), thiadiazoline (dihydrothiadiazole), dihydropyridine, tetrahydropyridine, dihydropyridazine, tetrahydropyridazine, dihydropyrimidine, tetrahydropyrimidine, dihydropyrazine, tetrahydropyrazine, pyran, dihydropyran, thiopyran, dihydrothiopyran, dioxane, dihydrodioxane, oxazine, dihydrooxazine, thiazine, and dihydrothiazine.

[0173] The term "substituted" refers to a moiety in which a substituent replaces one or more hydrogens on a carbon or a substitutable heteroatom, such as NH or NH2, of a compound. It is to be understood that "substitution" or "substituted" includes the implicit conditions that such substitution is in accordance with the allowed valences of the substituted atom and the substituent, and includes the condition that the substitution results in a stable compound, e.g., a compound that does not undergo rapid rearrangement, cyclization, elimination, etc. In certain embodiments, "substituted" refers to a moiety in which a substituent replaces two hydrogens on the same carbon atom, such as replacing two hydrogens on a single carbon with an oxo, imino, oxime, hydrazone, or thio group. As used herein, the term "substituted" is considered to include all permissible substituents of an organic compound. In broad aspects, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. For suitable organic compounds, the permissible substituents can be one or more and can be the same or different.

[0174] In some embodiments, the substituents can include any of the substituents described herein, e.g.: halogen, hydroxy, oxo(=O), thio(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oxime(=N-OH), hydrazino(=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2、-R b -O-R c -C(O)N(R a )2、-R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b-S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl, any of which may optionally be substituted by the following groups: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oximino(=N-OH), hydrazino(=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2、-R b -O-R c -C(O)N(R a )2、-R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) tN(R a )2 (where t is 1 or 2); wherein each R a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl, and wherein each R a may optionally be substituted with: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oxime(=N-OH), hydrazine(=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2、-R b -O-R c -C(O)N(R a )2、-R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2)、-R b -S(O) t R a (where t is 1 or 2)、-R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2); and wherein each R b is independently selected from a bond or a straight-chain or branched alkylene, alkenylene or alkynylene chain, and each R cAll are straight-chain or branched-chain alkylene, alkenylene or alkynylene chains.

[0175] Double bonds with oxygen atoms, such as oxo groups, are represented herein as "=O" and "(O)". Double bonds with nitrogen atoms are represented as "=NR" and "(NR)". Double bonds with sulfur atoms are represented as "=S" and "(S)".

[0176] As used herein, the phrases "parenteral administration" and "administered parenterally" refer to modes of administration other than enteral and topical administration, usually by injection, including but not limited to intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, intratracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0177] As used herein, the phrase "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms that are suitable for contact with the tissues of humans and animals within the scope of reasonable medical judgment without undue toxicity, irritation, allergic response or other problems or complications and having a reasonable benefit / risk ratio.

[0178] As used herein, the phrase "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients in the formulation and not injurious to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances for pharmaceutical formulations.

[0179] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and / or organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic bases and / or organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0180] As used herein, "therapy" or "treatment" refers to a method of obtaining a beneficial or desired result related to a disease, disorder, or medical condition, including but not limited to therapeutic benefits and / or prophylactic benefits. For example, a therapeutic benefit can include, for example, eradicating or ameliorating the underlying disease being treated. Additionally, a therapeutic benefit can also include, for example, eradicating or ameliorating one or more physiological symptoms associated with the underlying disease, such that an improvement is observed in the subject, even though the subject may still be afflicted with the underlying disease. In certain embodiments, for prophylactic benefits, the composition is administered to a subject at risk of developing a particular disease, or to a subject who has reported one or more physiological symptoms of a disease, even though a diagnosis of the disease has not yet been made. Therapy by administration of the compounds described herein does not require the involvement of a medical professional.

[0181] A chemical entity having a carbon-carbon double bond or a carbon-nitrogen double bond can exist in the Z- or E- (or cis- or trans-) form. Additionally, some chemical entities can exist in various tautomeric forms. Unless otherwise specified, all structures described herein are intended to disclose all Z-, E-, and tautomeric forms, either implicitly or explicitly.

[0182] A "tautomer" refers to a molecule in which a proton can be transferred from one atom of the molecule to another atom of the same molecule. The compounds described herein exist in tautomeric forms in certain embodiments. Where tautomerism can occur, there will be a chemical equilibrium between the tautomers. The exact ratio of tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibria include, but are not limited to:

[0183]

[0184] In some embodiments, the compounds disclosed herein are used in different enriched isotope forms, e.g., enriched 2 H, 3 H, 11 C, 13 C and / or 14 C content. In a particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be made by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve the metabolic stability and efficacy of a drug, thereby prolonging the duration of the drug's action.

[0185] Unless otherwise indicated, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, in addition to replacing one or more protons with one or more deuteria or tritia or a combination thereof, or in addition to replacing one or more 13 C atoms, one or more 14 C atoms or a combination thereof in the structure with one or more 12 C atoms, compounds having this structure are within the scope of this disclosure.

[0186] The compounds of this disclosure optionally contain unnatural proportions of atomic isotopes on one or more atoms that make up such compounds. For example, the compound can be labeled with one or more isotopes, such as deuterium ( 2 H), tritium ( 3 H), iodine-125 ( 125 I), or carbon-14 ( 14 C). With 2 H, 11 C, 13 C, 14 C, 15 C, 12 N, 13 N, 15 N, 16 N, 17 O, 18 O, 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl,79 Br, 81 Br and 125 isotopic substitution of I are all considered. All isotopic variants of the compounds of the present invention, whether radioactive or not, are included within the scope of the present invention.

[0187] In certain embodiments, some or all of the 1 H atoms in the compounds disclosed herein are 2 replaced by H atoms. Methods for the synthesis of deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0188] Deuterium-substituted compounds are synthesized by using various methods such as those described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0189] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to synthesize deuterium-containing compounds. A large number of deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as MilliporeSigma.

[0190] The present disclosure includes salts of the compounds described herein, specifically pharmaceutically acceptable salts. To form salts (specifically pharmaceutically acceptable salts), compounds of the present disclosure containing one or more sufficiently acidic functional groups, one or more sufficiently basic functional groups, or both one or more sufficiently acidic functional groups and one or more sufficiently basic functional groups can react with any of a variety of inorganic bases or organic bases or inorganic acids or organic acids to form salts; their combinations); or their combinations. Alternatively, inherently charged compounds such as those containing quaternary ammonium nitrogens can form salts with appropriate counterions.

[0191] The compounds and salts described herein can exist in some cases in diastereoisomeric, enantiomeric, or other stereoisomeric forms. Unless otherwise indicated (e.g., in a biological data sheet), the structures disclosed herein are intended to explicitly or implicitly include all diastereoisomeric (e.g., epimeric) and enantiomeric forms and their mixtures. Separation of stereoisomers can be carried out by chromatography or by forming diastereoisomers and separating them by recrystallization or chromatography or any combination thereof (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, incorporated herein by reference for the present disclosure). Stereoisomers can also be obtained by stereoselective synthesis.

[0192] In certain embodiments, the compound or a salt of the compound can be a prodrug. For example, in some embodiments, a hydroxyl group in the parent compound is present in the form of an ester or a carbonate, or a carboxylic acid present in the parent compound is present in the form of an ester. The term “prodrug” is intended to include compounds that are converted into the agents of the present disclosure under physiological conditions. One method of preparing a prodrug involves being hydrolyzed under physiological conditions to expose one or more selected moieties of the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal such as a specific target cell in the host animal. For example, an ester or a carbonate (e.g., an ester of an alcohol or a carboxylic acid or a carbonate and an ester of phosphoric acid) can be a prodrug of the present disclosure. In some embodiments, prodrugs for amines can rely on enzymatic activation. In some embodiments, prodrugs for amines can rely on the physiochemical conditions for releasing the drug. In some embodiments, prodrugs for amines can be selected from amides, carbonates, N-acyloxyalkyl derivatives, N-acyloxycarbonyl derivatives, b-aminoketones, (oxodioxolanyl)methyl derivatives, N-Mannich bases, imines (e.g., Schiff bases), enamines, enaminones, azo compounds, systems capable of lactonization, tetrahydrothiadiazine-2-thiones, redox systems, or PEGs.

[0193] Prodrug forms of the compounds described herein, wherein the prodrug is metabolized in vivo to produce the compounds described herein, are included within the scope of the claims. In some cases, some of the compounds described herein may be prodrugs of another derivative or active compound.

[0194] Prodrugs are often useful in some situations because they may be more readily administered than the parent drug. For example, a prodrug may be bioavailable by oral administration while the parent is not. Relative to the parent drug, a prodrug may help enhance the cellular permeability of the compound. Relative to the parent drug, a prodrug may also have improved solubility in a pharmaceutical composition. A prodrug can be designed as a reversible drug derivative and used as a modifier to enhance drug delivery to a site-specific tissue or increase drug retention within cells.

[0195] In some embodiments, the design of the prodrug increases the lipophilicity of the agent. In some embodiments, the design of the prodrug increases the effective water solubility. See, e.g., Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all of which are incorporated herein by reference for such disclosure). According to another embodiment, the present disclosure provides methods for preparing the compounds defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0196] Synthetic chemical transformations and methods useful for synthesizing the compounds described herein are known in the art and include, for example, those described in the following: R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser’s Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995).

[0197] Compound

[0198] The following includes a discussion of compounds and their salts that can be used in the methods of the present disclosure. In certain embodiments, the compounds and salts are described by Formulas (I), (II), and (III).

[0199] In one aspect, compounds represented by Formula (I) are disclosed herein:

[0200]

[0201] or a salt thereof, wherein:

[0202] X 1 、X 2 、X 3 and X 4 are each independently selected from C(R 1 )、N and N + (-O - ), where at least one of X 1 、X 2 、X 3 or X 4 is N; and no more than two of X 1 、X 2 、X 3 and X 4 are N;

[0203] Each R 1 is independently selected from:

[0204] Hydrogen;

[0205] Halogen, -NO2, -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)2R 10a ;

[0206] C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) -CN, C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, where the C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring are each optionally substituted by one or more R 9a substituents; and

[0207] C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, where C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted by one or more R 9a substituents;

[0208] R 2 is selected from:

[0209] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, where C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring are each optionally substituted by one or more R 9b substituents; and

[0210] C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -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 R 9b ;

[0211] R 3 and R 4 are each independently selected from:

[0212] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0213] optionally substituted independently with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN of C 1-6 alkyl; or

[0214] R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted with one or more R 9c ;

[0215] R 5 and R 6 are each independently selected from:

[0216] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN;

[0217] optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocyclic ring and a C alkyl substituted by one or more substituents selected from a 3- to 10-membered heterocyclic ring, where each C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted by one or more substituents independently selected from halogen, -OR 3-10 , -SR 10c , -N(R 10c )2, -NO2 and -CN; and 10c )2, -NO2 and -CN; or

[0218] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or

[0219] R 5 together with R 6 forms a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, where the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted by one or more R 9c ;

[0220] R 7 is selected from:

[0221] hydrogen, and a C alkyl optionally substituted by one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; 1-6 alkyl;

[0222] R 8 is selected from:

[0223] hydrogen; and

[0224] optionally substituted by one or more substituents independently selected from halogen, -OR 10e、 -SR 10e 、 -N(R 10e )2、 -NO2、 -CN、 C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein each C 1-6 alkyl, and each C 3-10 carbocycle and 3- to 10-membered heterocycle are optionally independently substituted with one or more substituents selected from halogen, -OR 10e 、 -SR 10e 、 -N(R 10e )2、 -NO2 and -CN; each R 9a is independently selected from:

[0225] 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)2R 10a 、 -NO2、 =O、 =S、 =N(R 10a ) and -CN; and

[0226] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), and -CN; each R 9b is independently selected from:

[0227] 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)2R 10b , -NO2, =O, =S, =N(R 10b ), and -CN; and

[0228] 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 the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), and -CN; each R 9c is independently selected from:

[0229] 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0230] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0231] each R 10a , R 10b , R 10c , R 10d and R 10e is independently selected from:

[0232] Hydrogen;

[0233] C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, ═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, 3- to 10-membered heterocycle; and

[0234] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, ═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.

[0235] In one aspect, the present disclosure provides a compound represented by formula (I):

[0236]

[0237] or a salt thereof, wherein:

[0238] X 1 、X 2 、X 3 and X 4 are each independently selected from C(R 1 ), N, and N + (-O - ), wherein at least one of X 1 、X 2 、X 3 or X 4 is N; and no more than two of X 1 、X 2 、X 3 and X 4 are N;

[0239] Each R 1 is independently selected from:

[0240] Hydrogen;

[0241] Halogen, -NO2, -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)2R 10a ;

[0242] C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 Carbocycle and 3- to 10-membered heterocycle, wherein C 3-10 Carbocycle and 3- to 10-membered heterocycle are each optionally substituted by one or more R 9a ; and

[0243] C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 R 9a substituents;

[0244] R 2 is selected from:

[0245] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein the C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9b substituents; and

[0246] C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b )', -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 R 9b substituents;

[0247] R 3 and R 4 are each independently selected from:

[0248] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0249] optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN of the C 1-6 alkyl; or

[0250] R 3 Together with R 4 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted by one or more R 9c substituents;

[0251] R 5 and R 6 are each independently selected from:

[0252] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN;

[0253] Optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocycle and a 3- to 10-membered heterocycle, and the C 1-6 alkyl group, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle are optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and

[0254] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or

[0255] R 5 together with R 6 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted by one or more R 9c substituents;

[0256] R 7 is selected from:

[0257] hydrogen, and optionally substituted by one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d) C alkyl substituted by one or more substituents selected from -NO2 and -CN; 1-6 alkyl;

[0258] R 8 selected from:

[0259] hydrogen; and

[0260] optionally substituted C alkyl independently selected from halogen, -OR 10e , -SR 10e , -N(R 10e )2, -NO2, -CN, C 3-10 alkyl substituted by one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, where each C 1-6 alkyl, and the carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted independently by one or more substituents selected from halogen, -OR 3-10 , -SR 10e , -N(R 10e )2, -NO2 and -CN; each R 10e is independently selected from:

[0261] halogen, -OR 9a , -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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and 10a C

[0262] alkyl, C 1-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -OR 2-3 , -SR 10a , -N(R 10a )2, -C(O)R 10a , -C(O)N(R 10a )2, 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; each R 9b is independently selected from:

[0263] 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and

[0264] 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 the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; each R 9c Independently selected from:

[0265] 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0266] 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 the group consisting of 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)2R 10c , -NO2, =O, =S, =N(R10c ) and -CN; and

[0267] Each R 10a 、R 10b 、R 10c 、R 10d and R 10e is independently selected from:

[0268] Hydrogen;

[0269] 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 the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0270] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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;

[0271] Wherein if X 3 and X 1 are both N, then R 8 is selected from hydrogen and C 10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10 、-SR 10 )2、-NO2 and -CN. 1-4 alkyl.

[0272] In one aspect, the present disclosure provides a compound represented by formula (IX):

[0273]

[0274] or a salt thereof, wherein:

[0275] X 1 、X 2 、X 3 and X 4 are each independently selected from C(R 1 ), N and N + (-O - ), wherein at least one of X 1 , X 2 , X 3 or X 4 is N; and no more than two of X 1 , X 2 , X 3 and X 4 are N;

[0276] Each R 1 is independently selected from:

[0277] hydrogen;

[0278] halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a and -C(O)N(R 10a )2;

[0279] optionally substituted C 10a alkyl, independently substituted by one or more substituents selected from halogen, -OR 10a , -SR 10a , -N(R 10a ), -C(O)R 3-10 , -NO2, -CN, C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9a substituents; and

[0280] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 10a , -SR 10a , -N(R 10a ), -C(O)R 10a , -C(O)N(R 10a ), -CN, optionally substituted C 9a alkyl substituted by one or more R 1-6 substituents;

[0281] R2 Selected from:

[0282] Optionally and independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -CN, =O, C 3-10 alkyl substituted with one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein the C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 3-10 ; and 9b

[0283] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, =O, -CN and C 1-6 alkyl, wherein each C 1-6 alkyl is optionally substituted with one or more R 9b ; R 3 and R 4 are each independently selected from:

[0284] hydrogen and -OH; and

[0285] Optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2 and -CN of C 1-6 alkyl; or

[0286] R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted with one or more R 9c ;

[0287] R 5 and R 6 are each independently selected from:

[0288] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and C 1-6 alkyl; or R 5 and R 6 together form a 3- to 10-membered heterocyclic ring or C 3-10 ​A carbocyclic ring, where a 3- to 10-membered heterocyclic ring or C 3-10 The carbocyclic ring is optionally substituted by one or more R 9c substituents;

[0289] R 7 is selected from hydrogen and C 1-6 alkyl;

[0290] R 8 is selected from hydrogen and C 1-6 alkyl;

[0291] Each R 9a , R 9b , R 9c is independently selected from halogen, -OH, -OMe, -CN and C 1-3 alkyl; Each R 10a , R 10b , R 10c , R 10d and R 10e is independently selected from:

[0292] hydrogen;

[0293] optionally substituted by one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic ring, a 3- to 10-membered heterocyclic ring-substituted C 1-6 alkyl.

[0294] In one aspect, compounds represented by formula (IY) are disclosed herein:

[0295]

[0296] or a salt thereof, wherein:

[0297] X 1 , X 2 , X 3 and X 4 are each independently selected from C(R 1 ), N and N + (-O - ), wherein at least one of X 1 , X 2 , X 3 or X 4 is N; and X 1 , X 2 , X 3 and X 4No more than two of them are N;

[0298] Each R 1 is independently selected from:

[0299] hydrogen, fluorine, chlorine, bromine, -CN, -OH, -O(C 1-6 alkyl), -O(C 1-6 haloalkyl), -O(C 3-10 carbocycle), -O(3- to 10-membered heterocycle), -C(O)NH2, C 1-6 alkyl, C 1-6 haloalkyl and C 3-10 carbocycle, where the C 3-10 carbocycle is optionally substituted with one or more halogens; R 2 is selected from:

[0300] optionally substituted with one or more substituents independently selected from -F, Cl, -OH, and C 3-10 carbocycle and 3- to 10-membered heterocycle of C 1-6 alkyl, where the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9b substituents; and

[0301] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from -F, -Cl, and -CN;

[0302] R 3 and R 4 are each independently selected from: hydrogen, -OH, and methyl;

[0303] R 5 and R 6 are each independently selected from hydrogen and C 1-3 alkyl;

[0304] R 7 is selected from: hydrogen and C 1-6 alkyl;

[0305] R 8 is selected from hydrogen and C 1-6 alkyl; and

[0306] Each R 9a 、R 9b 、R 9c is independently selected from halogen, -OH, -OMe, -CN, and C 1-3 alkyl.

[0307] In certain embodiments, for the compounds or salts of formula (I), X 1 、X 2, X 3 and X 4 each independently selected from C(R 1 ), N, and N + (-O - ). In some embodiments, at least one of X 1 , X 2 , X 3 , or X 4 is N. In some embodiments, no more than two of X 1 , X 2 , X 3 , and X 4 are N. In some embodiments, X 1 , X 2 , X 3 , and X 4 each independently selected from C(R 1 ), N, and N + (-O - ), where at least one of X 1 , X 2 , X 3 , or X 4 is N; and no more than two of X 1 , X 2 , X 3 , and X 4 are N. In some embodiments, no more than one of X 1 , X 2 , X 3 , and X 4 is N. In some embodiments, no more than two of X 1 , X 2 , X 3 , and X 4 are N. In some embodiments, no more than three of X 1 , X 2 , X 3 , and X 4 are N. In some embodiments, at least one of X 1 , X 2 , X 3 , or X 4 is N. In some embodiments, at least two of X 1 , X 2 , X 3 , or X 4 are N. In some embodiments, at least three of X 1 , X 2 , X 3 , or X 4 are N. In some embodiments, X 1, X 2 , X 3 or X 4 at least one of which is N, and X 1 , X 2 , X 3 and X 4 no more than two of which are N. In some embodiments, X 1 , X 2 , X 3 and X 4 are each independently selected from C(R 1 ), N, and N + (-O - ). In some embodiments, X 1 , X 2 , X 3 and X 4 are each independently selected from C(R 1 ) and N. In some embodiments, X 1 , X 2 , X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 1 , X 2 , X 3 or X 4 one of which is N. In some embodiments, X 1 , X 2 , X 3 and X 4 two of which are N. In some embodiments, X 1 , X 2 , X 3 and X 4 three of which are N. In some embodiments, X 1 , X 2 , X 3 or X 4 one of which is C(R 1 ). In some embodiments, X 1 , X 2 , X 3 and X 4 two of which are C(R 1 ). In some embodiments, X 1 , X 2 , X 3 and X 4 three of which are C(R 1 ). In some embodiments, X 1 , X 2 , X 3 and X4 Four of them are C(R 1 ). In some embodiments, X 1 is N. In some embodiments, X 2 is N. In some embodiments, X 3 is N. In some embodiments, X 4 is N. In some embodiments, X 1 is C(R 1 ). In some embodiments, X 2 is C(R 1 ). In some embodiments, X 3 is C(R 1 ). In some embodiments, X 4 is C(R 1 ). In some embodiments, X 1 is C(H). In some embodiments, X 2 is C(H). In some embodiments, X 3 is C(H). In some embodiments, X 4 is C(H). In some embodiments, X 1 , X 2 , X 3 and X 4 two of them are N. In some embodiments, X 1 , X 2 , X 3 and X 4 two of them are N, and X 1 , X 2 , X 3 and X 4 two of them that are N do not bind to each other (e.g., covalently). In some embodiments, X 1 and X 3 are N. In some embodiments, X 2 and X 4 are N. In some embodiments, X 1 is N, and X 2 , X 3 and X 4 are C(R 1 ). In some embodiments, X 2 is N, and X 1 , X 3 and X 4 are C(R 1 ). In some embodiments, X 3 is N, and X 1 , X 2 and X 4 are C(R1 )。In some embodiments, X 4 is N, and X 1 , X 2 and X 3 are C(R 1 ). In some embodiments, X 1 is N, and X 2 , X 3 and X 4 are C(H). In some embodiments, X 2 is N, and X 1 , X 3 and X 4 are C(H). In some embodiments, X 3 is N, and X 1 , X 2 and X 4 are C(H). In some embodiments, X 4 is N, and X 1 , X 2 and X 3 are C(H).

[0308] In some embodiments, X 2 is N, and X 1 is C(CF3). In some embodiments, X 2 is N, X 1 is C(CF3), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and R 2 is In some embodiments, X 2 is N, R 2 is and X 1 is C(CF3). In some embodiments, X 2 is N, R 2 is X 1 is C(CF3), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and X 1 is C(CN). In some embodiments, X 2 is N, X 1 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and R2 is In some embodiments, X 2 is N, R 2 is and X 1 is C(F). In some embodiments, X 2 is N, R 2 is X 1 is C(F), X 3 is C(H), and X 4 is C(H).

[0309] In some embodiments, X 2 is C(O(C 1-6 alkyl)). In some embodiments, X 2 is C(OMe). In some embodiments, X 1 is N, and X 2 is C(O(C 1-6 alkyl)). In some embodiments, X 1 is N, X 2 is C(O(C 1-6 alkyl)), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and X 2 is C(OMe). In some embodiments, X 1 is N, X 2 is C(OMe), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and X 2 is C(O(C 1-6 alkyl)), and R 3 and R 4 together form cyclopropyl. In some embodiments, X 1 is N, X 2 is C(O(C 1-6 alkyl)), X 3 is C(H), X 4 is C(H), and R 3 and R 4 together form cyclopropyl. In some embodiments, X 1 is N, X 2 is C(OMe), and R 3 and R 4 together form cyclopropyl. In some embodiments, X 1 is N, X2 is C(OMe), X 3 is C(H), X 4 is C(H), and R 3 and R 4 together form cyclopropyl.

[0310] In some embodiments, X 2 is N, and X 1 is C(F). In some embodiments, X 2 is N, X 1 is C(F), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and R 2 is In some embodiments, X 2 is N, R 2 is and X 1 is C(F). In some embodiments, X 2 is N, R 2 is X 1 is C(F), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and X 1 is C(Cl). In some embodiments, X 2 is N, X 1 is C(Cl), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, R 2 is and X 1 is C(Cl). In some embodiments, X 2 is N, R 2 is X 1 is C(Cl), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and X 1 is C(CN). In some embodiments, X 2 is N, X 1 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2is N, and R 2 is In some embodiments, X 2 is N, R 2 is and X 1 is C(CN). In some embodiments, X 2 is N, R 2 is X 1 is C(CN), X 3 is C(H), and X 4 is C(H).

[0311] In some embodiments, X 2 、X 3 and X 4 each independently selected from C(H). In some embodiments, X 1 is N, and X 2 、X 3 and X 4 each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X 2 、X 3 and X 4 each independently selected from C(H). In some embodiments, X 1 is N, and X 2 、X 3 and X 4 each independently selected from C(R 1 ), and R 3 and R 4 together form cyclopropyl. In some embodiments, X 1 is N, and X 2 、X 3 and X 4 each independently selected from C(H), and R 3 and R 4 together form cyclopropyl.

[0312] In some embodiments, X 2 is C(CN). In some embodiments, X 1 is N, and X 2 is C(Cl). In some embodiments, X 1 is N, and X 2 is C(Cl), and X 3 and X 4 each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X2 is C(Cl), and X 3 and X 4 are each independently selected from C(H).

[0313] In some embodiments, X 1 is N, and X 2 is C(CN). In some embodiments, X 1 is N, and X 2 is C(CN), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X 2 is C(CN), and X 3 and X 4 are each independently selected from C(H).

[0314] In some embodiments, X 1 is C(Br). In some embodiments, X 1 is N, and X 2 is C(Br). In some embodiments, X 1 is N, and X 2 is C(Br), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X 2 is C(Br), and X 3 and X 4 are each independently selected from C(H). In some embodiments, X 1 is N, and X 2 is C(Br), and R 5 is H, and R 6 is methyl. In some embodiments, X 1 is N, and X 2 is C(Br), and X 3 and X 4 are each independently selected from C(R 1 ), and R 5 is H, and R 6 is methyl. In some embodiments, X 1 is N, and X 2 is C(Br), and X 3 and X 4 are each independently selected from C(H), and R 5 is H, and R 6 is methyl.

[0315] In some embodiments, X 2 is C(F). In some embodiments, X 1 is N, and X 2 is C(F). In some embodiments, X 1 is N, and X 2 is C(F), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X 2 is C(F), and X 3 and X 4 are each independently selected from C(H).

[0316] In some embodiments, X 1 is C(CF3). In some embodiments, X 2 is N, and X 1 is C(CF3). In some embodiments, X 2 is N, and X 1 is C(CF3), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 2 is N, and X 1 is C(CF3), and X 3 and X 4 are each independently selected from C(H).

[0317] In some embodiments, X 1 is C(OCF3). In some embodiments, X 2 is N, and X 1 is C(OCF3). In some embodiments, X 2 is N, and X 1 is C(OCF3), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 2 is N, and X 1 is C(OCF3), and X 3 and X 4 are each independently selected from C(H).

[0318] In some embodiments, X 2 is N, and X 1 is C(CN). In some embodiments, X2 is N, X 1 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 2 is N, and R 2 is In some embodiments, X 2 is N, R 2 is and X 1 is C(CN). In some embodiments, X 2 is N, R 2 is X 1 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and X 2 is C(OR 10a ) 1 is N, and X 2 is C(OMe). In some embodiments, X 1 is N, X 2 is C(OR 10a ) 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, X 2 is C(OMe), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is and X 2 is C(OR 10a ) 1 is N, R 2 is and X 2 is C(OMe). In some embodiments, X 1 is N, R 2 is X 2 is C(OR 10a ) 3 is C(H), and X 4 is C(H). In some embodiments, X1 is N, R 2 is X 2 is C(OMe), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, R 2 is X 2 is C(OMe), X 3 is C(H), X 4 is C(H), and R 3 and R 4 together form a cyclopropyl ring. In some embodiments, X 1 is N, X 2 is C(H), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, R 2 is X 3 is C(H), X 4 is C(H), and R 3 and R 4 together form a cyclopropyl ring. In some embodiments, X 1 is N, and X 2 is C(Cl). In some embodiments, X 1 is N, X 2 is C(Cl), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is and X 2 is C(CN). In some embodiments, X 1 is N, R 2 is X 2 is C(CN), X 3is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and X 2 is C(CN). In some embodiments, X 1 is N, X 2 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is and X 2 is C(CN). In some embodiments, X 1 is N, R 2 is X 2 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, R 2 is X 2 is C(CN), X 3 is C(H), X 4 is C(H), and R 3 and R 4 together form a cyclopropyl ring. In some embodiments, X 1 is N, X 2 is C(H), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is and X 2 is C(H). In some embodiments, X 1 is N, R 2 is X 2 is C(H), X 3 is C(H), and X 4 is C(H). In some embodiments, some embodiments, X 1 is N, and X 2 is C(CN). In some embodiments, X 1 is N, X 2is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is X 2 is C(CN). In some embodiments, X 1 is N, R 2 is X 2 is C(CN), X 3 is C(H), and X 4 is C(H). In some embodiments, some embodiments, X 1 is N, and X 2 is C(F). In some embodiments, X 1 is N, X 2 is C(F), X 3 is C(H), and X 4 is C(H). In some embodiments, X 1 is N, and R 2 is In some embodiments, X 1 is N, R 2 is and X 2 is C(F). In some embodiments, X 1 is N, R 2 is X 2 is C(F), X 3 is C(H), and X 4 is C(H).

[0319] In some embodiments, X 2 is C(F). In some embodiments, for the compound or salt of formula (I), X 1 is N, X 2 is F, R 5 is methyl, and R 6 is hydrogen.

[0320] In some embodiments, X 2 is C(CF3). In some embodiments, X 1 is N, and X 2 is C(CF3). In some embodiments, X 1 is N, and X 2 is C(CF3), and X3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X 2 is C(CF3), and X 3 and X 4 are each independently selected from C(H).

[0321] In some embodiments, X 1 is C(Cl). In some embodiments, X 3 is N, and X 1 is C(R 1 ). In some embodiments, X 3 is N, and X 1 is C(R 1 ), and X 2 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 3 is N, and X 1 is C(Cl). In some embodiments, X 3 is N, and X 1 is C(Cl), and X 2 is C(R 1 ). In some embodiments, X 3 is N, and X 1 is C(Cl), and X 2 is C(R 1 ), and X 4 is C(R 1 ). In some embodiments, X 3 is N, and X 1 is C(Cl), and X 2 is C(H). In some embodiments, X 3 is N, and X 1 is C(Cl), and X 2 is C(H), and X 4 is C(H).

[0322] In some embodiments, X 1 is C(OCH2CHF2) (for example, in some embodiments, X 1 is carbon with a 2,2-difluoroethoxy moiety). In some embodiments, X 2 is N, and X 1 is C(OCH2CHF2). In some embodiments, X 2 is N, and X 1is C(OCH2CHF2), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 2 is N, and X 1 is C(OCH2CHF2), and X 3 and X 4 are each independently selected from C(H).

[0323] In some embodiments, X 1 is C(OCH2CH3). In some embodiments, X 2 is N, and X 1 is C(OCH2CH3). In some embodiments, X 2 is N, and X 1 is C(OCH2CH3), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 2 is N, and X 1 is C(OCH2CH3), and X 3 and X 4 are each independently selected from C(H).

[0324] In some embodiments, X 2 is C(OCH2CH3). In some embodiments, X 1 is N, and X 2 is C(OCH2CH3). In some embodiments, X 1 is N, and X 2 is C(OCH2CH3), and X 3 and X 4 are each independently selected from C(R 1 ). In some embodiments, X 1 is N, and X 2 is C(OCH2CH3), and X 3 and X 4 are each independently selected from C(H).

[0325] In some embodiments, X 1 is In some embodiments, X 2 is N, and X 1 is In some embodiments, X 2 is N, and X 1 is and X 3and X 4 each independently selected from C(R 1 ). In some embodiments, X 2 is N, and X 1 is and X 3 and X 4 each independently selected from C(H).

[0326] In certain embodiments, for a compound or salt of formula (I), each R 1 is independently selected from:

[0327] hydrogen;

[0328] halogen, -NO2, -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)2R 10a ;

[0329] 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 the following: 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)R10a 、 -S(O)2R 10a 、 -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic rings and 3 - to 10 - membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3 - to 10 - membered heterocyclic rings are each optionally substituted by one or more R 9a ; and

[0330] C 3-10 carbocyclic rings and 3 - to 10 - membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 by one or more R 9a .

[0331] In certain embodiments, for the compounds or salts of formula (I), each R 1 is independently selected from: hydrogen; halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a and -C(O)N(R 10a )2; optionally substituted by one or more independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, -CN, C3-10 C substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles 1-6 alkyl, wherein the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9a substituents; 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 the following: halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -C(O)N(R 10a )2, -CN, C 9a alkyl optionally substituted with one or more R 1-6 substituents.

[0332] In some embodiments, each R 1 is independently selected from: hydrogen; halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a and -C(O)N(R 10a )2; C 10a alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10a , -SR 10a and -N(R 1-6 )2; 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 and -N(R 10a )2.

[0333] In some embodiments, each R 1 is independently selected from: hydrogen; halogen, CN, -OR 10a and -C(O)N(R 10a )2; C 3-10 alkyl optionally substituted with one or more substituents independently selected from halogen and C 1-6 carbocycle, the C 3-10 carbocycle being optionally substituted with one or more substituents independently selected from halogen.

[0334] In some embodiments, R 1 is independently selected from hydrogen.

[0335] In some embodiments, each R 1Independently selected from hydrogen, halogen, -NO2, -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)2R 10a ;

[0336] In some embodiments, each R 1 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 the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 R 9a substituents.

[0337] In some embodiments, each R 1 is independently selected from hydrogen, C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 by one or more R 9a substituents.

[0338] In some embodiments, each R 1 is independently selected from: hydrogen; halogen, -NO2, -CN, -CN, -OH, -SH, -NO2, -NH2, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2 and -NH(C 1-6 alkyl); C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -NO2, -CN, -CN, -OH, -SH, -NO2, -NH2, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings; and C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -NO2, -CN, -CN, -OH, -SH, -NO2, -NH2, -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 and C 2-6 alkynyl.

[0339] In some embodiments, each R 1 is independently selected from C 1-3 alkyl, wherein the C 1-3 alkyl is optionally independently substituted with one or more substituents selected from the following: halogen, -NO2, -CN, -CN, -OH, -SH, -NO2, -NH2, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, each R 1 is independently selected from C 3-5 carbocyclic rings, wherein the C 3-5 carbocyclic rings are optionally independently substituted with one or more substituents selected from the following: halogen, -NO2, -CN, -CN, -OH, -SH, -NO2, -NH2, -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 and C 2-6 alkynyl. In some embodiments, each R 1 is independently selected from hydrogen, -CN, -OH, -OMe, -OEt, -OiPr, -F, -Cl, -Br, -Me, -Et, -CF3, -CHF2, -CH2F, OCF3, -OCHF2, -OCH2F, -C(O)NH2, In some embodiments, each R 1 is independently selected from hydrogen, -CN, -OH, -OMe, -OEt, -OiPr, -F, -Cl, -Br, -Me, -Et, -CF3, -CHF2, -CH2F, OCF3, -C(O)NH2, In some embodiments, each R 1 is independently selected from hydrogen, -CN, -OH, -OMe, -OEt, -OiPr, -F, -Cl, -Br, -Me, -Et, -CF3, OCF3, -C(O)NH2, In some embodiments, each R 1 is independently selected from hydrogen, -CN, -OH, -OMe, -OEt, -OiPr, -F, -Cl, -Br, -Me, -CF3, OCF3, -C(O)NH2, In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, -OR 10a (e.g., -OMe), -F, -Cl, -OCF3, and methyl. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, -OMe, -F, -Cl, -OCF3, and methyl. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, -OR 10a (e.g., -OMe), -F, -Cl, and -OCF3. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, -OMe, -F, -Cl, and -OCF3. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, -OMe, -F, and -Cl. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, -OMe, and -F. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, -CN, and -OMe. In some embodiments, each R 1 is independently selected from hydrogen, -CF3, and -CN. In some embodiments, each R 1 is independently selected from hydrogen and -CN. In some embodiments, each R 1 is independently selected from hydrogen and -CF3. In some embodiments, each R 1 is independently selected from hydrogen and -CN. In some embodiments, each R 1 is independently selected from hydrogen and -OR 10a . In some embodiments, each R 1 is independently selected from hydrogen and -OMe. In some embodiments, each R 1 is independently selected from hydrogen and -F. In some embodiments, each R 1 is independently selected from hydrogen and -Cl. In some embodiments, each R 1Independently selected from hydrogen and -OCF3. In some embodiments, each R 1 is independently selected from hydrogen and C 1-6 alkyl. In some embodiments, each R 1 is independently selected from hydrogen and methyl. In some embodiments, each R 1 is independently selected from hydrogen, F, and CN. In some embodiments, each R 1 is independently selected from hydrogen and CF2H. In some embodiments, each R 1 is independently selected from hydrogen, halogen, and -CN. In some embodiments, each R 1 is independently selected from hydrogen, F, and -CN. In some embodiments, each R 1 is independently selected from hydrogen and F. In some embodiments, each R 1 is independently selected from hydrogen and CN. In some embodiments, each R 1 is independently selected from hydrogen.

[0340] In certain embodiments, for a compound or salt of formula (I), R 2 is selected from: 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 the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocycle, and 3- to 10-membered heterocycle, where C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9b ; 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 the following: halogen, -OR10b 、 -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)2R 10b 、 -NO2, =O, =S, =N(R 10b )、 -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 by one or more R 9b .

[0341] In some embodiments, R 2 is selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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 , -NO2, =O, -CN, C 3-10 carbocycle and 3 - to 10 - membered heterocycle, wherein C 3-10 carbocycle and 3 - to 10 - membered heterocycle are each optionally substituted by one or more R 9b ; and C 3-10 carbocycle and 3 - to 10 - membered heterocycle, each of which is optionally substituted by one or more substituents independently selected from the following: 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 , -NO2, =O, -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 R 9b substituents.

[0342] In some embodiments, R 2 is selected from C 1-6 alkyl, said C 1-6 alkyl being 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 , -NO2, =O, -CN, C 3-10 carbocycle and 3 - to 10 - membered heterocycle, wherein C 3-10 carbocycle and 3 - to 10 - membered heterocycle are each optionally substituted with one or more R 9b substituents; 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 , -C(O)OR 10b , -OC(O)R 10b , -NO2, =O, -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 2-6Each alkynyl group is optionally substituted with one or more R 9b .

[0343] In some embodiments, R 2 is selected from: C 10b alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 3-10 , -NO2, =O, -CN, C 1-6 carbocyclic ring and C 3-10 alkyl substituted with one or more substituents selected from a 3- to 10-membered heterocyclic ring, wherein each of the C 9b carbocyclic ring and the 3- to 10-membered heterocyclic ring is optionally substituted with one or more R 3-10 ; and C 10b carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from the following: 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 1-6 , -NO2, =O, -CN, C 2-6 alkyl, C 2-6 alkenyl and C 1-6 alkynyl, wherein each of the C 2-6 alkyl, C 2-6 alkenyl and C 9b alkynyl is optionally substituted with one or more R

[0344] In some embodiments, R 2 is selected from: C 10b alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 3-10 , -NO2, =O, -CN, C 1-6 alkyl substituted with one or more substituents selected from a 3- to 10-membered heterocyclic ring, wherein each of the C 3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring is optionally substituted with one or more R 9b ; and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -OR10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -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 R 9b substituents.

[0345] In some embodiments, R 2 is selected from: C 10b alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10b , -SR 10b , -N(R 3-10 )2, -NO2, =O, -CN, C 1-6 carbocyclic ring and a 3- to 10-membered heterocyclic ring, wherein C 3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9b substituents; and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O, -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 R 9b substituents.

[0346] In some embodiments, R 2 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(R10b ) 2, -N(R 10b ) C(O)OR 10b , -S(O)R 10b , -S(O)₂R 10b , -NO₂, =O, =S, =N(R 10b ), -CN, C 3-10 alkyl substituted with one or more substituents from carbocycles and 3- to 10-membered heterocycles, wherein C 1-6 the carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R 3-10 . In some embodiments, R 9b is optionally independently selected from halogen, -OR 2 , -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 , -NO₂, =O, -CN, C 10b alkyl substituted with one or more substituents from carbocycles and 3- to 10-membered heterocycles, wherein C 3-10 the carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R 1-6 . In some embodiments, R 3-10 is optionally independently selected from halogen, -OR 9b , -SR 2 , -N(R 10b ), -C(O)R 10b , -NO₂, =O, -CN, C 10b alkyl substituted with one or more substituents from carbocycles and 3- to 10-membered heterocycles, wherein C 10b the carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R 3-10 . In some embodiments, R 1-6 is optionally independently selected from halogen, -OR 3-10 , -SR 9b , -N(R 2 )₂, -NO₂, =O, -CN, C 10b alkyl substituted with one or more substituents from carbocycles and 3- to 10-membered heterocycles, wherein C 10b the carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R 10b . In some embodiments, R 3-10 is optionally independently selected from halogen, -OR 1-6 alkyl substituted with one or more substituents from carbocycles and 3- to 10-membered heterocycles, wherein C 3-10 the carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R9b is substituted. In some embodiments, R 2 is optionally substituted by one or more substituents independently selected from halogen, -OR 10b , -N(R 10b )2, -NO2, =O, -CN, C 3-10 -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 1-6 -alkyl and the 3- to 10-membered heterocycle are each optionally substituted by one or more R 3-10 s. In some embodiments, R 9b is optionally substituted by one or more substituents independently selected from halogen, -OR 2 , C 10b -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 3-10 -alkyl and the 3- to 10-membered heterocycle are each optionally substituted by one or more R 1-6 s. In some embodiments, R 3-10 is optionally substituted by one or more substituents independently selected from F, OH, C 9b -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 2 -alkyl and the 3- to 10-membered heterocycle are each optionally substituted by one or more R 3-10 s. In some embodiments, R 1-6 is optionally substituted by one or more substituents independently selected from F, OH, C 3-10 -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein each C 9b -alkyl and the 3- to 10-membered heterocycle are independently selected from phenyl, 2-pyridyl, and 3-pyridyl, and each phenyl, 2-pyridyl, and 3-pyridyl is optionally substituted by one or more R 2 s. In some embodiments, R 3-10 is optionally substituted by one or more substituents independently selected from halogen, -OR 1-6 , C 3-10 -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 9b -alkyl and the 3- to 10-membered heterocycle are each optionally substituted by one or more R 2 s. In some embodiments, R 10b is optionally substituted by one or more substituents independently selected from F, OH, C 3-10 -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 3-10 -alkyl and the 3- to 10-membered heterocycle are each optionally substituted by one or more R 9b s. In some embodiments, R 2 is optionally substituted by one or more substituents independently selected from F, OH, C 3-10 -alkyl substituted by one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 3-10 -alkyl and the 3- to 10-membered heterocycle are each optionally substituted by one or more R 9bis substituted. In some embodiments, R 2 is a C2 alkyl group optionally substituted with one or more substituents independently selected from F, OH, C 3-10 carbocyclic rings, and 3- to 10-membered heterocyclic rings, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are independently selected from phenyl, 2-pyridyl, and 3-pyridyl, and each phenyl, 2-pyridyl, and 3-pyridyl is optionally substituted with one or more R 9b substituents.

[0347] In some embodiments, R 2 is selected from: optionally substituted independently with 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic rings, and 3- to 10-membered heterocyclic rings, and one or more substituents substituted C 1-6 alkyl group, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9b substituents; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O, -CN, C 1-6 alkyl group, C 2-6 alkenyl group, and C 2-6 alkynyl group, wherein C 1-6 alkyl group, C 2-6 alkenyl group, and C 2-6 alkynyl group are each optionally substituted with one or more R 9b substituents.

[0348] In some embodiments, R2 Selected from: optionally 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 , -NO2, =O, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 1-6 carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R 3-10 substituents; and C 9b carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 3-10 , -SR 10b , -N(R 10b )2, -NO2, =O, -CN and C 10b alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more R 1-6 substituents. 9b

[0349] In some embodiments, R 2 is selected from: optionally independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein the C 1-6 carbocycles and 3- to 10-membered heterocycles are each optionally substituted with one or more R 3-10 substituents; and C 9b carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 3-10 , -SR 10b , -N(R 10b )2, -NO2, =O, -CN and C 10b alkyl. 1-6

[0350] In some embodiments, R 2 is selected from: optionally independently selected from halogen, -OR 10b , -SR10b ,-N(R 10b )2, -NO2, =O, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, where the C 1-6 carbocyclic ring and the 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 3-10 substituents; and C 9b carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 3-10 , -SR 10b , -SR 10b , -N(R 10b )2, -NO2, =O, -CN, and C 1-6 alkyl.

[0351] In some embodiments, R 2 is selected from: C 10b alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10b , -N(R 3-10 )2, -NO2, =O, -CN, C 1-6 alkyl substituted with one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, where the C 3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9b substituents; and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O, -CN, and C 1-6 alkyl.

[0352] In some embodiments, R 2 is selected from: C 10b alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 3-10 , C 1-6 alkyl substituted with one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, where the C 3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9b substituents; and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen and -CN.

[0353] In some embodiments, R 2 is selected from: C 3-10C substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles 1-6 alkyl, wherein C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more R 9b substituents; and C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from F and -CN.

[0354] In some embodiments, R 2 is selected from: C 3-10 alkyl optionally substituted with one or more substituents selected from F, OH, and carbocycles and 3- to 10-membered heterocycles 1-6 wherein each C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is independently selected from phenyl, 2-pyridyl, and 3-pyridyl, and each phenyl, 2-pyridyl, and 3-pyridyl is optionally substituted with one or more R 9b substituents; and C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from F and -CN.

[0355] In some embodiments, R 2 is selected from: halogen, -OR 10b , C 3-10 C2 alkyl optionally substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more R 9b substituents; and C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from F and -CN.

[0356] In some embodiments, R 2 is selected from: F, OH, C 3-10 C2 alkyl optionally substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more R 9b substituents; and C 3-10 each of the carbocycle and the 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from F and -CN.

[0357] In some embodiments, R 2 is a substituent represented by the following formula: wherein Q 1is a C alkyl optionally substituted with one or more substituents selected from OH and halo; Y 1-3 alkyl; Y 1 and Y 2 each independently selected from N and C(Q 3 )); and each Q 2 is independently selected from halo and CN; each Q 3 is independently selected from hydrogen, halo and CN; and n is 0, 1 or 2.

[0358] In some embodiments, Q 1 is a C1 alkyl optionally substituted with one or more substituents selected from OH and fluorine; each Q 2 is independently selected from fluorine and CN; and each Q 3 is independently selected from hydrogen, fluorine and CN. In some embodiments, each Q 2 is selected from F and H. In some embodiments, each Q 2 is selected from CN and H. In some embodiments, each Q 3 is selected from F. In some embodiments, each Q 3 is selected from F and H. In some embodiments, each Q 3 is selected from CN and H. In some embodiments, each Q 3 is selected from F.

[0359] In some embodiments, R 2 is selected from

[0360] In some embodiments, R 2 is selected from

[0361] In some embodiments, R 2 is selected from: C alkyl optionally substituted with one or more substituents independently selected from OH and C 3-10 in one or more carbocycles, wherein the C 1-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen and -CN; and C 3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, R 3-10 is selected from: C alkyl optionally substituted with one or more C 2 carbocycles, wherein each C 3-10 carbocycle is optionally substituted with one or more substituents independently selected from halogen and -CN; and C 1-6 alkyl, wherein each C 3-10The carbocyclic ring is optionally substituted with one or more substituents independently selected from halogen and -CN; and C optionally substituted with one or more substituents independently selected from halogen and -CN 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring. In some embodiments, R 2 is selected from: C optionally substituted with one or more 3-10 carbocyclic rings 1-6 alkyl, wherein each C 3-10 carbocyclic ring is optionally substituted with one or more substituents independently selected from F and -CN; and C optionally substituted with one or more substituents independently selected from -F and -CN 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring. In some embodiments, R 2 is selected from: C2 alkyl optionally substituted with one or more 3-10 carbocyclic rings, wherein each C 3-10 carbocyclic ring is optionally substituted with one or more substituents independently selected from halogen and -CN; and C optionally substituted with one or more substituents independently selected from halogen and -CN 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring.

[0362] In some embodiments, R 2 is selected from: C2 alkyl optionally substituted with one or more 3-10 carbocyclic rings, wherein each C 3-10 carbocyclic ring is optionally substituted with one or more substituents independently selected from -F and -CN; and C optionally substituted with one or more substituents independently selected from -F and -CN 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring. In some embodiments, R 2 is C2 alkyl optionally substituted with one or more 3-10 carbocyclic rings, wherein each C 3-10 carbocyclic ring is optionally substituted with one or more substituents independently selected from -F and -CN. In some embodiments, R 2 is C2 alkyl optionally substituted with one or more 3-10 carbocyclic rings, wherein each C 3-10 carbocyclic ring is optionally substituted with one or more substituents independently selected from -F. In some embodiments, R 2 is C2 alkyl optionally substituted with one or more 3-10 carbocyclic rings, wherein each C 3-10 carbocyclic ring is optionally substituted with one or more substituents independently selected from -CN.

[0363] In some embodiments, R 2 is C optionally substituted with one or more substituents independently selected from -F and -CN3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings.

[0364] In certain embodiments, for a compound or salt of formula (I), R 3 and R 4 are each independently selected from:

[0365] hydrogen, halogen, -OR 10c -SR 10c -N(R 10c )2, -NO2 and -CN; and

[0366] optionally C 10c alkyl substituted independently by one or more substituents selected from halogen, -OR 10c -SR 10c )2, -NO2 and -CN; or 1-6 R

[0367] and R 3 together form a 3- to 10-membered heterocyclic ring or a C 4 carbocyclic ring, where the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted by one or more R 3-10 carbocyclic ring is optionally substituted by one or more R 9c .

[0368] In some embodiments, R 3 and R 4 are each independently selected from: hydrogen, halogen, -OR 10c -SR 10c -N(R 10c )2, -NO2 and -CN; and optionally C 10c alkyl substituted independently by one or more substituents selected from halogen, -OR 10c -SR 10c )2, -NO2 and -CN; or R 1-6 and R 3 together form a 3- to 10-membered heterocyclic ring or a C 4 carbocyclic ring, where the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted by one or more R 3-10 carbocyclic ring is optionally substituted by one or more R 9c .

[0369] In some embodiments, R 3 and R 4 are each independently selected from: hydrogen, halogen, -NO2 and -CN; and optionally C 1-6 alkyl substituted by one or more halogens; or R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or a C3-10 A carbocyclic ring, wherein a 3- to 10-membered heterocyclic ring or C 3-10 The carbocyclic ring is optionally substituted with one or more R 9c . In some embodiments, R 3 and R 4 are each independently selected from: hydrogen, halogen, -NO2, and -CN; and C 1-6 alkyl optionally substituted with one or more halogens; or R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring.

[0370] In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more halogens; or R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more halogens. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C1 alkyl. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen.

[0371] In some embodiments, R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring. In some embodiments, the 3- to 10-membered heterocyclic ring or C 3 carbocyclic ring formed by R 4 and R 3-10 together is selected from cyclopropyl and oxetanyl. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C1 alkyl; or R 3 and R 4 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C1 alkyl; or R 3 and R4 Together form C 3-10 a carbocyclic ring. In some embodiments, R 3 and R 4 are each independently selected from: hydrogen; and C1 alkyl; or

[0372] R 3 and R 4 together form a C 3-10 carbocyclic ring, wherein the C 3-10 carbocyclic ring is cyclopropane.

[0373] In some embodiments, R 3 and R 4 are each hydrogen. In some embodiments, R 3 is hydrogen. In some embodiments, R 4 is hydrogen. In some embodiments, R 3 is hydrogen, and R 4 is methyl. In some embodiments, R 3 is hydrogen, and R 4 is C 1-6 alkyl. In some embodiments, R 3 is -H, and R 4 is -OH. In some embodiments, R 3 is -OH, and R 4 is -H. In some embodiments, R 3 is -OH.

[0374] In certain embodiments, for the compound or salt of formula (I), R 5 and R 6 are each independently selected from:

[0375] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN;

[0376] optionally independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocyclic ring and one or more substituents selected from 3- to 10-membered heterocycles substituted C 1-6 alkyl, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocycle are optionally independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN substituted by one or more substituents; and

[0377] C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or

[0378] R 5 together with R 6 forms a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted by one or more R 9c substituents.

[0379] In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, and the C 1-6 alkyl group, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or R 5 together with R 6 forms a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted by one or more R 9c substituents.

[0380] In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and C 1-6 alkyl group; or R 5 together with R 6 forms a 3- to 10-membered heterocyclic ring or a C 3-10A carbocyclic ring, wherein a 3- to 10-membered heterocyclic ring or C 3-10 The carbocyclic ring is optionally substituted with one or more R 9c . In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN; and C 1-6 alkyl. In some embodiments, R 5 and R 6 are each independently selected from: hydrogen and C 1-3 alkyl. In some embodiments, R 5 is hydrogen. In some embodiments, R 6 is hydrogen. In some embodiments, R 5 and R 6 are each hydrogen. In some embodiments, R 5 is hydrogen, and R 6 is C 3-10 alkyl optionally substituted with one or more substituents independently selected from C 1-6 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, R 5 is hydrogen, and R 6 is methyl.

[0381] In some embodiments, the compound or salt of formula (I) is a compound or salt of formula (I-Q): In some embodiments, the compound or salt of formula (I-Q) is an activator of skeletal myosin. In some embodiments, the compound or salt of formula (I-Q) is used to treat obesity or cause weight loss. In some embodiments, for the compound or salt of formula (I-Q), R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN; C 10c alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein each C 1-10 carbocyclic ring and 3- to 10-membered heterocyclic ring is optionally substituted with one or more substituents independently selected from halogen, -OR 3-10 , -SR 10c , -N(R 10c , -N(R 10c)2. Substituted with one or more substituents selected from -NO2 and -CN; and C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted with a substituent selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN. In some embodiments, R 5 is -H, and R 6 is selected from: C alkyl optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted with a substituent selected from halogen, -OR 1-10 alkyl, wherein each C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring are optionally independently substituted with a substituent selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN; and C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted with a substituent selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN. In some embodiments, R 5 is -H, and R 6 is selected from: C alkyl optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted with a substituent selected from halogen, -OR 1-10 alkyl, wherein each C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring are optionally independently substituted with a substituent selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN. In some embodiments, R 5 is -H, and R 6 is selected from: C alkyl optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10C substituted with one or more substituents in a carbocyclic ring and a 3- to 10-membered heterocyclic ring 1-6 alkyl, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN. In some embodiments, R 5 is -H, and R 6 is optionally a branched (e.g., non-linear, e.g., primary, secondary or tertiary) C 10c alkyl substituted with one or more substituents in a carbocyclic ring and a 3- to 10-membered heterocyclic ring, wherein each C 10c carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 3-10 , -N(R 1-6 )2, -NO2 and -CN. In some embodiments, R 3-10 is -H, and R 10c is optionally a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety substituted with one or more substituents in a carbocyclic ring and a 3- to 10-membered heterocyclic ring, wherein each C 10c carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 5 , -N(R 6 )2, -NO2 and -CN. In some embodiments, R 10c is -H, and R 10c is optionally a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety substituted with one or more substituents in a C 10c carbocyclic ring, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted with one or more substituents independently selected from halogen, -OR 3-10 , -SR 10c , -N(R 10c )2, -NO2 and -CN. In some embodiments, R 10c is -H, and R 5 is optionally a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety substituted with one or more substituents in a C 6 carbocyclic ring, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted with one or more substituents independently selected from halogen, -OR 3-10The carbocyclic ring is optionally substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, R 5 is -H, and R 6 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety optionally substituted with one or more substituents independently selected from substituents in the C 3-10 carbocyclic ring. In some embodiments, R 5 is -H, and R 6 is n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety.

[0382] In certain embodiments, for the compound or salt of formula (I), R 7 is selected from: hydrogen, and C 10d alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 1-6 )2, -NO2 and -CN. In some embodiments, R 7 is selected from hydrogen, and C 3-10 alkyl optionally substituted with one or more substituents independently selected from halogen, CN, C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic ring. In some embodiments, R 7 is selected from hydrogen, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and CN. In some embodiments, R 7 is selected from hydrogen, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen. In some embodiments, R 7 is selected from hydrogen and C 1-6 alkyl. In some embodiments, R 7 is selected from hydrogen and methyl. In some embodiments, R 7 is selected from hydrogen.

[0383] In certain embodiments, for the compound or salt of formula (I), R 8 is selected from:

[0384] hydrogen; and

[0385] optionally substituted with one or more substituents independently selected from halogen, -OR 10e , -SR 10e , -N(R 10e )2, -NO2, -CN, C3-10 C substituted with one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings 1-6 alkyl, wherein each C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are optionally substituted with one or more substituents independently selected from halogen, -OR 10e , -SR 10e , -N(R 10e )2, -NO2 and -CN

[0386] In some embodiments, R 8 is selected from: hydrogen; and C 10e alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10e , -SR 10e , -N(R 1-6 )2, -NO2 and -CN. In some embodiments, R 8 is selected from hydrogen, and C 3-10 alkyl optionally substituted with one or more substituents independently selected from halogen, CN, C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic rings. In some embodiments, R 8 is selected from hydrogen, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and CN. In some embodiments, R 8 is selected from hydrogen, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen. In some embodiments, R 8 is selected from hydrogen and C 1-6 alkyl. In some embodiments, R 8 is selected from hydrogen

[0387] In certain embodiments, for the compounds or salts of formula (I), each R 9a is independently selected from:

[0388] 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)2R 10a , -NO2, =O, =S, =N(R 10a ), and -CN; and

[0389] C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), and -CN.

[0390] In some embodiments, each R 9a is independently selected from: halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, and -CN. In some embodiments, each R 9a is independently selected from: halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a, -NO2, =O, and -CN; and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, and -CN. In some embodiments, each R 1-3 is independently selected from: F, Cl, Br, -OR 9a , -N(R 10a )2, -NO2, =O, and -CN; and optionally C alkyl substituted with one or more substituents independently selected from F, Cl, Br, -OR 10a , -N(R 10a )2, -NO2, =O, and -CN. In some embodiments, each R 10a is independently selected from: F, Cl, -OR 1-3 , -N(R 9a )2, -NO2, =O, and -CN; and optionally C alkyl substituted with one or more substituents independently selected from F, Cl, -OR 10a , -N(R 10a )2, -NO2, =O, and -CN. In some embodiments, each R 10a is independently selected from: F, Cl, -NO2, =O, and -CN; and optionally C alkyl substituted with one or more substituents independently selected from F, Cl, -NO2, =O, and -CN 10a . In some embodiments, each R 1-3 is independently selected from: F, Cl, and -CN; and optionally C alkyl substituted with one or more substituents independently selected from F, Cl, and -CN 9a . In some embodiments, each R 1-3 is independently selected from: F, Cl, and -CN; and C 9a alkyl. In some embodiments, each R 1-3 is independently selected from: F, Cl, and -CN; and C 9a alkyl. In some embodiments, each R 1-3 is independently selected from: F and -CN; and C 9a alkyl. In some embodiments, each R 1-3 is independently selected from: F and -CN. In some embodiments, each R 9a is independently selected from: F and -CN. In some embodiments, each R 9a is independently selected from: F. In some embodiments, each R 9a is independently selected from: -CN.

[0391] In certain embodiments, for a compound or salt of formula (I), each R 9b is independently selected from: halogen, -OR10b 、-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)2R 10b , -NO2, =O, =S, =N(R 10b ) 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 the group consisting of 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN. In some embodiments, each R 9b 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, -NO2, =O and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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 , -NO2, =O and -CN. In some embodiments, each R 9b is independently selected from: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O and -CN; and optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O and -CN of C 1-3 alkyl. In some embodiments, each R 9b is independently selected from: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O and -CN; and optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -NO2, =O and -CN of C 1-3 alkyl. In some embodiments, each R 9b is independently selected from halogen and -CN. In some embodiments, each R 9b is independently selected from -F, -Cl and -CN. In some embodiments, each R 9b is independently selected from -F and -CN. In some embodiments, each R 9b is independently selected from -F. In some embodiments, each R 9b is independently selected from -CN.

[0392] In certain embodiments, for the compounds or salts of formula (I), each R 9c is independently selected from: halogen, -OR 10c , -SR 10c , -N(R10c ) 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN. In some embodiments, each R 9c is independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 10c , -NO2, =O and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -OR 10c , -SR 10c , -N(R10c ) 2, -C(O)R 10c , -NO2, ═O, and -CN. In some embodiments, each R 9c is independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 10c , -NO2, ═O, and -CN; and optionally C 10c alkyl substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 1-3 , -NO2, ═O, and -CN. In some embodiments, each R 9c is independently selected from F, Cl, Br, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 10c , -NO2, ═O, and -CN; and optionally C 10c alkyl substituted with one or more substituents independently selected from F, Cl, Br, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 1-3 , -NO2, ═O, and -CN. In some embodiments, each R 9c is independently selected from F, Cl, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 10c , -NO2, ═O, and -CN; and optionally C 10c alkyl substituted with one or more substituents independently selected from F, Cl, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 1-3 , -NO2, ═O, and -CN. In some embodiments, each R 9c is independently selected from F, Cl, Br, -OR 10c , -N(R 10c )2, -C(O)R 10c , -NO2, ═O, and -CN; and optionally C 10c alkyl substituted with one or more substituents independently selected from F, Cl, -OR 10c , -N(R 10c, a C alkyl substituted by one or more substituents selected from -NO2, =O, and -CN. In some embodiments, each R 1-3 is independently selected from F, Cl, Br, -NO2, =O, and -CN; and optionally a C alkyl substituted by one or more substituents independently selected from F, Cl, Br, -NO2, =O, and -CN. In some embodiments, each R 9c is independently selected from F, Cl, -NO2, =O, and -CN; and optionally a C alkyl substituted by one or more substituents independently selected from F, Cl, -NO2, =O, and -CN. In some embodiments, each R 1-3 is independently selected from F, Cl, -NO2, =O, and -CN; and optionally a C alkyl substituted by one or more substituents independently selected from F, Cl, -NO2, =O, and -CN. In some embodiments, each R 9c is independently selected from F, Cl, -NO2, =O, and -CN; and optionally a C alkyl substituted by one or more substituents independently selected from F, Cl, -NO2, =O, and -CN. In some embodiments, each R 1-3 is independently selected from: F, Cl, and -CN; and optionally a C alkyl substituted by one or more substituents independently selected from F, Cl, and -CN. In some embodiments, each R 9c is independently selected from: F, Cl, and -CN; and a C alkyl. In some embodiments, each R 1-3 is independently selected from: F, Cl, and -CN; and a C alkyl. In some embodiments, each R 9c is independently selected from: F and -CN; and a C alkyl. In some embodiments, each R 1-3 is independently selected from: F and -CN; and a C alkyl. In some embodiments, each R 9c is independently selected from: F and -CN; and a C alkyl. In some embodiments, each R 1-3 is independently selected from: F and -CN. In some embodiments, each R 9c is independently selected from: F. In some embodiments, each R 9c is independently selected from: -CN. 9c In certain embodiments, for the compounds or salts of formula (I), each R

[0393] is independently selected from: 10a R 10b R 10c R 10d and R 10e is independently selected from:

[0394] hydrogen;

[0395] C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0396] C3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings and C 1-6 haloalkyl.

[0397] In certain embodiments, for a compound or salt of formula (I), each R 10a is independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic ring, one or more substituents selected from 3- to 10-membered heterocyclic rings; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings and C 1-6 haloalkyl. In some embodiments, each R 10a is independently selected from hydrogen; and C 1-6 alkyl optionally substituted independently by one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -N(C 1-6 alkyl)2 and -NH(C 1-6 alkyl); and C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 1-6 alkyl and C 1-6 haloalkyl. In some embodiments, each R 10a is independently selected from hydrogen; and C 1-6 alkyl optionally substituted independently by one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2 and =O; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 1-6 alkyl and C 1-6 haloalkyl. In some embodiments, R 10a is independently selected from hydrogen; and C 1-6 alkyl optionally substituted independently by one or more substituents selected from halogen; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, R 10a is independently selected from hydrogen; and C 1-6 alkyl optionally substituted independently by one or more substituents selected from fluorine and chlorine; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, R 10a is independently selected from hydrogen; and C 1-6 alkyl optionally substituted by fluorine; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, R 10a is independently selected from hydrogen; and C 1-6 alkyl optionally substituted by fluorine; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings selected from cyclopropane and oxetane. In some embodiments, R 10a is hydrogen. In some embodiments, R 10a is methyl.

[0398] In certain embodiments, for the compounds or salts of formula (I), each R 10b is independently selected from:

[0399] hydrogen;

[0400] C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0401] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted independently with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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.

[0402] In some embodiments, each R 10b is independently selected from: hydrogen; and C 1-6 alkyl optionally substituted independently with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl)2, and -NH(C 1-6 alkyl); and C 1-6 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted independently with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 3-10 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 1-6 alkyl, C 1-6 alkyl, C 2-6 alkenyl, and C 1-6 haloalkyl. In some embodiments, each R 10b is independently selected from: hydrogen; and C1-6 alkyl group. In some embodiments, each R 10b is hydrogen. In some embodiments, R 10b is methyl.

[0403] In certain embodiments, for the compounds or salts of formula (I), each R 10c is independently selected from:

[0404] hydrogen;

[0405] 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 the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0406] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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.

[0407] In some embodiments, each R 10c is independently selected from: hydrogen; C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl); and C 3-10 carbocycle and 3- to 10-membered heterocycle. In some embodiments, each R 10c is independently selected from: hydrogen; and C 1-6Alkyl. In some embodiments, each R 10c is hydrogen. In some embodiments, R 10c is methyl.

[0408] In certain embodiments, for a compound or salt of formula (I), each R 10d is independently selected from:

[0409] Hydrogen;

[0410] 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, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0411] 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, -NO2, -NH2, =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.

[0412] In some embodiments, each R 10d is independently selected from: hydrogen; C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl); and C 3-10 carbocycle and 3- to 10-membered heterocycle. In some embodiments, each R 10d is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R10d All are hydrogen. In some embodiments, R 10d is methyl.

[0413] In certain embodiments, for a compound or salt of formula (I), each R 10e is independently selected from:

[0414] hydrogen;

[0415] 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, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0416] 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, -NO2, -NH2, =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.

[0417] In some embodiments, each R 10e is independently selected from: hydrogen; C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl); and C 3-10 carbocycle and 3- to 10-membered heterocycle. In some embodiments, each R 10e is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R 10eThey are all hydrogen. In some embodiments, R 10e is methyl.

[0418] In certain embodiments, for a compound or salt of formula (I), if X 1 , X 2 , X 3 and X 4 in two of them are N, then R 8 is selected from hydrogen and C 10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 ), -NO2 and -CN. In some embodiments, if X 1-4 , X 1 , X 2 and X 3 in two of them are N, then R 4 is selected from hydrogen and C 8 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10 and -CN. In some embodiments, if X 1-4 , X 1 , X 2 and X 3 in two of them are N, then R 4 is selected from hydrogen and C 8 alkyl optionally substituted with one or more substituents independently selected from fluorine, -OH and -CN. In some embodiments, if X 1-4 , X 1 , X 2 and X 3 in two of them are N, then R 4 is selected from hydrogen and C 8 alkyl. In some embodiments, if X 1-4 , X 1 , X 2 and X 3 in two of them are N, then R 4 is selected from hydrogen and C1 alkyl. In some embodiments, if X 8 , X 1 , X 2 and X 3 in two of them are N, then R 4 is selected from hydrogen. 8 is selected from hydrogen.

[0419] In certain embodiments, for a compound or salt of formula (I), if X 3 and X 1 are both N, then R 8 is selected from hydrogen and optionally independently selected from halogen, -OR10 , -SR 10 , -N(R 10 )2, -NO2 and -CN, and is substituted with one or more substituents selected from the group consisting of C 1-4 alkyl. In some embodiments, if X 3 and X 1 are both N, then R 8 is selected from hydrogen and C 10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 1-4 and -CN. In some embodiments, if X 3 and X 1 are both N, then R 8 is selected from hydrogen and C 1-4 alkyl optionally substituted with one or more substituents independently selected from fluorine, -OH and -CN. In some embodiments, if X 3 and X 1 are both N, then R 8 is selected from hydrogen and C 1-4 alkyl. In some embodiments, if X 3 and X 1 are both N, then R 8 is selected from hydrogen and C1 alkyl. In some embodiments, if X 3 and X 1 are both N, then R 8 is selected from hydrogen.

[0420] In certain embodiments, for a compound or salt of formula (I), if X 2 and X 4 are both N, then R 8 is selected from hydrogen and C 10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 , -N(R 1-4 )2, -NO2 and -CN. In some embodiments, if X 2 and X 4 are both N, then R 8 is selected from hydrogen and C 10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 1-4 and -CN. In some embodiments, if X 2 and X 4 are both N, then R 8 is selected from hydrogen and C 1-4 alkyl optionally substituted with one or more substituents independently selected from fluorine, -OH and -CN. In some embodiments, if X 2and X 4 are both N, then R 8 is selected from hydrogen and C 1-4 alkyl. In some embodiments, if X 2 and X 4 are both N, then R 8 is selected from hydrogen and C1 alkyl. In some embodiments, if X 2 and X 4 are both N, then R 8 is selected from hydrogen.

[0421] In certain embodiments, for a compound or salt of formula (I), if X 1 , X 2 , X 3 and X 4 of two are N, then R 7 is selected from hydrogen and optionally independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -NO2 and -CN one or more substituents substituted C 1-4 alkyl. In some embodiments, if X 1 , X 2 , X 3 and X 4 of two are N, then R 7 is selected from hydrogen and optionally independently selected from halogen, -OR 10 and -CN one or more substituents substituted C 1-4 alkyl. In some embodiments, if X 1 , X 2 , X 3 and X 4 of two are N, then R 7 is selected from hydrogen and optionally independently selected from fluorine, -OH and -CN one or more substituents substituted C 1-4 alkyl. In some embodiments, if X 1 , X 2 , X 3 and X 4 of two are N, then R 7 is selected from hydrogen and C 1-4 alkyl. In some embodiments, if X 1 , X 2 , X 3 and X 4 of two are N, then R 7 is selected from hydrogen and C1 alkyl. In some embodiments, if X 1 , X 2 , X 3 and X4 If two of them in 7 are N, then R

[0422] In certain embodiments, for a compound or salt of formula (I), if X 3 and X 1 are both N, then R 7 is selected from hydrogen, and optionally C 10 alkyl substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 , -N(R 1-4 3 1 and X 7 are both N, then R 10 is selected from hydrogen, and optionally C 1-4 alkyl substituted with one or more substituents independently selected from halogen, -OR 3 and -CN. In some embodiments, if X 1 and X 7 are both N, then R 1-4 is selected from hydrogen, and optionally C 3 alkyl substituted with one or more substituents independently selected from fluorine, -OH and -CN. In some embodiments, if X 1 and X 7 are both N, then R 1-4 is selected from hydrogen and C 3 alkyl. In some embodiments, if X 1 and X 7 are both N, then R 3 is selected from hydrogen and C1 alkyl. In some embodiments, if X 1 and X 7 are both N, then R 2 is selected from hydrogen.

[0423] In certain embodiments, for a compound or salt of formula (I), if X 4 and X 7 are both N, then R 10 is selected from hydrogen, and optionally C 10 alkyl substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 1-4 , -N(R 2 4 7 and X 10 ​​​​C substituted with one or more substituents selected from -CN 1-4 alkyl. In some embodiments, if X 2 and X 4 are both N, then R 7 is selected from hydrogen and C 1-4 alkyl optionally substituted with one or more substituents independently selected from fluorine, -OH, and -CN. In some embodiments, if X 2 and X 4 are both N, then R 7 is selected from hydrogen and C 1-4 alkyl. In some embodiments, if X 2 and X 4 are both N, then R 7 is selected from hydrogen and C1 alkyl. In some embodiments, if X 2 and X 4 are both N, then R 7 is selected from hydrogen.

[0424] In some embodiments, the compound or salt of formula (I) is selected from: N87, N4, N5, N13, N15, N123, N33, N111, N124, and N128.

[0425] In some embodiments, the compound or salt of formula (I) is selected from: N87, N4, N5, N13, N15, N123, N33, N111, N124, N128, N7, N18, N68, N88, N26, N103, N104, N117, N110, N37, N102, N94, N112, N81, N54, N101, N23, N136, N9, N98, N122, N31, N28, N115, N121, N74, N119, N16, N126, N47, N125, N83, N118, N10, and N62.

[0426] In some embodiments, the compound or salt of formula (I) is selected from: N87, N4, N5, N13, N15, N123, N33, N111, N124, N128, N7, N18, N68, N88, N26, N103, N104, N117, N110, N37, N102, N94, N112, N81, N54, N101, N23, N136, N9, N98, N122, N31, N28, N115, N121, N74, N119, N16, N126, N47, N125, N83, N118, N10, N62, N41, N60, N14, N44, N108, N130, N93, N19, N77, N8, N114, N106, N3, N133, N6, N24, N127, N72, N84, N95, N132, N129, N21, N116, N55, N109, N35, N135, N59, N12, N36, N80, N99, N34, N39, and N50.

[0427] In some embodiments, the compound or salt of formula (I) is selected from: N87, N4, N5, N13, N15, N123, N33, N111, N124, N128, N7, N18, N68, N88, N26, N103, N104, N117, N110, N37, N102, N94, N112, N81, N54, N101, N23, N136, N9, N98, N122, N31, N28, N115, N121, N74, N119, N16, N126, N47, N125, N83, N118, N10, N62, N41, N60, N14, N44, N108, N130, N93, N19, N77, N8, N114, N106, N3, N133, N6, N24, N127, N72, N84, N95, N132, N129, N21, N116, N55, N109, N35, N135, N59, N12, N36, N80, N99, N34, N39, N50, N57, N25, N45, N2, N85, N113, N64, N78, N66, N86, N43, N30, N131, N71, N91, N38, N1, N17, N40, and N52.

[0428] In some embodiments, the compound or salt of formula (I) is selected from: N87, N4, N5, N13, N15, N123, N33, N111, N124, N128, N7, N18, N68, N88, N26, N103, N104, N117, N110, N37, N102, N94, N112, N81, N54, N101, N23, N136, N9, N98, N122, N31, N28, N115, N121, N74, N119, N16, N126, N47, N125, N83, N118, N10, N62, N41, N60, N14, N44, N108, N130, N93, N19, N77, N8, N114, N106, N3, N133, N6, N24, N127, N72, N84, N95, N132, N129, N21, N116, N55, N109, N35, N135, N59, N12, N36, N80, N99, N34, N39, N50, N57, N25, N45, N2, N85, N113, N64, N78, N66, N86, N43, N30, N131, N71, N91, N38, N1, N17, N40, N52, N11, N20, N22, N27, N29, N32, N42, N46, N48, N49, N51, N53, N56, N58, N61, N63, N65, N67, N69, N70, N73, N75, N76, N79, N82, N89, N90, N92, N96, N97, N100, N105, N107 and N120.

[0429] In some embodiments, the compound or salt of formula (I) is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4 and N94

[0430] In some embodiments, the compound or salt of formula (I) is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13 and N123.

[0431] In some embodiments, the compound or salt of formula (I) is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13, N123, N31, N26, N18, N74, N68, N101, N102, N41, N125, N15, N54, N9, N119, N126, N104, N37, N129, N62, N118, N95, N121, N47, N28, N111, N114, N112 and N103.

[0432] In some embodiments, the compound or salt of formula (I) is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13, N123, N31, N26, N18, N74, N68, N101, N102, N41, N125, N15, N54, N9, N119, N126, N104, N37, N129, N62, N118, N95, N121, N47, N28, N111, N114, N112, N103, N136, N122, N19, N8, N10, N21, N133, N44, N110, N77, N36, N120, N78, N2, N24, N6, N72, N116, N108, N39, N98, N127, N113, N60 and N132.

[0433] In some embodiments, the compound or salt of formula (I) is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13, N123, N31, N26, N18, N74, N68, N101, N102, N41, N125, N15, N54, N9, N119, N126, N104, N37, N129, N62, N118, N95, N121, N47, N28, N111, N114, N112, N103, N136, N122, N19, N8, N10, N21, N133, N44, N110, N77, N36, N120, N78, N2, N24, N6, N72, N116, N108, N39, N98, N127, N113, N60, N132, N1, N3, N11, N12, N14, N16, N17, N20, N22, N25, N27, N29, N30, N32, N34, N35, N38, N40, N42, N43, N45, N46, N48, N49, N50, N51, N52, N53, N55, N56, N57, N58, N59, N61, N63, N64, N65, N66, N67, N69, N70, N71, N73, N75, N76, N79, N80, N82, N83, N84, N85, N86, N89, N90, N91, N92, N93, N96, N97, N99, N100, N105, N106, N107, N109, N130, N131 and N135.

[0434] In some embodiments, for the compound or salt of formula (I), each R 1 is independently selected from: hydrogen; deuterium, -N3, halogen, -NO2, -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)2R 10a; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: deuterium, -N3, 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein the C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9a ; and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted independently with one or more substituents selected from the following: deuterium, -N3, 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6Alkynyl, wherein C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more R 9a . In some embodiments, R 2 is selected from 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 the following: deuterium, -N3, 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocycle, and 3- to 10-membered heterocycle, wherein C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9b ; 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 the following: deuterium, -N3, 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -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 R 9b . In some embodiments, R 3 and R 4 are each independently selected from: hydrogen, deuterium, -N3, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and optionally substituted with one or more substituents independently selected from deuterium, -N3, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN of C 1-6 alkyl; or R 3 and R 4 together 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 R 9c . In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, deuterium, -N3, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; optionally substituted with one or more substituents independently selected from deuterium, -N3, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle of C 1-6 alkyl, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from deuterium, -N3, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; 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 deuterium, -N3, halogen, -OR 10c , -SR 10c , -N(R10c ) substituted by one or more substituents selected from -NO2 and -CN; or R 5 together with R 6 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted by one or more R 9c substituents. In some embodiments, R 7 is selected from: hydrogen, and C 10d alkyl optionally substituted independently by one or more substituents selected from deuterium, -N3, halogen, -OR 10d , -SR 10d , -N(R 1-6 )2, -NO2 and -CN. In some embodiments, R 8 is selected from: hydrogen; and C 10e alkyl optionally substituted independently by one or more substituents selected from deuterium, -N3, halogen, -OR 10e , -SR 10e , -N(R 3-10 )2, -NO2, -CN, C 1-6 carbocycle and 3- to 10-membered heterocycle, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle is optionally substituted independently by one or more substituents selected from deuterium, -N3, halogen, -OR 10e , -SR 10e , -N(R 10e )2, -NO2 and -CN. In some embodiments, each R 9a is independently selected from: deuterium, -N3, 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and C 1-3 alkyl, C2-3 Alkenyl and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: deuterium, -N3, 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN. In some embodiments, each R 9b is independently selected from: deuterium, -N3, 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted independently by deuterium, -N3, halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -C(O)N(R 10b )2, -N(R10b )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)2R 10b 、 -NO2、 =O、 =S、 =N(R 10b ) and -CN, and is substituted with one or more substituents selected from the group consisting of: 9c In some embodiments, each R is independently selected from: deuterium, -N3, 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)2R 10c 、 -NO2、 =O、 =S、 =N(R 10c ) 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 the group consisting of: deuterium, -N3, 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)OR10c 、 -OC(O)R 10c 、 -S(O)R 10c 、 -S(O)₂R 10c 、 -NO₂、 =O、 =S、 =N(R 10c ) and -CN. In some embodiments, each R 10a 、 R 10b 、 R 10c 、 R 10d and R 10e is independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from deuterium, -N₃, halogen, -CN, -OH, -SH, -NO₂, -NH₂, =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, one or more substituents in 3- to 10-membered heterocycles; and C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted by one or more substituents independently selected from the following: deuterium, -N₃, halogen, -CN, -OH, -SH, -NO₂, -NH₂, =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. In some embodiments, R 3 is -D. In some embodiments, R 4 is -D. In some embodiments, R 5 is -D. In some embodiments, R 6 is -D. In some embodiments, R 7 is -D. In some embodiments, R 8 is -D.

[0435] In one aspect, the present disclosure provides a compound represented by formula (II):

[0436]

[0437] or a salt thereof, wherein:

[0438] n is 0, 1, 2, 3 or 4;

[0439] Each R 1 is independently selected from:

[0440] halogen, -NO2, -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)2R 10a ;

[0441] 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 the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein the C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9a ; and

[0442] C 3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, where C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted by one or more R 9a ;

[0443] R 2 is selected from:

[0444] halogen, -NO2, -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)2R 10b ;

[0445] C 1-6Alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein the C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9b ; and

[0446] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6Alkynyl, wherein C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with one or more R 9b ; or

[0447] R 2 and R 11 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted with one or more R 9b’ ;

[0448] R 3 and R 4 are each independently selected from:

[0449] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN; and

[0450] optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN of C 1-6 alkyl; or

[0451] R 3 and R 4 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted with one or more R 9c ;

[0452] R 5 and R 6 are each independently selected from:

[0453] hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2, and -CN; and

[0454] optionally substituted with one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2, and -CN of C 1-6 alkyl; or

[0455] R 5 and R 6Together 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 by one or more R 9d substituents;

[0456] R 7 is selected from:

[0457] hydrogen, and C 10e alkyl optionally substituted by one or more substituents independently selected from halogen, -OR 10e , -SR 10e , -N(R 1-6 )2, -NO2 and -CN;

[0458] R 8 is selected from:

[0459] hydrogen;

[0460] and C 10f alkyl optionally substituted by one or more substituents independently selected from halogen, -OR 10f , -SR 10f , -N(R 1-6 )2, -NO2 and -CN;

[0461] R 11 is selected from:

[0462] halogen, -NO2, -CN, -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 and -S(O)2R 10g ; and

[0463] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 10g , -SR10g , -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)2R 10g , -NO2, =S, =N(R 10g ), -CN, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein the C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9g substituents;

[0464] R 12 is selected from:

[0465] hydrogen;

[0466] optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h substituted C 1-6 alkyl; and

[0467] each optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h substituted C 3-6 carbocyclic rings and 3- to 10-membered heterocyclic rings; or

[0468] R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system;

[0469] each R 9a is independently selected from:

[0470] 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and

[0471] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; each R 9b is independently selected from:

[0472] Halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -C(O)N(R 10b )2, -N(R 10b )C(O)R10b , -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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and

[0473] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; each R 9b’ is independently selected from:

[0474] 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)OR10b 、-OC(O)R 10b 、-S(O)R 10b 、-S(O)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and

[0475] 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 the group consisting of 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; each R 9c Independently selected from:

[0476] 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0477] C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; each R 9d is independently selected from:

[0478] 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN; and

[0479] C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN; each R 9g is independently selected from:

[0480] 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)2R 10g , -NO2, =O, =S, =N(R 10g ) and -CN; and

[0481] 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 the following: 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)2R 10g 、-NO2、=O、=S、=N(R 10g ) and -CN; each R 10a 、R 10b 、R 10c 、R 10d 、R 10e 、R 10f 、R 10g 、R 10h is independently selected from:

[0482] hydrogen;

[0483] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0484] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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.

[0485] In some embodiments, the compound of formula (II) has formula (II-X):

[0486]

[0487] or a salt thereof, wherein:

[0488] n is 1, 2, 3 or 4;

[0489] each R 1 is independently selected from:

[0490] halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a ;

[0491] optionally substituted by one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, =O, -CN, C 3-10 alkyl substituted by one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein the C 1-6 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 3-10 substituents; and 9a and

[0492] C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, =O, -CN and C 1-6 alkyl, wherein each C 1-6 alkyl is optionally substituted by one or more R 9a substituents; R 2 is selected from:

[0493] C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 alkyl substituted by one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are optionally substituted by one or more R9b Substitute; or

[0494] R 2 Together with R 11 Form a 3- to 10-membered heterocycle or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocycle or C 3-10 carbocyclic ring is optionally substituted by one or more R 9b’ substituents;

[0495] R 3 and R 4 Each independently selected from:

[0496] Hydrogen, halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN; and

[0497] Optionally substituted by one or more substituents independently selected from halogen, OH, -OMe, -SH, -NH2, -NO2, and -CN C 1-6 alkyl; or;

[0498] R 5 and R 6 Each independently selected from:

[0499] Hydrogen, halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN; and

[0500] Optionally substituted by one or more substituents independently selected from halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN C 1-6 alkyl;

[0501] R 7 Selected from:

[0502] Hydrogen, and optionally substituted by one or more substituents independently selected from halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN C 1-6 alkyl;

[0503] R 8 Selected from:

[0504] Hydrogen, and optionally substituted by one or more substituents independently selected from halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN C 1-6 alkyl;

[0505] R 11 Selected from:

[0506] Halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN; and

[0507] C optionally substituted by one or more substituents independently selected from halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN 1-6 alkyl;

[0508] R 12 selected from

[0509] hydrogen;

[0510] C optionally substituted by one or more substituents independently selected from halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN 1-6 alkyl; and

[0511] each C optionally substituted by one or more substituents independently selected from halogen, -OH, -OMe, -SH, -NH2, -NO2, and -CN 3-6 carbocyclic ring and 3- to 10-membered heterocyclic ring; or

[0512] R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system;

[0513] each R 9a independently selected from halogen, -OR 10a , -CN, and C 1-6 alkyl;

[0514] each R 9b independently selected from halogen, -OR 10b , -CN, and C 1-6 alkyl;

[0515] each R 9b’ independently selected from halogen, -OR 10b , -CN, and C 1-6 alkyl;

[0516] each R 10a , R 10b independently selected from hydrogen, C 1-6 alkyl, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring.

[0517] In some embodiments, the compound of formula II has the formula (II-Y): (II-Y):

[0518]

[0519] or a salt thereof, wherein:

[0520] n is 1 or 2;

[0521] each R1 Independently selected from:

[0522] halogen, -CN, -OR 10a , -SR 10a , -N(R 10a )2; and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, =O and -CN; 1-6 alkyl;

[0523] R 2 Selected from:

[0524] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 10b , =O, -CN, C 1-6 alkyl, C 2-6 alkynyl, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein each C 1-6 alkyl, C 2-6 alkynyl, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring is optionally substituted with one or more R 9b substituents;

[0525] R 3 and R 4 are each independently selected from:

[0526] hydrogen, halogen, -OH, -OMe- and -CN; and

[0527] optionally C alkyl substituted with one or more substituents independently selected from halogen, OH, -OMe and -CN; 1-3 alkyl;

[0528] R 5 and R 6 are each independently selected from:

[0529] hydrogen, halogen, -OH, -OMe- and -CN; and

[0530] optionally C alkyl substituted with one or more substituents independently selected from halogen, -OH, -OMe and -CN; 1-3 alkyl;

[0531] R 7 Selected from:

[0532] hydrogen, and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OH, -OMe and -CN1-3 alkyl;

[0533] R 8 selected from:

[0534] hydrogen, and optionally C 1-3 alkyl substituted with one or more substituents independently selected from halogen, -OH, -OMe, and -CN;

[0535] R 11 selected from:

[0536] optionally C 1-3 alkyl substituted with one or more substituents independently selected from halogen, -OH, -OMe, and -CN;

[0537] R 12 selected from hydrogen, C 1-3 alkyl, C 3-6 carbocycle and 3- to 10-membered; or

[0538] R 12 、R 11 and R 2 together form a C5-C 10 bridged ring system;

[0539] each R 9a is independently selected from halogen, -OH, -OMe, -CN, and C 1-3 alkyl;

[0540] each R 9b is independently selected from halogen, -OH, -OMe, -CN, and C 1-3 alkyl;

[0541] each R 9b’ is independently selected from halogen, -OH, -OMe, -CN, and C 1-3 alkyl;

[0542] each R 10a 、R 10b is independently selected from hydrogen, C 1-6 alkyl, C 6-10 carbocycle, and 5- to 10-membered heterocycle.

[0543] In some embodiments, for a compound or salt of formula (II), n is 0, 1, 2, 3, or 4. In some embodiments, n is 0, 1, 2, or 3. In some embodiments, n is 0, 1, 2, or 4. In some embodiments, n is 0, 1, 3, or 4. In some embodiments, n is 0, 2, 3, or 4. In some embodiments, n is 1, 2, 3, or 4. In some embodiments, n is 0, 1, or 2. In some embodiments, n is 0, 1, or 3. In some embodiments, n is 0, 1, or 4. In some embodiments, n is 0, 2, or 3. In some embodiments, n is 0, 2, or 4. In some embodiments, n is 0, 3, or 4. In some embodiments, n is 1, 2, or 3. In some embodiments, n is 1, 2, or 4. In some embodiments, n is 0 or 1. In some embodiments, n is 0 or 2. In some embodiments, n is 0 or 3. In some embodiments, n is 0 or 4. In some embodiments, n is 1 or 2. In some embodiments, n is 1 or 3. In some embodiments, n is 1 or 4. In some embodiments, n is 2 or 3. In some embodiments, n is 2 or 4. In some embodiments, n is 3 or 4. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 0. In some embodiments, n is 1 or 2. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 0 or 1. In some embodiments, n is 0 or 2.

[0544] In some embodiments, for a compound or salt of formula (II), each R 1 is independently selected from:

[0545] halogen, -NO2, -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)2R 10a ;

[0546] C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, where C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9a ; and

[0547] C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 1-6Alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, where C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted by one or more R 9a substituents;

[0548] In some embodiments, each R 1 is independently selected from: halogen, -NO2, -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 , -C(O)OR 10a , and -OC(O)R 10a ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted by 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 , -NO2, =O, -CN, C 3-10 carbocyclic ring, and 3 - to 10 - membered heterocyclic ring, where C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring are each optionally substituted by one or more R 9a substituents; and C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally substituted by 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 , -NO2, =O, -CN, C 1-6 alkyl, and C 2-6Alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9a substituents.

[0549] In some embodiments, each R 1 is independently selected from: halogen, -NO2, -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 , -C(O)OR 10a and -OC(O)R 10a ; C 1-6 alkyl and C 2-6 alkenyl, 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 , -NO2, =O, -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9a substituents; and C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, 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 , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9ais substituted. In some embodiments, each R 1 is independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, and -C(O)R 10a ; C 1-6 alkyl and C 2-6 alkenyl, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, where the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted by one or more R 9a ; and C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, where the C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted by one or more R 9a . In some embodiments, each R 1 is independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, and -C(O)R 10a ; C 1-6 alkyl and C 2-6 alkenyl, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, where the C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted by one or more R 9a ; and C 3-10 carbocycle and 3- to 10-membered heterocycle. In some embodiments, each R 1Independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2 and -C(O)R 10a ; and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, -CN, C 3-10 carbocyclic ring and a 3- to 10-membered heterocyclic ring, wherein the C 1-6 alkyl is optionally substituted with one or more Rs 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more Rs 9a . In some embodiments, each R 1 is independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2 and -C(O)R 10a ; and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, -CN, C 3-10 carbocyclic ring and a 3- to 10-membered heterocyclic ring, wherein the C 1-6 alkyl is optionally substituted with one or more Rs 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted with one or more Rs 9a . In some embodiments, each R 1 is independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2 and -C(O)R 10a ; and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O and -CN, wherein the C 1-6 alkyl. In some embodiments, each R 1 is independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2 and -C(O)R 10a ; and C1-6 alkyl group. In some embodiments, each R 1 is independently selected from: halogen, -NO2, -CN, -OR 10a , -SR 10a and -N(R 10a )2. In some embodiments, each R 1 is independently selected from: halogen and -CN. In some embodiments, each R 1 is independently selected from: fluorine, bromine and -CN. In some embodiments, each R 1 is independently selected from fluorine and CN. In some embodiments, each R 1 is independently selected from fluorine and bromine. In some embodiments, each R 1 is independently selected from bromine and CN. In some embodiments, each R 1 is independently selected from fluorine. In some embodiments, each R 1 is independently selected from bromine. In some embodiments, each R 1 is independently selected from CN. In some embodiments, each R 1 is independently selected from: halogen, -CN, -OR 10a and C 1-6 alkyl group. In some embodiments, each R 1 is independently selected from: halogen, -CN, -OR 10a and C 1-6 alkyl group. In some embodiments, each R 1 is independently selected from: -F, -Br, -Cl, -CN, -OH and -CH3. In some embodiments, each R 1 is independently selected from: -F, -Br, -CN, -OH and -CH3.

[0550] In some embodiments, n is 2, and each R 1 is independently selected from -F, -Cl and -CN. In some embodiments, n is 2, and each R 1 is independently selected from -F and -CN. In some embodiments, n is 2, and each R 1 is independently selected from -F. In some embodiments, on the carbon adjacent to the carbon bearing R 3 and R 4 the R 1 is -F. In some embodiments, on the carbon meta to the carbon bearing R 3 and R 4 the R 1 is -F. In some embodiments, on the carbon para to the carbon bearing R 3 and R 4 the R 1 is -F. In some embodiments, on the carbon bearing R3 and R 4 at the carbon ortho to R 1 is -F, and at the carbon meta to R 3 and R 4 is -F. In some embodiments, n is 2, and at the carbon ortho to R 1 and R 3 and R 4 is -F, and at the carbon meta to R 1 and R 3 and R 4 is -F. 1 is -F.

[0551] In some embodiments, the compound of formula (II) is selected from formula (II-A),

[0552]

[0553] In some embodiments, the compound of formula (II) is selected from formula (II-B)

[0554] where each Y is independently selected from -(CR 9b )- and N.

[0555] In some embodiments, the compound of formula (II) is selected from formula (II-C),

[0556]

[0557] In some embodiments, the compound of formula (II) is selected from formula (II-D)

[0558] where each Y is independently selected from -(CR 9b )- and N.

[0559] In some embodiments, the compound of formula (II) is selected from formula (II-E),

[0560]

[0561] In some embodiments, the compound of formula (II) is selected from formula (II-F)

[0562] where each Y is independently selected from -(CR 9b )- and N.

[0563] In some embodiments, for the compound or salt of formula (II), R 2 is selected from:

[0564] halogen, -NO2, -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)2R 10b ;

[0565] C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) -CN, C 3-10 carbocyclic and 3 - to 10 - membered heterocyclic rings, where C 3-10 carbocyclic and 3 - to 10 - membered heterocyclic rings are each optionally substituted by one or more R 9b ; and

[0566] C 3-10 carbocyclic and 3 - to 10 - membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R10b , -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)2R 10b , -NO2, =O, =S, =N(R 10b ), -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 by one or more R 9b ; or

[0567] R 2 together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted by one or more R 9b’ .

[0568] In some embodiments, R 2 together with R 11 and R 12 forms a bridged 5- to 20-membered heterocycle or a bridged C 9b’ carbocycle, optionally substituted by one or more R 5-20 . In some embodiments, R 2 together with R 11 and R 12 forms a bridged 5- to 18-membered heterocycle or a bridged C 9b’ carbocycle, optionally substituted by one or more R 5-18 . In some embodiments, R 2 together with R 11 and R 12 forms a bridged 5- to 15-membered heterocycle or a bridged C 9b’ carbocycle, optionally substituted by one or more R 5-15 . In some embodiments, R 2 together with R 11 and R 12Together form an optionally one or more R 9b’ substituted bridged 5- to 12-membered heterocycle or bridged C 5-12 carbocycle. In some embodiments, R 2 together with R 11 and R 12 together form an optionally one or more R 9b’ substituted bridged 5- to 10-membered heterocycle or bridged C 5-10 carbocycle.

[0569] In some embodiments, R 2 is selected from: halogen, -NO2, -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 , -C(O)OR 10b and -OC(O)R 10b ; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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 , -NO2, =O, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, where C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9b ; and C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally independently substituted with one or more substituents selected from the following: 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)R10b , -NO2, =O, -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 by one or more R 9b ; or R 2 and R 11 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted by one or more R 9b’ .

[0570] In some embodiments, for the compounds or salts of formula (II), R 2 is selected from: halogen, -NO2, -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 , -C(O)OR 10b and -OC(O)R 10b ; C 1-6 alkyl and C 2-6 alkenyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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 , -NO2, =O, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle, wherein C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted by one or more R 9b ; and C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted by one or more substituents independently selected from the following: 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 , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein the C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted by one or more R 9b ; or R 2 and R 11 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9b’ . In some embodiments, R 2 is selected from: halogen, -NO2, -CN, -OR 10b , -SR 10b and -N(R 10b )2; C 1-6 alkyl and C 2-6 alkenyl, each of which is optionally independently substituted by one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -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 by one or more R 9b ; and C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally independently substituted by one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein the C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted by one or more R 9b ; or R 2 and R 11 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9b’Substituted. In some embodiments, R 2 is selected from: halogen, -NO2, -CN, -OR 10b , -SR 10b and -N(R 10b )2; optionally substituted C 10b alkyl independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 1-6 , -NO2, =O, -CN; and C 3-10 carbocyclic and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9b ; or R 2 and R 11 together form a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted with one or more R 9b’ . In some embodiments, R 2 is selected from: halogen, -NO2, -CN, -OR 10b , -SR 10b and -N(R 10b )2; optionally substituted C 10b alkyl with one or more -OR 1-6 ; and C 3-10 carbocyclic and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9b ; or R 2 and R 11 together form a 3- to 10-membered heterocyclic ring or a C3-10 A carbocyclic ring, in which a 3- to 10-membered heterocyclic ring or C 3-10 The carbocyclic ring is optionally substituted with one or more R 9b’ substituents.

[0571] In some embodiments, R 2 is selected from: halogen, -NO2, -CN, -OR 10b , -SR 10b and -N(R 10b )2; C 1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9b substituents; or R 2 and R 11 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring, in which the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted with one or more R 9b’ substituents. In some embodiments, R 2 is selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9b substituents; or R 2 and R 11 together form a 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring, in which the 3- to 10-membered heterocyclic ring or C 3-10 carbocyclic ring is optionally substituted with one or more R 9b’ substituents.

[0572] In some embodiments, R 2 is selected from: C 3-10Carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -CN, C 1-6 alkyl and C 2-6 alkenyl, wherein C 1-6 alkyl and C 2-6 alkenyl are each optionally substituted with one or more R 9b ; or R 2 together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9b’ . In some embodiments, R 2 is selected from: C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -CN and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more R 9b ; or R 2 together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9b’ . In some embodiments, R 2 is selected from: C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from fluorine, bromine, -OR 10b , -CN and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more R 9b ; or R 2 together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9b’ . In some embodiments, R 2 is selected from: C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from fluorine, bromine, -OMe, -CN and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more R 9b . In some embodiments, R2 Selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from fluorine, bromine, -OMe, -CN, and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more fluorines. In some embodiments, R 2 Selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from fluorine, bromine, -OMe, -CN, and C1 alkyl, wherein the C1 alkyl is optionally substituted with one or more fluorines.

[0573] In some embodiments, R 2 Selected from pyrazinyl (e.g., 2-pyrazinyl, 3-pyrazinyl), pyridazinyl (e.g., 3-pyridazine, 4-pyridazine, 5-pyridazine, or 6-pyridazine), phenyl, pyridinyl (e.g., 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl), and pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, or 6-pyrimidinyl), wherein each pyrazinyl, pyridazinyl (pyridizyl), phenyl, pyridinyl, and pyrimidinyl is optionally substituted with one or more substituents independently selected from fluorine, bromine, -OMe, -CN, and C1 alkyl, wherein each C1 alkyl is optionally substituted with one or more fluorines. In some embodiments, R 2 Selected from phenyl, pyridinyl, and pyrimidinyl, wherein each phenyl, pyridinyl, and pyrimidinyl is optionally substituted with one or more substituents independently selected from fluorine, bromine, -OMe, -CN, and C1 alkyl, wherein each C1 alkyl is optionally substituted with one or more fluorines. In some embodiments, R 2 Selected from phenyl, 2-pyridinyl, 2-pyrimidinyl, and 6-pyrimidinyl, wherein each phenyl, 2-pyridinyl, 2-pyrimidinyl, and 6-pyrimidinyl is optionally substituted with one or more substituents independently selected from fluorine, bromine, -OMe, -CN, and C1 alkyl, wherein each C1 alkyl is optionally substituted with one or more fluorines. In some embodiments, R 2 Selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 10b 、=O, -CN, C 1-6 alkyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and one or more substituents of 3- to 10-membered heterocyclic rings. In some embodiments, R 2 Selected from: C 3-10Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from -F, -Cl, -Br, -CN, -OH, -OCH3, -CH3, -CF3, -C(O)NH2, and -CCH.

[0574] In some embodiments, R 2 is selected from

[0575] In some embodiments, R 2 together with R 11 forms a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted by one or more R 9b’ substituents. In some embodiments, wherein R 2 together with R 11 forms a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, and wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted by one or more fluorine or CN. In some embodiments, wherein R 2 together with R 11 forms a C 3-10 carbocyclic ring or a 3- to 10-membered heterocyclic ring selected from dihydrobenzofuran and indene, each of which is optionally substituted by one or more substituents independently selected from fluorine and CN.

[0576] In some embodiments, R 2 together with R 11 is selected from In some embodiments, R 12 is H, and R 2 together with R 11 is selected from In some embodiments, R 12 is H, and R 2 together with R 11 is selected from

[0577] In some embodiments, R 2 and R 11 form a 3- to 10-membered heterocyclic ring or a C 3-10 carbocyclic ring, wherein the 3- to 10-membered heterocyclic ring or the C 3-10 carbocyclic ring is optionally substituted by one or more R 9b’ substituents. In some embodiments, R 2 and R 11Form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents selected from halogen and CN. In some embodiments, R 2 and R 11 form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents selected from fluorine and CN. In some embodiments, R 2 and R 11 form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents selected from halogen. In some embodiments, R 2 and R 11 form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents selected from fluorine. In some embodiments, R 2 and R 11 form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more substituents selected from CN.

[0578] In some embodiments, R 2 is selected from: C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from fluorine, bromine, -OMe, -CN, and C1 alkyl, wherein the C1 alkyl is optionally substituted with one or more fluorines. In some embodiments, R 2 is selected from: C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from fluorine, bromine, -CN, and C1 alkyl. In some embodiments, R 2 is selected from: C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from fluorine, bromine, -CN, and C1 alkyl.

[0579] In some embodiments, R 2 is a C 3-10 carbocycle optionally independently substituted with one or more substituents selected from fluorine, bromine, -CN, and C1 alkyl. In some embodiments, R 2is a C carbon ring optionally substituted with one or more substituents independently selected from fluorine, -CN, and C1 alkyl 3-10 In some embodiments, R 2 is a C carbon ring optionally substituted with one or more substituents independently selected from fluorine and -CN 3-10 In some embodiments, R 2 is a C carbon ring optionally substituted with one or more substituents independently selected from fluorine 3-10 In some embodiments, R 2 is a C carbon ring optionally substituted with one or more substituents independently selected from chlorine 3-10 carbon ring.

[0580] In some embodiments, for the compound or salt of formula (II), R 3 and R 4 each independently selected from:

[0581] hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN; and

[0582] optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN of a C 1-6 alkyl; or

[0583] R 3 and R 4 together form a 3- to 10-membered heterocycle or a C 3-10 carbon ring, wherein the 3- to 10-membered heterocycle or C 3-10 carbon ring is optionally substituted with one or more R 9c substituents.

[0584] In some embodiments, R 3 and R 4 each independently selected from: hydrogen; and optionally substituted with one or more substituents independently selected from halogen of a C 1-6 alkyl; or R 3 and R 4 together form a 3- to 10-membered heterocycle or a C 3-10 carbon ring, wherein the 3- to 10-membered heterocycle or C 3-10 carbon ring is optionally substituted with one or more R 9c substituents. In some embodiments, R 3 and R 4Each independently selected from: hydrogen; and optionally C alkyl substituted with one or more substituents independently selected from halogens. 1-6 alkyl.

[0585] In some embodiments, R 3 and R 4 Each independently selected from: hydrogen; and optionally C1 alkyl substituted with one or more substituents independently selected from fluorine.

[0586] In some embodiments, R 3 and R 4 Each independently selected from: hydrogen; and C1 alkyl. In some embodiments, R 3 and R 4 Each independently selected from: hydrogen. In some embodiments, R 3 Selected from: hydrogen. In some embodiments, R 4 Selected from: hydrogen. In some embodiments, R 3 is -H, and R 4 is -OH. In some embodiments, R 3 is -OH, and R 4 is -H. In some embodiments, R 3 is -OH.

[0587] In some embodiments, R 3 and R 4 Together form a 3- to 10-membered heterocycle or C 3-10 carbocycle, the 3- to 10-membered heterocycle or C 3-10 carbocycle optionally substituted with one or more R 9c substituents. In some embodiments, R 3 and R 4 Together form a C 3-10 carbocycle, the C 3-10 carbocycle optionally substituted with one or more R 9c substituents. In some embodiments, R 3 and R 4 Together form a C 3-10 carbocycle. In some embodiments, R 3 and R 4 Together form a C selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl 3-10 carbocycle. In some embodiments, R 3 and R 4 Together form a ring selected from among.

[0588] In some embodiments, for the compound or salt of formula (II), R 5 and R 6 Each independently selected from:

[0589] Hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; and

[0590] optionally independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN and substituted with one or more substituents selected from C 1-6 alkyl; or

[0591] R 5 together with R 6 forms 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 R 9d .

[0592] In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; and C 1-6 alkyl; or R 5 together with R 6 forms 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 R 9d . In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; and C 1-6 alkyl; or R 5 together with R 6 forms a 3- to 10-membered heterocycle or C 3-10 carbocycle. In some embodiments, R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; and C 1-6 alkyl. In some embodiments, R 5 and R 6Each independently selected from: hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN. In some embodiments, R 5 and R 6 are hydrogen. In some embodiments, R 5 is hydrogen. In some embodiments, R 6 is hydrogen. In some embodiments, R 5 and R 6 are each independently selected from: hydrogen; or R 5 and R 6 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9d . A compound or salt according to any one of claims 92 to 137 or claim 141, wherein R 5 and R 6 are each independently selected from: hydrogen; or R 5 and R 6 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle. In some embodiments, R 5 and R 6 are each independently selected from: hydrogen and -CH3, or R 5 and R 6 together form cyclopropyl.

[0593] In some embodiments, the compound or salt of formula (II) is a compound or salt of formula (II-Q): In some embodiments, the compound or salt of formula (II-Q) is an activator of skeletal myosin. In some embodiments, the compound or salt of formula (II-Q) is used for treating obesity or inducing weight loss. In some embodiments, for the compound or salt of formula (I-Q), R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; optionally substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 carbocycle and 3- to 10-membered heterocycle of a C 1-10 alkyl, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle is optionally independently selected from halogen, -OR10c 、 -SR 10c 、 -N(R 10c )2, -NO2 and -CN, or one or more substituents selected therefrom; and C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c )2, -NO2 and -CN, or one or more substituents selected therefrom. In some embodiments, R 5 is -H, and R 6 is selected from: C alkyl optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c )2, -NO2, -CN, C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 1-10 alkyl, wherein each C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring is optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c )2, -NO2 and -CN, or one or more substituents selected therefrom; and C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c )2, -NO2 and -CN, or one or more substituents selected therefrom. In some embodiments, R 5 is -H, and R 6 is selected from: C alkyl optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c )2, -NO2, -CN, C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 1-10 alkyl, wherein each C 3-10 carbocyclic ring and 3 - to 10 - membered heterocyclic ring is optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c )2, -NO2 and -CN, or one or more substituents selected therefrom. In some embodiments, R 5 is -H, and R 6 is selected from: C alkyl optionally independently substituted with one or more substituents selected from halogen, -OR 10c 、 -SR 10c 、 -N(R 10c)2, -NO2, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein each C 1-6 alkyl, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle are optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN. In some embodiments, R 5 is -H, and R 6 is a branched-chain (e.g., non-linear, e.g., primary, secondary, or tertiary) C 10c alkyl optionally substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 3-10 )2, -NO2, -CN, C 1-6 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle are optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN. In some embodiments, R 5 is -H, and R 6 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl, or 2-methylbutyl moiety, which is optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein each C 3-10 carbocycle and 3- to 10-membered heterocycle are optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN. In some embodiments, R 5 is -H, and R 6 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl, or 2-methylbutyl moiety, which is optionally independently substituted with one or more substituents selected from C 3-10 one or more substituents of carbocycles, wherein each C3-10 The carbocyclic ring is optionally substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, R 5 is -H, and R 6 is a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety, which is optionally substituted with one or more substituents independently selected from C 3-10 in the carbocyclic ring. In some embodiments, R 5 is -H, and R 6 is a n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, tert-pentyl, neopentyl, isopentyl, sec-pentyl, 3-pentyl, sec-isopentyl or 2-methylbutyl moiety.

[0594] In some embodiments, for the compound or salt of formula (II), R 7 is selected from: hydrogen, and C 10e alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10e , -SR 10e , -N(R 1-6 )2, -NO2 and -CN. In some embodiments, R 7 is selected from: hydrogen and C 1-3 alkyl. In some embodiments, R 7 is selected from: hydrogen.

[0595] In some embodiments, for the compound or salt of formula (II), R 8 is selected from: hydrogen, and C 10f alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10f , -SR 10f , -N(R 1-6 )2, -NO2 and -CN. In some embodiments, R 8 is selected from: hydrogen, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, R 8 is selected from: hydrogen, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from fluorine and -CN. In some embodiments, R 8 is selected from: hydrogen and C 1-3 alkyl. In some embodiments, for the compound or salt of formula (II), R 8 is selected from: hydrogen and C1 alkyl. In some embodiments, R 8 is selected from: hydrogen.

[0596] In some embodiments, for a compound or salt of formula (II), R 11 is selected from:

[0597] halogen, -NO2, -CN, -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 and -S(O)2R 10g ; and

[0598] 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 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)2R 10g , -NO2, =S, =N(R 10g ), -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 R 9g .

[0599] In some embodiments, R11 Selected from: halogen, -NO2, -CN, -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 and -OC(O)R 10g ; and C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently substituted with one or more substituents 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 , -NO2, =O, -CN and C 3-10 carbocyclic ring and one or more substituents of a 3- to 10-membered heterocyclic ring, wherein the C 3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9g substituents. In some embodiments, R 11 is selected from: halogen, -NO2, -CN, -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 and -OC(O)R 10g ; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from the following: 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, -NO2, =O, -CN, and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9g . In some embodiments, R 11 is selected from: halogen, -NO2, -CN, -OR 10g , -SR 10g and -N(R 10g )2; and optionally substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g , -N(R 10g )2, -NO2, =O, -CN, and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings of one or more substituents substituted C 1-6 alkyl, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9g . In some embodiments, R 11 is selected from: halogen, -NO2, -CN, -OR 10g , -SR 10g and -N(R 10g )2; and optionally substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g , -N(R 10g )2, -NO2, =O, and -CN of one or more substituents substituted C 1-6 alkyl. In some embodiments, R 11 is selected from: optionally substituted with one or more substituents independently selected from the following C 1-6 alkyl: 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)2R 10g , -NO2, =O, =S, =N(R 10g)、 -CN, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9g substituents. In some embodiments, R 11 is selected from: C 1-6 alkyl optionally substituted with one or more substituents independently selected from the following: 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 , -NO2, =O, -CN and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9g substituents. In some embodiments, R 11 is selected from: C 10g alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g , -N(R 10g )2, -C(O)R 3-10 , -NO2, =O, -CN and C 1-6 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more R 9g substituents. In some embodiments, R 11 is selected from: C 10g alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g , -N(R 10g )2, -C(O)R 3-10 , -NO2, =O, -CN and C 1-6 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, R 11 is selected from: C 10g alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g , -N(R 10g )2, -C(O)R 1-6Alkyl. In some embodiments, R 11 is selected from: C 10g alkyl optionally substituted with one or more substituents independently selected from halogen and -OR 1-3 Alkyl. In some embodiments, R 11 is selected from: C 10g alkyl optionally substituted with one or more -OR 1-3 substituents. In some embodiments, R 11 is selected from: C 1-3 alkyl optionally substituted with one or more -OH substituents.

[0600] In some embodiments, for a compound or salt of formula (II), R 12 is selected from:

[0601] hydrogen;

[0602] C 10h alkyl optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 1-6 ; and

[0603] C 3-6 carbocyclic and 3- to 10-membered heterocyclic rings, each optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h ; or

[0604] R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system.

[0605] In some embodiments, R 12 is selected from hydrogen; C 10h alkyl optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 1-6 ; and C 3-6 carbocyclic and 3- to 10-membered heterocyclic rings, each optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR10h , N(R 10h ), NO2, C(O)R 10h , SR 10h and S(O)R 10h ; or R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system. In some embodiments, R 12 is selected from hydrogen; C 10h alkyl optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h ), NO2, C(O)R 10h , SR 10h and S(O)R 10h ; and C 1-6 carbocyclic and 3- to 10-membered heterocyclic rings, each optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 3-6 , N(R 10h ), NO2, C(O)R 10h ), SR 10h and S(O)R 10h . In some embodiments, R 10h is selected from hydrogen; and C 12 alkyl optionally substituted with one or more substituents independently selected from halogen, CN, OH, OR 10h , N(R 10h ), NO2, C(O)R 10h and SR 10h . In some embodiments, R 1-6 is selected from hydrogen; and C 12 alkyl. 1-6

[0606] In some embodiments, R 12 is hydrogen. In some embodiments, R 12 is methyl. In some embodiments, R 12 is ethyl. In some embodiments, R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system. In some embodiments, R 12 , R 11 and R 2 together form a C5-C 10 bridged ring system selected from [1.1.1]bicyclopentane.

[0607] ​In some embodiments, for a compound or salt of formula (II), 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)2R 10a , -NO2, =O, =S, =N(R 10a ) 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 the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN. In some embodiments, each R 9a is independently selected from: halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, =O, -CN; and optionally substituted with one or more substituents independently selected from halogen, -OR 10a , -SR10a -N(R 10a )2, -C(O)R 10a , -NO2, =O, and -CN, and is substituted with one or more substituents on the C 1-3 alkyl group. In some embodiments, each R 9a is independently selected from: halogen, -NO2, =O, -CN; and optionally C 1-3 alkyl group substituted with one or more substituents independently selected from halogen, -NO2, =O, and -CN. In some embodiments, each R 9a is independently selected from: halogen and -CN; and optionally C 1-3 alkyl group substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, each R 9a is independently selected from: fluorine and -CN; and optionally C1 alkyl group substituted with one or more substituents independently selected from fluorine and -CN. In some embodiments, each R 9a is independently selected from: fluorine and -CN; and C1 alkyl group. In some embodiments, each R 9a is independently selected from: fluorine and -CN. In some embodiments, each R 9a is independently selected from: fluorine. In some embodiments, each R 9a is independently selected from: -CN.

[0608] In some embodiments, for the compound or salt of formula (II), each R 9b is independently selected from:

[0609] 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and

[0610] C 1-3 alkyl, C2-3 Alkenyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN.

[0611] In some embodiments, each R 9b is independently selected from: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN; and optionally C 10b alkyl independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 1-3 , -NO2, =O and -CN. In some embodiments, each R 9b is independently selected from: halogen, -NO2, =O, -CN; and optionally C 1-3 alkyl independently substituted with one or more substituents selected from halogen, -NO2, =O and -CN. In some embodiments, each R 9b is independently selected from: halogen. In some embodiments, each R 9b is independently selected from: fluorine. In some embodiments, each R 9b is independently selected from: halogen and -CN; and optionally C 1-3 alkyl independently substituted with one or more substituents selected from halogen and -CN. In some embodiments, each R 9bIndependently selected from: fluorine and -CN; and optionally a C1 alkyl group substituted with one or more substituents independently selected from fluorine and -CN. In some embodiments, each R 9b Independently selected from: fluorine and -CN; and a C1 alkyl group. In some embodiments, each R 9b Independently selected from: fluorine and -CN. In some embodiments, each R 9b Independently selected from: fluorine. In some embodiments, each R 9b Independently selected from: -CN. In some embodiments, each R 9b Independently selected from: -F, -Cl, -Br, -CN, -OH, -OCH3, -CH3, -CF3, -C(O)NH2, and -CCH. In some embodiments, each R 9b Independently selected from: -F, -Cl, -Br, -CN, -OH, -OCH3, -CH3 and -CF3.

[0612] In some embodiments, for the compound or salt of formula (II), each R 9b’ Independently selected from:

[0613] 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and

[0614] 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 the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN.

[0615] In some embodiments, each R 9b’ Independently selected from: halogen, -OR 10b 、-SR 10b 、-N(R 10b )2. -C(O)R 10b , -NO2, =O, -CN; and optionally independently selected from halogen, -OR 10b 、-SR 10b 、-N(R 10b )2. -C(O)R 10b C substituted with one or more of -NO2, =O and -CN 1-3 In some embodiments, each R 9b’ independently selected from: halogen, -NO2, =O, -CN; and C optionally substituted with one or more substituents independently selected from halogen, -NO2, =O and -CN 1-3 In some embodiments, each R 9b’ In some embodiments, each R 9b’ In some embodiments, each R 9b’ In some embodiments, each R 9b’ is independently selected from: fluorine, bromine and CN. 9b’ independently selected from: halogen and -CN; and C optionally substituted by one or more substituents independently selected from halogen and -CN 1-3 In some embodiments, each R 9b’ In some embodiments, each R 9b’Independently selected from: fluorine and -CN; and C1 alkyl. In some embodiments, each R 9b’ Independently selected from: fluorine and -CN. In some embodiments, each R 9b’ Independently selected from: fluorine. In some embodiments, each R 9b’ Independently selected from: -CN.

[0616] In some embodiments, for the compound or salt of formula (II), each R 9c Independently selected from:

[0617] 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and

[0618] 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 the following: 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)2R10c ,-NO2, =O, =S, =N(R 10c ), and -CN.

[0619] In some embodiments, each R 9c is independently selected from: halogen, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 10c , -NO2, =O, -CN; and optionally C 10c alkyl substituted with one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -C(O)R 1-3 , -NO2, =O, and -CN. In some embodiments, each R 9c is independently selected from: halogen, -NO2, =O, -CN; and optionally C 1-3 alkyl substituted with one or more substituents independently selected from halogen, -NO2, =O, and -CN. In some embodiments, each R 9c is independently selected from: halogen and -CN; and optionally C 1-3 alkyl substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, each R 9c is independently selected from: fluorine and -CN; and optionally C1 alkyl substituted with one or more substituents independently selected from fluorine and -CN. In some embodiments, each R 9c is independently selected from: fluorine and -CN; and C1 alkyl. In some embodiments, each R 9c is independently selected from: fluorine and -CN. In some embodiments, each R 9c is independently selected from: fluorine. In some embodiments, each R 9c is independently selected from: -CN.

[0620] In some embodiments, for the compounds or salts of formula (II), each R 9d is independently selected from:

[0621] 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN; and

[0622] C 1-3 alkyl, C 2-3 alkenyl and C 2-3 alkynyl, each of which is optionally substituted by one or more substituents independently selected from the following: 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN;

[0623] In some embodiments, each R 9d is independently selected from: halogen, -OR 10d , -SR 10d , -N(R 10d )2, -C(O)R 10d , -NO2, =O, -CN; and optionally C 10d alkyl substituted by one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -C(O)R 1-3 alkyl substituted by one or more of -NO2, =O and -CN. In some embodiments, each R 9dIndependently selected from: halogen, -NO2, =O, -CN; and optionally C1-C6 alkyl substituted with one or more substituents independently selected from halogen, -NO2, =O and -CN. 1-3 In some embodiments, each R 9d is independently selected from: halogen and -CN; and optionally C1-C6 alkyl substituted with one or more substituents independently selected from halogen and -CN. 1-3 In some embodiments, each R 9d is independently selected from: fluorine and -CN; and optionally C1 alkyl substituted with one or more substituents independently selected from fluorine and -CN. In some embodiments, each R 9d is independently selected from: fluorine and -CN; and C1 alkyl. In some embodiments, each R 9d is independently selected from: fluorine and -CN. In some embodiments, each R 9d is independently selected from: fluorine. In some embodiments, each R 9d is independently selected from: -CN.

[0624] In some embodiments, for the compound or salt of formula (II), each R 9g is independently selected from:

[0625] 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)2R 10g , -NO2, =O, =S, =N(R 10g ) and -CN; and

[0626] C1-C6 1-3 alkyl, C2-C6 2-3 alkenyl and C2-C6 2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from the following: 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)2R 10g , -NO2, =O, =S, =N(R 10g ) and -CN.

[0627] In some embodiments, each R 9g is independently selected from: halogen, -OR 10g , -SR 10g , -N(R 10g )2, -C(O)R 10g , -NO2, =O, -CN; and optionally C 10g alkyl substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g )2, -C(O)R 10g , -NO2, =O and -CN. In some embodiments, each R 1-3 is independently selected from: halogen, -NO2, =O, -CN; and optionally C 9g alkyl substituted with one or more substituents independently selected from halogen, -NO2, =O and -CN. In some embodiments, each R 1-3 is independently selected from: halogen and -CN; and optionally C 9g alkyl substituted with one or more substituents independently selected from halogen and -CN. In some embodiments, each R 1-3 is independently selected from: fluorine and -CN; and optionally C1 alkyl substituted with one or more substituents independently selected from fluorine and -CN. In some embodiments, each R 9g is independently selected from: fluorine and -CN; and C1 alkyl. In some embodiments, each R 9g is independently selected from: fluorine and -CN. In some embodiments, each R 9g is independently selected from: fluorine and -CN. In some embodiments, each R 9g is independently selected from: fluorine. In some embodiments, each R 9b is independently selected from: -CN.

[0628] In some embodiments, for a compound or salt of formula (II), each R 10a is independently selected from:

[0629] hydrogen;

[0630] 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 the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and

[0631] C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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.

[0632] In some embodiments, each R 10a is independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 3-10 carbocycle, 3- to 10-membered heterocycle; and C 1-6 carbocycle and 3- to 10-membered heterocycle. In some embodiments, each R 3-10 is independently selected from: hydrogen; and C 10a alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6An alkyl group, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl) with one or more substituents selected from the group consisting of: C 1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings.

[0633] In some embodiments, each R 10a is independently selected from: hydrogen; and optionally substituted by one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl) with one or more substituents selected from the group consisting of: C 1-6 alkyl. In some embodiments, each R 10a is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R 10a is independently selected from: hydrogen.

[0634] In some embodiments, for the compounds or salts of formula (II), each R 10b is independently selected from: each R 10b is independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic ring, 3- to 10-membered heterocyclic ring; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings and C 1-6 haloalkyl. In some embodiments, each R 10bare each independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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, a 3- to 10-membered heterocycle; and C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocycles, 3- to 10-membered heterocycles, and C 1-6 haloalkyl; In some embodiments, each R 10b is independently selected from: hydrogen; and C 1-6 alkyl optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 3-10 alkyl), C 1-6 carbocycle, a 3- to 10-membered heterocycle; and C 3-10 carbocycles and 3- to 10-membered heterocycles.

[0635] In some embodiments, each R 10b is independently selected from: hydrogen; and C 1-6 alkyl optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl); and C 3-10 carbocycles and 3- to 10-membered heterocycles. In some embodiments, each R 10bIndependently selected from: hydrogen; and optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl) and one or more substituents selected from C 1-6 alkyl. In some embodiments, each R 10b is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R 10b is independently selected from: C 1-3 alkyl.

[0636] In some embodiments, each R 10b is methyl. In some embodiments, each R 10b is hydrogen.

[0637] In some embodiments, for the compound or salt of formula (II), each R 10c is independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle and one or more substituents selected from C 3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 and one or more substituents selected from.

[0638] In some embodiments, each R 10c is independently selected from: hydrogen; and optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl), C 3-10 alkyl substituted with one or more substituents selected from carbocyclic rings, 3- to 10-membered heterocyclic rings; and C 1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, each R 10c is independently selected from: hydrogen; and optionally C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl) substituted with one or more substituents selected from: halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, each R 10c is independently selected from: hydrogen; and optionally C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl) substituted with one or more substituents selected from: halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl. In some embodiments, each R 10c is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R 10c is hydrogen.

[0639] In some embodiments, for a compound or salt of formula (II), each R 10d 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, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings; and C 3-10Carbocycles and 3- to 10-membered heterocycles, each of which is optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocycles, 3- to 10-membered heterocycles, and C 1-6 haloalkyl. In some embodiments, each R 10d is independently selected from: hydrogen; and C 1-6 alkyl optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 3-10 alkyl), C 1-6 carbocycles, 3- to 10-membered heterocycles; and C 3-10 carbocycles and 3- to 10-membered heterocycles. In some embodiments, each R 10d is independently selected from: hydrogen; and C 1-6 alkyl optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl); and C 3-10 carbocycles and 3- to 10-membered heterocycles. In some embodiments, each R 10d is independently selected from: hydrogen; and C 1-6 alkyl optionally independently substituted with one or more substituents selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl). In some embodiments, each R 10d is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R 10d is hydrogen.

[0640] In some embodiments, for a compound or salt of formula (II), each R 10e 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, -NO2, -NH2, =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 one or more substituents selected from 3- to 10-membered heterocycles; and C 3-10 carbocycles and 3- to 10-membered heterocycles, each of which is optionally substituted with one or more substituents independently selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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. In some embodiments, each R 10e is independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 3-10 alkyl), C 1-6 carbocycle, and 3- to 10-membered heterocycle; and C 3-10 carbocycles and 3- to 10-membered heterocycles. In some embodiments, each R 10e is independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl); and C 3-10 carbocycles and 3- to 10-membered heterocycles. In some embodiments, each R10e independently selected from: hydrogen; and optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -NH(C 1-6 Alkyl) substituted with one or more substituents in C 1-6 In some embodiments, each R 10e are independently selected from: hydrogen; and C 1-6 In some embodiments, each R 10e It's all hydrogen.

[0641] In some embodiments, for the compound or salt of formula (II), each R 10f Independently selected from: hydrogen; C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Alkynyl, each of which is optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -NH(C 1-6 Alkyl), C 3-10 One or more substituents in a carbocyclic ring or a 3- to 10-membered heterocyclic ring; and C 3-10 carbocyclic and 3- to 10-membered heterocyclic rings, each of which is optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, =S, -OC 1-6 Alkyl, -SC 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 Carbocyclic ring, 3- to 10-membered heterocyclic ring and C 1-6 In some embodiments, each R 10f independently selected from: hydrogen; and optionally independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -OC 1-6 Alkyl, -SC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -NH(C 1-6 Alkyl), C 3-10 One or more substituents in a carbocyclic ring or a 3- to 10-membered heterocyclic ring substituted with C1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, each R 10f is independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings. In some embodiments, each R 10f is independently selected from: hydrogen; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =O, -O-C 1-6 alkyl, -S-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH(C 1-6 alkyl. In some embodiments, each R 10f is independently selected from: hydrogen; and C 1-6 alkyl. In some embodiments, each R 10f is hydrogen.

[0642] In some embodiments, for a compound or salt of formula (II), each 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, -NO2, -NH2, =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 carbocyclic ring, 3- to 10-membered heterocyclic ring; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -OH, -SH, -NO2, -NH2, =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, C2-6 Alkynyl, C 3-10 carbocyclic ring, 3- to 10-membered het...

Claims

1. A compound represented by formula (I): or a salt thereof, wherein: X 1 , X 2 , X 3 and X 4 are each independently selected from C(R 1 ), N, and N + (-O - ), where at least one of X 1 , X 2 , X 3 or X 4 is N; and no more than two of X 1 , X 2 , X 3 and X 4 are N; Each R 1 is independently selected from: hydrogen; halogen, -NO2, -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)2R 10a ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9a ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 R 9a substituents; R 2 Selected from: C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9b ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -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 R 9b substituents; R 3 and R 4 are each independently selected from: Hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and Optionally independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN, and is substituted by one or more substituents; or 1-6 alkyl; or R 3 Together with R 4 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9c substituents; R 5 and R 6 each independently selected from: Hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; Optionally independently selected from halogen, -OR 10c 、-SR 10c 、-N(R 10c )2, -NO2, -CN, C 3-10 One or more substituents in a carbocyclic ring or a 3- to 10-membered heterocyclic ring substituted with C 1-6 Alkyl, where each C 3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are optionally independently selected from halogen, -OR 10c 、-SR 10c 、-N(R 10c )2, -NO2 and -CN are substituted with one or more substituents; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or R 5 Together with R 6 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9c substituents; R 7 Selected from: Hydrogen, and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; 1-6 alkyl; R 8 Selected from: hydrogen; and Optionally independently selected from halogen, -OR 10e 、-SR 10e 、-N(R 10e )2, -NO2, -CN, C 3-10 One or more substituents in a carbocyclic ring or a 3- to 10-membered heterocyclic ring substituted with C 1-6 Alkyl, where each C 3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are optionally independently selected from halogen, -OR 10e 、-SR 10e 、-N(R 10e )2, -NO2 and -CN are substituted with one or more substituents; 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; Each R 9b is 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and Each R 10a , R 10b , R 10c , R 10d , and R 10e is independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings and C 1-6 haloalkyl; Wherein if X 3 and X 1 are both N, then R 8 is selected from hydrogen and optionally C 10 alkyl substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 , -N(R 1-4 )2, -NO2 and -CN; and Wherein if X 4 and X 2 are both N, then R 8 is selected from hydrogen and optionally C 10 alkyl substituted with one or more substituents independently selected from halogen, -OR 10 , -SR 10 , -N(R 1-4 ). The compound or salt according to claim 1, wherein X 1 , X 2 , X 3 and X 4 are each independently selected from C(R 1 ) and N.

2. The compound or salt according to claim 1, wherein one of X 1 , X 2 , X 3 or X 4 is N.

3. The compound or salt according to claim 2, wherein X 1 is N.

4. The compound or salt according to claim 2, wherein X 2 is N.

5. The compound or salt according to claim 2, wherein X 3 is N.

6. The compound or salt according to claim 2, wherein X 4 is N.

7. The compound or salt according to claim 1, wherein two of X 1 , X 2 , X 3 and X 4 are N.

8. A compound or salt according to any one of claims 1 to 7, wherein each R 1 is independently selected from: hydrogen; halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a and -C(O)N(R 10a )2; Optionally and independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -NO2, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein said C 1-6 alkyl, and wherein said C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9a ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a , -C(O)N(R 10a )2, -CN, C 9a alkyl optionally substituted by one or more R 1-6 groups.

9. The compound or salt according to any one of claims 1 to 8, wherein each R 1 is independently selected from: hydrogen; halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a and -C(O)N(R 10a )2; Optionally independently selected from halogen, -OR 10a , -SR 10a and -N(R 10a )2, and one or more substituents substituted C 1-6 alkyl; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10a , -SR 10a and -N(R 10a )2 10. A compound or salt according to any one of claims 1 to 9, wherein each R 1 is independently selected from: hydrogen, fluorine, chlorine, bromine, -CN, -OH, -O(C 1-6 alkyl), -O(C 1-6 haloalkyl), -O(C 3-10 carbocycle), -O(3- to 10-membered heterocycle), -C(O)NH2, C 1-6 alkyl, C 1-6 haloalkyl and C 3-10 carbocycle, wherein the C 3-10 carbocycle is optionally substituted with one or more halogens.

11. The compound or salt according to any one of claims 1 to 10, wherein each R 1 is independently selected from hydrogen, -CN, -OH, -OMe, -OEt, -OiPr, -F, -Cl, -Br, -Me, -Et, -CF3, -CHF2, -CH2F, OCF3, -OCHF2, -OCH2F, -C(O)NH2, 12. A compound or salt according to any one of claims 1 to 11, wherein each R 1 is independently selected from hydrogen, -CN and -F.

13. The compound or salt according to any one of claims 1 to 12, wherein R 2 is selected from: Optionally independently selected from halogen, -OR 10b 、-SR 10b 、-N(R 10b )2, -CN, =O, C 3-10 One or more substituents in a carbocyclic ring or a 3- to 10-membered heterocyclic ring substituted with C 1-6 Alkyl, wherein the C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring are each optionally substituted with one or more R 9b Replacement; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, =O, -CN and C 1-6 alkyl groups, where each C 1-6 alkyl group is optionally substituted with one or more R 9b substituents.

14. A compound or salt according to any one of claims 1 to 13, wherein R 2 is selected from: Optionally independently selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, -CN, =O, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein said C 1-6 alkyl, and wherein said C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9b ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , -SR 10b , -N(R 10b )2, =O, -CN and C 1-6 alkyl groups, where each C 1-6 alkyl group is optionally substituted with one or more R 9b substituents.

15. The compound or salt according to any one of claims 1 to 14, wherein R 2 is selected from: Optionally and independently selected from -F, Cl, -OH, and C 3-10 alkyl substituted by one or more substituents selected from carbocyclic rings and 3- to 10-membered heterocyclic rings 1-6 alkyl, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9b substituents; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from -F, -Cl and -CN.

16. The compound or salt according to any one of claims 1 to 15, wherein R 2 is selected from C2 alkyl optionally substituted with one or more substituents independently selected from C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein the C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are each optionally substituted with one or more substituents independently selected from -F, -Cl, and -CN.

17. The compound or salt according to any one of claims 1 to 16, wherein R 2 is a substituent represented by the following formula: wherein, Q 1 is a C1 alkyl optionally substituted with one or more substituents selected from -OH and -F; Y 1 and Y 2 each independently selected from N and C(Q 3 )); and Each Q 2 is independently selected from halogen and -CN; Each Q 3 is independently selected from hydrogen, halogen, and -CN; and n is 0, 1 or 2.

18. The compound or salt according to claim 17, wherein Q 1 is -CH3; each Q 2 is independently selected from -F and -CN; and each Q 3 is independently selected from hydrogen, -F and -CN.

19. A compound or salt according to any one of claims 1 to 14, wherein R 2 is selected from:

20. A compound or salt according to any one of claims 1 to 19, wherein R 3 and R 4 are each independently selected from: hydrogen and -OH; and Optionally independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2 and -CN, and is substituted with one or more substituents; or a C 1-6 alkyl; or R 3 Together with R 4 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9c substituents.

21. The compound or salt according to any one of claims 1 to 20, wherein R 3 and R 4 are each independently selected from: hydrogen, -OH and C1 alkyl.

22. The compound or salt according to any one of claims 1 to 21, wherein R 5 and R 6 are each independently selected from: hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and C 1-6 alkyl; or R 5 and R 6 together form a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted with one or more R 9c .

23. The compound or salt according to any one of claims 1 to 22, wherein R 5 and R 6 are each independently selected from: hydrogen and C 1-3 alkyl.

24. The compound or salt according to any one of claims 1 to 23, wherein R 7 is selected from hydrogen and C 1-6 alkyl.

25. The compound or salt according to any one of claims 1 to 24, wherein R 8 is selected from: hydrogen; and C 1-6 alkyl.

26. The compound or salt according to any one of claims 1 to 25, wherein R 8 is selected from hydrogen.

27. The compound or salt according to any one of claims 1 to 26, wherein each R 9a is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

28. The compound or salt according to any one of claims 1 to 27, wherein each R 9b is 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 , -NO2, =O and -CN; and Optionally and 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 , -NO2, =O and -CN, and is substituted with one or more substituents on the C 1-3 alkyl group.

29. The compound or salt according to any one of claims 1 to 28, wherein each R 9b is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

30. The compound or salt according to any one of claims 1 to 29, wherein each R 9b is independently selected from halogen and -CN.

31. The compound or salt according to any one of claims 1 to 30, wherein each R 9c is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

32. The compound or salt according to any one of claims 1 to 31, wherein each R 10a , R 10b , R 10c , R 10d , and R 10e is independently selected from hydrogen, C 1-6 alkyl, C 3-10 carbocycle, and 3- to 10-membered heterocycle.

33. The compound or salt according to any one of claims 1 to 32, wherein each R 10a , R 10b , R 10c , R 10d , and R 10e is independently selected from hydrogen.

34. A compound or salt according to any one of claims 1 to 33, wherein if X 3 and X 1 are both N, then R 8 is selected from hydrogen.

35. The compound according to claim 1, wherein the compound is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13, N123, N31, N26, N18, N74, N68, N101, N102, N41, N125, N15, N54, N9, N119, N126, N104, N37, N129, N62, N118, N95, N121, N47, N28, N111, N114, N112, N103, N136, N122, N19, N8, N10, N21, N133, N44, N110, N77, N36, N120, N78, N2, N24, N6, N72, N116, N108, N39, N98, N127, N113, N60, N132, N1, N3, N11, N12, N14, N16, N17, N20, N22, N25, N27, N29, N30, N32, N34, N35, N38, N40, N42, N43, N45, N46, N48, N49, N50, N51, N52, N53, N55, N56, N57, N58, N59, N61, N63, N64, N65, N66, N67, N69, N70, N71, N73, N75, N76, N79, N80, N82, N83, N84, N85, N86, N89, N90, N91, N92, N93, N96, N97, N99, N100, N105, N106, N107, N109, N130, N131 and N135 or a salt of any one thereof.

36. The compound according to claim 1, wherein the compound is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13, N123, N31, N26, N18, N74, N68, N101, N102, N41, N125, N15, N54, N9, N119, N126, N104, N37, N129, N62, N118, N95, N121, N47, N28, N111, N114, N112 and N103 or a salt of any one thereof.

37. The compound according to claim 1, wherein the compound is selected from: N5, N23, N87, N124, N128, N7, N33, N117, N4, N94, N81, N88, N115, N13 and N123 or a salt of any one thereof.

38. A compound represented by formula (II): or a salt thereof, wherein: n is 0, 1, 2, 3 or 4; Each R 1 is independently selected from: halogen, -NO2, -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)2R 10a ; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9a ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 R 9a ; R 2 Selected from: halogen, -NO2, -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)2R 10b ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9b ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, where C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with one or more R 9b ; or R 2 Together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9b’ substituents; R 3 and R 4 each independently selected from: Hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and Optionally independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN, and is substituted by one or more substituents; or 1-6 alkyl; or R 3 Together with R 4 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9c substituents; R 5 and R 6 are each independently selected from: Hydrogen, halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; and Optionally independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN, and substituted by one or more substituents of C 1-6 alkyl; or R 5 Together with R 6 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9d substituents; R 7 Selected from: Hydrogen, and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10e , -SR 10e , -N(R 10e )2, -NO2 and -CN; 1-6 alkyl; R 8 Selected from: Hydrogen, and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10f , -SR 10f , -N(R 10f )2, -NO2 and -CN; 1-6 alkyl; R 11 Selected from: halogen, -NO2, -CN, -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 and -S(O)2R 10g ; and C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10g , -NO2, =S, =N(R 10g ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, where the C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9g ; R 12 Selected from: hydrogen; Optionally independently selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h substituted C 1-6 alkyl; and C 3-6 carbocyclic rings and 3- to 10-membered heterocyclic rings, each optionally independently substituted with one or more substituents selected from halogen, CN, OH, OR 10h , N(R 10h )2, NO2, C(O)R 10h , SR 10h and S(O)R 10h ; or R 12 , R 11 and R 2 Together they form C5-C 10 Bridged ring system; 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; Each R 9b is 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the group consisting of: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; Each R 9b’ is 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently with one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) 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)2R 10d , -NO2, =O, =S, =N(R 10d ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10d , -NO2, =O, =S, =N(R 10d ) 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)2R 10g , -NO2, =O, =S, =N(R 10g ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the group consisting of: 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)2R 10g , -NO2, =O, =S, =N(R 10g ) and -CN; Each R 10a 、R 10b 、R 10c 、R 10d 、R 10e 、R 10f 、R 10g 、R 10h is independently selected from: hydrogen; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently substituted by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently by one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings and C 1-6 haloalkyl.

39. The compound or salt according to claim 38, wherein n is 1.

40. The compound or salt according to claim 38, wherein n is 2.

41. A compound or salt according to any one of claims 38 to 40, wherein each R 1 is independently selected from: Halogen, -NO2, -CN, -OR 10a , -SR 10a , -N(R 10a )2, -C(O)R 10a ; Optionally independently selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, =O, -CN, C 3-10 alkyl substituted with one or more substituents selected from carbocycles and 3- to 10-membered heterocycles, wherein said C 1-6 alkyl, and said C 3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R 9a ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10a , -SR 10a , -N(R 10a )2, =O, -CN and C 1-6 alkyl groups, wherein each C 1-6 alkyl group is optionally substituted with one or more R 9a substituents.

42. A compound or salt according to any one of claims 38 to 41, wherein each R 1 is independently selected from: halogen, -CN, -OR 10a , -SR 10a , -N(R 10a )2; and optionally C 10a alkyl which is independently substituted with one or more substituents selected from halogen, -OR 10a , -SR 10a , -N(R 1-6 ), =O and -CN.

43. A compound or salt according to any one of claims 38 to 42, wherein each R 1 is independently selected from: halogen, -CN, -OR 10a and C 1-6 alkyl.

44. A compound or salt according to any one of claims 38 to 43, wherein each R 1 is independently selected from: -F, -Br, -CN, -OH and -CH3.

45. A compound or salt according to any one of claims 38 to 44, wherein each R 1 is independently selected from: -F and -CN.

46. A compound or salt according to any one of claims 38 to 45, wherein R 2 is selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -OR 10b , -SR 10b , -N(R 10b )2, -C(O)R 10b , -NO2, =O, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, where each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings are optionally substituted with one or more R 9b ; or R 2 Together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9b’ substituents.

47. A compound or salt according to any one of claims 38 to 46, wherein R 2 is selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted by one or more substituents selected from halogen, -OR 10b , =O, -CN, C 1-6 alkyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, wherein each C 1-6 alkyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings is optionally substituted by one or more R 9b .

48. A compound or salt according to any one of claims 38 to 47, wherein R 2 is selected from: C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10b , =O, -CN, C 1-6 alkyl, C 2-6 alkynyl, C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings.

49. A compound or salt according to any one of claims 38 to 48, wherein R 2 is selected from: C 6-10 carbocyclic rings and 5- to 10-membered heterocyclic rings, each of which is optionally substituted by one or more substituents independently selected from -F, -Cl, -Br, -CN, -OH, -OCH3, -CH3 and -CF3.

50. A compound or salt according to any one of claims 38 to 49, wherein R 2 is selected from: C 6-10 carbocyclic rings and 5- to 10-membered heterocyclic rings, each of which is optionally substituted with one or more substituents independently selected from -F and -CN.

51. The compound or salt according to any one of claims 38 to 50, wherein R 2 is selected from:

52. The compound or salt according to any one of claims 38 to 45, wherein R 2 together with R 11 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted with one or more R 9b’ substituents.

53. A compound or salt according to any one of claims 38 to 45 or claim 52, wherein R 2 With R 11 Together they form C 3-10 A carbocyclic ring or a 3- to 10-membered heterocyclic ring selected from dihydrobenzofuran and indene, each of which is optionally substituted with one or more substituents independently selected from fluorine and CN.

54. The compound or salt according to claim 53, wherein R 12 is H; and R 2 together with R 11 forms a moiety selected from the following:

55. A compound or salt according to any one of claims 38 to 54, wherein R 3 and R 4 are each independently selected from: hydrogen, -OH, and C1 alkyl.

56. The compound or salt according to any one of claims 38 to 55, wherein R 3 together with R 4 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or the C 3-10 carbocycle is optionally substituted with one or more R 9c substituents.

57. A compound or salt according to any one of claims 38 to 55, wherein R 3 together with R 4 forms a ring selected from the following:

58. A compound or salt according to any one of claims 38 to 57, wherein R 5 and R 6 are each independently selected from: hydrogen and C 1-6 alkyl.

59. A compound or salt according to any one of claims 38 to 58, wherein R 5 and R 6 are each independently selected from: hydrogen and -CH3, or R 5 and R 6 together form cyclopropyl.

60. A compound or salt according to any one of claims 38 to 59, wherein R 7 is selected from hydrogen and C 1-6 alkyl.

61. The compound or salt according to any one of claims 38 to 60, wherein R 8 is selected from: hydrogen; and C 1-6 alkyl.

62. The compound or salt according to any one of claims 38 to 61, wherein R 11 is selected from: C 10g alkyl optionally substituted with one or more substituents independently selected from halogen, -OR 10g , -SR 10g , -N(R 10g )2, -C(O)R 1-6 , -NO2, =O and -CN.

63. A compound or salt according to any one of claims 38 to 62, wherein R 11 is selected from: C 1-3 alkyl optionally substituted by one or more -OH.

64. A compound or salt according to any one of claims 38 to 63, wherein R 12 is hydrogen.

65. A compound or salt according to any one of claims 38 to 64, wherein each R 9a is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

66. A compound or salt according to any one of claims 38 to 65, wherein each R 9b is 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 , -NO2, =O and -CN; C 1-3 alkyl and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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 , -NO2, =O and -CN; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings.

67. A compound or salt according to any one of claims 38 to 66, wherein each R 9b is independently selected from: -F, -Cl, -Br, -CN, -OH, -OCH3, -CH3, -CF3, -C(O)NH2, and -CCH.

68. A compound or salt according to any one of claims 38 to 67, wherein each R 9b is independently selected from: -F, -Cl, -Br, -CN, -OH, -OCH3, -CH3 and -CF3.

69. A compound or salt according to any one of claims 38 to 68, wherein each R 9b’ is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

70. A compound or salt according to any one of claims 38 to 69, wherein each R 9c is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

71. A compound or salt according to any one of claims 38 to 70, wherein each R 9d is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

72. A compound or salt according to any one of claims 38 to 71, wherein each R 9g is independently selected from: halogen, -OR 10a , -CN and C 1-3 alkyl.

73. A compound or salt according to any one of claims 38 to 72, wherein each R 10a , R 10b , R 10c , R 10d , R 10e , R 10f , R 10g and R 10h is independently selected from hydrogen, C 1-6 alkyl, C 3-10 carbocycle and 3- to 10-membered heterocycle.

74. The compound according to claim 38, selected from: B75, B36, B23, B9, B62, B31, B45, B123, B43, B206, B39, B324, B145, B92, B83, B55, B142, B82, B1, B322, B326, B33, B307, B77, B189, B147, B120, B14, B13, B57, B278, B303, B315, B319, B332, B128, B221, B78, B118, B4, B139, B355, B356, B12, B238, B6, B269, B281, B229, B121, B65, B114, B132, B306, B312, B17, B225, B330, B191, B226, B236, B113, B320, B214, B89, B227, B233, B336, B248, B152, B247, B69, B323, B358, B164, B126, B76, B295, B341, B310, B176, B296, B232, B81, B329, B222, B284, B79, B106, B37, B314, B350, B44, B292, B94, B32, B367, B110, B199, B101, B64, B8, B249, B116, B29, B137, B279, B100, B272, B136, B366, B91, B349, B264, B217, B130, B35, B59, B54, B321, B202, B362, B16, B70, B103, B68, B241, B169, B266, B327, B41, B204, B300, B52, B84, B234, B231, B334, B346, B338, B188, B230, B46, B291, B124, B181, B133, B117, B56, B87, B228, B339, B73, B297, B353, B210, B112, B88, B352, B25, B154, B80, B7, B302, B268, B141, B155, B42, B325, B108, B34, B223, B38, B354, B313, B267, B304, B58, B160, B97, B244, B342, B290, B288, B265, B93, B148, B102, B105, B22, B283, B280, B348, B337, B53, B119, B2, B237, B10, B286, B344, B67, B360, B309, B156, B243, B245, B301, B212, B27The salt of B135, B205, B40, B172, B273, B150, B203, B276, B85, B163, B170, B294, B193, B71, B50, B161, B49, B256, B144, B190, B3, B271, B140, B184, B250, B252, B48, B331, B146, B98, B277, B246, B194, B200, B311, B134, B274, B127, B47, B5, B11, B15, B18, B19, B20, B21, B24, B26, B28, B30, B51, B60, B61, B63, B66, B72, B74, B86, B90, B95, B96, B99, B104, B107, B109, B111, B115, B122, B125, B129, B131, B138, B143, B149, B151, B153, B157, B158, B159, B162, B165, B166, B167, B168, B171, B173, B174, B175, B177, B178, B179, B180, B182, B183, B185, B186, B187, B192, B195, B196, B197, B198, B201, B207, B208, B209, B211, B213, B215, B216, B218, B219, B220, B224, B235, B239, B240, B242, B251, B253, B254, B255, B270, B275, B282, B285, B287, B289, B299, B308, B328, B333, B335, B340, B343, B345, B347, B351, B357, B359, B361, B363, B364, B365, B257, B258, B259, B262, B263 and B293 or any one of them.、 75. The compound according to claim 38, selected from: B75, B36, B23, B9, B62, B31, B45, B123, B43, B206, B39, B324, B145, B92, B83, B55, B142, B82, B1, B322, B326, B33, B307, B77, B189, B147, B120, B14, B13, B57, B278, B303, B315, B319, B332, B128, B221, B78, B118, B4, B139, B355, B356, B12, B238, B6, B269, B281, B229, B121, B65, B114, B132, B306, B312, B17, B225, B330, B191, B226, B236, B113, B320, B214, B89, B227, B233, B336, B248, B152, B247, B69, B323, B358, B164, B126, B76, B295, B341, B310, B176, B296, B232, B81, B329, B222, B284, B79, B106, B37, B314, B350, B44, B292, B94, B32, B367, B110, B199, B101, B64, B8, B249, B116, B29, B137, B279, B100, B272, B136, B366, B91, B349, B264, B217, B130, B35, B59, B54, B321, B202, B362, B16, B70, B103, B68, B241, B169, B266, B327, B41, B204, B300, B52, B84, B234, B231, B334, B346, B338, B188, B230, B46, B291, B124, B181, B133, B117, B56, B87, B228, B339, B73, B297, B353, B210, B112, B88, B352, B25, B154, B80, B7, B302, B268, B141, B155, B42, B325, B108, B34, B223, B38, B354, B313, B267, B304, B58, B160, B97, B244, B342, B290, B288, B265, B93, B148, B102, B105, B22, B283, B280, B348, B337, B53, B119, B2, B237, B10, B286, B344, B67 and B360 or a salt of any one thereof.

76. The compound according to claim 38, selected from: B75, B36, B23, B9, B62, B31, B45, B123, B43, B206, B39, B324, B145, B92, B83, B55, B142, B82, B1, B322, B326, B33, B307, B77, B189, B147, B120, B14, B13, B57, B278, B303, B315, B319, B332, B128, B221, B78, B118, B4, B139, B355, B356, B12, B238, B6, B269, B281, B229, B121, B65, B114, B132, B306, B312, B17, B225, B330, B191, B226, B236, B113, B320, B214, B89, B227, B233, B336, B248, B152, B247, B69, B323, B358, B164, B126, B76, B295, B341, B310, B176, B296, B232, B81, B329, B222, B284, B79, B106, B37, B314, B350, B44, B292, B94, B32, B367, B110, B199, B101, B64, B8, B249, B116, B29, B137, B279, B100, B272, B136, B366, B91, B349, B264, B217, B130, B35, B59, B54 and B321 or a salt of any one thereof.

77. A method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

78. A method of treating diastolic dysfunction or related conditions, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

79. A method of treating a condition selected from: hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); heart failure with mid-range ejection fraction; relaxation disorders; chamber stiffness disorders (diabetic HFpEF); dilated cardiomyopathy (dCM); ischemic cardiomyopathy; cardiac allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease; left ventricular (LV) hypertrophy; right ventricular (RV) hypertrophy; acute myocardial infarction; acute revascularization; ischemia; and angina. The method comprises administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

80. The method according to claim 79, wherein the heart failure with preserved ejection fraction (HFpEF) comprises one or more conditions selected from relaxation disorders and chamber stiffness disorders.

81. The method according to claim 79, wherein the left ventricular (LV) hypertrophy is malignant left ventricular (LV) hypertrophy.

82. The method according to claim 79, wherein the restrictive cardiomyopathy comprises one or more subgroups selected from the inflammatory subgroup, the infiltrative subgroup, the storage subgroup, the idiopathic / hereditary subgroup, and the congenital heart disease subgroup.

83. The method according to claim 79, wherein the inflammatory subgroup comprises one or more subgroups selected from Loefller and EMF.

84. The method according to claim 79, wherein the inflammatory subgroup comprises one or more subgroups selected from amyloidosis, sarcoidosis, and XRT.

85. The method according to claim 79, wherein the storage subgroup comprises one or more subgroups selected from hemochromatosis, Fabry disease, and glycogen storage diseases.

86. The method according to claim 79, wherein the idiopathic / hereditary subgroup comprises one or more subgroups selected from Trop I (β-myosin HC), Trop T (α-cardiac actin), and desmin-related subgroups.

87. The method according to claim 79, wherein the congenital heart disease subgroup comprises one or more subgroups selected from pressure-overloaded RV, tetralogy of Fallot, and pulmonary stenosis.

88. A method of treating hypertrophic cardiomyopathy or related conditions, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

89. A method of treating obstructive hypertrophic cardiomyopathy, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

90. A method of treating non-obstructive hypertrophic cardiomyopathy, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

91. A method of treating heart failure with preserved ejection fraction, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

92. A method of treating left ventricular stiffness, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 76.

93. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 76 and a pharmaceutically acceptable excipient.

94. A method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a compound or salt of formula (III): or a salt thereof, wherein X 1 , X 2 , X 3 and X 4 Each independently selected from C(R 1 ), N and N + (-O - ); Each R 1 is independently selected from: hydrogen; Halogen, -NO2, -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)2R 10a ; C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9a ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10a , -NO2, =O, =S, =N(R 10a ), -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 R 9a ; R 2 Selected from: C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is optionally substituted independently by one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -CN, C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring, wherein said C 3-10 carbocyclic ring and 3- to 10-membered heterocyclic ring are each optionally substituted by one or more R 9b ; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ), -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 R 9b ; R 3 and R 4 are each independently selected from: Hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; and Optionally independently selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN, and is substituted with one or more substituents; or 1-6 alkyl; or R 3 Together with R 4 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9c substituents; R 5 and R 6 each independently selected from: Hydrogen, halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which, upon each occurrence, is optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, -CN, and C 3-10 carbocyclic ring and one or more substituents of a 3- to 10-membered heterocyclic ring, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2, and -CN; and C 3-10 carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally independently substituted with one or more substituents selected from halogen, -OR 10c , -SR 10c , -N(R 10c )2, -NO2 and -CN; or R 5 Together with R 6 forms a 3- to 10-membered heterocycle or a C 3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C 3-10 carbocycle is optionally substituted by one or more R 9c substituents; R 7 Selected from: Hydrogen, and optionally C alkyl substituted with one or more substituents independently selected from halogen, -OR 10d , -SR 10d , -N(R 10d )2, -NO2 and -CN; 1-6 alkyl; R 8 Selected from: hydrogen; and Optionally independently selected from halogen, -OR 10e 、-SR 10e 、-N(R 10e )2, -NO2, -CN, C 3-10 One or more substituents in a carbocyclic ring or a 3- to 10-membered heterocyclic ring substituted with C 1-6 Alkyl, where each C 3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings are optionally independently selected from halogen, -OR 10e 、-SR 10e 、-N(R 10e )2, -NO2 and -CN are substituted with one or more substituents; 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the group consisting of: 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)2R 10a , -NO2, =O, =S, =N(R 10a ) and -CN; Each R 9b is 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)2R 10b , -NO2, =O, =S, =N(R 10b ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10b , -NO2, =O, =S, =N(R 10b ) 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; and C 1-3 alkyl, C 2-3 alkenyl, and C 2-3 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: 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)2R 10c , -NO2, =O, =S, =N(R 10c ) and -CN; Each R 10a 、R 10b 、R 10c 、R 10d 、R 10e is independently selected from: hydrogen; and C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, each of which is optionally independently substituted with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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, 3- to 10-membered heterocycle; and C 3-10 Carbocyclic rings and 3- to 10-membered heterocyclic rings, each of which is optionally substituted independently with one or more substituents selected from the following: halogen, -CN, -OH, -SH, -NO2, -NH2, =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 carbocyclic rings, 3- to 10-membered heterocyclic rings and C 1-6 haloalkyl.

95. The method according to claim 94, wherein the cardiovascular disease or related condition is selected from: hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); heart failure with mid-range ejection fraction; relaxation disorders; chamber stiffness disorders (diabetic HFpEF); dilated cardiomyopathy (dCM); ischemic cardiomyopathy; cardiac allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease; left ventricular (LV) hypertrophy; right ventricular (RV) hypertrophy; acute myocardial infarction; acute revascularization; ischemia; and angina.

96. The method according to claim 95, wherein the heart failure with preserved ejection fraction (HFpEF) comprises one or more conditions selected from relaxation disorders and chamber stiffness disorders (diabetic HFpEF).

97. The method according to claim 95, wherein the left ventricular (LV) hypertrophy is malignant left ventricular (LV) hypertrophy.

98. The method according to claim 95, wherein the restrictive cardiomyopathy comprises one or more subgroups selected from an inflammatory subgroup, an infiltrative subgroup, a storage subgroup, an idiopathic / hereditary subgroup, and a congenital heart disease subgroup.

99. The method according to claim 98, wherein the inflammatory subgroup comprises one or more subgroups selected from Loefller and EMF.

100. The method according to claim 98, wherein the inflammatory subgroup comprises one or more subgroups selected from amyloidosis, sarcoidosis, and XRT.

101. The method according to claim 98, wherein the storage subgroup comprises one or more subgroups selected from hemochromatosis, Fabry disease, and glycogen storage diseases.

102. The method according to claim 98, wherein the idiopathic / hereditary subgroup comprises one or more subgroups selected from Trop I (β-myosin HC), Trop T (α-cardiac actin), and desmin-related subgroups. The method according to claim 98, wherein the congenital heart disease subgroup comprises one or more subgroups selected from pressure-overloaded RV, tetralogy of Fallot, and pulmonary artery.

103. The method according to claim 94, wherein the cardiovascular disease or related condition is obstructive hypertrophic cardiomyopathy.

104. The method according to claim 94, wherein the cardiovascular disease or related condition is non-obstructive hypertrophic cardiomyopathy.

105. The method according to claim 94, wherein the cardiovascular disease or related condition is heart failure with preserved ejection fraction.

106. The method according to claim 94, wherein the cardiovascular disease or related condition is left ventricular stiffness.

107. The method according to any one of claims 94 to 106, further comprising administering an additional active agent.

108. A method of modulating myosin regulatory light chain, the method comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 73.

109. The method according to claim 108, wherein the regulatory light chain is cardiac myosin regulatory light chain.

110. The method according to claim 108 or claim 109, wherein administering to a subject in need thereof a compound or salt according to any one of claims 1 to 73 inhibits the regulatory light chain.

111. The method according to claim 108 or claim 109, wherein administering to a subject in need thereof a compound or salt according to any one of claims 1 to 73 activates the regulatory light chain.

112. The method according to any one of claims 108 to 111, wherein administering to a subject in need a compound or salt according to any one of claims 1 to 73 enhances the ability of the myosin lever arm to exert force.

113. The method according to any one of claims 108 to 112, wherein administering to a subject in need a compound or salt according to any one of claims 1 to 73 reduces the ability of the myosin lever arm to exert force.

114. The method according to any one of claims 108 to 113, wherein administering to a subject in need a compound or salt according to any one of claims 1 to 73 overcomes a dysregulation of the interaction between the myosin regulatory light chain and the myosin heavy chain.

115. The method according to claim 114, wherein the dysregulation is caused by a gene mutation.

116. A method of treating a cardiovascular disease or related condition, the method comprising administering to a subject in need a compound that modulates the myosin regulatory light chain.

117. The method according to claim 116, wherein the cardiovascular disease or related condition is selected from hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); heart failure with mid-range ejection fraction; relaxation disorders; chamber stiffness disorders (diabetic HFpEF); dilated cardiomyopathy (dCM); ischemic cardiomyopathy; cardiac allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease; left ventricular (LV) hypertrophy; right ventricular (RV) hypertrophy; acute myocardial infarction; acute revascularization; ischemia; and angina.

118. The method according to claim 117, wherein the cardiovascular disease or related condition is selected from hypertrophic cardiomyopathy (HCM).

119. The method according to any one of claims 116 to 118, wherein the compound is a compound or salt according to any one of claims 1 to 73.

120. The method according to any one of claims 116 to 119, wherein the compound is not mavacamten.

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