Sars-cov2 main protease inhibitors

Abstract

The present disclosure relates to compounds of Formula (I) useful for treating viral infections, such as coronavirus infections: (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof.

Description

Cross-references to related applications

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 550,933, filed on February 7, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This disclosure relates to compounds and methods for treating or preventing viral infections. Background Technology

[0003] Coronaviruses, named for the crown-like spikes on their surface, primarily infect bats, pigs, and small mammals. Coronaviruses are prone to mutation and can transfer from animals to humans and from one person to another. In recent years, they have become significant players in infectious disease outbreaks worldwide. There is a need for compounds and methods for treating viral infections, such as coronavirus infections. This disclosure addresses the above and other needs. Summary of the Invention

[0004] In one embodiment, this disclosure provides a compound of formula (I): I Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, Each X 4 and X 5 Independently N or C; Alternatively, choose a location, surrounding It does not exist, where X 4 For N or CL x4-R x4 And X 5 For N or CL x5 -R x5 ; Each L x4 and L x5 Independently 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)-; Each R x4 and R x5 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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; Where R x4 and R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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, Where R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 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 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 Independently 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)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl groups, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2 or -OC 3-8 cycloalkyl; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to four R groups. 3a replace; Each R 3a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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, Where R 3a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 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 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2、-NHC(O)(C 1-6Alkyl), -NHC(O)(C 1-6 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 Independently hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-8 cycloalkyl; n is an integer from 0 to 3; Each X 6 and X 7 Independently N, CH or CF, Where X 4 X 5 X 6 and X 7 The two numbers in the range do not exceed N; ring C 6-10 Aryl or 5- to 10-membered heteroaryl groups; Each L 1 Independently for the key, -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)(C1-6 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 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Alternatively, two R locations 1 With the rings to which they are attached The atoms come together to form an optional combination of one to three R atoms. 1a Replacement of 5- to 10-membered heterocyclic groups; Each R 1a Independently for C1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, O(C 1-6 alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2, -N(5- to 10-membered heterocyclic)2, -N(phenyl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl group (5- to 10-membered heteroaryl group), -C(O) group (5- to 10-membered heterocyclic group), -C(O) group (5- to 10-membered heteroaryl group), -C(O)O(C 1-6 Alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O (5- to 10-membered heterocyclic group), -C(O)O (phenyl), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C 3-8 Cycloalkyl)2, -C(O)N (5- to 10-membered heterocyclic)2, -C(O)N (phenyl)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 heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 3-8cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 cycloalkyl), -NHC(O)NH (5- to 10-membered heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -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 heterocyclic), -S(O)2 (phenyl), -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, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Alternatively, R 1 It is a phenyl group, and both R groups are phenyl. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one to three R atoms. 1b Replacement of 5- to 10-membered heterocyclic groups; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH, -NH2, CO2H, -O(C) 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic group), -NH (phenyl), -NH (5- to 10-membered heterocyclic group), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2、-NHC(O)(C1-6 Alkyl), -NHC(O)(C 1-6 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -S(O)2(C 3-8 cycloalkyl), -S(O)2 (5- to 10-membered heterocyclic), -S(O)2 (phenyl), -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 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 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-、-(C1-6 alkyl)S(O)2N(R L2 (C) 1-6 alkyl)- or -(C 1-6 Alkyl)S(O)2-(C 1-6 alkyl)-; R L2 It is hydrogen or C 1-6 alkyl; R 5 For 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, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independently halogen, oxo group, cyclopropyl group, hydroxyl group, -CN, C 1-3 Alkyl, C 1-3 Alkyl group, -OCF3 or -OCF2H.

[0005] In another embodiment, this disclosure provides a pharmaceutical composition comprising a pharmaceutically effective amount of a compound of the disclosure or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0006] In another embodiment, this disclosure provides a method for treating a viral infection in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound of this disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this disclosure. Detailed Implementation

[0007] This disclosure generally relates to methods and compounds for treating or preventing viral infections, such as coronavirus infections.

[0008] definition As used in this specification, the following words, phrases and symbols are generally intended to have the meanings described below, unless the context in which they are used indicates otherwise.

[0009] "Alkyl" refers to a saturated hydrocarbon chain that is unbranched or branched. For example, an alkyl group can have 1 to 20 carbon atoms (i.e., C1-C2). 20 Alkyl groups, having 1 to 8 carbon atoms (i.e., C1-C8 alkyl), 1 to 6 carbon atoms (i.e., C1-C6 alkyl), or 1 to 3 carbon atoms (i.e., C1-C3 alkyl). Examples of suitable alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl ( n -Pr、 n -propyl, -CH2CH2CH3), 2-propyl ( i -Pr、 i -propyl, -CH(CH3)2), 1-butyl ( n -Bu、 n -Butyl, -CH2CH2CH2CH3), 2-methyl-1-propyl ( i -Bu、 i -Butyl, -CH2CH(CH3)2), 2-Butyl ( s -Bu、 s -Butyl, -CH(CH3)CH2CH3), 2-methyl-2-propyl ( t -Bu、 t -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 (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), and 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3))3。

[0010] "Alkenyl" refers to a straight-chain or branched hydrocarbon having at least two carbon atoms and at least one double bond. Alkenyl groups can include any number of carbon atoms, such as C2, C3, C4, C5, C6, C7, C8, C9 ... 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 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, vinyl, 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-hextrienyl. The alkenyl group may be substituted or unsubstituted.

[0011] "Alynyl" refers to a straight-chain or branched hydrocarbon having at least two carbon atoms and at least one triple bond. Alynyl groups can include any number of carbon atoms, such as C2, C3, C4, C5, etc. 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 And C6. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, butyrynyl, 1-pentynyl, 2-pentynyl, isopentenynyl, 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-hextriynyl. The alkynyl group may be substituted or unsubstituted.

[0012] "Alkoxy" refers to an alkyl group having an oxygen atom attached to the alkyl group at the attachment point: 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, pentoxy, hexoxy, etc. Alkoxy groups may be further substituted by various substituents described herein. Alkoxy groups may be substituted or unsubstituted.

[0013] "Alkoxyalkyl" refers to a compound in which an alkoxy group is attached to an alkyl group, which in turn is attached to the remainder of the compound, making the alkyl group divalent. Alkoxyalkyl groups can have any suitable number of carbon atoms, such as 2 to 6 (C6+). 2-6 alkoxyalkyl), 2 to 5 (C 2-5 alkoxyalkyl), 2 to 4 (C 2-4 alkoxyalkyl), or 2 to 3 (C 2-3 Alkoxyalkyl). Alkoxy and alkyl are as defined above, wherein the alkyl is divalent and may include, but is not limited to, methoxymethyl (CH3OCH2-), methoxyethyl (CH3OCH2CH2-), etc.

[0014] "Alkoxy-alkoxy" refers to an alkoxy group attached to a second alkoxy group, which is attached to the remainder of the compound. Alkoxy groups are as defined above and may include, but are not limited to, methoxy-methoxy (CH3OCH2O-), methoxy-ethoxy (CH3OCH2CH2O-), etc.

[0015] As used in this article, "halogen" or "halogen" refers to fluorine (-F), chlorine (-Cl), bromine (-Br), and iodine (-I).

[0016] As used herein, the term "oxo-substituent" is intended to refer to an oxygen atom attached to a carbon atom via a double bond (=O) as a substituent.

[0017] "Hydroxy" is used interchangeably and refers to -OH.

[0018] As used herein, “haloalkyl” means an alkyl group as defined herein, wherein one or more hydrogen atoms of the alkyl group are independently replaced by a halosubstituent, which may be the same or different. For example, C 1-4 The alkyl halide is C 1-4 Alkyl, wherein C 1-4 One or more hydrogen atoms in the alkyl group have been replaced by a halogenated substituent. Examples of halogenated alkyl groups include, but are not limited to, fluoromethyl, fluorochloromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and pentafluoroethyl.

[0019] "Haloalkoxy" refers to an alkoxy group in which some or all of its hydrogen atoms are replaced by halogen atoms. Regarding alkyl groups, haloalkoxy groups can have any suitable number of carbon atoms, such as C0... 1-6 The alkoxy group can be substituted with one, two, three or more halogens. When all hydrogens are replaced by a halogen (e.g., fluorine), the compound is fully substituted, such as perfluorinated. Haloalkoxy groups include, but are not limited to, trifluoromethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, etc.

[0020] "Cycloalkyl" refers to a compound having 3 to 20 cyclic carbon atoms (i.e., C6 ... 3-20 A cycloalkyl group (e.g., 3 to 12 cyclic atoms, such as 3 to 10 cyclic atoms, 3 to 8 cyclic atoms, 3 to 6 cyclic atoms, 3 to 5 cyclic atoms, or 3 to 4 cyclic atoms) is a single saturated or partially unsaturated full-carbon ring. The term "cycloalkyl" also includes multiple fused, saturated, and partially unsaturated full-carbon ring systems (e.g., ring systems containing 2, 3, or 4 carbon rings). Thus, cycloalkyl groups include polycyclic carbon rings, such as bicyclic carbon rings (e.g., bicyclic carbon rings having 6 to 12 cyclic carbon atoms, such as bicyclo[3.1.0]hexane and bicyclo[2.1.1]hexane) and polycyclic carbon rings (e.g., tricyclic and tetracyclic carbon rings having up to 20 cyclic carbon atoms). When valence requirements permit, the rings of a polyfused ring system may be linked to each other via fusion, spirocyclic, and bridging 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.

[0021] "alkyl-cycloalkyl" refers to a group having an alkyl component and a cycloalkyl component, wherein the alkyl component attaches the cycloalkyl component to the attachment point. The alkyl component is as defined above, except that it is at least a divalent alkylene group attached to the cycloalkyl component and the attachment point. In some cases, the alkyl component may be absent. The alkyl component may include any number of carbon atoms, such as C10. 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 5-6Cycloalkyl components are as defined herein. Exemplary alkyl-cycloalkyl groups include, but are not limited to, methyl-cyclopropyl, methyl-cyclobutyl, methyl-cyclopentyl, and methyl-cyclohexyl.

[0022] As used herein, "heterocyclic group" or "heterocyclic" or "heterocyclic alkyl" refers to a single saturated or partially unsaturated non-aromatic ring or a system of rings having at least one heteroatom (i.e., at least one cyclic heteroatom selected from oxygen, nitrogen, and sulfur), wherein the system of rings comprises at least one non-aromatic ring containing at least one heteroatom. The system of rings may also include other aromatic and non-aromatic rings. Unless otherwise stated, a heterocyclic group has 3 to 20 cyclic atoms, for example 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 4 to 6 cyclic atoms, or 4 to 5 cyclic atoms. Therefore, the term includes a single saturated or partially unsaturated ring (e.g., a 3-, 4-, 5-, 6-, or 7-membered ring) having 1 to 6 cyclic carbon atoms and 1 to 3 cyclic heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Heteroatoms can optionally be oxidized to form –N(-OH)-, =N(-O)-, etc. - -, -S(=O)- or –S(=O)2-. When valence requirements permit, the rings of a polyfused ring (e.g., bicyclic heterocyclic group) system can be connected to each other via fusion, spirocyclic and bridging bonds. Heterocyclic rings include, but are not limited to, aziridine, imidazoline, morpholine, ethylene oxide (epoxide), oxacyclobutane, thiobutane, piperazine, piperidine, pyrazolidine, piperidine, pyrrolidine, pyrrolidone, tetrahydrofuran, tetrahydrothiophene, dihydropyridine, tetrahydropyridine, quinine ring, 2-oxa-6-azaspiro[3.3]heptane-6-yl, 6-oxa-1-azaspiro[3.3]heptane-1-yl, 2-thia- 6-azaspiro[3.3]heptane-6-yl, 2,6-diazaspiro[3.3]heptane-2-yl, 2-azabicyclo[3.1.0]hexane-2-yl, 3-azabicyclo[3.1.0]hexyl, 2-azabicyclo[2.1.1]hexyl, 2-azabicyclo[2.2.1]heptane-2-yl, 4-azaspiro[2.4]heptyl, 5-azaspiro[2.4]heptyl, etc.

[0023] "alkyl-heterocyclic alkyl" refers to a group having an alkyl component and a heterocyclic alkyl component, wherein the alkyl component attaches the heterocyclic alkyl component to the attachment site. The alkyl component is as defined above, except that it is at least a divalent alkylene group attached to the heterocyclic alkyl component and the attachment site. The alkyl component may include any number of carbons, such as C64. 0-6 C 1-2 C 1-3 C 1-4 C 1-5 C 1-6C 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. Heterocyclic alkyl components are as defined above. Alkyl-heterocyclic alkyl groups may be substituted or unsubstituted.

[0024] As used herein, “aryl” refers to a single all-carbon aromatic ring or a polyfused 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 groups include phenyl radicals. Aryl groups also include polyfused ring systems having 9 to 20 carbon atoms (e.g., ring systems comprising 2, 3, or 4 rings), wherein at least one ring is aromatic, and wherein the other rings may be aromatic or non-aromatic (i.e., carbon rings) and may be saturated or partially saturated. Such polyfused ring systems may optionally have one or more (e.g., 1, 2, or 3) oxo groups substituted on any carbon ring portion of the polyfused ring system. When valence requirements permit, the rings of a polyfused ring system may be linked to each other via fusion, spirocyclic, and bridging bonds. It should also be understood that when referring to a range of aryl groups (e.g., 6-10 aryl groups), the range of atoms refers to the total number of ring atoms in that aryl group. For example, a 6-membered aryl group would include a phenyl group, and a 10-membered aryl group would include a naphthyl group and a 1,2,3,4-tetrahydronaphthyl group. Non-limiting examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthraceneyl, etc.

[0025] "alkyl-aryl" refers to a group having an alkyl component and an aryl component, wherein the alkyl component attaches the aryl component to the attachment site. The alkyl component is as defined above, except that it is at least a divalent alkylene group attached to the aryl component and the attachment site. The alkyl component may include any number of carbons, such as C10. 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 5-6In some cases, the alkyl component may be absent. The aryl component is as defined above. Examples of alkyl-aryl groups include, but are not limited to, benzyl and ethyl-phenyl. The alkyl-aryl group may be substituted or unsubstituted.

[0026] As used herein, "heteroaryl" refers to a monoaromatic 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 polyfused ring systems having at least one such aromatic ring, which will be further described below. Thus, "heteroaryl" comprises a single aromatic ring with 1 to 6 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. Sulfur and nitrogen atoms may also be present in oxidized forms, provided that the ring is aromatic. Exemplary heteroaryl ring systems include, but are not limited to, pyridinyl, pyrimidinyl, oxazolyl, or furanyl. "Heteroaryl" also includes polyfused ring systems (e.g., ring systems containing 2, 3, or 4 rings), wherein the heteroaryl group as defined above is fused with one or more rings selected from heteroaryl (to form, for example, 1,8-naphthidyl), heterocyclic (to form, for example, 1,2,3,4-tetrahydro-1,8-naphthidyl), carbocyclic (to form, for example, 5,6,7,8-tetrahydroquinolinyl), and aryl (to form, for example, indazole) to form a polyfused ring system. The other rings may be aromatic or non-aromatic (i.e., carbocyclic) and may be saturated or partially saturated. Thus, a heteroaryl (a single aromatic ring or a system of multiple condensed rings) has 1-20 carbon atoms and 1-6 heteroatoms within the heteroaryl ring. Such polyfused ring systems may optionally be substituted with one or more (e.g., 1, 2, 3, or 4) oxo groups on the carbocyclic or heterocyclic portion of the fused ring. When valence requirements permit, the rings of a polyfused ring system may be connected to each other via fusion, spirocyclic, and bridging bonds. It should be understood that the individual rings of the polyfused ring system may be connected relative to each other in any order. It should be understood that the connection points of a heteroaryl or heteroaryl polyfused ring system may be located on any suitable atom of the heteroaryl or heteroaryl polyfused ring system, including carbon atoms and heteroatoms (e.g., nitrogen). It should also be understood that when referring to a range of atomic-membered heteroaryl groups (e.g., 5- to 10-membered heteroaryl groups), the atomic range is the total number of ring atoms of the heteroaryl group and includes carbon atoms and heteroatoms. For example, a 5-membered heteroaryl group would include a thiazolyl group, and a 10-membered heteroaryl group would include a quinolinyl group. Exemplary heteroaryl groups include, but are not limited to, pyridyl, pyrroloyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiophenyl, indolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furanyl, oxadiazolyl, thiazolyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzooxazolyl, inzolyl, quinoxolinyl, quinazolinyl, 5,6,7,8-tetrahydroisoquinolinylbenzofuranyl, benzimidazolyl, thioindyl, pyrrolo[2,3-b]pyridyl, quinazolinyl-4(3H)-one, and triazolyl.

[0027] "alkyl-heteroaryl" refers to a group having an alkyl component and a heteroaryl component, wherein the alkyl component attaches the heteroaryl component to a junction. The alkyl component is as defined above, except that it is at least a divalent alkylene group attached to the heteroaryl component and the junction. The alkyl component may include any number of carbons, such as C10. 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 be absent. Heteroaryl components are as defined herein. Alkyl-heteroaryl groups may be substituted or unsubstituted.

[0028] "Compounds of this disclosure" includes compounds disclosed herein, such as compounds of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), and (VII-D), including the compounds of the examples.

[0029] As used herein, “composition” is intended to cover products containing a specified amount of a specified ingredient and any product formed directly or indirectly from a combination of the specified amounts of the specified ingredients. “Pharmaceutically acceptable” means that the carrier, diluent, or excipient must be compatible with the other components of the formulation and be harmful to the recipient.

[0030] "Pharmaceutically effective amount" means the amount of the compound of this disclosure in a formulation or combination thereof that provides the desired therapeutic or pharmaceutical outcome.

[0031] "Pharmaceutically acceptable excipients" include, but are not limited to, any adjuvants, carriers, excipients, glidants, sweeteners, diluents, preservatives, dyes / colorants, flavor enhancers, surfactants, wetting agents, dispersants, suspending agents, stabilizers, isotonic agents, solvents, or emulsifiers that have been approved by the U.S. Food and Drug Administration for acceptable use in humans or livestock.

[0032] As used herein, “treatment” refers to a method for achieving a beneficial or desired outcome. For the purposes of this disclosure, beneficial or desired outcomes include, but are not limited to, the reduction of symptoms and / or the lessening of the severity of symptoms and / or the prevention of the worsening of symptoms associated with a disease or condition. In one embodiment, “treatment” includes one or more of the following: a) suppressing a disease or condition (e.g., reducing one or more symptoms caused by a disease or condition, and / or lessening the severity of a disease or condition); b) slowing or halting the development of one or more symptoms associated with a disease or condition (e.g., stabilizing a disease or condition, delaying the worsening or progression of a disease or condition); and c) alleviating a disease or condition, such as causing the disappearance of clinical symptoms, improving the disease state, delaying the progression of the disease, improving quality of life, and / or prolonging survival.

[0033] The term "treatment" also covers the relief or elimination of symptoms of viral infection and / or the reduction of viral load in a patient. The term "treatment" also covers the administration of a compound or composition according to the embodiments disclosed herein after an individual's exposure to a virus but before the onset of disease symptoms and / or before the virus is detected in the blood, to prevent the onset of disease symptoms and / or prevent the virus from reaching detectable levels in the blood.

[0034] As used herein, "therapeutic effective amount" or "effective amount" means an amount capable of effectively evoking the desired biological or medical response, including amounts of such a treatment sufficient to affect the disease when administered to a subject to treat that disease. Effective amounts may vary depending on the compound, the subject's disease and its severity, and age, weight, etc. Effective amounts may include a range of amounts. As understood in the art, an effective amount may be one or more doses; that is, a single dose or multiple doses may be required to achieve the desired therapeutic endpoint. Effective amounts may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered if, in combination with one or more other agents, a desired or beneficial result can be achieved or realized. The appropriate dose of any co-administered compound may optionally be reduced due to the combined effects of the compounds (e.g., additive or synergistic effects).

[0035] "Administration" refers to oral administration to a subject, as a suppository, local contact, parenteral administration, intravenous administration, intraperitoneal administration, intramuscular administration, intralesional administration, intranasal or subcutaneous administration, intrathecal administration, or implantation of a slow-release device (e.g., a micro-osmotic pump). Administration may be performed according to a schedule based on the specified administration frequency, dosage, and other factors.

[0036] As used herein, “co-administration” means administering a unit dose of the compound disclosed herein before or after administering a unit dose of one or more additional therapeutic agents, for example, administering the compound disclosed herein within seconds, minutes, or hours after administering one or more additional therapeutic agents. For example, in some embodiments, a unit dose of the compound disclosed herein is administered first, followed by 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 a unit dose of the compound disclosed herein within seconds or minutes. In some embodiments, a unit dose of the compound disclosed herein is administered first, followed by a unit dose of one or more additional therapeutic agents after several hours (e.g., 1 hour to 12 hours). In other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed by a unit dose of the compound disclosed herein after several hours (e.g., 1 to 12 hours). Co-administration of the compound disclosed herein with one or more additional therapeutic agents generally means administering the 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.

[0037] "Subject" refers to an animal, such as a mammal, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc. In some implementations, the subject is a human.

[0038] "Disease" or "condition" refers to the state of being or health status of a patient or subject who can be treated with the compounds, pharmaceutical compositions or methods provided herein.

[0039] Pharmaceutically acceptable salts, hydrates, solvates, tautomers, polymorphs, and prodrugs of the compounds described herein are also provided. "Pharmaceutically acceptable" or "physiologically acceptable" means compounds, salts, compositions, dosage forms, and other substances that can be used to prepare pharmaceutical compositions suitable for veterinary or human use.

[0040] 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 a compound that possess the desired pharmacological activity of a 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, hydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, octanoates, acrylates, formates, isobutyrates, hexanoates, heptarates, propynates, oxalates, malonates, succinates, octanoates, sebates, fumarates, maleates, and butynedi-1. ,4-Diosyl salt, hexyn-1,6-diosyl salt, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methanesulfonate, propylsulfonate, benzenesulfonate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, γ-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.

[0041] Examples of pharmaceutically acceptable salts of the compounds disclosed herein also include those derived from suitable bases such as alkali metals (e.g., sodium, potassium), alkaline earth metals (e.g., magnesium), ammonium, and NX4. + (where X is C1) Salts of C4 alkyl groups. Also includes base addition salts, such as sodium or potassium salts.

[0042] Also provided are compounds described herein, or pharmaceutically acceptable salts, isomers, or mixtures thereof, wherein one to n hydrogen atoms bonded to a carbon atom may be substituted with a deuterium atom or D, where n is the number of hydrogen atoms in the molecule. As is known in the art, a deuterium atom is a non-radioactive isotope of a hydrogen atom. Such compounds can increase resistance to metabolism and are therefore used to increase the half-life of compounds 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 substituted with deuterium.

[0043] Examples of isotopes that can be incorporated into the disclosed compounds 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. Using positron-emitting isotopes such as 11 C 18 F, 15 O and 13 Substitution of N can be used in positron emission tomography (PET) studies to examine substrate acceptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared using conventional techniques known to those skilled in the art, or by methods similar to those described in the examples listed below, using a suitable isotopically labeled reagent instead of the previously used unlabeled reagent.

[0044] The compounds of the embodiments disclosed herein, or their pharmaceutically acceptable salts, may include one or more asymmetric centers, and thus may produce enantiomers, diastereomers, and compounds that can be defined according to absolute stereochemistry (…). R )-or( S(D)- or other stereoisomers defined for amino acids as (D)- or (L)-. The compounds of the embodiments disclosed herein, or their pharmaceutically acceptable salts, may be “restricted rotation isomers,” stereoisomers resulting from restricted rotation around a single bond, wherein the barrier to rotation around that bond is sufficiently high to allow the separation of individual stereoisomers. This disclosure is intended to include all such possible isomers as well as their racemic and optically pure forms. Optically active (+) and (-), ( R )-and( S (D)- and (L)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques such as chromatography and fractional crystallization. Conventional techniques for the preparation / separation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of racemic mixtures (or racemic mixtures of salts or derivatives) using, for example, chiral high-performance liquid chromatography (HPLC). When the compounds described herein contain alkene double bonds or other geometrically asymmetric centers, and unless otherwise specified, these compounds are intended to include E and Z geometric isomers. Similarly, all tautomeric forms are also intended to be included. When a compound is represented in its chiral form, it should be understood that the embodiments cover, but are not limited to, specific diastereomeric or enantiomerically enriched forms. When chirality is not specified but is present, it should be understood that the embodiments relate to specific diastereomeric or enantiomerically enriched forms; or racemic or non-racemic mixtures of such compounds. As used herein, a “non-racemic mixture” is a mixture of stereoisomers in a ratio not equal to 1:1.

[0045] A "racemate" is a mixture of enantiomers. The mixture may contain equal or unequal amounts of each enantiomer.

[0046] One or more “stereoisomers” refer to compounds with different chiralities of one or more stereocenters. Stereoisomers include enantiomers and diastereomers. If a compound has one or more asymmetric centers or has asymmetric substituted double bonds, these compounds can exist in stereoisomeric forms and can therefore be prepared as individual stereoisomers or as mixtures. Unless otherwise specified, this specification is intended to include individual stereoisomers as well as mixtures. Methods for determining stereochemistry and isolating 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).

[0047] The rotation-restricted isomers described herein can be used in a manner well known to those skilled in the art using bolded links (“ wedge key (") ("), dashed key (") ") and dashed wedge key (" This indicates that the pair of isomers is represented by ''. For example, the following shows a pair of isomers that are blocked from transoxidation: "Tautomers" refer to alternative forms of compounds with different proton positions, such as enol-ketone and imine-enamine tautomers, or tautomers containing heteroaryl groups that are simultaneously attached to the ring atoms of the ring-NH- and ring=N-, such as pyrazoles, imidazoles, benzimidazoles, triazoles, and tetraazoles.

[0048] 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 chemical groups are for convenience; chemical groups may be depicted without one or more dashes without losing their ordinary meaning. Wavy lines drawn through lines in the structure indicate the attachment points of groups. Dashed lines indicate optional bonds. Unless chemically or structurally required, the order in which chemical groups are written or the points where they connect to the rest of the molecule do not indicate or imply directionality. For example, the group “-SO2CH2-” is equivalent to “-CH2SO2-”, and both can be attached in either direction. Similarly, “arylalkyl” groups may, for example, be attached to the rest of the molecule at the aryl or alkyl portion of the group. Prefixes such as “C…” u-v "or (C u -C v The ) indicates that the following group has u to v carbon atoms. For example, "C 1-6 Both "alkyl" and "C1-C6 alkyl" indicate that the alkyl group has 1 to 6 carbon atoms.

[0049] As used herein, the term "antiviral agent" is intended to mean an agent that effectively inhibits the formation and / or replication of viruses in mammals, including but not limited to agents that interfere with the host or viral mechanisms necessary for the formation and / or replication of viruses in mammals.

[0050] Unless otherwise stated, whenever a compound described herein is substituted with more than one of the same designated groups (e.g., “R” or “R”), it should be understood that these groups may be the same or different, i.e., each group is chosen independently.

[0051] Waveform, It indicates the position where a covalent bond is attached to an adjacent substructure, group, part, or atom.

[0052] prefix "C" u-v " and "(C u-v ")" indicates that the following groups have u to v carbon atoms. For example, "C 1-8 "alkyl" indicates that the alkyl group has 1 to 8 carbon atoms.

[0053] Some commonly used alternative chemical names may be used. For example, divalent groups (such as divalent "alkyl" groups and divalent "aryl" groups) may also be called "alkylene" groups and "aryene" groups, respectively.

[0054] Unless otherwise explicitly stated, the combination of groups herein refers to a part, such as arylalkyl, and the last mentioned group contains the atoms of that part that are attached to the rest of the molecule.

[0055] The term "substituted" means that any one or more hydrogen atoms on a specified atom or group are replaced by one or more substituents other than hydrogen, provided that the substitution does not exceed the normal valence of the specified atom. Unless otherwise specified, one or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, amide, amidine, aryl, azide, carbamoyl, carboxyl, carboxyl ester, cyano, guanidinyl, halogen, haloalkyl, heteroalkyl, heteroaryl, heterocyclic, hydroxyl, hydrazine, imino, oxo, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thion, or combinations thereof.

[0056] The term "optionally substituted" means that any one or more hydrogen atoms on a specified atom or group may or may not be substituted by any part other than hydrogen.

[0057] compound This disclosure provides compounds as inhibitors of the SARS-CoV-2 main protease. In some embodiments, this 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: And / or its pharmaceutically acceptable salts.

[0058] In some implementations, the compound of formula (I) is I Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, Each X 4 and X 5 Independently N or C; Alternatively, choose a location, surrounding It does not exist, where X 4 For N or CL x4 -R x4 And X 5 For N or CL x5 -R x5 ; Each L x4 and L x5 Independently 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)-; Each R x4 and R x5 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 5- to 10-membered heteroaryl, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)2、-O(C 1-6 alkyl) or -OC3-8 cycloalkyl; Where R x4 and R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C 1-6 (halogenated alkyl)2、-C(O)N(C3-8 cycloalkyl)2、-NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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, Where R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 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 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8cycloalkyl), -NH (5- to 10-membered heterocyclic), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 Independently 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)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl groups, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2 or -OC 3-8 cycloalkyl; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to four R groups. 3a replace; Each R 3a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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, Where R 3a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 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 Halogenated alkyl), -O(C) 3-8cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 Independently hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-8 cycloalkyl; n is an integer from 0 to 3; Each X 6 and X 7 Independently N, CH or CF, Where X 4 X 5 X 6 and X 7 The two numbers in the range do not exceed N; ring C 6-10 Aryl or 5- to 10-membered heteroaryl groups; Each L 1 Independently for the key, -O-, -(C 1-6 Alkyl)O-, -O(C1-6 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 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Alternatively, two R locations 1 With the rings to which they are attached The atoms come together to form an optional combination of one to three R atoms. 1a Replacement of 5- to 10-membered heterocyclic groups; Each R 1a Independently for C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, O(C 1-6 alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2, -N(5- to 10-membered heterocyclic)2, -N(phenyl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl group (5- to 10-membered heteroaryl group), -C(O) group (5- to 10-membered heterocyclic group), -C(O) group (5- to 10-membered heteroaryl group), -C(O)O(C 1-6 Alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O (5- to 10-membered heterocyclic group), -C(O)O (phenyl), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C 3-8Cycloalkyl)2, -C(O)N (5- to 10-membered heterocyclic)2, -C(O)N (phenyl)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 heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 cycloalkyl), -NHC(O)NH (5- to 10-membered heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -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 heterocyclic), -S(O)2 (phenyl), -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, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Alternatively, R 1 It is a phenyl group, and both R groups are phenyl. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one to three R atoms. 1b Replacement of 5- to 10-membered heterocyclic groups; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH, -NH2, CO2H, -O(C) 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic group), -NH (phenyl), -NH (5- to 10-membered heterocyclic group), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2、-NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -S(O)2(C 3-8 cycloalkyl), -S(O)2 (5- to 10-membered heterocyclic), -S(O)2 (phenyl), -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 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O-, -(C 1-6Alkyl)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 It is hydrogen or C 1-6 alkyl; R 5 For 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, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independently halogen, oxo group, cyclopropyl group, hydroxyl group, -CN, C 1-3 Alkyl, C 1-3 Alkyl group, -OCF3 or -OCF2H.

[0059] In some implementations, the compound of formula (I) is I Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, Each X 4 and X 5 Independently N or C; Alternatively, choose a location, surrounding It does not exist, where X 4 For N or CL x4 -R x4 And X 5 For N or CL x5 -R x5 ; Each L x4 and L x5 Independently for bonds or N(R) L S(O)2-; Each R x4 and R x5 Independently hydrogen, C 1-6 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 heterocyclic groups; Where R x4 and R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 cycloalkyl), Where R 4a Each C 1-6Alkyl, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b replace; Each R 4b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (halogenated alkyl); Each L 3 Independently for the key, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)-, -C(O)- or -(C 1-6 Alkyl)C(O)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic groups; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 3a replace; Each R 3a Independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2; n is an integer from 0 to 3; Each X 6 and X 7 Independently N or CH, Where X 4 X 5 X 6 and X 7 The two numbers in the range do not exceed N; ring C 6-10 Aryl; Each L 1 Independently for the key, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-; Each R1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH or -NH2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-; R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

[0060] In some embodiments, this disclosure provides compounds according to the structure of formula (IA): IA Or a pharmaceutically acceptable salt thereof, wherein the ring ,ring X 1 X 2 X 4 X 5 X 6 X 7 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0061] In some embodiments, this disclosure provides compounds according to the structure of formula (II-A): II-A Or a pharmaceutically acceptable salt thereof, wherein the ring ,ring R x1 X 4 X 5 X 6 X 7 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0062] In some embodiments, this disclosure provides compounds according to the structure of formula (II-B): II-B Or a pharmaceutically acceptable salt thereof, wherein the ring ,ring R x2 X 4 X 5 X 6 X 7 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0063] In some embodiments, this disclosure provides compounds according to the structure of formula (II-C): II-C Or a pharmaceutically acceptable salt thereof, wherein the ring ,ring X 4 X 5 X 6 X 7 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0064] In some embodiments, this disclosure provides compounds according to the structure of formula (II-D): II-D Or a pharmaceutically acceptable salt thereof, wherein the ring ,ring X 4 X 5 X 6 X 7 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0065] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 2 For -O-. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein X 2 For -O- and X 1 -C(R) x1 =. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 2 For -O- and X 1 It is -N-.

[0066] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 1 For -O-. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein X 1 For -O- and X 2 -C(R) x2 =. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 1 For -O- and X 2 It is -N-.

[0067] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 Halogen, C 1-3 Alkyl or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 It can be chlorine, fluorine, methyl, or methoxy.

[0068] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 Halogen or C 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 It can be chlorine, fluorine, or methyl.

[0069] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 It is hydrogen or C 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 It can be hydrogen or methyl.

[0070] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x1 It is hydrogen.

[0071] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 Halogen, C 1-3 Alkyl or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 It can be chlorine, fluorine, methyl, or methoxy.

[0072] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 Halogen or C 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 It can be chlorine, fluorine, or methyl.

[0073] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 It is hydrogen or C 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 It can be hydrogen or methyl.

[0074] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x2 It is hydrogen.

[0075] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 It is N or CH. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 For N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 For CH.

[0076] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 7 It is N or CH. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 7 For N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 7 For CH.

[0077] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 and X 7 For CH.

[0078] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 4 X 5 X 6 and X 7 The number of compounds is not greater than or equal to N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 4 X 5 X 6 and X 7 Both of them are N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 4 X 5 X 6 and X 7 One of them is N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein 4 X 5 X 6 and X 7 X is not N.

[0079] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, and X 4 and X 5 Each is C.

[0080] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl or C 5-10 cycloalkyl, and X 4 and X 5 Each is C.

[0081] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein ring With X 4 and X 5 Together they form 5 to 6 yuan of heteroaryl compounds, and X 4 and X 5 Each can be either C or N independently.

[0082] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It is a phenyl group.

[0083] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring C 5–7 Cycloalkyl.

[0084] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It is a 5-membered heteroaryl group.

[0085] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It is a 6-membered heteroaryl group.

[0086] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 For CH and X 7 For N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 For N and X 7 For CH. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein X 6 and X 7 For CH.

[0087] In some embodiments, this disclosure provides compounds according to the structure of formula (III): III Or a pharmaceutically acceptable salt thereof, wherein the ring X 1 X 2 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0088] In some embodiments, the compound of formula (III) is: III Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; Each L 3 Independently for the key, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)-, -C(O)- or -(C 1-6 Alkyl)C(O)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic groups; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 3a replace; Each R 3a Independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2; n is an integer from 0 to 3; ring C 6-10 Aryl; Each L 1 Independently for the key, -O-, -(C1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-; Each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH or -NH2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C1-6 Alkyl)O(C 1-6 alkyl)-; R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

[0089] In some embodiments, this disclosure provides compounds according to the structure of formula (IV-A): IV-A Or a pharmaceutically acceptable salt thereof, wherein the ring R x1 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0090] In some embodiments, this disclosure provides compounds according to the structure of formula (IV-B): IV-B Or a pharmaceutically acceptable salt thereof, wherein the ring R x2 L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0091] In some embodiments, this disclosure provides compounds according to the structure of formula (IV-C): IV-C Or a pharmaceutically acceptable salt thereof, wherein the ring L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0092] In some embodiments, this disclosure provides compounds according to the structure of formula (IV-D): IV-D Or a pharmaceutically acceptable salt thereof, wherein the ring L 1 L 2 L 3 R 1 R 2 R 3 R 5 m and n are as described in this article.

[0093] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one L 3 Independently 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)-, where R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one L 3 Independently for -(C 1-3 Alkyl)O-, -(C 1-3Alkyl)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)-, where R L As described in this article.

[0094] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 3 Independently 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)-, where R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 3 Independently for -(C 1-3 Alkyl)O-, -(C 1-3 Alkyl)N(R L )C(O)-、-(C 1-3 alkyl)C(O)N(R L )-、-(C1-3 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)-, where R L As described in this article.

[0095] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 3 Independently for the key, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)-, -C(O)- or -(C 1-6 Alkyl)C(O)-. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 3 Independently for the key, -(C 1-3 Alkyl)O-, -(C 1-3 Alkyl)-, -C(O)- or -(C 1-3 Alkyl)C(O)-. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 3 For key.

[0096] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl groups, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2 or -OC 3-8 cycloalkyl, wherein R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 3a Replace, where R 3a As described in this article. In some implementations, R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 3a Replace, where R 3a As described in this article. In some implementations, R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by an R 3a Replace, where R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl groups, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2 or -OC 3-8 Cycloalkyl.

[0097] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independent of halogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy or 5- to 10-membered heterocyclic group, wherein R 3 Each C 1-6 Alkyl, C 1-6 Alkoxy groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 3a Replace, where R 3a As described in this article. In some implementations, each R 3 Independent of halogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy or 5- to 10-membered heterocyclic group, wherein R 3 Each C 1-6 Alkyl, C 1-6 The alkoxy group and the 5- to 10-membered heterocyclic group are optionally separated by one or two R groups. 3a Replace, where R 3a As described in this article. In some implementations, R 3 Each C 1-6 Alkyl, C 1-6 Alkoxy groups and 5- to 10-membered heterocyclic groups are optionally separated by an R 3a Replace, where R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independent of halogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy or 5- to 10-membered heterocyclic groups.

[0098] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts 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 R 3 Each C 1-3 Alkyl groups are independently and optionally surrounded by one or two R groups. 3a Replace, where R 3a As described in this article. In some implementations, R 3 Each C 1-3 Alkyl groups are independently and optionally enclosed by an R 3a Replace, where R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts 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).

[0099] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 To be arbitrarily selected by one to three R 3a The substituted 5- to 7-membered heterocyclic groups, wherein R3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 To be arbitrarily controlled by one or two R 3a The substituted 5- to 7-membered heterocyclic groups, wherein R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 To be arbitrarily used by an R 3a The substituted 5- to 7-membered heterocyclic groups, wherein R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 It consists of 5- to 7-membered heterocyclic groups.

[0100] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independent of halogen, C 1-6 Alkyl or C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independently for C 1-6 Alkyl or C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independently for C 1-6 Alkyl or C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3 Independently for C 1-6 alkyl.

[0101] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 To be optionally controlled by one or two R 3a Replacement C 1-6 alkoxy group, where R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 To be arbitrarily used by an R 3a Replacement C 1-6 alkoxy group, where R 3a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 C 1-6Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 It is a methoxy group.

[0102] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 C 1-6 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 C 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 It is a methyl group.

[0103] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 It is a halogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3 It is either fluorine or chlorine.

[0104] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 R 3a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 3bReplace, where R 3b As described in this article. In some implementations, R 3a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by an R 3b Replace, where R 3b As described in this article.

[0105] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C1-6 (halogenated alkyl)2、-C(O)N(C 3-8 cycloalkyl)2、-NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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.

[0106] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently halogen, -C(O)(C 1-6 Alkyl groups, -OH groups, -O groups 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C 1-6 alkyl) or -C(O)N(C 1-6 alkyl)2, wherein R 3a Each C 1-6 Alkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one or two R groups. 3b Replace, where R 3b As described in this article. In some implementations, R 3a Each C 1-6 Alkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by an R 3b Replace, where R3b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently halogen, -C(O)(C 1-6 Alkyl groups, -OH groups, -O groups 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C 1-6 alkyl) or -C(O)N(C 1-6 Alkyl)2.

[0107] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a -O(C) 1-3 Alkyl groups, 5- to 7-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C3 alkyl groups) or -C(O)N(C 1-3 alkyl)2, wherein R 3a Each C 1-3 Alkyl groups and 5- to 7-membered heterocyclic groups are optionally separated by one or two R groups. 3b Replace, where R 3b As described in this article. In some implementations, R 3a Each C 1-3 Alkyl groups and 5- to 7-membered heterocyclic groups are optionally separated by an R 3b Replace, where R 3b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a -O(C) 1-3 Alkyl groups, 5- to 7-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C3 alkyl groups) or -C(O)N(C 1-3 Alkyl)2.

[0108] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a Halogen or -C(O)(C 1-6 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a Halogen or C(O)(C 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a It is chlorine, fluorine or -C(O)(C 1-3 alkyl).

[0109] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently halogenated or -C(O)(C 1-6 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently halogenated or -C(O)(C 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a It can be chlorine, fluorine, or -C(O)(C) independently. 1-3 alkyl).

[0110] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a -OH or -O(C) 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a It is -OH or -O (methyl).

[0111] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently -OH or -O(C) 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a It can be -OH or -O (methyl) independently.

[0112] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a -O(C) 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a It is -O (methyl).

[0113] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently for -O(C 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently -O (methyl).

[0114] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3aIt is a halogen or -OH. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 3a It can be chlorine, fluorine, or -OH.

[0115] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a Independently, it is a halogen or -OH. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3a It can be chlorine, fluorine, or -OH on its own.

[0116] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (Haloalkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 3b Independently fluorine, chlorine, -O(C) 1-3 alkyl) or -O(C 1-3 (Halogenated alkyl groups).

[0117] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R L Independently hydrogen or C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R L Independently hydrogen or C 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R L For hydrogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R L It is a methyl group.

[0118] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is an integer from 0 to 2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is an integer from 1 to 3. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 0 or 1. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 1 or 2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 2 or 3. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 0. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 1. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where n is 3.

[0119] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring With X 4 X 5 X 6 and X 7 The rings are joined together to form or .

[0120] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring With X 4 X 5 X 6 and X 7 The rings are joined together to form .

[0121] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring With X 4 X 5 X 6 and X 7 The rings are joined together to form .

[0122] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring With X 4 X 5 X 6 and X 7 The rings are joined together to form .

[0123] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring With X 4 X 5 X 6 and X 7 The rings are joined together to form .

[0124] In some embodiments, this disclosure provides compounds with a structure according to formula (VA): VA Or a pharmaceutically acceptable salt thereof, wherein the ring R x1 L 1 L 2 R 1 R 2 R 5 And m as described in this article.

[0125] In some embodiments, this disclosure provides compounds with a structure according to formula (VB): VB Or a pharmaceutically acceptable salt thereof, wherein the ring R x2 L 1 L 2 R 1 R 2 R 5 And m as described in this article.

[0126] In some embodiments, this disclosure provides compounds with a structure according to formula (VC): VC Or a pharmaceutically acceptable salt thereof, wherein the ring L 1 L 2 R 1 R 2 R 5 And m as described in this article.

[0127] In some embodiments, this disclosure provides compounds with a structure according to formula (VD): VD Or a pharmaceutically acceptable salt thereof, wherein the ring L 1 L 2 R 1 R 2 R 5 And m as described in this article.

[0128] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It does not exist.

[0129] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It does not exist, where X 4 For N or CL x4 -R x4 And X 5 For N or CL x5 -R x5 In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It does not exist, where X 4 Let N be the number of elements, and X be the number of elements. 5 For CL x5 -R x5 In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It does not exist, where X 4 For CL x4 -R x4 And X 5 For N. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It does not exist, where X 4 For CL x4 -R x4 And X 5 For CL x5 -R x5 .

[0130] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x4 For 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)-, -(C1-3 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)-, where R L As described in this article.

[0131] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: 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)-, where R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: 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 1-3Alkyl)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)-, where R L As described in this article.

[0132] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x4 For bond or N(R) L )S(O)2-, where R L As defined herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x4 For N(R) L )S(O)2-, where R L As defined herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x4 For key.

[0133] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x5 For 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 1-3 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)-, where R L As described in this article.

[0134] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x5 For -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)N(RL )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)-, where R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: 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(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)-, where R L As described in this article.

[0135] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x5 For bond or N(R) L )S(O)2-, where R L As defined herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x5 For N(R) L )S(O)2-, where R LAs defined herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x5 For key.

[0136] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L x4 and L x5 Independently for bonds or N(R) L )S(O)2-, where R L As defined herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L x4 and L x5 Each is a key.

[0137] In some embodiments, this disclosure provides compounds according to the structure of formula (VI): VI Or a pharmaceutically acceptable salt thereof, wherein the ring X 1 X 2 X 6 X 7 L 1 L 2 R 1 R 2 R 5 R x4 R x5 And m as described in this article.

[0138] In some embodiments, the compound of formula (VI) is: VI Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; Each Rx4 and R x5 Independently hydrogen, C 1-6 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 heterocyclic groups; Where R x4 and R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 cycloalkyl), Where R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b replace; Each R 4b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (halogenated alkyl); Each X 6 and X 7 Independently N or CH; ring C 6-10 Aryl; Each L 1 Independently for the key, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-; Each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH or -NH2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-; R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

[0139] In some embodiments, this disclosure provides compounds according to the structure of formula (VII-A): VII-A Or a pharmaceutically acceptable salt thereof, wherein the ring X 6 X 7 L 1 L 2 R 1 R 2 R 5 R x1 R x4 R x5 And m as described in this article.

[0140] In some embodiments, this disclosure provides compounds according to the structure of formula (VII-B): VII-B Or a pharmaceutically acceptable salt thereof, wherein the ring X 6 X 7 L 1 L 2 R 1 R 2 R 5 R x2 R x4 R x5 And m as described in this article.

[0141] In some embodiments, this disclosure provides compounds according to the structure of formula (VII-C): VII-C Or a pharmaceutically acceptable salt thereof, wherein the ring X 6 X 7 L 1 L 2 R 1 R 2 R 5 R x4 R x5 And m as described in this article.

[0142] In some embodiments, this disclosure provides compounds according to the structure of formula (VII-D): VII-D Or a pharmaceutically acceptable salt thereof, wherein the ring X 6 X 7 L 1 L 2 R 1 R 2 R 5 R x4 R x5 And m as described in this article.

[0143] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 R x4 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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.

[0144] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 cycloalkyl, wherein R x4 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 Hydrogen, halogen, hydroxyl, -CN, C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 Cycloalkyl.

[0145] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 R x4 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by an R4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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.

[0146] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 For hydrogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heterocyclic groups, wherein R x4 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one or two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x4 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 For hydrogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heterocyclic groups.

[0147] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 It is a methyl group.

[0148] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 It is hydrogen.

[0149] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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.

[0150] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 cycloalkyl, wherein R x5 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to two R groups. 4a Replace, where R4a As described in this article. In some implementations, R x5 Each C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 Hydrogen, halogen, hydroxyl, -CN, C 1-3 Alkyl, C 2-3 alkynyl group, C 1-3 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 Cycloalkyl.

[0151] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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 x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 Hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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.

[0152] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 For hydrogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heterocyclic groups, wherein R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one or two R groups. 4a Replace, where R 4a As described in this article. In some implementations, R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by an R 4a Replace, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein Rx5 Independently hydrogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heterocyclic groups.

[0153] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 It is a methyl group.

[0154] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x5 It is hydrogen.

[0155] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is optionally separated by one or two R. 4a Replacement C 3-8 cycloalkyl, wherein R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is optionally replaced by an R 4a Replacement C 3-8 cycloalkyl, wherein R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is C. 3-8 Cycloalkyl.

[0156] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is optionally separated by one or two R. 4a Replacement C 1-6 alkoxy group, where R 4aAs described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is optionally replaced by an R 4a Replacement C 1-6 alkoxy group, where R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is C. 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is methoxy.

[0157] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is optionally separated by one or two R. 4a Replacement C 1-6 Alkyl, wherein R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is optionally replaced by an R 4a Replacement C 1-6 Alkyl, wherein R 4a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is C. 1-6 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is C. 1-3 Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R x4 and R x5 One of them is hydrogen and the other is methyl.

[0158] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently for C 1-6 Alkyl, C 1-6Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 4b Replace, where R 4b As described in this article. In some implementations, R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 4b Replace, where R 4b As described in this article. In some implementations, R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by an R 4b Replace, where R 4b As described in this article.

[0159] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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.

[0160] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently halogen, -C(O)(C1-6 alkyl), -OH, -O(C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2, wherein R 4a Each C 1-6 Alkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b Replace, where R 4b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently, it can be chlorine, fluorine, -C(O)(C1-C3 alkyl), -OH, -O(C 1-3 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2, wherein R 4a Each C 1-3 Alkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b Replace, where R 4b As described in this article. In some implementations, R 4a Each C 1-3 Alkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one or two R groups. 4b Replace, where R 4b As described in this article. In some implementations, R 4a Each C 1-3 Alkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by an R 4b Replace, where R 4b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4aIndependently, it can be chlorine, fluorine, -C(O)(C1-C3 alkyl), -OH, -O(C 1-3 Alkyl), 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2.

[0161] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently for -O(C 1-3 Alkyl groups, 5- to 7-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C 1-3 alkyl) or -C(O)N(C1-C3 alkyl)2, wherein each C 1-3 Alkyl groups and 5- to 7-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b Replace, where R 4b As described in this article. In some implementations, each C 1-3 Alkyl groups and 5- to 7-membered heterocyclic groups are optionally surrounded by one or two R groups. 4b Replace, where R 4b As described in this article. In some implementations, each C 1-3 Alkyl groups and 5- to 7-membered heterocyclic groups are optionally separated by an R 4b Replace, where R 4b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently for -O(C 1-3 Alkyl groups, 5- to 7-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C 1-3 Alkyl), or -C(O)N(C1-C3 alkyl)2.

[0162] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently halogenated or -C(O)(C 1-6 Alkyl), wherein the alkyl group is optionally surrounded by one to three R 4b Replacement. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently halogenated or -C(O)(C 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a It can be chlorine, fluorine, or -C(O)(methyl) independently.

[0163] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently -OH or -O(C) 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a It can be -OH or methoxy group independently.

[0164] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 4a -O(C) 1-3 Alkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 4a It is a methoxy group.

[0165] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently, it is a halogen or -OH. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a It can be chlorine, fluorine, or -OH on its own.

[0166] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently for C 1-6 Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 cycloalkyl), wherein R 4a Each C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups and C 3-8 cycloalkyl groups are optionally surrounded by one to three R groups. 4b Replace, where R 4b As described in this article. In some implementations, R 4a Each C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups and C 3-8 cycloalkyl groups are optionally surrounded by one or two R groups. 4b Replace, where R 4b As described in this article. In some implementations, R 4a Each C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups and C 3-8 cycloalkyl group is optionally surrounded by an R 4b Replace, where R 4b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4a Independently for C 1-6Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 (cycloalkyl).

[0167] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (Haloalkyl). In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 4b Independently fluorine, chlorine, -O(C) 1-3 alkyl) or -O(C 1-3 (Halogenated alkyl groups).

[0168] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring C 6-10 Aryl or 5- to 10-membered heteroaryl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... C 6-10 Aryl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... The compound is phenyl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... C 10 Aryl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... For Indene.

[0169] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring It is a 5- to 10-membered heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It is a 5- to 9-membered heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It is a 6- to 10-membered heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It is a 6- to 9-membered heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... The compounds are 5, 6, 7, 8, 9, or 10-membered heteroaryl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It is a nitrogen-containing heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It is a sulfur-containing heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... It is an oxygen-containing heteroaryl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... The ring is a pyridine, pyrimidine, oxazole, pyrrole, pyrazole, imidazole, triazole, or thiophene, each of which optionally fuses with another ring to form a ring. In some implementation schemes, the ring The pyrimidine is a pyrimidine dione.

[0170] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one L 1 Independently -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 1-6alkyl)-, -(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)-, wherein R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one L 1 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(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 1-6 alkyl)-, wherein RL As described in this article.

[0171] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently -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)-, wherein R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently -O-, -(C 1-3 Alkyl)O-, -O(C 1-3alkyl)-, -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 1-6 alkyl)-, wherein R L As described in this article.

[0172] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently for the key, -(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 1-6Alkyl)(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)- or -(C 1-6 alkyl)C(O)N(R L (C) 1-6 alkyl)-, wherein R L As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently for the key, -(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)- or -(C 1-3 alkyl)C(O)N(R L (C) 1-3 alkyl)-, wherein R L As described in this article.

[0173] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently for -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 Alkyl)-. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L1 Independently for -(C 1-3 Alkyl)O-, -O(C 1-3 alkyl)- or -C 1-3 Alkyl-O(C) 1-3 Alkyl)-. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 It can be independently -(methyl)O-, -O(methyl)- or -methyl-O(methyl)-.

[0174] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently for -(C 1-6 Alkyl)O- or -O(C 1-6 Alkyl)-. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 Independently for -(C 1-3 Alkyl)O- or -O(C 1-3 Alkyl)-. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 It can be -(methyl)O- or -O(methyl)- independently.

[0175] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one L 1 For bonds. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein each L 1 For key.

[0176] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl or 4- to 10-membered heterocyclic, wherein R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 1a Replace, where R 1aAs described in this article. In some implementations, R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one or two R groups. 1a Replace, where R 1a As described in this article. In some implementations, R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by an R 1a Replace, where R 1a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl or 4- to 10-membered heterocyclic group.

[0177] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, wherein R 1 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally surrounded by one to three R groups. 1a Replace, where R 1a As described in this article. In some implementations, R 1 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups.1a Replace, where R 1a As described in this article. In some implementations, R 1 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by an R 1a Replace, where R 1a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl groups.

[0178] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heteroaryl, wherein R 1 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl and 5- to 10-membered heteroaryl groups are optionally separated by one or two R 1a Replace, where R 1a As described in this article. In some implementations, R 1 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl and 5- to 10-membered heteroaryl groups are optionally separated by an R 1a Replace, where R 1a As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heteroaryl groups.

[0179] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independent of halogen, -CN or C 1-6 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independent of halogen, -CN or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently chlorine, fluorine, -CN, or methoxy. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 It can be fluorine, -CN, or methoxy on its own.

[0180] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently halogen or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 Independently chlorine, fluorine, or methoxy. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1 It is independently fluorine or methoxy.

[0181] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently for C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2, -N(5- to 10-membered heterocyclic)2, -N(phenyl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C)1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl group (5- to 10-membered heteroaryl group), -C(O) group (5- to 10-membered heterocyclic group), -C(O) group (5- to 10-membered heteroaryl group), -C(O)O(C 1-6 Alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O (5- to 10-membered heterocyclic group), -C(O)O (phenyl), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C 3-8 Cycloalkyl)2, -C(O)N (5- to 10-membered heterocyclic)2, -C(O)N (phenyl)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 heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 cycloalkyl), -NHC(O)NH (5- to 10-membered heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -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 heterocyclic), -S(O)2 (phenyl), -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 R 1a Each C1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 1b Replace, where R 1b As described in this article. In some implementations, R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by an R 1b Replace, where R 1b As described in this article.

[0182] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently for C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2, -N(5- to 10-membered heterocyclic)2, -N(phenyl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl group (5- to 10-membered heteroaryl group), -C(O) group (5- to 10-membered heterocyclic group), -C(O) group (5- to 10-membered heteroaryl group), -C(O)O(C 1-6 Alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O (5- to 10-membered heterocyclic group), -C(O)O (phenyl), -C(O)O (5- to 10-membered heteroaryl), -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)NH(C 3-8cycloalkyl), -C(O)NH (5- to 10-membered heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C 3-8 Cycloalkyl)2, -C(O)N (5- to 10-membered heterocyclic)2, -C(O)N (phenyl)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 heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 cycloalkyl), -NHC(O)NH (5- to 10-membered heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -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 heterocyclic), -S(O)2 (phenyl), -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.

[0183] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, wherein R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 1b Replace, where R1b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently, it can be fluorine, chlorine, -OH, -CN, -C(O)NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, wherein R 1a Each C 1-3 Alkyl, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 1b Replace, where R 1b As described in this article. In some implementations, R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by an R 1b Replace, where R 1b As described in this article.

[0184] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently, it can be fluorine, chlorine, -OH, -CN, -C(O)NH2, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl groups.

[0185] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently halogen, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 alkoxy or phenyl, wherein R 1a Each C 1-6 Alkyl and phenyl groups are optionally separated by one or two R groups. 1b Replace, where R 1b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently, it can be chlorine, fluorine, -OH, -C(O)NH2, C1-3 Alkyl, C 1-3 alkoxy or phenyl, wherein R 1a Each C 1-3 Alkyl and phenyl groups are optionally separated by one or two R groups. 1b Replace, where R 1b As described in this article. In some implementations, R 1a Each C 1-6 Alkyl and phenyl groups are optionally separated by an R 1b Replace, where R 1b As described in this article.

[0186] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently halogen, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkyl or phenyl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1a Independently, it can be chlorine, fluorine, -OH, -C(O)NH2, C 1-3 Alkyl, C 1-3 Alkyl or phenyl.

[0187] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 1a It is a halogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 1a It is chlorine or fluorine. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 1a It is chlorine. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein at least one R 1a It is fluorine.

[0188] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 1 It is a phenyl group and has two R groups. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one to three R atoms. 1b The substituted 5- to 10-membered heterocyclic groups, wherein R 1b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 1 It is a phenyl group and has two R groups. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one to three R atoms. 1bThe substituted 5- to 7-membered heterocyclic groups, wherein R 1b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 1 It is a phenyl group and has two R groups. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one or two R atoms. 1b The substituted 5- to 7-membered heterocyclic groups, wherein R 1b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 1 It is a phenyl group and has two R groups. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one or two R atoms. 1b Substituted 5-membered heterocyclic group, wherein R 1b As described in this article.

[0189] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1b Independently for C 1-3 Alkyl, C 1-3 Halogenated alkyl groups, halogens, oxo groups, -OH, -NH2, CO2H, -O(C) 1-3 alkyl), -O(C) 1-3 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-3 alkyl), -NH(C) 1-3 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-3 Alkyl)2, -N(C 3-8 cycloalkyl)2、-NHC(O)(C 1-3 Alkyl), -NHC(O)(C 1-3 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-3 Alkyl), -NHC(O)O(C 1-3 Halogenated alkyl groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-8cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-3 Alkyl), S(O)2(C 1-3 Alkyl), -S(O)2(C 1-3 Halogenated alkyl groups), -S(O)2(C 3-8 cycloalkyl), -S(O)2 (5- to 10-membered heterocyclic), -S(O)2 (phenyl), -S(O)2 (5- to 10-membered heteroaryl), -S(O)(NH)(C 1-3 Alkyl), -S(O)2NH(C 1-3 alkyl) or -S(O)2N(C 1-3 Alkyl)2.

[0190] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH, or -NH2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1b Independently for C 1-3 Alkyl, C 1-3 Halogenated alkyl groups, halogens, oxo groups, -OH, or -NH2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1b Independently, it is a halogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 1b It can be chlorine or fluorine on its own.

[0191] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is an integer from 0 to 2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is an integer from 1 to 3. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 0 or 1. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 1 or 2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 2 or 3. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 0. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 1. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 2. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: where m is 3.

[0192] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring The phenyl group is present, and the meta-substituent at the attachment site is hydrogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: Among them rings for .

[0193] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for , , , , or .

[0194] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for or .

[0195] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for or .

[0196] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for , , , , , , , , , , or .

[0197] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for , , , , or .

[0198] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for .

[0199] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for , , or In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for .

[0200] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for .

[0201] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring for In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein the ring... for .

[0202] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 Hydrogen, halogen, -CN, C 1-3 Alkyl or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 It can be hydrogen, fluorine, chlorine, -CN, methyl, or methoxy.

[0203] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 For hydrogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 It is a halogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 It is chlorine or fluorine. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 For chlorine. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 2 It is fluorine.

[0204] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 For key, C 1-3 Alkyl, -(C 0-3 alkyl)-cyclopropyl-(C 0-3 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 1-3Alkyl)N(R L2 S(O)2-、-(C 1-3 alkyl)S(O)2N(R L2 (C) 1-3 alkyl)- or -(C 1-3 Alkyl)S(O)2-(C 1-3 alkyl), wherein R L2 As described in this article.

[0205] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-, wherein R L2 As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 For key, C 1-3 Alkyl, -(C 0-3 alkyl)-cyclopropyl-(C 0-3 alkyl)-, -(C 1-3 Alkyl)O- or -(C 1-3 Alkyl)O(C 1-3 alkyl)-, wherein R L2 As described in this article.

[0206] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 For key.

[0207] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 Methyl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 Ethyl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein L 2 It is propyl.

[0208] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R L2 It is hydrogen or C 1-3Alkyl group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R L2 For hydrogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R L2 It is a methyl group.

[0209] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 For hydrogen, -CN, -OR 5a -C(O)NR 5a 2. -NR 5a C(O)R 5a -NR 5a 2C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, wherein R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by an R 5b Replace, where R 5b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 For 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, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl.

[0210] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 For hydrogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, wherein R 5 Each C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b Replace, where R 5b As described in this article. In some implementations, R 5 Each C 3-8Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by an R 5b Replace, where R 5b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 For hydrogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl.

[0211] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 C 1-3 Alkyl, C 5-6 Cycloalkyl, phenyl, 5- to 7-membered heterocyclic or 5- to 9-membered heteroaryl, wherein R 5 Each C 5-6 Cycloalkyl, phenyl, 5- to 7-membered heterocyclic and 5- to 9-membered heteroaryl groups are optionally surrounded by one or two R groups. 5b Replace, where R 5b As described in this article. In some implementations, R 5 Each C 5-6 Cycloalkyl, phenyl, 5- to 7-membered heterocyclic and 5- to 9-membered heteroaryl groups are optionally separated by an R 5b Replace, where R 5b As described herein. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 C 1-3 Alkyl, C 5-6 Cycloalkyl, phenyl, 5- to 7-membered heterocyclic or 5- to 9-membered heteroaryl.

[0212] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 For hydrogen. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein R 5 For -CN.

[0213] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5a Independently hydrogen or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5a Independently hydrogen. In some embodiments, the compounds of this disclosure are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5a Independently for C1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5a Independently, it is methyl.

[0214] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5b It can be fluorine, chlorine, oxo, cyclopropyl, hydroxyl, -CN, methyl, methoxy, -OCF3 or -OCF2H independently.

[0215] In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl groups. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5b Independently, it is an oxo group, methyl group, or methoxy group. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5b The compound is methyl. In some embodiments, the compounds disclosed herein are the following compounds or pharmaceutically acceptable salts thereof: wherein each R 5b It is an oxo group.

[0216] In some embodiments, the compounds disclosed herein are compounds having the structure shown in Scheme A or pharmaceutically acceptable salts thereof: plan A : , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and , Or its pharmaceutically acceptable salt.

[0217] In some embodiments, the compounds disclosed herein are Or, or a pharmaceutically acceptable salt thereof.

[0218] In some embodiments, the compounds disclosed herein are Or, or a pharmaceutically acceptable salt thereof.

[0219] In some embodiments, the compounds disclosed herein are Or, or a pharmaceutically acceptable salt thereof.

[0220] In some embodiments, the compounds disclosed herein are Or, or a pharmaceutically acceptable salt thereof.

[0221] In some embodiments, the compounds disclosed herein are Or, or a pharmaceutically acceptable salt thereof.

[0222] In some embodiments, the compounds disclosed herein are compounds selected from any of Examples 1 to 66 or pharmaceutically acceptable salts thereof.

[0223] The in vivo metabolites of the compounds described herein also fall within the scope of this document, and to some extent, such products are novel and unobservable relative to the prior art. These products can be generated, for example, by oxidation, reduction, hydrolysis, amidation, esterification, etc., of the applied compound, primarily due to enzymatic processes. Therefore, methods including the generation of novel and unobservable compounds by means of exposing the compound to mammals for a period sufficient to produce its metabolites are included. Such products are typically identified by the following steps: preparing a radiolabel (e.g., 14 C or 3 The radiolabeled compound (H) is administered parenterally to animals (such as rats, mice, guinea pigs, monkeys, or humans) at a detectable dose (e.g., greater than about 0.5 mg / kg), allowing sufficient time for metabolism (typically about 30 seconds to about 30 hours) and separation of its metabolites from urine, blood, or other biological samples. These products are readily separated because they are labeled (other products are separated using antibodies capable of binding to epitopes that survive in the metabolites). The metabolite structure is determined in a conventional manner, such as by MS or NMR analysis. Typically, the analysis of metabolites is performed in the same manner as routine drug metabolism studies well known to those skilled in the art.

[0224] The compounds disclosed herein can be prepared by a variety of methods. For example, Schemes 1-5 illustrate representative syntheses of the compounds disclosed herein. The variables shown in the following schemes are for illustrative purposes only and are independent of those described elsewhere herein.

[0225] General reaction scheme 1 : Intermediate 1.1 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 1.2. Intermediates 1.2 and 1.3 are condensed in the presence of a base and heated to give intermediate 1.4. Metal-mediated CH arylation with a suitable coupling partner BX (where B is aryl or heteroaryl and X is -Cl, -Br, -I, or OTf) in the presence of a suitable catalyst (e.g., Pd) can be used to give compounds of formula (1.a).

[0226] General reaction scheme 2 : Iridium-mediated borylation can be used to give intermediate 1.5 in the presence of intermediate 1.1, bis(pinacolyl)diboron, and a suitable Ir catalyst. Metal-mediated cross-coupling with a suitable coupling partner BX (where B is aryl or heteroaryl and X is -Cl, -Br, -I, or OTf) in the presence of a suitable catalyst (e.g., Pd or Ni) can be used to give intermediate 1.6. Intermediate 1.6 can be reacted with intermediate 1.7 in the presence of a suitable base (e.g., DIPEA) and under heating to give intermediate 1.7. Condensation of intermediate 1.7 with intermediate 1.3 in the presence of a base and under heating can be used to give the compound of formula (1.a).

[0227] General reaction scheme 3 : Phosphine-mediated O-alkylation in the presence of intermediate 2.1, triarylphosphine, ethyl glycolate, and a suitable carbodiimide can be used to give intermediate 2.2. Base-mediated cyclization with a suitable base (e.g., NaH) can be used to provide intermediate 1.6. Intermediate 1.6 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 1.7. Condensation of intermediate 1.7 with intermediate 1.3 in the presence of a base and under heating can be used to give the compound of formula (1.a).

[0228] General reaction scheme 4 : In the presence of a suitable catalyst (e.g., Pd or Ni), intermediate 3.1 (where X is -Cl, -Br, -I, or -OTf) can undergo metal-mediated cross-coupling with a suitable coupling partner BM (where B is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si, or -Mg) to give intermediate 3.2. Intermediate 3.2 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 3.3. The condensation of intermediate 3.3 with intermediate 1.3 in the presence of a base and under heating gives the compound of formula (1.b).

[0229] General reaction scheme 5 : Intermediate 4.1 (where B is aryl) can react with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 4.2. The condensation of intermediate 4.2 with intermediate 1.3 in the presence of a base and under heating can be used to give the compound of formula (1.c).

[0230] pharmaceutical preparations In some embodiments, this disclosure provides a pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of the disclosed formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D) a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0231] In some implementations, the pharmaceutical composition is used to treat viruses.

[0232] In some embodiments, the pharmaceutical composition further comprises one or more additional therapeutic agents. Any suitable additional therapeutic agent or combination therapy may be used with compounds of formulas (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), and (VII-D) or pharmaceutically acceptable salts thereof (such as the pharmaceutical agents and therapies described herein).

[0233] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D) and an additional therapeutic agent, wherein the additional therapeutic agent is as described herein under the title “Combination Therapy”.

[0234] In some embodiments, the compounds disclosed herein are formulated with conventional carriers and excipients, which will be selected according to conventional practice. Tablets may contain excipients, flow aids, fillers, binders, etc. Aqueous formulations may be prepared aseptically and may be isotonic, for example, when intended for delivery via 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, etc. The pH range of the formulation is from about 3 to about 11, for example from about 7 to about 10.

[0235] In some embodiments, the compounds disclosed herein are administered alone. In some embodiments, the compounds disclosed herein are administered as pharmaceutical formulations. In some embodiments, formulations for veterinary and / or human use comprise at least one compound of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), and (VII-D) or a pharmaceutically acceptable salt thereof, as well as one or more acceptable carriers and optional other therapeutic components, such as those additional therapeutic components discussed herein. In some embodiments, the carrier is "acceptable," meaning it is compatible with the other components of the formulation and physiologically harmless to the recipient.

[0236] In some embodiments, the formulations disclosed herein include those suitable for the aforementioned routes of administration. In some embodiments, the formulation is present in a unit dosage form. The formulation can be prepared by methods known in the pharmaceutical field. Techniques and formulations can be found, for example, in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA). Such methods include, for example, the step of associating an active ingredient with a carrier comprising one or more excipients. In some embodiments, the formulation is prepared by associating an active ingredient with a liquid carrier or a finely dispersed solid carrier, or both, and then, in some embodiments, shaping the product.

[0237] In some implementations, the pharmaceutical preparation is used for subcutaneous, intramuscular, intravenous, oral, or inhalation administration.

[0238] Formulations suitable for oral administration may be presented as discrete units, such as capsules, pouches, or tablets each containing a predetermined amount of an active ingredient, the active ingredient being a compound of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D) or a pharmaceutically acceptable salt thereof; as powders or granules; as solutions or suspensions in aqueous or non-aqueous liquids; or as oil-in-water or water-in-oil liquid emulsions. In some embodiments, the active ingredient is administered as a pill, saccharin, or paste.

[0239] Tablets can be prepared, for example, by compression or molding with one or more excipients. Compressed tablets can be prepared, for example, by compressing a free-flowing form of the active ingredient (such as powder or granules) 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 powdered active ingredients moistened with an inert liquid diluent in a suitable machine. Tablets may optionally be coated or indented. In some embodiments, tablets are formulated to provide a slow or controlled release of the active ingredient.

[0240] For infections of the eyes or other external tissues (e.g., the mouth and skin), the formulation may be applied as a topical ointment or cream containing, for example, about 0.075% w / w to about 20% w / w (including an increment of about 0.1% w / w of an active ingredient in the range between about 0.1% and about 20% (e.g., about 0.6% w / w, about 0.7% w / w, etc.)) of a compound of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D). When formulated into an ointment, compounds of formulas (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D) may be used with a paraffin or water-miscible ointment base. Alternatively, compounds of formulas (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D) may be formulated into an oil-in-water emulsion base.

[0241] If desired, the aqueous phase of the cream matrix may contain, for example, at least about 30% w / w polyols, i.e., alcohols having two or more hydroxyl groups such as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerin, and polyethylene glycol (including PEG 400), and mixtures thereof. Topical formulations may include, in some embodiments, compounds that enhance the absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogues.

[0242] The oil phase of an emulsion can be composed of known ingredients in a known manner. While this phase may consist only of emulsifiers (or simply emulsifiers), it may include, for example, at least one emulsifier with fats or oils, or with a mixture of both fats and oils. In some embodiments, hydrophilic emulsifiers are included together with lipophilic emulsifiers that act as stabilizers. In some embodiments, the emulsion comprises both oils and fats. Emulsifiers, with or without stabilizers, together constitute a so-called emulsified wax, and the wax, together with the oils and fats, constitutes a so-called emulsified ointment matrix, which forms the oily dispersed phase of the ointment formulation.

[0243] Emulsifiers and emulsion stabilizers suitable for formulations include, for example, Tween. ® 60. Span ® 80. Cetearyl alcohol, benzyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate. Other emulsifiers and emulsion stabilizers suitable for formulations include Tween. ® 80.

[0244] Choose a suitable oil or fat for the formulation based on the desired properties. Creams can be non-greasy, non-staining, and washable products with a suitable consistency to prevent leakage from tubes or other containers. Straight-chain or branched monoalkyl or dialkyl esters can be used, such as diisohexyl adipate, isohexadecanoyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or mixtures of branched esters known as CrodamolCAP. These esters can be used alone or in combination, depending on the desired properties. Alternatively, high-melting-point lipids, such as white soft paraffin and / or liquid paraffin or other mineral oils, can be used.

[0245] Pharmaceutical formulations according to this disclosure comprise compounds according to this disclosure, as well as one or more pharmaceutically acceptable carriers or excipients and optional other therapeutic agents. Pharmaceutical formulations containing the active ingredient may be in any form suitable for the intended method of administration. For example, when intended for oral use, they may be prepared as tablets, lozenges, tablets, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups, or elixirs. Compositions intended for oral use may be prepared according to any method known in the art for manufacturing pharmaceutical compositions, and such compositions may contain one or more pharmaceutical agents, including sweeteners, flavoring agents, coloring agents, and preservatives, to provide a palatable formulation. Tablets containing the active ingredient mixed with non-toxic, pharmaceutically acceptable excipients suitable for manufacturing 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 and disintegrants such as corn starch or alginic acid; binders such as starch, gelatin, or gum arabic; and lubricants such as magnesium stearate, stearic acid, or talc. Tablets may be uncoated or coated using known techniques, including microencapsulation, to delay disintegration and adsorption in the gastrointestinal tract, thereby providing sustained action over a longer period. For example, delaying materials, such as glyceryl monostearate or glyceryl distearate, may be used alone or in combination with waxes.

[0246] Formulations intended for oral use may also be provided as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent (such as calcium phosphate or kaolin) or as soft gelatin capsules in which the active ingredient is mixed with an aqueous or oily medium (such as peanut oil, liquid paraffin, or olive oil).

[0247] The aqueous suspension of the present invention contains an active substance mixed with excipients suitable for manufacturing aqueous suspensions. Such excipients include suspending agents such as sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, sodium alginate, polyvinylpyrrolidone, tragacanth gum, and gum arabic; and dispersants or wetting agents such as naturally occurring phospholipids (e.g., lecithin), condensation products of olefinic oxygen and fatty acids (e.g., polyoxyethylene stearate), condensation products of ethylene oxide and long-chain fatty alcohols (e.g., heptadecanethoxycetyl alcohol), and condensation products of ethylene oxide and esters derived from fatty acids and hexyl anhydrides (e.g., polyoxyethylene sorbitan monooleate). The aqueous suspension may also contain one or more preservatives, such as ethylparaben or n-propylparaben, one or more colorants, one or more flavoring agents, and one or more sweeteners such as sucrose or saccharin. Other non-limiting examples of suspending agents include cyclodextrin. In some examples, the suspending agent is sulfobutyl ether β-cyclodextrin (SEB-β-CD), such as Captisol. ® .

[0248] Oily suspensions can be prepared by suspending the active ingredients in vegetable oils (such as peanut oil, olive oil, sesame oil, or coconut oil) or mineral oils (such as liquid paraffin). Oral suspensions may contain thickeners such as beeswax, hard paraffin, or cetyl alcohol. Sweeteners (such as those mentioned above) and flavoring agents may be added to provide palatable oral formulations. These compositions may be preserved by adding antioxidants (such as ascorbic acid).

[0249] The dispersible powders and granules of this disclosure, suitable for preparing aqueous suspensions by adding water, provide an active ingredient that can be mixed 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, flavoring agents, and coloring agents, may also be present.

[0250] The pharmaceutical compositions disclosed herein may also be in the form of an oil-in-water emulsion. The oil phase may 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 soybean lecithin; esters or metaesters derived from fatty acids and hexitan anhydrides, such as sorbitan monooleate; and condensation products of these metaesters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. The emulsion may also contain sweeteners and flavoring agents. Syrups and elixirs may be formulated with sweeteners such as glycerin, sorbitol, or sucrose. Such formulations may also contain modifiers, preservatives, flavoring agents, or coloring agents.

[0251] The pharmaceutical compositions disclosed herein can be in the form of sterile injectable formulations, such as sterile injectable aqueous or oily suspensions. These suspensions can be formulated using suitable dispersants or wetting agents and suspending agents mentioned above, according to known techniques. The sterile injectable preparations can also be sterile injectable solutions or suspensions in non-toxic, parenteral-acceptable diluents or solvents (such as solutions in 1,3-butanediol), or prepared as lyophilized powders. Acceptable solvents and media are water, Ringer's solution, and isotonic sodium chloride solution. Furthermore, sterile non-volatile oils are generally used as solvents or suspension media. For this purpose, any mild non-volatile oil can be used, including synthetic monoglycerides or diglycerides. Additionally, fatty acids such as oleic acid can also be used in the preparation of injectable formulations. Acceptable solvents and media are water, Ringer's solution, isotonic sodium chloride solution, and hypertonic sodium chloride solution.

[0252] The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the host being treated and the specific route of administration. For example, a sustained-release formulation intended for oral administration to humans may contain approximately 1 mg to 1000 mg of the active material, which is compounded with an appropriate and convenient amount of a carrier material, which may vary between approximately 5% to approximately 95% (weight:weight) of the total composition. Pharmaceutical compositions can be prepared to provide easily measurable dosages. For example, an aqueous solution intended for intravenous infusion may contain approximately 3 mg to 500 mg of the active ingredient per milliliter of solution to allow for the infusion of an appropriate volume at a rate of approximately 30 mL / hr.

[0253] Formulations suitable for topical application to the eyes also include eye drops, wherein the active ingredient is dissolved or suspended in a suitable carrier, particularly in an aqueous solution of 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 particularly about 1.5% w / w.

[0254] Preparations suitable for topical application in the oral cavity include lozenges containing flavoring active ingredients, typically sucrose and gum arabic or tragacanth; tablets containing inert active ingredients, such as gelatin and glycerin, or sucrose and gum arabic; and mouthwashes containing active ingredients in a suitable liquid carrier.

[0255] Formulations for rectal administration may be provided as suppositories with a suitable matrix, including, for example, cocoa butter or salicylates.

[0256] In some embodiments, the compounds disclosed herein are administered by inhalation. In some embodiments, formulations suitable for intrapulmonary or intranasal administration have particle sizes, such as 0.5 micrometers, 1 micrometer, 30 micrometers, 35 micrometers, etc., in the range of 0.1 micrometers to 500 micrometers, and are administered by rapid inhalation through the nasal passage or by inhalation through the mouth to reach the alveolar sacs. Suitable formulations include aqueous or oily solutions of the active ingredient. Formulations 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 nebulized formulations. In some embodiments, the compounds used herein are formulated for delivery via a face mask. In some embodiments, the compounds used herein are formulated for delivery via a face mask inhaler.

[0257] Another embodiment provides an inhalable composition comprising a compound of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D), or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt, including hydrochloride, hydrobromide, sulfate, or phosphate. For example, such salts may cause less lung irritation compared to other salts. In some embodiments, the inhalable composition is delivered as an aerosol into the bronchial space, the aerosol comprising particles with a median mass aerodynamic diameter (MMAD) between about 1 µm and about 5 µm. In some embodiments, compounds of formula (I), (IA), (II-A), (II-B), (II-C), (II-D), (III), (IV-A), (IV-B), (IV-C), (IV-D), (VA), (VB), (VC), (VD), (VI), (VII-A), (VII-B), (VII-C), or (VII-D), or pharmaceutically acceptable salts thereof, are formulated for aerosol delivery using a nebulizer, a metered-dose inhaler (pMDI), or a dry powder inhaler (DPI).

[0258] Preparations suitable for vaginal application may be provided in the form of pessaries, tampons, creams, gels, pastes, foams or sprays, and contain, in addition to the active ingredient, a suitable carrier known in the art.

[0259] Preparations suitable for parenteral administration include aqueous and non-aqueous sterile injectable solutions that may contain antioxidants, buffers, antibacterial agents and solutes to make the preparation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions that may include suspending agents and thickeners.

[0260] The formulation is present in single-dose or multi-dose containers, such as sealed ampoules and vials, and can be stored under lyophilized (freeze-dried) conditions, requiring only the addition of a sterile liquid carrier, such as water for injection, immediately before use. Temporary injectable solutions and suspensions are prepared from sterile powders, granules, and tablets of the aforementioned types. Preferred single-dose formulations are those containing a daily dose or a sub-daily dose of the active ingredient as described above, or a suitable portion thereof.

[0261] It should be understood that, in addition to the ingredients specifically mentioned above, the formulations disclosed herein may include other agents conventional in the art in relation to the type of formulation discussed, such as those suitable for oral administration, which may include flavoring agents.

[0262] This disclosure also provides veterinary drug compositions comprising at least one active ingredient as defined above and its veterinary drug carrier.

[0263] Veterinary drug carriers are materials that can be used to administer compositions and can be solid, liquid, or gaseous materials. They are otherwise inert or acceptable in the veterinary field and compatible with the active ingredient. These veterinary drug compositions can be administered orally, parenterally, or via any other desired route.

[0264] The compounds disclosed herein are used to provide controlled-release pharmaceutical formulations (“controlled-release formulations”) containing one or more of the compounds disclosed herein as active ingredients, wherein the release of the active ingredient is controlled and regulated to allow administration at a lower frequency or to improve the pharmacokinetic or toxicological characteristics of a given active ingredient.

[0265] The effective dose of the active ingredient depends at least on the nature of the condition being treated, its toxicity, the method of delivery, and the pharmaceutical formulation, and can be determined by clinicians using routine dose-escalation studies. This dose is expected to be from about 0.0001 mg / kg body weight to about 100 mg / kg body weight daily; typically, from about 0.01 mg / kg body weight to about 10 mg / kg body weight daily; more typically, from about 0.01 mg / kg body weight to about 5 mg / kg body weight daily; and most typically, from about 0.05 mg / kg body weight to about 0.5 mg / kg body weight daily. For example, the candidate daily dose range for an adult weighing about 70 kg could be from about 1 mg to about 1000 mg, such as between about 5 mg and about 500 mg, and could be in the form of a single dose or multiple doses.

[0266] How to use This disclosure also provides a method for treating or preventing viral infection in a subject (e.g., a person) in need, the method comprising administering the compound described herein to the subject.

[0267] In some embodiments, this disclosure provides a method for treating a viral infection in a subject (e.g., a person) in need, the method comprising administering the compound described herein to the subject in need.

[0268] In some embodiments, the compounds described herein are administered to humans via oral, intramuscular, intravenous, subcutaneous, or inhalation administration.

[0269] In some embodiments, this disclosure provides a method for treating or preventing viral infection in a subject (e.g., a person) in need, the method comprising administering to the subject a compound disclosed herein and at least one additional active therapeutic or preventative agent.

[0270] In some embodiments, this disclosure provides a method for treating a viral infection in a subject (e.g., a person) in need, the method comprising administering to the subject a compound disclosed herein and at least one additional active therapeutic or preventative agent.

[0271] In one embodiment, this disclosure provides a method for inhibiting viral polymerase in cells, the method comprising contacting virus-infected cells with a compound disclosed herein, thereby inhibiting the viral polymerase.

[0272] In one embodiment, this disclosure provides a method for inhibiting viral proteases in cells, the method comprising contacting virus-infected cells with the compounds disclosed herein and at least one additional active therapeutic agent, thereby inhibiting the viral proteases.

[0273] This document also provides for the use of the disclosed compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the treatment or prevention of viral infections in persons in need. For example, this document provides for the use of the disclosed compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the treatment of viral infections in persons in need.

[0274] This document also provides for the use of the disclosed compounds or pharmaceutically acceptable salts thereof or pharmaceutical compositions thereof in the manufacture of medicaments for the treatment or prevention of viral infections in persons in need.

[0275] This article also provides a method for manufacturing a medicament for treating or preventing viral infections in people in need, characterized by using a compound disclosed herein or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof.

[0276] This article also provides compositions comprising the compounds disclosed herein or pharmaceutically acceptable salts thereof or pharmaceutical compositions thereof, for use in treating or preventing viral infections in persons in need.

[0277] In some embodiments, the viral infection is a coronavirus infection in a person in need, wherein the method includes administering the compound provided herein to that person. In some embodiments, the 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), or zoonotic coronaviruses (PEDV or HKU CoV isolates, such as HKU3, HKU5, or HKU9). 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 with a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, viral infection is caused by a virus having at least 80% sequence homology with a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, viral infection is caused by a virus having at least 90% sequence homology with a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, viral infection is caused by a virus having at least 95% sequence homology with a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

[0278] In some embodiments, viral infection is caused by a variant of SARS-CoV-2, such as variant B.1.1.7 (UK variant), variant B.1.351 (South African variant), variant P.1 (Brazilian variant), variants B.1.1.7 and E484K, variant B.1.1.207, variant B.1.1.317, variant B.1.1.318, variant B.1.429, variant B.1.525, or variant P.3. In some embodiments, viral infection is caused by variant B.1.1.7 of SARS-CoV-2. In some embodiments, viral infection is caused by variant B.1.351 of SARS-CoV-2. In some embodiments, viral infection is caused by variant P.1 of SARS-CoV-2.

[0279] In some embodiments, this disclosure provides compounds for treating coronavirus infections in people in need. In some embodiments, the 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), and zoonotic coronaviruses (PEDV or HKU CoV isolates, such as HKU3, HKU5, or HKU9). 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 (COVID-19).

[0280] 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 adjunctive therapeutic agents. The adjunctive therapeutic agents can be administered to the infected individual simultaneously with, before, or after the administration of the compounds of this disclosure.

[0281] application One or more compounds of this disclosure may be administered via any route suitable for the condition to be treated. Suitable routes include oral, rectal, inhalation, pulmonary, local (including buccal and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural). In some embodiments, the compounds disclosed herein are administered by inhalation or intravenous administration. In some embodiments, the compounds disclosed herein are administered orally. It should be understood that preferred routes may vary depending on, for example, the condition of the recipient.

[0282] In the methods of treating viral infections disclosed herein, the compounds of this disclosure can be administered at any time to persons who may have been exposed to the virus or who already have a viral infection. In some embodiments, the compounds of this disclosure can be administered prophylactically to persons who have been in contact with or are at risk of contact with persons who have been in ...

[0283] In some embodiments, the methods disclosed herein include event-driven administration of the disclosed compound or a pharmaceutically acceptable salt thereof to a subject.

[0284] As used herein, the terms “event-driven” or “event-driven administration” mean that a compound described herein (e.g., a compound of this disclosure) or a pharmaceutically acceptable salt thereof is administered (1) prior to an event that will expose an individual to a virus (or otherwise increase the individual’s risk of acquiring a viral infection) (e.g., 2 hours, 1 day, 2 days, 5 days, or 7 days or more prior to the event); and / or (2) during an event that will expose an individual to a virus (or otherwise increase the individual’s risk of acquiring a viral infection) (or more than one repeated event); and / or (3) after an event that will expose an individual to a virus (or otherwise increase the individual’s risk of acquiring a viral infection) (or after the final event in a series of repeated events). In some embodiments, event-driven administration is performed before the subject is exposed to a virus. In some embodiments, event-driven administration is performed after the subject is exposed to a virus. In some embodiments, event-driven administration is performed both before and after the subject is exposed to a virus.

[0285] In some embodiments, the methods disclosed herein involve administration, for example as pre-exposure prophylaxis (PrEP) and / or post-exposure prophylaxis (PEP), before and / or after an event that will expose an individual to a virus or otherwise increase the individual's risk of acquiring a viral infection. In some embodiments, the methods disclosed herein include pre-exposure prophylaxis (PrEP). In some embodiments, the methods disclosed herein include post-exposure prophylaxis (PEP).

[0286] In some implementations, the compound of this disclosure or a pharmaceutically acceptable salt thereof is administered to the subject prior to exposure to the virus.

[0287] In some implementations, the compound of this disclosure or a pharmaceutically acceptable salt thereof is administered to the subject before and after exposure to the virus.

[0288] In some implementations, the compound of this disclosure or a pharmaceutically acceptable salt thereof is administered to the subject after exposure to the virus.

[0289] Examples of event-driven dosing regimens include administering a compound of the present disclosure or a pharmaceutically acceptable salt thereof 24 to 2 hours before exposure to the virus, followed by administering a compound of the present disclosure or a pharmaceutically acceptable salt thereof every 24 hours during exposure, 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 B or a pharmaceutically acceptable salt thereof 24 hours later.

[0290] Another example of an event-driven dosing regimen involves administering the compound disclosed herein or a pharmaceutically acceptable salt thereof within 24 hours prior to viral exposure, followed by daily administration during exposure, and then a final administration approximately 24 hours after the last exposure (which may be an increased dose, such as a double dose).

[0291] The specific dose level of the compounds disclosed herein for any particular subject will depend on a variety of factors, including the activity of the specific compound used, the age, weight, general health condition, sex, diet, time of administration, route of administration and excretion rate, drug combination, and severity of the specific disease. For example, the dose may be expressed as milligrams (mg / kg) of the compound described herein per kilogram of subject body weight. A dose between about 0.1 mg / kg and 150 mg / kg may be appropriate. In some embodiments, a dose between about 0.1 mg / kg and 100 mg / kg may be appropriate. In other embodiments, a dose between 0.5 mg / kg and 60 mg / kg may be appropriate. Normalization based on the subject's weight is particularly useful when adjusting doses among subjects with large differences in size, such as when using the drug in children and adults, or when converting an effective dose for a non-human subject, such as a dog, to a dose suitable for a human subject.

[0292] The daily dose can also be described as the total amount of the compound described herein administered per dose or per day. The daily dose of the compounds disclosed herein or their pharmaceutically acceptable salts may be from about 1 mg to 4,000 mg, from about 2,000 mg / day to 4,000 mg / day, from about 1 mg / day to 2,000 mg / day, from about 1 mg / day to 1,000 mg / day, from about 10 mg / day to 500 mg / day, from about 20 mg / day to 500 mg / day, from about 50 mg / day to 300 mg / day, from about 75 mg / day to 200 mg / day, or from about 15 mg / day to 150 mg / day.

[0293] The dosage or frequency of administration of the disclosed compounds may be adjusted during treatment based on the judgment of the physician administering the medication.

[0294] The compounds disclosed herein can be administered in therapeutically effective amounts to an individual (e.g., a human). In some embodiments, the compounds are administered once daily.

[0295] The compounds provided herein may be administered by any useful route and means, such as by oral or parenteral (e.g., intravenous) administration. Therapeutic amounts of the compounds may include from about 0.00001 mg / kg body weight / day to about 10 mg / kg body weight / day, such as from about 0.0001 mg / kg body weight / day to about 10 mg / kg body weight / day, or such as from about 0.001 mg / kg body weight / day to about 1 mg / kg body weight / day, or such as from about 0.01 mg / kg body weight / day to about 1 mg / kg body weight / day, or such as from about 0.05 mg / kg body weight / day to about 0.5 mg / kg body weight / day. In some embodiments, therapeutic amounts of the compounds provided herein include from about 0.3 mg / day to about 30 mg / day, or from about 30 mg / day to about 300 mg / day, or from about 0.3 mg / day to about 30 mg / day, or from about 30 mg / day to about 300 mg / day.

[0296] The compounds disclosed herein may be combined with one or more additional therapeutic agents at any dose of the disclosed compounds (e.g., 1 mg to 1000 mg of the compound). Therapeuticly effective doses may include about 0.1 mg / dose to about 1000 mg / dose, such as about 50 mg / dose to about 500 mg / dose, or such as about 100 mg / dose to about 400 mg / dose, or such as about 150 mg / dose to about 350 mg / dose, or such as about 200 mg / dose to about 300 mg / dose, or such as about 0.01 mg / dose to about 100 mg / dose, or such as about 0.01 mg / dose to about 100 mg / dose, or such as about 0.1 mg / dose to about 100 mg / dose, or such as about 1 mg / dose to about 100 mg / dose, or such as about 1 mg / dose to about 100 mg / dose, or such as about 1 mg / dose to about 1000 mg / dose. Other therapeutically effective doses of the compounds disclosed herein 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 doses of the compounds disclosed herein are approximately 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, and 525 mg / dose. g / dose, 550mg / dose, 575mg / dose, 600mg / dose, 625mg / dose, 650mg / dose, 675mg / dose, 700mg / dose, 725mg / dose, 750mg / dose, 775mg / dose, 800mg / dose, 825mg / dose, 850mg / dose, 875mg / dose, 900mg / dose, 925mg / dose, 950mg / dose, 975mg / dose or approximately 1000mg / dose.

[0297] In some embodiments, the method described herein involves administering an initial daily dose of about 1 mg to 500 mg of the compound provided herein to a subject, 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, once a week, once every two weeks, once every three weeks, or once a month.

[0298] When administered orally, the total daily dose for human subjects may range from about 1 mg / day to 4,000 mg / day, from about 1 mg / day to 3,000 mg / day, from 1 mg / day to 2,000 mg / day, from about 1 mg / day to 1,000 mg / day, from about 10 mg / day to 500 mg / day, from about 50 mg / day to 300 mg / day, from about 75 mg / day to 200 mg / day, or from about 100 mg / day to 150 mg / day. In some implementations, the total daily dose for human subjects may be approximately 100 mg / day, 200 mg / day, 300 mg / day, 400 mg / day, 500 mg / day, 600 mg / day, 700 mg / day, 800 mg / day, 900 mg / day, 1000 mg / day, 1100 mg / day, 1200 mg / day, 1300 mg / day, or 1400 mg / day, administered as a single dose. The daily doses for human subjects may be approximately 200 mg / day, 300 mg / day, 400 mg / day, 500 mg / day, 600 mg / day, 700 mg / day, or 800 mg / day, administered as a single dose. In some embodiments, the total daily dose for human subjects may be approximately 300 mg / day, 400 mg / day, 500 mg / day, 600 mg / day, or 600 mg / day, administered as a single dose. In some implementations, the total daily dose for human subjects may be 100 mg / day, 200 mg / day, 300 mg / day, 400 mg / day, 500 mg / day, 600 mg / day, 700 mg / day, 800 mg / day, 900 mg / day, 1000 mg / day, 1100 mg / day, 1200 mg / day, 1300 mg / day, 1400 mg / day, 1500 mg / day, 1600 mg / day, 1700 mg / day, 1800 mg / day, 1900 mg / day, 200 mg / day, etc. 0 mg / day, 2100 mg / day, 2200 mg / day, 2300 mg / day, 2400 mg / day, 2500 mg / day, 2600 mg / day, 2700 mg / day, 2800 mg / day, 2900 mg / day, 3000 mg / day, 3100 mg / day, 3200 mg / day, 3300 mg / day, 3400 mg / day, 3500 mg / day, 3600 mg / day, 3700 mg / day, 3800 mg / day, 3900 mg / day, or 4000 mg / day.In some implementation schemes, the total daily dose for human subjects may be approximately 100-200 mg / day, 100-300 mg / day, 100-400 mg / day, 100-500 mg / day, 100-600 mg / day, 100-700 mg / day, 100-800 mg / day, 100-900 mg / day, 100-1000 mg / day, 500-1100 mg / day, 500-1200 mg / day, 500-1300 mg / day, 500-1400 mg / day, 500-1500 mg / day, 500-1600 mg / day, 500-1700 mg / day, 500-1800 mg / day, 500-1900 mg / day, 500-2000 mg / day, or 1500-2100 mg / day. mg / day, 1500-2200mg / day, 1500-2300mg / day, 1500-2400mg / day, 1500-2500mg / day, 2000-2600mg / day, 2000-2700mg / day, 2000-2800mg / day, 2000-2900mg / day, 2000-3000mg / day, 2500mg / day -3100mg / day, 2500-3200mg / day, 2500-3300mg / day, 2500-3400mg / day, 2500-3500mg / day, 3000-3600mg / day, 3000-3700mg / day, 3000-3800mg / day, 3000-3900mg / day, or 3000-4000mg / day.

[0299] In some embodiments, the total daily dose for a human subject may be about 100 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 150 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 200 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 250 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 300 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 350 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 400 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 450 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 500 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 550 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 600 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 650 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 700 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 750 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 800 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 850 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 900 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 950 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 1000 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 1500 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 2000 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 2500 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 3000 mg / day, administered as a single dose. In some embodiments, the total daily dose for a human subject may be about 4000 mg / day, administered as a single dose.

[0300] A single dose may be administered hourly, daily, weekly, or monthly. For example, a single dose may be administered every 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, or every 24 hours. A single dose may also be administered every 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or every 7 days. A single dose may also be administered every 1 week, 2 weeks, 3 weeks, or every 4 weeks. In some embodiments, a single dose may be administered weekly. A single dose may also be administered monthly. In some embodiments, the compounds disclosed herein are administered once daily using the methods disclosed herein. In some embodiments, the compounds disclosed herein are administered twice daily using the methods disclosed herein. In some embodiments, the compounds disclosed herein are administered three times daily using the methods disclosed herein.

[0301] 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.

[0302] The frequency of dosage of the disclosed compound will be determined by the individual patient's needs and may be, for example, once daily or twice daily or more. Administration of the compound will continue as long as treatment of the viral infection is required. For example, the compound may be administered to a person infected with the virus for a period of 20 to 180 days, or for a period of, for example, 20 to 90 days, or for example, 30 to 60 days.

[0303] Administration may be intermittent, with the patient receiving a daily dose of the disclosed compound over periods of several days or more, followed by periods without receiving the same daily dose. For example, the patient may receive a dose of the compound every other day or three times a week. Again, by way of example, the patient may receive a daily dose of the compound over periods of 1 to 14 days, followed by periods without receiving the compound over periods of 7 to 21 days, and then receive a daily dose of the compound again over subsequent periods (e.g., 1 to 14 days). The alternating periods of compound administration followed by non-administration may be repeated as needed to treat the patient's clinical needs.

[0304] The compounds or pharmaceutical compositions thereof disclosed herein may be administered once, twice, three times, or four times daily in any of the suitable modes described above. Furthermore, administration of the compound or treatment may continue for multiple days; for example, for a treatment cycle, treatment typically continues for at least 7, 14, or 28 days. Treatment cycles may alternate with rest periods of approximately 1 to 28 days, typically approximately 7 or 14 days, between cycles. In other embodiments, treatment cycles may also be continuous.

[0305] Combination therapy The compounds described herein can also be used in combination with one or more additional therapeutic agents. Therefore, this document also provides methods for treating viral infections in subjects in need, wherein these methods include administering to the subject the disclosed compounds and a therapeutically effective amount of one or more additional therapeutic or prophylactic agents.

[0306] In some implementations, the additional treatment is an antiviral agent. Any suitable antiviral agent can be used in the methods described herein.

[0307] In some implementations, the adjunctive therapeutic agents are 2,5-oligoadenylate synthase stimulators, 5-HT 2a receptor antagonists, 5-lipoxygenase inhibitors, ABL family tyrosine kinase inhibitors, Abl tyrosine kinase inhibitors, aldehyde dehydrogenase inhibitors, acetyl-CoA carboxylase inhibitors, actin antagonists, actin modulators, activity-dependent neuroprotective modulators, adenosine A3 receptor agonists, adrenergic receptor antagonists, adrenal medullary ligands, adrenal medullary ligand inhibitors, late glycosylation product receptor antagonists, late glycosylation product receptor modulators, AKT protein kinase inhibitors, alanine-proline-rich secretory protein stimulators, aldose reductase inhibitors, alkaline phosphatase stimulators, α2-adrenergic receptor antagonists, α2B-adrenergic receptor agonists, AMP-activated protein kinase stimulators, AMPA receptor modulators, amyloid deposition inhibitors, androgen receptor antagonists, and 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. Inhibitors, anticoagulants, antihistamines, antihyperxia agents, antithrombotic agents, AP1 transcription factor regulators, apralin receptor agonists, APOA1 gene stimulators, apolipoprotein A1 agonists, apolipoprotein B antagonists, apolipoprotein B regulators, apolipoprotein C3 antagonists, aryl hydrocarbon receptor agonists, aryl hydrocarbon receptor antagonists, ATP-binding cassette transporter B5 regulators, Axl tyrosine kinase receptor inhibitors, bactericidal permeability-increasing protein inhibitors, basigin inhibitors, basigin regulators, BCL2 gene inhibitors, BCL2L11 gene stimulators, Bcr protein inhibitors, β1-adrenergic receptor regulators, β2-adrenergic receptor agonists, β-adrenergic receptor agonists, β-inhibitory protein stimulators, coagulation regulators, BMP10 gene inhibitors, BMP15 gene inhibitors. Due to inhibitors, including bone morphogenetic protein-10 ligand inhibitors, bone morphogenetic protein-15 ligand inhibitors, bradykinin B2 receptor antagonists, brain-derived neurotrophic factor ligands, bromine-domain-containing protein 2 inhibitors, bromine-domain-containing protein 4 inhibitors, Btk tyrosine kinase inhibitors, C-reactive protein modulators, Ca2+ release-activated Ca2+ channel 1 inhibitors, cadherin-5 modulators, calcium-activated chloride channel inhibitors, calcium channel modulators, calpain-I inhibitors, calpain-II inhibitors, calpain-IX inhibitors, cannabinoid CB2 receptor agonists, cannabinoid receptor modulators, casein kinase II inhibitors, CASP8-FADD-like regulatory factor inhibitors, caspase inhibitors, catalase stimulators, CCL26 gene inhibitors, and CCR2 chemokine antagonists.CCR5 chemokine antagonists, 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 enterotoxin subunit B inhibitors, cholesterol ester transporter inhibitors, collagen modulators. Complement C1s subfraction inhibitors, complement C3 inhibitors, complement C5 factor inhibitors, complement C5a factor inhibitors, complement factor H stimulants, 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, COVID-19 envelope small membrane protein modulators, COVID-19 non-structural protein 8 modulators, COVID-19 nucleoprotein modulators, COVID-19 protein 3a inhibitors, CO COVID-19 replicase polyprotein 1a inhibitor, COVID-19 replicase polyprotein 1a modulator, COVID-19 replicase polyprotein 1ab inhibitor, COVID-19 replicase polyprotein 1ab modulator, COVID-19 spike glycoprotein inhibitor, COVID-19 spike glycoprotein modulator, COVID-19 structural glycoprotein modulator, CRF-2 receptor agonist, CSF-1 agonist, CSF-1 antagonist, CX3CR1 chemokine antagonist, CXC10 chemokine ligand inhibitor, CXC5 chemokine ligand inhibitor, CXCL1 gene modulator CXCL2 gene regulators, CXCL3 gene regulators, 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 P450. 3A4 inhibitors, cytokine receptor antagonists, cytotoxic T lymphocyte protein gene modulators, cytotoxic T lymphocyte protein-4 inhibitors, cytotoxic T lymphocyte protein-4 stimulators, dehydrogenase inhibitors, dehydropeptidase-1 modulators, deoxyribonuclease I stimulators, deoxyribonuclease gamma stimulators, deoxyribonuclease stimulators, dihydroceramide δ4 dehydrogenase 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 regulators, endoplasmic reticulum regulators, endonuclease DICER regulators, endothelin ET-A receptor antagonists, epidermal growth factor receptor antagonists, estrogen receptor β agonists, estrogen receptor regulators, eukaryotic initiation factor 4A-I inhibitors, exo-α-sialidase regulators, export protein 1 inhibitors, factor Ia regulators, factor IIa regulators, factor VII antagonists, factor Xa antagonists, factor XIa 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 protease inhibitors, Fyn tyrosine kinase inhibitors, FYVE (phosphatidylinositol kinase inhibitors), G protein-coupled bile acid receptor 1 agonists, GABA Alpha receptor modulators, galactoglobulin-3 inhibitors, gamma-secretase inhibitors, GDF agonists, colloid stimulants, glial cell neurotrophic factor ligands, glucocorticoid receptor agonists, glutathione peroxidase stimulants, GM-CSF ligand inhibitors, GM-CSF receptor agonists, GM-CSF receptor modulators, Griffithsin modulators, growth regulator protein α-ligand inhibitors, Grp78 calcium-binding protein inhibitors, heat shock protein HSP90α inhibitors, heat shock protein HSP90β inhibitors Inhibitors, heat shock protein inhibitors, heat shock protein stimulants, hemagglutinin modulators, hemoglobin modulators, hemolysin α inhibitors, heparanase 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 box B1 inhibitors, histamine H1 receptor antagonists, histamine H2 receptor antagonists, histone deacetylase-6 inhibitors, histone inhibitors, HIV protease inhibitors, HIV-1 gp120 protein inhibitor, HIV-1 protease inhibitor, HIV-1 reverse transcriptase inhibitor, HLA class I antigen modulator, HLA class II antigen modulator, host cytokine modulator, Hsp90 inhibitor, human papillomavirus E6 protein modulator, human papillomavirus E7 protein modulator, hypoxia-inducible factor inhibitor gene inhibitor, hypoxia-inducible factor-2α modulator, I-κB kinase inhibitor, I-κB kinase modulator, ICAM-1 stimulator, IgG receptor FcRn large subunit p51 modulator, IL-12 receptor antagonist, IL-15 receptor agonist, IL-15 receptor modulator.IL-17 antagonists, IL-18 receptor cofactor 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, IL-12 gene stimulators, IL-8 gene modulators, immunoglobulin G modulators, immunoglobulin G1 agonists, immunoglobulin G1 modulators, immunoglobulin agonists, immunoglobulin γFc receptor I modulators, immunoglobulin κ modulators, inosine monophosphate dehydrogenase inhibitors, insulin sensitizers, integrin agonists, integrin α-4 / β-7 antagonists, integrin α-V / β-1 antagonists, integrin α-V / β-6 antagonists, interferon agonists, interferon α14 ligands, interferon α2 ligands, interferon... Interleukin α2 ligand modulators, interleukin α ligands, interleukin α ligand inhibitors, interleukin α ligand modulators, interleukin β ligands, interleukin γ ligand inhibitors, interleukin γ receptor agonists, interleukin γ receptor antagonists, interleukin receptor modulators, interleukin type I receptor agonists, interleukin 17A ligand inhibitors, interleukin 17F ligand inhibitors, interleukin 18 ligand inhibitors, interleukin 22 ligands, interleukin-1β ligand inhibitors, interleukin-1β 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-associated protein 1 modulators, Kit tyrosine kinase inhibitors, KLKB1 gene inhibitors, lactoferrin stimulants, 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, Listeria hemolysin stimulants, liver X receptor antagonists, low molecular weight heparin, lung surfactant-associated protein B stimulants, lung surfactant-associated protein D modulators, Lyn tyrosine kinase inhibitors, Lyn tyrosine kinase stimulants, lysine-specific histone demethylase 1 inhibitors, macrophage migration 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 Potassium K channel inhibitors, MCL1 gene inhibitors, MEK protein kinase inhibitors, MEK-1 protein kinase inhibitors, melanocortin MC1 receptor agonists, melanocortin MC3 receptor agonistsMetalloproteinase-12 inhibitors, METTL3 gene inhibitors, membrane spike protein inhibitors, membrane spike protein modulators, monocyte chemotactic protein 1 ligand inhibitors, monocyte differentiation antigen CD14 inhibitors, mRNA guanine N7 methyltransferase modulators, mTOR complex 1 inhibitors, mTOR complex 2 inhibitors, mTOR inhibitors, mucoprotein modulators, muscarinic receptor antagonists, myeloperoxidase inhibitors, NACHT LRRPYD domain protein 3 inhibitors, NAD synthase regulators, NADPH oxidase inhibitors, neurocilia protein 2 regulators, neuroplastic 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, nucleoside erythroid 2-related factor 2 stimulators, nuclear factor κB inhibitors, nuclear factor κB regulators, nuclease stimulators, nucleolarine inhibitors, nucleoprotein inhibitors, nucleoprotein regulators, nucleoside reverse transcriptase inhibitors, opioid receptor agonists, opioid receptor μ regulators, opioid receptor σ antagonists, ornithine decarboxylase inhibitors, outer membrane protein inhibitors, OX40 ligands, p38 MAP kinase α 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 α antagonists, PDGF receptor antagonists, PDGF receptor β antagonists, peptidyl prolyl cis-trans isomerase A inhibitors, peroxidase 6 modulators, PGD2 antagonists, PGI2 agonists, P-glycoprotein inhibitors, phosphoinositol 3-kinase inhibitors, phosphoinositol-3-kinase δ inhibitors, phosphoinositol-3-kinase γ 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 modulators, 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 responsive protein 2 stimulators, Rev protein modulators, 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, CD24 signal transducer 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-1- Phosphoceptor-1 antagonists, sphingosine-1-phosphate receptor-1 modulators, sphingosine-1-phosphate receptor-5 agonists, sphingosine-1-phosphate receptor-5 modulators, spike glycoprotein inhibitors, Src tyrosine kinase inhibitors, STAT-1 modulators, STAT-3 inhibitors, STAT-5 inhibitors, STAT3 gene inhibitors, stem cell antigen-1 inhibitors, interferon gene stimulators, sulfatase inhibitors, superoxide dismutase modulators, superoxide dismutase stimulators, Syk tyrosine kinase inhibitors, T-cell immune receptor 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, anchoring polymerase-1 inhibitors, anchoring polymerase-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 modulators, transketolase inhibitors, translocation-related protein inhibitors, transmembrane serine protease 2 inhibitors, thyroxine transporter modulators, TREM receptor 1 antagonists, TRP cation channel C1 modulators, 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, ubiquinone cytochrome C reductase 14 kDa inhibitors.Ubiquitin ligase modulators, unspecified GPCR agonists, unspecified cytokine receptor modulators, unspecified enzyme stimulators, unspecified gene inhibitors, unspecified receptor modulators, urokinase plasminogen activator inhibitors, vascular cell adhesion protein 1 agonists, vasodilators, VEGF ligand inhibitors, VEGF receptor antagonists, VEGF-1 receptor antagonists, VEGF-1 receptor modulators, VEGF-2 receptor antagonists, VEGF-3 receptor antagonists, vimentin inhibitors, vimentin modulators, VIP receptor agonists, viral envelope protein inhibitors, viral protease inhibitors, viral protease modulators, viral protein target modulators, viral ribonuclease inhibitors, viral structural protein modulators, vitamin D3 receptor agonists, X-linked apoptosis inhibitor protein inhibitors, xanthine oxidase inhibitors, or ligand inhibitors.

[0308] In some embodiments, the compounds and compositions of this disclosure may be administered in combination with Sars-Cov-2 treatments such as parenteral fluids (including glucose 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).

[0309] In some implementations, the adjunctive treatment is an Abl tyrosine kinase inhibitor, such as ladotinib or imatinib.

[0310] In some implementations, the additional therapeutic agent is an acetaldehyde dehydrogenase inhibitor, such as ADX-629.

[0311] In some implementations, the additional therapeutic agent is an adenosine A3 receptor agonist, such as piclidenoson.

[0312] In some implementations, the additional therapeutic agent is an adrenomedullin ligand, such as adrenomedullin.

[0313] In some implementations, the additional therapeutic agent is a p38 MAPK + PPAR γ agonist / insulin sensitizer, such as KIN-001.

[0314] In some implementations, the additional therapeutic agent is an aldose reductase inhibitor, such as cabifrestat.

[0315] In some implementations, the additional therapeutic agent is an AMPA receptor modulator, such as traneurocin.

[0316] In some implementations, the additional therapeutic agent is an annexin A5 stimulant, such as AP-01 or SY-005.

[0317] In some implementations, the adjunctive therapeutic agent is an anticoagulant, such as heparin (heparin and low molecular weight heparin), aspirin, apixaban, dabigatran, edoxaban, argatroban, enoxaparin, or fondaparin.

[0318] In some implementations, the adjunctive therapeutic agent is an androgen receptor antagonist, such as bicalutamide, enzalutamide, or proxalutamide.

[0319] In some implementations, the additional treatment is an anti-hypoxia drug, such as disodium crocin.

[0320] In some implementations, the adjunctive therapeutic agent is an antithrombotic agent, such as defibrinoside, rivaroxaban, alteplase, tirofiban, clopidogrel, prasugrel, bemiparin, bivalirudin, sulodexide, or tenecteplase.

[0321] In some implementations, the additional treatment is an antihistamine, such as clopidogrel or clomaste.

[0322] In some implementations, the additional therapeutic agent is an apolipoprotein A1 agonist, such as CER-001.

[0323] In some implementations, the additional therapeutic agent is a phospholipase A2 inhibitor, such as icosapentaenoic acid ethyl.

[0324] In some implementations, the additional therapeutic agent is an axl tyrosine kinase receptor inhibitor, such as besentinib.

[0325] In some implementations, the adjunctive treatment is a corticosteroid / β2-adrenergic receptor agonist, such as budesonide plus formoterol fumarate.

[0326] In some implementations, the additional therapeutic agent is a BET bromide domain inhibitor / APOA1 gene stimulator, such as apabetalone.

[0327] In some implementations, the adjunctive therapeutic agent is a blood coagulation modifier, such as lanaruzumab.

[0328] In some implementations, the additional therapeutic agent is a bradykinin B2 receptor antagonist, such as ateband.

[0329] In some implementations, the adjunctive therapeutic agent is an EGFR gene inhibitor / Btk tyrosine kinase inhibitor, such as abivertinib.

[0330] In some implementations, the adjunctive treatment is a Btk tyrosine kinase inhibitor, such as ibrutinib or zanubrutinib.

[0331] In some implementations, the additional therapeutic agent is a calpain-I / II / IX inhibitor, such as BLD-2660.

[0332] In some implementations, the additional therapeutic agent is a Ca2+ release-activating Ca2+ channel 1 inhibitor, such as zegocractin (CM-4620).

[0333] In some implementations, the additional therapeutic agent is a cadherin-5 modulator, such as FX-06.

[0334] In some implementations, the additional therapeutic agent is a casein kinase II inhibitor, such as silicataserb.

[0335] In some implementations, the additional therapeutic agent is a caspase inhibitor, such as emricasan.

[0336] In some implementations, the additional therapeutic agent is a catalase stimulator / superoxide dismutase stimulator, such as MP-1032.

[0337] In some implementations, the additional therapeutic agent is a CCR2 chemokine antagonist / CCR5 chemokine antagonist, such as cineviro.

[0338] In some implementations, the additional therapeutic agent is a CCR5 chemokine antagonist, such as maraviro.

[0339] In some implementations, the additional therapeutic agent is a CD122 agonist / IL-2 receptor agonist, such as beempegaldesleukin.

[0340] In some implementations, the additional therapeutic agent is a CD73 agonist / interferon beta ligand, such as FP-1201.

[0341] In some implementations, the additional therapeutic agent is a cholesterol ester transporter inhibitor, such as dacetropeptide.

[0342] In some implementations, the additional therapeutic agent is a mannan-binding lectin serine protease / complement C1s subcomponent inhibitor / myeloperoxidase inhibitor, such as RLS-0071.

[0343] In some implementations, the additional therapeutic agent is a complement C5 factor inhibitor / leukotriene BLT receptor antagonist, such as nomacopan.

[0344] In some implementations, the adjunctive treatment is a complement factor C5 inhibitor, such as zilucoplan.

[0345] In some implementations, the additional therapeutic agent is a CXCR4 chemokine antagonist, such as motixafotide.

[0346] In some implementations, the adjunctive therapeutic agent is a cytochrome P450 3A4 inhibitor / peptidyl prolyl cis-trans isomerase A inhibitor, such as arapovir.

[0347] In some implementations, the additional therapeutic agent is a cysteine ​​protease inhibitor, such as SLV-213.

[0348] In some implementations, the additional treatment agent is a dihydroorotate dehydrogenase inhibitor, such as brequinar, RP-7214, or emvododstat.

[0349] In some implementations, the additional therapeutic agent is a dehydropeptidase-1 modulator, such as Metablok.

[0350] In some implementations, the additional treatment is a dihydroorotate dehydrogenase inhibitor / IL-17 antagonist, such as vidofluradim.

[0351] In some implementations, the additional therapeutic agent is a diuretic, such as an aldosterone antagonist, such as spironolactone.

[0352] In some implementations, the additional therapeutic agent is a deoxyribonuclease I stimulator, such as GNR-039 or dornase alfa.

[0353] In some implementations, the additional treatment agent is a NET inhibitor, such as NTR-441.

[0354] In some implementations, the additional therapeutic agent is a dihydroceramide δ4 desaturase inhibitor / sphingosine kinase 2 inhibitor, such as opaganib.

[0355] In some implementations, the additional therapeutic agent is a DNA methyltransferase inhibitor, such as azoxymidine.

[0356] In some implementations, the additional treatment agent is an LXR antagonist, such as larsucosterol.

[0357] In some implementations, the additional therapeutic agent is a dipeptidyl peptidase I inhibitor, such as brensocatib.

[0358] In some implementations, the additional therapeutic agent is an extension factor 1 α2 regulator, such as privitin.

[0359] In some implementations, the adjunctive therapeutic agent is a eukaryotic initiation factor 4A-I inhibitor, such as zotatifin.

[0360] In some implementations, the additional therapeutic agent is an exocrine α-sialidase modulator, such as DAS-181.

[0361] In some implementations, the additional therapeutic agent is an export protein 1 inhibitor, such as selinexor.

[0362] In some implementations, the additional therapeutic agent is a fractalkine ligand inhibitor, such as KAND-567.

[0363] In some implementations, the additional therapeutic agent is an FYVE finger phosphoinositol kinase inhibitor / IL-12 receptor antagonist / IL-23 antagonist, such as apimod dimethylsulfonate.

[0364] In some implementations, the additional therapeutic agent is a GABA A receptor modulator, such as brinolone.

[0365] In some implementations, the adjunctive therapeutic agent is a glucocorticoid receptor agonist, such as ccyclosone, hydrocortisone, dexamethasone, dexamethasone phosphate, or 101-PGC-005.

[0366] In some implementations, the additional therapeutic agent is a GM-CSF receptor agonist, such as saxaglastine.

[0367] In some implementations, the additional therapeutic agent is a GPCR agonist, such as esuberaprostsodium.

[0368] In some implementations, the additional therapeutic agent is a Griffithsin modulator, such as Q-Griffithsin.

[0369] In some implementations, the additional therapeutic agent is a leukotriene D4 antagonist, such as montelukast.

[0370] In some implementations, the additional therapeutic agent is a histamine H1 receptor antagonist, such as ebastine, tranilast, or levocetirizine hydrochloride.

[0371] In some implementations, the additional therapeutic agent is a histamine H2 receptor antagonist, such as famotidine.

[0372] In some implementations, the additional therapeutic agent is a heat shock protein stimulator / insulin sensitizer / PARP inhibitor, such as BGP-15.

[0373] In some implementations, the additional therapeutic agent is a histone inhibitor, such as STC-3141.

[0374] In some implementations, the additional therapeutic agent is a histone deacetylase-6 inhibitor, such as CKD-506.

[0375] In some implementations, the additional treatment agent is a HIF prolyl hydroxylase-2 inhibitor, such as dedustat.

[0376] In some implementations, the additional treatment agent is a HIF prolyl hydroxylase inhibitor, such as valdustat.

[0377] In some implementations, the additional treatment agent is an IL-8 receptor antagonist, such as reparixin.

[0378] In some implementations, the additional therapeutic agent is an IL-7 receptor agonist, such as CYT-107.

[0379] In some implementations, the additional therapeutic agent is an IL-7 receptor agonist / interleukin-7 ligand, such as efineptakin alfa.

[0380] In some implementations, the additional therapeutic agent is an IL-22 agonist, such as efmarodocokin alfa.

[0381] In some implementations, the additional therapeutic agent is an IL-22 agonist / interleukin-22 ligand, such as F-652.

[0382] In some implementations, the additional therapeutic agent is an integrin α-V / β-1 antagonist / integrin α-V / β-6 antagonist, such as bexotegrast.

[0383] In some implementations, the additional therapeutic agent is an interferon alpha2 ligand, such as interferon alpha-2b or Virafin.

[0384] In some implementations, the additional therapeutic agent is an interferon β ligand, such as a follow-up biologic to interferon β-1a, interferon β-1b, or SNG-001.

[0385] In some implementations, the additional therapeutic agent is an interferon receptor modulator, such as peginterferon lambda-1a.

[0386] In some implementations, the additional therapeutic agent is an interleukin-2 ligand, such as adeleukin.

[0387] In some implementations, the additional treatment is an IRAK-4 protein kinase inhibitor, such as zimlovisertib.

[0388] In some implementations, the adjunctive therapy is a JAK inhibitor, such as baricitinib, filgortinib, jaktinib, tofacitinib, or nezulcitinib (TD-0903).

[0389] In some implementations, the additional therapeutic agent is a neutral leukocyte elastase inhibitor, such as avelestat.

[0390] In some implementations, the additional therapeutic agent is a lung surfactant-associated protein D modulator, such as AT-100.

[0391] In some implementations, the additional therapeutic agent is a plasma kallikrein inhibitor, such as donidalorsen.

[0392] In some implementations, the adjunctive therapeutic agent is a lysine-specific histone demethylase 1 / MAO B inhibitor, such as varifidestat.

[0393] In some implementations, the additional therapeutic agent is a mannan-binding lectin serine protease inhibitor, such as conestat alfa.

[0394] In some implementations, the additional therapeutic agent is a maxi K potassium channel inhibitor, such as ENA-001.

[0395] In some implementations, the adjunctive therapeutic agent is a MEK protein kinase inhibitor, such as zapnometinib.

[0396] In some implementations, the adjunctive therapeutic agent is a MEK-1 protein kinase inhibitor / Ras gene inhibitor, such as androidquinolol.

[0397] In some implementations, the additional therapeutic agent is a melanocortin MC1 receptor agonist, such as PL-8177.

[0398] In some implementations, the additional therapeutic agent is a matrix metalloproteinase-12 inhibitor, such as FP-025.

[0399] In some implementations, the additional therapeutic agent is a NACHT LRR PYD domain protein 3 inhibitor, such as dapansutrile, DFV-890, or ZYIL-1.

[0400] In some implementations, the additional therapeutic agent is an NADPH oxidase inhibitor, such as isuzinaxib.

[0401] In some implementations, the adjunctive therapeutic agent is a neuropilin 2 modulator, such as efzofitimod.

[0402] In some implementations, the additional therapeutic agent is an NK1 receptor antagonist, such as aprepitant or tripipitant.

[0403] In some implementations, the additional therapeutic agent is an NMDA receptor antagonist, such as crocin or fenfenidil.

[0404] In some implementations, the adjunctive therapeutic agent is a nuclear factor κB inhibitor / p38 MAP kinase inhibitor, such as zenuzolac.

[0405] In some implementations, the additional therapeutic agent is an ornithine decarboxylase inhibitor, such as efornithine.

[0406] In some implementations, the additional therapeutic agent is an opioid receptor σ antagonist, such as MR-309.

[0407] In some implementations, the additional therapeutic agent is a PGD2 antagonist, such as asapiprant.

[0408] In some implementations, the additional therapeutic agent is a PDGF receptor antagonist / TGFβ receptor antagonist / p38 MAP kinase inhibitor, such as deupirfenidone.

[0409] In some implementations, the additional therapeutic agent is a phospholipase A2 inhibitor, such as methylvarenaradil.

[0410] In some implementations, the adjunctive therapeutic agent is a phosphoinositol 3-kinase inhibitor / mTOR complex inhibitor, such as dactolisib.

[0411] In some implementations, the additional therapeutic agent is a phosphoinositol-3 kinase δ / γ inhibitor, such as duveliximab.

[0412] In some implementations, the additional therapeutic agent is a plasminogen activator inhibitor 1 inhibitor, such as TM-5614.

[0413] In some implementations, the additional therapeutic agent is a protein tyrosine phosphatase β inhibitor, such as ralotafine.

[0414] In some implementations, the additional therapeutic agent is a RIP-1 kinase inhibitor, such as DNL-758 or SIR-0365.

[0415] In some implementations, the additional therapeutic agent is a Rev protein modulator, such as obefazimod.

[0416] In some implementations, the adjunctive therapeutic agent is an S-phase kinase-associated protein 2 inhibitor, such as niclosamide or DWRX-2003.

[0417] In some implementations, the additional therapeutic agent is a CD24 signal transduction protein stimulator, such as EXO-CD24.

[0418] In some implementations, the additional therapeutic agent is a sodium glucose transporter-2 inhibitor, such as dapagliflozin propylene glycol.

[0419] In some implementations, the additional therapeutic agent is a sodium channel inhibitor, such as solnatide.

[0420] In some implementations, the additional therapeutic agent is a sphingosine-1-phosphate-1 agonist / sphingosine-1-phosphate-5 agonist, such as ozamod.

[0421] In some implementations, the adjunctive therapeutic agent is a nonsteroidal anti-inflammatory drug, such as Ampion.

[0422] In some implementations, the additional therapeutic agent is a superoxide dismutase agonist, such as avasopasem manganese.

[0423] In some implementations, the additional therapeutic agent is a Syk tyrosine kinase inhibitor, such as futtatinib disodium salt.

[0424] In some implementations, the additional therapeutic agent is a Tie2 tyrosine kinase receptor agonist, such as AV-001.

[0425] In some implementations, the adjunctive therapeutic agent is a TGFB2 gene inhibitor, such as trabedsen.

[0426] In some implementations, the adjunctive therapeutic agent is a tissue factor inhibitor, such as AB-201.

[0427] In some implementations, the additional treatment is a TLR-3 agonist, such as lentamod.

[0428] In some implementations, the additional treatment agent is a TLR-4 antagonist, such as ApTLR-4FT, EB-05, or iritolen.

[0429] In some implementations, the additional treatment is a TLR-7 / 8 antagonist, such as enpatoran.

[0430] In some implementations, the additional therapeutic agent is a TLR-2 / 6 agonist, such as INNA-051.

[0431] In some implementations, the additional therapeutic agent is a TLR-7 agonist, such as PRTX-007.

[0432] In some implementations, the additional therapeutic agent is a TLR agonist, such as PUL-042.

[0433] In some implementations, the additional therapeutic agent is a TLR-4 agonist, such as REVTx-99.

[0434] In some implementations, the additional therapeutic agent is a TLR-2 / 4 antagonist, such as VB-201.

[0435] In some implementations, the additional therapeutic agent is a TNF α ligand inhibitor, such as pegipanermin.

[0436] In some implementations, the additional therapeutic agent is a type I IL-1 receptor antagonist, such as anaspirin.

[0437] In some implementations, the additional therapeutic agent is a TREM receptor 1 antagonist, such as nangibotide.

[0438] In some implementations, the additional therapeutic agent is a trypsin inhibitor, such as ulinastatin.

[0439] In some implementations, the adjunctive therapeutic agent is a microtubule inhibitor, such as sabizabulin, CCI-001, PCNT-13, CR-42-24, albendazole, entabulin, SAR-132885, or ON-24160.

[0440] In some implementations, the additional therapeutic agent is a VIP receptor agonist, such as aviptadil.

[0441] In some implementations, the additional therapeutic agent is a xanthine oxidase inhibitor, such as hydroxypurine alcohol.

[0442] In some implementations, the adjunctive therapeutic agent is a vasodilator, such as iloprost, evoraprost (VentaProst), vazegepant, TXA-127, USB-002, ambesentan, nitric oxide nasal spray (NORS), pentoxifylline, propranolol, RESP301, sodium nitrite, or dipyridamole.

[0443] In some implementations, the additional therapeutic agent is a vitamin D3 receptor agonist, such as cholecalciferol.

[0444] In some implementations, the additional therapeutic agent is a zonulin inhibitor, such as larazotideacetate.

[0445] In some implementations, the additional therapeutic agent is a synthetic retinoic acid derivative, such as fenivel-Amin.

[0446] In some implementations, the additional therapeutic agent is a glucose metabolism inhibitor, such as WP-1122.

[0447] In some implementations, the adjunctive therapeutic agents are AT-H201, 2-deoxy-D-glucose, AD-17002, AIC-649, astodrimer, AZD-1656, spiramycin, bucilamine, budesonide, CNM-AgZn-17, codivir, methotrexate, DW-2008S (DW-2008), EDP-1815, EG-009A, Fabencov, Gamnonex, genistein, GLS-1200, hzVSF-v13, imidazolylacetamide glutaric acid, IMM-101, MAS-825, MRG-001, Nasitrol, Nylexa, OP-1 01, OPN-019, Orynotide (macrothecal defensin-1), phenazine + artesunate, dapsone, RPH-104, sodium pyruvate, Sulforadex, tafenoxine, TB-006, telacebec, Tempol, TL-895, thimerosal, trimodulin, XC-221, XC-7, zunsemetinib, glycine metformin, lucinactant, EOM-613, mosedimod, ivermectin, leflunomide, isobutylasteride, RBT-9, raloxifene, prothione, gemcabene, or idronoxil.

[0448] In some implementations, the additional treatment agent is a CD73 antagonist, such as AK-119.

[0449] In some implementations, the additional therapeutic agent is a CD95 protein fusion, such as asunercept.

[0450] In some implementations, the additional therapeutic agent is a complement factor C2 modulator, such as ARGX-117.

[0451] In some implementations, the additional treatment agent is a complement C3 inhibitor, such as NGM-621.

[0452] In some implementations, the additional therapeutic agent is a CXC10 chemokine ligand inhibitor, such as EB-06.

[0453] In some implementations, the adjunctive therapeutic agent is a cytotoxic T-lymphocyte protein-4 fusion protein, such as abatacept.

[0454] In some implementations, the adjunctive therapeutic agent is an anti-Staphylococcus aureus antibody, such as tosatoxumab.

[0455] In some implementations, the additional therapeutic agent is an anti-LPS antibody, such as IMM-124-E.

[0456] In some implementations, the adjunctive therapeutic agent is an adrenaline ligand inhibitor, such as embarreximab.

[0457] In some implementations, the additional treatment is a basigin inhibitor, such as meperizumab.

[0458] In some implementations, the adjunctive treatment is a CD3 antagonist, such as francirumab.

[0459] In some implementations, the adjunctive therapeutic agent is a connective tissue growth factor ligand inhibitor, such as perriluzumab.

[0460] In some implementations, the adjunctive therapeutic agent is a complement C5a factor inhibitor, such as BDB-1 or virolimab.

[0461] In some implementations, the adjunctive therapeutic agent is a complement factor C5 inhibitor, such as eculizumab.

[0462] In some implementations, the adjunctive therapeutic agent is a mannan-binding lectin serine protease-2 inhibitor, such as nasoribimab.

[0463] In some implementations, the adjunctive treatment is a GM-CSF modulator, such as netlimumab, namexilumab, punalimumab, otelilimumab, or lenzrumuzumab.

[0464] In some implementations, the adjunctive therapeutic agent is a heat shock protein inhibitor / IL-6 receptor antagonist, such as sutuximab.

[0465] In some implementations, the adjunctive therapeutic agent is an IL-6 receptor antagonist, such as clazazumab, levilimab, olokizumab, tocilizumab, or sirukumab.

[0466] In some implementations, the additional therapeutic agent is an IL-8 receptor antagonist, such as BMS-986253.

[0467] In some implementations, the additional therapeutic agent is an interleukin-1β ligand inhibitor, such as canakinumab.

[0468] In some implementations, the additional therapeutic agent is an interferon-gamma ligand inhibitor, such as epavamab.

[0469] In some implementations, the additional therapeutic agent is an anti-ILT7 antibody, such as daxdilimab.

[0470] In some implementations, the adjunctive therapeutic agent is a CD14 inhibitor, such as atibuclimab.

[0471] In some implementations, the additional therapeutic agent is a plasma kallikrein inhibitor, such as lanarumab.

[0472] In some implementations, the adjunctive treatment is a platelet glycoprotein VI inhibitor, such as glenzocimab.

[0473] In some implementations, the adjunctive therapeutic agent is a T-cell differentiation antigen CD6 inhibitor, such as itolizumab.

[0474] In some implementations, the adjunctive therapeutic agent is a TNF α ligand inhibitor / TNF binder, such as infliximab.

[0475] In some implementations, the additional therapeutic agent is an anti-LIGHT antibody, such as AVTX-002.

[0476] In some implementations, the additional treatment is COVID-HIG.

[0477] In some embodiments, the compounds disclosed herein or pharmaceutically acceptable salts thereof are co-administered with one or more agents that can be used to treat and / or prevent COVID-19.

[0478] Non-limiting examples of such agents include corticosteroids such as dexamethasone, hydrocortisone, methylprednisolone, or prednisone; interleukin-6 (IL-6) receptor blockers such as tocilizumab or thalidomab; Janus kinase (JAK) inhibitors such as baricitinib, ruxolitinib, or tofacitinib; and antiviral agents such as monopivir, sotromab, or remdesivir.

[0479] In another embodiment, the compounds of this disclosure or pharmaceutically acceptable salts thereof are co-administered with two or more agents that can be used to treat COVID-19. Agents that can be used to treat and / or prevent COVID-19 include, but are not limited to, the compounds of this disclosure and two additional therapeutic agents, such as nematvir and ritonavir, camrelizumab and edevimab, or ruxolitinib and tofacitinib.

[0480] In some embodiments, the adjunctive therapeutic agent is an antiviral agent. In some embodiments, the antiviral agent is an entry inhibitor. In some embodiments, the antiviral agent is a protease inhibitor. In some embodiments, the antiviral agent is an RNA polymerase inhibitor. In some embodiments, the adjunctive therapeutic agent is an RNA-dependent RNA polymerase (RdRp) inhibitor.

[0481] In some embodiments, the antiviral agent is selected from angiotensin-converting enzyme 2 inhibitors, angiotensin-converting enzyme 2 modulators, angiotensin-converting enzyme 2 stimulators, angiotensin II AT-2 receptor agonists, angiotensin II AT-2 receptor antagonists, angiotensin II receptor modulators, coronavirus nucleoprotein modulators, coronavirus small envelope protein modulators, coronavirus spike glycoprotein inhibitors, coronavirus spike glycoprotein modulators, COVID19 envelope small membrane protein inhibitors, COVID19 envelope small membrane protein modulators, and COVID19... MPro inhibitors, COVID19 nonstructural protein 8 modulators, COVID19 nucleoprotein inhibitors, 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, COVID19 spike glycoprotein modulators, COVID19 structural glycoprotein modulators, papain inhibitors, protease inhibitors, protease modulators, RNA polymerase inhibitors, RNA polymerase modulators, RNA-dependent RNA polymerase (RdRp) inhibitors, SARS coronavirus 3C protease-like inhibitors, 3CLpro / Mpro inhibitors, serine protease inhibitors, transmembrane serine protease 2 inhibitors, transmembrane serine protease 2 modulators, viral envelope protein inhibitors, viral protease inhibitors, viral protease modulators, viral protein target modulators, viral ribonuclease inhibitors, and viral structural protein modulators.

[0482] In some implementations, the adjunctive therapeutic agent is an entry inhibitor. For example, in some implementations, the adjunctive therapeutic agent is an ACE2 inhibitor, a fusion inhibitor, or a protease inhibitor.

[0483] In some implementations, the additional therapeutic agent is an angiotensin-converting enzyme 2 inhibitor, such as SBK-001.

[0484] In some implementations, the additional therapeutic agent is an angiotensin-converting enzyme 2 modulator, such as neumifil or JN-2019.

[0485] In some implementations, the additional therapeutic agent is an entry inhibitor, such as MU-UNMC-1.

[0486] In some implementations, the additional therapeutic agent is an angiotensin-converting enzyme 2 stimulator, such as alunase alfa.

[0487] In some implementations, the additional therapeutic agent is an angiotensin II AT-2 receptor agonist, such as VP-01.

[0488] In some implementations, the additional therapeutic agent is an ACE II receptor antagonist, such as DX-600.

[0489] In some implementations, the additional therapeutic agent is an angiotensin II receptor modulator, such as TXA-127.

[0490] In some implementations, the additional therapeutic agent is a transmembrane serine protease 2 modulator, such as BC-201.

[0491] In some implementations, the additional therapeutic agent is a viral envelope protein inhibitor, such as MXB-9 or MXB-004.

[0492] In some implementations, the adjunctive therapeutic agent is a vaccine. For example, in some implementations, the adjunctive therapeutic agent is a DNA vaccine, an RNA vaccine, a live attenuated vaccine, an inactivated vaccine (i.e., an inactivated SARS-CoV-2 vaccine), a therapeutic vaccine, a prophylactic vaccine, a protein-based vaccine, a viral vector vaccine, a cell vaccine, or a dendritic cell vaccine.

[0493] In some implementations, the adjunctive therapeutic agent is a vaccine, such as tozinameran, NVX-CoV2373, elasomeran, KD-414, Janssen COVID-19 vaccine, Vaxzevria, SCB-2019, AKS-452, VLA-2001, S-268019, MVC-COV1901, mRNA-1273.214, NVX-CoV2515, Covaxin, BBIBP-CorV, GBP-510, mRNA-1273.351 + mRNA-1273.617 (SARS-CoV-2 multivalent mRNA vaccine, COVID-19), Ad5-nCoV, Omicron-based COVID-19 vaccine (mRNA vaccine, COVID-19), SARS-CoV-2 protein subunit recombinant vaccine, Sputnik M, ZyCoV-D, and COVID-19. XWG-03, mRNA-1273.529, mRNA-1010, CoronaVac, AZD-2816, Sputnik V, inactivated SARS-CoV-2 vaccine (Vero cells, COVID-19), DS-5670, PHH-1V, INO-4800, UB-612, coronavirus vaccine (whole virus particles, inactivated / purified), ReCOV, MT-2766, ARCT-154, SP-0253, CORBEVAX, mRNA-1273.211, ZF-2001, Sputnik Light, recombinant protein vaccine (COVID-19 / SARS-CoV-2 infection), VSV vector-based vaccine targeting spike glycoprotein (COVID-19), VLA-2101, GRAd-COV2, VPM-1002, COViran Barekat, Ad5-nCoV-IH, ARCoV, Covax-19, Recombinant SARS-CoV-2 Vaccine (protein subunit / CHO cells, COVID-19), BBV-154, RAZI Cov Pars, COVID-19 Vaccine (inactivated / Vero cells / intramuscular, SARS-CoV-2 infection), COVID-19 Vaccine (inactivated, Vero cells / intramuscular), BNT-162b2s01, CIGB-66, mRNA-1273.617. Mycobacterium w, ERUCOV-VAC, AG-0301-COVID19, fakhravac, AV-COVID-19, peptide vaccine (COVID-19), Nanocovax, SARS-CoV-2 vaccine (inactivated / Vero cell / intramuscular, COVID-19), QAZCOVID-IN, S-875670 nasal vaccine, or BNT162b5.

[0494] In some embodiments, the adjunctive therapeutic agent is a protease inhibitor. For example, in some embodiments, the adjunctive therapeutic agent is a 3C-like cysteine ​​protease inhibitor (3CLpro, also known as the main protease, Mpro), a papain-like protease inhibitor (PLpro), a serine protease inhibitor, or a transmembrane serine protease 2 inhibitor (TMPRSS2).

[0495] In some implementations, the adjunctive treatment is a 3CLpro / Mpro inhibitor, such as CDI-873, GC-373, GC-376, PBI-0451, UCI-1, DC-402234, DC-402267, RAY-1216, MPI-8, SH-879, SH-580, EDP-235, VV-993, CDI-988, MI-30, nirmatrelvir, enstrelvir, ASC-11, EDDC-2214, SIM-0417, CDI-45205, COR-803, ALG-097111, TJC-642, CVD-0013943, epivacycline, cynarine, or prexasertib.

[0496] In some implementations, the additional therapeutic agent is a papain-like protease inhibitor (PLpro), such as SBFM-PL4 or GRL-0617.

[0497] In some implementations, the additional therapeutic agent is a SARS-CoV-2 helicase Nsp13 inhibitor, such as EIS-4363.

[0498] In some implementations, the additional therapeutic agents are the SARS-CoV-2 spike protein (S) and protease modulators, such as ENU-200.

[0499] In some implementations, the additional therapeutic agent is a protease inhibitor, such as ALG-097558 or MRX-18.

[0500] In some implementations, the adjunctive therapeutic agent is a serine protease inhibitor, such as upparstat, naphthostat, carmostat mesylate, naphthostat mesylate, or carmostat.

[0501] In some implementations, the additional therapeutic agent is a 3CLpro / transmembrane serine protease 2 inhibitor, such as SNB-01 or SNB-02.

[0502] In some implementations, the additional therapeutic agent is a viral protease inhibitor such as Pan-Corona, Cov-X, or benprodil.

[0503] In some embodiments, the adjunctive therapeutic agent is an RNA polymerase inhibitor. For example, in some embodiments, the adjunctive therapeutic agent is an RNA polymerase inhibitor, or an RNA-dependent RNA polymerase (RdRp) inhibitor.

[0504] In some implementations, the adjunctive therapeutic agent is an RNA-dependent RNA polymerase (RdRp) inhibitor, such as remdesivir, NV-CoV-2-R, NV-CoV-1-encapsulated remdesivir, GS-621763, GS-5245, GS-441524, DEP remdesivir, ATV-006, VV-116, LGN-20, CMX-521, and compounds disclosed in WO2022142477, WO2021213288, and WO2022047065.

[0505] In some implementations, the adjunctive treatment is an RNA polymerase inhibitor, such as monoupivir (EIDD-2801), favipiravir, bemnifosbuvir, sofosbuvir, ASC-10, or galidivir.

[0506] In some implementations, the additional treatment is a viral entry inhibitor, such as brilacidin.

[0507] In some implementations, the additional therapeutic agent is an antibody that binds to the coronavirus, such as an antibody that binds to SARS or MERS.

[0508] In some implementations, the adjunctive therapeutic agent is an antibody, such as a monoclonal antibody. For example, adjunctive therapeutic agents are antibodies against SARS-CoV-2, neutralizing nanobodies, antibodies targeting the SARS-CoV-2 spike protein, fusion proteins, multispecific antibodies, and antibodies capable of neutralizing SARS-CoV-2 (SARS-CoV-2 neutralizing antibodies).

[0509] In some implementations, the adjunctive therapeutic agent is an antibody that targets a specific site on ACE2. In some implementations, the adjunctive therapeutic agent is a peptide that targets the SARS-CoV-2 spike protein (S-protein).

[0510] In some implementations, the additional treatment is a SARS-CoV-2 virus antibody.

[0511] In some implementations, the antibody is ABBV-47D11, COVI-GUARD (STI-1499), C144-LS + C135-LS, DXP-604, JMB-2002, LY-CovMab, bamlanivimab (LY-CoV555), S309, SAB-185, etesevimab (CB6), COR-101, JS016, VNAR, VIR-7832 and / or sotramab (VIR-7831), camrelizumab + edevimab (REGN-COV2 or REGN10933 + RGN10987), BAT2020, BAT2019, 47D11, YBSW-015, or PA-001.

[0512] In some implementations, the additional treatment agent is STI-9199 (COVI-SHIELD) or AR-701 (AR-703 and AR-720).

[0513] In some implementations, the adjunctive treatment agents are BRII-196, BRII-198, ADG-10, ADG-20, ABP-300, BI-767551, CT-P63, JS-026, sotraza (GSK-4182136), tixagevimab + cilgavimab (AZD-7442), regdanvimab, SAB-301, AOD-01, plutavimab (COVI-AMG), 9MW-3311 (MW-33), DXP-593, BSVEQAb, and anti-SARS-CoV-2. IgY, COVID-EIG, CSL-760, REGN-3048-3051, SARS-CoV-2 monoclonal antibody (COVID-19, ADM-03820), enuzovimab (HFB-30132A), INM-005, SCTA01, TY-027, XAV-19, ambavirbinavir (amubarvimab) + romluse (romluse) Vimab), SCTA-01, bebtelovimab, beludavimab, IBI-O123, IGM-6268, FYB-207, REGN-14256, XVR-011, TB202-3, TB181-36, LQ-050, COVAB-36, MAD-0004J08, STI-2099 or ACV-200-17.

[0514] In some implementations, the adjunctive therapeutic agent is an engineered ACE-2-IgG1-Fc fusion protein that targets the SARS-CoV-2 RBD, such as EU-129 or a bivalent ACE2-IgG Fc zero fusion protein (SI-F019).

[0515] In some implementations, the additional therapeutic agent is an ACE2-Fc receptor fusion protein, such as HLX-71.

[0516] In some implementations, the additional treatment is ensovibep.

[0517] In some implementations, the additional therapeutic agent is SYZJ-001.

[0518] In some implementations, the adjunctive treatment is an HIV-1 protease inhibitor, such as ASC-09F (ASC-09 + ritonavir) or lopinavir + ritonavir.

[0519] In some implementations, the additional therapeutic agent is a non-nucleoside reverse transcriptase inhibitor, such as favirine.

[0520] In some implementations, the additional therapeutic agent is a nucleoside reverse transcriptase inhibitor, such as azvudine.

[0521] In some implementations, the adjunctive treatment agents are AbbV-990, NED-260, ALG-097431, ENOB-CV-01, EIS-10700, β-521, SIM-0417, molnupiravir, Pan-Corona, Tollovir, and nematradivir + ritonavir. ®Favipiravir, GC-376, Upamostat, LeSoleil-01, LeSoleil-02+, Benfovir, VV-116, VV-993, SNB-01, EDP-235, Cov-X, Ensetrelvir, MPI-8, Masatitinib, ALG-097558, ASC-11, PBI-0451, Naphamostat, Naphamostat Mesylate, CDI-45205, COR-803, ALG-097111, BC-2 01, SH-879, CDI-873, CDI-988, Remdesivir, NV-CoV-2-R, NV-CoV-1 encapsulated Remdesivir, NA-831+ Remdesivir, DEP Remdesivir, GS-621763, GS-5245, GLS-5310, Benifosbuvir, QLS-1128, ASC-10, SBFM-PL4, Carmostat Mesylate, UCI-1, DC-402234, Ebuselenium, SH-580, LeSoleil-01, LeSoleil-02+, MRX-18, MXB-9, MI-09, MI-3 0, SNB-02, TJC-642, ENU-200, CVD-0013943, GS-441524, bepridil, MXB-004, eracycline, GRL-0617, carmostat, GC-373, nitazoxanide, cinarin, precretin, RAY-1216, SACT-COVID-19, MP-18, EIDD-1931, EDDC-2214, nitric oxide, apabetalone, AnQlar, SBK-001, LQ-050, C G-SpikeDown, bamlanivimab, HLX-71, FYB-207, ensovibep, SYZJ-001, EU-129, neumifil, JN-2019, AR-701, vostesyl, PLM-402, PJS-539, CTB-ACE2, TB181-36, TB202-3, ABP-300, XVR-011, MU-UNMC-1, MU-UNMC-2, alunase alfa, VP-01, TRV-027, DX-600, TXA-127, mRNA-1273.214. Omicron-based COVID-19 vaccines, NVX-CoV2515, Toznamil, Elasomycin, Ad5-nCoV, BBIBP-CorV, CoronaVac, MVC-COV1901, NVX-CoV2373, Sotriamab, Sputnik V, Vaxzevria, ZF-2001, or ZyCoV-D.

[0522] Any compound of this disclosure can also be combined with one or more additional active therapeutic agents in a single dosage form for simultaneous or sequential administration to a patient. Combination therapy can be administered as a simultaneous or sequential regimen. When administered sequentially, the combination can be administered in two or more doses.

[0523] Co-administration of the compounds disclosed herein with one or more other active therapeutic agents generally means the simultaneous or sequential administration of the compounds disclosed herein and one or more other active therapeutic agents such that therapeutically effective amounts of the compounds disclosed herein and one or more other active therapeutic agents are present in the patient.

[0524] Co-administration includes administering a unit dose of the disclosed compound before or after administering a unit dose of one or more other active therapeutic agents, for example, administering the disclosed compound within seconds, minutes, or hours of administering one or more other active therapeutic agents. For example, a unit dose of the disclosed compound may be administered first, followed by a unit dose of one or more other active therapeutic agents over several seconds or minutes. Alternatively, a unit dose of one or more other therapeutic agents may be administered first, followed by a unit dose of the disclosed compound over several seconds or minutes. In some cases, it may be necessary to administer a unit dose of the disclosed compound first, followed by a unit dose of one or more other active therapeutic agents several hours (e.g., 1 to 12 hours). In other cases, it may be necessary to administer a unit dose of one or more other active therapeutic agents first, followed by a unit dose of the disclosed compound several hours (e.g., 1 to 12 hours).

[0525] Combination therapy can provide “synergistic” or “synergistic” effects, meaning that the combined effect of active ingredients is greater than the sum of the effects of using the compounds alone. Synergistic effects are achieved when the active ingredients are: (1) co-formulated and administered or delivered simultaneously in a combination formulation; (2) delivered alternately or in parallel as individual formulations; or (3) through some other protocol. Synergistic effects are achieved when delivered in alternating therapy, such as in separate tablets, pills, or capsules, or by different injection sequences in separate syringes. Generally, in alternating therapy, each active ingredient is administered in an effective dose sequentially (i.e., consecutively), while in combination therapy, two or more active ingredients are administered together in effective doses. A synergistic antiviral effect indicates that the antiviral effect is greater than the predicted additive effect of the individual compounds in the combination.

[0526] Reagent test kit This document also provides kits comprising the compounds disclosed herein, pharmaceutically acceptable salts thereof, stereoisomers, mixtures of stereoisomers, or tautomers. In some embodiments, the kits described herein may include labeling and / or instructions for use to treat a disease or condition in a subject (e.g., a human) in need of the compound. In some embodiments, the disease or condition is a viral infection.

[0527] In some embodiments, the kit may also include instructions for use of one or more additional therapeutic agents and / or the use of additional therapeutic agents in combination with the compounds described herein to treat a disease or condition of a subject in need (e.g., a person).

[0528] In some embodiments, the kits provided herein contain a single dose unit of the compound as described herein, or a pharmaceutically acceptable salt, racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, amorphous form, hydrate, or solvation thereof. Examples of single dose units may include pills, tablets, capsules, pre-filled syringes or syringes, IV bags, inhalers, nebulizers, etc., each comprising a therapeutically effective amount of the compound in question, or a pharmaceutically acceptable salt, racemate, enantiomer, diastereomer, tautomer, polymorph, pseudopolymorph, amorphous form, hydrate, or solvation thereof. In some embodiments, the kit may contain a single dose unit, and in other embodiments, multiple dose units are present, e.g., the number of dose units required for a specified regimen or cycle.

[0529] Articles of manufacture are also provided, comprising: the compound described herein or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, and a container. In some embodiments, the container for the article of manufacture is a vial, can, ampoule, pre-filled syringe, blister pack, can, canister, bottle, box, intravenous bag, inhaler, or nebulizer.

[0530] The invention will be described in more detail through specific embodiments. The following embodiments are provided for illustrative purposes and are not intended to limit the invention in any way. Those skilled in the art will readily recognize that various non-critical parameters can be changed or modified to produce substantially the same results.

[0531] Example Certain abbreviations and acronyms are used to describe experimental details. Although most of these abbreviations and acronyms are understandable to those skilled in the art, Table 1 contains a list of many of these abbreviations and acronyms.

[0532] Table 1. List of Abbreviations and Acronyms

[0533] I. Intermediates Intermediate I-1 Methyl 3-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)furan-2-carboxylate: Methyl 3-amino-5-bromofuran-2-carboxylate (500 mg, 3.5 mmol), bis(pinacol)diboron (630 mg, 2.5 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (9.5 mg, 0.04 mmol), and (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (12 mg, 0.02 mmol) were added to a microwave-safe vial. The solids were suspended in Me-THF (10 mL). The mixture was bubbled with argon, sealed, and heated to 80 °C overnight. The mixture was cooled to room temperature, filtered through diatomaceous earth, washed w...

Claims

1. A compound of formula (I): I Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, Each X 4 and X 5 Independently N or C; Alternatively, choose a location, surrounding It does not exist, where X 4 For N or CL x4 -R x4 And X 5 For N or CL x5 -R x5 ; Each L x4 and L x5 Independently 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)-; Each R x4 and R x5 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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; Where R x4 and R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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, Where R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 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 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 Independently 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)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl groups, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2 or -OC 3-8 cycloalkyl; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to four R groups. 3a replace; Each R 3a Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 1-6 (halogenated alkyl)2, -N(C) 3-8 cycloalkyl)2, -N(C 1-6 Alkyl)(C 1-6 Halogenated alkyl), -N(C) 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heteroaryl groups), -C(O) (5- to 10-membered heterocyclic groups), -C(O) (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -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 heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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, Where R 3a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 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 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic groups), -O (C 6-10 aryl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -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 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -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 Independently hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-8 cycloalkyl; n is an integer from 0 to 3; Each X 6 and X 7 Independently N, CH or CF, Where X 4 X 5 X 6 and X 7 The two numbers in the range do not exceed N; ring C 6-10 Aryl or 5- to 10-membered heteroaryl groups; Each L 1 Independently for the key, -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 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Alternatively, two R locations 1 With the rings to which they are attached The atoms come together to form an optional combination of one to three R atoms. 1a Replacement of 5- to 10-membered heterocyclic groups; Each R 1a Independently for C 1-6 Alkyl, halogen, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl, oxo, -OH, -CN, -NH2, O(C 1-6 alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic), -NH (phenyl), -NH (5- to 10-membered heteroaryl), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2, -N(5- to 10-membered heterocyclic)2, -N(phenyl)2, -N(5- to 10-membered heteroaryl)2, -N(C 1-6 Alkyl)(C 3-8 cycloalkyl), -N(C) 1-6 Alkyl groups (5- to 10-membered heterocyclic groups), -N(C) 1-6 Alkyl)(phenyl), -N(C) 1-6 Alkyl group (5- to 10-membered heteroaryl group), -C(O) group (5- to 10-membered heterocyclic group), -C(O) group (5- to 10-membered heteroaryl group), -C(O)O(C 1-6 Alkyl), -C(O)O(C 3-8 cycloalkyl), -C(O)O (5- to 10-membered heterocyclic group), -C(O)O (phenyl), -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 heterocyclic group), -C(O)NH (phenyl), -C(O)NH (5- to 10-membered heteroaryl group), -C(O)N(C 1-6 Alkyl)2、-C(O)N(C 3-8 Cycloalkyl)2, -C(O)N (5- to 10-membered heterocyclic)2, -C(O)N (phenyl)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 heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 alkyl), -NHC(O)NH(C 3-8 cycloalkyl), -NHC(O)NH (5- to 10-membered heterocyclic group), -NHC(O)NH (phenyl), -NHC(O)NH (5- to 10-membered heteroaryl group), -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 heterocyclic), -S(O)2 (phenyl), -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, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Alternatively, R 1 It is a phenyl group, and both R groups are phenyl. 1a Together with the phenyl atoms to which they are attached, they form a group optionally bounded by one to three R atoms. 1b Replacement of 5- to 10-membered heterocyclic groups; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH, -NH2, CO2H, -O(C) 1-6 alkyl), -O(C) 1-6 Halogenated alkyl), -O(C) 3-8 cycloalkyl), -O (5- to 10-membered heterocyclic), -O (phenyl), -O (5- to 10-membered heteroaryl), -NH (C 1-6 alkyl), -NH(C) 1-6 Halogenated alkyl), -NH(C) 3-8 cycloalkyl), -NH (5- to 10-membered heterocyclic group), -NH (phenyl), -NH (5- to 10-membered heterocyclic group), -N (C 1-6 Alkyl)2, -N(C 3-8 cycloalkyl)2、-NHC(O)(C 1-6 Alkyl), -NHC(O)(C 1-6 Halogenated alkyl groups), -NHC(O)(C 3-8 cycloalkyl), -NHC(O) (5- to 10-membered heterocyclic groups), -NHC(O) (phenyl), -NHC(O) (5- to 10-membered heteroaryl groups), -NHC(O)O(C 1-6 Alkyl), -NHC(O)O(C 1-6 Halogenated alkyl groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-8 cycloalkyl), -NHC(O)O (5- to 10-membered heterocyclic groups), -NHC(O)O (phenyl), -NHC(O)O (5- to 10-membered heteroaryl groups), -NHC(O)NH(C 1-6 Alkyl), S(O)2(C 1-6 Alkyl), -S(O)2(C 1-6 Halogenated alkyl groups), -S(O)2(C 3-8 cycloalkyl), -S(O)2 (5- to 10-membered heterocyclic), -S(O)2 (phenyl), -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 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 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-、-(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 It is hydrogen or C 1-6 alkyl; R 5 For 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, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independently halogen, oxo group, cyclopropyl group, hydroxyl group, -CN, C 1-3 Alkyl, C 1-3 Alkyl group, -OCF3 or -OCF2H.

2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, having the structure of formula (IA): IA.

3. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein X 2 It is -O-.

4. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein X 2 It is -O-, and X 1 -C(R) x1 = ).

5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (II-A): II-A.

6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R x1 Halogen or C 1-3 alkyl.

7. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R x1 It is hydrogen or C 1-3 alkyl.

8. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R x1 It is hydrogen.

9. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein X 1 It is -O-.

10. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein X 1 It is -O-, and X 2 -C(R) x2 = ).

11. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, having the structure of formula (II-B): II-B.

12. The compound according to any one of claims 1, 2 and 9 to 11, or a pharmaceutically acceptable salt thereof, wherein R x2 It is hydrogen.

13. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein X 2 It is -O-, and X 1 It is -N-.

14. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (II-C): II-C.

15. The compound according to claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein X 1 It is -O-, and X 2 It is -N-.

16. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, having the structure of formula (II-D): II-D.

17. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein... ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, and X 4 and X 5 Each is C.

18. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein... ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl or C 5-10 cycloalkyl, and X 4 and X 5 Each is C.

19. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... It is a phenyl group.

20. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... C 5–7 Cycloalkyl.

21. The 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.

22. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... It is a 6-membered heteroaryl group.

23. The compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein X 6 and X 7 For CH.

24. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, having the structure of formula (III): III.

25. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, having the structure of formula (IV-A): IV-A.

26. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (IV-B): IV-B.

27. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (IV-C): IV-C.

28. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (IV-D): IV-D.

29. The compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein L 3 For key.

30. The compound according to any one of claims 1 to 29, wherein each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic groups, phenyl, 5- to 10-membered heteroaryl groups, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)2、-O(C 1-6 alkyl) or -O(C 3-8 cycloalkyl); Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 3a replace.

31. The compound according to any one of claims 1 to 30, wherein at least one R 3 -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 alkyl)2 or -O(C 1-3 alkyl), Where R 3 Each C 1-6 Alkyl groups are optionally surrounded by one to three R groups. 3a replace.

32. The compound according to any one of claims 1 to 31, wherein at least one R 3 To be arbitrarily selected by one to three R 3a Replacement of 5- to 7-membered heterocyclic groups.

33. The compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 To be optionally controlled by one or two R 3a Replacement C 1-6 Alkyl group.

34. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 33, wherein at least one R 3 C 1-3 Alkyl group.

35. The compound according to any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 To be optionally controlled by one or two R 3a Replacement C 1-6 alkyl.

36. The compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 It is a methyl group.

37. The compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein at least one R 3 It is a halogen.

38. The compound according to any one of claims 1 to 37, or a pharmaceutically acceptable salt thereof, wherein each R 3a Independently halogen, -C(O)(C 1-6 Alkyl groups, -OH groups, -O groups 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C 1-6 alkyl) or -C(O)N(C 1-6 Alkyl)2.

39. The compound according to any one of claims 1 to 38, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a -O(C) 1-3 Alkyl), 5- to 7-membered heterocyclic groups, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl) or -C(O)N(C1-C3 alkyl)2.

40. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 39, wherein at least one R 3a It is a halogen or a -C(O)(C1-C6 alkyl).

41. The compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a -OH or -O(C) 1-3 alkyl).

42. The compound according to any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a -O(C) 1-3 alkyl).

43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein at least one R 3a It is a halogen or -OH.

44. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 43, wherein n is 0.

45. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 43, wherein n is 1.

46. ​​The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... With X 4 X 5 X 6 and X 7 The rings are joined together to form or .

47. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... With X 4 X 5 X 6 and X 7 The rings are joined together to form .

48. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... With X 4 X 5 X 6 and X 7 The rings are joined together to form .

49. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... With X 4 X 5 X 6 and X 7 The rings are joined together to form .

50. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... With X 4 X 5 X 6 and X 7 The rings are joined together to form .

51. The compound according to any one of claims 1 and 6 to 8, or a pharmaceutically acceptable salt thereof, having the structure of formula (VA): VA.

52. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (VB): VB.

53. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (VC): VC.

54. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (VD): VD.

55. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein the ring... It does not exist.

56. The compound of claim 55 or a pharmaceutically acceptable salt thereof, wherein each L x4 and L x5 Independently for bonds or N(R) L )S(O)2-.

57. The compound of claim 55 or claim 56, or a pharmaceutically acceptable salt thereof, wherein L x4 For key.

58. The compound according to any one of claims 55 to 57, or a pharmaceutically acceptable salt thereof, wherein L x5 For key.

59. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, having the structure of formula (VI): VI.

60. The compound according to any one of claims 1 and 6 to 8, or a pharmaceutically acceptable salt thereof, having the structure of formula (VII-A): VII-A.

61. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, having the structure of formula (VII-B): VII-B.

62. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (VII-C): VII-C.

63. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of formula (VII-D): VII-D.

64. The compound according to any one of claims 55 to 63, wherein X 6 For CH and X 7 Let N be the number of elements in the array.

65. The compound according to any one of claims 55 to 63, wherein X 6 For N and X 7 For CH.

66. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein X 6 and X 7 For CH.

67. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein each R x4 and R x5 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, 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; Where R x4 and R x5 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 4a replace.

68. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein each R x4 and R x5 Independently hydrogen, C 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 5- to 10-membered heterocyclic groups, Where R x4 and R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4a replace.

69. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein R x4 and R x5 One of them is hydrogen and the other is optionally separated by one or two R. 4a Replacement C 3-8 Cycloalkyl.

70. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein R x4 and R x5 One of them is hydrogen and the other is optionally separated by one or two R. 4a Replacement C 1-6 Alkyl group.

71. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein R x4 and R x5 One of them is hydrogen and the other is optionally separated by one or two R. 4a Replacement C 1-6 alkyl.

72. The compound according to any one of claims 55 to 63, or a pharmaceutically acceptable salt thereof, wherein R x4 and R x5 One of them is hydrogen and the other is C. 1-6 alkyl.

73. The compound according to any one of claims 55 to 71, or a pharmaceutically acceptable salt thereof, wherein each R 4a Independently for C 1-6 Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 cycloalkyl), Where R 4a Each C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups and C 3-8 cycloalkyl groups are optionally surrounded by one to three R groups. 4b replace.

74. The compound according to any one of claims 55 to 71 and 73, or a pharmaceutically acceptable salt thereof, wherein each R 4b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (Halogenated alkyl groups).

75. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... It is a phenyl group.

76. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... It is a heteroaryl compound with a value of 5 to 10 yuan.

77. The compound according to any one of claims 1 to 76, or a pharmaceutically acceptable salt thereof, wherein each L 1 Independently for the key, -(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)- or -(C 1-6 alkyl)C(O)N(R L (C) 1-6 alkyl)-.

78. The compound according to any one of claims 1 to 76, or a pharmaceutically acceptable salt thereof, wherein each L 1 For key.

79. The compound according to any one of claims 1 to 76, or a pharmaceutically acceptable salt thereof, wherein each L 1 Independently for -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-.

80. The compound according to any one of claims 1 to 76, or a pharmaceutically acceptable salt thereof, wherein each L 1 Independently for -(C 1-6 Alkyl)O- or -O(C 1-6 alkyl)-.

81. The compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein each R 1 Independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to three R groups. 1a replace.

82. The compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein each R 1 Independently halogen, -CN, -C(O)NH2, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 1a replace.

83. The compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein each R 1 Independent of halogen, -CN or C 1-6 Alkyl group.

84. The compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein each R 1 Independently halogen or C 1-3 Alkyl group.

85. The compound according to any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein each R 1 It can be fluorine, chlorine, or methoxy on its own.

86. The compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, wherein each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl groups.

87. The compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, wherein each R 1a Independently halogen, -OH, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkyl or phenyl.

88. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 82, 86 and 87, wherein at least one R 1a It is a halogen.

89. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 88, wherein m is 0.

90. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 88, wherein m is 1 or 2.

91. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 88, wherein m is 3.

92. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for .

93. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for , , , , or .

94. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for or .

95. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for or .

96. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for , , , , , , , , , , or .

97. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for , , , , or .

98. The compound according to any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the ring... for , , or .

99. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 92, wherein R 2 Hydrogen, halogen, -CN, C 1-3 Alkyl or C 1-3 Alkyl group.

100. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 92, wherein R 2 It is hydrogen.

101. The compound according to any one of claims 1 to 92, or a pharmaceutically acceptable salt thereof, wherein R 2 It is a halogen.

102. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 101, wherein L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-.

103. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 101, wherein L 2 For key, C 1-6 Alkyl or -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-.

104. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 101, wherein L 2 For -(C 0-6 Alkyl)-cyclopropyl-.

105. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 101, wherein L 2 For key.

106. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 101, wherein L 2 C 1-3 alkyl.

107. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 106, wherein R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace.

108. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 106, wherein R 5 C 1-3 Alkyl, C 5-6 Cycloalkyl, phenyl, 5- to 7-membered heterocyclic or 5- to 9-membered heteroaryl, Where R 5 Each C 1-3 Alkyl, C 5-6 Cycloalkyl, phenyl, 5- to 7-membered heterocyclic and 5- to 9-membered heteroaryl groups are optionally surrounded by one or two R groups. 5b replace.

109. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 106, wherein R 5 It is hydrogen, -CN or C 1-6 alkyl.

110. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 106, wherein R 5 C 1-3 alkyl.

111. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 106, wherein R 5 It is hydrogen.

112. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 106, wherein R 5 For -CN.

113. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 108, wherein each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

114. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 108, wherein R 5b It is a methyl group.

115. The compound according to claim 1, wherein... X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; ring With X 4 and X 5 Together they form phenyl, 5- to 6-membered heteroaryl, C 5-10 Cycloalkyl or 5- to 10-membered heterocyclic groups, Each X 4 and X 5 Independently N or C; Alternatively, choose a location, surrounding It does not exist, where X 4 For N or CL x4 -R x4 And X 5 For N or CL x5 -R x5 ; Each L x4 and L x5 Independently for bonds or N(R) L S(O)2-; Each R x4 and R x5 Independently hydrogen, C 1-6 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 heterocyclic groups; Where R x4 and R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 cycloalkyl), Where R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b replace; Each R 4b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (halogenated alkyl); Each L 3 Independently for the key, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)-, -C(O)- or -(C 1-6 Alkyl)C(O)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic groups; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 3a replace; Each R 3a Independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2; n is an integer from 0 to 3; Each X 6 and X 7 Independently N or CH, Where X 4 X 5 X 6 and X 7 The two numbers in the range do not exceed N; ring C 6-10 Aryl; Each L 1 Independently for the key, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-; Each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH or -NH2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-; R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

116. The compound according to claim 1, having the structure of formula (III): III Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; Each L 3 Independently for the key, -(C 1-6 Alkyl)O-, -(C 1-6 Alkyl)-, -C(O)- or -(C 1-6 Alkyl)C(O)-; Each R 3 Independently hydrogen, halogen, hydroxyl, -CN, C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl or 4- to 10-membered heterocyclic groups; Where R 3 Each C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 3a replace; Each R 3a Independently halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1-6 Alkyl groups, 5- to 10-membered heterocyclic groups, -C(O)NH2, -C(O)N(H) (C1-C6 alkyl) or -C(O)N(C1-C6 alkyl)2; n is an integer from 0 to 3; ring C 6-10 Aryl; Each L 1 Independently for the key, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-; Each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH or -NH2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-; R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

117. The compound according to claim 1, having the structure of formula (VI): VI Or its pharmaceutically acceptable salt, wherein X 1 It is -O-, and X 2 -N- or -C(R) x2 =; or X 2 It is -O-, and X 1 -N- or -C(R) x1 = Each R x1 and R x2 Independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, -O(C) 1-3 (halogenated alkyl), C 1-3 Alkoxy, cyclopropyl, or O-cyclopropyl; Each R x4 and R x5 Independently hydrogen, C 1-6 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 heterocyclic groups; Where R x4 and R x5 Each C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 4a replace; Each R 4a Independently for C 1-6 Alkyl, -C(O) (5- to 10-membered heterocyclic groups) or -O(C 3-8 cycloalkyl), Where R 4a Each C 1-6 Alkyl, C 3-8 Cycloalkyl groups and 5- to 10-membered heterocyclic groups are optionally surrounded by one to three R groups. 4b replace; Each R 4b Independently halogen, -O(C 1-6 alkyl) or -O(C 1-6 (halogenated alkyl); Each X 6 and X 7 Independently N or CH; ring C 6-10 Aryl; Each L 1 Independently for the key, -O-, -(C 1-6 Alkyl)O-, -O(C 1-6 alkyl)- or -C 1-6 Alkyl-O(C) 1-6 alkyl)-; Each R 1 Independently halogen, -OH, -CN, C 1-6 Alkyl group, -C(O)NH2, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclic groups, Where R 1 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, 5- to 12-membered heteroaryl and 4- to 10-membered heterocyclic groups are optionally separated by one to four R groups. 1a replace; Each R 1a Independently halogen, -OH, -CN, -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, phenyl, or 5- to 10-membered heteroaryl, Where R 1a Each C 1-6 Alkyl, C 3-8 Cycloalkyl, 4- to 10-membered heterocyclic, phenyl, and 5- to 10-membered heteroaryl groups are optionally separated by one to three R groups. 1b replace; Each R 1b Independently for C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, oxo groups, -OH or -NH2; m is an integer from 0 to 3; R 2 For hydrogen, C 1-3 Alkyl, C 1-3 Halogenated alkyl, cyclopropyl, C 1-3 Alkyloxy group, -O(C 1-3 Halogenated alkyl groups, -O (cyclopropyl), halogens, or -CN; L 2 For key, C 1-6 Alkyl, -(C 0-6 alkyl)-cyclopropyl-(C 0-6 alkyl)-, -(C 1-6 Alkyl)O- or -(C 1-6 Alkyl)O(C 1-6 alkyl)-; R 5 For hydrogen, -CN, C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic or 5- to 10-membered heteroaryl, Where R 5 Each C 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl, 4- to 10-membered heterocyclic and 5- to 10-membered heteroaryl groups are optionally separated by one or two R groups. 5b replace; Each R 5a Independently hydrogen or C 1-6 Alkyl; and Each R 5b Independent of oxygen group, C 1-3 Alkyl or C 1-3 Alkyl group.

118. The compound according to any one of claims 115 to 117, or a pharmaceutically acceptable salt thereof, wherein X 6 and X 7 For CH.

119. The compound according to any one of claims 115 to 118, or a pharmaceutically acceptable salt thereof, wherein X 2 It is -O-, and X 1 = -C(H) =.

120. The compound according to any one of claims 115 to 119, or a pharmaceutically acceptable salt thereof, wherein the ring... for .

121. A compound selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and , Or its pharmaceutically acceptable salt.

122. A pharmaceutical composition comprising a compound according to any one of claims 1 to 121 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

123. A method for treating or preventing viral infection in a person in need, wherein the method comprises administering to the person a compound according to any one of claims 1 to 121 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 122.

124. The method of claim 123, wherein the viral infection is a coronavirus infection.

125. The method according to claim 123 or 124, wherein the viral infection is caused by a virus having at least 70% sequence homology with a viral polymerase selected from SARS-CoV polymerase, MERS-CoV polymerase and SARS-CoV-2.

126. The method according to claim 123 or 124, wherein the viral infection is caused by a virus having at least 80% sequence homology with a viral polymerase selected from SARS-CoV polymerase, MERS-CoV polymerase and SARS-CoV-2.

127. The method according to claim 123 or 124, wherein the viral infection is caused by a virus having at least 90% sequence homology with a viral polymerase selected from SARS-CoV polymerase, MERS-CoV polymerase and SARS-CoV-2.

128. The method according to claim 123 or 124, wherein the viral infection is caused by a virus having at least 95% sequence homology with a viral polymerase selected from SARS-CoV polymerase, MERS-CoV polymerase and SARS-CoV-2.

129. The method according to any one of claims 123 to 128, wherein the viral infection is SARS-CoV-2 infection (COVID-19).

130. A method for manufacturing a medicament for treating or preventing viral infections in people in need, characterized in that, Use the compound according to any one of claims 1 to 121 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 122.

131. Use of the compound of any one of claims 1 to 121 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition of claim 122 for the manufacture of a medicament for the treatment or prevention of viral infections in persons in need.

132. A composition comprising any one of the compounds according to claims 1 to 121 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 122, for use in the treatment or prevention of viral infections in persons in need.

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