CD73 inhibitors

Abstract

Described herein are CD73 inhibitors and pharmaceutical compositions comprising the compounds. The compounds and compositions of the invention are useful for the treatment of cancer, infections and neurodegenerative diseases.

Description

[0001] This application is a divisional application of the Chinese patent application with an application date of April 30, 2019, application number 201980044455.4, and invention name “CD73 inhibitor” (the corresponding PCT application with an application date of April 30, 2019, application number PCT / US2019 / 030068).

[0002] Cross-references

[0003] This application claims the benefit of U.S. application serial number 62 / 664,841, filed April 30, 2018, U.S. application serial number 62 / 737,647, filed September 27, 2018, U.S. application serial number 62 / 757,714, filed November 8, 2018, U.S. application serial number 62 / 777,697, filed December 10, 2018, and U.S. application serial number 62 / 810,790, filed February 26, 2019, which are incorporated herein by reference in their entireties. Background Art

[0004] There is a need in the art for effective treatments for cancer, infection, and neurodegenerative diseases. Summary of the Invention

[0005] Provided herein are compounds of formula (II) and (IV) or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof, and pharmaceutical compositions comprising the compounds. The compounds and compositions of the present invention can be used as CD73 inhibitors. In addition, the compounds and compositions of the present invention can be used to treat cancer, infection, and neurodegenerative diseases.

[0006] Provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variations thereof:

[0007]

[0008] in:

[0009] Ring A is Q 1 N and Q 2 CW or Q 1 N and Q 2 is N;

[0010] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0011] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0012] A is -O-;

[0013] X is -S- or -O-;

[0014] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0015] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0016] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NRb C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0017] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0018] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0019] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0020] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0021] R 8 For hydrogen, halogen, -OR b 、-NRc R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0022] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0023] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0024] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0025] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0026] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0027] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0028] Each R 13R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0029] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0030] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0031] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0032] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0033] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0034] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0035] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0036] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0037] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0038] Each R c and R dis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0039] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0040] Also provided herein are compounds having the structure of Formula (IV), or pharmaceutically acceptable salts, solvates, stereoisomers or isotopic variations thereof:

[0041]

[0042] in:

[0043] Ring A is

[0044] Q 2 N or CW;

[0045] Q 3 N and Q 4 For CW;

[0046] or Q 3 CW and Q 4 is N;

[0047] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0048] A is -O- or -CH2-;

[0049] X is -O-, -S-, -S(=O)2-, -NR 17 -or-C(R 18 )2-;

[0050] R 1 and R 2R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0051] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0052] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0053] R 3 For hydrogen, halogen, -CN, -OR b 、-SRb 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0054] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0055] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0056] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0057] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0058] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0059] R 11 For hydrogen, halogen, -CN, -OR 13 、-SR 13、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0060] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0061] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0062] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R11c replace;

[0063] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0064] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0065] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0066] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0067] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0068] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -ORb 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0069] R 17 is hydrogen, -CN, -OR b 、-S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0070] Each R 18 are independently hydrogen, halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR bC(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0071] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0072] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0073] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0074] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0075] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0076] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0077] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0078] Also disclosed herein are pharmaceutical compositions comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, and a pharmaceutically acceptable excipient.

[0079] Also disclosed herein are methods of inhibiting CD73 comprising contacting CD73 with a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof.

[0080] Also disclosed herein are methods of treating cancer in a subject, comprising administering to the subject a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, or administering to the subject a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, and a pharmaceutically acceptable excipient.

[0081] Also disclosed herein are methods of treating an infection in a subject, comprising administering to the subject a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, or administering to the subject a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, and a pharmaceutically acceptable excipient.

[0082] Also disclosed herein are methods of treating a neurodegenerative disease in a subject, comprising administering to the subject a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, or administering to the subject a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof, and a pharmaceutically acceptable excipient.

[0083] Incorporation by reference

[0084] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference for the specific purposes described herein. DETAILED DESCRIPTION

[0085] CD73 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that catalyzes the hydrolysis of AMP to adenosine and works in conjunction with CD39, which converts ATP to AMP. The resulting adenosine acts as a signaling molecule that activates P1 receptors expressed on the surface of cells in many different tissues. Four G-protein-coupled P1 or adenosine receptors have been cloned and designated A1, A2A, A2B, and A3. Adenosine affects a wide range of physiological processes, including neural function, vascular perfusion, and immune responses. In this context, for example, this metabolite regulates CNS, cardiovascular, and immune system function.

[0086] Increasing evidence suggests that the interaction between tumor cells and their microenvironment is crucial for tumorigenesis. The purinergic signaling pathway, in which CD73 plays a key role, has been proposed as a key player in cancer progression. In recent years, it has become clear that adenosine is one of the most important immunosuppressive regulatory molecules in the tumor microenvironment and contributes to immune evasion and tumor progression.

[0087] CD73 is a key protein molecule in cancer development. It has been found to be overexpressed in many cancer cell lines and tumor types, including breast cancer, colorectal cancer, ovarian cancer, gastric cancer, gallbladder cancer, and cancers associated with poor prognosis.

[0088] CD73 expression in tumors is regulated by multiple mechanisms. In breast cancer, CD73 expression is negatively regulated by the estrogen receptor (ER). Therefore, CD73 is highly expressed in patients with ER-negative breast cancer. It has also been shown that hypoxia-inducible factor-1α (HIF-1a) regulates CD73 transcription. In addition, inflammatory factors such as IFN-γ affect CD73 levels. CD73 expression is also epigenetically regulated by CpG island methylation in cell lines and clinical tumor samples.

[0089] In addition to serving as a prognostic biomarker for cancer patients, overexpression of CD73 has also been found to be functionally associated with therapy resistance. Elevated CD73 levels were initially associated with resistance to multiple chemotherapeutic agents, including vincristine and doxorubicin.

[0090] CD73 has been implicated in resistance to immunotherapy. This ectonucleotidase participates in tumor immune evasion by: inhibiting the activation, clonal expansion, and homing of tumor-specific T cells (particularly helper and cytotoxic T cells); impairing tumor cell killing by cytolytic effector T lymphocytes; driving the suppressive capacity of Treg and Th17 cells by generating adenosine around cells; enhancing the conversion of type 1 macrophages to pro-tumor type 2 macrophages; and promoting the accumulation of MDSCs.

[0091] Small molecule inhibitors and monoclonal antibodies targeting CD73 have shown antitumor activity in a variety of immunocompetent mouse tumor models, but not in immunodeficient mouse tumor models. Taken together, these studies suggest that the activity of anti-CD73 therapeutics depends on their ability to elicit an immune response in vivo.

[0092] Antibodies that block PD-1, PD-L1, and CTLA-4 have demonstrated impressive objective responses in cancer patients. Recent data indicate that anti-CD73 mAbs significantly enhance the activity of both anti-CTLA-4 and anti-PD-1 mAbs in some mouse tumor models. In addition to checkpoint blockade, CD73-mediated adenosine production may also contribute to resistance to other immunotherapies, including CAR-T cells and cancer vaccines.

[0093] Interfering with CD73 activity represents a strategy to resensitize tumors to therapy. Based on the association between CD73 and therapy resistance, combining anti-CD73 therapy with chemotherapy or immunotherapy is an effective approach to enhance their activity in patients with cancers that have high CD73 levels. In some cases, CD73 expression serves as a biomarker to identify patients who may benefit from anti-CD73 combination therapy.

[0094] In some cases, the CD39 / CD73 pair shifts ATP-driven pro-inflammatory cellular activity toward an adenosine-mediated anti-inflammatory state. Many studies have shown that the activity of the CD39 / CD73 axis changes during infection by a variety of microorganisms. Increased CD73 expression has also been observed in the brains of mice infected with Toxoplasma gondii, where it promotes the parasite's life cycle by producing adenosine. Therefore, pharmacological blockade of CD73 is a promising therapeutic approach for the treatment of toxoplasmosis in humans.

[0095] Increased expression and activity of CD39 and CD73 have been observed in endothelial cells infected with cytomegalovirus (CMV). Increased local adenosine production, associated with upregulation of ectonucleotidases, creates an immunosuppressive and antithrombotic microenvironment that favors viral entry into target cells.

[0096] In some cases, CD73 inhibitors can be used as antiviral drugs by driving a reduction in adenosine production. Elevated expression / activity of CD39 and CD73 on lymphocytes of individuals infected with human immunodeficiency virus (HIV) indicates a role for ectonucleases in the immune dysfunction associated with the disease. Indeed, an increased proportion of Tregs expressing CD39 and a positive correlation between CD39 expression on Tregs and disease progression have been observed in different cohorts of HIV-infected patients. It has also been shown that HIV-positive patients have higher numbers of CD39+ Tregs and that their Teffs exhibit increased sensitivity to the inhibitory effects of adenosine in vitro, which is associated with increased expression of the immunosuppressive A2A receptor.

[0097] In the central nervous system, adenosine plays a key role in controlling a variety of neural functions. By activating P1 receptors, adenosine participates in a variety of physiological and pathological processes, such as regulating sleep, general arousal states and activity, local neuronal excitability, and the coupling of cerebral blood flow to energy demand. In some cases, manipulating adenosine production through CD73 inhibitors could be used to treat neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as psychiatric disorders such as schizophrenia and autism.

[0098] definition

[0099] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties such as molecular weight or chemical properties such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments herein are intended to be included. The term "about" when used in reference to a number or numerical range means that the number or numerical range referred to is an approximation within the range of experimental variability (or within the range of statistical experimental error), and thus, in some cases, the number or numerical range will vary between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "including" or "having" or "containing") is not intended to exclude that, in certain other embodiments, for example, embodiments of any composition of matter, composition, method, process, etc. described herein "consist of" or "consist essentially of" the stated features.

[0100] As used in this specification and the appended claims, the following terms have the meanings set forth below unless indicated otherwise.

[0101] "Alkyl" refers to an optionally substituted straight-chain or optionally substituted branched-chain saturated hydrocarbon monovalent group having 1 to about 10 carbon atoms, or 1 to 6 carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl, as well as longer alkyl groups such as heptyl, octyl, and the like. Whenever a numerical range such as "C1-C6 alkyl" appears herein, it means that the alkyl group consists of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, but this definition also covers the term "alkyl" appearing without specifying a numerical range. In some embodiments, the alkyl group C1-C6 is alkyl. 10In some embodiments, the alkyl group is optionally substituted with oxo, halogen, -CN, -CF , -OH, -OMe, -NH or -NO . In some embodiments, the alkyl group is optionally substituted with oxo, halogen, -CN, -CF , -OH or -OMe. In some embodiments, the alkyl group is optionally substituted with oxo, halogen, -CN, -CF , -OH or -OMe. In some embodiments, the alkyl group is optionally substituted with halogen.

[0102] "Alkenyl" refers to an optionally substituted straight-chain or optionally substituted branched hydrocarbon monovalent group having one or more carbon-carbon double bonds and having 2 to about 10 carbon atoms, more preferably 2 to about 6 carbon atoms. The group can be in cis or trans conformation around the double bond and is understood to include both isomers. Examples include, but are not limited to, vinyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl, etc. Whenever it appears in this document, a numerical range such as "C2-C6 alkenyl" means that the alkenyl can be composed of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, but this definition also covers the term "alkenyl" that appears without specifying a numerical range. In some embodiments, the alkenyl is C2-C6. 10 Alkenyl, C2-C9 alkenyl, C2-C8 alkenyl, C2-C7 alkenyl, C2-C6 alkenyl, C2-C5 alkenyl, C2-C4 alkenyl, C2-C3 alkenyl or C2 alkenyl.Unless specifically indicated in addition in this manual, alkenyl is optionally replaced by such as oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl etc. In some embodiments, alkenyl is optionally replaced by oxo, halogen ,-CN ,-CF ,-OH ,-OMe ,-NH or-NO Replace.In some embodiments, alkenyl is optionally replaced by oxo, halogen ,-CN ,-CF ,-OH or-OMe.In some embodiments, alkenyl is optionally replaced by halogen.

[0103] "Alkynyl" refers to an optionally substituted straight-chain or optionally substituted branched hydrocarbon monovalent group having one or more carbon-carbon triple bonds and having 2 to about 10 carbon atoms, more preferably 2 to about 6 carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl, and the like. Whenever a numerical range such as "C2-C6 alkynyl" appears herein, it means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, but this definition also encompasses the term "alkynyl" appearing without specifying a numerical range. In some embodiments, the alkynyl group is C2-C6. 10 Alkynyl, C2-C9 alkynyl, C2-C8 alkynyl, C2-C7 alkynyl, C2-C6 alkynyl, C2-C5 alkynyl, C2-C4 alkynyl, C2-C3 alkynyl or C2 alkynyl.Unless specifically indicated otherwise in this specification sheets, alkynyl is optionally substituted by, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl etc. In some embodiments, alkynyl is optionally substituted by oxo, halogen ,-CN ,-CF ,-OH ,-OMe ,-NH or-NO .In some embodiments, alkynyl is optionally substituted by oxo, halogen ,-CN ,-CF ,-OH or-OMe.In some embodiments, alkynyl is optionally substituted by halogen.

[0104] " alkylene " refers to the divalent hydrocarbon chain of straight or branched chain.Unless specifically indicated otherwise in this specification, alkylene can be optionally substituted by, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl etc. In some embodiments, alkylene is optionally substituted by oxo, halogen, -CN, -CF , -OH, -OMe, -NH or -NO .In some embodiments, alkylene is optionally substituted by oxo, halogen, -CN, -CF , -OH or -OMe.In some embodiments, this alkylene is optionally substituted by halogen.

[0105] "Alkoxy" refers to a group of the formula -OR a A group in which R a For alkyl groups as defined above. Unless specifically indicated in addition in this specification sheets, alkoxy can optionally be replaced by, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl etc. In some embodiments, alkoxy is optionally replaced by oxo, halogen ,-CN ,-CF ,-OH ,-OMe ,-NH or-NO . In some embodiments, alkoxy is optionally replaced by oxo, halogen ,-CN ,-CF ,-OH or-OMe. In some embodiments, this alkoxy is optionally replaced by halogen.

[0106] "Aryl" refers to a group derived from a hydrocarbon ring system comprising hydrogen, 6 to 30 carbon atoms and at least one aromatic ring. The aryl group can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include a fused (when fused to a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through aromatic ring atoms) or bridged ring system. In some embodiments, the aryl is a 6 to 10 membered aryl. In some embodiments, the aryl is a 6 membered aryl. Aryl groups include, but are not limited to, anthracene, naphthylene, phenanthrenyl, anthracene, azulene, benzene, In some embodiments, the aryl group is an aryl group derived from the hydrocarbon ring system of fluoranthene, fluorene, asymmetric indacene, symmetric indacene, indane, indene, naphthalene, phenanthene, phenanthren, pyrene and triphenylene. In some embodiments, the aryl group is phenyl. Unless otherwise specifically indicated in this specification, the aryl group can be optionally substituted by halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the aryl group is optionally substituted by halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2 or -NO2. In some embodiments, the aryl group is optionally substituted by halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the aryl group is optionally substituted by halogen.

[0107] "Cycloalkyl" refers to a stable, partially or fully saturated monocyclic or polycyclic carbocyclic ring, which may include fused (when fused to an aryl or heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom) or bridged ring systems. Representative cycloalkyl groups include, but are not limited to, groups having 3 to 15 carbon atoms (C3-C 15 cycloalkyl), 3 to 10 carbon atoms (C3-C 10In some embodiments, the cycloalkyl group is a 3- to 6-membered cycloalkyl group. In some embodiments, the cycloalkyl group is a 5- to 6-membered cycloalkyl group. Monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl or carbocyclic ring include, for example, adamantyl, norbornyl, decalinyl, bicyclo [3.3.0] octane, bicyclo [4.3.0] nonane, cis-decalin, trans-decalin, bicyclo [2.1.1] hexane, bicyclo [2.2.1] heptane, bicyclo [2.2.2] octane, bicyclo [3.2.2] nonane and bicyclo [3.3.2] decane and 7,7-dimethyl-bicyclo [2.2.1] heptane. Partially saturated cycloalkyl include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. Unless otherwise specifically indicated in this specification, cycloalkyl is optionally substituted, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl etc. In some embodiments, cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF , -OH, -OMe, -NH or -NO . In some embodiments, cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF , -OH or -OMe. In some embodiments, the cycloalkyl is optionally substituted with halogen.

[0108] "Halo" or "halogen" refers to bromo, chloro, fluoro, or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro.

[0109] "Haloalkyl" refers to an alkyl group as defined above substituted with one or more halo groups as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like.

[0110] "Heterocycloalkyl" refers to a stable 3 to 24-membered partially or fully saturated ring group containing 2 to 23 carbon atoms and 1 to 8 heteroatoms selected from nitrogen, oxygen, phosphorus and sulfur. Unless otherwise specifically indicated in this specification, the heterocycloalkyl group can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include a fused (when fused to an aryl or heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom) or bridged ring system; and the nitrogen, carbon or sulfur atoms in the heterocycloalkyl group can be optionally oxidized; the nitrogen atom can be optionally quaternized. In some embodiments, the heterocycloalkyl is a 3 to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5 to 6-membered heterocycloalkyl. Examples of such heterocycloalkyl groups include, but are not limited to, aziridinyl, azetidinyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidine, thiazolidinyl, tetrahydrofuran ... The term "heterocycloalkyl" refers to a group consisting of 2 to 10 carbon atoms in a ring. ... Unless specifically indicated in addition in this specification sheets, Heterocycloalkyl is optionally substituted by oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, Heterocycloalkyl, heteroaryl etc. In some embodiments, Heterocycloalkyl is optionally substituted by oxo, halogen, methyl, ethyl ,-CN ,-CF ,-OH ,-OMe ,-NH or-NO Replacement. In some embodiments, Heterocycloalkyl is optionally substituted by oxo, halogen, methyl, ethyl ,-CN ,-CF ,-OH or-OMe Replacement. In some embodiments, this Heterocycloalkyl is optionally substituted by halogen.

[0111] " assorted alkyl " refers to such alkyl, wherein the one or more skeleton atoms of the alkyl are selected from the atom other than carbon, for example, oxygen, nitrogen (for example-NH-,-N (alkyl)-), sulphur or its combination.Assorted alkyl is connected to the remainder of the molecule at the carbon atom of the assorted alkyl. On the one hand, assorted alkyl is C1-C6 assorted alkyl, wherein the assorted alkyl comprises 1 to 6 carbon atoms and one or more atoms other than carbon, for example, oxygen, nitrogen (for example-NH-,-N (alkyl)-), sulphur or its combination, wherein the assorted alkyl is connected to the remainder of the molecule at the carbon atom of the assorted alkyl. The example of such assorted alkyl is, for example,-CH2OCH3,-CH2CH2OCH3 or-CH(CH3)OCH3. Unless specifically indicated otherwise in this specification, assorted alkyl is optionally substituted by oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl etc. In some embodiments, heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF , -OH, -OMe, -NH , or -NO . In some embodiments, heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF , -OH, or -OMe. In some embodiments, the heteroalkyl is optionally substituted with halogen.

[0112] "Heteroaryl" refers to a 5- to 14-membered ring system radical comprising hydrogen atoms, 1 to 13 carbon atoms, 1 to 6 heteroatoms selected from nitrogen, oxygen, phosphorus and sulfur, and at least one aromatic ring. A heteroaryl group can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include a fused (when fused to a cycloalkyl or heterocycloalkyl ring, the heteroaryl group is bonded through an aromatic ring atom) or a bridged ring system; and the nitrogen, carbon or sulfur atoms in the heteroaryl group can be optionally oxidized; the nitrogen atom can be optionally quaternized. In some embodiments, the heteroaryl group is a 5- to 10-membered heteroaryl group. In some embodiments, the heteroaryl group is a 5- to 6-membered heteroaryl group. Examples include, but are not limited to, aza benzo[b][1,4]dioxolane, benzo[b][1,4]dioxane ... benzothiophenyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolyl, isoindolyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepine Unless otherwise specifically stated in the specification, heteroaryl is optionally substituted, for example, by halogen, amino, nitrile, nitro, hydroxy, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroaryl is optionally substituted by halogen, methyl, ethyl, -CN, -CF , -OH, -OMe, -NH or -NO . In some embodiments, heteroaryl is optionally substituted by halogen, methyl, ethyl, -CN, -CF , -OH or -OMe. In some embodiments, the heteroaryl is optionally substituted by halogen.

[0113] "Hydroxyalkyl" refers to an alkyl group as defined above substituted with one or more -OH groups, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, dihydroxymethyl, dihydroxyethyl, dihydroxypropyl, dihydroxybutyl, dihydroxypentyl, and the like.

[0114] "Oxo" refers to =0.

[0115] The term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where said event or circumstance does not occur. For example, "optionally substituted alkyl" means "alkyl" or "substituted alkyl" as defined above. In addition, an optionally substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F), or substituted at any level between fully substituted and monosubstituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc.). With respect to any group comprising one or more substituents, it will be understood by those skilled in the art that such groups are not intended to introduce any substitution or substitution pattern that is sterically impractical and / or synthetically infeasible (e.g., substituted alkyl includes optionally substituted cycloalkyl, which in turn is defined to include optionally substituted alkyl, which is potentially infinite). Thus, any substituents described will generally be understood to have a maximum molecular weight of about 1,000 Daltons, and more typically, up to about 500 Daltons.

[0116] The terms "inhibit," "block," "suppress," and grammatical variations thereof are used interchangeably herein to refer to any statistically significant decrease in a biological activity, including complete blockade of the activity. In some embodiments, "inhibit" refers to a decrease in biological activity by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100%. Thus, when the terms "inhibit" or "suppress" are used to describe, for example, an effect on the enzymatic activity of CD73, the terms refer to the ability of the compounds disclosed herein to statistically significantly reduce the 5'-nucleotidase activity (catabolism that hydrolyzes adenosine monophosphate AMP to adenosine) of CD73 relative to the 5'-nucleotidase activity mediated by CD73 in untreated (control) cells. In some cases, the cells expressing CD73 are naturally occurring cells or cell lines (e.g., cancer cells), or are recombinantly produced by introducing a nucleic acid encoding CD73 into a host cell. In some aspects, the compounds disclosed herein statistically significantly reduce the 5'-nucleotidase activity of a soluble form of CD73 in a biological fluid. In one aspect, the compounds disclosed herein inhibit CD73-mediated 5'-nucleotidase activity by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or about 100%, for example, as determined by the methods described in the Examples and / or methods known in the art.

[0117] As used herein, "treat," "treat," "treat," "alleviate," or "ameliorate" are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results, including but not limited to therapeutic benefit and / or prophylactic benefit. By "therapeutic benefit" is meant the elimination or amelioration of the underlying condition being treated. Additionally, therapeutic benefit can be achieved by eradication or amelioration of one or more physiological symptoms associated with the underlying condition, such that improvement is observed in the patient, although the patient is still suffering from the underlying condition. For prophylactic benefit, in some embodiments, the composition is administered to a patient at risk for developing a particular disease, or to a patient reporting one or more physiological symptoms of a disease, even if a diagnosis of the disease has not yet been made.

[0118] Compound

[0119] Described herein are compounds that are CD73 inhibitors. These compounds and compositions comprising these compounds are useful in treating cancer, infections, and neurodegenerative diseases.

[0120] In some embodiments, provided herein are compounds having the structure of Formula (I), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0121]

[0122] in:

[0123] Ring A is

[0124] Q 1 and 2 Independently N or CW;

[0125] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0126] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0127] A is -O- or -CH2-;

[0128] X is -S(=O)2-;

[0129] R 1 and R 2R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0130] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0131] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0132] R 3 For hydrogen, halogen, -CN, -OR b 、-SRb 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0133] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0134] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0135] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0136] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0137] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0138] R 11 Halogen, -CN, -OR 13 、-SR 13、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0139] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0140] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0141] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R11c replace;

[0142] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0143] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0144] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0145] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0146] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0147] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -ORb 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0148] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0149] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0150] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c Rd 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0151] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0152] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0153] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0154] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0155] In some embodiments, provided herein are compounds having the structure of Formula (I), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0156]

[0157] in:

[0158] Ring A is Q 1 and 2 Independently N or CW;

[0159] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0160] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0161] A is -O- or -CH2-;

[0162] X is -S(=O)2-;

[0163] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0164] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0165] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0166] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0167] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0168] R 4 and R 7 are independently hydrogen, halogen, -OR b, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0169] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0170] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0171] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0172] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0173] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0174] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0175] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0176] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NRb C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0177] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0178] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0179] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0180] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0181] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0182] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0183] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0184] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0185] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0186] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0187] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0188] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0189] In some embodiments, provided herein are compounds having the structure of Formula (I), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0190]

[0191] in:

[0192] Ring A is Q 1 and 2 Independently N or CW;

[0193] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0194] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0195] A is -O- or -CH2-;

[0196] X is -S(=O)2-;

[0197] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0198] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0199] Each R 1a and R 1bare independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0200] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0201] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0202] R 5 and R 6are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0203] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0204] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0205] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0206] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0207] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0208] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0209] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0210] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0211] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0212] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0213] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0214] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NRc R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0215] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0216] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0217] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c Rd 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0218] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0219] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0220] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0221] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl; provided that the compound is not:

[0222]

[0223] In some embodiments of the compound of Formula (I), Q 1N and Q 2 In some embodiments of the compound of formula (I), Q 1 CW and Q 2 is N. In some embodiments of the compound of Formula (I), Q 1 N and Q 2 is N. In some embodiments of the compound of Formula (I), Q 1 CW and Q 2 In some embodiments of the compound of formula (I), Q 1 N and Q 2 N or Q 1 N and Q 2 For CW.

[0224] In some embodiments of the compound of Formula (I), Q 3 N and Q 4 In some embodiments of the compound of formula (I), Q 4 N and Q 3 In some embodiments of the compound of formula (I), Q 3 N and Q 4 is N.

[0225] In some embodiments of compounds of formula (I), each W is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of compounds of formula (I), each W is independently hydrogen, halogen, or C1-C6 alkyl. In some embodiments of compounds of formula (I), each W is hydrogen.

[0226] In some embodiments of the compound of Formula (I), R 3 Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkynyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (I), R 3 is halogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a replace.

[0227] In some embodiments of the compound of Formula (I), R 3 Halogen, -CN, -OR b 、-NR cR d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), R 3 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), R 3 is halogen or C1-C6 hydroxyalkyl, C1-C6 heteroalkyl. In some embodiments of the compound of formula (I), R 3 It is a halogen.

[0228] In some embodiments of the compound of Formula (I), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (I), each R 3a is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (I), each R 3a are independently halogen, -OR b , C1-C6 alkyl or cycloalkyl.

[0229] In some embodiments of the compound of Formula (I), R 1is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (I), R 1 is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (I), R 1 is cycloalkyl or C1-C6 alkyl (cycloalkyl); wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R 1a In some embodiments of the compound of formula (I), R 1 is optionally replaced by one, two or three R 1a Substituted cycloalkyl.

[0230] In some embodiments of the compound of Formula (I), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (I), each R 1a are independently halogen or C1-C6 alkyl.

[0231] In some embodiments of the compound of Formula (I), R 2 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (I), R 2 In some embodiments of the compound of formula (I), R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b Substituted heterocycloalkyl.

[0232] In some embodiments of the compound of Formula (I), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (I), each R 1b are independently halogen or C1-C6 alkyl.

[0233] In some embodiments of the compound of Formula (I), R 8 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (I), R 8 For hydrogen.

[0234] In some embodiments of the compound of Formula (I), R 9 and R 10 are independently hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (I), R 9 and R 10 For hydrogen.

[0235] In some embodiments of the compound of formula (I), A is -O-. In some embodiments of the compound of formula (I), A is -CH2-.

[0236] In some embodiments of the compound of Formula (I), R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (I), R 5 and R 6 are independently hydrogen, halogen, -OR b or C1-C6 alkyl. In some embodiments of the compound of formula (I), R 5 and R 6 For hydrogen.

[0237] In some embodiments of the compound of Formula (I), R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (I), R 4 and R 7 are independently hydrogen, halogen, -OR b or C1-C6 alkyl. In some embodiments of the compound of formula (I), R 4 and R 7 are independently hydrogen, halogen or -OR b In some embodiments of the compound of formula (I), R 4 and R 7 are independently hydrogen, halogen or -OH. In some embodiments of the compound of formula (I), R 4 and R 7 are independently halogen or -OH. In some embodiments of the compound of formula (I), R 4 and R 7 are independently hydrogen or -OH. In some embodiments of the compound of formula (I), R 4 and R 7 It is -OH.

[0238] In some embodiments of the compound of Formula (I), R 5 and R 6 is hydrogen and R 4 and R 7 In some embodiments of the compound of formula (I), R 5 and R 6 is hydrogen and R 4 and R 7 are independently halogen or -OH. In some embodiments of the compound of formula (I), R5 and R 6 is hydrogen and R 4 and R 7 are independently hydrogen or -OH.

[0239] In some embodiments of the compound of Formula (I), R 21 and R 22 are independently hydrogen, C1-C 20 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (I), R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl or aryl; wherein each alkyl and aryl group is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (I), R 21 and R 22 are independently hydrogen, optionally substituted by one, two or three R 21a Substituted C1-C 20 In some embodiments of the compound of formula (I), R 21 and R 22 For hydrogen.

[0240] In some embodiments of the compound of Formula (I), each R 21a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b or C1-C6 alkyl. In some embodiments of the compound of formula (I), each R 21a are independently -C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)ORb or -OC(=O)NR c R d In some embodiments of the compound of formula (I), each R 21a are independently -C(=O)OR b OR-OC(=O)OR b .

[0241] In some embodiments of the compound of Formula (I), R 21 and R 22 Together with the atoms to which they are attached, they form a 21b Substituted heterocycloalkyl.

[0242] In some embodiments of the compound of Formula (I), each R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 21b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 21b are independently halogen or C1-C6 alkyl.

[0243] In some embodiments of the compound of Formula (I), R 12 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), R 12 Halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), R 12 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (I), R 12 In some embodiments of the compound of formula (I), R 12 is C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (I), R 12 In some embodiments of the compound of formula (I), R 12 Not hydrogen.

[0244] In some embodiments of the compound of Formula (I), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace.

[0245] In some embodiments of the compound of Formula (I), each R 12aare independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace.

[0246] In some embodiments of the compound of Formula (I), each R 12a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c replace.

[0247] In some embodiments of the compound of Formula (I), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (I), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (I), R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted by one, two or three R 11a In some embodiments of the compound of formula (I), R 11 is optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (I), R 11 To be an R 11a In some embodiments of the compound of formula (I), R 11 It is a C1-C6 hydroxyalkyl group.

[0248] In some embodiments of the compound of Formula (I), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (I), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (I), each R 11a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c In some embodiments of the compound of formula (I), each R 11a is independently optionally replaced by one, two or three R 11c Substituted aryl.

[0249] In some embodiments of the compound of Formula (I), each R 11a Independently -OR 13 In some embodiments of the compound of formula (I), each R 11a are independently -S(=O)2R 14 In some embodiments of the compound of formula (I), each R 11a is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of Formula (I), each R 11a are independently -NR 13 C(=O)R 14 .

[0250] In some embodiments of the compound of Formula (I), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (I), each R 11c are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (I), each R 11c are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0251] In some embodiments of the compound of Formula (I), R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b In some embodiments of the compound of formula (I), R 11 and R 12 Together forming optionally one, two or three R 11b- In some embodiments of the compound of Formula (I), R 11 and R 12 Together forming optionally one, two or three R 11b Substituted heterocycloalkyl.

[0252] In some embodiments of the compound of Formula (I), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (I), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (I), each R 11b is independently oxo (where applicable), halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0253] In some embodiments of the compound of Formula (I), each R 13are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (I), each R 13 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (I), each R 13 are independently hydrogen or C1-C6 alkyl.

[0254] In some embodiments of the compound of Formula (I), each R 13a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 13a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 13a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0255] In some embodiments of the compound of Formula (I), each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (I), each R 14 is independently C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (I), each R 14 are independently C1-C6 alkyl.

[0256] In some embodiments of the compound of Formula (I), each R 14aare independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 14a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 14a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0257] In some embodiments of the compound of Formula (I), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (I), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (I), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (I), each R 15 and R 16 are independently hydrogen or C1-C6 alkyl.

[0258] In some embodiments of the compound of Formula (I), each R 15a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 15a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 15a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0259] In some embodiments of the compound of Formula (I), R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b In some embodiments of the compound of Formula (I), R 15 and R 16 Together with the nitrogen atom to which they are attached they form a heterocycloalkyl group.

[0260] In some embodiments of the compound of Formula (I), each R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 15b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (I), each R 15b are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0261] In some embodiments, provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof:

[0262]

[0263] in:

[0264] Ring A is Q1 N and Q 2 CW or Q 1 N and Q 2 is N;

[0265] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0266] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0267] A is -O-;

[0268] X is -S- or -O-;

[0269] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0270] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0271] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0272] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0273] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0274] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0275] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0276] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0277] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0278] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0279] R 12For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0280] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0281] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0282] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0283] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0284] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0285] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0286] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0287] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NRc R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0288] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0289] or R 21 and R 22 Together with the atoms to which they are attached, they form a21b substituted heterocycloalkyl;

[0290] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0291] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0292] Each R bis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0293] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0294] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0295] In some embodiments, provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof:

[0296]

[0297] in:

[0298] Ring A is Q 1 N and Q 2 CW or Q 1 N and Q 2 is N;

[0299] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0300] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0301] A is -O-;

[0302] X is -S- or -O-;

[0303] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0304] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0305] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0306] R3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0307] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0308] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0309] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0310] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0311] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0312] R 11Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0313] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0314] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0315] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0316] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0317] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0318] Each R 14is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0319] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0320] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0321] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0322] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0323] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0324] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0325] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0326] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0327] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0328] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0329] In some embodiments, provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof:

[0330]

[0331] in:

[0332] Ring A is Q 1 N and Q 2 CW or Q 1N and Q 2 is N;

[0333] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0334] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0335] A is -O-;

[0336] X is -S- or -O-;

[0337] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0338] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0339] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR cR d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0340] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0341] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0342] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0343] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0344] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0345] R 11Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0346] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-

[0347] OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0348] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0349] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0350] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0351] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0352] Each R 14is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0353] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0354] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0355] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0356] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0357] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0358] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0359] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0360] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0361] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0362] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl; provided that the compound is not:

[0363]

[0364] In some embodiments, provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof:

[0365]

[0366] in:

[0367] Ring A is Q 1 N and Q 2 CW or Q 1 N and Q 2 is N;

[0368] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0369] Each W is independently hydrogen, halogen or C1-C6 alkyl;

[0370] A is -O-;

[0371] X is -O-;

[0372] R 1 and R 2 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0373] Each R 1a are independently oxo (when applicable), halogen, -CN, -OR b , C1-C6 alkyl or C1-C6 fluoroalkyl;

[0374] R 3 Halogen, -OR b , C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a replace;

[0375] Each R 3a are independently oxo (when applicable), halogen or -OR b ;

[0376] R 4 and R 7 are independently hydrogen, halogen or -OR b ;

[0377] R 5 and R 6 are independently hydrogen, halogen or C1-C6 alkyl;

[0378] R 8 is hydrogen;

[0379] R 9 and R 10 is hydrogen;

[0380] R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a replace;

[0381] R 12 For hydrogen, halogen, -OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 12a replace;

[0382] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0383] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace;

[0384] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0385] Each R 13 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 13a replace;

[0386] Each R 14 is independently C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 14a replace;

[0387] Each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a replace;

[0388] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0389] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)ORb 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl substitution;

[0390] R 21 and R 22 are independently hydrogen or C1-C 20 alkyl;

[0391] Each R a is independently C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0392] Each R b is independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0393] Each R c and R d are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0394] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0395] In some embodiments, provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof:

[0396]

[0397] in:

[0398] Ring A is Q 1 N and Q 2 CW or Q 1 N and Q 2 is N;

[0399] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0400] Each W is hydrogen;

[0401] A is -O-;

[0402] X is -O-;

[0403] R 1 and R 2 independently hydrogen, C1-C6 alkyl, cycloalkyl, C1-C6 alkyl(aryl) or C1-C6 alkyl(cycloalkyl); wherein each alkyl, cycloalkyl and aryl group is independently optionally replaced by one, two or three R 1a replace;

[0404] Each R 1a are independently halogen or C1-C6 alkyl;

[0405] R 3 Halogen, -OR b , C2-C6 alkynyl or C1-C6 hydroxyalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a replace;

[0406] Each R 3a are independently oxo (when applicable), halogen or -OR b ;

[0407] R 4 and R 7 are independently hydrogen, halogen or -OR b ;

[0408] R 5 and R 6 are independently hydrogen, halogen or C1-C6 alkyl;

[0409] R 8 is hydrogen;

[0410] R 9 and R 10 is hydrogen;

[0411] R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-

[0412] C6 hydroxyalkyl, C2-C6 alkynyl or heteroaryl; wherein each alkyl, alkynyl and heteroaryl is independently optionally substituted by one, two or three R 11a replace;

[0413] R 12 is hydrogen, C1-C6 alkyl, C1-C6 hydroxyalkyl or C2-C6 alkynyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 12a replace;

[0414] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0415] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -OR 13 、-SR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)OR 13 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , heterocycloalkyl, aryl or heteroaryl; wherein each heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace;

[0416] Each R 11c Independently -OR b 、-C(=O)OR b or C1-C6 hydroxyalkyl;

[0417] Each R 13 is independently C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl; wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R13a replace;

[0418] Each R 14 are independently C1-C6 alkyl;

[0419] Each R 15 and R 16 are independently hydrogen or C1-C6 alkyl;

[0420] Each R 13a Independently -OR b 、-C(=O)OR b , cycloalkyl, aryl or heteroaryl;

[0421] R 21 and R 22 is hydrogen;

[0422] Each R a are independently optionally substituted with one, two or three oxo (where applicable), halogen, -

[0423] OH, C1-C6 alkyl or C1-C6 haloalkyl substituted C1-C6 alkyl;

[0424] Each R b are independently hydrogen or C1-C6 alkyl optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and each R c and R d are independently hydrogen or optionally substituted with one, two or three oxo groups (when feasible)

[0425] ), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl substituted C1-C6 alkyl; or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0426] In some embodiments, provided herein are compounds having the structure of Formula (II), or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof:

[0427]

[0428] in:

[0429] Ring A is Q 1 N and Q 2 CW or Q 1 N and Q 2 is N;

[0430] Q 3 and Q 4 is N;

[0431] W is hydrogen;

[0432] A is -O-;

[0433] X is -O-;

[0434] R 1 is a cycloalkyl group or a C1-C6 alkyl group (cycloalkyl group);

[0435] R 2 is hydrogen;

[0436] R 3 is halogen or C1-C6 hydroxyalkyl;

[0437] R 4 and R 7 Independently -OR b ;

[0438] R 5 and R 6 is hydrogen;

[0439] R 8 is hydrogen;

[0440] R 9 and R 10 is hydrogen;

[0441] R 11 is C1-C6 alkyl or C1-C6 hydroxyalkyl; wherein each alkyl group is independently optionally substituted by one R 11a replace;

[0442] R 12 is a C1-C6 alkyl group or a C1-C6 hydroxyalkyl group;

[0443] Each R 11a For-OR 13 or heteroaryl;

[0444] R 13 is a C1-C6 alkyl group;

[0445] R 21 and R 22 is hydrogen;

[0446] Each R a is independently C1-C6 alkyl optionally substituted with one, two or three halogens, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0447] Each R bare independently hydrogen or C1-C6 alkyl optionally substituted with one, two or three halogens, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0448] Each R c and R d are independently hydrogen or C1-C6 alkyl optionally substituted with one, two or three halogens, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0449] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0450] In some embodiments of the compound of Formula (II), Q 1 N and Q 2 In some embodiments of the compound of formula (II), Q 1 N and Q 2 is N.

[0451] In some embodiments of the compound of Formula (II), Q 3 N and Q 4 In some embodiments of the compound of formula (II), Q 4 N and Q 3 In some embodiments of the compound of formula (II), Q 3 N and Q 4 is N.

[0452] In some embodiments of the compound of Formula (II), Q 1 N, Q 2 For CW, Q 3 is N, and Q 4 In some embodiments of the compound of formula (II), Q 1 N, Q 2 For CW, Q 3 is CW, and Q 4 is N. In some embodiments of the compound of formula (II), Q 1 N, Q 2 For CW, Q 3 is N, and Q 4 is N. In some embodiments of the compound of formula (II), Q 1 N, Q 2 N, Q 3 is N, and Q 4 In some embodiments of the compound of formula (II), Q1 N, Q 2 N, Q 3 is CW, and Q 4 is N. In some embodiments of the compound of formula (II), Q 1 N, Q 2 N, Q 3 is N, and Q 4 is N.

[0453] In some embodiments of compounds of formula (II), each W is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of compounds of formula (II), each W is independently hydrogen, halogen, or C1-C6 alkyl. In some embodiments of compounds of formula (II), each W is hydrogen.

[0454] In some embodiments of the compound of Formula (II), R 3 Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkynyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (II), R 3 is halogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (II), R 3 Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), R 3 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), R 3 is halogen or C1-C6 hydroxyalkyl, C1-C6 heteroalkyl. In some embodiments of the compound of formula (II), R 3 In some embodiments of the compound of formula (II), R 3 Halogen, -OR b, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (II), R 3 Halogen, -OR b , C2-C6 alkynyl or C1-C6 hydroxyalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (II), R 3 is halogen or C1-C6 hydroxyalkyl.

[0455] In some embodiments of the compound of Formula (II), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (II), each R 3a is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (II), each R 3a are independently halogen, -OR b , C1-C6 alkyl or cycloalkyl. In some embodiments of the compound of formula (II), each R 3a are independently oxo (when applicable), halogen or -OR b .

[0456] In some embodiments of the compound of Formula (II), R 1is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (II), R 1 is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (II), R 1 is cycloalkyl or C1-C6 alkyl (cycloalkyl); wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R 1a In some embodiments of the compound of formula (II), R 1 is optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (II), R 1 is C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (II), R 1 is C1-C6 alkyl, cycloalkyl, C1-C6 alkyl (aryl) or C1-C6 alkyl (cycloalkyl); wherein each alkyl, cycloalkyl and aryl group is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (II), R 1 It is a cycloalkyl group or a C1-C6 alkyl group (cycloalkyl group).

[0457] In some embodiments of the compound of Formula (II), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (II), each R 1a is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (II), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b , C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (II), each R 1a are independently halogen or C1-C6 alkyl.

[0458] In some embodiments of the compound of Formula (II), R 2 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (II), R 2 In some embodiments of the compound of formula (II), R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b Substituted heterocycloalkyl.

[0459] In some embodiments of the compound of Formula (II), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NRc R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (II), each R 1b are independently halogen or C1-C6 alkyl.

[0460] In some embodiments of the compound of Formula (II), R 8 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (II), R 8 For hydrogen.

[0461] In some embodiments of the compound of Formula (II), R 9 and R 10 are independently hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (II), R 9 and R 10 For hydrogen.

[0462] In some embodiments of the compound of formula (II), X is -O-. In some embodiments of the compound of formula (II), X is -S-.

[0463] In some embodiments of the compound of Formula (II), R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), R 5 and R 6 are independently hydrogen, halogen, -OR b or C1-C6 alkyl. In some embodiments of the compound of formula (II), R 5 and R 6 For hydrogen.

[0464] In some embodiments of the compound of Formula (II), R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), R 4 and R 7 are independently hydrogen, halogen, -OR bor C1-C6 alkyl. In some embodiments of the compound of formula (II), R 4 and R 7 are independently hydrogen, halogen or -OR b In some embodiments of the compound of formula (II), R 4 and R 7 are independently hydrogen, halogen or -OH. In some embodiments of the compound of formula (II), R 4 and R 7 are independently halogen or -OH. In some embodiments of the compound of formula (II), R 4 and R 7 are independently hydrogen or -OH. In some embodiments of the compound of formula (II), R 4 and R 7 It is -OH.

[0465] In some embodiments of the compound of Formula (II), R 5 and R 6 is hydrogen and R 4 and R 7 In some embodiments of the compound of formula (II), R 5 and R 6 is hydrogen and R 4 and R 7 are independently halogen or -OH. In some embodiments of the compound of formula (II), R 5 and R 6 is hydrogen and R 4 and R 7 are independently hydrogen or -OH.

[0466] In some embodiments of the compound of Formula (II), R 21 and R 22 are independently hydrogen, C1-C 20 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (II), R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl or aryl; wherein each alkyl and aryl group is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (II), R 21 and R 22 are independently hydrogen, optionally substituted by one, two or three R 21a Substituted C1-C 20In some embodiments of the compound of formula (II), R 21 and R 22 For hydrogen.

[0467] In some embodiments of the compound of Formula (II), each R 21a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b or C1-C6 alkyl. In some embodiments of the compound of formula (II), each R 21a are independently -C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b or -OC(=O)NR c R d In some embodiments of the compound of formula (II), each R 21a are independently -C(=O)OR b OR-OC(=O)OR b .

[0468] In some embodiments of the compound of Formula (II), R 21 and R 22 Together with the atoms to which they are attached, they form a 21b Substituted heterocycloalkyl.

[0469] In some embodiments of the compound of Formula (II), each R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 21b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 21b are independently halogen or C1-C6 alkyl.

[0470] In some embodiments of the compound of Formula (II), R 12 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), R 12 Halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), R 12 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (II), R 12 is C1-C6 alkyl. In some embodiments of the compound of formula (II), R 12 is C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (II), R 12In some embodiments of the compound of formula (II), R 12 In some embodiments of the compound of formula (II), R 12 For hydrogen, halogen, -OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 12a In some embodiments of the compound of formula (II), R 12 is hydrogen, C1-C6 alkyl, C1-C6 hydroxyalkyl or C2-C6 alkynyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 12a replace.

[0471] In some embodiments of the compound of Formula (II), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 12a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c In some embodiments of the compound of formula (II), each R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 12a are independently oxo (when applicable), halogen, -OR 13 、-SR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16、-C(=O)OR 13 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , heterocycloalkyl, aryl or heteroaryl; wherein each heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace.

[0472] In some embodiments of the compound of Formula (II), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (II), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (II), R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted by one, two or three R 11a In some embodiments of the compound of formula (II), R 11 is optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (II), R 11 To be an R 11a In some embodiments of the compound of formula (II), R 11is C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (II), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (II), R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl or heteroaryl; wherein each alkyl, alkynyl and heteroaryl is independently optionally substituted by one, two or three R 11a In some embodiments of the compound of formula (II), R 11 is C1-C6 alkyl or C1-C6 hydroxyalkyl; wherein each alkyl group is independently optionally substituted by one R 11a replace.

[0473] In some embodiments of the compound of Formula (II), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11aare independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a Independently -OR 13 In some embodiments of the compound of formula (II), each R 11a are independently -S(=O)2R 14 In some embodiments of the compound of formula (II), each R 11a is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a are independently -NR 13 C(=O)R 14 In some embodiments of the compound of formula (II), each R 11a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NR 15 R 16、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a are independently oxo (when applicable), halogen, -OR 13 、-SR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)OR 13 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , heterocycloalkyl, aryl or heteroaryl; wherein each heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a Independently -OR 13 or heteroaryl.

[0474] In some embodiments of the compound of Formula (II), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (II), each R 11c are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 11c is independently halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl. In some embodiments of the compound of formula (II), each R 11c Independently -OR b 、-C(=O)OR b or C1-C6 hydroxyalkyl.

[0475] In some embodiments of the compound of Formula (II), R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b In some embodiments of the compound of formula (II), R 11 and R 12 Together forming optionally one, two or three R 11b In some embodiments of the compound of formula (II), R 11 and R 12 Together forming optionally one, two or three R 11b Substituted heterocycloalkyl.

[0476] In some embodiments of the compound of Formula (II), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 11b is independently oxo (where applicable), halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0477] In some embodiments of the compound of Formula (II), each R 13 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (II), each R 13 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (II), each R 13 are independently hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (II), each R 13 are independently C1-C6 alkyl. In some embodiments of the compound of formula (II), each R 13 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 13a In some embodiments of the compound of formula (II), each R 13 is independently C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl; wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R 13a replace.

[0478] In some embodiments of the compound of Formula (II), each R 13a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 13a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 13a is independently halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 13a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 13a Independently -OR b 、-C(=O)OR b , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (II), each R 13a Independently -OR b 、-C(=O)ORb , cycloalkyl, aryl or heteroaryl.

[0479] In some embodiments of the compound of Formula (II), each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (II), each R 14 is independently C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (II), each R 14 are independently C1-C6 alkyl.

[0480] In some embodiments of the compound of Formula (II), each R 14a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 14a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 14a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0481] In some embodiments of the compound of Formula (II), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (II), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15aIn some embodiments of the compound of formula (II), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (II), each R 15 and R 16 are independently hydrogen or C1-C6 alkyl.

[0482] In some embodiments of the compound of Formula (II), each R 15a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 15a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 15a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0483] In some embodiments of the compound of Formula (II), R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b In some embodiments of the compound of formula (II), R 15 and R 16 Together with the nitrogen atom to which they are attached they form a heterocycloalkyl group.

[0484] In some embodiments of the compound of Formula (II), each R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 15b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (II), each R 15b are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0485] In some embodiments, provided herein are compounds having the structure of Formula (III), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0486]

[0487] in:

[0488] Ring A is Q 1 CW and Q 2 is N;

[0489] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0490] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0491] A is -O- or -CH2-;

[0492] X is -O-, -S- or -S(=O)2-;

[0493] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0494] or R 1 and R2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0495] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0496] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3areplace;

[0497] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0498] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0499] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0500] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0501] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0502] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0503] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0504] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0505] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0506] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0507] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0508] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0509] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0510] or R 15 and R 16Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0511] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0512] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0513] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0514] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0515] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0516] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0517] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0518] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0519] In some embodiments, provided herein are compounds having the structure of Formula (III), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0520]

[0521] in:

[0522] Ring A is Q 1 CW and Q 2 is N;

[0523] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0524] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0525] A is -O- or -CH2-;

[0526] X is -O-, -S- or -S(=O)2-;

[0527] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0528] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0529] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)Ra 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0530] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0531] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0532] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0533] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0534] R 8 For hydrogen, halogen, -ORb 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0535] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0536] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0537] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0538] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0539] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0540] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl,

[0541] Heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0542] Each R 13R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0543] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0544] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0545] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0546] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0547] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0548] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0549] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NRb C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0550] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0551] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0552] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0553] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0554] In some embodiments, provided herein are compounds having the structure of Formula (III), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0555]

[0556] in:

[0557] Ring A is

[0558] Q 1 CW and Q 2 is N;

[0559] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0560] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0561] A is -O- or -CH2-;

[0562] X is -O-, -S- or -S(=O)2-;

[0563] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0564] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0565] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR cR d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0566] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0567] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0568] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0569] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0570] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0571] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0572] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0573] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0574] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0575] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0576] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0577] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0578] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0579] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0580] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)ORb , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0581] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0582] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0583] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0584] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0585] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0586] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0587] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0588]

[0589] in:

[0590] Ring A is Q 1 CW and Q 2 is N;

[0591] Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4At least one of them is N;

[0592] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0593] A is -O- or -CH2-;

[0594] X is -O-, -S- or -S(=O)2-;

[0595] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a Replacement; provided that R 1 or R 2 One is not hydrogen;

[0596] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0597] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NRb C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0598] R 3 Halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0599] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0600] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0601] R 5 and R 6 are independently hydrogen, halogen, -OR b, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0602] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0603] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0604] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-OC(=O)OR 13 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a Replacement; provided that R 11 Not CF3;

[0605] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0606] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0607] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0608] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0609] Each R 13R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0610] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0611] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0612] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0613] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0614] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0615] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0616] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0617] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0618] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0619] Each R c and R dis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 heteroalkyl.

[0620] C6 haloalkyl substitution;

[0621] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0622] In some embodiments of the compound of formula (III), Q 3 N and Q 4 In some embodiments of the compound of formula (III), Q 4 N and Q 3 In some embodiments of the compound of formula (III), Q 3 N and Q 4 is N.

[0623] In some embodiments of compounds of formula (III), each W is independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of compounds of formula (III), each W is independently hydrogen, halogen, or C1-C6 alkyl. In some embodiments of compounds of formula (III), each W is hydrogen.

[0624] In some embodiments of the compound of formula (III), R 3 Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkynyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (III), R 3 is halogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a replace.

[0625] In some embodiments of the compound of formula (III), R 3Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), R 3 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), R 3 is halogen or C1-C6 hydroxyalkyl, C1-C6 heteroalkyl. In some embodiments of the compound of formula (III), R 3 In some embodiments of the compound of formula (III), R 3 Not hydrogen.

[0626] In some embodiments of the compound of formula (III), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (III), each R 3a are independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (III), each R 3a are independently halogen, -OR b , C1-C6 alkyl or cycloalkyl.

[0627] In some embodiments of the compound of formula (III), R 1is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (III), R 1 is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (III), R 1 is C1-C6 alkyl, cycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl) or C1-C6 alkyl (cycloalkyl); wherein each alkyl, cycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (III), R 1 is C1-C6 alkyl, cycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl) or C1-C6 alkyl (cycloalkyl); wherein each alkyl, cycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (III), R 1 is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (III), R 1 is cycloalkyl or C1-C6 alkyl (cycloalkyl); wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R 1a In some embodiments of the compound of formula (III), R 1 is optionally replaced by one, two or three R 1a Substituted cycloalkyl.

[0628] In some embodiments of the compound of formula (III), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (III), each R 1a are independently halogen or C1-C6 alkyl.

[0629] In some embodiments of the compound of formula (III), R 2 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (III), R 2 In some embodiments of the compound of formula (III), R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b Substituted heterocycloalkyl.

[0630] In some embodiments of the compound of formula (III), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (III), each R 1b are independently halogen or C1-C6 alkyl.

[0631] In some embodiments of the compound of formula (III), R 8 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (III), R 8 For hydrogen.

[0632] In some embodiments of the compound of formula (III), R 9 and R 10 are independently hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (III), R 9 and R 10 For hydrogen.

[0633] In some embodiments of the compound of formula (III), X is -O- or -S-. In some embodiments of the compound of formula (III), X is -O-. In some embodiments of the compound of formula (III), X is -S-.

[0634] In some embodiments of the compound of formula (III), A is -O-. In some embodiments of the compound of formula (III), A is -CH2-.

[0635] In some embodiments of the compound of formula (III), R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), R 5 and R 6 are independently hydrogen, halogen, -OR b or C1-C6 alkyl. In some embodiments of the compound of formula (III), R 5 and R 6 For hydrogen.

[0636] In some embodiments of the compound of formula (III), R 4 and R 7 are independently hydrogen, halogen, -OR b, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), R 4 and R 7 are independently hydrogen, halogen, -OR b or C1-C6 alkyl. In some embodiments of the compound of formula (III), R 4 and R 7 are independently hydrogen, halogen or -OR b In some embodiments of the compound of formula (III), R 4 and R 7 are independently hydrogen, halogen or -OH. In some embodiments of the compound of formula (III), R 4 and R 7 In some embodiments of the compound of formula (III), R 4 and R 7 are independently hydrogen or -OH. In some embodiments of the compound of formula (III), R 4 and R 7 It is -OH.

[0637] In some embodiments of the compound of formula (III), R 5 and R 6 is hydrogen and R 4 and R 7 In some embodiments of the compound of formula (III), R 5 and R 6 is hydrogen and R 4 and R 7 In some embodiments of the compound of formula (III), R 5 and R 6 is hydrogen and R 4 and R 7 are independently hydrogen or -OH.

[0638] In some embodiments of the compound of formula (III), R 21 and R 22 are independently hydrogen, C1-C 20 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (III), R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl or aryl; wherein each alkyl and aryl group is independently optionally substituted by one, two or three R 21aIn some embodiments of the compound of formula (III), R 21 and R 22 are independently hydrogen, optionally substituted by one, two or three R 21a Substituted C1-C 20 In some embodiments of the compound of formula (III), R 21 and R 22 For hydrogen.

[0639] In some embodiments of the compound of formula (III), each R 21a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b or C1-C6 alkyl. In some embodiments of the compound of formula (III), each R 21a are independently -C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b or -OC(=O)NR c R d In some embodiments of the compound of formula (III), each R 21a are independently -C(=O)OR b OR-OC(=O)OR b .

[0640] In some embodiments of the compound of formula (III), R 21 and R 22 Together with the atoms to which they are attached, they form a 21b Substituted heterocycloalkyl.

[0641] In some embodiments of the compound of formula (III), each R 21b are independently oxo (when applicable), halogen, -CN, -ORb 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 21b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 21b are independently halogen or C1-C6 alkyl.

[0642] In some embodiments of the compound of formula (III), R 12 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), R 12 Halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), R 12is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (III), R 12 is halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (III), R 12 In some embodiments of the compound of formula (III), R 12 is C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (III), R 12 In some embodiments of the compound of formula (III), R 12 Not hydrogen.

[0643] In some embodiments of the compound of formula (III), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (III), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (III), each R 12a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c replace.

[0644] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a replace.

[0645] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a Replacement; provided that R 11 Not CF3.

[0646] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -OR 13 、-NR 15 R16 、-S(=O)2R 14 、-C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl or aryl; wherein each alkyl, cycloalkyl, heterocycloalkyl and aryl are independently optionally substituted by one, two or three R 11a replace.

[0647] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a replace.

[0648] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl or aryl; wherein each alkyl, cycloalkyl, heterocycloalkyl and aryl are independently optionally substituted by one, two or three R 11a replace.

[0649] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a replace.

[0650] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a replace.

[0651] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a Replacement; provided that R 11 Not CF3.

[0652] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl or aryl; wherein each alkyl, cycloalkyl, heterocycloalkyl and aryl are independently optionally substituted by one, two or three R 11a replace.

[0653] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a replace.

[0654] In some embodiments of the compound of formula (III), R 11 Halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl or aryl; wherein each alkyl, cycloalkyl, heterocycloalkyl and aryl are independently optionally substituted by one, two or three R 11a replace.

[0655] In some embodiments of the compound of formula (III), R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted by one, two or three R 11a replace.

[0656] In some embodiments of the compound of formula (III), R 11 -CN, -S(=O)2R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted by one, two or three R 11a Replacement; provided that R 11 Not CF3.

[0657] In some embodiments of the compound of formula (III), R 11 -CN, -S(=O)2R 14 , C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 11a replace.

[0658] In some embodiments of the compound of formula (III), R 11 -CN, -S(=O)2R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted by one, two or three R 11a replace.

[0659] In some embodiments of the compound of formula (III), R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 11a replace.

[0660] In some embodiments of the compound of formula (III), R 11 is optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (III), R 11 is optionally replaced by one, two or three R 11a Substituted C1-C6 alkyl; provided that R 11 In some embodiments of the compound of formula (III), R 11 To be an R 11a In some embodiments of the compound of formula (III), R 11 It is a C1-C6 hydroxyalkyl group.

[0661] In some embodiments of the compound of formula (III), R 11 Not CF3.

[0662] In some embodiments of the compound of formula (III), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (III), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (III), each R 11a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c In some embodiments of the compound of formula (III), each R 11a is independently optionally replaced by one, two or three R 11c Substituted aryl.

[0663] In some embodiments of the compound of formula (III), each R 11a Independently -OR 13 In some embodiments of the compound of formula (III), each R 11a are independently -S(=O)2R 14 In some embodiments of the compound of formula (III), each R 11a is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (III), each R 11a are independently -NR 13 C(=O)R 14 .

[0664] In some embodiments of the compound of formula (III), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR cR d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), each R 11c are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), each R 11c are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0665] In some embodiments of the compound of formula (III), R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b In some embodiments of the compound of formula (III), R 11 and R 12 Together forming optionally one, two or three R 11b In some embodiments of the compound of formula (III), R 11 and R 12 Together forming optionally one, two or three R 11b Substituted heterocycloalkyl.

[0666] In some embodiments of the compound of formula (III), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), each R 11b is independently oxo (where applicable), halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0667] In some embodiments of the compound of formula (III), each R 13are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (III), each R 13 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (III), each R 13 are independently hydrogen or C1-C6 alkyl.

[0668] In some embodiments of the compound of formula (III), each R 13a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 13a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 13a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0669] In some embodiments of the compound of formula (III), each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (III), each R 14 is independently C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (III), each R 14 are independently C1-C6 alkyl.

[0670] In some embodiments of the compound of formula (III), each R 14aare independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 14a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 14a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0671] In some embodiments of the compound of formula (III), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (III), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (III), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (III), each R 15 and R 16 are independently hydrogen or C1-C6 alkyl.

[0672] In some embodiments of the compound of formula (III), each R 15a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c Rd , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 15a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 15a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0673] In some embodiments of the compound of formula (III), R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b In some embodiments of the compound of formula (III), R 15 and R 16 Together with the nitrogen atom to which they are attached they form a heterocycloalkyl group.

[0674] In some embodiments of the compound of formula (III), each R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 15b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (III), each R 15b are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0675] In some embodiments, provided herein are compounds having the structure of Formula (IV), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0676]

[0677] in:

[0678] Ring A is Q 2 N or CW;

[0679] Q 3 N and Q 4 For CW;

[0680] or Q 3 CW and Q 4 is N;

[0681] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0682] A is -O- or -CH2-;

[0683] X is -O-, -S-, -S(=O)2-, -NR 17 -or-C(R 18 )2-;

[0684] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0685] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0686] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0687] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0688] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0689] R 4 and R 7 are independently hydrogen, halogen, -OR b, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0690] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0691] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0692] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0693] R 11 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0694] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0695] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0696] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0697] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NRb C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0698] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0699] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0700] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0701] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0702] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)Ra 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0703] R 17 is hydrogen, -CN, -OR b 、-S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0704] Each R 18 are independently hydrogen, halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0705] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0706] or R 21 and R 22Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0707] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0708] Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0709] Each R bis independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0710] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 heteroalkyl.

[0711] C6 haloalkyl substitution;

[0712] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0713] In some embodiments, provided herein are compounds having the structure of Formula (IV), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0714]

[0715] in:

[0716] Ring A is Q 2 N or CW;

[0717] Q 3 N and Q 4 For CW;

[0718] or Q 3 CW and Q 4 is N;

[0719] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0720] A is -O- or -CH2-;

[0721] X is -O-, -S-, -S(=O)2-, -NR 17 -or-C(R 18 )2-;

[0722] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0723] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0724] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b, C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0725] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0726] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0727] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0728] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0729] R 8 For hydrogen, halogen, -OR b 、-NR c R d, C1-C6 alkyl or C1-C6 haloalkyl;

[0730] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0731] R 11 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0732] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0733] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0734] Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0735] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0736] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0737] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0738] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0739] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0740] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)ORb , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0741] R 17 is hydrogen, -CN, -OR b 、-S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0742] Each R 18 are independently hydrogen, halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0743] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace;

[0744] or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl;

[0745] Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0746] Each R ais independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0747] Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and

[0748] Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl;

[0749] or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0750] In some embodiments of the compound of Formula (IV), Q 2 In some embodiments of the compound of formula (IV), Q 2 is N.

[0751] In some embodiments of the compound of Formula (IV), Q 3 N and Q 4 In some embodiments of the compound of formula (IV), Q 4 N and Q 3 For CW.

[0752] In some embodiments of the compound of Formula (IV), Q 2 For CW, Q 3 is N, and Q 4 In some embodiments of the compound of formula (IV), Q 2 For CW, Q 3is CW, and Q 4 is N. In some embodiments of the compound of formula (IV), Q 2 N, Q 3 is N, and Q 4 In some embodiments of the compound of formula (IV), Q 2 N, Q 3 is CW, and Q 4 is N.

[0753] In some embodiments of the compound of formula (IV), each W is independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each W is independently hydrogen, halogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), each W is hydrogen.

[0754] In some embodiments of the compound of Formula (IV), R 3 Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkynyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (IV), R 3 is halogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (IV), R 3 Halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 3 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 3 is halogen or C1-C6 hydroxyalkyl, C1-C6 heteroalkyl. In some embodiments of the compound of formula (IV), R 3 In some embodiments of the compound of formula (IV), R 3 Halogen, -OR b, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (IV), R 3 Halogen, -OR b , C2-C6 alkynyl or C1-C6 hydroxyalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 3a In some embodiments of the compound of formula (IV), R 3 is halogen or C1-C6 hydroxyalkyl.

[0755] In some embodiments of the compound of formula (IV), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 3a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (IV), each R 3a are independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), each R 3a are independently halogen, -OR b , C1-C6 alkyl or cycloalkyl. In some embodiments of the compound of formula (IV), each R 3a are independently oxo (when applicable), halogen or -OR b .

[0756] In some embodiments of the compound of Formula (IV), R 1is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (IV), R 1 is C1-C6 alkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (IV), R 1 is cycloalkyl or C1-C6 alkyl (cycloalkyl); wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R 1a In some embodiments of the compound of formula (IV), R 1 is optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (IV), R 1 is C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (IV), R 1 is C1-C6 alkyl, cycloalkyl, C1-C6 alkyl (aryl) or C1-C6 alkyl (cycloalkyl); wherein each alkyl, cycloalkyl and aryl group is independently optionally replaced by one, two or three R 1a In some embodiments of the compound of formula (IV), R 1 It is a cycloalkyl group or a C1-C6 alkyl group (cycloalkyl group).

[0757] In some embodiments of the compound of formula (IV), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 1a is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (IV), each R 1a are independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), each R 1a are independently oxo (when applicable), halogen, -CN, -OR b , C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (IV), each R 1a are independently halogen or C1-C6 alkyl.

[0758] In some embodiments of the compound of Formula (IV), R 2 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 2 In some embodiments of the compound of formula (IV), R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b Substituted heterocycloalkyl.

[0759] In some embodiments of the compound of formula (IV), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-NRc R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 1b is independently oxo (when applicable), halogen, C1-C6 alkyl or C1-C6 fluoroalkyl. In some embodiments of the compound of formula (IV), each R 1b are independently halogen or C1-C6 alkyl.

[0760] In some embodiments of the compound of Formula (IV), R 8 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 8 For hydrogen.

[0761] In some embodiments of the compound of Formula (IV), R 9 and R 10 are independently hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 9 and R 10 For hydrogen.

[0762] In some embodiments of the compound of formula (IV), A is -O-. In some embodiments of the compound of formula (IV), A is -CH2-.

[0763] In some embodiments of the compound of Formula (IV), R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), R 5 and R 6 are independently hydrogen, halogen, -OR b or C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 5 and R 6 For hydrogen.

[0764] In some embodiments of the compound of Formula (IV), R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), R 4 and R 7 are independently hydrogen, halogen, -OR bor C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 4 and R 7 are independently hydrogen, halogen or -OR b In some embodiments of the compound of formula (IV), R 4 and R 7 are independently hydrogen, halogen or -OH. In some embodiments of the compound of formula (IV), R 4 and R 7 are independently halogen or -OH. In some embodiments of the compound of formula (IV), R 4 and R 7 are independently hydrogen or -OH. In some embodiments of the compound of formula (IV), R 4 and R 7 It is -OH.

[0765] In some embodiments of the compound of Formula (IV), R 5 and R 6 is hydrogen and R 4 and R 7 In some embodiments of the compound of formula (IV), R 5 and R 6 is hydrogen and R 4 and R 7 are independently halogen or -OH. In some embodiments of the compound of formula (IV), R 5 and R 6 is hydrogen and R 4 and R 7 are independently hydrogen or -OH.

[0766] In some embodiments of the compound of formula (IV), X is -O- or -S(=O)2-. In some embodiments of the compound of formula (IV), X is -O-. In some embodiments of the compound of formula (IV), X is -S(=O)2-. In some embodiments of the compound of formula (IV), X is -NR 17 In some embodiments of the compound of formula (IV), X is -C(R 18 )2-.

[0767] In some embodiments of the compound of Formula (IV), R 17 is hydrogen, -C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 17is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 17 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 17 For hydrogen.

[0768] In some embodiments of the compound of formula (IV), each R 18 are independently hydrogen, halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 18 are independently hydrogen, halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 18 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 18 In some embodiments of the compound of formula (IV), each R 18 For hydrogen.

[0769] In some embodiments of the compound of Formula (IV), R 21 and R 22 are independently hydrogen, C1-C 20 alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (IV), R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl or aryl; wherein each alkyl and aryl group is independently optionally substituted by one, two or three R 21a In some embodiments of the compound of formula (IV), R 21 and R 22 are independently hydrogen, optionally substituted by one, two or three R 21a Substituted C1-C 20In some embodiments of the compound of formula (IV), R 21 and R 22 For hydrogen.

[0770] In some embodiments of the compound of formula (IV), each R 21a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b or C1-C6 alkyl. In some embodiments of the compound of formula (IV), each R 21a are independently -C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b or -OC(=O)NR c R d In some embodiments of the compound of formula (IV), each R 21a are independently -C(=O)OR b OR-OC(=O)OR b .

[0771] In some embodiments of the compound of Formula (IV), R 21 and R 22 Together with the atoms to which they are attached, they form a 21b Substituted heterocycloalkyl.

[0772] In some embodiments of the compound of formula (IV), each R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b、-OC(=O)OR b 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 21b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 21b are independently halogen or C1-C6 alkyl.

[0773] In some embodiments of the compound of Formula (IV), R 12 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 12 Halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 12 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (IV), R 12 is C1-C6 alkyl. In some embodiments of the compound of formula (IV), R 12 is C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (IV), R 12In some embodiments of the compound of formula (IV), R 12 In some embodiments of the compound of formula (IV), R 12 For hydrogen, halogen, -OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl or C1-C6 heteroalkyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 12a In some embodiments of the compound of formula (IV), R 12 is hydrogen, C1-C6 alkyl, C1-C6 hydroxyalkyl or C2-C6 alkynyl; wherein each alkyl and alkynyl group is independently optionally substituted by one, two or three R 12a In some embodiments of the compound of formula (IV),

[0774] R 12 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 12 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl.

[0775] In some embodiments of the compound of formula (IV), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace.

[0776] In some embodiments of the compound of formula (IV), each R 12a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace.

[0777] In some embodiments of the compound of formula (IV), each R 12a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 12a are independently oxo (when applicable), halogen, -OR 13 、-SR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)OR 13 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , heterocycloalkyl, aryl or heteroaryl; wherein each heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c replace.

[0778] In some embodiments of the compound of Formula (IV), R 11 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (IV), R 11 is hydrogen, halogen, -CN, -S(=O)2R 14 、-C(=O)R 14 、-C(=O)OR13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (IV), R 11 is hydrogen, -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted by one, two or three R 11a In some embodiments of the compound of formula (IV), R 11 is hydrogen or optionally substituted by one, two or three R 11a In some embodiments of the compound of formula (IV), R 11 is hydrogen or is replaced by an R 11a In some embodiments of the compound of formula (IV), R 11 It is a C1-C6 hydroxyalkyl group.

[0779] In some embodiments of the compound of Formula (IV), R 11 For hydrogen, halogen, -CN, -OR 13 、-NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), R 11 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (IV), R 11 In some embodiments of the compound of formula (IV), R 11 Not hydrogen.

[0780] In some embodiments of the compound of Formula (IV), R 11 Halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-C(=O)OR 13, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11a In some embodiments of the compound of formula (IV), R 11 -CN, -S(=O)2R 14 、-C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkynyl or heteroaryl; wherein each alkyl, alkynyl and heteroaryl is independently optionally substituted by one, two or three R 11a In some embodiments of the compound of formula (IV), R 11 is C1-C6 alkyl or C1-C6 hydroxyalkyl; wherein each alkyl group is independently optionally substituted by one R 11a replace.

[0781] In some embodiments of the compound of formula (IV), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 11a are independently halogen, -CN, -OR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 14 S(=O)2R 14 、-S(=O)2NR 15 R16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 11a Independently -OR 13 、-S(=O)2R 14 、-NR 13 C(=O)R 14 , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 11a is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 11a Independently -OR 13 In some embodiments of the compound of formula (IV), each R 11a are independently -S(=O)2R 14 In some embodiments of the compound of formula (IV), each R 11a is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 11a are independently -NR 13 C(=O)R 14 In some embodiments of the compound of formula (IV), each R 11a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-C(=O)OR 13 、-C(=O)NR15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (IV), each R 11a are independently oxo (when applicable), halogen, -OR 13 、-SR 13 、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)OR 13 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)R 14 , heterocycloalkyl, aryl or heteroaryl; wherein each heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 11c In some embodiments of the compound of formula (II), each R 11a Independently -OR 13 or heteroaryl.

[0782] In some embodiments of the compound of formula (IV), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl. In some embodiments of the compound of formula (IV), each R 11c are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 11c is independently halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl. In some embodiments of the compound of formula (IV), each R 11c Independently -OR b 、-C(=O)OR b or C1-C6 hydroxyalkyl.

[0783] In some embodiments of the compound of Formula (IV), R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b In some embodiments of the compound of formula (IV), R 11 and R 12 Together forming optionally one, two or three R 11b In some embodiments of the compound of formula (IV), R 11 and R 12 Together forming optionally one, two or three R 11b Substituted heterocycloalkyl.

[0784] In some embodiments of the compound of formula (IV), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)ORb 、-C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 11b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 11b is independently oxo (where applicable), halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0785] In some embodiments of the compound of formula (IV), each R 13 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (IV), each R 13 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 13a In some embodiments of the compound of formula (IV), each R 13 are independently hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), each R 13 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 13a In some embodiments of the compound of formula (IV), each R 13 is independently C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl; wherein each alkyl and cycloalkyl group is independently optionally substituted by one, two or three R 13a replace.

[0786] In some embodiments of the compound of formula (IV), each R 13a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 13a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 13a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0787] In some embodiments of the compound of formula (IV), each R 13a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 13a Independently -OR b 、-C(=O)OR b , cycloalkyl, aryl or heteroaryl; wherein each cycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (when applicable), halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compound of formula (IV), each R 13a Independently -OR b 、-C(=O)OR b , cycloalkyl, aryl or heteroaryl.

[0788] In some embodiments of the compound of formula (IV), each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 14aIn some embodiments of the compound of formula (IV), each R 14 is independently C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 14a In some embodiments of the compound of formula (IV), each R 14 are independently C1-C6 alkyl.

[0789] In some embodiments of the compound of formula (IV), each R 14a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 14a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 14a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0790] In some embodiments of the compound of formula (IV), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (IV), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (IV), each R 15 and R 16 are independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; wherein each alkyl group is independently optionally substituted by one, two or three R 15a In some embodiments of the compound of formula (IV), each R 15 and R 16 are independently hydrogen or C1-C6 alkyl.

[0791] In some embodiments of the compound of formula (IV), each R 15a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 15a are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 15a are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0792] In some embodiments of the compound of Formula (IV), R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b In some embodiments of the compound of formula (IV), R 15 and R 16 Together with the nitrogen atom to which they are attached they form a heterocycloalkyl group.

[0793] In some embodiments of the compound of formula (IV), each R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 15b are independently halogen, -CN, -OR b 、-NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl. In some embodiments of the compound of formula (IV), each R 15bare independently halogen, C1-C6 alkyl or C1-C6 haloalkyl.

[0794] In some embodiments, provided herein are compounds having the structure of Formula (V), or a pharmaceutically acceptable salt, solvate, stereoisomer, or isotopic variant thereof:

[0795]

[0796] in:

[0797] Ring A is Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of them is N;

[0798] Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0799] A is -O-;

[0800] X is -O-, -S-, -S(=O)2-, -NR 17 -or-C(R 18 )2-;

[0801] R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace;

[0802] or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl;

[0803] Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c Rd 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0804] R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace;

[0805] Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d, C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0806] R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0807] R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0808] R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl;

[0809] R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0810] R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace;

[0811] R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace;

[0812] or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace;

[0813] Each R 11a 、R 11b and R 12aare independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace;

[0814] Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0815] Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace;

[0816] Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace;

[0817] Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace;

[0818] or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl;

[0819] Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -ORb 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;

[0820] R 17 is hydrogen, -CN, -OR b 、-S(=O)2R a 、-C(=O)R a 、-C(=O)OR b、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0821] Each R 18 are independently hydrogen, halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl);

[0822] R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); where...

Claims

1. A compound of formula (II), or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof: in: Ring A is Q 1 N and Q 2 CW or Q 1 N and Q 2 is N; Q 3 and Q 4 are independently N or CW; provided that Q 3 or Q 4 At least one of is N; Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl; A is -O-; X is -S- or -O-; R 1 and R 2 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl) or C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 1a replace; or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl; Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace; Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl; R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl; R 11 Halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace; R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace; or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace; Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace; Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace; Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace; Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace; or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl; Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl; R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace; or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl; Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

2. The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Q 1 is N; and Q 2 For CW.

3. The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Q 1 is N; and Q 2 is N.

4. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Q 3 N and Q 4 For CW.

5. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Q 4 N and Q 3 For CW.

6. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Q 3 N and Q 4 is N.

7. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Each W is independently hydrogen, halogen or C1-C6 alkyl.

8. The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof, wherein: Each W is hydrogen.

9. A compound of formula (IV), or a pharmaceutically acceptable salt, solvate, stereoisomer or isotopic variant thereof: in: Ring A is Q 2 N or CW; Q 3 N and Q 4 For CW; or Q 3 CW and Q 4 is N; Each W is independently hydrogen, halogen, -CN, -OR b NR c R d , C1-C6 alkyl or C1-C6 haloalkyl; A is -O- or -CH2-; X is -O-, -S-, -S(=O)2-, -NR 17 -or-C(R 18 )2-; R 1 and R 2 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 1a replace; or R 1 and R 2 Together with the nitrogen atom to which they are attached, they form a 1b substituted heterocycloalkyl; Each R 1a and R 1b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); R 3 For hydrogen, halogen, -CN, -OR b 、-SR b 、-NR c R d , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 3a replace; Each R 3a are independently oxo (when applicable), halogen, -CN, -OR b 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 4 and R 7 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 5 and R 6 are independently hydrogen, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 8 For hydrogen, halogen, -OR b 、-NR c R d , C1-C6 alkyl or C1-C6 haloalkyl; R 9 and R 10 are independently hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl; R 11 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11a replace; R 12 For hydrogen, halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 12a replace; or R 11 and R 12 together to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one, two or three R 11b replace; Each R 11a 、R 11b and R 12a are independently oxo (when applicable), halogen, -CN, -OR 13 、-SR 13 、-S(=O)R 14 、-NO2、-NR 15 R 16 、-S(=O)2R 14 、-NR 13 S(=O)2R 14 、-S(=O)2NR 15 R 16 、-C(=O)R 14 、-OC(=O)R 14 、-C(=O)OR 13 、-OC(=O)OR 13 、-C(=O)NR 15 R 16 、-OC(=O)NR 15 R 16 、-NR 13 C(=O)NR 15 R 16 、-NR 13 C(=O)R 14 、-NR 13 C(=O)OR 13 , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 11c replace; Each R 11c are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NR b S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); Each R 13 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 13a replace; Each R 14 is independently C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally replaced by one, two or three R 14a replace; Each R 15 and R 16 R is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted by one, two or three R 15a replace; or R 15 and R 16 Together with the nitrogen atom to which they are attached, they form a 15b substituted heterocycloalkyl; Each R 13a 、R 14a 、R 15a and R 15b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one, two or three oxo (where applicable), halogen, -CN, -OR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl; R 17 is hydrogen, -CN, -OR b 、-S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); Each R 18 are independently hydrogen, halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); R 21 and R 22 are independently hydrogen, C1-C 20 Alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl (aryl), C1-C6 alkyl (heteroaryl), C1-C6 alkyl (cycloalkyl), C1-C6 alkyl (heterocycloalkyl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally replaced by one, two or three R 21a replace; or R 21 and R 22 Together with the atoms to which they are attached, they form a 21b substituted heterocycloalkyl; Each R 21a and R 21b are independently oxo (when applicable), halogen, -CN, -OR b 、-SR b 、-S(=O)R a 、-NO2、-NR c R d 、-S(=O)2R a 、-NHS(=O)2R a 、-S(=O)2NR c R d 、-C(=O)R a 、-OC(=O)R a 、-C(=O)OR b 、-OC(=O)OR b 、-C(=O)NR c R d 、-OC(=O)NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl) or C1-C6 alkyl(heterocycloalkyl); Each R a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; Each R b is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; and Each R c and R d is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently optionally substituted with one, two or three oxo (where applicable), halogen, -OH, C1-C6 alkyl or C1-C6 haloalkyl; or R c and R d Together with the nitrogen atom to which they are attached, they form a heterocycloalkyl group which is optionally substituted with one, two or three oxo, halogen, C1-C6 alkyl or C1-C6 haloalkyl.

10. A compound selected from:

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