SARS-CoV2 major protease inhibitors

Abstract

The present disclosure relates to compounds of formula (I): # imgabs0 # and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, useful in the treatment of viral infections, such as coronavirus infections.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 370,629 filed on August 5, 2022, U.S. Provisional Patent Application No. 63 / 375,522 filed on September 13, 2022, U.S. Provisional Patent Application No. 63 / 476,359 filed on December 20, 2022, U.S. Provisional Patent Application No. 63 / 482,750 filed on February 1, 2023, U.S. Provisional Patent Application No. 63 / 486,156 filed on February 21, 2023, and U.S. Provisional Patent Application No. 63 / 508,350 filed on June 15, 2023, each of which is hereby incorporated by reference in its entirety. Background Art

[0003] Coronaviruses, named for the crown-like spikes on their surface, primarily infect bats, pigs, and small mammals. Coronaviruses are prone to mutation, and they can jump from animals to humans and from one person to another. In recent years, they have become a major player in infectious disease outbreaks worldwide. Compounds and methods for treating viral infections, such as coronavirus infections, are needed. The present disclosure addresses these and other needs. Summary of the Invention

[0004] In one embodiment, the present disclosure provides a compound of formula (I):

[0005]

[0006] or a pharmaceutically acceptable salt thereof, wherein

[0007] ring C 6-10 aryl or 5- to 10-membered heteroaryl;

[0008] Each L 1 are independently a bond, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or –(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-;

[0009] Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic group,

[0010] wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace;

[0011] Alternatively, two R 1 and the rings to which they are attached The atoms are taken together to form a 5- to 10-membered heterocyclic group;

[0012] Each R 1a Independently C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C1-6 alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2、-C(O)N(5- to 10-membered heterocyclyl)2、-C(O)N(C6 aryl)2、-C(O)N(5- to 10-membered heteroaryl)2、-NHC(O)(C 1-6 alkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0013] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace;

[0014] Each R 1b Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 2-6 Alkynyl), -NHC(O)O(C 3-8Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0015] m is an integer from 0 to 3;

[0016] R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3 haloalkyl), -O(cyclopropyl), halogen or -CN;

[0017] X 1 S, N or C(R x1 );

[0018] X 2 S, N or C(R x2 );

[0019] X 3 N or C(R x3 ), the condition is X 1 and X 2 Not for S;

[0020] Alternatively, X 3 is a key, where X 1 and X 2 One of them is S;

[0021] Each R x1 、R x2 and R x3 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 Alkoxy, cyclopropyl or O-cyclopropyl;

[0022] ring With X4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 a cycloalkyl group or a 5- to 10-membered heterocyclic group,

[0023] Each X 4 and X 5 are independently N or C;

[0024] Alternatively, the ring does not exist, where X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 ;

[0025] Each L x4 and L x5 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0026] Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 Cycloalkyl;

[0027] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 4a replace;

[0028] Each R 4a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0029] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace;

[0030] Each R 4b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0031] Each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0032] Each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6alkyl)2 or -OC 3-8 Cycloalkyl;

[0033] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 3a replace;

[0034] Each R 3a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0035] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace;

[0036] Each R 3b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0037] Each R L are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 Cycloalkyl;

[0038] n is an integer from 0 to 3;

[0039] Each X 6 and X 7 are independently N or CH,

[0040] where X 4 、X 5 、X 6 and X 7 No more than two of them are N;

[0041] L 2 is a bond, C1-C6 alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(RL2 )S(O)2- or -(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-;

[0042] R L2 is hydrogen or C 1-6 alkyl;

[0043] R 5 is hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a C(O)R 5a 、-NR 5a 2. C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace;

[0044] Each R 5a are independently hydrogen or C 1-6 alkyl;

[0045] Each R 5b are independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3 Alkoxy, -OCF3 or -OCF2H; and

[0046] Z is O or S.

[0047] In one embodiment, the present disclosure provides a compound of formula (I):

[0048]

[0049] or a pharmaceutically acceptable salt thereof, wherein

[0050] ring C 6-10 aryl or 5- to 10-membered heteroaryl;

[0051] Each L 1 are independently a bond, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L)NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or –(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-;

[0052] Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic group,

[0053] wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace;

[0054] Each R 1a Independently C 1-6 Alkyl, halogen, C 3-8Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2、-C(O)N(5- to 10-membered heterocyclyl)2、-C(O)N(C6 aryl)2、-C(O)N(5- to 10-membered heteroaryl)2、-NHC(O)(C 1-6 alkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0055] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace;

[0056] Each R 1b Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 2-6 Alkynyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0057] m is an integer from 0 to 3;

[0058] R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3 haloalkyl), -O(cyclopropyl), halogen or -CN;

[0059] X 1 S, N or C(R x1 );

[0060] X 2 S, N or C(R x2 );

[0061] X 3 N or C(R x3 ), the condition is X 1 and X 2 Not for S;

[0062] Alternatively, X 3 is a key, where X 1 and X 2 One of them is S;

[0063] Each R x1 Rx2 and R x3 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 Alkoxy, cyclopropyl or O-cyclopropyl;

[0064] ring With X 4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 a cycloalkyl group or a 5- to 10-membered heterocyclic group,

[0065] Each X 4 and X 5 are independently N or C;

[0066] Alternatively, the ring does not exist, where X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 ;

[0067] Each L x4 and L x5 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0068] Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 Cycloalkyl;

[0069] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 4a replace;

[0070] Each R 4a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0071] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace;

[0072] Each R 4b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0073] Each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6alkyl)C(O)- or -N(R L )C(O)-;

[0074] Each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 or -OC 3-8 Cycloalkyl;

[0075] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 3a replace;

[0076] Each R 3a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0077] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace;

[0078] Each R 3b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0079] Each R L are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 Cycloalkyl;

[0080] n is an integer from 0 to 3;

[0081] Each X 6 and X 7 are independently N or CH,

[0082] where X 4 、X 5 、X 6 and X 7 No more than two of them are N;

[0083] L 2is a bond, C1-C6 alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(R L2 )S(O)2- or -(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-;

[0084] R L2 is hydrogen or C 1-6 alkyl;

[0085] R 5 is hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a 2. C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace;

[0086] Each R 5a are independently hydrogen or C 1-6 alkyl;

[0087] Each R 5b are independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3 Alkoxy, -OCF3 or -OCF2H; and

[0088] Z is O or S.

[0089] In another embodiment, the present disclosure provides a pharmaceutical composition comprising a pharmaceutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0090] In another embodiment, the present disclosure provides a method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure. DETAILED DESCRIPTION

[0091] The present disclosure generally relates to methods and compounds for treating or preventing viral infections, such as coronavirus infections.

[0092] definition

[0093] As used in this specification, the following words, phrases, and symbols are generally intended to have the meanings set forth below, unless the context in which they are used indicates otherwise.

[0094] "Alkyl" refers to an unbranched or branched saturated hydrocarbon chain. For example, an alkyl group can have 1 to 20 carbon atoms (i.e., C1-C 20Examples of suitable alkyl groups include, but are not limited to, methyl (Me, -CH), ethyl (Et, -CHCH), 1-propyl (n-Pr, n-propyl, -CHCHCH), 2-propyl (i-Pr, isopropyl, -CH(CH)), 1-butyl (n-Bu, n-butyl, -CHCHCHCH), 2-methyl-1-propyl (i-Bu, isobutyl, -CHCH(CH)), 2-butyl (s-Bu, sec-butyl, -C H(CH3)CH2CH3), 2-methyl-2-propyl (t-Bu, tert-butyl, -C(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1 -butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (- 2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), and 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3).

[0095] "Alkenyl" refers to a straight or branched chain hydrocarbon having at least 2 carbon atoms and at least one double bond. Alkenyl groups may include any number of carbon atoms, such as C2, C 2-3 、C 2-4 、C 2-5 、C 2-6 、C 2-7 、C 2-8 、C 2-9 、C 2-10 , C3, C 3-4 、C 3-5 、C 3-6 , C4, C4-5 、C 4-6 , C5, C 5-6 and C6. The alkenyl group may have any suitable number of double bonds, including but not limited to 1, 2, 3, 4, 5 or more. Examples of alkenyl groups include but are not limited to ethenyl, propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl or 1,3,5-hexatrienyl. The alkenyl group may be substituted or unsubstituted.

[0096] "Alkynyl" refers to a straight or branched chain hydrocarbon having at least 2 carbon atoms and at least one triple bond. Alkynyl groups may include any number of carbon atoms, such as C2, C 2-3 、C 2-4 、C 2-5 、C 2-6 、C 2-7 、C 2-8 、C 2-9 、C 2-10 , C3, C 3-4 、C 3-5 、C 3-6 , C4, C 4-5 、C 4-6 , C5, C 5-6 Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentenyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexatriynyl. Alkynyl groups may be substituted or unsubstituted.

[0097] "Alkoxy" refers to an alkyl group with an oxygen atom connecting the alkyl group to the point of attachment: alkyl-O-. Like alkyl groups, alkoxy groups can have any suitable number of carbon atoms, such as C 1-6 Alkoxy groups include, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 2-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, and the like. Alkoxy groups may be further substituted with various substituents as described herein. Alkoxy groups may be substituted or unsubstituted.

[0098] "Alkoxyalkyl" refers to an alkoxy group attached to an alkyl group, which is attached to the rest of the compound, such that the alkyl group is divalent. Alkoxyalkyl groups can have any suitable number of carbon atoms, such as 2 to 6 (C2-6 alkoxyalkyl), 2 to 5 (C 2-5 Alkoxyalkyl), 2 to 4 (C 2-4 alkoxyalkyl), or 2 to 3 (C 2-3 Alkoxy and alkyl are as defined above, wherein alkyl is divalent and may include, but is not limited to, methoxymethyl (CH3OCH2-), methoxyethyl (CH3OCH2CH2-), and the like.

[0099] "Alkoxy-alkoxy" refers to an alkoxy group connected to a second alkoxy group, which is connected to the rest of the compound. Alkoxy is as defined above and may include, but is not limited to, methoxy-methoxy (CH3OCH2O-), methoxy-ethoxy (CH3OCH2CH2O-), and the like.

[0100] As used herein, "halo" or "halogen" refers to fluoro (-F), chloro (-Cl), bromo (-Br), and iodo (-I).

[0101] As used herein, the term "oxo" is intended to mean an oxygen atom as a substituent attached to a carbon atom through a double bond (=0).

[0102] "Hydroxyl" is used interchangeably and refers to -OH.

[0103] As used herein, "haloalkyl" refers to an alkyl group as defined herein, wherein one or more hydrogen atoms of the alkyl group are independently replaced by a halo substituent, which halo substituents can be the same or different. For example, C 1-4 Haloalkyl is C 1-4 Alkyl, where C 1-4 One or more of the hydrogen atoms of the alkyl group has been replaced by a halo substituent. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, fluorochloromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and pentafluoroethyl.

[0104] "Haloalkoxy" refers to an alkoxy group in which some or all of the hydrogen atoms are replaced by halogen atoms. With respect to alkyl groups, a haloalkoxy group can have any suitable number of carbon atoms, such as C 1-6 Alkoxy groups may be substituted with 1, 2, 3, or more halogens. When all hydrogens are replaced with halogens (e.g., fluorine), the compound is fully substituted, e.g., perfluorinated. Haloalkoxy groups include, but are not limited to, trifluoromethoxy, 2,2,2,-trifluoroethoxy, perfluoroethoxy, and the like.

[0105] "Cycloalkyl" refers to a ring having 3 to 20 carbon atoms (i.e., C 3-20The term "cycloalkyl" also includes a single saturated or partially unsaturated full carbocycle of a cycloalkyl group (e.g., 3 to 12 cyclic atoms, such as 3 to 10 cyclic atoms or 3 to 8 cyclic atoms or 3 to 6 cyclic atoms or 3 to 5 cyclic atoms or 3 to 4 cyclic atoms). The term "cycloalkyl" also includes multiple fused, saturated and partially unsaturated full carbocycle systems (e.g., a ring system comprising 2, 3 or 4 carbocycles). Therefore, cycloalkyl includes polycyclic carbocycles, such as bicyclic carbocycles (e.g., bicyclic carbocycles with 6 to 12 cyclic carbon atoms, such as bicyclo [3.1.0] hexane and bicyclo [2.1.1] hexane) and polycyclic carbocycles (e.g., tricyclic and tetracyclic carbocycles with up to 20 cyclic carbon atoms). When valence requirements allow, the rings of multiple fused ring systems can be connected to each other via fusion, spirocycles and bridge bonds. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, and 1-cyclohex-3-enyl.

[0106] "Alkyl-cycloalkyl" refers to a group having an alkyl component and a cycloalkyl component, wherein the alkyl component is connected to the cycloalkyl component at the point of attachment. The alkyl component is as defined above, except that the alkyl component is an at least divalent alkylene group connected to the cycloalkyl component and the point of attachment. In some cases, the alkyl component may not be present. The alkyl component may include any number of carbon atoms, such as C 1-6 、C 1-2 、C 1-3 、C 1-4 、C 1-5 、C 2-3 、C 2-4 、C 2-5 、C 2-6 、C 3-4 、C 3-5 、C 3-6 、C 4-5 、C 4-6 and C 5-6 The cycloalkyl component is as defined herein. Exemplary alkyl-cycloalkyl groups include, but are not limited to, methyl-cyclopropyl, methyl-cyclobutyl, methyl-cyclopentyl, and methyl-cyclohexyl.

[0107] As used herein, "heterocyclyl" or "heterocycle" or "heterocycloalkyl" refers to a single saturated or partially unsaturated non-aromatic ring or multiple ring systems having at least one heteroatom (i.e., at least one cyclic heteroatom selected from oxygen, nitrogen and sulfur) in the ring, wherein the multiple ring systems include at least one non-aromatic ring containing at least one heteroatom. The multiple ring systems may also include other aromatic rings and non-aromatic rings. Unless otherwise specified, a heterocyclyl group has 3 to 20 ring atoms, such as 3 to 12 ring atoms, such as 3 to 10 ring atoms, or 3 to 8 ring atoms, or 3 to 6 ring atoms, or 3 to 5 ring atoms, or 4 to 6 ring atoms, or 4 to 5 ring atoms. Thus, the term includes single saturated or partially unsaturated rings (e.g., 3-membered, 4-membered, 5-membered, 6-membered or 7-membered rings) having 1 to 6 ring carbon atoms and 1 to 3 cyclic heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur in the ring. The heteroatom may be optionally oxidized to form –N(-OH)-, =N(-O-)-, -S(=O)- or –S(=O)2-. When valence requirements permit, the rings of multiple fused rings (e.g., bicyclic heterocyclyl) systems may be connected to each other via fusion, spirocycles, and bridge bonds. Heterocycles include, but are not limited to, azetidine, aziridine, imidazolidine, morpholine, oxirane (epoxide), oxetane, thietane, piperazine, piperidine, pyrazolidine, piperidine, pyrrolidine, pyrrolidone, tetrahydrofuran, tetrahydrothiophene, dihydropyridine, tetrahydropyridine, quinuclidine, 2-oxa-6-azaspiro[3.3]heptane-6-yl, 6-oxa-1-azaspiro[3.3]heptane-1-yl, 2-thio 1.0]hexan-2-yl, 3-azabicyclo[3.1.0]hexan-2-yl, 2-azabicyclo[2.1.1]hexan-2-yl, 2-azabicyclo[2.2.1]heptan-2-yl, 4-azaspiro[2.4]heptan-6-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2-azabicyclo[3.1.0]hexan-2-yl, 3-azabicyclo[3.1.0]hexan-2-yl, 2-azabicyclo[2.1.1]hexan-2-yl, 4-azaspiro[2.4]heptan-6-yl, 5-azaspiro[2.4]heptan-2-yl, and the like.

[0108] "Alkyl-heterocycloalkyl" refers to a group having an alkyl component and a heterocycloalkyl component, wherein the alkyl component is connected to the heterocycloalkyl component at a point of attachment. The alkyl component is as defined above, except that the alkyl component is an at least divalent alkylene group connected to the heterocycloalkyl component and the point of attachment. The alkyl component may include any number of carbon atoms, such as C 0-6 、C 1-2 、C 1-3 、C 1-4 、C 1-5 、C 1-6 、C 2-3 、C 2-4 、C 2-5 、C 2-6 、C 3-4 、C 3-5 、C3-6 、C 4-5 、C 4-6 and C 5-6 In some cases, the alkyl component may not be present. The heterocycloalkyl component is as defined above. The alkyl-heterocycloalkyl group may be substituted or unsubstituted.

[0109] As used herein, "aryl" refers to a single all-carbon aromatic ring or a polycondensed all-carbon ring system, wherein at least one ring is aromatic. For example, in some embodiments, the aryl group has 6 to 20 carbon atoms, 6 to 14 carbon atoms, or 6 to 12 carbon atoms. Aryl includes a phenyl radical. Aryl also includes a polycondensed ring system (for example, a ring system comprising 2, 3 or 4 rings) with 9 to 20 carbon atoms, wherein at least one ring is aromatic, and wherein the other rings may be aromatic or not aromatic (i.e., carbocycle) and may be saturated or partially saturated. Such polycondensed ring systems are optionally substituted by one or more (for example, 1, 2 or 3) oxo groups on any carbocyclic ring portion of the polycondensed ring system. When valence requirements allow, the rings of the polycondensed ring systems may be connected to each other via fusion, spirocycles and bridge bonds. It should also be understood that when a certain atomic range of aryl groups (e.g., 6-10 membered aryl groups) is cited, the atomic range is the total ring atoms of the aryl group. For example, a 6-membered aryl group would include phenyl, and a 10-membered aryl group would include naphthyl and 1,2,3,4-tetrahydronaphthyl. Non-limiting examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, and the like.

[0110] "Alkyl-aryl" refers to a group having an alkyl component and an aryl component, wherein the alkyl component is connected to the aryl component at the point of attachment. The alkyl component is as defined above, except that the alkyl component is an at least divalent alkylene group connected to the aryl component and the point of attachment. The alkyl component may include any number of carbon atoms, such as C 0-6 、C 1-2 、C 1-3 、C 1-4 、C 1-5 、C 1-6 、C 2-3 、C 2-4 、C 2-5 、C 2-6 、C 3-4 、C 3-5 、C 3-6 、C 4-5 、C 4-6 and C 5-6 In some cases, the alkyl component may not be present. The aryl component is as defined above. Examples of alkyl-aryl groups include, but are not limited to, benzyl and ethyl-benzene. Alkyl-aryl groups may be substituted or unsubstituted.

[0111] As used herein, "heteroaryl" refers to a single aromatic ring having at least one atom other than carbon in the ring, wherein the atom is selected from the group consisting of oxygen, nitrogen, and sulfur; "heteroaryl" also includes multiple fused ring systems having at least one such aromatic ring, which are further described below. Thus, "heteroaryl" includes a single aromatic ring of 1 to 6 carbon atoms and 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. The sulfur and nitrogen atoms may also exist in oxidized form, provided that the ring is aromatic. Exemplary heteroaryl ring systems include, but are not limited to, pyridyl, pyrimidinyl, oxazolyl, or furanyl. "Heteroaryl" also includes polycondensed ring systems (e.g., ring systems containing 2, 3, or 4 rings), wherein a heteroaryl group as defined above is fused to one or more rings selected from heteroaryl (to form, for example, 1,8-naphthyridinyl), heterocyclic ring (to form, for example, 1,2,3,4-tetrahydro-1,8-naphthyridinyl), carbocyclic ring (to form, for example, 5,6,7,8-tetrahydroquinolinyl), and aryl (to form, for example, indazolyl) to form a polycondensed ring system. The other rings may be aromatic or non-aromatic (i.e., carbocyclic rings) and may be saturated or partially saturated. Thus, heteroaryl (single aromatic ring or multiple condensed ring systems) has 1-20 carbon atoms and 1-6 heteroatoms within the heteroaryl ring. Such polycondensed ring systems may be optionally substituted with one or more (e.g., 1, 2, 3, or 4) oxo groups on the carbocyclic or heterocyclic ring portions of the condensed rings. When valence requirements allow, the rings of the polycondensed ring systems can be connected to each other via fusion, spirocycles and bridge bonds. It should be understood that the individual rings of the polycondensed ring systems can be connected in any order relative to each other. It should be understood that the attachment point of the heteroaryl or heteroaryl polycondensed ring systems can be located on any suitable atom of the heteroaryl or heteroaryl polycondensed ring systems, including carbon atoms and heteroatoms (e.g., nitrogen). It should also be understood that when citing a certain atomic range unit heteroaryl (e.g., 5 to 10 yuan heteroaryl), the atomic range is the total ring atoms of the heteroaryl and includes carbon atoms and heteroatoms. For example, a 5 yuan heteroaryl will include thiazolyl, and a 10 yuan heteroaryl will include quinolyl. Exemplary heteroaryl groups include, but are not limited to, pyridinyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, thienyl, indolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furanyl, oxadiazolyl, thiadiazolyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzoxazolyl, indazolyl, quinoxalinyl, quinazolinyl, 5,6,7,8-tetrahydroisoquinolinyl, benzofuranyl, benzimidazolyl, thienyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl-4(3H)-one, and triazolyl.

[0112] "Alkyl-heteroaryl" refers to a group having an alkyl component and a heteroaryl component, wherein the alkyl component is connected to the heteroaryl component at a point of attachment. The alkyl component is as defined above, except that the alkyl component is an at least divalent alkylene group connected to the heteroaryl component and the point of attachment. The alkyl component may include any number of carbon atoms, such as C0-6 、C 1-2 、C 1-3 、C 1-4 、C 1-5 、C 1-6 、C 2-3 、C 2-4 、C 2-5 、C 2-6 、C 3-4 、C 3-5 、C 3-6 、C 4-5 、C 4-6 and C 5-6 In some cases, the alkyl component may be absent. The heteroaryl component is as defined herein. The alkyl-heteroaryl group may be substituted or unsubstituted.

[0113] "Compounds of the present disclosure" include compounds disclosed herein, for example, compounds of the present disclosure include compounds of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va) and (Vb), including the compounds of the Examples.

[0114] As used herein, "composition" is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. "Pharmaceutically acceptable" means the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0115] "Pharmaceutically effective amount" refers to that amount of a compound of the present disclosure in a formulation or combination thereof that provides the desired therapeutic or pharmaceutical result.

[0116] "Pharmaceutically acceptable excipients" include, but are not limited to, any adjuvant, carrier, vehicle, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier that has been approved by the U.S. Food and Drug Administration as acceptable for use in humans or veterinary animals.

[0117] As used herein, "treatment" refers to a method for obtaining a beneficial or desired result. For the purposes of this disclosure, a beneficial or desired result includes, but is not limited to, alleviation of symptoms and / or reduction of the degree of symptoms and / or prevention of worsening of symptoms associated with a disease or condition. In one embodiment, "treatment" includes one or more of the following: a) inhibiting a disease or condition (e.g., reducing one or more symptoms caused by the disease or condition, and / or reducing the degree of the disease or condition); b) slowing down or preventing the development of one or more symptoms associated with a disease or condition (e.g., stabilizing the disease or condition, delaying the worsening or progression of the disease or condition); and c) alleviating a disease or condition, such as causing regression of clinical symptoms, improving the disease state, delaying the progression of the disease, improving the quality of life, and / or prolonging survival.

[0118] The term "treating" also encompasses alleviating or eliminating the symptoms of viral infection and / or reducing the viral load in a patient. The term "treating" also encompasses administering a compound or composition according to the embodiments disclosed herein after an individual has been exposed to a virus but before disease symptoms appear and / or before the virus is detected in the blood, to prevent the appearance of disease symptoms and / or prevent the virus from reaching detectable levels in the blood.

[0119] As used herein, "therapeutically effective amount" or "effective amount" refers to an amount that is effective to elicit a desired biological or medical response, including an amount of a compound that is sufficient to affect such treatment of a disease when administered to a subject for the treatment of a disease. The effective amount may vary depending on the compound, the disease to be treated and its severity, as well as the age, weight, etc. of the subject. The effective amount may include a range of amounts. As understood in the art, an effective amount may be one or more doses, i.e., a single dose or multiple doses may be required to achieve the desired therapeutic endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents, and if a desired or beneficial result can be achieved or realized in combination with one or more other agents, then a single agent may be considered to be administered in an effective amount. The appropriate dosage of any co-administered compound may optionally be reduced due to the combined action of the compounds (e.g., additive or synergistic effect).

[0120] "Administering" refers to oral administration, administration as a suppository, topical contact, parenteral administration, intravenous, intraperitoneal, intramuscular, intralesional, intranasal or subcutaneous administration, intrathecal administration or implantation of a slow-release device (e.g., a mini-osmotic pump) to a subject. Administration can be carried out according to a schedule specifying the frequency of administration, the dosage administered, and other factors.

[0121] As used herein, "co-administration" refers to administering a unit dose of a compound disclosed herein before or after administering a unit dose of one or more additional therapeutic agents, for example, administering a compound disclosed herein within seconds, minutes, or hours of administering one or more additional therapeutic agents. For example, in some embodiments, a unit dose of a compound of the present disclosure is administered first, followed by administration of a unit dose of one or more additional therapeutic agents within seconds or minutes. Alternatively, in other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed by administration of a unit dose of a compound of the present disclosure within seconds or minutes. In some embodiments, a unit dose of a compound of the present disclosure is administered first, followed by administration of a unit dose of one or more additional therapeutic agents a few hours (e.g., 1 hour to 12 hours) later. In other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed by administration of a unit dose of a compound of the present disclosure a few hours (e.g., 1 hour to 12 hours) later. Co-administration of a compound disclosed herein with one or more additional therapeutic agents generally refers to administering a compound disclosed herein and one or more additional therapeutic agents simultaneously or sequentially, such that a therapeutically effective amount of each agent is present in the patient's body.

[0122] "Subject" refers to an animal, such as a mammal, including but not limited to primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc. In certain embodiments, the subject is a human.

[0123] "Disease" or "disorder" refers to a state of being or health in a patient or subject that can be treated with the compounds, pharmaceutical compositions, or methods provided herein.

[0124] Also provided are pharmaceutically acceptable salts, hydrates, solvates, tautomeric forms, polymorphs, and prodrugs of the compounds described herein. "Pharmaceutically acceptable" or "physiologically acceptable" refers to compounds, salts, compositions, dosage forms, and other materials that can be used to prepare pharmaceutical compositions suitable for veterinary or human pharmaceutical use.

[0125] The compounds described herein can be prepared and / or formulated as pharmaceutically acceptable salts or, where appropriate, as free bases. Pharmaceutically acceptable salts are non-toxic salts of the free base form of the compound that have the desired pharmacological activity of the free base. These salts can be derived from inorganic acids, organic acids, or bases. For example, compounds containing basic nitrogen can be prepared as pharmaceutically acceptable salts by contacting the compound with an inorganic or organic acid. Non-limiting examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, octanoates, acrylates, formates, isobutyrates, hexanoates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyrates, succinates, octanedioates ... Pharmaceutically acceptable salts include benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methylsulfonate, propylsulfonate, benzenesulfonate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, gamma-hydroxybutyrate, glycolate, tartrate, and mandelate. A list of other suitable pharmaceutically acceptable salts can be found in "Remington: The Science and Practice of Pharmacy," 21st edition, Lippincott Wiliams and Wilkins, Philadelphia, Pa., 2006.

[0126] Examples of "pharmaceutically acceptable salts" of the compounds disclosed herein also include those derived from suitable bases such as alkali metals (eg, sodium, potassium), alkaline earth metals (eg, magnesium), ammonium, and NX4. + (wherein X is C1-C4 alkyl). Also included are base addition salts such as sodium or potassium salts.

[0127] Also provided are compounds as described herein or pharmaceutically acceptable salts, isomers or mixtures thereof, wherein 1 to n hydrogen atoms attached to a carbon atom may be replaced by deuterium atoms or D, where n is the number of hydrogen atoms in the molecule. As known in the art, deuterium atoms are non-radioactive isotopes of hydrogen atoms. Such compounds can increase resistance to metabolism and are therefore useful for increasing the half-life of compounds as described herein or pharmaceutically acceptable salts, isomers or mixtures thereof when administered to mammals. See, for example, Foster, "Deuterium Isotope Effects in Studies of Drug Metabolism", Trends Pharmacol. Sci., Vol. 5, No. 12, pp. 524-527, 1984. Such compounds are synthesized by methods well known in the art, for example, by using starting materials in which one or more hydrogen atoms have been replaced by deuterium.

[0128] Examples of isotopes that may be incorporated into the disclosed compounds also include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, such as 2 H. 3 H. 11 C. 13 C. 14 C. 13 N. 15 N. 15 O. 17 O. 18 O. 31 P. 32 P. 35 S. 18 F. 36 Cl, 123 I and 125 I. Use of positron-emitting isotopes such as 11 C. 18 F. 15 O and 13 N substitution can be used in positron emission tomography (PET) studies to examine substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art, or by methods analogous to those described in the Examples listed below, using an appropriate isotopically labeled reagent in place of the non-labeled reagent previously employed.

[0129] The compounds of the embodiments disclosed herein, or their pharmaceutically acceptable salts, may include one or more asymmetric centers and, thus, may give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined as (R)- or (S)- in terms of absolute stereochemistry or as (D)- or (L)- for amino acids. The compounds of the embodiments disclosed herein, or their pharmaceutically acceptable salts, may be "atropisomers," i.e., stereoisomers that arise due to hindered rotation about a single bond, where the barrier to rotation about the bond is sufficiently high to allow separation of individual stereoisomers. The present disclosure is intended to include all such possible isomers and their racemic and optically pure forms. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, such as chromatography and fractional crystallization. Conventional techniques for preparing / isolating individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of racemates (or racemates of salts or derivatives) using, for example, chiral high pressure liquid chromatography (HPLC). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include E and Z geometric isomers. Likewise, all tautomeric forms are also intended to be included. When a compound is represented in its chiral form, it is understood that the embodiment encompasses but is not limited to the specific diastereoisomer or enantiomerically enriched form. When chirality is not specified but exists, it is understood that the embodiment relates to a specific diastereoisomer or enantiomerically enriched form; or a racemic or non-racemic mixture of such a compound. As used herein, a "non-racemic mixture" is a mixture of stereoisomers that is not in a 1:1 ratio.

[0130] "Racemate" refers to a mixture of enantiomers. The mixture may contain equal or unequal amounts of each enantiomer.

[0131] One or more "stereoisomers" refer to compounds with different chirality of one or more stereocenters. Stereoisomers include enantiomers and diastereomers. If a compound has one or more asymmetric centers or a double bond with asymmetrical substitution, these compounds can exist in stereoisomeric forms and therefore can be prepared as individual stereoisomers or as a mixture. Unless otherwise indicated, this specification is intended to include individual stereoisomers and mixtures. Methods for determining stereochemistry and separating stereoisomers are well known in the art (see, for example, Chapter 4 of Advanced Organic Chemistry, 4th edition, J. March, John Wiley and Sons, New York, 1992).

[0132] Atropisomers described herein may be identified using boldfaced keys in a manner well known to those skilled in the art. wedge key Dotted key and dotted wedge keys For example, the following shows the representation of various atropisomer pairs:

[0133]

[0134] "Tautomer" refers to alternative forms of a compound that differ in the position of a proton, such as enol-keto and imine-enamine tautomers, or tautomeric forms of heteroaryl groups containing ring atoms attached to both ring -NH- and ring=N-, such as pyrazole, imidazole, benzimidazole, triazole, and tetrazole.

[0135] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Dashes at the beginning or end of a chemical group are for convenience; a chemical group can be depicted without one or more dashes without losing its ordinary meaning. A wavy line drawn through the line in the structure indicates the point of attachment of the group. A dotted line represents an optional bond. Unless chemically or structurally required, the order in which the chemical groups are written or the points at which they are attached to the rest of the molecule do not indicate or imply directionality. For example, the group "-SO2CH2-" is equivalent to "-CH2SO2-", and the two can be attached in either direction. Similarly, an "arylalkyl" group can be attached to the rest of the molecule, for example, at the aryl or alkyl portion of the group. Prefixes such as "C u-v " or (C u -C v ) means that the group that follows has u to v carbon atoms. For example, "C 1-6 "C1-C6 alkyl" and "C1-C6 alkyl" both mean an alkyl group having 1 to 6 carbon atoms.

[0136] As used herein, the term "antiviral agent" is intended to mean an agent that effectively inhibits the establishment and / or replication of a virus in a mammal, including but not limited to agents that interfere with host or viral mechanisms necessary for the establishment and / or replication of a virus in a mammal.

[0137] Unless otherwise indicated, whenever a compound described herein is substituted with more than one of the same designated group (e.g., "R" or "R"), it is understood that these groups may be the same or different, i.e., each group is independently selected.

[0138] Wave line, Indicates the locations of covalent bonds to adjacent substructures, groups, moieties, or atoms.

[0139] The prefix "C u-v ” and “(C u-v )" indicates that the following group has u to v carbon atoms. For example, "C1-8 "Alkyl" indicates that the alkyl group has 1 to 8 carbon atoms.

[0140] Certain commonly used alternative chemical names may be used. For example, divalent groups such as divalent "alkyl" groups, divalent "aryl" groups, etc. may also be referred to as "alkylene" groups, "arylene" groups, etc., respectively.

[0141] Unless expressly stated otherwise, where a combination of groups is referred to herein as a moiety, e.g., arylalkyl, the last-mentioned group includes the atom through which the moiety is attached to the rest of the molecule.

[0142] The term "substituted" means that any one or more hydrogen atoms on a designated atom or group are replaced by one or more substituents other than hydrogen, provided that the normal valence of the designated atom is not exceeded. Unless otherwise indicated, the one or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amine, amido, amidino, aryl, azido, carbamoyl, carboxyl, carboxyl ester, cyano, guanidino, halo, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxyl, hydrazino, imino, oxo, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thioketone, or a combination thereof.

[0143] The term "optionally substituted" means that any one or more hydrogen atoms on the designated atom or group may or may not be replaced with a moiety other than hydrogen.

[0144] Compound

[0145] The present disclosure provides compounds that are inhibitors of the SARS-CoV-2 main protease. In some embodiments, the present disclosure provides compounds of formula (I) as described herein and / or pharmaceutically acceptable salts thereof. In some embodiments, compounds according to formula (I) are provided:

[0146]

[0147] and / or pharmaceutically acceptable salts thereof.

[0148] In some embodiments, the compound of formula (I) is

[0149]

[0150] or a pharmaceutically acceptable salt thereof, wherein

[0151] ring C 6-10 aryl or 5- to 10-membered heteroaryl;

[0152] Each L 1 are independently a bond, -O-, -(C1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or –(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-;

[0153] Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic group,

[0154] wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace;

[0155] Alternatively, two R 1 and the rings to which they are attached The atoms are taken together to form a 5- to 10-membered heterocyclic group;

[0156] Each R 1a Independently C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8Cycloalkyl)2、-C(O)N(5- to 10-membered heterocyclyl)2、-C(O)N(C6 aryl)2、-C(O)N(5- to 10-membered heteroaryl)2、-NHC(O)(C 1-6 alkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0157] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace;

[0158] Each R 1b Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 2-6 Alkynyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0159] m is an integer from 0 to 3;

[0160] R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3 haloalkyl), -O(cyclopropyl), halogen or -CN;

[0161] X 1 S, N or C(R x1 );

[0162] X 2 S, N or C(R x2 );

[0163] X 3 N or C(R x3), the condition is X 1 and X 2 Not for S;

[0164] Alternatively, X 3 is a key, where X 1 and X 2 One of them is S;

[0165] Each R x1 、R x2 and R x3 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 Alkoxy, cyclopropyl or O-cyclopropyl;

[0166] ring With X 4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 a cycloalkyl group or a 5- to 10-membered heterocyclic group,

[0167] Each X 4 and X 5 are independently N or C;

[0168] Alternatively, the ring does not exist, where X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 ;

[0169] Each L x4 and L x5 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L)S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0170] Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 Cycloalkyl;

[0171] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 4a replace;

[0172] Each R 4a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0173] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace;

[0174] Each R 4b Independently C 1-6 Alkyl, C 1-6Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0175] Each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0176] Each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 or -OC 3-8 Cycloalkyl;

[0177] wherein each alkyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to four R 3a replace;

[0178] Each R 3a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0179] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace;

[0180] Each R 3bIndependently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0181] Each R L are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 Cycloalkyl;

[0182] n is an integer from 0 to 3;

[0183] Each X 6 and X 7 are independently N, CH or CF,

[0184] where X 4 、X 5 、X 6 and X 7 No more than two of them are N;

[0185] L 2 is a bond, C1-C6 alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(R L2 )S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)- or -(C 1-6 alkyl)S(O)2-(C 1-6 alkyl)-;

[0186] R L2 is hydrogen or C 1-6 alkyl;

[0187] R 5 is hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a C(O)R 5a 、-NR 5a 2. C 1-6 Alkyl, C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each alkyl, cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace;

[0188] Each R 5a are independently hydrogen or C 1-6 alkyl;

[0189] Each R 5b are independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3 Alkoxy, -OCF3 or -OCF2H; and

[0190] Z is O or S.

[0191] In some embodiments, the compound of formula (I) is

[0192]

[0193] or a pharmaceutically acceptable salt thereof, wherein

[0194] ring C 6-10 aryl or 5- to 10-membered heteroaryl;

[0195] Each L 1 are independently a bond, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or –(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-;

[0196] Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic group,

[0197] wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace;

[0198] Alternatively, two R 1 and the rings to which they are attached The atoms are taken together to form a 5- to 10-membered heterocyclic group;

[0199] Each R 1a Independently C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2、-C(O)N(5- to 10-membered heterocyclyl)2、-C(O)N(C6 aryl)2、-C(O)N(5- to 10-membered heteroaryl)2、-NHC(O)(C 1-6 alkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0200] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace;

[0201] Each R 1b Independently C 1-6 Alkyl, C1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 2-6 Alkynyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0202] m is an integer from 0 to 3;

[0203] R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3haloalkyl), -O(cyclopropyl), halogen or -CN;

[0204] X 1 S, N or C(R x1 );

[0205] X 2 S, N or C(R x2 );

[0206] X 3 N or C(R x3 ), the condition is X 1 and X 2 Not for S;

[0207] Alternatively, X 3 is a key, where X 1 and X 2 One of them is S;

[0208] Each R x1 、R x2 and R x3 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 Alkoxy, cyclopropyl or O-cyclopropyl;

[0209] ring With X 4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 a cycloalkyl group or a 5- to 10-membered heterocyclic group,

[0210] Each X 4 and X 5 are independently N or C;

[0211] Alternatively, the ring does not exist, where X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 ;

[0212] Each L x4 and L x5 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0213] Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 Cycloalkyl;

[0214] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 4a replace;

[0215] Each R 4a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0216] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace;

[0217] Each R 4b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0218] Each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0219] Each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 or -OC 3-8 Cycloalkyl;

[0220] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 3a replace;

[0221] Each R 3a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0222] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace;

[0223] Each R 3b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0224] Each R L are independently hydrogen, C1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 Cycloalkyl;

[0225] n is an integer from 0 to 3;

[0226] Each X 6 and X 7 are independently N or CH,

[0227] where X 4 、X 5 、X 6 and X 7 No more than two of them are N;

[0228] L 2 is a bond, C1-C6 alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(R L2 )S(O)2- or -(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-;

[0229] R L2 is hydrogen or C 1-6 alkyl;

[0230] R 5 is hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a C(O)R 5a 、-NR 5a 2. C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace;

[0231] Each R 5a are independently hydrogen or C 1-6 alkyl;

[0232] Each R 5bare independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3 Alkoxy, -OCF3 or -OCF2H; and

[0233] Z is O or S.

[0234] In some embodiments, the compound of formula (I) is

[0235]

[0236] or a pharmaceutically acceptable salt thereof, wherein

[0237] ring C 6-10 aryl or 5- to 10-membered heteroaryl;

[0238] Each L 1 are independently a bond, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or -(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-;

[0239] Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic group,

[0240] wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace;

[0241] Each R 1a Independently C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2、-C(O)N(5- to 10-membered heterocyclyl)2、-C(O)N(C6 aryl)2、-C(O)N(5- to 10-membered heteroaryl)2、-NHC(O)(C 1-6 alkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0242] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace;

[0243] Each R 1b Independently C 1-6 Alkyl, C1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 2-6 Alkynyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0244] m is an integer from 0 to 3;

[0245] R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3haloalkyl), -O(cyclopropyl), halogen or -CN;

[0246] X 1 S, N or C(R x1 );

[0247] X 2 S, N or C(R x2 );

[0248] X 3 N or C(R x3 ), the condition is X 1 and X 2 Not for S;

[0249] Alternatively, X 3 is a key, where X 1 and X 2 One of them is S;

[0250] Each R x1 R x2 and R x3 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 Alkoxy, cyclopropyl or O-cyclopropyl;

[0251] ring With X 4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 a cycloalkyl group or a 5- to 10-membered heterocyclic group,

[0252] Each X 4 and X 5 are independently N or C;

[0253] Alternatively, the ring does not exist, where X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 ;

[0254] Each L x4 and L x5 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0255] Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 Cycloalkyl;

[0256] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 4a replace;

[0257] Each R 4a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0258] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace;

[0259] Each R 4b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0260] Each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-;

[0261] Each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2 or -OC 3-8 Cycloalkyl;

[0262] wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 3a replace;

[0263] Each R 3a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2,

[0264] wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace;

[0265] Each R 3b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2;

[0266] Each R L are independently hydrogen, C1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 Cycloalkyl;

[0267] n is an integer from 0 to 3;

[0268] Each X 6 and X 7 are independently N or CH,

[0269] where X 4 、X 5 、X 6 and X 7 No more than two of them are N;

[0270] L 2 is a bond, C1-C6 alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(R L2 )S(O)2- or -(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-;

[0271] R L2 is hydrogen or C 1-6 alkyl;

[0272] R 5 is hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a 2. C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace;

[0273] Each R 5a are independently hydrogen or C 1-6 alkyl;

[0274] Each R 5b are independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3Alkoxy, -OCF3 or -OCF2H; and

[0275] Z is O or S.

[0276] In some embodiments, the present disclosure provides compounds according to the structure of Formula (I-1):

[0277]

[0278] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、X 1 、X 2 、X 3 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0279] In some embodiments, the compounds of the present disclosure are those wherein X 3 N or C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 3 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 3 C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are wherein N or C (R x3 ) and X 1 and X 2 A compound other than S or a pharmaceutically acceptable salt thereof.

[0280] In some embodiments, the compounds of the present disclosure are those wherein X 1 S, N or C(R x1 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 In some embodiments, the compound of the present disclosure is a compound wherein X 1 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 C(R x1 ) or a pharmaceutically acceptable salt thereof.

[0281] In some embodiments, the compounds of the present disclosure are those wherein X 2 S, N or C(R x1 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 2 In some embodiments, the compound of the present disclosure is a compound wherein X 2 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 2 C(R x1 ) or a pharmaceutically acceptable salt thereof.

[0282] In some embodiments, the compounds of the present disclosure are those wherein X 1 and X 2 is not a compound of S or a pharmaceutically acceptable salt thereof. In some embodiments, X 1 and X 2 Exactly one of them is S.

[0283] In some embodiments, the compounds of the present disclosure are those wherein X 3 is a bond, N or C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 3 N or C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 3 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 3 C(R x3 ) or a pharmaceutically acceptable salt thereof.

[0284] In some embodiments, the compounds of the present disclosure are those wherein X 1 C(R x1 ), X 2 C(R x2 ) and X 3 C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 C(R x1 ), X 2 C(R x2 ) and X 3 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 N, X 2 C(Rx2 ) and X 3 C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 N, X 2 C(R x2 ) and X 3 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 C(R x1 ), X 2 is N and X 3 C(R x3 ) or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 1 C(R x1 ), X 2 is N and X 3 is a compound wherein N or a pharmaceutically acceptable salt thereof.

[0285] In some embodiments, the present disclosure provides compounds according to the structure of Formula (III):

[0286]

[0287] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、X 1 、X 2 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0288] In some embodiments, the present disclosure provides compounds according to the structure of Formula (III-a):

[0289]

[0290] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、Rx1 、R x2 、R x3 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0291] In some embodiments, the present disclosure provides compounds according to the structure of Formula (III-b):

[0292]

[0293] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、R x1 、R x3 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0294] In some embodiments, the present disclosure provides compounds according to the structure of Formula (III-c):

[0295]

[0296] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、R x2 、R x3 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0297] In some embodiments, the present disclosure provides compounds according to the structure of Formula (III-d):

[0298]

[0299] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L2 、L 3 、R 1 、R 2 、R 3 、R 5 、R x1 、R x2 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0300] In some embodiments, the compounds of the present disclosure are those wherein X 1 S, X 2 C(R x2 ) and X 3 In some embodiments, the compound of the present disclosure is a compound wherein X 1 S, X 2 is N and X 3 In some embodiments, the compound of the present disclosure is a compound wherein X 1 C(R x2 ), X 2 is S and X 3 In some embodiments, the compound of the present disclosure is a compound wherein X 1 N, X 2 is S and X 3 A compound or a pharmaceutically acceptable salt thereof.

[0301] In some embodiments, the present disclosure provides compounds according to the structure of formula (II)

[0302]

[0303] and / or a pharmaceutically acceptable salt thereof, wherein

[0304] L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、X 1 、X 2 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0305] In some embodiments, the present disclosure provides compounds according to the structure of formula (II-a)

[0306]

[0307] and / or a pharmaceutically acceptable salt thereof, wherein

[0308] L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、R x1 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0309] In some embodiments, the present disclosure provides compounds according to the structure of formula (II-b)

[0310]

[0311] and / or a pharmaceutically acceptable salt thereof, wherein

[0312] L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、R x2 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0313] In some embodiments, the present disclosure provides compounds according to the structure of formula (II-c)

[0314]

[0315] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、X 4 、X 5 、X6 、X 7 , Z, m and n are as described herein.

[0316] In some embodiments, the present disclosure provides compounds according to the structure of formula (II-d)

[0317]

[0318] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、X 4 、X 5 、X 6 、X 7 , Z, m and n are as described herein.

[0319] In some embodiments, the compounds of the present disclosure are wherein cyclic C 6-10 In some embodiments, the compounds of the present disclosure are compounds wherein the ring C 6-10 In some embodiments, the compounds of the present disclosure are compounds wherein the ring is a C6 aryl compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein the ring C 10 In some embodiments, C 6-10 In some embodiments, C 6-10 Aryl is indanyl.

[0320] In some embodiments, the compounds of the present disclosure are wherein cyclic is a C6 aryl group and the substituent at the meta position of the attachment point is hydrogen, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for or a pharmaceutically acceptable salt thereof.

[0321] In some embodiments, the compounds of the present disclosure are wherein cyclic is a compound wherein the cyclic is a compound wherein the cyclic is a compound wherein the cyclic is a compound wherein the cyclic is a 5-membered, 6-membered, 7-membered, 8-membered, 9-membered or 10-membered heteroaryl compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are wherein the cyclic is a nitrogen-containing heteroaryl compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein the cyclic is a compound containing a sulfur heteroaryl group or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is a compound wherein the cyclic In some embodiments, the heteroaryl group includes pyridine, pyrimidine (such as pyrimidinedione), oxazole, pyrrole, pyrazole, imidazole, triazole or thiophene, each of which is optionally fused with another ring to form a ring.

[0322] In some embodiments, the compounds of the present disclosure are wherein cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for In some embodiments, the compound of the present disclosure is a compound wherein the cyclic for or a pharmaceutically acceptable salt thereof.

[0323] In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently a bond, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or -(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R LAs described herein. In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently a bond, -O-, -(C 1-3 Alkyl)O-, -O(C 1-3 Alkyl)-, -C 1-3 Alkyl-O(C 1-3 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-3 Alkyl)(R L )NC(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-3 alkyl)-、-C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 alkyl)N(R L )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-3 Alkyl)S(O)2N(R L )-、-(C 1-3 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-3 Alkyl)-, -N(R L )S(O)2(C 1-3 Alkyl)-, -(C 1-3 Alkyl)S(O)2N(R L )(C 1-3 alkyl)- or -(C 1-3 alkyl)N(R L )S(O)2(C 1-3 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0324] In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C1-6 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 alkyl)-、-C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 alkyl)- or -(C 1-6 alkyl)N(R L )S(O)2(C 1-6 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L As defined herein. In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently -O-, -(C 1-3 Alkyl)O-, -O(C 1-3 Alkyl)-, -C 1-3 Alkyl-O(C 1-3 alkyl)-、-C(O)-、-N(R L )C(O)-、-C(O)N(R L )-、-(C 1-3 Alkyl)(R L )NC(O)-、-(C 1-3 alkyl)C(O)N(RL )-、-N(R L )C(O)(C 1-3 alkyl)-、-C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 alkyl)N(R L )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-、-S(O)2-、-S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-3 Alkyl)S(O)2N(R L )-、-(C 1-3 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-3 Alkyl)-, -N(R L )S(O)2(C 1-3 Alkyl)-, -(C 1-3 Alkyl)S(O)2N(R L )(C 1-3 alkyl)- or -(C 1-3 alkyl)N(R L )S(O)2(C 1-3 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L As defined herein.

[0325] In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently -O-, -(C 1-3 Alkyl)O-, -O(C 1-3 Alkyl)- or -C 1-3 Alkyl-O(C 1-3 alkyl)-compound or a pharmaceutically acceptable salt thereof.

[0326] In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently -C(O)-, -N(R L )C(O)-、-C(O)N(R L )-、-(C 1-3 Alkyl)(R L )NC(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-N(R L)C(O)(C 1-3 alkyl)-、-C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 alkyl)N(R L )C(O)(C 1-3 alkyl)- or -(C 1-3 alkyl)C(O)N(R L )(C 1-3 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L As defined herein.

[0327] In some embodiments, the compounds of the present disclosure are wherein each L 1 are independently -S(O)2-, -S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-3 Alkyl)S(O)2N(R L )-、-(C 1-3 alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-3 Alkyl)-, -N(R L )S(O)2(C 1-3 Alkyl)-, -(C 1-3 Alkyl)S(O)2N(R L )(C 1-3 alkyl)- or -(C 1-3 alkyl)N(R L )S(O)2(C 1-3 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0328] In some embodiments, the compounds of the present disclosure are wherein each L 1 A compound or a pharmaceutically acceptable salt thereof.

[0329] In some embodiments, the compounds of the present disclosure are wherein each L 1 Independently -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)- or -C 1-6 Alkyl-O(C 1-6 In some embodiments, the compound of the present disclosure is wherein each L 1 Independently -(C 1-3 Alkyl)O-, -O(C 1-3Alkyl)- or -C 1-3 Alkyl-O(C 1-3 In some embodiments, the compound of the present disclosure is wherein each L 1 A compound independently being -(methyl)O-, -O(methyl)- or -methyl-O(methyl)-, or a pharmaceutically acceptable salt thereof.

[0330] In some embodiments, the compounds of the present disclosure are wherein each L 1 Independently -(C 1-6 alkyl)O- or -O(C 1-6 In some embodiments, the compound of the present disclosure is wherein each L 1 Independently -(C 1-3 alkyl)O- or -O(C 1-3 In some embodiments, the compound of the present disclosure is wherein each L 1 A compound independently being -(methyl)O- or -O(methyl)-, or a pharmaceutically acceptable salt thereof.

[0331] In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 a compound comprising a cycloalkyl group, a C6 aryl group, a 5- to 12-membered heteroaryl group, or a 4- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkenyl group, alkynyl group, alkoxy group, cycloalkyl group, aryl group, heteroaryl group, and heterocyclic group is optionally substituted by one to four R 1a In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently fluorine, chlorine, -OH, -CN, C 1-3 Alkyl, -CN, -C(O)NH2, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-8 a compound comprising a cycloalkyl group, a C6 aryl group, a 5- to 10-membered heteroaryl group, or a 4- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkenyl group, alkynyl group, alkoxy group, cycloalkyl group, aryl group, heteroaryl group, and heterocyclic group is optionally substituted by one to four R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted by one to three R1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or two R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one R 1a replace.

[0332] In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl group, wherein each alkyl, alkynyl, alkoxy, cycloalkyl, aryl and heteroaryl group is optionally substituted by one to three R 1a In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently fluorine, chlorine, -CN, -C(O)NH2, C 1-3 Alkyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl group, wherein each alkyl, alkynyl, alkoxy, cycloalkyl, aryl and heteroaryl group is optionally substituted by one to three R 1a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl group is optionally substituted with one or two R 1a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl group is optionally replaced by one R 1a replace.

[0333] In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heteroaryl group is optionally substituted by one or two R 1a In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently fluorine, chlorine, -CN, -C(O)NH2, C 1-3 Alkyl, C 2-3 Alkynyl, C1-3 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heteroaryl group is optionally substituted by one or two R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one R 1a replace.

[0334] In some embodiments, the compounds of the present disclosure are wherein each R 1 are independently halogen, -CN or C 1-6 In some embodiments, the compound of the present disclosure is wherein each R 1 In some embodiments, the compounds of the present disclosure are compounds wherein each R 1 In some embodiments, the compound of the present disclosure is a compound wherein each R 1 are independently halogen or C 1-3 In some embodiments, the compound of the present disclosure is wherein each R 1 A compound which is independently chloro, fluoro or methoxy, or a pharmaceutically acceptable salt thereof.

[0335] In some embodiments, the compounds of the present disclosure are wherein each R 1a Independently C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclic group, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2、-C(O)N(5- to 10-membered heterocyclyl)2、-C(O)N(C6 aryl)2、-C(O)N(5- to 10-membered heteroaryl)2、-NHC(O)(C 1-6 alkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C1-6 alkyl) 2 or a pharmaceutically acceptable salt thereof, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl group is optionally substituted by one to three R 1b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl group is optionally substituted by one or two R 1b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl group is optionally replaced by one R 1b replace.

[0336] In some embodiments, the compounds of the present disclosure are wherein each R 1a are independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl group, wherein each alkyl, alkoxy, cycloalkyl, aryl and heteroaryl group is optionally substituted by one to three R 1b In some embodiments, the compounds of the present disclosure are wherein each R 1a are independently fluorine, chlorine, -OH, -CN, -C(O)NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl group, wherein each alkyl, alkoxy, cycloalkyl, aryl and heteroaryl group is optionally substituted by one to three R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl group is optionally substituted with one or two R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl group is optionally substituted with one or two R 1b replace.

[0337] In some embodiments, the compounds of the present disclosure are those wherein at least one R 1a are independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl group, wherein each alkyl, alkoxy, cycloalkyl, aryl and heteroaryl group is optionally substituted by one to three R 1b In some embodiments, the compounds of the present disclosure are wherein at least one R 1a are independently fluorine, chlorine, -OH, -CN, -C(O)NH2, C 1-3 Alkyl, C 1-3Alkoxy, C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl group, wherein each alkyl, alkoxy, cycloalkyl, aryl and heteroaryl group is optionally substituted by one to three R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl group is optionally substituted with one or two R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl group is optionally substituted with one or two R 1b replace.

[0338] In some embodiments, the compounds of the present disclosure are wherein each R 1a are independently halogen, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 A compound containing an alkyl group or a C6 aryl group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and aryl group is optionally substituted by one to three R 1b In some embodiments, the compounds of the present disclosure are wherein each R 1a are independently fluorine, chlorine, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 A compound containing an alkyl group or a C6 aryl group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and aryl group is optionally substituted by one to three R 1b In some embodiments, each alkyl, alkoxy, and aryl group is optionally substituted with one or two R 1b In some embodiments, each alkyl, alkoxy, and aryl group is optionally substituted with one or two R 1b replace.

[0339] In some embodiments, the compounds of the present disclosure are those wherein at least one R 1a are independently halogen, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 A compound containing an alkyl group or a C6 aryl group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and aryl group is optionally substituted by one to three R 1b In some embodiments, the compounds of the present disclosure are wherein at least one R 1a are independently fluorine, chlorine, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 A compound containing an alkyl group or a C6 aryl group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and aryl group is optionally substituted by one to three R 1b In some embodiments, each alkyl, alkoxy, and aryl group is optionally substituted with one or two R 1bIn some embodiments, each alkyl, alkoxy, and aryl group is optionally substituted with one or two R 1b replace.

[0340] In some embodiments, the compounds of the present disclosure are those wherein R 1a In some embodiments, the compound of the present disclosure is a compound wherein R 1a In some embodiments, the compound of the present disclosure is a compound wherein R 1a A compound wherein chlorine is present or a pharmaceutically acceptable salt thereof.

[0341] In some embodiments, the compounds of the present disclosure are those wherein at least one R 1a In some embodiments, the compound of the present disclosure is a compound wherein at least one R 1a In some embodiments, the compounds of the present disclosure are compounds wherein at least one R 1a A compound wherein chlorine is present or a pharmaceutically acceptable salt thereof.

[0342] In some embodiments, the compounds of the present disclosure are wherein each R 1b Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5- to 10-membered heterocyclyl), -NH (C6 aryl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C2-6 Alkynyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 alkyl)2 or a pharmaceutically acceptable salt thereof.

[0343] In some embodiments, the compounds of the present disclosure are compounds wherein m is an integer from 0 to 3, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is an integer from 0 to 2, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is 0, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is 1 or 2, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is 0, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is 1, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is 2, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein m is 3, or pharmaceutically acceptable salts thereof.

[0344] In some embodiments, the compounds of the present disclosure are those wherein R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3 haloalkyl), -O(cyclopropyl), halogen or -CN, or a pharmaceutically acceptable salt thereof.

[0345] In some embodiments, the compounds of the present disclosure are those wherein R 2 For hydrogen, halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein R2 A compound wherein the moiety is hydrogen, fluorine, chlorine, methyl or methoxy, or a pharmaceutically acceptable salt thereof.

[0346] In some embodiments, the compounds of the present disclosure are those wherein R 2 is a hydrogen compound or a pharmaceutically acceptable salt thereof.

[0347] In some embodiments, the compounds of the present disclosure are those wherein R 2 In some embodiments, the compound of the present disclosure is a compound wherein R 2 A compound wherein chlorine is present or a pharmaceutically acceptable salt thereof.

[0348] In some embodiments, the compounds of the present disclosure are those wherein R x1 For hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 An alkoxy, cyclopropyl or O-cyclopropyl compound or a pharmaceutically acceptable salt thereof.

[0349] In some embodiments, the compounds of the present disclosure are those wherein R x1 Halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein R x1 A compound containing fluoro, chloro, methyl or methoxy or a pharmaceutically acceptable salt thereof.

[0350] In some embodiments, the compounds of the present disclosure are those wherein R x1 Halogen or C 1-3 In some embodiments, the compound of the present disclosure is a compound wherein R x1 is a fluoro, chloro or methyl compound or a pharmaceutically acceptable salt thereof.

[0351] In some embodiments, the compounds of the present disclosure are those wherein R x1 Halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein R x1 A compound containing fluorine, chlorine or methoxy or a pharmaceutically acceptable salt thereof.

[0352] In some embodiments, the compounds of the present disclosure are those wherein R x1 is a hydrogen compound or a pharmaceutically acceptable salt thereof.

[0353] In some embodiments, the compounds of the present disclosure are those wherein R x2 For hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 An alkoxy, cyclopropyl or O-cyclopropyl compound or a pharmaceutically acceptable salt thereof.

[0354] In some embodiments, the compounds of the present disclosure are those wherein R x2 Halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein R x2 A compound containing fluoro, chloro, methyl or methoxy or a pharmaceutically acceptable salt thereof.

[0355] In some embodiments, the compounds of the present disclosure are those wherein R x2 Halogen or C 1-3 In some embodiments, the compound of the present disclosure is a compound wherein R x2 is a fluoro, chloro or methyl compound or a pharmaceutically acceptable salt thereof.

[0356] In some embodiments, the compounds of the present disclosure are those wherein R x2 Halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein R x2 A compound containing fluorine, chlorine or methoxy or a pharmaceutically acceptable salt thereof.

[0357] In some embodiments, the compounds of the present disclosure are those wherein R x2 is a hydrogen compound or a pharmaceutically acceptable salt thereof.

[0358] In some embodiments, the compounds of the present disclosure are those wherein R x3 For hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Halogenated alkyl, C 1-3 An alkoxy, cyclopropyl or O-cyclopropyl compound or a pharmaceutically acceptable salt thereof.

[0359] In some embodiments, the compounds of the present disclosure are those wherein R x3 Halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein Rx3 A compound containing fluoro, chloro, methyl or methoxy or a pharmaceutically acceptable salt thereof.

[0360] In some embodiments, the compounds of the present disclosure are those wherein R x3 Halogen or C 1-3 In some embodiments, the compound of the present disclosure is a compound wherein R x3 is a fluoro, chloro or methyl compound or a pharmaceutically acceptable salt thereof.

[0361] In some embodiments, the compounds of the present disclosure are those wherein R x3 Halogen, C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein R x3 A compound containing fluorine, chlorine or methoxy or a pharmaceutically acceptable salt thereof.

[0362] In some embodiments, the compounds of the present disclosure are those wherein R x3 is a hydrogen compound or a pharmaceutically acceptable salt thereof.

[0363] In some embodiments, the compounds of the present disclosure are wherein cyclic With X 4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 A compound containing a cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof.

[0364] In some embodiments, the compounds of the present disclosure are wherein cyclic With X 4 and X 5 A compound or a pharmaceutically acceptable salt thereof, wherein each X 4 and X 5 is independently N or C. In some embodiments, the compounds of the present disclosure are wherein With X 4 and X 5 A compound or a pharmaceutically acceptable salt thereof, wherein each X 4 and X 5 is independently N or C. In some embodiments, the compounds of the present disclosure are wherein With X 4 and X 5 Together they form C 5-10 A cycloalkyl compound or a pharmaceutically acceptable salt thereof, wherein each X 4 and X 5is independently N or C. In some embodiments, the compounds of the present disclosure are wherein With X 4 and X 5 A compound or a pharmaceutically acceptable salt thereof which is a 5- to 10-membered heterocyclic group, wherein each X 4 and X 5 are independently N or C.

[0365] In some embodiments, the compounds of the present disclosure are those wherein each X 4 and X 5 is independently N or C or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 4 and X 5 Each is a compound of C or a pharmaceutically acceptable salt thereof.

[0366] In some embodiments, the present disclosure provides compounds according to the structure of formula (IV)

[0367]

[0368] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、X 1 、X 2 、X 3 , Z, m and n are as described herein.

[0369] In some embodiments, the compounds of the present disclosure are wherein cyclic and contains X 4 、X 5 、X 6 and X 7 The rings are put together to form or a pharmaceutically acceptable salt thereof.

[0370] In some embodiments, the present disclosure provides compounds according to the structure of formula (IV-a)

[0371]

[0372] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R3 、R 5 、R x1 , Z, m and n are as described herein.

[0373] In some embodiments, the present disclosure provides compounds according to the structure of formula (IV-b)

[0374]

[0375] and / or a pharmaceutically acceptable salt thereof, wherein L 1 、L 2 、L 3 、R 1 、R 2 、R 3 、R 5 、R x1 、R x2 、R x3 , Z, m and n are as described herein.

[0376] In some embodiments, the compounds of the present disclosure are wherein cyclic is a 5-membered heteroaryl compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein the cyclic and contains X 4 、X 5 、X 6 and X 7 The rings are put together to form or a pharmaceutically acceptable salt thereof.

[0377] In some embodiments, the compounds of the present disclosure are wherein cyclic The compound or a pharmaceutically acceptable salt thereof, wherein X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 In some embodiments, the compounds of the present disclosure are wherein The compound or a pharmaceutically acceptable salt thereof, wherein X 4 is N, and X 5 CL x5 -R x5 In some embodiments, the compounds of the present disclosure are wherein The compound or a pharmaceutically acceptable salt thereof, wherein X 4 CL x4 -R x4 , and X 5is N. In some embodiments, the compounds of the present disclosure are wherein The compound or a pharmaceutically acceptable salt thereof, wherein X 4 CL x4 -R x4 , and X 5 CL x5 -R x5 .

[0378] In some embodiments, the compounds of the present disclosure are those wherein X 4 is N, and X 5 CL x5 -R x5 or a pharmaceutically acceptable salt thereof.

[0379] In some embodiments, the present disclosure provides compounds according to the structure of formula (V)

[0380]

[0381] and / or a pharmaceutically acceptable salt thereof, wherein

[0382] L 1 、L 2 、R 1 、R 2 、R 5 、R x4 、R x5 、X 1 、X 2 、X 3 , Z, m and n are as described herein.

[0383] In some embodiments, the present disclosure provides compounds according to the structure of formula (Va)

[0384]

[0385] and / or a pharmaceutically acceptable salt thereof, wherein

[0386] L 1 、L 2 、R 1 、R 2 、R 5 、R x1 、R x4 、R x5 , Z, m and n are as described herein.

[0387] In some embodiments, the present disclosure provides compounds according to the structure of Formula (Vb)

[0388]

[0389] and / or a pharmaceutically acceptable salt thereof, wherein

[0390] L 1 、L 2 、R 1 、R 2 、R 5 、R x1 、R x2 、R x3 、R x4 、R x5 , Z, m and n are as described herein.

[0391] In some embodiments, the compounds of the present disclosure are wherein L x4 For the key, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described herein. In some embodiments, the compounds of the present disclosure are wherein L x4 For the key, -(C 1-3 Alkyl)O-, -(C 1-3 alkyl)N(R L )C(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-(C 1-3 alkyl)N(R L )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3Alkyl), -(C 1-3 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-3 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0392] In some embodiments, the compounds of the present disclosure are wherein L x4 For-(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described herein. In some embodiments, the compounds of the present disclosure are wherein L x4 For-(C 1-3 Alkyl)O-, -(C 1-3 alkyl)N(R L )C(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-(C 1-3 alkyl)N(R L )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 Alkyl), -(C 1-3 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-3alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0393] In some embodiments, the compounds of the present disclosure are wherein L x4 is a bond or N(R L )S(O)2- or a pharmaceutically acceptable salt thereof, wherein R L As defined herein. In some embodiments, the compounds of the present disclosure are wherein L x4 N(R L )S(O)2- or a pharmaceutically acceptable salt thereof, wherein R L As defined herein.

[0394] In some embodiments, the compounds of the present disclosure are wherein L x4 A compound or a pharmaceutically acceptable salt thereof.

[0395] In some embodiments, the compounds of the present disclosure are wherein L x5 For-(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described herein. In some embodiments, the compounds of the present disclosure are wherein L x5 For-(C 1-3 Alkyl)O-, -(C 1-3 alkyl)N(R L )C(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-(C 1-3 alkyl)N(RL )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 Alkyl), -(C 1-3 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-3 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0396] In some embodiments, the compounds of the present disclosure are wherein L x5 is a bond or N(R L )S(O)2- or a pharmaceutically acceptable salt thereof, wherein R L As defined herein. In some embodiments, the compounds of the present disclosure are wherein L x5 N(R L )S(O)2- or a pharmaceutically acceptable salt thereof, wherein R L As defined herein.

[0397] In some embodiments, the compounds of the present disclosure are wherein L x5 A compound or a pharmaceutically acceptable salt thereof.

[0398] In some embodiments, the compounds of the present disclosure are those wherein R x4 For hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 A compound or a pharmaceutically acceptable salt thereof, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl group is optionally replaced by one to four R 4a In some embodiments, the compounds of the present disclosure are wherein R x4 For hydrogen, halogen, hydroxyl, -CN, C 1-3 Alkyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-8Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -O(C 1-3 alkyl) or -OC 3-8 A compound or a pharmaceutically acceptable salt thereof, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl group is optionally replaced by one to four R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted by one to three R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally replaced by one R 4a replace.

[0399] In some embodiments, the compounds of the present disclosure are those wherein R x4 is hydrogen, C1-C6 alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 A compound comprising an alkoxy group, a C3-C8 cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group, cycloalkyl group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, the compounds of the present disclosure are wherein R x4 is hydrogen, C1-C3 alkyl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, C 1-3 A compound comprising an alkoxy group, a C3-C8 cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group, cycloalkyl group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one R 4a replace.

[0400] In some embodiments, the compounds of the present disclosure are those wherein R x4 is a C3-C8 cycloalkyl compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein R x4 is a C3-C8 cycloalkyl compound or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group is optionally replaced by one or two R 4aReplace, and R x5 In some embodiments, the cycloalkyl group is optionally replaced by one R 4a replace.

[0401] In some embodiments, the compounds of the present disclosure are those wherein R x4 C 1-6 In some embodiments, the compound of the present disclosure is wherein R x4 C 1-6 Alkoxy compounds or pharmaceutically acceptable salts thereof, wherein the alkoxy group is optionally replaced by one or two R 4a Replace, and R x5 In some embodiments, the alkoxy group is optionally replaced by one R 4a In some embodiments, the alkoxy group is methoxy.

[0402] In some embodiments, the compounds of the present disclosure are those wherein R x4 C1-C6 alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 A compound containing an alkoxy group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, the compounds of the present disclosure are wherein R x4 C1-C3 alkyl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, C 1-3 A compound containing an alkoxy group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl group is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl group is optionally replaced by one R 4a replace.

[0403] In some embodiments, the compounds of the present disclosure are those wherein R x4 is optionally replaced by one to three R 4a In some embodiments, the heterocyclic group is optionally replaced by one or two R 4a In some embodiments, the heterocyclyl group is optionally substituted with one R 4a replace.

[0404] In some embodiments, the compounds of the present disclosure are those wherein R x4 -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 alkyl)2 or -O(C 1-3 alkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl is independently optionally replaced by one or two R 4a In some embodiments, each alkyl group is optionally replaced by one R 4a replace.

[0405] In some embodiments, the compounds of the present disclosure are those wherein R x4 A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0406] In some embodiments, the compounds of the present disclosure are those wherein R x5 For hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 A compound or a pharmaceutically acceptable salt thereof, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl group is optionally replaced by one to four R 4a In some embodiments, the compounds of the present disclosure are wherein R x5 For hydrogen, halogen, hydroxyl, -CN, C 1-3 Alkyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -O(C 1-3 alkyl) or -OC 3-8 A compound or a pharmaceutically acceptable salt thereof, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl group is optionally replaced by one to four R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted by one to three R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one or two R 4aIn some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally replaced by one R 4a replace.

[0407] In some embodiments, the compounds of the present disclosure are those wherein R x5 is hydrogen, C1-C6 alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 A compound comprising an alkoxy group, a C3-C8 cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group, cycloalkyl group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, the compounds of the present disclosure are wherein R x5 is hydrogen, C1-C3 alkyl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, C 1-3 A compound comprising an alkoxy group, a C3-C8 cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group, cycloalkyl group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one R 4a replace.

[0408] In some embodiments, the compounds of the present disclosure are those wherein R x5 is a C3-C8 cycloalkyl compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein R x5 is a C3-C8 cycloalkyl compound or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group is optionally replaced by one or two R 4a Replace, and R x4 In some embodiments, the cycloalkyl group is optionally replaced by one R 4a replace.

[0409] In some embodiments, the compounds of the present disclosure are those wherein R x5 C 1-6 In some embodiments, the compound of the present disclosure is wherein R x5 C 1-6 Alkoxy compounds or pharmaceutically acceptable salts thereof, wherein the alkoxy group is optionally replaced by one or two R 4a Replace, and R x4In some embodiments, the alkoxy group is optionally replaced by one R 4a In some embodiments, the alkoxy group is methoxy.

[0410] In some embodiments, the compounds of the present disclosure are those wherein R x5 C1-C6 alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 A compound containing an alkoxy group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, the compounds of the present disclosure are wherein R x5 C1-C3 alkyl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, C 1-3 A compound containing an alkoxy group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and heterocyclic group is optionally substituted by one to three R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl group is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl group is optionally replaced by one R 4a replace.

[0411] In some embodiments, the compounds of the present disclosure are those wherein R x5 is optionally replaced by one to three R 4a In some embodiments, the heterocyclic group is optionally replaced by one or two R 4a In some embodiments, the heterocyclyl group is optionally substituted with one R 4a replace.

[0412] In some embodiments, the compounds of the present disclosure are those wherein R x5 -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 alkyl)2 or -O(C 1-3 alkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl is independently optionally replaced by one or two R 4a In some embodiments, each alkyl group is optionally replaced by one R 4a replace.

[0413] In some embodiments, the compounds of the present disclosure are those wherein R x5 A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0414] In some embodiments, the compounds of the present disclosure are wherein each R 4a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5-membered 10-membered heterocyclic group, C6 aryl, 5-membered 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5-membered 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5-membered 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5-membered 10-membered heterocyclic group), -NH (C6 aryl), -NH (5-membered 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5-membered to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5-membered 10-membered heteroaryl), -C(O)(5-membered 10-membered heterocyclic group), -C(O)(5-membered 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C 3-8 Cycloalkyl), -C(O)NH(5-membered 10-membered heterocyclic group), -C(O)NH(C6 aryl), -C(O)NH(5-membered 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8Cycloalkyl), -NHC(O)(5-membered 10-membered heterocyclic group), -NHC(O)(C6 aryl), -NHC(O)(5-membered 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5-membered 10-membered heterocyclic group), -NHC(O)O(C6 aryl), -NHC(O)O(5-membered 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5-membered 10-membered heterocyclic group), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-membered 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 alkyl) 2 or a pharmaceutically acceptable salt thereof, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl group is optionally substituted by one to three R 4b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl group is optionally substituted by one or two R 4b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl group is optionally replaced by one R 4b replace.

[0415] In some embodiments, the compounds of the present disclosure are wherein each R 4a Independently C 1-6 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 4b In some embodiments, the compounds of the present disclosure are wherein each R 4a Independently C 1-3 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 4bIn some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally substituted with one or two R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally replaced by one R 4b replace.

[0416] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a C 1-6 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 4b In some embodiments, the compounds of the present disclosure are wherein at least one R 4a Independently C 1-3 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally substituted with one or two R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally replaced by one R 4b replace.

[0417] In some embodiments, the compounds of the present disclosure are wherein each R 4a are independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 4b In some embodiments, the compounds of the present disclosure are wherein each R 4a are independently chlorine, fluorine, -C(O)(C1-C3 alkyl), -OH, -O(C 1-3 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 4b replace.

[0418] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a Halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 4b In some embodiments, the compounds of the present disclosure are wherein at least one R 4a Chloro, fluoro, -C(O)(C1-C3 alkyl), -OH, -O(C 1-3 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 4b replace.

[0419] In some embodiments, the compounds of the present disclosure are wherein each R 4a are independently -O(C 1-3 alkyl), 5- to 7-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally substituted by one to three R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 4b replace.

[0420] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a -O(C 1-3 alkyl), 5- to 7-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally substituted by one to three R 4b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 4bIn some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 4b replace.

[0421] In some embodiments, the compounds of the present disclosure are wherein each R 4a is independently halogen or -C(O)(C1-C6 alkyl) or a pharmaceutically acceptable salt thereof, wherein the alkyl group is optionally replaced by one to three R 4b In some embodiments, the compounds of the present disclosure are wherein each R 4a is independently a halogen or -C(O)(C1-C3 alkyl) compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein each R 4a A compound which is independently chloro, fluoro or -C(O)(methyl) or a pharmaceutically acceptable salt thereof.

[0422] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a is a compound or a pharmaceutically acceptable salt thereof, wherein the alkyl group is optionally replaced by one to three R 4b In some embodiments, the compounds of the present disclosure are wherein at least one R 4a is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is one in which at least one R 4a A compound wherein the moiety is chloro, fluoro or -C(O)(methyl) or a pharmaceutically acceptable salt thereof.

[0423] In some embodiments, the compounds of the present disclosure are wherein each R 4a are independently -OH or -O(C 1-3 In some embodiments, the compound of the present disclosure is wherein each R 4a A compound which is independently -OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0424] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a -OH or -O(C 1-3 In some embodiments, the compounds of the present disclosure are compounds wherein at least one R 4a A compound wherein the group consisting of -OH and methoxy is -OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0425] In some embodiments, the compounds of the present disclosure are those wherein R 4a -O(C 1-3In some embodiments, the compound of the present disclosure is wherein R 4a A compound or a pharmaceutically acceptable salt thereof wherein the compound is methoxy.

[0426] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a -O(C 1-3 In some embodiments, the compounds of the present disclosure are compounds wherein at least one R 4a A compound or a pharmaceutically acceptable salt thereof wherein the compound is methoxy.

[0427] In some embodiments, the compounds of the present disclosure are wherein each R 4a In some embodiments, the compound of the present disclosure is one in which each R 4a A compound which is independently chloro, fluoro or -OH, or a pharmaceutically acceptable salt thereof.

[0428] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4a is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is one in which at least one R 4a A compound wherein the group is chlorine, fluorine or -OH, or a pharmaceutically acceptable salt thereof.

[0429] In some embodiments, the compounds of the present disclosure are wherein each R 4b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 alkyl)2 or a pharmaceutically acceptable salt thereof.

[0430] In some embodiments, the compounds of the present disclosure are wherein each R 4b are independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 In some embodiments, the compound of the present disclosure is wherein each R 4b are independently fluorine, chlorine, -O(C 1-3 alkyl) or -O(C 1-3 haloalkyl) or a pharmaceutically acceptable salt thereof.

[0431] In some embodiments, the compounds of the present disclosure are those wherein at least one R 4b Halogen, -O(C 1-6 alkyl) or -O(C 1-6 In some embodiments, the compounds of the present disclosure are compounds wherein at least one R 4b are independently halogen, fluorine, chlorine, -O(C 1-3 alkyl) or -O(C 1-3 haloalkyl) or a pharmaceutically acceptable salt thereof.

[0432] In some embodiments, the compounds of the present disclosure are wherein each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L)-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described herein. In some embodiments, the compounds of the present disclosure are wherein each L 3 are independently a bond, -(C 1-3 Alkyl)O-, -(C 1-3 alkyl)N(R L )C(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-(C 1-3 alkyl)N(R L )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 Alkyl), -(C 1-3 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-3 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0433] In some embodiments, the compounds of the present disclosure are wherein each L 3 Independently -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)N(R L )C(O)-、-(C 1-6 alkyl)C(O)N(R L )-、-(C 1-6 alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described herein. In some embodiments, the compounds of the present disclosure are wherein each L 3 Independently -(C 1-3 Alkyl)O-, -(C 1-3 alkyl)N(R L )C(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-(C 1-3 alkyl)N(R L )C(O)(C 1-3 Alkyl)-, -(C 1-3 alkyl)C(O)N(R L )(C 1-3 Alkyl)-, -(C 1-3 Alkyl), -(C 1-3 alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-3 alkyl)C(O)- or -N(R L )C(O)- or a pharmaceutically acceptable salt thereof, wherein R L As described in this article.

[0434] In some embodiments, the compounds of the present disclosure are wherein L 3 is a bond or N(R L )S(O)2- or a pharmaceutically acceptable salt thereof, wherein R L As defined herein. In some embodiments, the compounds of the present disclosure are wherein L 3 N(R L )S(O)2- or a pharmaceutically acceptable salt thereof, wherein R L As defined herein.

[0435] In some embodiments, the compounds of the present disclosure are wherein L 3 A compound or a pharmaceutically acceptable salt thereof.

[0436] In some embodiments, the compounds of the present disclosure are wherein each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 alkyl) or -OC 3-8 A compound or a pharmaceutically acceptable salt thereof, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl group is optionally replaced by one to four R 3a In some embodiments, the compounds of the present disclosure are wherein each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-3 Alkyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -O(C 1-3 alkyl) or -OC 3-8 A compound or a pharmaceutically acceptable salt thereof, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl group is optionally replaced by one to four R 3a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted by one to three R 3a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one or two R 3a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally replaced by one R 3a replace.

[0437] In some embodiments, the compounds of the present disclosure are wherein each R 3 are independently a bond, a C1-C6 alkyl group, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 A compound comprising an alkoxy group, a C3-C8 cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group, cycloalkyl group and heterocyclic group is optionally substituted by one to three R 3a In some embodiments, the compounds of the present disclosure are wherein each R 3are independently a bond, C1-C3 alkyl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, C 1-3 A compound comprising an alkoxy group, a C3-C8 cycloalkyl group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group, cycloalkyl group and heterocyclic group is optionally substituted by one to three R 3a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one or two R 3a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl group is optionally substituted with one R 3a replace.

[0438] In some embodiments, the compounds of the present disclosure are those wherein R 3 is a C3-C8 cycloalkyl compound or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group is optionally replaced by one R 3a In some embodiments, the cycloalkyl group is optionally substituted with one R 3a replace.

[0439] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3 is a C3-C8 cycloalkyl compound or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group is optionally replaced by one or two R 3a In some embodiments, the cycloalkyl group is optionally substituted with one R 3a replace.

[0440] In some embodiments, the compounds of the present disclosure are those wherein R 3 C 1-6 Alkoxy compounds or pharmaceutically acceptable salts thereof, wherein the alkoxy group is optionally replaced by one or two R 3a In some embodiments, the alkoxy group is optionally replaced by one R 3a In some embodiments, the alkoxy group is methoxy.

[0441] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3 C 1-6 Alkoxy compounds or pharmaceutically acceptable salts thereof, wherein the alkoxy group is optionally replaced by one or two R 3a In some embodiments, the alkoxy group is optionally replaced by one R 3a In some embodiments, the alkoxy group is methoxy.

[0442] In some embodiments, the compounds of the present disclosure are wherein each R 3 are independently C1-C6 alkyl, -NH2, -NH(C1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 A compound containing an alkoxy group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and heterocyclic group is optionally substituted by one to three R 3a In some embodiments, the compounds of the present disclosure are wherein each R 3 are independently C1-C3 alkyl, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, C 1-3 A compound containing an alkoxy group or a 5- to 10-membered heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein each alkyl group, alkoxy group and heterocyclic group is optionally substituted by one to three R 3a In some embodiments, each alkyl, alkoxy, and heterocyclyl group is optionally substituted with one or two R 3a In some embodiments, each alkyl, alkoxy, and heterocyclyl group is optionally replaced by one R 3a replace.

[0443] In some embodiments, the compounds of the present disclosure are those wherein R 3 is optionally replaced by one to three R 3a In some embodiments, the heterocyclic group is optionally replaced by one or two R 3a In some embodiments, the heterocyclyl group is optionally substituted with one R 3a replace.

[0444] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3 is optionally replaced by one to three R 3a In some embodiments, the heterocyclic group is optionally replaced by one or two R 3a In some embodiments, the heterocyclyl group is optionally substituted with one R 3a replace.

[0445] In some embodiments, the compounds of the present disclosure are wherein each R 3 are independently -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 alkyl)2 or -O(C 1-3 alkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl is independently optionally replaced by one or two R 3a In some embodiments, each alkyl group is optionally replaced by one R 3a replace.

[0446] In some embodiments, the compounds of the present disclosure are those wherein R 3 A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0447] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3 A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0448] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3 In some embodiments, the compound of the present disclosure is a compound wherein at least one R 3 A compound containing fluorine or chlorine, or a pharmaceutically acceptable salt thereof.

[0449] In some embodiments, the compounds of the present disclosure are wherein each R 3a Independently C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5-membered 10-membered heterocyclic group, C6 aryl, 5-membered 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5-membered 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5-membered 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 Cycloalkyl), -NH (5-membered 10-membered heterocyclic group), -NH (C6 aryl), -NH (5-membered 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5-membered to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5-membered 10-membered heteroaryl), -C(O)(5-membered 10-membered heterocyclic group), -C(O)(5-membered 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 Halogenated alkyl), -C(O)NH(C3-8 Cycloalkyl), -C(O)NH(5-membered 10-membered heterocyclic group), -C(O)NH(C6 aryl), -C(O)NH(5-membered 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Halogenated alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 Cycloalkyl), -NHC(O)(5-membered 10-membered heterocyclic group), -NHC(O)(C6 aryl), -NHC(O)(5-membered 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5-membered 10-membered heterocyclic group), -NHC(O)O(C6 aryl), -NHC(O)O(5-membered 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 Halogenated alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5-membered 10-membered heterocyclic group), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-membered 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 alkyl) 2 or a pharmaceutically acceptable salt thereof, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl group is optionally substituted by one to three R 3b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl group is optionally substituted by one or two R 3b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl group is optionally replaced by one R 3b replace.

[0450] In some embodiments, the compounds of the present disclosure are wherein each R 3a Independently C 1-6 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 3b In some embodiments, the compounds of the present disclosure are wherein each R 3a Independently C 1-3 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally substituted with one or two R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally replaced by one R 3b replace.

[0451] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a C 1-6 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 3b In some embodiments, the compounds of the present disclosure are wherein at least one R 3a Independently C 1-3 Alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl) or a pharmaceutically acceptable salt thereof, wherein each alkyl, heterocyclyl and cycloalkyl is optionally substituted by one to three R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally substituted with one or two R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl group is optionally replaced by one R 3b replace.

[0452] In some embodiments, the compounds of the present disclosure are wherein each R 3a are independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 3b In some embodiments, the compounds of the present disclosure are wherein each R 3a are independently chlorine, fluorine, -C(O)(C1-C3 alkyl), -OH, -O(C1-3 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 3b replace.

[0453] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a Halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 3b In some embodiments, the compounds of the present disclosure are wherein at least one R 3a Chloro, fluoro, -C(O)(C1-C3 alkyl), -OH, -O(C 1-3 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally replaced by one to three R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 3b replace.

[0454] In some embodiments, the compounds of the present disclosure are wherein each R 3a are independently -O(C 1-3 alkyl), 5- to 7-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally substituted by one to three R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 3b replace.

[0455] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a -O(C 1-3 alkyl), 5- to 7-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, or a pharmaceutically acceptable salt thereof, wherein each alkyl and heterocyclyl is optionally substituted by one to three R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted by one or two R 3b In some embodiments, each alkyl and heterocyclyl group is optionally substituted with one R 3b replace.

[0456] In some embodiments, the compounds of the present disclosure are wherein each R 3a is independently halogen or -C(O)(C1-C6 alkyl) or a pharmaceutically acceptable salt thereof, wherein the alkyl group is optionally replaced by one to three R 3b In some embodiments, the compounds of the present disclosure are wherein each R 3a is independently a halogen or -C(O)(C1-C3 alkyl) compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein each R 3a A compound which is independently chloro, fluoro or -C(O)(methyl) or a pharmaceutically acceptable salt thereof.

[0457] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a is a compound or a pharmaceutically acceptable salt thereof, wherein the alkyl group is optionally replaced by one to three R 3b In some embodiments, the compounds of the present disclosure are wherein at least one R 3a is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is one in which at least one R 3a A compound wherein the moiety is chloro, fluoro or -C(O)(methyl) or a pharmaceutically acceptable salt thereof.

[0458] In some embodiments, the compounds of the present disclosure are wherein each R 3a are independently -OH or -O(C 1-3 In some embodiments, the compound of the present disclosure is wherein each R 3a A compound which is independently -OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0459] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a-OH or -O(C 1-3 In some embodiments, the compounds of the present disclosure are compounds wherein at least one R 3a A compound wherein the group consisting of -OH and methoxy is -OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0460] In some embodiments, the compounds of the present disclosure are those wherein R 3a -O(C 1-3 In some embodiments, the compound of the present disclosure is wherein R 3a A compound or a pharmaceutically acceptable salt thereof wherein the compound is methoxy.

[0461] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a -O(C 1-3 In some embodiments, the compounds of the present disclosure are compounds wherein at least one R 3a A compound or a pharmaceutically acceptable salt thereof wherein the compound is methoxy.

[0462] In some embodiments, the compounds of the present disclosure are wherein each R 3a In some embodiments, the compound of the present disclosure is one in which each R 3a A compound which is independently chloro, fluoro or -OH, or a pharmaceutically acceptable salt thereof.

[0463] In some embodiments, the compounds of the present disclosure are those wherein at least one R 3a is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is one in which at least one R 3a A compound wherein the group is chlorine, fluorine or -OH, or a pharmaceutically acceptable salt thereof.

[0464] In some embodiments, the compounds of the present disclosure are wherein each R 3b Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Halogenated alkyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 alkyl)2 or a pharmaceutically acceptable salt thereof.

[0465] In some embodiments, the compounds of the present disclosure are wherein each R 3b are independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 In some embodiments, the compound of the present disclosure is wherein each R 3b are independently fluorine, chlorine, -O(C 1-3 alkyl) or -O(C 1-3 haloalkyl) or a pharmaceutically acceptable salt thereof.

[0466] In some embodiments, the compounds of the present disclosure are wherein each R L are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 In some embodiments, the compounds of the present disclosure are compounds wherein each R L are independently hydrogen or C 1-6 In some embodiments, the compound of the present disclosure is wherein each RL are independently hydrogen or C 1-3 In some embodiments, the compound of the present disclosure is a compound wherein R L In some embodiments, the compound of the present disclosure is a compound wherein R L A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0467] In some embodiments, the compounds of the present disclosure are compounds wherein n is an integer from 0 to 3, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein n is an integer from 0 to 2, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein n is 0, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein n is 1 or 2, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein n is 0, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein n is 1, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein n is 2, or pharmaceutically acceptable salts thereof.

[0468] In some embodiments, the compounds of the present disclosure are those wherein X 6 is N or CH or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 6 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 6 A compound wherein CH or a pharmaceutically acceptable salt thereof.

[0469] In some embodiments, the compounds of the present disclosure are those wherein X 7 is N or CH or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 7 is a compound or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of the present disclosure is wherein X 7 A compound wherein CH or a pharmaceutically acceptable salt thereof.

[0470] In some embodiments, the compounds of the present disclosure are those wherein X 6 and X 7 A compound wherein CH or a pharmaceutically acceptable salt thereof.

[0471] In some embodiments, the compounds of the present disclosure are those wherein X 4 、X 5 、X 6 and X 7In some embodiments, the compound of the present disclosure is wherein X 4 、X 5 、X 6 and X 7 In some embodiments, the compound of the present disclosure is a compound wherein both of X are N or a pharmaceutically acceptable salt thereof. 4 、X 5 、X 6 and X 7 In some embodiments, the compound of the present disclosure is a compound wherein one of X is N or a pharmaceutically acceptable salt thereof. 4 、X 5 、X 6 and X 7 A compound wherein none of the above is N, or a pharmaceutically acceptable salt thereof.

[0472] In some embodiments, the compounds of the present disclosure are wherein L 2 For key, C 1-6 Alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(R L2 )S(O)2- or -(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L2 As described herein. In some embodiments, the compounds of the present disclosure are wherein L 2 For key, C 1-3 Alkyl, -(C 1-3 Alkyl)O-, -(C 1-3 alkyl)O(C 1-3 Alkyl)-, -(C 1-3 Alkyl)(R L2 )NC(O)-、-(C 1-3 alkyl)C(O)N(R L2 )-、-(C 1-3 Alkyl)S(O)2N(R L2 )-、-(C 1-3 alkyl)N(R L2)S(O)2- or -(C 1-3 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L2 As described in this article.

[0473] In some embodiments, the compounds of the present disclosure are wherein L 2 C 1-6 Alkyl, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 alkyl)N(R L2 )S(O)2- or -(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L2 As described herein. In some embodiments, the compounds of the present disclosure are wherein L 2 C 1-3 Alkyl, -(C 1-3 Alkyl)O-, -(C 1-3 alkyl)O(C 1-3 Alkyl)-, -(C 1-3 Alkyl)(R L2 )NC(O)-、-(C 1-3 alkyl)C(O)N(R L2 )-、-(C 1-3 Alkyl)S(O)2N(R L2 )-、-(C 1-3 alkyl)N(R L2 )S(O)2- or -(C 1-3 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-compound or a pharmaceutically acceptable salt thereof, wherein R L2 As described in this article.

[0474] In some embodiments, the compounds of the present disclosure are wherein L 2 A compound or a pharmaceutically acceptable salt thereof.

[0475] In some embodiments, the compounds of the present disclosure are wherein L 2 is a compound wherein L is a C1-C3 alkyl group or a pharmaceutically acceptable salt thereof. 2 In some embodiments, the compound of the present disclosure is a compound wherein L 2 In some embodiments, the compound of the present disclosure is a compound wherein L 2 The compound wherein propyl is propyl or a pharmaceutically acceptable salt thereof.

[0476] In some embodiments, the compounds of the present disclosure are those wherein R L2 is hydrogen or C 1-6 In some embodiments, the compound of the present disclosure is a compound wherein R L2 is hydrogen or C 1-3 In some embodiments, the compound of the present disclosure is a compound wherein R L2 In some embodiments, the compound of the present disclosure is a compound wherein R L2 A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0477] In some embodiments, the compounds of the present disclosure are those wherein R 5 is hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a 2. C 3-8 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl group, a C6 aryl group, a 4- to 10-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein each cycloalkyl group, aryl group, heterocyclyl group and heteroaryl group is optionally replaced by one or two R 5b In some embodiments, each cycloalkyl, aryl, heterocyclyl, and heteroaryl group is optionally replaced by one R 5b replace.

[0478] In some embodiments, the compounds of the present disclosure are those wherein R 5 is a hydrogen compound or a pharmaceutically acceptable salt thereof.

[0479] In some embodiments, the compounds of the present disclosure are those wherein R 5 A compound wherein -CN or a pharmaceutically acceptable salt thereof.

[0480] In some embodiments, the compounds of the present disclosure are those wherein R 5 C 3-8A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl group, a C6 aryl group, a 4- to 10-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein each cycloalkyl group, aryl group, heterocyclyl group and heteroaryl group is optionally replaced by one or two R 5b In some embodiments, each cycloalkyl, aryl, heterocyclyl, and heteroaryl group is optionally replaced by one R 5b replace.

[0481] In some embodiments, the compounds of the present disclosure are those wherein R 5 C 5-6 A compound or a pharmaceutically acceptable salt thereof comprising a cycloalkyl group, a C6 aryl group, a 5- to 7-membered heterocyclyl group or a 5- to 9-membered heteroaryl group, wherein each cycloalkyl group, aryl group, heterocyclyl group and heteroaryl group is optionally replaced by one or two R 5b In some embodiments, each cycloalkyl, aryl, heterocyclyl, and heteroaryl group is optionally replaced by one R 5b replace.

[0482] In some embodiments, the compounds of the present disclosure are wherein each R 5a are independently hydrogen or C 1-6 In some embodiments, the compound of the present disclosure is wherein each R 5a are independently hydrogen or C 1-3 In some embodiments, the compound of the present disclosure is a compound wherein R 5a In some embodiments, the compound of the present disclosure is a compound wherein R 5a A compound wherein the group consisting of: a methyl group and a pharmaceutically acceptable salt thereof.

[0483] In some embodiments, the compounds of the present disclosure are wherein each R 5b are independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3 In some embodiments, the compounds of the present disclosure are compounds wherein each R 5b A compound or a pharmaceutically acceptable salt thereof which is independently fluoro, chloro, cyclopropyl, hydroxy, -CN, methyl, methoxy, -OCF3 or -OCF2H.

[0484] In some embodiments, the compounds of the present disclosure are wherein each R 5b Independently C 1-3 Alkyl or C 1-3 In some embodiments, the compound of the present disclosure is wherein each R 5bIn some embodiments, the compound of the present disclosure is a compound wherein each R 5b In some embodiments, the compound of the present disclosure is a compound wherein each R 5b A compound independently comprising methoxy or a pharmaceutically acceptable salt thereof.

[0485] In some embodiments, the compounds of the present disclosure are compounds wherein Z is O or S, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein Z is O, or pharmaceutically acceptable salts thereof. In some embodiments, the compounds of the present disclosure are compounds wherein Z is S, or pharmaceutically acceptable salts thereof.

[0486] In some embodiments, the compound of the present disclosure is a compound having the structure as shown in Scheme A, or a pharmaceutically acceptable salt thereof:

[0487] Plan A :

[0488]

[0489]

[0490]

[0491]

[0492]

[0493]

[0494]

[0495]

[0496]

[0497]

[0498]

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[0501]

[0502]

[0503]

[0504]

[0505]

[0506]

[0507]

[0508]

[0509]

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[0511]

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[0517]

[0518]

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[0520]

[0521]

[0522]

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[0527]

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[0530]

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[0536]

[0537]

[0538]

[0539]

[0540]

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[0571]

[0572]

[0573]

[0574]

[0575]

[0576] In some embodiments, the compound of the present disclosure is a compound having the structure as shown in Scheme B, or a pharmaceutically acceptable salt thereof:

[0577] Plan B :

[0578]

[0579]

[0580]

[0581]

[0582]

[0583]

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[0585]

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[0594]

[0595] In some embodiments, the compounds of the present disclosure are selected from or pharmaceutically acceptable salts thereof.

[0596] In some embodiments, the compounds of the present disclosure are selected from or pharmaceutically acceptable salts thereof.

[0597] In some embodiments, the compounds of the present disclosure are or a pharmaceutically acceptable salt thereof.

[0598] In some embodiments, the compounds of the present disclosure are or a pharmaceutically acceptable salt thereof.

[0599] In some embodiments, the compounds of the present disclosure are or a pharmaceutically acceptable salt thereof.

[0600] In some embodiments, the compounds of the present disclosure are or a pharmaceutically acceptable salt thereof.

[0601] In some embodiments, the compounds of the present disclosure are or a pharmaceutically acceptable salt thereof.

[0602] In some embodiments, the compounds of the present disclosure are or a pharmaceutically acceptable salt thereof.

[0603] In some embodiments, the compound of the present disclosure is a compound selected from any one of Examples 1 to 1102, or a pharmaceutically acceptable salt thereof.

[0604] Also within the scope of this disclosure are the in vivo metabolic products of the compounds described herein, to the extent such products are novel and unobvious relative to the prior art. Such products may be produced, for example, by oxidation, reduction, hydrolysis, amidation, esterification, etc., of the administered compound, primarily due to enzymatic processes. Thus, the production of novel and unobvious compounds by methods comprising contacting the compound with a mammal for a period of time sufficient to produce its metabolic products is contemplated. Such products are typically identified by preparing radiolabeled (e.g., 14 C or 3 H) compound, which is administered parenterally to an animal (such as a rat, mouse, guinea pig, monkey or human) at a detectable dose (e.g., greater than about 0.5 mg / kg), allowed sufficient time for metabolism (usually about 30 seconds to about 30 hours), and its conversion products are isolated from urine, blood or other biological samples. These products are easily isolated because they are labeled (other products are isolated by using antibodies that can bind to epitopes that survive in the metabolites). The metabolite structure is determined in a conventional manner, for example, by MS or NMR analysis. Generally, the analysis of metabolites is performed in the same manner as conventional drug metabolism studies well known to those skilled in the art.

[0605] The compounds of the present disclosure can be prepared by a variety of methods. For example, Schemes 1-11 illustrate representative syntheses of compounds of the present disclosure. The variables shown in the following schemes are for illustrative purposes only and are independent of those variables described elsewhere herein.

[0606] General reaction scheme 1:

[0607]

[0608] Intermediate 1.1 (wherein X is -OTf, -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 1.2. Intermediate 1.2 and intermediate 1.3 are condensed in the presence of a base and heated to give intermediate 1.4. Metal-mediated cross-coupling with a suitable coupling partner BM (wherein B is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to give compounds of formula (1.a).

[0609] General reaction scheme 2:

[0610]

[0611] Palladium-mediated borylation in the presence of intermediate 1.4, bis(pinacolato)diboron, and a suitable Pd catalyst can be used to provide intermediate 2.1. Metal-mediated cross-coupling with a suitable coupling partner BX (wherein B is aryl or heteroaryl and X is -Cl, -Br, -I, or OTf) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (1.a).

[0612] General reaction scheme 3:

[0613]

[0614] Intermediate 3.1 (wherein X is -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to provide intermediate 3.2. Intermediate 3.2 and intermediate 1.3 are condensed in the presence of a base and heated to provide intermediate 3.3. Metal-mediated cross-coupling with a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (1.b).

[0615] General reaction scheme 4:

[0616]

[0617] Intermediate 4.1 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to provide intermediate 4.2. Intermediate 4.2 and intermediate 1.3 can be condensed in the presence of a base and heated to provide intermediate 4.3. Intermediate 4.3 can be reacted with NBS to provide intermediate 4.4. Metal-mediated cross-coupling with a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (1.c).

[0618] General reaction scheme 5:

[0619]

[0620] Intermediate 5.1 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 5.2. Intermediate 5.2 and intermediate 1.3 are condensed in the presence of a base and heated to give intermediate 5.3. Metal-mediated C-H arylation with a suitable coupling partner BX (wherein B is aryl, heteroaryl, and X is -Cl, -Br, -I, or OTf) in the presence of a suitable catalyst (i.e., Pd) can be used to give compounds of formula (1.d).

[0621] General reaction scheme 6:

[0622]

[0623] Intermediate 6.1 (wherein X is -OTf, -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and with heating to afford intermediate 6.2. Intermediate 6.2 and intermediate 1.3 are condensed in the presence of a base and with heating to afford intermediate 6.3. Metal-mediated cross-coupling with a suitable coupling partner BM (wherein B is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to afford compounds of formula (I.e).

[0624] General reaction scheme 7:

[0625]

[0626] Intermediate 7.1 (wherein X is -OTf, -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to provide intermediate 7.2. Intermediate 7.2 and intermediate 1.3 are condensed in the presence of a base and heated to provide intermediate 7.3. Metal-mediated cross-coupling with a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (I.f).

[0627] General Reaction Scheme 8:

[0628]

[0629] Metal-mediated cross-coupling with intermediate 1.1 (wherein X is -OTf, -Cl, Br, or -I) and a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to prepare intermediate 8.1. Intermediate 8.1 can be reacted with intermediate 8.2 in the presence of a suitable base (e.g., DIPEA) under heating to give intermediate 8.3. Condensation of intermediate 8.3 with intermediate 1.3 in the presence of a base under heating can be used to give compounds of formula (1.g).

[0630] General reaction scheme 9:

[0631]

[0632] Metal-mediated cross-coupling with intermediate 3.1 (wherein X is -OTf, -Cl, Br, or -I) and a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to prepare intermediate 9.1. Intermediate 9.1 can be reacted with intermediate 8.2 in the presence of a suitable base (e.g., DIPEA) with heating to provide intermediate 9.2. Condensation of intermediate 9.2 with intermediate 1.3 in the presence of a base with heating can be used to provide compounds of formula (1.h).

[0633] General reaction scheme 10:

[0634]

[0635] Metal-mediated cross-coupling of compounds of formula 1.a (wherein X is -OTf, -Cl, Br or -I) with suitable coupling partners Ar-M (wherein Ar is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to obtain compounds of formula (1.i).

[0636] General Reaction Scheme 11:

[0637]

[0638] Metal-mediated cross-coupling of compounds of formula 1.b (wherein X is -OTf, -Cl, Br or -I) with suitable coupling partners Ar-M (wherein Ar is aryl, heteroaryl and M is -B, -Sn, -Zn, -Si or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to obtain compounds of formula (1.j).

[0639] pharmaceutical preparations

[0640] In some embodiments, the present disclosure provides a pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Also provided herein is a pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va) and (Vb) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0641] In some embodiments, the pharmaceutical composition is used to treat a virus.

[0642] In some embodiments, the pharmaceutical composition further comprises one or more additional therapeutic agents. Any suitable additional therapeutic agent or combination therapy can be used with a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof, such as the agents and therapies described herein.

[0643] In some embodiments, the pharmaceutical composition comprises a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb) and an additional therapeutic agent, wherein the additional therapeutic agent is as described herein under the heading "Combination Therapy."

[0644] In some embodiments, the compounds disclosed herein are formulated with conventional carriers and excipients, which are selected according to conventional practice. Tablets may contain excipients, glidants, fillers, binders, and the like. Aqueous formulations can be prepared in a sterile form and may be isotonic, for example, when intended for delivery by non-oral administration. In some embodiments, the formulation may optionally contain excipients such as those described in the "Handbook of Pharmaceutical Excipients" (1986). Excipients may include, for example, ascorbic acid and other antioxidants, chelating agents such as EDTA, carbohydrates such as dextran, hydroxyalkyl cellulose, hydroxyalkyl methyl cellulose, stearic acid, and the like. The pH range of the formulation is from about 3 to about 11, for example, from about 7 to about 10.

[0645] In some embodiments, the compounds disclosed herein are administered alone. In some embodiments, the compounds disclosed herein are administered in pharmaceutical formulations. In some embodiments, the formulations for veterinary and / or human use comprise at least one compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof, together with one or more acceptable carriers and optional other therapeutic ingredients, such as those discussed herein. In some embodiments, the carrier is "acceptable" in the sense that it is compatible with the other ingredients of the formulation and is physiologically harmless to its recipient.

[0646] In some embodiments, the formulations of the present disclosure include those suitable for the aforementioned routes of administration. In some embodiments, the formulations are in unit dosage form. The formulations can be prepared by methods known in the pharmaceutical field. Technology and formulations can be found in, for example, "Remington's Pharmaceutical Sciences" (Mack Publishing Co., Easton, PA). Such methods include, for example, the step of associating the active ingredient with a carrier comprising one or more auxiliary ingredients. In some embodiments, the formulations are prepared by associating the active ingredient with a liquid carrier or a finely dispersed solid carrier or both and then, in some embodiments, shaping the product.

[0647] In some embodiments, the pharmaceutical formulation is for subcutaneous, intramuscular, intravenous, oral, or inhalation administration.

[0648] Formulations suitable for oral administration may be presented as discrete units such as capsules, cachets, or tablets, each containing a predetermined amount of the active ingredient, such as a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. In some embodiments, the active ingredient is administered as a bolus, electuary, or paste.

[0649] Tablets can be prepared, for example, by optionally compressing or molding with one or more auxiliary ingredients. Compressed tablets can be prepared, for example, by compressing the active ingredient of a free-flowing form (such as a powder or granular form) in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, preservative, surfactant or dispersant. Molded tablets can be prepared, for example, by molding a mixture of a powdered active ingredient moistened with an inert liquid diluent in a suitable machine. Tablets can optionally be coated or indented. In some embodiments, tablets are formulated to provide a slow or controlled release of the active ingredient therefrom.

[0650] For infections of the eye or other external tissues (e.g., mouth and skin), the formulations can be applied as a topical ointment or cream containing, for example, a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va) and (Vb) in an amount ranging from about 0.075% w / w to about 20% w / w (including increments of about 0.1% w / w in the range of about 0.1% to about 20% (such as about 0.6% w / w, about 0.7% w / w, etc.), such as about 0.2% w / w to about 15% w / w, and such as about 0.5% w / w to about 10% w / w. When formulated into an ointment, the compound of Formula (I), (II-a), (II-b), (II-c), (III-a) or (III-b) may be used with a paraffinic or water-miscible ointment base. Alternatively, the compound of Formula (I), (II-a), (II-b), (II-c), (III-a) or (III-b) may be formulated into a cream with an oil-in-water cream base.

[0651] If desired, the aqueous phase of the cream base may contain, for example, at least about 30% w / w of a polyol, i.e., an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol, and polyethylene glycol (including PEG 400), and mixtures thereof. Topical formulations may, in some embodiments, include compounds that enhance the absorption or penetration of the active ingredient through the skin or other affected area. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogs.

[0652] The oil phase of the emulsion can be composed of known ingredients in a known manner. Although this phase can include only an emulsifier (or alternatively referred to as an emulsifier), it can include, for example, a mixture of at least one emulsifier with a fat or oil or with both a fat and an oil. In some embodiments, a hydrophilic emulsifier is included together with a lipophilic emulsifier that acts as a stabilizer. In some embodiments, the emulsion includes both oil and fat. The emulsifier, with or without a stabilizer, together constitutes a so-called emulsifying wax, and the wax, together with the oil and fat, constitutes a so-called emulsifying ointment base, which forms the oily dispersed phase of the cream formulation.

[0653] Emulsifiers and emulsion stabilizers suitable for use in the formulation include, for example, 60. 80, cetearyl alcohol, benzyl alcohol, myristyl alcohol, glyceryl monostearate and sodium lauryl sulfate. Additional emulsifiers and emulsion stabilizers suitable for the formulation include 80.

[0654] The present invention also can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.For example, the present invention can be used for the preparation of the present invention.

[0655] Pharmaceutical formulations according to the present invention comprise a compound according to the present invention and one or more pharmaceutically acceptable carriers or excipients and optionally other therapeutic agents. Pharmaceutical formulations containing active ingredients may be in any form suitable for the intended method of administration. For example, when used for oral administration, tablets, lozenges, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups, or elixirs may be prepared. Compositions intended for oral use may be prepared according to any method known in the art for making pharmaceutical compositions, and such compositions may contain one or more agents, including sweeteners, flavorings, colorants, and preservatives, in order to provide a palatable formulation. Tablets containing the active ingredient mixed with non-toxic pharmaceutically acceptable excipients suitable for making tablets are acceptable. These excipients may be, for example, inert diluents such as calcium carbonate or sodium carbonate, lactose, calcium phosphate, or sodium phosphate; granulating agents and disintegrants such as corn starch or alginic acid; binding agents such as starch, gelatin, or gum arabic; and lubricants such as magnesium stearate, stearic acid, or talc. Tablets may be uncoated or may be coated by known techniques including microencapsulation to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed alone or with a wax.

[0656] Formulations for oral use may also be provided as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, such as peanut oil, liquid paraffin or olive oil.

[0657] The aqueous suspension of the present invention contains an active substance mixed with an excipient suitable for making an aqueous suspension. Such excipients include suspending agents, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methylcellulose, sodium alginate, polyvinyl pyrrolidone, tragacanth and gum arabic; and dispersants or wetting agents, such as naturally occurring phosphatides (e.g., lecithin), condensation products of alkylene oxides and fatty acids (e.g., polyoxyethylene stearate), condensation products of ethylene oxide and long-chain fatty alcohols (e.g., heptadecanethoxycetanol), condensation products of ethylene oxide and partial esters derived from fatty acids and hexitol anhydrides (e.g., polyoxyethylene sorbitan monooleate). Aqueous suspensions may also contain one or more preservatives, such as ethyl parahydroxybenzoate or n-propyl parahydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweeteners such as sucrose or saccharin. Other non-limiting examples of suspending agents include cyclodextrins. In some examples, the suspending agent is sulfobutyl ether beta-cyclodextrin (SEB-beta-CD), e.g.

[0658] Oily suspensions can be prepared by suspending the active ingredient in a vegetable oil (such as peanut oil, olive oil, sesame oil or coconut oil), or by suspending it in a mineral oil (such as liquid paraffin). Oral suspensions can contain thickeners such as beeswax, hard paraffin or cetyl alcohol. Sweeteners (such as those mentioned above) and flavorings can be added to provide a palatable oral formulation. These compositions can be preserved by adding an antioxidant (such as ascorbic acid).

[0659] The dispersible powders and granules of the present invention suitable for preparing an aqueous suspension by adding water provide the active ingredient in admixture with a dispersant or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersants or wetting agents and suspending agents are exemplified by those disclosed above. Additional excipients, such as sweeteners, flavorings, and coloring agents, may also be present.

[0660] The pharmaceutical compositions of the present invention can also be in the form of oil-in-water emulsions. The oil phase can be a vegetable oil (such as olive oil or peanut oil), a mineral oil (such as liquid paraffin), or a mixture thereof. Suitable emulsifiers include naturally occurring gums such as gum arabic and tragacanth; naturally occurring phospholipids such as soy lecithin; esters or partial esters derived from fatty acids and hexitol anhydrides such as sorbitan monooleate; and condensation products of these partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. Emulsions may also contain sweeteners and flavorings. Syrups and elixirs may be formulated with sweeteners such as glycerol, sorbitol, or sucrose. Such preparations may also contain a demulcent, preservative, flavoring, or coloring agent.

[0661] The pharmaceutical compositions of the present invention may be in the form of sterile injectable preparations, such as sterile injectable aqueous or oily suspensions. The suspensions may be prepared according to known techniques using suitable dispersants or wetting agents and suspending agents as mentioned above. Sterile injectable preparations may also be sterile injectable solutions or suspensions in non-toxic parenterally acceptable diluents or solvents (such as solutions in 1,3-butanediol), or may be prepared as lyophilized powders. Acceptable solvents and solvents that may be used are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile fixed oils are generally used as solvents or suspending media. For this purpose, any mild fixed oil may be used, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid may also be used to prepare injections. Acceptable solvents and solvents that may be used are water, Ringer's solution, isotonic sodium chloride solution, and hypertonic sodium chloride solution.

[0662] The amount of active component that can be combined with carrier material to produce single dosage form will change according to the host being treated and specific mode of administration.For example, be intended for the sustained-release preparation for people's oral administration and can contain about 1mg to 1000mg active material, this active material and suitable and convenient amount of carrier material compounding, this carrier material can be about 5% to about 95% (weight: weight) of total composition and change between.Can prepare pharmaceutical composition to provide the dosage that is easy to measure.For example, be intended for aqueous solution every milliliter of solution of intravenous infusion and can contain about 3mg to 500mg active component, so that with the suitable volume of about 30mL / hr rate infusion.

[0663] Formulations suitable for topical administration to the eye also include eye drops in which the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient. The active ingredient is preferably present in such formulations at a concentration of 0.5% to 20%, advantageously 0.5% to 10%, and especially about 1.5% w / w.

[0664] Formulations suitable for topical administration in the mouth include lozenges containing the active ingredient in a flavored form, usually sucrose and acacia or tragacanth; lozenges containing an inert active ingredient, such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.

[0665] Formulations for rectal administration may be presented as a suppository with a suitable base comprising for example cocoa butter or a salicylate.

[0666] In some embodiments, the compounds disclosed herein are administered by inhalation. In some embodiments, preparations suitable for intrapulmonary or intranasal administration have, for example, a particle size in the range of 0.1 micron to 500 microns, such as 0.5 micron, 1 micron, 30 microns, 35 microns, etc., and the preparation is administered by rapid inhalation of the nasal passage or by inhalation into the oral cavity to reach the alveolar sacs. Suitable preparations include aqueous or oily solutions of the active ingredient. Preparations suitable for aerosol or dry powder administration can be prepared according to conventional methods and can be delivered together with other therapeutic agents. In some embodiments, the compounds used herein are formulated and administered as dry powders. In some embodiments, the compounds used herein are formulated and administered as aerosol preparations. In some embodiments, the compounds used herein are formulated for delivery by a mask. In some embodiments, the compounds used herein are formulated for delivery by a mask inhaler.

[0667] Another embodiment provides an inhalable composition comprising a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt, including a hydrochloride, a hydrobromide, a sulfate, or a phosphate. For example, such salts may cause less lung irritation relative to other salts. In some embodiments, the inhalable composition is delivered to the endobronchial space as an aerosol comprising particles having a mass median aerodynamic diameter (MMAD) between about 1 μm and about 5 μm. In some embodiments, the compounds of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or pharmaceutically acceptable salts thereof, are formulated for aerosol delivery using a nebulizer, a pressurized metered dose inhaler (pMDI), or a dry powder inhaler (DPI).

[0668] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

[0669] Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats and solutes to render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.

[0670] The preparation is present in unit dose or multidose containers, such as sealed ampoules and vials, and can be stored under freeze-dried (lyophilized) conditions, requiring only the addition of a sterile liquid carrier, such as water for injection, immediately before use. Extemporaneous injections and suspensions are prepared from sterile powders, granules, and tablets of the aforementioned type. Preferred unit dose preparations are preparations containing a daily dose or unit daily subdose of the active ingredient as described above, or an appropriate fraction thereof.

[0671] It should be understood that in addition to the ingredients particularly mentioned above, the formulations of this invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents.

[0672] The present invention further provides a veterinary composition comprising at least one active ingredient as defined above and a veterinary carrier thereof.

[0673] Veterinary carriers are materials useful for administering the composition and may be solid, liquid or gaseous materials which are otherwise inert or acceptable in the veterinary art and are compatible with the active ingredient. These veterinary compositions may be administered orally, parenterally or by any other desired route.

[0674] The compounds of the present invention are useful in providing controlled-release pharmaceutical formulations ("controlled-release formulations") containing one or more compounds of the present invention as active ingredients, wherein the release of the active ingredient is controlled and regulated to allow less frequent dosing or to improve the pharmacokinetic or toxicity profile of a given active ingredient.

[0675] The effective dose of the active ingredient depends at least on the nature, toxicity, delivery method and pharmaceutical formulation of the condition being treated, and can be determined by a clinician using conventional dose escalation studies. The dose can be expected to be from about 0.0001 mg / kg body weight to about 100 mg / kg body weight per day; typically, from about 0.01 mg / kg body weight to about 10 mg / kg body weight per day; more typically, from about 0.01 mg / kg to about 5 mg / kg body weight per day; most typically, from about 0.05 mg / kg to about 0.5 mg / kg body weight per day. For example, the daily candidate dose range for an adult weighing about 70 kg can be from about 1 mg to about 1000 mg, such as between about 5 mg and about 500 mg, and can be in the form of a single dose or multiple doses.

[0676] How to use

[0677] The present disclosure also provides methods of treating or preventing a viral infection in a subject (eg, a human) in need thereof, comprising administering to the subject a compound described herein.

[0678] In some embodiments, the present disclosure provides methods of treating a viral infection in a subject (eg, a human) in need thereof, comprising administering to the subject in need thereof a compound described herein.

[0679] In some embodiments, the compounds described herein are administered to humans via oral, intramuscular, intravenous, subcutaneous, or inhalation administration.

[0680] In some embodiments, the present disclosure provides methods of treating or preventing a viral infection in a subject (e.g., a human) in need thereof, comprising administering to the subject a compound disclosed herein and at least one additional active therapeutic or prophylactic agent.

[0681] In some embodiments, the present disclosure provides methods of treating a viral infection in a subject (e.g., a human) in need thereof, comprising administering to the subject a compound disclosed herein and at least one additional active therapeutic or prophylactic agent.

[0682] In one embodiment, the present disclosure provides methods of inhibiting viral polymerase in a cell, comprising contacting a cell infected with a virus with a compound disclosed herein, thereby inhibiting the viral polymerase.

[0683] In one embodiment, the present disclosure provides methods of inhibiting viral proteases in cells, comprising contacting a cell infected with a virus with a compound disclosed herein and at least one additional active therapeutic agent, thereby inhibiting the viral protease.

[0684] Also provided herein are uses of the compounds disclosed herein for treating or preventing a viral infection in a subject in need thereof. For example, provided herein are uses of the compounds disclosed herein for treating a viral infection in a subject in need thereof.

[0685] In some embodiments, the viral infection is a coronavirus infection. Therefore, in some embodiments, provided herein is a method for treating a coronavirus infection in a person in need, wherein the method includes administering a compound provided herein to the person. In some embodiments, coronavirus infection is severe acute respiratory syndrome (SARS-CoV) infection, Middle East respiratory syndrome (MERS) infection, SARS-CoV-2 infection, other human coronaviruses (229E, NL63, OC43, HKU1 or WIV1) infection, zoonotic coronavirus (PEDV or HKU CoV isolates, such as HKU3, HKU5 or HKU9) infection. In some embodiments, the viral infection is severe acute respiratory syndrome (SARS) infection. In some embodiments, the viral infection is Middle East respiratory syndrome (MERS) infection. In some embodiments, the viral infection is SARS-CoV-2 infection. In some embodiments, the viral infection is a zoonotic coronavirus infection. In some embodiments, the viral infection is caused by a virus having at least 70% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase and SARS-CoV-2. In some embodiments, the viral infection is caused by a virus that has at least 80% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, the viral infection is caused by a virus that has at least 90% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, the viral infection is caused by a virus that has at least 95% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

[0686] In some embodiments, the viral infection is caused by a variant of SARS-CoV-2, such as a B.1.1.7 variant (British variant), a B.1.351 variant (South African variant), a P.1 variant (Brazilian variant), a B.1.1.7 and E484K variant, a B.1.1.207 variant, a B.1.1.317 variant, a B.1.1.318 variant, a B.1.429 variant, a B.1.525 variant, or a P.3 variant. In some embodiments, the viral infection is caused by a B.1.1.7 variant of SARS-CoV-2. In some embodiments, the viral infection is caused by a B.1.351 variant of SARS-CoV-2. In some embodiments, the viral infection is caused by a P.1 variant of SARS-CoV-2.

[0687] In some embodiments, the present disclosure provides compounds for treating coronavirus infections in people in need. In some embodiments, coronavirus infection is severe acute respiratory syndrome (SARS) infection, Middle East respiratory syndrome (MERS) infection, SARS-CoV-2 infection, other human coronaviruses (229E, NL63, OC43, HKU1 or WIV1) infection, and zoonotic coronavirus (PEDV or HKU CoV isolates, such as HKU3, HKU5 or HKU9) infection. In some embodiments, viral infection is severe acute respiratory syndrome (SARS) infection. In some embodiments, viral infection is Middle East respiratory syndrome (MERS) infection. In some embodiments, viral infection is SARS-CoV-2 infection (COVID19).

[0688] As described more fully herein, the compounds described herein can be administered to an individual (e.g., a human) infected with a virus together with one or more additional therapeutic agents. The additional therapeutic agent can be administered to the infected individual simultaneously with the compounds of the present disclosure or before or after administration of the compounds of the present disclosure.

[0689] Application

[0690] One or more compounds of the present invention may be administered by any route appropriate to the condition to be treated. Suitable routes include oral, rectal, inhalation, pulmonary, topical (including buccal and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural), etc. In some embodiments, the compounds disclosed herein are administered by inhalation or intravenously. In some embodiments, the compounds disclosed herein are administered orally. It should be understood that the preferred route may vary, for example, depending on the condition of the recipient.

[0691] In the method for treating viral infection of the present invention, the compounds of the present invention can be applied to people who may be exposed to viruses or have already suffered from viral infection at any time. In some embodiments, the compounds of the present invention can be applied prophylactically to people who are in contact with people suffering from viral infection or are at risk of contacting people suffering from viral infection, such as health care providers. In some embodiments, the application of the compounds of the present invention can be to people who are positive for viral infection tests but have not yet shown symptoms of viral infection. In some embodiments, the compounds of the present invention can be applied to people when the symptoms of viral infection begin.

[0692] In some embodiments, the methods disclosed herein comprise event-driven administration of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, to a subject.

[0693] As used herein, the term "event-driven" or "event-driven administration" refers to administration of a compound described herein (e.g., a compound of the present disclosure) or a pharmaceutically acceptable salt thereof (1) prior to (e.g., 2 hours, 1 day, 2 days, 5 days, or 7 days or more prior to) an event that will expose an individual to a virus (or will otherwise increase the risk of an individual acquiring a viral infection); and / or (2) during an event (or more than one recurring event) that will expose an individual to a virus (or will otherwise increase the risk of an individual acquiring a viral infection); and / or (3) after (or after the final event in a series of recurring events) an event that will expose an individual to a virus (or will otherwise increase the risk of an individual acquiring a viral infection). In some embodiments, event-driven administration is performed before the subject is exposed to the virus. In some embodiments, event-driven administration is performed after the subject is exposed to the virus. In some embodiments, event-driven administration is performed before and after the subject is exposed to the virus.

[0694] In certain embodiments, the methods disclosed herein involve administration before and / or after an event that will expose an individual to a virus or otherwise increase the risk of an individual acquiring a viral infection, for example, as pre-exposure prophylaxis (PrEP) and / or as post-exposure prophylaxis (PEP). In some embodiments, the methods disclosed herein include pre-exposure prophylaxis (PrEP). In some embodiments, the methods disclosed herein include post-exposure prophylaxis (PEP).

[0695] In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is administered to a subject prior to exposure to a virus.

[0696] In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is administered to a subject both before and after exposure to a virus.

[0697] In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is administered to a subject after exposure to a virus.

[0698] An example of an event-driven dosing regimen includes administering a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, within 24 to 2 hours prior to the virus, followed by administration of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, every 24 hours during the exposure period, followed by further administration of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, after the last exposure, and a final administration of a compound of Formula A or Formula B, or a pharmaceutically acceptable salt thereof, 24 hours later.

[0699] Another example of an event-driven dosing regimen includes administering a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, within 24 hours prior to viral exposure, followed by daily administration during exposure, and then a final administration (which may be in increasing doses, such as a double dose) approximately 24 hours after the last exposure.

[0700] The specific dosage level of the compound of the present disclosure for any particular subject will depend on a variety of factors, including the activity of the specific compound used, the age, weight, general health, sex, diet, administration time, route of administration and excretion rate, drug combination and the severity of the specific disease of the subject receiving therapy. For example, dosage can be expressed as milligrams (mg / kg) of the compound described herein per kilogram of subject body weight. A dosage between about 0.1 mg / kg and 150 mg / kg may be appropriate. In some embodiments, a dosage between about 0.1 mg / kg and 100 mg / kg may be appropriate. In other embodiments, a dosage between 0.5 mg / kg and 60 mg / kg may be appropriate. Normalizing according to the subject's weight is particularly useful when adjusting the dosage between subjects with very different sizes (such as when using drugs in children and adults, or when converting the effective dose of non-human subjects such as dogs to a dosage suitable for human subjects).

[0701] The daily dose can also be described as the total amount of a compound described herein administered per dose or per day. The daily dose of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, can be about 1 mg to 4,000 mg, about 2,000 mg / day to 4,000 mg / day, about 1 mg / day to 2,000 mg / day, about 1 mg / day to 1,000 mg / day, about 10 mg / day to 500 mg / day, about 20 mg / day to 500 mg / day, about 50 mg / day to 300 mg / day, about 75 mg / day to 200 mg / day, or about 15 mg / day to 150 mg / day.

[0702] The dosage or frequency of administration of the disclosed compounds may be adjusted during the course of treatment according to the judgment of the administering physician.

[0703] The compounds of the present disclosure can be administered to an individual (eg, a human) in a therapeutically effective amount. In some embodiments, the compound is administered once daily.

[0704] Provided herein is compound and can be used by any useful approach and means, such as by oral or parenteral (for example, intravenous) administration.The therapeutically effective amount of compound can include about 0.00001mg / kg body weight / day to about 10mg / kg body weight / day, such as about 0.0001mg / kg body weight / day to about 10mg / kg body weight / day, or such as about 0.001mg / kg body weight / day to about 1mg / kg body weight / day, or such as about 0.01mg / kg body weight / day to about 1mg / kg body weight / day, or such as about 0.05mg / kg body weight / day to about 0.5mg / kg body weight / day. In some embodiments, provided herein is compound and therapeutically effective amount include about 0.3mg / day to about 30mg / day or about 30mg / day to about 300mg / day or about 0.3mg / day to about 30mg / day or about 30mg / day to about 300mg / day.

[0705] The compounds of the present disclosure can be combined with one or more additional therapeutic agents at any dose of the compounds of the present disclosure (e.g., 1 mg to 1000 mg of compound). A therapeutically effective amount may include from about 0.1 mg / agent to about 1000 mg / agent, such as from about 50 mg / agent to about 500 mg / agent, or such as from about 100 mg / agent to about 400 mg / agent, or such as from about 150 mg / agent to about 350 mg / agent, or such as from about 200 mg / agent to about 300 mg / agent, or such as from about 0.01 mg / agent to about 1000 mg / agent, or such as from about 0.01 mg / agent to about 100 mg / agent, or such as from about 0.1 mg / agent to about 100 mg / agent, or such as from about 1 mg / agent to about 100 mg / agent, or such as from about 1 mg / agent to about 10 mg / agent, or such as from about 1 mg / agent to about 1000 mg / agent. Other therapeutically effective amounts of a compound of the present disclosure are about 1 mg / dose, or about 2 mg / dose, 3 mg / dose, 4 mg / dose, 5 mg / dose, 6 mg / dose, 7 mg / dose, 8 mg / dose, 9 mg / dose, 10 mg / dose, 15 mg / dose, 20 mg / dose, 25 mg / dose, 30 mg / dose, 35 mg / dose, 40 mg / dose, 45 mg / dose, 50 mg / dose, 55 mg / dose, 60 mg / dose, 65 mg / dose, 70 mg / dose, 75 mg / dose, 80 mg / dose, 85 mg / dose, 90 mg / dose, 95 mg / dose, or about 100 mg / dose. Other therapeutically effective amounts of the compounds of the present disclosure are about 100 mg / dose, 125 mg / dose, 150 mg / dose, 175 mg / dose, 200 mg / dose, 225 mg / dose, 250 mg / dose, 275 mg / dose, 300 mg / dose, 325 mg / dose, 350 mg / dose, 375 mg / dose, 400 mg / dose, 425 mg / dose, 450 mg / dose, 475 mg / dose, 500 mg / dose, 525 mg / dose, g / dose, 550 mg / dose, 575 mg / dose, 600 mg / dose, 625 mg / dose, 650 mg / dose, 675 mg / dose, 700 mg / dose, 725 mg / dose, 750 mg / dose, 775 mg / dose, 800 mg / dose, 825 mg / dose, 850 mg / dose, 875 mg / dose, 900 mg / dose, 925 mg / dose, 950 mg / dose, 975 mg / dose or about 1000 mg / dose.

[0706] In some embodiments, the methods described herein comprise administering to a subject an initial daily dose of about 1 mg to 500 mg of a compound provided herein, and gradually increasing the dose until clinical efficacy is achieved. Increments of about 5 mg, 10 mg, 25 mg, 50 mg, or 100 mg may be used to increase the dose. The dose may be increased daily, every other day, twice a week, weekly, biweekly, every three weeks, or monthly.

[0707] When administered orally, the total daily dose for a human subject can be between about 1 mg / day-4,000 mg / day, between about 1 mg / day-3,000 mg / day, between 1 mg / day-2,000 mg / day, between about 1 mg / day-1,000 mg / day, between about 10 mg / day-500 mg / day, between about 50 mg / day-300 mg / day, between about 75 mg / day-200 mg / day, or between about 100 mg / day-150 mg / day. In some embodiments, the total daily dose for a human subject may be about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 200, 300, 400, 500, 600, 700, or 800 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 300 mg / day, 400 mg / day, 500 mg / day, or 600 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, or 4000 mg / day.In some embodiments, the total daily dose for a human subject can be about 100 mg / day to 200 mg / day, 100 mg / day to 300 mg / day, 100 mg / day to 400 mg / day, 100 mg / day to 500 mg / day, 100 mg / day to 600 mg / day, 100 mg / day to 700 mg / day, 100 mg / day to 800 mg / day, 100 mg / day to 900 mg / day, 100 mg / day to 1000 mg / day, 500 mg / day -1100mg / day, 500mg / day-1200mg / day, 500mg / day-1300mg / day, 500mg / day-1400mg / day, 500mg / day-1500mg / day, 500mg / day-1600mg / day, 500mg / day-1700mg / day, 500mg / day-1800mg / day, 500mg / day-1900mg / day, 500mg / day-2000mg / day, 1500mg / day-21 00mg / day, 1500mg / day-2200mg / day, 1500mg / day-2300mg / day, 1500mg / day-2400mg / day, 1500mg / day-2500mg / day, 2000mg / day-2600mg / day, 2000mg / day-2700mg / day, 2000mg / day-2800mg / day, 2000mg / day-2900mg / day, 2000mg / day-3000mg / day, 2500mg / day g / day-3100 mg / day, 2500 mg / day-3200 mg / day, 2500 mg / day-3300 mg / day, 2500 mg / day-3400 mg / day, 2500 mg / day-3500 mg / day, 3000 mg / day-3600 mg / day, 3000 mg / day-3700 mg / day, 3000 mg / day-3800 mg / day, 3000 mg / day-3900 mg / day or 3000 mg / day-4000 mg / day.

[0708] In some embodiments, the total daily dose for a human subject may be about 100 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 150 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 200 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 250 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 300 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 350 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 400 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 450 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 500 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 550 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 600 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 650 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 700 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 750 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 800 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 850 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 900 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 950 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 1000 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 1500 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 2000 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 2500 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 3000 mg / day administered in a single dose. In some embodiments, the total daily dose for a human subject may be about 4000 mg / day administered in a single dose.

[0709] A single dose can be administered hourly, daily, weekly, or monthly. For example, a single dose can be administered once every 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, or once every 24 hours. A single dose can also be administered once every 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or once every 7 days. A single dose can also be administered once every 1 week, 2 weeks, 3 weeks, or once every 4 weeks. In certain embodiments, a single dose can be administered once a week. A single dose can also be administered once a month. In some embodiments, the compounds disclosed herein are administered once a day in the methods disclosed herein. In some embodiments, the compounds disclosed herein are administered twice a day in the methods disclosed herein. In some embodiments, the compounds disclosed herein are administered three times a day in the methods disclosed herein.

[0710] In some embodiments, the compounds disclosed herein are administered once daily at a total daily dose of 100 mg / day to 4000 mg / day. In some embodiments, the compounds disclosed herein are administered twice daily at a total daily dose of 100 mg / day to 4000 mg / day. In some embodiments, the compounds disclosed herein are administered three times daily at a total daily dose of 100 mg / day to 4000 mg / day.

[0711] The frequency of the dosage of the compound of the present disclosure will be determined by the needs of the individual patient and can be, for example, once a day or twice a day or more. As long as the treatment of viral infection requires, the administration of the compound is continued. For example, the compound can be administered to a person infected with the virus for a period of 20 to 180 days, or for example, a period of 20 to 90 days, or for example, a period of 30 to 60 days.

[0712] Administration can be intermittent, with the patient receiving a daily dose of a compound of the present disclosure over a period of several or more days, followed by a period of several or more days in which the patient does not receive a daily dose of the compound. For example, the patient may receive a daily dose of the compound three times a week or every other day. Again by way of example, the patient may receive a daily dose of the compound over a period of 1 to 14 days, followed by a period of 7 to 21 days in which the patient does not receive a daily dose of the compound, followed by a subsequent period of time (e.g., 1 to 14 days) in which the patient again receives a daily dose of the compound. Depending on the clinical needs of the patient being treated, alternating periods of administration of the compound followed by no administration of the compound may be repeated.

[0713] The compounds of the present disclosure, or pharmaceutical compositions thereof, can be administered once, twice, three times, or four times daily using any suitable mode described above. Furthermore, administration or treatment with the compounds can continue for multiple days; for example, for one treatment cycle, treatment will typically continue for at least 7, 14, or 28 days. Treatment cycles can alternate with rest periods of about 1 to 28 days, typically about 7 or about 14 days, between cycles. In other embodiments, treatment cycles can also be continuous.

[0714] Combination therapy

[0715] The compounds described herein can also be used in combination with one or more additional therapeutic agents. Thus, also provided herein are methods of treating viral infections in subjects in need thereof, wherein these methods comprise administering to the subject a compound disclosed herein and a therapeutically effective amount of one or more additional therapeutic or prophylactic agents.

[0716] In some embodiments, the additional therapeutic agent is an antiviral agent.Any suitable antiviral agent can be used in the methods described herein.

[0717] In some embodiments, the additional therapeutic agent is a 2,5-oligoadenylate synthetase stimulator, a 5-HT2a receptor antagonist, a 5-lipoxygenase inhibitor, an ABL family tyrosine kinase inhibitor, an Abl tyrosine kinase inhibitor, an aldehyde dehydrogenase inhibitor, an acetyl-CoA carboxylase inhibitor, an actin antagonist, an actin modulator, an activity-dependent neuroprotectant modulator, an adenosine A3 receptor agonist, an adrenergic receptor antagonist, an adrenomedullin ligand, an adrenomedullin ligand inhibitor, an advanced glycation products receptor antagonist, an advanced glycation products receptor modulator, an AKT protein kinase inhibitor, a stimulator of alanine-proline-rich secretory protein, an aldose reductase inhibitor, an alkaline phosphatase stimulator, an α2 adrenergic receptor antagonist, an α2B adrenergic receptor agonist, an AMP-activated protein kinase stimulator, an AMPA receptor modulator, an amyloid deposition inhibitor, an androgen receptor antagonist, an angiotensin II AT-1 receptor antagonists, angiotensin II AT-2 receptor agonists, angiotensin II receptor modulators, angiotensin-converting enzyme 2 inhibitors, angiotensin-converting enzyme 2 modulators, angiotensin-converting enzyme 2 stimulators, angiotensin receptor modulators, annexin A5 stimulators, anoctamin 1 inhibitor, anticoagulant, antihistamine, anti-hypoxic agent, antithrombotic agent, AP1 transcription factor regulator, Apelin receptor agonist, APOA1 gene stimulator, apolipoprotein A1 agonist, apolipoprotein B antagonist, apolipoprotein B regulator, apolipoprotein C3 antagonist, aryl hydrocarbon receptor agonist, aryl hydrocarbon receptor antagonist, ATP-binding cassette transporter B5 regulator, Axl tyrosine kinase receptor inhibitor, bactericidal permeability protein inhibitor, Basigin inhibitor, Basigin regulator, BCL2 gene inhibitor, BCL2L11 gene stimulator, Bcr protein inhibitor, β1 adrenergic receptor modulator, β2 adrenergic receptor agonist, β-adrenergic receptor agonist, β-arrestin stimulator, coagulation regulator, BMP10 gene inhibitor, BMP15 gene inhibitor, Bone morphogenetic protein-10 ligand inhibitor, bone morphogenetic protein-15 ligand inhibitor, bradykinin B2 receptor antagonist, brain-derived neurotrophic factor ligand, bromodomain-containing protein 2 inhibitor, bromodomain-containing protein 4 inhibitor, Btk tyrosine kinase inhibitor, C-reactive protein modulator, Ca2+ release-activated Ca2+ channel 1 inhibitor, cadherin-5 modulator, calcium-activated chloride channel inhibitor, calcium channel modulator, calpain-I inhibitor, calpain-II inhibitor, calpain-IX inhibitor, cannabinoid CB2 receptor agonist, cannabinoid receptor modulator, casein kinase II inhibitor, CASP8-FADD-like regulator inhibitor, caspase inhibitor, catalase stimulator, CCL26 gene inhibitor, CCR2 chemokine antagonist, CCR5 chemokine antagonist,CD11a agonists, CD122 agonists, CD3 antagonists, CD4 agonists, CD40 ligands, CD40 ligand modulators, CD40 ligand receptor agonists, CD40 ligand receptor modulators, CD49d agonists, CD70 antigen modulators, CD73 agonists, CD73 antagonists, CD95 antagonists, CFTR inhibitors, CGRP receptor antagonists, chemokine receptor-like 1 agonists, chloride channel inhibitors, chloride channel modulators, cholera toxin subunit B inhibitors, cholesterol ester transfer protein inhibitors, collagen modulators, complement C1s subcomponent inhibitors, complement C3 inhibitors, complement factor C5 inhibitors, complement factor C5a inhibitors, complement factor H stimulators, complement Cascade inhibitors, complement factor C2 inhibitors, complement factor D inhibitors, connective tissue growth factor ligand inhibitors, coronavirus nucleoprotein modulators, coronavirus small envelope protein modulators, coronavirus spike glycoprotein inhibitors, coronavirus spike glycoprotein modulators, COVID19 small envelope membrane protein modulators, COVID19 nonstructural protein 8 modulators, COVID19 nucleoprotein modulators, COVID19 protein 3a inhibitors, COVID19 replicase polyprotein 1a inhibitors, COVID19 replicase polyprotein 1a modulators, COVID19 replicase polyprotein 1ab inhibitors, COVID19 replicase polyprotein 1ab modulators, COVID19 spike glycoprotein inhibitors Agents, COVID19 spike glycoprotein modulators, COVID19 structural glycoprotein modulators, CRF-2 receptor agonists, CSF-1 agonists, CSF-1 antagonists, CX3CR1 chemokine antagonists, CXC10 chemokine ligand inhibitors, CXC5 chemokine ligand inhibitors, CXCL1 gene modulators, CXCL2 gene modulators, CXCL3 gene modulators, CXCR1 chemokine antagonists, CXCR2 chemokine antagonists, CXCR4 chemokine antagonists, cyclin D1 inhibitors, cyclin E inhibitors, cyclin-dependent kinase-1 inhibitors, cyclin-dependent kinase-2 inhibitors, cyclin-dependent kinase-5 inhibitors, cyclin-dependent kinase-7 inhibitors, cyclin-dependent kinase-9 inhibitors, cyclooxygenase 2 inhibitors, cyclooxygenase inhibitors, cysteine ​​protease inhibitors, cytochrome P4503A4 inhibitors, cytokine receptor antagonists, cytotoxic T-lymphocyte protein gene regulators, cytotoxic T-lymphocyte protein-4 inhibitors, cytotoxic T-lymphocyte protein-4 stimulators, dehydrogenase inhibitors, dehydropeptidase-1 regulators, deoxyribonuclease I stimulators, deoxyribonuclease gamma stimulators, deoxyribonuclease stimulators, dihydroceramide delta 4 desaturase inhibitors, dihydroorotate dehydrogenase inhibitors, dipeptidyl peptidase I inhibitors, dipeptidyl peptidase III inhibitors, diuretics,DNA binding protein inhibitors, DNA methyltransferase inhibitors, dopamine transporter inhibitors, E-selectin antagonists, Ecto NOX disulfide thiol exchanger 2 inhibitors, EGFR gene inhibitors, elongation factor 1α2 modulators, endoplasmic reticulum regulators, endoribonuclease DICER regulators, endothelin ET-A receptor antagonists, epidermal growth factor receptor antagonists, estrogen receptor beta agonists, estrogen receptor modulators, eukaryotic initiation factor 4A-I inhibitors, Exo-α sialidase regulators, exoportin 1 inhibitors, factor Ia regulators, factor IIa regulators, factor VII antagonists, factor Xa antagonists, factor XIa antagonists Antagonists, FGF receptor antagonists, FGF-1 ligands, FGF-1 ligand inhibitors, FGF-2 ligand inhibitors, FGF1 receptor antagonists, FGF2 receptor antagonists, FGF3 receptor antagonists, Flt3 tyrosine kinase inhibitors, Fractalkine ligand inhibitors, free fatty acid receptor 2 agonists, free fatty acid receptor 3 agonists, furin inhibitors, Fyn tyrosine kinase inhibitors, FYVE finger phosphoinositide kinase inhibitors, G protein-coupled bile acid receptor 1 agonists, GABA A receptor modulators, galectin-3 inhibitors, gamma-secretase inhibitors, GDF agonists, gelsolin stimulators, glial cell line neurotrophic factor ligands, glucocorticoid receptor agonists, glutathione peroxidase stimulators, GM-CSF ligand inhibitors, GM-CSF receptor agonists, GM-CSF receptor modulators, Griffithsin modulators, somatomedin alpha ligand inhibitors, Grp78 calcium-binding protein inhibitors, heat shock protein HSP90α inhibitors, heat shock protein HSP90β inhibitors, heat shock protein inhibitors, heat shock protein Stimulants, hemagglutinin regulators, hemoglobin regulators, hemolysin α inhibitors, heparinase inhibitors, heparin agonists, hepatitis B structural protein inhibitors, hepatitis C virus NS5B polymerase inhibitors, HIF prolyl hydroxylase inhibitors, HIF prolyl hydroxylase-2 inhibitors, high mobility group protein B1 inhibitors, histamine H1 receptor antagonists, histamine H2 receptor antagonists, histone deacetylase-6 inhibitors, histone inhibitors, HIV protease inhibitors, HIV-1 gp120 protein inhibitors, HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HLA Class I antigen modulators, HLA class II antigen modulators, host cell factor modulators, Hsp 90 inhibitors, human papillomavirus E6 protein modulators, human papillomavirus E7 protein modulators, hypoxia-inducible factor inhibitor gene inhibitors, hypoxia-inducible factor-2α modulators, I-κB kinase inhibitors, I-κB kinase modulators, ICAM-1 stimulators, IgG receptor FcRn large subunit p51 modulators, IL-12 receptor antagonists, IL-15 receptor agonists, IL-15 receptor modulators,IL-17 antagonists, IL-18 receptor accessory protein antagonists, IL-2 receptor agonists, IL-22 agonists, IL-23 antagonists, IL-6 receptor agonists, IL-6 receptor antagonists, IL-6 receptor modulators, IL-7 receptor agonists, IL-8 receptor antagonists, IL12 gene stimulators, IL8 gene modulators, immunoglobulin G modulators, immunoglobulin G1 agonists, immunoglobulin G1 modulators, immunoglobulin agonists, immunoglobulin gamma Fc receptor I modulators, immunoglobulin kappa modulators, inosine monophosphate dehydrogenase inhibitors, insulin sensitizers, integrin agonists, integrin alpha-4 / beta-7 antagonists, integrin alpha-V / beta-1 antagonists, integrin alpha-V / beta-6 antagonists, interferon agonists, interferon alpha 14 ligands, interferon alpha 2 ligands, interferon alpha 2 Ligand modulators, interferon alpha ligands, interferon alpha ligand inhibitors, interferon alpha ligand modulators, interferon beta ligands, interferon gamma ligand inhibitors, interferon gamma receptor agonists, interferon gamma receptor antagonists, interferon receptor modulators, interferon type I receptor agonists, interleukin 17A ligand inhibitors, interleukin 17F ligand inhibitors, interleukin 18 ligand inhibitors, interleukin 22 ligands, interleukin-1 beta ligand inhibitors, interleukin-1 beta ligand modulators, interleukin-1 ligand inhibitors, interleukin-2 ligands, interleukin-29 ligands, interleukin-6 ligand inhibitors, interleukin-7 ligands, interleukin-8 ligand inhibitors, IRAK-4 protein kinase inhibitors, JAK tyrosine kinase inhibitors, Jak1 tyrosine kinase inhibitors, Jak2 tyrosine kinase inhibitors, Jak3 tyrosine kinase inhibitors, Jun N-terminal kinase inhibitors, Jun N-terminal kinase modulators, kallikrein modulators, Kelch-like ECH-related protein 1 modulators, Kit tyrosine kinase inhibitors, KLKB1 gene inhibitors, lactoferrin stimulators, lanosterol-14 demethylase inhibitors, Lck tyrosine kinase inhibitors, leukocyte Ig-like receptor A4 modulators, leukocyte elastase inhibitors, leukotriene BLT receptor antagonists, leukotriene D4 antagonists, leukotriene receptor antagonists, listeriolysin stimulators, liver X receptor antagonists, low molecular weight heparin, pulmonary surfactant-associated protein B stimulators, pulmonary surfactant-associated protein D modulators, Lyn tyrosine kinase inhibitors, Lyn tyrosine kinase stimulators, lysine-specific histone demethylase 1 inhibitors, macrophage migration inhibitory factor inhibitors, mannan-binding lectin serine protease inhibitors, mannan-binding lectin serine protease-2 inhibitors, MAO B inhibitors, MAP kinase inhibitors, MAPK gene modulators, matrix metalloproteinase modulators, Maxi K potassium channel inhibitors, MCL1 gene inhibitors, MEK protein kinase inhibitors, MEK-1 protein kinase inhibitors, melanocortin MC1 receptor agonists, melanocortin MC3 receptor agonists,Metalloproteinase-12 inhibitors, METTL3 gene inhibitors, moesin inhibitors, moesin modulators, monocyte chemoattractant protein 1 ligand inhibitors, monocyte differentiation antigen CD14 inhibitors, mRNA cap guanine N7 methyltransferase modulators, mTOR complex 1 inhibitors, mTOR complex 2 inhibitors, mTOR inhibitors, mucolipin modulators, muscarinic receptor antagonists, myeloperoxidase inhibitors, NACHT LRR PYD domain protein 3 inhibitors, NAD synthase modulators, NADPH oxidase inhibitors, neuropilin 2 modulators, neuroplasticity protein inhibitors, NFE2L2 gene stimulators, NK cell receptor agonists, NK1 receptor antagonists, NMDA receptor antagonists, NMDA receptor ε2 subunit inhibitors, non-receptor tyrosine kinase TYK2 antagonists, non-nucleoside reverse transcriptase inhibitors, erythroid 2-related factor 2 stimulators, nuclear factor κB inhibitors, nuclear factor κB modulators, nuclease stimulators, nucleolin inhibitors, nucleoprotein inhibitors, nucleoprotein modulators, nucleoside reverse transcriptase inhibitors, opioid receptor agonists, opioid receptor antagonists, opioid receptor mu modulators, opioid receptor sigma antagonists 1, ornithine decarboxylase inhibitors, outer membrane protein inhibitors, OX40 ligands, p38 MAP kinase alpha inhibitors, p38 MAP kinase inhibitors, p38 MAP kinase modulators, p53 tumor suppressor protein stimulators, palmitoyl protein thioesterase 1 inhibitors, papain inhibitors, PARP inhibitors, PARP modulators, PDE 10 inhibitors, PDE 3 inhibitors, PDE 4 inhibitors, PDGF receptor alpha antagonists, PDGF receptor antagonists, PDGF receptor beta antagonists, peptidylprolyl cis-trans isomerase A inhibitors, peroxidase 6 modulators, PGD2 antagonists, PGI2 agonists, P-glycoprotein inhibitors, phosphatidylinositol 3-kinase inhibitors, phosphatidylinositol-3 kinase delta inhibitors, phosphatidylinositol-3 kinase gamma inhibitors, phospholipase A2 inhibitors, plasma kallikrein inhibitors, plasminogen activator inhibitor 1 inhibitors, platelet inhibitors, platelet glycoprotein VI inhibitors, Polo-like kinase 1 inhibitors, poly ADP-ribose polymerase 1 inhibitors, poly ADP-ribose polymerase 2 inhibitors, polymerase Cofactor VP35 inhibitors, PPARα agonists, progesterone receptor agonists, programmed cell death protein 1 regulators, prolyl hydroxylase inhibitors, prostaglandin E synthase-1 inhibitors, protease inhibitors, proteasome inhibitors, protein arginine deiminase IV inhibitors, protein tyrosine kinase inhibitors, protein tyrosine phosphatase β inhibitors, protein tyrosine phosphatase-2C inhibitors, proto-oncogene Mas agonists, purine receptor antagonists, Raf protein kinase inhibitors, RANTES ligands, Ras gene inhibitors, retinoic acid receptor response protein 2 stimulators, Rev protein regulators, ribonuclease stimulators, RIP-1 kinase inhibitors,RNA helicase inhibitors, RNA polymerase inhibitors, RNA polymerase modulators, S phase kinase-associated protein 2 inhibitors, SARS coronavirus 3C protease-like inhibitors, serine protease inhibitors, serine threonine protein kinase ATR inhibitors, serine threonine protein kinase TBK1 inhibitors, serum amyloid A protein modulators, signal transduction protein CD24 stimulators, sodium channel stimulators, sodium glucose transporter-2 inhibitors, sphingosine kinase 1 inhibitors, sphingosine kinase 2 inhibitors, sphingosine kinase inhibitors, sphingosine-1-phosphate receptor-1 agonists, sphingosine Sphingosine-1-phosphate receptor-1 antagonist, sphingosine-1-phosphate receptor-1 modulator, sphingosine-1-phosphate receptor-5 agonist, sphingosine-1-phosphate receptor-5 modulator, spike glycoprotein inhibitor, Src tyrosine kinase inhibitor, STAT-1 modulator, STAT-3 inhibitor, STAT-5 inhibitor, STAT3 gene inhibitor, stem cell antigen-1 inhibitor, interferon gene protein stimulator, sulfatase inhibitor, superoxide dismutase modulator, superoxide dismutase stimulator, Syk tyrosine kinase inhibitor, T cell immunoreceptor Ig ITIM protein inhibitors, T cell receptor agonists, T cell surface glycoprotein CD28 inhibitors, T cell differentiation antigen CD6 inhibitors, T cell surface glycoprotein CD8 stimulators, T cell transcription factor NFAT regulators, tankyrase-1 inhibitors, tankyrase-2 inhibitors, Tek tyrosine kinase receptor stimulators, telomerase regulators, tetanus toxin regulators, TGFβ receptor antagonists, TGFB2 gene inhibitors, thymosin β4 ligands, thyroid hormone receptor β agonists, tissue factor inhibitors, tissue plasminogen activator regulators, tissue plasminogen activator stimulators, TLR agonists, TLR regulators, TLR-2 agonists, TLR-2 antagonists, TLR-3 agonists, TLR-4 agonists, TLR-4 antagonists, TLR-6 agonists, TLR-7 agonists, TLR-7 antagonists, TLR-8 antagonists, TLR-9 agonists, TMPRSS2 gene inhibitors, TNFα ligand inhibitors, TNFα ligand modulators, TNF binders, TNF gene inhibitors, topoisomerase inhibitors, transcription factor EB stimulators, transferrin regulators, transketolase inhibitors, translocation-associated protein inhibitors, transmembrane serine protease 2 inhibitors, transthyretin regulators, TREM receptor 1 antagonists, TRP cation channel C1 regulators, TRP cation channel C6 inhibitors, TRP cation channel V6 inhibitors, trypsin 1 inhibitors, trypsin 2 inhibitors, trypsin 3 inhibitors, trypsin inhibitors, tubulin α inhibitors, tubulin β inhibitors, tumor necrosis factor 14 ligand inhibitors, TYK2 gene inhibitors, type I IL-1 receptor antagonists, tyrosine protein kinase ABL1 inhibitors,Ubiquitin cytochrome c reductase 14kDa inhibitor, ubiquitin ligase modulator, unspecified GPCR agonist, unspecified cytokine receptor modulator, unspecified enzyme stimulator, unspecified gene inhibitor, unspecified receptor modulator, urokinase plasminogen activator inhibitor, vascular cell adhesion protein 1 agonist, vasodilator, VEGF ligand inhibitor, VEGF receptor antagonist, VEGF-1 receptor antagonist, VEGF-1 receptor modulator, VEGF-2 receptor antagonist, VEGF-3 receptor antagonist, vimentin inhibitor, vimentin modulator, VIP receptor agonist, viral envelope protein inhibitor, viral protease inhibitor, viral protease modulator, viral protein target modulator, viral ribonuclease inhibitor, viral structural protein modulator, vitamin D3 receptor agonist, X-linked inhibitor of apoptosis protein inhibitor, xanthine oxidase inhibitor, or disintegrin inhibitor.

[0718] In some embodiments, the compounds and compositions of the present disclosure may be administered in combination with Sars-Cov-2 treatments such as parenteral fluids (including dextrose saline and Ringer's lactate), nutrients, antibiotics (including azithromycin, metronidazole, amphotericin B, amoxicillin / clavulanic acid, trimethoprim / sulfamethoxazole, R-327, and cephalosporin antibiotics such as ceftriaxone and cefuroxime), antifungal prophylaxis, antipyretics and analgesics, antiemetics (such as metoclopramide) and / or antidiarrheals, vitamin and mineral supplements (including vitamin K, vitamin D, cholecalciferol, vitamin C, and zinc sulfate), anti-inflammatory agents (such as ibuprofen or steroids), corticosteroids (such as dexamethasone, methylprednisolone, prednisone, mometasone), immunomodulatory drugs (e.g., interferon), vaccines, and analgesics.

[0719] In some embodiments, the additional therapeutic agent is an Abl tyrosine kinase inhibitor, such as radotinib or imatinib.

[0720] In some embodiments, the additional therapeutic agent is an aldehyde dehydrogenase inhibitor, such as ADX-629.

[0721] In some embodiments, the additional therapeutic agent is an adenosine A3 receptor agonist, such as piclidenoson.

[0722] In some embodiments, the additional therapeutic agent is an adrenomedullin ligand, such as adrenomedullin.

[0723] In some embodiments, the additional therapeutic agent is a p38 MAPK+PPARγ agonist / insulin sensitizer, such as KIN-001.

[0724] In some embodiments, the additional therapeutic agent is an aldose reductase inhibitor, such as caficrestat.

[0725] In some embodiments, the additional therapeutic agent is an AMPA receptor modulator, such as traneurocin.

[0726] In some embodiments, the additional therapeutic agent is an Annexin A5 stimulator, such as AP-01 or SY-005.

[0727] In some embodiments, the additional therapeutic agent is an anticoagulant, such as heparins (heparin and low molecular weight heparin), aspirin, apixaban, dabigatran, edoxaban, argatroban, enoxaparin, or fondaparinux.

[0728] In some embodiments, the additional therapeutic agent is an androgen receptor antagonist, such as bicalutamide, enzalutamide, or pruxelutamide (proxalutamide).

[0729] In some embodiments, the additional therapeutic agent is an anti-hypoxic drug, such as disodium crocetin.

[0730] In some embodiments, the additional therapeutic agent is an antithrombotic agent, such as defibrotide, rivaroxaban, alteplase, tirofiban, clopidogrel, prasugrel, bemiparin, bivalirudin, sulodexide, or tenecteplase.

[0731] In some embodiments, the additional therapeutic agent is an antihistamine, such as cloperastine or clemastine.

[0732] In some embodiments, the additional therapeutic agent is an apolipoprotein A1 agonist, such as CER-001.

[0733] In some embodiments, the additional therapeutic agent is a phospholipase A2 inhibitor, such as icosapent ethyl.

[0734] In some embodiments, the additional therapeutic agent is an axl tyrosine kinase receptor inhibitor, such as besentinib.

[0735] In some embodiments, the additional therapeutic agent is a corticosteroid / β2 adrenergic receptor agonist, such as budesonide + formoterol fumarate.

[0736] In some embodiments, the additional therapeutic agent is a BET bromodomain inhibitor / APOA1 gene stimulator, such as apabetalone.

[0737] In some embodiments, the additional therapeutic agent is a blood coagulation regulator, such as lanarumab.

[0738] In some embodiments, the additional therapeutic agent is a bradykinin B2 receptor antagonist, such as icatibant.

[0739] In some embodiments, the additional therapeutic agent is an EGFR gene inhibitor / Btk tyrosine kinase inhibitor, such as abivertinib.

[0740] In some embodiments, the additional therapeutic agent is a Btk tyrosine kinase inhibitor, such as ibrutinib or zanubrutinib.

[0741] In some embodiments, the additional therapeutic agent is a calpain-I / II / IX inhibitor, such as BLD-2660.

[0742] In some embodiments, the additional therapeutic agent is a Ca2+ release-activated Ca2+ channel 1 inhibitor, such as zegocractin (CM-4620).

[0743] In some embodiments, the additional therapeutic agent is a Cadherin-5 modulator, such as FX-06.

[0744] In some embodiments, the additional therapeutic agent is a casein kinase II inhibitor, such as silmitasertib.

[0745] In some embodiments, the additional therapeutic agent is a caspase inhibitor, such as emricasan.

[0746] In some embodiments, the additional therapeutic agent is a catalase stimulator / superoxide dismutase stimulator, such as MP-1032.

[0747] In some embodiments, the additional therapeutic agent is a CCR2 chemokine antagonist / CCR5 chemokine antagonist, such as cenikvir.

[0748] In some embodiments, the additional therapeutic agent is a CCR5 chemokine antagonist, such as maraviroc.

[0749] In some embodiments, the additional therapeutic agent is a CD122 agonist / IL-2 receptor agonist, such as bempegaldesleukin.

[0750] In some embodiments, the additional therapeutic agent is a CD73 agonist / interferon beta ligand, such as FP-1201.

[0751] In some embodiments, the additional therapeutic agent is a cholesteryl ester transfer protein inhibitor, such as dalcetrapib.

[0752] In some embodiments, the additional therapeutic agent is a mannan-binding lectin serine protease / complement C1s subcomponent inhibitor / myeloperoxidase inhibitor, such as RLS-0071.

[0753] In some embodiments, the additional therapeutic agent is a complement factor C5 inhibitor / leukotriene BLT receptor antagonist, such as nomacopan.

[0754] In some embodiments, the additional therapeutic agent is a complement factor C5 inhibitor, such as zilucoplan.

[0755] In some embodiments, the additional therapeutic agent is a CXCR4 chemokine antagonist, such as motexafortide.

[0756] In some embodiments, the additional therapeutic agent is a cytochrome P450 3A4 inhibitor / peptidylprolyl cis-trans isomerase A inhibitor, such as alisporivir.

[0757] In some embodiments, the additional therapeutic agent is a cysteine ​​protease inhibitor, such as SLV-213.

[0758] In some embodiments, the additional therapeutic agent is a dihydroorotate dehydrogenase inhibitor, such as brequinar, RP-7214, or emvododstat.

[0759] In some embodiments, the additional therapeutic agent is a dehydropeptidase-1 modulator, such as Metablok.

[0760] In some embodiments, the additional therapeutic agent is a dihydroorotate dehydrogenase inhibitor / IL-17 antagonist, such as vedofluanimol.

[0761] In some embodiments, the additional therapeutic agent is a diuretic, such as an aldosterone antagonist, such as spironolactone.

[0762] In some embodiments, the additional therapeutic agent is a deoxyribonuclease I stimulator, such as GNR-039 or dornase alfa.

[0763] In some embodiments, the additional therapeutic agent is a NET inhibitor, such as NTR-441.

[0764] In some embodiments, the additional therapeutic agent is a dihydroceramide delta 4 desaturase inhibitor / sphingosine kinase 2 inhibitor, such as opaganib.

[0765] In some embodiments, the additional therapeutic agent is a DNA methyltransferase inhibitor, such as azacytidine.

[0766] In some embodiments, the additional therapeutic agent is an LXR antagonist, such as larsucosterol.

[0767] In some embodiments, the additional therapeutic agent is a dipeptidyl peptidase I inhibitor, such as brensocatib.

[0768] In some embodiments, the additional therapeutic agent is an elongation factor 1 α2 modulator, such as prilotide.

[0769] In some embodiments, the additional therapeutic agent is a eukaryotic initiation factor 4A-I inhibitor, such as zotatifin.

[0770] In some embodiments, the additional therapeutic agent is an exo-alpha sialidase modulator, such as DAS-181.

[0771] In some embodiments, the additional therapeutic agent is an exportin 1 inhibitor, such as selinexor.

[0772] In some embodiments, the additional therapeutic agent is a fractalkine ligand inhibitor, such as KAND-567.

[0773] In some embodiments, the additional therapeutic agent is a FYVE finger phosphoinositide kinase inhibitor / IL-12 receptor antagonist / IL-23 antagonist, such as alpimod dimesylate.

[0774] In some embodiments, the additional therapeutic agent is a GABA A receptor modulator, such as brexanolone.

[0775] In some embodiments, the additional therapeutic agent is a glucocorticoid receptor agonist, such as ciclesonide, hydrocortisone, dexamethasone, dexamethasone phosphate, or 101-PGC-005.

[0776] In some embodiments, the additional therapeutic agent is a GM-CSF receptor agonist, such as sargramostim.

[0777] In some embodiments, the additional therapeutic agent is a GPCR agonist, such as esuberaprost sodium.

[0778] In some embodiments, the additional therapeutic agent is a Griffithsin modulator, such as Q-Griffithsin.

[0779] In some embodiments, the additional therapeutic agent is a leukotriene D4 antagonist, such as montelukast.

[0780] In some embodiments, the additional therapeutic agent is a histamine H1 receptor antagonist, such as ebastine, tranilast, levocetirizine hydrochloride.

[0781] In some embodiments, the additional therapeutic agent is a histamine H2 receptor antagonist, such as famotidine.

[0782] In some embodiments, the additional therapeutic agent is a heat shock protein stimulator / insulin sensitizer / PARP inhibitor, such as BGP-15.

[0783] In some embodiments, the additional therapeutic agent is a histone inhibitor, such as STC-3141.

[0784] In some embodiments, the additional therapeutic agent is a histone deacetylase-6 inhibitor, such as CKD-506.

[0785] In some embodiments, the additional therapeutic agent is a HIF prolyl hydroxylase-2 inhibitor, such as dexamethasone.

[0786] In some embodiments, the additional therapeutic agent is a HIF prolyl hydroxylase inhibitor, such as valdustat.

[0787] In some embodiments, the additional therapeutic agent is an IL-8 receptor antagonist, such as reparixin.

[0788] In some embodiments, the additional therapeutic agent is an IL-7 receptor agonist, such as CYT-107.

[0789] In some embodiments, the additional therapeutic agent is an IL-7 receptor agonist / interleukin-7 ligand, such as efineptakin alfa.

[0790] In some embodiments, the additional therapeutic agent is an IL-22 agonist, such as efmarodocokin alfa.

[0791] In some embodiments, the additional therapeutic agent is an IL-22 agonist / interleukin 22 ligand, such as F-652.

[0792] In some embodiments, the additional therapeutic agent is an integrin α-V / β-1 antagonist / integrin α-V / β-6 antagonist, such as bexotegrast.

[0793] In some embodiments, the additional therapeutic agent is an interferon alpha 2 ligand, such as interferon alpha-2b or Virafin.

[0794] In some embodiments, the additional therapeutic agent is an interferon beta ligand, such as interferon beta-1a follow-on biologic, interferon beta-1b, or SNG-001.

[0795] In some embodiments, the additional therapeutic agent is an interferon receptor modulator, such as peginterferon lambda-1a.

[0796] In some embodiments, the additional therapeutic agent is an interleukin-2 ligand, such as aldesleukin.

[0797] In some embodiments, the additional therapeutic agent is an IRAK-4 protein kinase inhibitor, such as zimlovisertib.

[0798] In some embodiments, the additional therapeutic agent is a JAK inhibitor, for example, the additional therapeutic agent is baricitinib, filgotinib, jaktinib, tofacitinib, or nezulcitinib (TD-0903).

[0799] In some embodiments, the additional therapeutic agent is a neutrophil elastase inhibitor, such as alvilestat.

[0800] In some embodiments, the additional therapeutic agent is a pulmonary surfactant-associated protein D modulator, such as AT-100.

[0801] In some embodiments, the additional therapeutic agent is a plasma kallikrein inhibitor, such as donidalorsen.

[0802] In some embodiments, the additional therapeutic agent is a lysine-specific histone demethylase 1 / MAO B inhibitor, such as vafidenostat.

[0803] In some embodiments, the additional therapeutic agent is a mannan-binding lectin serine protease inhibitor, such as conestat alfa.

[0804] In some embodiments, the additional therapeutic agent is a maxi K potassium channel inhibitor, such as ENA-001.

[0805] In some embodiments, the additional therapeutic agent is a MEK protein kinase inhibitor, such as zapnometinib.

[0806] In some embodiments, the additional therapeutic agent is a MEK-1 protein kinase inhibitor / Ras gene inhibitor, such as antroquinolone.

[0807] In some embodiments, the additional therapeutic agent is a melanocortin MC1 receptor agonist, such as PL-8177.

[0808] In some embodiments, the additional therapeutic agent is a matrix metalloproteinase-12 inhibitor, such as FP-025.

[0809] In some embodiments, the additional therapeutic agent is a NACHT LRR PYD domain protein 3 inhibitor, such as dapansutrile, DFV-890, or ZYIL-1.

[0810] In some embodiments, the additional therapeutic agent is an NADPH oxidase inhibitor, such as isuzinaxib.

[0811] In some embodiments, the additional therapeutic agent is a neuropilin 2 modulator, such as efzofitimod.

[0812] In some embodiments, the additional therapeutic agent is an NK1 receptor antagonist, such as aprepitant or tradipitant.

[0813] In some embodiments, the additional therapeutic agent is an NMDA receptor antagonist, such as crocetin or ifenprodil.

[0814] In some embodiments, the additional therapeutic agent is a nuclear factor kappa B inhibitor / p38 MAP kinase inhibitor, such as zenuzolac.

[0815] In some embodiments, the additional therapeutic agent is an ornithine decarboxylase inhibitor, such as eflornithine.

[0816] In some embodiments, the additional therapeutic agent is an opioid receptor sigma antagonist 1, such as MR-309.

[0817] In some embodiments, the additional therapeutic agent is a PGD2 antagonist, such as asapiprant.

[0818] In some embodiments, the additional therapeutic agent is a PDGF receptor antagonist / TGF[beta] receptor antagonist / p38 MAP kinase inhibitor, such as deupirfenidone.

[0819] In some embodiments, the additional therapeutic agent is a phospholipase A2 inhibitor, such as methylvarespladib.

[0820] In some embodiments, the additional therapeutic agent is a phosphoinositide 3-kinase inhibitor / mTOR complex inhibitor, such as dactolisib.

[0821] In some embodiments, the additional therapeutic agent is a phosphoinositide-3 kinase delta / gamma inhibitor, such as duvelisib.

[0822] In some embodiments, the additional therapeutic agent is a plasminogen activator inhibitor 1 inhibitor, such as TM-5614.

[0823] In some embodiments, the additional therapeutic agent is a protein tyrosine phosphatase beta inhibitor, such as ralostadine.

[0824] In some embodiments, the additional therapeutic agent is a RIP-1 kinase inhibitor, such as DNL-758 or SIR-0365.

[0825] In some embodiments, the additional therapeutic agent is a Rev protein modulator, such as obefazimod.

[0826] In some embodiments, the additional therapeutic agent is an S phase kinase-associated protein 2 inhibitor, such as niclosamide or DWRX-2003.

[0827] In some embodiments, the additional therapeutic agent is a stimulator of the signaling protein CD24, such as EXO-CD24.

[0828] In some embodiments, the additional therapeutic agent is a sodium glucose transporter-2 inhibitor, such as dapagliflozin propylene glycol.

[0829] In some embodiments, the additional therapeutic agent is a sodium channel inhibitor, such as solnatide.

[0830] In some embodiments, the additional therapeutic agent is a sphingosine-1-phosphate-1 agonist / sphingosine-1-phosphate-5 agonist, such as ozanimod.

[0831] In some embodiments, the additional therapeutic agent is a nonsteroidal anti-inflammatory drug, such as Ampion.

[0832] In some embodiments, the additional therapeutic agent is a superoxide dismutase agonist, such as avasopasem manganese.

[0833] In some embodiments, the additional therapeutic agent is a Syk tyrosine kinase inhibitor, such as fostamatinib disodium salt.

[0834] In some embodiments, the additional therapeutic agent is a Tie2 tyrosine kinase receptor agonist, such as AV-001.

[0835] In some embodiments, the additional therapeutic agent is a TGFB2 gene inhibitor, such as trabedocranolol.

[0836] In some embodiments, the additional therapeutic agent is a tissue factor inhibitor, such as AB-201.

[0837] In some embodiments, the additional therapeutic agent is a TLR-3 agonist, such as rentatimod.

[0838] In some embodiments, the additional therapeutic agent is a TLR-4 antagonist, such as ApTLR-4FT, EB-05, or eritoran.

[0839] In some embodiments, the additional therapeutic agent is a TLR-7 / 8 antagonist, such as enpatoran.

[0840] In some embodiments, the additional therapeutic agent is a TLR-2 / 6 agonist, such as INNA-051.

[0841] In some embodiments, the additional therapeutic agent is a TLR-7 agonist, such as PRTX-007.

[0842] In some embodiments, the additional therapeutic agent is a TLR agonist, such as PUL-042.

[0843] In some embodiments, the additional therapeutic agent is a TLR-4 agonist, such as REVTx-99.

[0844] In some embodiments, the additional therapeutic agent is a TLR-2 / 4 antagonist, such as VB-201.

[0845] In some embodiments, the additional therapeutic agent is a TNFα ligand inhibitor, such as pegipanermin.

[0846] In some embodiments, the additional therapeutic agent is a type I IL-1 receptor antagonist, such as anakinra.

[0847] In some embodiments, the additional therapeutic agent is a TREM receptor 1 antagonist, such as nangibotide.

[0848] In some embodiments, the additional therapeutic agent is a trypsin inhibitor, such as ulinastatin.

[0849] In some embodiments, the additional therapeutic agent is a tubulin inhibitor, such as sabizabulin, CCI-001, PCNT-13, CR-42-24, albendazole, entabulin, SAR-132885, or ON-24160.

[0850] In some embodiments, the additional therapeutic agent is a VIP receptor agonist, such as aviptadil.

[0851] In some embodiments, the additional therapeutic agent is a xanthine oxidase inhibitor, such as oxypurinol.

[0852] In some embodiments, the additional therapeutic agent is a vasodilator, such as iloprost, VentaProst, vazegepant, TXA-127, USB-002, ambrisentan, nitric oxide nasal spray (NORS), pentoxifylline, propranolol, RESP301, sodium nitrite, or dipyridamole.

[0853] In some embodiments, the additional therapeutic agent is a vitamin D3 receptor agonist, such as cholecalciferol.

[0854] In some embodiments, the additional therapeutic agent is a zonulin inhibitor, such as larazotideacetate.

[0855] In some embodiments, the additional therapeutic agent is a synthetic retinoid derivative, such as fenretinide.

[0856] In some embodiments, the additional therapeutic agent is a glucose metabolism inhibitor, such as WP-1122.

[0857] In some embodiments, the additional therapeutic agent is AT-H201, 2-deoxy-D-glucose, AD-17002, AIC-649, astodrimer, AZD-1656, bitespiramycin, bucillamine, budesonide, CNM-AgZn-17, Codivir, didodecyl methotrexate, DW-2008S (DW-2008), EDP-1815, EG-009A, Fabencov, Gamunex, genistein, GLS-1200, hzVSF-v13, imidazole acetamide glutarate, IMM-101, MAS-825, MRG-001, Nasitr ol, Nylexa, OP-101, OPN-019, orynotide rhesus theta defensin-1, pyronaridine + artesunate, dapsone, RPH-104, sodium pyruvate, Sulforadex, tafenoquine, TB-006, telacebec, Tempol, TL-895, thimerosal, trimodulin, XC-221, XC-7, sanmetinib, metformin glycine, lucinactant, EOM-613, mosimod, ivermectin, leflunomide, ibudilast, RBT-9, raloxifene, prothione, gemcabene, or idronoxil.

[0858] In some embodiments, the additional therapeutic agent is a CD73 antagonist, such as AK-119.

[0859] In some embodiments, the additional therapeutic agent is a CD95 protein fusion, such as asunercept.

[0860] In some embodiments, the additional therapeutic agent is a complement factor C2 modulator, such as ARGX-117.

[0861] In some embodiments, the additional therapeutic agent is a complement C3 inhibitor, such as NGM-621.

[0862] In some embodiments, the additional therapeutic agent is a CXC10 chemokine ligand inhibitor, such as EB-06.

[0863] In some embodiments, the additional therapeutic agent is a cytotoxic T-lymphocyte protein-4 fusion protein, such as abatacept.

[0864] In some embodiments, the additional therapeutic agent is an anti-S. aureus antibody, such as tosatoxumab.

[0865] In some embodiments, the additional therapeutic agent is an anti-LPS antibody,...

Claims

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein ring C 6-10 Aryl or 5- to 10-membered heteroaryl; Each L 1 are independently a bond, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)-, -C 1-6 Alkyl-O(C 1-6 alkyl)-, -C(O)-, -N(R L )C(O)-、-C(O)N(R L )-、-(C 1-6 Alkyl)(R L )NC(O)-、-(C 1-6 Alkyl)C(O)N(R L )-、-N(R L )C(O)(C 1-6 Alkyl)-, -C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 Alkyl)C(O)N(R L )(C 1-6 alkyl)-, -S(O)2-, -S(O)2N(R L )-、-N(R L )-S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L )-、-(C 1-6 Alkyl)N(R L )S(O)2-、-S(O)2N(R L )(C 1-6 Alkyl)-, -N(R L )S(O)2(C 1-6 Alkyl)-, -(C 1-6 Alkyl)S(O)2N(R L )(C 1-6 Alkyl)- or –(C 1-6 Alkyl)N(R L )S(O)2(C 1-6 alkyl)-; Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl or 4- to 10-membered heterocyclic group, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace; Alternatively, two R 1 with the rings to which they are attached The atoms are combined to form a 5- to 10-membered heterocyclic group; Each R 1a Independently for C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 Alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -C(O)N(5- to 10-membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5- to 10-membered heteroaryl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 2-6 Alkynyl), -NHC(O)O(C 3-8 Cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclic group), -NHC(O)O(C 6- aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl, cyclopropyl, C 1-3 Alkoxy, -O(C 1-3 haloalkyl), -O(cyclopropyl), halogen or -CN; X 1 S, N or C (R x1 ); X 2 S, N or C (R x2 ); X 3 N or C (R x3 ), the condition is X 1 and X 2 Not for S; Alternatively, X 3 is a key, where X 1 and X 2 One of them is S; Each R x1 , R x2 and R x3 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, OC 1-3 Haloalkyl, C 1-3 Alkoxy, cyclopropyl or O-cyclopropyl; ring With X 4 and X 5 Together they are C6 aryl, 5-membered to 6-membered heteroaryl, C 5-10 a cycloalkyl group or a 5- to 10-membered heterocyclic group, Each X 4 and X 5 are independently N or C; Alternatively, the ring does not exist, where X 4 N or CL x4 -R x4 , and X 5 N or CL x5 -R x5 ; Each L x4 and L x5 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)N(R L )C(O)-、-(C 1-6 Alkyl)C(O)N(R L )-、-(C 1-6 Alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 Alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 Alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-; Each R x4 and R x5 are independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -O(C 1-6 Alkyl) or -OC 3-8 Cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 4a replace; Each R 4a Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 haloalkyl), -C(O)NH(C 3-8 cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Haloalkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 haloalkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace; Each R 4b Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2; Each L 3 are independently a bond, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)N(R L )C(O)-、-(C 1-6 Alkyl)C(O)N(R L )-、-(C 1-6 Alkyl)N(R L )C(O)(C 1-6 Alkyl)-, -(C 1-6 Alkyl)C(O)N(R L )(C 1-6 Alkyl)-, -(C 1-6 Alkyl), -(C 1-6 Alkyl)N(R L )S(O)2-、-N(R L )S(O)2-、-C(O)-、-(C 1-6 alkyl)C(O)- or -N(R L )C(O)-; Each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2 or -OC 3-8 Cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to four R 3a replace; Each R 3a Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 haloalkyl), -C(O)NH(C 3-8 cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Haloalkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 haloalkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace; Each R 3b Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2; Each R L are independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-8 Cycloalkyl; n is an integer from 0 to 3; Each X 6 and X 7 are independently N, CH or CF, Where X 4 , X 5 , X 6 and X 7 No more than two of them are N; L 2 is a bond, a C1-C6 alkyl group, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 Alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 Alkyl)N(R L2 )S(O)2-、-(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 Alkyl)- or -(C 1-6 Alkyl)S(O)2-(C 1-6 alkyl)-; R L2 is hydrogen or C 1-6 alkyl; R 5 Hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a C(O)R 5a 、-NR 5a 2. C 1-6 Alkyl, C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each alkyl, cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace; Each R 5a are independently hydrogen or C 1-6 alkyl; Each R 5b are independently halogen, cyclopropyl, hydroxy, -CN, C 1-3 Alkyl, C 1-3 Alkoxy, -OCF3 or -OCF2H; and Z is O or S.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein or a pharmaceutically acceptable salt thereof, wherein each R 3 are independently a bond, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2 or -OC 3-8 Cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to four R 3a replace; Each X 6 and X 7 are independently N or CH, Where X 4 , X 5 , X 6 and X 7 No more than two of them are N; L 2 is a bond, a C1-C6 alkyl group, -(C 1-6 Alkyl)O-, -(C 1-6 alkyl)O(C 1-6 Alkyl)-, -(C 1-6 Alkyl)(R L2 )NC(O)-、-(C 1-6 Alkyl)C(O)N(R L2 )-、-(C 1-6 Alkyl)S(O)2N(R L2 )-、-(C 1-6 Alkyl)N(R L2 )S(O)2-or-(C 1-6 Alkyl)S(O)2N(R L2 )(C 1-6 alkyl)-; and R 5 Hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a C(O)R 5a 、-NR 5a 2. C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace.

3. The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein or a pharmaceutically acceptable salt thereof, wherein Each R 1 are independently halogen, -OH, -CN, C 1-6 Alkyl, -CN, -C(O)NH2, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl or 4- to 10-membered heterocyclic group, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by one to four R 1a replace; Each R 1a Independently for C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 Alkyl), -O(C 3-8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C6 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 3-8 Cycloalkyl)2, -N(5- to 10-membered heterocyclyl)2, -N(C6 aryl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)O(C 1-6 alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O(5- to 10-membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 3-8 cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -C(O)N(5- to 10-membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5- to 10-membered heteroaryl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -NHS(O)(C 1-6 Alkyl), -N(C 1-6 Alkyl)(S(O)(C 1-6 Alkyl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 3-8 cycloalkyl), -S(O)2(5- to 10-membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5- to 10-membered heteroaryl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 1b replace; Each R 4a Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 haloalkyl), -C(O)NH(C 3-8 cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Haloalkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 haloalkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 4b replace; Each R 3a Independently for C 1-6 Alkyl, C 1-6 Haloalkyl, halogen, C 3-8 Cycloalkyl, 5- to 10-membered heterocyclyl, C6 aryl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 Alkyl), -O(C 1-6 Haloalkyl), -O(C 3-8 Cycloalkyl), -O(5- to 10-membered heterocyclic group), -O(C 6-10 aryl), -O(5- to 10-membered heteroaryl), -NH(C 1-6 Alkyl), -NH(C 1-6 Haloalkyl), -NH(C 3-8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C6 aryl), -NH(5- to 10-membered heteroaryl), -N(C 1-6 Alkyl)2, -N(C 1-6 Haloalkyl)2, -N(C 3-8 Cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Haloalkyl), -N(C 1-6 Alkyl)(C 3-8 Cycloalkyl), -N(C 1-6 alkyl)(5- to 10-membered heterocyclic group), -N(C 1-6 alkyl)(C6 aryl), -N(C 1-6 alkyl)(5- to 10-membered heteroaryl), -C(O)(5- to 10-membered heterocyclyl), -C(O)(5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 alkyl), -C(O)NH(C 1-6 haloalkyl), -C(O)NH(C 3-8 cycloalkyl), -C(O)NH(5- to 10-membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5- to 10-membered heteroaryl), -C(O)N(C 1-6 Alkyl)2, -C(O)N(C 1-6 Haloalkyl)2, -C(O)N(C 3-8 Cycloalkyl)2, -NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Haloalkyl), -NHC(O)(C 3-8 cycloalkyl), -NHC(O)(5- to 10-membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C 1-6 alkyl), -NHC(O)O(C 1-6 Haloalkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5- to 10-membered heteroaryl), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 1-6 haloalkyl), -NHC(O)NH(C 3-8 Cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5- to 10-membered heteroaryl), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl), -S(O)2(C 3-8 Cycloalkyl), -S(O)(NH)(C 1-6 alkyl), -S(O)2NH(C 1-6 alkyl) or -S(O)2N(C 1-6 Alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted by one to three R 3b replace; and R 5 Hydrogen, -CN, -OR 5a 、-C(O)NR 5a 2. -NR 5a 2. C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace.

4. The compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (I-1):

5. The compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (II):

6. The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (II-a):

7. The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (II-b):

8. The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (II-c):

9. The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (II-d):

10. The compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (III):

11. A compound according to any one of claims 1 to 4 and 10 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (III-a):

12. The compound according to any one of claims 1 to 4 and 10 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (III-b):

13. A compound according to any one of claims 1 to 4 and 10 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (III-c):

14. The compound according to any one of claims 1 to 4 and 10 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (III-d):

15. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein X 6 and X 7 For CH.

16. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein X 4 and X 5 Each is C.

17. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the ring It is a C6 aryl group.

18. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (IV):

19. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the ring With X 4 , X 5 , X 6 and X 7 The rings are put together as 20. The compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (IV-a):

21. A compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (IV-b):

22. A compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof, wherein the ring It is a 5-membered heteroaryl group.

23. The compound according to claim 22 or a pharmaceutically acceptable salt thereof, wherein the ring With X 4 , X 5 , X 6 and X 7 The rings are combined to form 24. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein L 3 is the key.

25. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 is optionally replaced by one to three R 3a Substituted 5- to 7-membered heterocyclic group.

26. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 is optionally replaced by one or two R 3a Substituted C 1-6 Alkoxy.

27. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 alkyl)2 or -O(C 1-3 alkyl), wherein each alkyl group is independently optionally substituted by one or two R 3a replace.

28. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 It is methyl.

29. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 3 are independently C1-C6 alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 alkoxy or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy and heterocyclyl is optionally substituted by one to three R 3a replace.

30. A compound according to any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 It is a halogen.

31. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 3a are independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 alkyl), 5- to 10-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2.

32. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a -O(C 1-3 alkyl), 5- to 7-membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2.

33. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a It is halogen or -C(O)(C1-C6 alkyl).

34. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a is -OH or -O(C 1-3 alkyl).

35. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a -O(C 1-3 alkyl).

36. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a It is halogen or -OH.

37. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein n is 0.

38. A compound according to any one of claims 1 to 37, or a pharmaceutically acceptable salt thereof, wherein n is 1.

39. A compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof, wherein the ring Does not exist.

40. The compound according to claim 39 or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (V):

41. The compound according to claim 39 or 40, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (Va):

42. The compound according to claim 39 or 40, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (Vb):

43. A compound according to any one of claims 39 to 42, or a pharmaceutically acceptable salt thereof, wherein each L x4 and L x4 are independently a bond or N(R L )S(O)2-.

44. A compound according to any one of claims 39 to 43, or a pharmaceutically acceptable salt thereof, wherein L x4 is the key.

45. A compound according to any one of claims 39 to 44, or a pharmaceutically acceptable salt thereof, wherein L x5 is the key.

46. ​​A compound according to any one of claims 39 to 42, or a pharmaceutically acceptable salt thereof, wherein each R x4 and R x5 are independently hydrogen, C1-C6 alkyl, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 1-6 alkoxy, C3-C8 cycloalkyl or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl and heterocyclyl is optionally substituted by one to three R 4a replace.

47. A compound according to any one of claims 39 to 42 and 46, or a pharmaceutically acceptable salt thereof, wherein R x4 and R x5 One of them is C3-C8 cycloalkyl and the other is hydrogen, wherein the cycloalkyl is optionally substituted by one or two R 4a replace.

48. A compound according to any one of claims 39 to 42 and 46, or a pharmaceutically acceptable salt thereof, wherein R x4 and R x5 One of them is C 1-6 alkoxy and the other is hydrogen, wherein the alkoxy is optionally substituted by one or two R 4a replace.

49. A compound according to any one of claims 39 to 48, or a pharmaceutically acceptable salt thereof, wherein each R 4a Independently for C 1-6 alkyl, -C(O)(5- to 10-membered heterocyclic) or -O(C 3-8 cycloalkyl), wherein each alkyl, heterocyclyl and cycloalkyl group is optionally substituted by one or three R 4b replace.

50. A compound according to any one of claims 39 to 42 and 49, or a pharmaceutically acceptable salt thereof, wherein each R 4b are independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 haloalkyl).

51. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the ring It is a C6 aryl group.

52. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the ring for 53. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the ring for 54. A compound according to any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, wherein the ring It is a 5- to 10-membered heteroaryl group.

55. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein L 1 is the key.

56. A compound according to any one of claims 1 to 54, or a pharmaceutically acceptable salt thereof, wherein each L 1 Independently -(C 1-6 Alkyl)O-, -O(C 1-6 Alkyl)- or -C 1-6 Alkyl-O(C 1-6 alkyl)-.

57. A compound according to any one of claims 1 to 54, or a pharmaceutically acceptable salt thereof, wherein each L 1 Independently -(C 1-6 alkyl)O- or -O(C 1-6 alkyl)-.

58. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1 are independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl, wherein each alkyl, alkynyl, alkoxy, cycloalkyl, aryl and heteroaryl is optionally substituted by one to three R 1a replace.

59. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1 are independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-8 cycloalkyl or 5- to 10-membered heteroaryl, wherein each alkyl, alkynyl, alkoxy, cycloalkyl and heteroaryl is optionally substituted by one or two R 1a replace.

60. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1 are independently halogen, -CN or C 1-6 Alkoxy.

61. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1 are independently halogen or C 1-3 Alkoxy.

62. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1 are independently fluoro, chloro or methoxy.

63. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1a are independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, C6 aryl or 5- to 10-membered heteroaryl.

64. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 1a are independently halogen, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy or C6 aryl.

65. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one R 1a It is a halogen.

66. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein m is 0.

67. A compound according to any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein m is 1 or 2.

68. A compound according to any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein m is 3.

69. A compound according to any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, wherein the ring for 70. A compound according to any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, wherein the ring for 71. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 2 For hydrogen, halogen, C 1-3 Alkyl or C 1-3 Alkoxy.

72. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 2 For hydrogen.

73. A compound according to any one of claims 1 to 71, or a pharmaceutically acceptable salt thereof, wherein R 2 It is a halogen.

74. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R x1 Halogen or C 1-3 alkyl.

75. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R x1 For hydrogen.

76. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R x2 For hydrogen.

77. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R x3 For halogen, C 1-3 Alkyl or C 1-3 Alkoxy.

78. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R x3 For hydrogen.

79. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein L 2 is the key.

80. A compound according to any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof, wherein L 2 It is a C1-C3 alkyl group.

81. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 5 For hydrogen.

82. A compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein R 5 It is -CN.

83. A compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein R 5 C 3-8 Cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace.

84. A compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein R 5 C 5-6 Cycloalkyl, C6 aryl, 5- to 7-membered heterocyclyl or 5- to 9-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted by one or two R 5b replace.

85. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 5b Independently for C 1-3 Alkyl or C 1-3 Alkoxy.

86. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 5b It is methyl.

87. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Z is O.

88. A compound selected from or pharmaceutically acceptable salts thereof.

89. A compound selected from or pharmaceutically acceptable salts thereof.

90. A compound selected from or pharmaceutically acceptable salts thereof.

91. A compound, the compound being or a pharmaceutically acceptable salt thereof.

92. A compound, the compound being or a pharmaceutically acceptable salt thereof.

93. A compound, the compound is or a pharmaceutically acceptable salt thereof.

94. A compound, the compound is or a pharmaceutically acceptable salt thereof.

95. A compound, the compound is or a pharmaceutically acceptable salt thereof.

96. A compound, the compound is or a pharmaceutically acceptable salt thereof.

97. A compound, said compound being or a pharmaceutically acceptable salt thereof.

98. A compound, the compound is or a pharmaceutically acceptable salt thereof.

99. A compound, the compound being or a pharmaceutically acceptable salt thereof.

100. A compound, said compound being or a pharmaceutically acceptable salt thereof.

101. A compound, the compound being or a pharmaceutically acceptable salt thereof.

102. A compound, the compound being or a pharmaceutically acceptable salt thereof.

103. A pharmaceutical composition comprising a compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

104. A method of treating or preventing a viral infection in a human in need thereof, wherein the method comprises administering to the human a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 103.

105. The method of claim 104, wherein the viral infection is a coronavirus infection.

106. The method of claim 104 or 105, wherein the viral infection is caused by a virus having at least 70% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

107. The method of claim 104 or 105, wherein the viral infection is caused by a virus having at least 80% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

108. The method of claim 104 or 105, wherein the viral infection is caused by a virus having at least 90% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

109. The method of claim 104 or 105, wherein the viral infection is caused by a virus having at least 95% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

110. The method of any one of claims 104 to 109, wherein the viral infection is SARS-CoV-2 infection (COVID-19).

111. A method for preparing a medicament for treating or preventing a viral infection in a human in need thereof, wherein the medicament is a compound according to any one of claims 1 to 102 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 103.

112. Use of a compound according to any one of claims 1 to 102 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 103 for the preparation of a medicament for treating or preventing a viral infection in a human in need thereof.

113. A composition comprising a compound according to any one of claims 1 to 102 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 103, for use in treating or preventing a viral infection in a human in need thereof.

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