SARS-CoV2 key protease inhibitor

Abstract

The present disclosure provides compounds of formula I: TIFF2025525948001137.tif52128, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. In another embodiment, the present disclosure provides a method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure. The present disclosure generally relates to methods and compounds for treating or preventing viral infections, such as coronavirus infections.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 63 / 370,629, filed August 5, 2022, U.S. Provisional Patent Application No. 63 / 375,522, filed September 13, 2022, U.S. Provisional Patent Application No. 63 / 476,359, filed December 20, 2022, U.S. Provisional Patent Application No. 63 / 482,750, filed February 1, 2023, U.S. Provisional Patent Application No. 63 / 486,156, filed February 21, 2023, and U.S. Provisional Patent Application No. 63 / 508,350, filed June 15, 2023, each of which is incorporated by reference herein in its entirety. [Background technology]

[0002] Coronaviruses, named for the crown-like spikes on their surface, mostly infect bats, pigs, and small mammals. Coronaviruses mutate easily and can jump from animals to humans and from one human to another. In recent years, they have become central to infectious disease outbreaks worldwide. There is a need for compounds and methods for treating viral infections, such as coronavirus infections. The present disclosure addresses these and other needs. Summary of the Invention [Means for solving the problem]

[0003] In one embodiment, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof [wherein: ring [ka] is C 6~10 aryl or 5-10 membered heteroaryl; Each L 1are independently a bond, -O-, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)-, -C 1~6 Alkyl-O(C 1~6 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~6 alkyl)(R L )NC(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~6 alkyl)-, -C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~6 alkyl)S(O)2N(R L )-, -(C 1~6 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~6 alkyl)-, -N(R L )S(O)2(C 1~6 alkyl)-, -(C 1~6 alkyl)S(O)2N(R L )(C 1~6 alkyl)- or -(C 1~6 alkyl)N(R L )S(O)2(C 1~6 alkyl)-; Each R 1 are independently halogen, -OH, -CN, C 1~6 Alkyl, -CN, -C(O)NH2, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a optionally substituted with; Or, two R 1 are the rings to which they are attached. [ka] together with the atom to form a 5- to 10-membered heterocyclyl; Each R 1a independently, C 1~6 Alkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -N(5-10 membered heterocyclyl)2, -N(C6 aryl)2, -N(5-10 membered heteroaryl)2, -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)O(C 1~6 alkyl), -C(O)O(C 3~8Cycloalkyl), -C(O)O(5-10 membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -C(O)N(5-10 membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5-10 membered heteroaryl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 3~8 cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -NHS(O)(C 1~6 alkyl), -N(C 1~6 alkyl)(S(O)(C 1~6 alkyl), -S(O)2(C 1~6 alkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 1b optionally substituted with; Each R 1b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 2~6 alkynyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C 6- aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; m is an integer from 0 to 3; R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Haloalkyl, cyclopropyl, C 1~3 Alkoxy, -O(C 1~3 haloalkyl), -O(cyclopropyl), halogen, or -CN; X 1 is S, N, or C(R x1 ) and; X 2 is S, N, or C(R x2 ) and; X 3 is N or C(R x3 ), where X 1 and X 2 is not S; Or X 3 is a bond, where X 1 and X 2 One of them is S; Each R x1 , R x2 , and R x3 are independently hydrogen, halogen, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl; X 4 and X 5 Tamaki who became friends with [ka] C6 aryl, 5-6 membered heteroaryl, C 5~10 cycloalkyl, or 5- to 10-membered heterocyclyl; Here, each X 4 and X 5 are independently N or C; Or, ring [ka] does not exist, where X 4 is N or CL x4 -R x4 and X 5 is N or CL x5 -R x5 and; Each L x4 and L x5 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4aoptionally substituted with; Each R 4a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 4b optionally substituted with; Each R 4b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each L 3 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6alkyl)C(O)-, or -N(R L )C(O)-; Each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 3a optionally substituted with; Each R 3a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 3b optionally substituted with; Each R 3b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each RL are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, or C 3~8 is cycloalkyl; n is an integer from 0 to 3; each X 6 and X 7 are independently N or CH; where X 4 , X 5 , X 6 , and X 7 At most two of are N; L 2 is a bond, C1-C6 alkyl, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)O(C 1~6 alkyl)-, -(C 1~6 alkyl)(R L2 )NC(O)-, -(C 1~6 alkyl)C(O)N(R L2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, or -(C 1~6 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-; R L2 is hydrogen or C 1~6 is alkyl; R 5 is hydrogen, -CN, -OR 5a , -C(O)NR 5a 2, -NR 5a C(O)R 5a , -NR 5a 2、 C 3~8 cycloalkyl, C aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b optionally substituted with; Each R 5a are independently hydrogen or C 1~6is alkyl; Each R 5b are independently selected from halogen, cyclopropyl, hydroxy, -CN, C 1~3 Alkyl, C 1~3 alkoxy, -OCF3, or -OCF2H; and Z is O or S.

[0004] In one embodiment, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof [wherein: ring [ka] is C 6~10 aryl or 5-10 membered heteroaryl; Each L 1 are independently a bond, -O-, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)-, -C 1~6 Alkyl-O(C 1~6 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~6 alkyl)(R L )NC(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~6 alkyl)-, -C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~6alkyl)S(O)2N(R L )-, -(C 1~6 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~6 alkyl)-, -N(R L )S(O)2(C 1~6 alkyl)-, -(C 1~6 alkyl)S(O)2N(R L )(C 1~6 alkyl)- or -(C 1~6 alkyl)N(R L )S(O)2(C 1~6 alkyl)-; Each R 1 are independently halogen, -OH, -CN, C 1~6 Alkyl, -CN, -C(O)NH2, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a optionally substituted with; Each R 1a independently, C 1~6 Alkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8cycloalkyl)2, -N(5-10 membered heterocyclyl)2, -N(C6 aryl)2, -N(5-10 membered heteroaryl)2, -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)O(C 1~6 alkyl), -C(O)O(C 3~8 Cycloalkyl), -C(O)O(5-10 membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -C(O)N(5-10 membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5-10 membered heteroaryl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 3~8 cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -NHS(O)(C1~6 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(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 1b optionally substituted with; Each R 1b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 2~6alkynyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C 6- aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; m is an integer from 0 to 3; R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Haloalkyl, cyclopropyl, C 1~3 Alkoxy, -O(C 1~3 haloalkyl), -O(cyclopropyl), halogen, or -CN; X 1 is S, N, or C(R x1 ) and; X 2 is S, N, or C(R x2 ) and; X 3 is N or C(R x3 ), where X 1 and X 2 is not S; Or X 3 is a bond, where X 1 and X 2 One of them is S; Each R x1 R x2 , and R x3 are independently hydrogen, halogen, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3alkoxy, cyclopropyl, or O-cyclopropyl; X 4 and X 5 Tamaki who became friends with [ka] C6 aryl, 5-6 membered heteroaryl, C 5~10 cycloalkyl, or 5- to 10-membered heterocyclyl; Here, each X 4 and X 5 are independently N or C; Or, ring [ka] does not exist, where X 4 is N or CL x4 -R x4 and X 5 is N or CL x5 -R x5 and; Each L x4 and L x5 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a optionally substituted with; Each R 4a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 4b optionally substituted with; Each R 4b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each L 3 are independently a bond, -(C1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 3a optionally substituted with; Each R 3a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 3b optionally substituted with; Each R 3b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each R L are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, or C 3~8 is cycloalkyl; n is an integer from 0 to 3; each X 6 and X 7 are independently N or CH; where X 4 , X 5 , X 6 , and X 7 At most two of are N; L 2 is a bond, C1-C6 alkyl, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)O(C 1~6 alkyl)-, -(C 1~6 alkyl)(R L2 )NC(O)-, -(C 1~6 alkyl)C(O)N(R L2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, or -(C 1~6 alkyl)S(O)2N(RL2 )(C 1~6 alkyl)-; R L2 is hydrogen or C 1~6 is alkyl; R 5 is hydrogen, -CN, -OR 5a , -C(O)NR 5a 2, -NR 5a 2、 C 3~8 cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b optionally substituted with; Each R 5a are independently hydrogen or C 1~6 is alkyl; Each R 5b are independently selected from halogen, cyclopropyl, hydroxy, -CN, C 1~3 Alkyl, C 1~3 alkoxy, -OCF3, or -OCF2H; and Z is O or S.

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

[0006] In another embodiment, the present disclosure provides a method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

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

[0008] As used herein, the following words, phrases, and symbols are generally intended to have the meanings set forth below, unless the context in which they are used indicates otherwise.

[0009] "Alkyl" refers to an unbranched or branched saturated hydrocarbon chain. For example, an alkyl group can have 1 to 20 carbon atoms (i.e., C1 to C6). 20The alkyl group may have 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 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, -C H(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 butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH( These include, but are not limited to, 4-methyl-2-pentyl (-CH(CH)CHCH(CH)), 3-methyl-3-pentyl (-C(CH)(CHCH)), 2-methyl-3-pentyl (-CH(CHCH)CH(CH)), and 2,3-dimethyl-2-butyl (-C(CH)CH(CH)), 3,3-dimethyl-2-butyl (-CH(CH)C(CH)).

[0010] "Alkenyl" refers to a straight or branched chain hydrocarbon having at least two carbon atoms and at least one double bond. Alkenyl includes, for example, C, C 2~3 ,C2~4 ,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 Alkenyl groups can contain any number of carbons, such as C, C, and C6. Alkenyl groups can 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 (ethenyl), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexatrienyl. Alkenyl groups can be substituted or unsubstituted.

[0011] "Alkynyl" refers to either a straight or branched chain hydrocarbon containing at least two carbon atoms and at least one triple bond. Alkynyl includes C, C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 2~7 , C 2~8 , C 2~9 , C 2~10 , C3, C 3~4 , C 3~5 , C 3~6 , C4, C 4~5 , C 4~6 , C5, C 5~6and C6. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexatriynyl. Alkynyl groups can be substituted or unsubstituted.

[0012] "Alkoxy" refers to an alkyl group having an oxygen atom connecting the alkyl group to the point of attachment (alkyl-O-). With respect to alkyl groups, alkoxy groups include C 1~6 Alkoxy groups can have any suitable number of carbon atoms, such as , ...

[0013] "Alkoxyalkyl" refers to an alkoxy group linked to an alkyl group which is linked to the remainder of the compound, such that the alkyl group is divalent. Alkoxyalkyls are those having 2 to 6 (C 2~6 alkoxyalkyl), 2 to 5 (C 2~5 alkoxyalkyl), 2 to 4 (C 2~4 alkoxyalkyl), or 2 to 3 (C 2~3 Alkoxy and alkyl are as defined above, and alkyl is divalent and can include, but is not limited to, methoxymethyl (CH3OCH2-), methoxyethyl (CH3OCH2CH2-), and the like.

[0014] "Alkoxy-alkoxy" refers to an alkoxy group linked to a second alkoxy group that is linked to the remainder of the compound. Alkoxy is as defined above and can include, but is not limited to, methoxy-methoxy (CH3OCH2O-), methoxy-ethoxy (CHOCH2CHO-), and the like.

[0015] As used herein, "halo" or "halogen" refers to fluoro (-F), chloro (-Cl), bromo (-Br), and iodo (-I).

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

[0017] "Hydroxyl" and "hydroxy" are used interchangeably and refer to --OH.

[0018] As used herein, "haloalkyl" refers to an alkyl, as defined herein, wherein one or more hydrogen atoms of the alkyl are independently replaced by halo substituents, which may be the same or different. For example, C 1~4 Haloalkyl is C 1~4 alkyl, 1~4 and C1-4 alkyl, in which one or more of the alkyl's hydrogen atoms are replaced by halo substituents. Examples of haloalkyl 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 the hydrogen atoms are replaced with halogen atoms. With respect to alkyl groups, haloalkoxy groups include C 1~6The alkoxy group may have any suitable number of carbon atoms, such as 1, 2, 3, or more. The alkoxy group may be substituted with one, two, three, or more halogens. When all hydrogens are replaced with halogens, such as fluorine, the compound is persubstituted, e.g., perfluorinated. Haloalkoxy includes, but is not limited to, trifluoromethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, and the like.

[0020] "Cycloalkyl" refers to a group of 3 to 20 cyclic carbon atoms (i.e., C 3~20 Cycloalkyl) refers to a saturated or partially unsaturated all-carbon monocyclic ring, e.g., having 3 to 12 ring atoms, e.g., 3 to 10 ring atoms, or 3 to 8 ring atoms, or 3 to 6 ring atoms, or 3 to 5 ring atoms, or 3 to 4 ring atoms. The term "cycloalkyl" also encompasses saturated and partially unsaturated all-carbon multiple condensed ring systems (e.g., ring systems containing 2, 3, or 4 carbocyclic rings). Thus, cycloalkyl includes polycyclic carbocycles, e.g., bicyclic carbocycles (e.g., bicyclic carbocycles having 6 to 12 ring carbon atoms, e.g., bicyclo[3.1.0]hexane and bicyclo[2.1.1]hexane) and polycyclic carbocycles (e.g., tricyclic and tetracyclic carbocycles having up to 20 ring carbon atoms). The rings of multiple condensed ring systems may be connected to each other by fused, spiro, and bridged bonds, where permitted by valency requirements. Non-limiting examples of monocyclic cycloalkyls 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 radical having an alkyl component and a cycloalkyl component, where the alkyl component connects the cycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene in order to connect the cycloalkyl component and the point of attachment. In some cases, the alkyl component can be absent. The alkyl component can be any of C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 The cycloalkyl moiety is 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, "heterocyclyl" or "heterocycle" or "heterocycloalkyl" refers to a saturated or partially unsaturated non-aromatic monocyclic or multiple ring system having at least one heteroatom (i.e., at least one ring heteroatom selected from oxygen, nitrogen, and sulfur) in the ring, where the multiple ring system includes at least a non-aromatic ring containing at least one heteroatom. The multiple ring system may also include other aromatic and non-aromatic rings. Unless otherwise specified, a heterocyclyl group has 3 to 20 ring atoms, e.g., 3 to 12 ring atoms, e.g., 3 to 10 ring atoms, or 3 to 8 ring atoms, or 3 to 6 ring atoms, or 3 to 5 ring atoms, or 4 to 6 ring atoms, or 4 to 5 ring atoms. Thus, the term encompasses saturated or partially unsaturated monocyclic rings (e.g., 3-, 4-, 5-, 6-, or 7-membered rings) having 1 to 6 ring carbon atoms and 1 to 3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. The heteroatoms are optionally oxidized to form -N(-OH)-, =N(-O) - )-, -S(=O)-, or -S(=O)2-. The rings of fused polycyclic (e.g., bicyclic heterocyclyl) systems can be connected to each other via fused, spiro, and bridged bonds, where permitted by valence requirements. Heterocycles include azetidine, aziridine, imidazolidine, morpholine, oxirane (epoxide), oxetane, thietane, piperazine, piperidine, pyrazolidine, piperidine, pyrrolidine, pyrrolidinone, tetrahydrofuran, tetrahydrothiophene, dihydropyridine, tetrahydropyridine, quinuclidine, 2-oxa-6-azaspiro[3.3]heptan-6-yl, 6-oxa-1-azaspiro[3.3]heptan-1-yl , 2-thia-6-azaspiro[3.3]heptan-6-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2-azabicyclo[3.1.0]hexan-2-yl, 3-azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 2-azabicyclo[2.2.1]heptan-2-yl, 4-azaspiro[2.4]heptanyl, 5-azaspiro[2.4]heptanyl, and the like.

[0023] "Alkyl-heterocycloalkyl" refers to a radical having an alkyl component and a heterocycloalkyl component, where the alkyl component connects the heterocycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least a divalent alkylene in order to connect the heterocycloalkyl component and the point of attachment. The alkyl component is selected from the group consisting of C 0~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 The alkyl-heterocycloalkyl group may contain any number of carbons, such as . In some cases, the alkyl component may be absent. The heterocycloalkyl component is as defined above. The alkyl-heterocycloalkyl group may be substituted or unsubstituted.

[0024] As used herein, "aryl" refers to an all-carbon aromatic monocyclic ring or an all-carbon multiple condensed ring system in which at least one of the rings is aromatic. For example, in some embodiments, an aryl group has 6 to 20 carbon atoms, 6 to 14 carbon atoms, or 6 to 12 carbon atoms. Aryl includes phenyl radicals. Aryl also includes multiple condensed ring systems (e.g., ring systems containing 2, 3, or 4 rings) having 9 to 20 carbon atoms in which at least one ring is aromatic and the other rings may or may not be aromatic (i.e., carbocyclic), and may be saturated or partially saturated. Such multiple condensed ring systems are optionally substituted with one or more (e.g., 1, 2, or 3) oxo groups on any carbocyclic moiety of the multiple condensed ring system. The rings of a multiple condensed ring system may be connected to each other by fused, spiro, and bridged bonds, where permitted by valency requirements. When referring to an aryl having a particular range of atom numbers (e.g., a 6- to 10-membered aryl), it is also understood that the atom range refers to the total ring atoms of the aryl. For example, a 6-membered aryl includes phenyl, and a 10-membered aryl includes naphthyl and 1,2,3,4-tetrahydronaphthyl. Non-limiting examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, and the like.

[0025] "Alkyl-aryl" refers to a radical having an alkyl component and an aryl component, where the alkyl component connects the aryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene in order to connect the aryl component and the point of attachment. The alkyl component is selected from the group consisting of C 0~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C3~6 , C 4~5 , C 4~6 , and C 5~6 The alkyl group may contain any number of carbon atoms, such as , ...

[0026] As used herein, "heteroaryl" refers to a monocyclic aromatic ring having at least one atom other than carbon within the ring, where that atom is selected from the group consisting of oxygen, nitrogen, and sulfur; "heteroaryl" also encompasses multiple condensed ring systems having at least one such aromatic ring, which are further described below. Thus, "heteroaryl" encompasses a monocyclic aromatic ring of 1 to 6 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. The sulfur and nitrogen atoms may be present in oxidized form, provided the ring is aromatic. Exemplary heteroaryl ring systems include, but are not limited to, pyridyl, pyrimidinyl, oxazolyl, or furyl. "Heteroaryl" also encompasses multiple condensed ring systems (e.g., ring systems containing 2, 3, or 4 rings), where a heteroaryl group as defined above is fused with one or more rings selected from heteroaryl (e.g., to form 1,8-naphthyridinyl), heterocycle (e.g., to form 1,2,3,4-tetrahydro-1,8-naphthyridinyl), carbocycle (e.g., to form 5,6,7,8-tetrahydroquinolyl), and aryl (e.g., to form indazolyl) to form a multiple condensed ring system. The other rings may or may not be aromatic (i.e., carbocyclic) and may be saturated or partially saturated. Thus, a heteroaryl (aromatic monocyclic or multiple condensed ring system) has 1 to 20 carbon atoms and 1 to 6 heteroatoms in the heteroaryl ring. Such fused polycyclic ring systems may be optionally substituted with one or more (e.g., 1, 2, 3, or 4) oxo groups on the carbocyclic or heterocyclic portions of the fused rings. The rings of a fused polycyclic ring system may be connected to each other by fused bonds, spiro bonds, and bridged bonds, where permitted by valency requirements. It is understood that the individual rings of a fused polycyclic ring system may be connected to each other in any order. It is understood that the point of attachment of a heteroaryl or heteroaryl to a fused polycyclic ring system may be at any suitable atom of the heteroaryl or heteroaryl, including a carbon atom and a heteroatom (e.g., nitrogen).When a heteroaryl having a particular range of atom members (e.g., a 5- to 10-membered heteroaryl) is referred to, it is understood that the atom range is for the total ring atoms of the heteroaryl and includes carbon atoms and heteroatoms. For example, a 5-membered heteroaryl includes thiazolyl, and a 10-membered heteroaryl includes quinolinyl. Exemplary heteroaryls include, but are not limited to, pyridyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, thienyl, indolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furyl, oxadiazolyl, thiadiazolyl, quinolyl, isoquinolyl, benzothiazolyl, benzoxazolyl, indazolyl, quinoxalyl, quinazolyl, 5,6,7,8-tetrahydroisoquinolinyl, benzofuranyl, benzimidazolyl, thianaphthenyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl-4(3H)-one, and triazolyl.

[0027] "Alkyl-heteroaryl" refers to a radical having an alkyl component and a heteroaryl component, where the alkyl component connects the heteroaryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene in order to connect the heteroaryl component and the point of attachment. The alkyl component is selected from the group consisting of C 0~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 In some cases, the alkyl component may be absent. The heteroaryl component is as defined herein. The alkyl-heteroaryl group may be substituted or unsubstituted.

[0028] "Compounds of the present disclosure" include compounds disclosed herein, for example, compounds of the present disclosure include compounds of formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), including the compounds of the Examples.

[0029] As used herein, "composition" is intended to encompass a product containing the specified ingredients in the specified amounts, and any product that results directly or indirectly from combining the specified ingredients in the specified amounts. "Pharmaceutically acceptable" means the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0030] "Pharmaceutically effective amount" refers to the amount of a compound of the present disclosure in a formulation or combination thereof that produces the desired therapeutic or pharmaceutical result.

[0031] "Pharmaceutically acceptable excipients" include, but are not limited to, any adjuvant, carrier, filler, glidant, sweetener, diluent, preservative, dye / colorant, flavoring, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier approved by the U.S. Food and Drug Administration as acceptable for use in humans or veterinary medicine.

[0032] As used herein, "treatment" or "treating" or "treating" refers to an approach for obtaining a beneficial or desired result. For purposes of this disclosure, a beneficial or desired result includes, but is not limited to, alleviating symptoms and / or reducing the severity of symptoms and / or preventing worsening of symptoms associated with a disease or condition. In one embodiment, "treatment" or "treating" includes one or more of the following: a) inhibiting the disease or condition (e.g., reducing one or more symptoms caused by the disease or condition and / or reducing the severity of the disease or condition); b) delaying the onset of or inhibiting one or more symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, slowing the worsening or progression of the disease or condition); and c) alleviating the disease or condition, e.g., causing regression of clinical symptoms, ameliorating the pathology, slowing disease progression, improving quality of life, and / or prolonging survival.

[0033] The term "treatment" or "treat" or "treating" also encompasses alleviating or eliminating symptoms of a viral infection and / or reducing the viral load in a patient. The term "treatment" also encompasses administration of a compound or composition according to embodiments disclosed herein after exposure of an individual to a virus, but before the appearance of disease symptoms and / or detection of the virus in the blood, to prevent the appearance of disease symptoms and / or to prevent the virus from reaching detectable levels in the blood.

[0034] As used herein, a "therapeutically effective amount" or "effective amount" refers to an amount that, when administered to a subject to treat a disease, is effective to elicit a desired biological or medical response, including an amount of compound sufficient to achieve such treatment of the disease. An effective amount may vary depending on the compound, the disease and its severity, and the age, weight, etc., of the subject being treated. An effective amount may include a range of amounts. As understood in the art, an effective amount may be one or more doses, i.e., a single dose or multiple doses may be required to achieve a desired therapeutic endpoint. An effective amount may be considered in relation to the administration of one or more therapeutic agents, and a single agent may be considered to be administered in an effective amount when a desired or beneficial result can be or is achieved in combination with one or more other agents. The suitable dose of any co-administered compound may, optionally, be reduced due to the combined effects (e.g., additive or synergistic effects) of the compounds.

[0035] "Administering" refers to oral administration, administration as a suppository, topical contact, parenteral administration, intravenous administration, intraperitoneal administration, intramuscular administration, intralesional administration, intranasal or subcutaneous administration, intrathecal administration, or implantation of a sustained-release device, e.g., a mini-osmotic pump, to a subject. Administration can be carried out according to a schedule that dictates the frequency of administration, the dosage administered, and other factors.

[0036] As used herein, "co-administration" refers to administration of a unit dose of a compound disclosed herein before or after administration of a unit dose of one or more additional therapeutic agents, e.g., administration of a compound disclosed herein within seconds, minutes, or hours of administration of one or more additional therapeutic agents. For example, in some embodiments, a unit dose of a compound disclosed herein is administered first, followed within seconds or minutes by a unit dose of one or more additional therapeutic agents. Alternatively, in other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed within seconds or minutes by a unit dose of a compound disclosed herein. In some embodiments, a unit dose of a compound disclosed herein is administered first, followed several hours (e.g., 1-12 hours) later by a unit dose of one or more additional therapeutic agents. In other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed several hours (e.g., 1-12 hours) later by a unit dose of a compound disclosed herein. Co-administration of a compound disclosed herein with one or more additional therapeutic agents generally refers to the simultaneous or sequential administration of a compound disclosed herein and one or more additional therapeutic agents such that a therapeutically effective amount of each agent is present in the patient's body.

[0037] "Subject" refers to animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc. In certain embodiments, the subject is a human.

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

[0039] Pharmaceutically acceptable salts, hydrates, solvates, tautomeric forms, polymorphs, and prodrugs of the compounds described herein are also provided. "Pharmaceutically acceptable" or "physiologically acceptable" refers to compounds, salts, compositions, dosage forms, and other substances that are useful in preparing pharmaceutical compositions suitable for veterinary or human pharmaceutical 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 possesses the desired pharmacological activity of the free base. These salts can be derived from inorganic or organic acids or inorganic or organic 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 sulfate, pyrosulfate, bisulfite, sulfite, bisulfite, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caproate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne, hexyne-1,4-diol, hexyne-2 ... 1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methylsulfonate, propylsulfonate, besylate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, gamma-hydroxybutyrate, glycolate, tartrate, and mandelate. A list of other suitable pharmaceutically acceptable salts can be found in Remington: The Science and Practice of Pharmacy, 21 st Edition, Lippincott Williams and Wilkins, Philadelphia, Pa., 2006.

[0041] Examples of "pharmaceutically acceptable salts" of the compounds disclosed herein include alkali metal (e.g., sodium, potassium), alkaline earth metal (e.g., magnesium), ammonium, and NX4 salts. +(X is C1-C4 alkyl). Base addition salts such as sodium or potassium salts are also included.

[0042] Also provided are compounds described herein, or pharmaceutically acceptable salts, isomers, or mixtures thereof, in which 1 to n hydrogen atoms bonded to a carbon atom may be replaced by deuterium atoms or D, where n is the number of hydrogen atoms in the molecule. As is known in the art, deuterium atoms are non-radioactive isotopes of hydrogen atoms. Such compounds may have enhanced resistance to metabolism and may therefore be useful for increasing the half-life of the compounds described herein, or pharmaceutically acceptable salts, isomers, or mixtures thereof, when administered to a mammal. See, for example, Foster, "Deuterium Isotope Effects in Studies of Drug Metabolism," Trends Pharmacol. Sci., 5(12):524-527 (1984). Such compounds are synthesized by means well known in the art, for example, by using starting materials in which one or more hydrogen atoms have been replaced 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 can also be mentioned. 11 C. 18 F, 15 O, and 13Substitution with positron emitting isotopes, such as N, can be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art, or by processes analogous to those described in the Examples below, using appropriate isotopically labeled reagents in place of conventionally used non-labeled reagents.

[0044] The compounds of the embodiments disclosed herein, or pharmaceutically acceptable salts thereof, may contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined with respect to absolute stereochemistry as (R)- or (S)-, or, for amino acids, as (D)- or (L)-. The compounds of the embodiments disclosed herein, or pharmaceutically acceptable salts thereof, may be "atropisomers," i.e., stereoisomers resulting from hindrance of rotation about a single bond, where the barrier to rotation about that bond is high enough to permit isolation of individual stereoisomers. The present disclosure is meant to include all such possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, such as chromatography and fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of the racemate (or racemate of a salt or derivative) using, for example, chiral high-pressure liquid chromatography (HPLC). When compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, these compounds are intended to include both E and Z geometric isomers. Likewise, all tautomeric forms are also intended to be included. When compounds are represented in their chiral form, it is understood that embodiments include, but are not limited to, the specific diastereomerically or enantiomerically enriched forms. Where chirality is not specified, it is understood that embodiments are directed to either the specific diastereomerically or enantiomerically enriched form, or racemic or scalemic mixtures of such compounds. As used herein, a "scalemic mixture" is a mixture of stereoisomers in a ratio other than 1:1.

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

[0046] "Stereoisomers" refer to compounds that differ in the chirality of one or more stereocenters. Stereoisomers include enantiomers and diastereomers. Compounds can exist in stereoisomeric forms if they have one or more asymmetric centers or double bonds with asymmetric substitution and can therefore be produced as individual stereoisomers or mixtures. Unless otherwise specified, the description is intended to include individual stereoisomers and mixtures. Methods for the determination of stereochemistry and the separation of stereoisomers are well known in the art (see, for example, Chapter 4 of Advanced Organic Chemistry, 4th ed., J. March, John Wiley and Sons, New York, 1992).

[0047] Atropisomers as described herein are represented by bold bonds. [ka] Wedge-shaped bond [ka] Hashed Joins [ka] and hashed wedge joins [ka] can be represented using in a manner well understood by those skilled in the art. By way of example, the following shows various representations of atropisomeric pairs: [ka]

[0048] "Tautomer" refers to alternative forms of a compound that differ in the location of a proton, such as enol-keto and imine-enamine tautomers, or tautomeric forms of heteroaryl groups that contain ring atoms attached to both the -NH- and =N- rings, such as pyrazole, imidazole, benzimidazole, triazole, and tetrazole.

[0049] 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 before or after chemical groups are for convenience; chemical groups may be designated with or without one or more dashes without losing their ordinary meaning. Wavy lines drawn across lines in structures indicate points of attachment of groups. Dashed lines indicate optional bonds. Unless chemically or structurally required, no directionality is indicated or implied in the order in which chemical groups are written or their point of attachment to the rest of the molecule. For example, the group "-SO2CH2-" is equivalent to "-CH2SO2-" and both can be linked in either direction. Similarly, for example, an "arylalkyl" group may be attached to the rest of the molecule at either the aryl or alkyl portion of the group. "C u~v " or (C u ~C v ) 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 from 1 to 6 carbon atoms.

[0050] As used herein, the term "antiviral agent" is intended to mean an agent effective to inhibit the formation and / or replication of a virus in a mammal, including, but not limited to, an agent that interferes with either host or viral mechanisms necessary for the formation and / or replication of a virus in a mammal.

[0051] Whenever a compound described herein is substituted with two or more of the same group, e.g., designated "R" or "R", it will be understood that unless otherwise indicated, the groups can be the same or different, i.e., each group is independently selected.

[0052] Wavy Lines [ka] indicates the site of covalent attachment to an adjacent substructure, group, moiety, or atom.

[0053] "C u~v " and "(C u~v The prefix "C )" indicates that the following group has carbon atoms u to v. For example, "C 1~8 "Alkyl" indicates that the alkyl group has from 1 to 8 carbon atoms.

[0054] Certain commonly used alternative chemical names may be used, for example, divalent groups such as divalent "alkyl" groups, divalent "aryl" groups, etc. may also be referred to as "alkylene" or "alkylenyl" groups, "arylene" or "arylenyl" groups, respectively.

[0055] Also, unless expressly stated otherwise, when a combination of groups is referred to herein as a single moiety, e.g., arylalkyl, the last-mentioned group contains the atom by which that moiety is attached to the remainder of the molecule.

[0056] The term "substituted" means that any one or more hydrogen atoms on the specified atom or group are replaced with one or more substituents other than hydrogen, provided that the normal valence of the specified atom is not exceeded. The one or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, amido, amidino, aryl, azido, carbamoyl, carboxyl, carboxyl ester, cyano, guanidino, halo, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxy, hydrazino, imino, oxo, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thione, or combinations thereof, unless otherwise indicated.

[0057] Additionally, the term "optionally substituted" refers to any one or more hydrogen atoms on a specified atom or group that may or may not be replaced by a non-hydrogen moiety. compound

[0058] The present disclosure provides compounds that are inhibitors of the SARS-CoV-2 main protease. In some embodiments, the present disclosure provides compounds of formula (I) and / or pharmaceutically acceptable salt(s) thereof as described herein. In some embodiments, the compounds have formula (I): [ka] and / or a pharmaceutically acceptable salt thereof.

[0059] In some embodiments, the compound of formula (I) is [ka] or a pharmaceutically acceptable salt thereof [wherein: ring [ka] is C 6~10aryl or 5-10 membered heteroaryl; Each L 1 are independently a bond, -O-, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)-, -C 1~6 Alkyl-O(C 1~6 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~6 alkyl)(R L )NC(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~6 alkyl)-, -C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~6 alkyl)S(O)2N(R L )-, -(C 1~6 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~6 alkyl)-, -N(R L )S(O)2(C 1~6 alkyl)-, -(C 1~6 alkyl)S(O)2N(R L )(C 1~6 alkyl)- or -(C 1~6 alkyl)N(R L )S(O)2(C 1~6 alkyl)-; Each R 1 are independently halogen, -OH, -CN, C 1~6 Alkyl, -CN, -C(O)NH2, C 2~6 Alkenyl, C 2~6Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a optionally substituted with; Or, two R 1 are the rings to which they are attached. [ka] together with the atom to form a 5- to 10-membered heterocyclyl; Each R 1a independently, C 1~6 Alkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -N(5-10 membered heterocyclyl)2, -N(C6 aryl)2, -N(5-10 membered heteroaryl)2, -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)O(C 1~6 alkyl), -C(O)O(C 3~8Cycloalkyl), -C(O)O(5-10 membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -C(O)N(5-10 membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5-10 membered heteroaryl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 3~8 cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -NHS(O)(C 1~6 alkyl), -N(C 1~6 alkyl)(S(O)(C 1~6 alkyl), -S(O)2(C 1~6 alkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 1b optionally substituted with; Each R 1b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 2~6 alkynyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C 6- aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; m is an integer from 0 to 3; R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Haloalkyl, cyclopropyl, C 1~3 Alkoxy, -O(C 1~3 haloalkyl), -O(cyclopropyl), halogen, or -CN; X 1 is S, N, or C(R x1 ) and; X 2 is S, N, or C(R x2 ) and; X 3 is N or C(R x3 ), where X 1 and X 2 is not S; Or X 3 is a bond, where X 1 and X 2 One of them is S; Each R x1 , R x2 , and R x3 are independently hydrogen, halogen, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl; X 4 and X 5 Tamaki who became friends with [ka] C6 aryl, 5-6 membered heteroaryl, C 5~10 cycloalkyl, or 5- to 10-membered heterocyclyl; Here, each X 4 and X 5 are independently N or C; Or, ring [ka] does not exist, where X 4 is N or CL x4 -R x4 and X 5 is N or CL x5 -R x5 and; Each L x4 and L x5 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4aoptionally substituted with; Each R 4a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 4b optionally substituted with; Each R 4b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each L 3 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6alkyl)C(O)-, or -N(R L )C(O)-; Each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 4 R 3a optionally substituted with; Each R 3a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 3b optionally substituted with; Each R 3b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6alkyl)2; Each R L are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, or C 3~8 is cycloalkyl; n is an integer from 0 to 3; each X 6 and X 7 are independently N, CH, or CF; where X 4 , X 5 , X 6 , and X 7 At most two of are N; L 2 is a bond, C1-C6 alkyl, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)O(C 1~6 alkyl)-, -(C 1~6 alkyl)(R L2 )NC(O)-, -(C 1~6 alkyl)C(O)N(R L2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, -(C 1~6 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)- or -(C 1~6 alkyl)S(O)2-(C 1~6 alkyl)-; R L2 is hydrogen or C 1~6 is alkyl; R 5 is hydrogen, -CN, -OR 5a , -C(O)NR 5a 2, -NR 5a C(O)R 5a , -NR 5a 2、 C 1~6 Alkyl, C 3~8cycloalkyl, C aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b optionally substituted with; Each R 5a are independently hydrogen or C 1~6 is alkyl; Each R 5b are independently selected from halogen, cyclopropyl, hydroxy, -CN, C 1~3 Alkyl, C 1~3 alkoxy, -OCF3, or -OCF2H; and Z is O or S.

[0060] In some embodiments, the compound of formula (I) is [ka] or a pharmaceutically acceptable salt thereof [wherein: ring [ka] is C 6~10 aryl or 5-10 membered heteroaryl; Each L 1 are independently a bond, -O-, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)-, -C 1~6 Alkyl-O(C 1~6 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~6 alkyl)(R L )NC(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~6 alkyl)-, -C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl)N(R L)C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~6 alkyl)S(O)2N(R L )-, -(C 1~6 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~6 alkyl)-, -N(R L )S(O)2(C 1~6 alkyl)-, -(C 1~6 alkyl)S(O)2N(R L )(C 1~6 alkyl)- or -(C 1~6 alkyl)N(R L )S(O)2(C 1~6 alkyl)-; Each R 1 are independently halogen, -OH, -CN, C 1~6 Alkyl, -CN, -C(O)NH2, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a optionally substituted with; Or, two R 1 are the rings to which they are attached. [ka] together with the atom to form a 5- to 10-membered heterocyclyl; Each R 1a independently, C 1~6 Alkyl, halogen, C 3~8Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -N(5-10 membered heterocyclyl)2, -N(C6 aryl)2, -N(5-10 membered heteroaryl)2, -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)O(C 1~6 alkyl), -C(O)O(C 3~8 Cycloalkyl), -C(O)O(5-10 membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -C(O)N(5-10 membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5-10 membered heteroaryl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 3~8cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 3~8 cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -NHS(O)(C 1~6 alkyl), -N(C 1~6 alkyl)(S(O)(C 1~6 alkyl), -S(O)2(C 1~6 alkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 1b optionally substituted with; Each R 1b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 2~6 alkynyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C 6- aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; m is an integer from 0 to 3; R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Haloalkyl, cyclopropyl, C 1~3 Alkoxy, -O(C 1~3 haloalkyl), -O(cyclopropyl), halogen, or -CN; X 1 is S, N, or C(R x1 ) and; X 2 is S, N, or C(R x2) and; X 3 is N or C(R x3 ), where X 1 and X 2 is not S; Or X 3 is a bond, where X 1 and X 2 One of them is S; Each R x1 , R x2 , and R x3 are independently hydrogen, halogen, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl; X 4 and X 5 Tamaki who became friends with [ka] C6 aryl, 5-6 membered heteroaryl, C 5~10 cycloalkyl, or 5- to 10-membered heterocyclyl; Here, each X 4 and X 5 are independently N or C; Or, ring [ka] does not exist, where X 4 is N or CL x4 -R x4 and X 5 is N or CL x5 -R x5 and; Each L x4 and L x5 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a optionally substituted with; Each R 4a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 4b optionally substituted with; Each R 4b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each L 3 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 3a optionally substituted with; Each R 3a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 3b optionally substituted with; Each R 3b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each R L are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, or C 3~8 is cycloalkyl; n is an integer from 0 to 3; each X 6 and X 7 are independently N or CH; where X 4 , X 5 , X 6 , and X 7 At most two of are N; L 2 is a bond, C1-C6 alkyl, -(C1~6 alkyl)O-, -(C 1~6 alkyl)O(C 1~6 alkyl)-, -(C 1~6 alkyl)(R L2 )NC(O)-, -(C 1~6 alkyl)C(O)N(R L2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, or -(C 1~6 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-; R L2 is hydrogen or C 1~6 is alkyl; R 5 is hydrogen, -CN, -OR 5a , -C(O)NR 5a 2, -NR 5a C(O)R 5a , -NR 5a 2、 C 3~8 cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b optionally substituted with; Each R 5a are independently hydrogen or C 1~6 is alkyl; Each R 5b are independently selected from halogen, cyclopropyl, hydroxy, -CN, C 1~3 Alkyl, C 1~3 alkoxy, -OCF3, or -OCF2H; and Z is O or S.

[0061] In some embodiments, the compound of formula (I) is [ka] or a pharmaceutically acceptable salt thereof [wherein: ring [ka] is C 6~10 aryl or 5-10 membered heteroaryl; Each L 1 are independently a bond, -O-, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)-, -C 1~6 Alkyl-O(C 1~6 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~6 alkyl)(R L )NC(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~6 alkyl)-, -C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~6 alkyl)S(O)2N(R L )-, -(C 1~6 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~6 alkyl)-, -N(R L )S(O)2(C 1~6 alkyl)-, -(C 1~6 alkyl)S(O)2N(R L )(C 1~6 alkyl)- or -(C 1~6 alkyl)N(R L )S(O)2(C 1~6 alkyl)-; Each R 1are independently halogen, -OH, -CN, C 1~6 Alkyl, -CN, -C(O)NH2, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C6 aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a optionally substituted with; Each R 1a independently, C 1~6 Alkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -N(5-10 membered heterocyclyl)2, -N(C6 aryl)2, -N(5-10 membered heteroaryl)2, -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)O(C 1~6 alkyl), -C(O)O(C 3~8Cycloalkyl), -C(O)O(5-10 membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -C(O)N(5-10 membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5-10 membered heteroaryl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 3~8 cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -NHS(O)(C 1~6 alkyl), -N(C 1~6 alkyl)(S(O)(C 1~6 alkyl), -S(O)2(C 1~6 alkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 1b optionally substituted with; Each R 1b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 2~6 alkynyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C 6- aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; m is an integer from 0 to 3; R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Haloalkyl, cyclopropyl, C 1~3 Alkoxy, -O(C 1~3 haloalkyl), -O(cyclopropyl), halogen, or -CN; X 1 is S, N, or C(R x1 ) and; X 2 is S, N, or C(R x2 ) and; X 3 is N or C(R x3 ), where X 1 and X 2 is not S; Or X 3 is a bond, where X 1 and X 2 One of them is S; Each R x1 R x2 , and R x3 are independently hydrogen, halogen, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl; X 4 and X 5 Tamaki who became friends with [ka] C6 aryl, 5-6 membered heteroaryl, C 5~10 cycloalkyl, or 5- to 10-membered heterocyclyl; Here, each X 4 and X 5 are independently N or C; Or, ring [ka] does not exist, where X 4 is N or CL x4 -R x4 and X 5 is N or CL x5 -R x5 and; Each L x4 and L x5 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)-; Each R x4 and R x5 are independently hydrogen, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a optionally substituted with; Each R 4a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 4b optionally substituted with; Each R 4b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each L 3 are independently a bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6alkyl)C(O)-, or -N(R L )C(O)-; Each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, or -OC 3~8 is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 3a optionally substituted with; Each R 3a independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 3b optionally substituted with; Each R 3b independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2; Each RL are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, or C 3~8 is cycloalkyl; n is an integer from 0 to 3; each X 6 and X 7 are independently N or CH; where X 4 , X 5 , X 6 , and X 7 At most two of are N; L 2 is a bond, C1-C6 alkyl, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)O(C 1~6 alkyl)-, -(C 1~6 alkyl)(R L2 )NC(O)-, -(C 1~6 alkyl)C(O)N(R L2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, or -(C 1~6 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-; R L2 is hydrogen or C 1~6 is alkyl; R 5 is hydrogen, -CN, -OR 5a , -C(O)NR 5a 2, -NR 5a 2、 C 3~8 cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b optionally substituted with; Each R 5a are independently hydrogen or C 1~6 is alkyl; Each R 5bare independently selected from halogen, cyclopropyl, hydroxy, -CN, C 1~3 Alkyl, C 1~3 alkoxy, -OCF3, or -OCF2H; and Z is O or S.

[0062] In some embodiments, the present disclosure provides a compound according to the structure of formula (I-1): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0063] In some embodiments, the compounds of the present disclosure include X 3 However, N or C(R x3 In some embodiments, the compounds of the present disclosure are compounds wherein X 3 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 3 is C(R x3 ), or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds wherein N or C(R x3 ) and X 1 and X 2 is not S, or a pharmaceutically acceptable salt thereof.

[0064] In some embodiments, the compounds of the present disclosure include X 1 is S, N, or C(R x1 In some embodiments, the compounds of the present disclosure are compounds wherein X 1 is S, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 1 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 1 is C(R x1 ), or a pharmaceutically acceptable salt thereof.

[0065] In some embodiments, the compounds of the present disclosure include X 2 is S, N, or C(R x1 In some embodiments, the compounds of the present disclosure are compounds wherein X 2 is S, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 2 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 2 is C(R x1 ), or a pharmaceutically acceptable salt thereof.

[0066] In some embodiments, the compounds of the present disclosure include X 1 and X 2 is not S, or a pharmaceutically acceptable salt thereof. 1 and X 2 Exactly one of is S.

[0067] In some embodiments, the compounds of the present disclosure include X 3 is a bond, N, or C(R x3 In some embodiments, the compounds of the present disclosure are compounds wherein X 3 However, N or C(R x3In some embodiments, the compounds of the present disclosure are compounds wherein X 3 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 3 is C(R x3 ), or a pharmaceutically acceptable salt thereof.

[0068] In some embodiments, the compounds of the present disclosure include X 1 is C(R x1 ) and X 2 is C(R x2 ) and X 3 is C(R x3 In some embodiments, the compounds of the present disclosure are compounds wherein X 1 is C(R x1 ) and X 2 is C(R x2 ) and X 3 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 1 is N and X 2 is C(R x2 ) and X 3 is C(R x3 In some embodiments, the compounds of the present disclosure are compounds wherein X 1 is N and X 2 is C(R x2 ) and X 3 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 1 is C(R x1 ) and X 2 is N, and X 3 is C(R x3 In some embodiments, the compounds of the present disclosure are compounds wherein X 1 is C(R x1 ) and X 2 is N, and X 3is N, or a pharmaceutically acceptable salt thereof.

[0069] In some embodiments, the present disclosure provides a compound according to the structure of formula (III): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , X 1 , X 2 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0070] In some embodiments, the present disclosure provides a compound according to the structure of formula (III-a): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x1 , R x2 , R x3 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0071] In some embodiments, the present disclosure provides a compound according to the structure of formula (III-b): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x1 , R x3 , X 4 , X 5 , X 6 , X 7 is as described herein.

[0072] In some embodiments, the present disclosure provides a compound according to the structure of formula (III-c): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x2 , R x3 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0073] In some embodiments, the present disclosure provides a compound according to the structure of formula (III-d): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x1 , R x2 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0074] In some embodiments, the compounds of the present disclosure include X 1 is S and X 2 is C(R x2 ) and X 3 is a bond, or a pharmaceutically acceptable salt thereof. 1 is S and X 2 is N, and X 3 is a bond, or a pharmaceutically acceptable salt thereof. 1 is C(R x2 ) and X 2 is S, and X 3 is a bond, or a pharmaceutically acceptable salt thereof. 1 is N and X 2 is S, and X 3 is a bond, or a pharmaceutically acceptable salt thereof.

[0075] In some embodiments, the present disclosure provides a compound according to the structure of formula (II): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , X 1 , X 2 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0076] In some embodiments, the present disclosure provides a compound according to the structure of formula (II-a): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x1 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0077] In some embodiments, the present disclosure provides a compound according to the structure of formula (II-b): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x2 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0078] In some embodiments, the present disclosure provides a compound according to the structure of formula (II-c): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , X 4 , X 5 , X 6 , X 7 , Z, m, and n are as described herein.

[0079] In some embodiments, the present disclosure provides a compound according to the structure of formula (II-d): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , X 4 , X5 , X 6 , X 7 , Z, m, and n are as described herein.

[0080] In some embodiments, the compounds of the present disclosure include a ring [ka] But C 6~10 In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein the ring is aryl or 5-10 membered heteroaryl. [ka] C 6~10 In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein the ring is aryl. [ka] is C6 aryl, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are [ka] C 10 aryl, or a pharmaceutically acceptable salt thereof. 6~10 Aryl is phenyl. In some embodiments, C 6~10 The aryl is indanyl.

[0081] In some embodiments, the compounds of the present disclosure include a ring [ka] is C6 aryl and the substituent meta to the point of attachment is hydrogen, or a pharmaceutically acceptable salt thereof. [ka] or a pharmaceutically acceptable salt thereof.

[0082] In some embodiments, the compounds of the present disclosure include a ring [ka] is a 5- to 10-membered heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is a 5- to 9-membered heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is a 6- to 10-membered heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is a 6- to 9-membered heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is a 5-, 6-, 7-, 8-, 9-, or 10-membered heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is a nitrogen-containing heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is a sulfur-containing heteroaryl, or a pharmaceutically acceptable salt thereof. [ka] is an oxygen-containing heteroaryl, or a pharmaceutically acceptable salt thereof. In some embodiments, heteroaryl comprises pyridine, pyrimidine such as pyrimidinedione, oxazole, pyrrole, pyrazole, imidazole, triazole, or thiophene, each of which is independently selected from the group consisting of aryl, ... [ka] is optionally fused to another ring forming

[0083] In some embodiments, the compounds of the present disclosure include a ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] or a pharmaceutically acceptable salt thereof.

[0084] In some embodiments, the compounds of the present disclosure each L 1 are independently a bond, -O-, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)-, -C 1~6 Alkyl-O(C 1~6 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~6 alkyl)(R L )NC(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~6 alkyl)-, -C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -S(O)2-, -S(O)2N(RL )-, -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)-, where R L or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds in which each L 1 are independently a bond, -O-, -(C 1~3 alkyl)O-, -O(C 1~3 alkyl)-, -C 1~3 Alkyl-O(C 1~3 alkyl)-, -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~3 alkyl)(R L )NC(O)-, -(C 1~3 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~3 alkyl)-, -C(O)N(R L )(C 1~3 alkyl)-, -(C 1~3 alkyl)N(R L )C(O)(C 1~3 alkyl)-, -(C 1~3 alkyl)C(O)N(R L )(C 1~3 alkyl)-, -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~3 alkyl)S(O)2N(RL )-, -(C 1~3 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~3 alkyl)-, -N(R L )S(O)2(C 1~3 alkyl)-, -(C 1~3 alkyl)S(O)2N(R L )(C 1~3 alkyl)- or -(C 1~3 alkyl)N(R L )S(O)2(C 1~3 alkyl)-, where R L is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0085] In some embodiments, the compounds of the present disclosure each L 1 However, 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(RL )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)-, where R L or a pharmaceutically acceptable salt thereof, wherein each L 1 However, 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(RL )S(O)2(C 1~3 alkyl)-, -(C 1~3 alkyl)S(O)2N(R L )(C 1~3 alkyl)- or -(C 1~3 alkyl)N(R L )S(O)2(C 1~3 alkyl)-, where R L is a compound, or a pharmaceutically acceptable salt thereof, as defined herein.

[0086] In some embodiments, the compounds of the present disclosure each L 1 However, independently, -O-, -(C 1~3 alkyl)O-, -O(C 1~3 alkyl)- or -C 1~3 Alkyl-O(C 1~3 alkyl)-, or a pharmaceutically acceptable salt thereof.

[0087] In some embodiments, the compounds of the present disclosure each L 1 are independently -C(O)-, -N(R L )C(O)-, -C(O)N(R L )-, -(C 1~3 alkyl)(R L )NC(O)-, -(C 1~3 alkyl)C(O)N(R L )-, -N(R L )C(O)(C 1~3 alkyl)-, -C(O)N(R L )(C 1~3 alkyl)-, -(C 1~3 alkyl)N(R L )C(O)(C 1~3 alkyl)- or -(C 1~3 alkyl)C(O)N(R L )(C 1~3 alkyl)-, where R L is a compound, or a pharmaceutically acceptable salt thereof, as defined herein.

[0088] In some embodiments, the compounds of the present disclosure each L1 are independently -S(O)2-, -S(O)2N(R L )-, -N(R L )-S(O)2-, -(C 1~3 alkyl)S(O)2N(R L )-, -(C 1~3 alkyl)N(R L )S(O)2-, -S(O)2N(R L )(C 1~3 alkyl)-, -N(R L )S(O)2(C 1~3 alkyl)-, -(C 1~3 alkyl)S(O)2N(R L )(C 1~3 alkyl)- or -(C 1~3 alkyl)N(R L )S(O)2(C 1~3 alkyl)-, where R L is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0089] In some embodiments, the compounds of the present disclosure each L 1 is a bond, or a pharmaceutically acceptable salt thereof.

[0090] In some embodiments, the compounds of the present disclosure each L 1 However, independently, -(C 1~6 alkyl)O-, -O(C 1~6 alkyl)- or -C 1~6 Alkyl-O(C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein each L 1 However, independently, -(C 1~3 alkyl)O-, -O(C 1~3 alkyl)- or -C 1~3 Alkyl-O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each L 1are independently -(methyl)O-, -O(methyl)-, or -methyl-O(methyl)-, or a pharmaceutically acceptable salt thereof.

[0091] In some embodiments, the compounds of the present disclosure each L 1 However, independently, -(C 1~6 alkyl)O-, or -O(C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein each L 1 However, independently, -(C 1~3 alkyl)O-, or -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each L 1 are independently -(methyl)O-, or -O(methyl)-, or a pharmaceutically acceptable salt thereof.

[0092] In some embodiments, compounds of the present disclosure include compounds in which each R 1 are independently halogen, -OH, -CN, C 1~6 Alkyl, -CN, -C(O)NH2, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 1 are independently fluoro, chloro, -OH, -CN, C 1~3 Alkyl, -CN, -C(O)NH2, C 2~3 Alkenyl, C 2~3 Alkynyl, C 1~3 Alkoxy, C 3~8cycloalkyl, C aryl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocyclyl, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with 1 to 3 R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one or two R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one R 1a is optionally substituted with

[0093] In some embodiments, compounds of the present disclosure include compounds in which each R 1 are independently halogen, -CN, -C(O)NH2, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C aryl, or 5-10 membered heteroaryl, wherein each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl is selected from 1 to 3 R 1a In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 1 are independently fluoro, chloro, -CN, -C(O)NH2, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Alkoxy, C 3~8 Each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl is cycloalkyl, C aryl, or 5- to 10-membered heteroaryl, and each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl is selected from 1 to 3 R1a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl is optionally substituted with one or two R 1a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, aryl, and heteroaryl is optionally substituted with one R 1a is optionally substituted with

[0094] In some embodiments, compounds of the present disclosure include compounds in which each R 1 are independently halogen, -CN, -C(O)NH2, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, or 5- to 10-membered heteroaryl, wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heteroaryl is selected from one or two R 1a In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 1 are independently fluoro, chloro -CN, -C(O)NH2, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Alkoxy, C 3~8 cycloalkyl, or 5- to 10-membered heteroaryl, wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heteroaryl is selected from one or two R 1a In some embodiments, each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one R 1a is optionally substituted with

[0095] In some embodiments, compounds of the present disclosure include compounds in which each R 1 are independently halogen, -CN, or C 1~6In some embodiments, the compounds of the present disclosure are compounds wherein each R is alkoxy, or a pharmaceutically acceptable salt thereof. 1 is independently chloro, fluoro, —CN, or methoxy, or a pharmaceutically acceptable salt thereof. 1 is independently fluoro, —CN, or methoxy, or a pharmaceutically acceptable salt thereof. 1 are independently halogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each R is alkoxy, or a pharmaceutically acceptable salt thereof. 1 is independently chloro, fluoro, or methoxy, or a pharmaceutically acceptable salt thereof.

[0096] In some embodiments, compounds of the present disclosure include compounds in which each R 1a But independently, C 1~6 Alkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -N(5-10 membered heterocyclyl)2, -N(C6 aryl)2, -N(5-10 membered heteroaryl)2, -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)O(C 1~6 alkyl), -C(O)O(C 3~8 Cycloalkyl), -C(O)O(5-10 membered heterocyclyl), -C(O)O(C6 aryl), -C(O)O(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -C(O)N(5-10 membered heterocyclyl)2, -C(O)N(C6 aryl)2, -C(O)N(5-10 membered heteroaryl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 3~8 cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -NHS(O)(C 1~6 alkyl), -N(C 1~6 alkyl)(S(O)(C 1~6 alkyl), -S(O)2(C 1~6 alkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, where each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 1b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or two R 1b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one R 1b is optionally substituted with

[0097] In some embodiments, compounds of the present disclosure include compounds in which each R 1a are independently halogen, -OH, -CN, -C(O)NH2, C 1~6 Alkyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C aryl, or 5-10 membered heteroaryl, wherein each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is selected from 1-3 R 1b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 1a are independently fluoro, chloro, -OH, -CN, -C(O)NH2, C 1~3 Alkyl, C 1~3 Alkoxy, C 3~8 cycloalkyl, C aryl, or 5-10 membered heteroaryl, wherein each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is selected from 1-3 R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is optionally substituted with one or two R 1bIn some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is optionally substituted with one or two R 1b is optionally substituted with

[0098] In some embodiments, compounds of the present disclosure comprise at least one R 1a are independently halogen, -OH, -CN, -C(O)NH2, C 1~6 Alkyl, C 1~6 Alkoxy, C 3~8 cycloalkyl, C aryl, or 5-10 membered heteroaryl, wherein each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is selected from 1-3 R 1b In some embodiments, the compounds of the present disclosure are compounds having at least one R 1a are independently fluoro, chloro, -OH, -CN, -C(O)NH2, C 1~3 Alkyl, C 1~3 Alkoxy, C 3~8 cycloalkyl, C aryl, or 5-10 membered heteroaryl, wherein each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is selected from 1-3 R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is optionally substituted with one or two R 1b In some embodiments, each alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl is optionally substituted with one or two R 1b is optionally substituted with

[0099] In some embodiments, compounds of the present disclosure include compounds in which each R 1a are independently halogen, -OH, -C(O)NH2, C 1~6 Alkyl, C 1~6 alkoxy, or C6 aryl, wherein each alkyl, alkoxy, and aryl is selected from 1 to 3 R1b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 1a are independently fluoro, chloro, -OH, -C(O)NH2, C 1~6 Alkyl, C 1~6 alkoxy, or C6 aryl, wherein each alkyl, alkoxy, and aryl is selected from 1 to 3 R 1b In some embodiments, each alkyl, alkoxy, and aryl is optionally substituted with one or two R 1b In some embodiments, each alkyl, alkoxy, and aryl is optionally substituted with one or two R 1b is optionally substituted with

[0100] In some embodiments, compounds of the present disclosure comprise at least one R 1a are independently halogen, -OH, -C(O)NH2, C 1~6 Alkyl, C 1~6 alkoxy, or C6 aryl, wherein each alkyl, alkoxy, and aryl is selected from 1 to 3 R 1b In some embodiments, the compounds of the present disclosure are compounds having at least one R 1a are independently fluoro, chloro, -OH, -C(O)NH2, C 1~6 Alkyl, C 1~6 alkoxy, or C6 aryl, wherein each alkyl, alkoxy, and aryl is selected from 1 to 3 R 1b In some embodiments, each alkyl, alkoxy, and aryl is optionally substituted with one or two R 1b In some embodiments, each alkyl, alkoxy, and aryl is optionally substituted with one or two R 1b is optionally substituted with

[0101] In some embodiments, compounds of the present disclosure include R 1a is a halogen, or a pharmaceutically acceptable salt thereof. 1a is fluoro. In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein R 1a is chloro, or a pharmaceutically acceptable salt thereof.

[0102] In some embodiments, compounds of the present disclosure comprise at least one R 1a is halogen. In some embodiments, the compounds of the present disclosure have at least one R 1a In some embodiments, the compounds of the present disclosure have at least one R 1a is chloro, or a pharmaceutically acceptable salt thereof.

[0103] In some embodiments, compounds of the present disclosure include compounds in which each R 1b But independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 2~6 alkynyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C 6- aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 Cycloalkyl), -S(O)2(5-10 membered heterocyclyl), -S(O)2(C6 aryl), -S(O)2(5-10 membered heteroaryl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, or a pharmaceutically acceptable salt thereof.

[0104] In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is an integer from 0 to 3. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is an integer from 0 to 2. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is 0. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is 1 or 2. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is 0. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is 1. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is 2. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where m is 3.

[0105] In some embodiments, compounds of the present disclosure include R 2 But hydrogen, C 1~3 Alkyl, C 1~3 Haloalkyl, cyclopropyl, C 1~3 Alkoxy, -O(C 1~3 -O(haloalkyl), -O(cyclopropyl), halogen, or -CN, or a pharmaceutically acceptable salt thereof.

[0106] In some embodiments, compounds of the present disclosure include R 2 But hydrogen, halogens, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. 2 is hydrogen, fluoro, chloro, methyl, or methoxy, or a pharmaceutically acceptable salt thereof.

[0107] In some embodiments, compounds of the present disclosure include R 2 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0108] In some embodiments, compounds of the present disclosure include R 2 is fluoro. In some embodiments, the compounds of the present disclosure have the formula R 2 is chloro, or a pharmaceutically acceptable salt thereof.

[0109] In some embodiments, compounds of the present disclosure include R x1 But hydrogen, halogens, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0110] In some embodiments, compounds of the present disclosure include R x1 But halogen, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x1 is fluoro, chloro, methyl, or methoxy, or a pharmaceutically acceptable salt thereof.

[0111] In some embodiments, compounds of the present disclosure include R x1 But halogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. x1 is fluoro, chloro, or methyl, or a pharmaceutically acceptable salt thereof.

[0112] In some embodiments, compounds of the present disclosure include R x1 But halogen, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x1is fluoro, chloro, or methoxy, or a pharmaceutically acceptable salt thereof.

[0113] In some embodiments, compounds of the present disclosure include R x1 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0114] In some embodiments, compounds of the present disclosure include R x2 But hydrogen, halogens, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0115] In some embodiments, compounds of the present disclosure include R x2 But halogen, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x2 is fluoro, chloro, methyl, or methoxy, or a pharmaceutically acceptable salt thereof.

[0116] In some embodiments, compounds of the present disclosure include R x2 But halogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. x2 is fluoro, chloro, or methyl, or a pharmaceutically acceptable salt thereof.

[0117] In some embodiments, compounds of the present disclosure include R x2 But halogen, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x2is fluoro, chloro, or methoxy, or a pharmaceutically acceptable salt thereof.

[0118] In some embodiments, compounds of the present disclosure include R x2 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0119] In some embodiments, compounds of the present disclosure include R x3 But hydrogen, halogens, C 1~3 Alkyl, C 1~3 Haloalkyl, OC 1~3 Haloalkyl, C 1~3 alkoxy, cyclopropyl, or O-cyclopropyl, or a pharmaceutically acceptable salt thereof.

[0120] In some embodiments, compounds of the present disclosure include R x3 But halogen, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x3 is fluoro, chloro, methyl, or methoxy, or a pharmaceutically acceptable salt thereof.

[0121] In some embodiments, compounds of the present disclosure include R x3 But halogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. x3 is fluoro, chloro, or methyl, or a pharmaceutically acceptable salt thereof.

[0122] In some embodiments, compounds of the present disclosure include R x3 But halogen, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x3is fluoro, chloro, or methoxy, or a pharmaceutically acceptable salt thereof.

[0123] In some embodiments, compounds of the present disclosure include R x3 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0124] In some embodiments, the compounds of the present disclosure include X 4 and X 5 Tamaki who became friends with [ka] C6 aryl, 5-6 membered heteroaryl, C 5~10 cycloalkyl, or 5- to 10-membered heterocyclyl, or a pharmaceutically acceptable salt thereof.

[0125] In some embodiments, the compounds of the present disclosure include X 4 and X 5 Tamaki who became friends with [ka] is a C6 aryl, where each X 4 and X 5 is independently N or C, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 4 and X 5 Tamaki who became friends with [ka] is a 5- to 6-membered heteroaryl, where each X 4 and X 5 is independently N or C, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 4 and X 5 Tamaki who became friends with [ka] C 5~10cycloalkyl, where each X 4 and X 5 is independently N or C, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 4 and X 5 Tamaki who became friends with [ka] is a 5- to 10-membered heterocyclyl, where each X 4 and X 5 is independently N or C, or a pharmaceutically acceptable salt thereof.

[0126] In some embodiments, compounds of the present disclosure each X 4 and X 5 is independently N or C, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 4 and X 5 and each is C, or a pharmaceutically acceptable salt thereof.

[0127] In some embodiments, the present disclosure provides a compound according to the structure of formula (IV): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , X 1 , X 2 , X 3 , Z, m, and n are as described herein.

[0128] In some embodiments, the compounds of the present disclosure include X 4 , X5 , X 6 and X 7 A ring containing a ring [ka] or a pharmaceutically acceptable salt thereof.

[0129] In some embodiments, the present disclosure provides a compound according to the structure of formula (IV-a): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x1 , Z, m, and n are as described herein.

[0130] In some embodiments, the present disclosure provides a compound according to the structure of formula (IV-b): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 5 , R x1 , R x2 , R x3 , Z, m, and n are as described herein.

[0131] In some embodiments, the compounds of the present disclosure include a ring [ka] is a 5-membered heteroaryl, or a pharmaceutically acceptable salt thereof. 4 , X 5 , X 6 and X 7 A ring containing a ring [ka] or a pharmaceutically acceptable salt thereof.

[0132] In some embodiments, the compounds of the present disclosure include a ring [ka] does not exist and X 4 But N or CL x4 -R x4 and X 5 But N or CL x5 -R x5 In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] does not exist and X 4 is N and X 5 But CL x5 -R x5 In some embodiments, the compounds of the present disclosure are compounds having the ring [ka] does not exist and X 4 But CL x4 -R x4 and X 5 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are [ka] does not exist and X 4 But CL x4 -R x4 and X 5 But CL x5 -R x5 or a pharmaceutically acceptable salt thereof.

[0133] In some embodiments, the compounds of the present disclosure include X 4 is N and X 5 But CL x5 -R x5 or a pharmaceutically acceptable salt thereof.

[0134] In some embodiments, the present disclosure provides a compound according to the structure of formula (V): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , R 1 , R 2 , R 5 , R x4 , R x5 , X 1 , X 2 , X 3 , Z, m, and n are as described herein.

[0135] In some embodiments, the present disclosure provides a compound according to the structure of formula (Va): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1, L 2 , R 1 , R 2 , R 5 , R x1 , R x4 , R x5 , Z, m, and n are as described herein.

[0136] In some embodiments, the present disclosure provides a compound according to the structure of formula (Vb): [ka] and / or pharmaceutically acceptable salt(s) thereof, wherein: [ka] L 1 , L 2 , R 1 , R 2 , R 5 , R x1 , R x2 , R x3 , R x4 , R x5 , Z, m, and are as described herein.

[0137] In some embodiments, the compounds of the present disclosure include L x4 is the bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(RL )C(O)—, where R L or a pharmaceutically acceptable salt thereof, wherein: x4 is the bond, -(C 1~3 alkyl)O-, -(C 1~3 alkyl)N(R L )C(O)-, -(C 1~3 alkyl)C(O)N(R L )-, -(C 1~3 alkyl)N(R L )C(O)(C 1~3 alkyl)-, -(C 1~3 alkyl)C(O)N(R L )(C 1~3 alkyl)-, -(C 1~3 alkyl), -(C 1~3 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~3 alkyl)C(O)-, or -N(R L )C(O)—, where R L is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0138] In some embodiments, the compounds of the present disclosure include L x4 But -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6alkyl)C(O)-, or -N(R L )C(O)—, where R L or a pharmaceutically acceptable salt thereof, wherein: x4 But -(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 is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0139] In some embodiments, the compounds of the present disclosure include L x4 is a bond or N(R L )S(O)2- and R L or a pharmaceutically acceptable salt thereof, wherein L x4 But N(R L )S(O)2- and R L is a compound, or a pharmaceutically acceptable salt thereof, as defined herein.

[0140] In some embodiments, the compounds of the present disclosure include L x4 is a bond, or a pharmaceutically acceptable salt thereof.

[0141] In some embodiments, the compounds of the present disclosure include L x5 But -(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 or a pharmaceutically acceptable salt thereof, wherein: x5 But -(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 is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0142] In some embodiments, the compounds of the present disclosure include L x5 is a bond or N(R L )S(O)2- and R L or a pharmaceutically acceptable salt thereof, wherein L x5 is N(R L )S(O)2- and R L is a compound, or a pharmaceutically acceptable salt thereof, as defined herein.

[0143] In some embodiments, the compounds of the present disclosure include L x5 is a bond, or a pharmaceutically acceptable salt thereof.

[0144] In some embodiments, compounds of the present disclosure include R x4 is hydrogen, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 cycloalkyl, where each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a In some embodiments, the compounds of the present disclosure are compounds optionally substituted with R x4 is hydrogen, halogen, hydroxy, -CN, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 alkyl)2, -O(C 1~3 alkyl), or -OC3~8 cycloalkyl, where each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with 1 to 3 R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0145] In some embodiments, compounds of the present disclosure include R x4 is hydrogen, C1-C6 alkyl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl)2, C 1~6 alkoxy, C3-C8 cycloalkyl, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, the compounds of the present disclosure are compounds optionally substituted with R x4 is hydrogen, C1-C3 alkyl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 Alkyl)2, C 1~3 alkoxy, C3-C8 cycloalkyl, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one or two R 4aIn some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0146] In some embodiments, compounds of the present disclosure include R x4 is C3-C8 cycloalkyl, or a pharmaceutically acceptable salt thereof. x4 is a C3-C8 cycloalkyl, and the cycloalkyl is selected from the group consisting of one or two R 4a and optionally substituted with R x5 is hydrogen, or a pharmaceutically acceptable salt thereof. In some embodiments, a cycloalkyl is a compound having one R 4a is optionally substituted with

[0147] In some embodiments, compounds of the present disclosure include R x4 But C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x4 But C 1~6 alkoxy, wherein the alkoxy is one or two R 4a and optionally substituted with R x5 is hydrogen, or a pharmaceutically acceptable salt thereof. In some embodiments, an alkoxy is a compound having one R 4a In some embodiments, the alkoxy is methoxy.

[0148] In some embodiments, compounds of the present disclosure include R x4 C1-C6 alkyl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl)2, C 1~6 alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R 4aIn some embodiments, the compounds of the present disclosure are compounds optionally substituted with R x4 C1-C3 alkyl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 Alkyl)2, C 1~3 alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0149] In some embodiments, compounds of the present disclosure include R x4 However, 1 to 3 R 4a In some embodiments, the heterocyclyl is a 5- to 7-membered heterocyclyl optionally substituted with one or two R 4a In some embodiments, the heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0150] In some embodiments, compounds of the present disclosure include R x4 However, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 alkyl)2, or -O(C 1~3 alkyl), where each alkyl is independently selected from one or two R 4a In some embodiments, each alkyl is optionally substituted with one R 4a is optionally substituted with

[0151] In some embodiments, compounds of the present disclosure include Rx4 is methyl, or a pharmaceutically acceptable salt thereof.

[0152] In some embodiments, compounds of the present disclosure include R x5 is hydrogen, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 cycloalkyl, where each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a In some embodiments, the compounds of the present disclosure are compounds optionally substituted with R x5 is hydrogen, halogen, hydroxy, -CN, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 alkyl)2, -O(C 1~3 alkyl), or -OC 3~8 cycloalkyl, where each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with 1 to 3 R 4a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one or two R 4aIn some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0153] In some embodiments, compounds of the present disclosure include R x5 is hydrogen, C1-C6 alkyl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl)2, C 1~6 alkoxy, C3-C8 cycloalkyl, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, the compounds of the present disclosure are compounds optionally substituted with R x5 is hydrogen, C1-C3 alkyl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 Alkyl)2, C 1~3 alkoxy, C3-C8 cycloalkyl, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one or two R 4a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0154] In some embodiments, compounds of the present disclosure include R x5 is C3-C8 cycloalkyl, or a pharmaceutically acceptable salt thereof. x5 is a C3-C8 cycloalkyl, and the cycloalkyl is selected from the group consisting of one or two R 4a and optionally substituted with R x4is hydrogen, or a pharmaceutically acceptable salt thereof. In some embodiments, a cycloalkyl is a compound having one R 4a is optionally substituted with

[0155] In some embodiments, compounds of the present disclosure include R x5 But C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkoxy, or a pharmaceutically acceptable salt thereof. x5 But C 1~6 alkoxy, wherein the alkoxy is one or two R 4a and optionally substituted with R x4 is hydrogen, or a pharmaceutically acceptable salt thereof. In some embodiments, an alkoxy is a compound having one R 4a In some embodiments, the alkoxy is methoxy.

[0156] In some embodiments, compounds of the present disclosure include R x5 C1-C6 alkyl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl)2, C 1~6 alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, the compounds of the present disclosure are compounds optionally substituted with R x5 C1-C3 alkyl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 Alkyl)2, C 1~3 alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R 4a In some embodiments, each alkyl, alkoxy, and heterocyclyl is optionally substituted with one or two R 4aIn some embodiments, each alkyl, alkoxy, and heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0157] In some embodiments, compounds of the present disclosure include R x5 However, 1 to 3 R 4a In some embodiments, the heterocyclyl is a 5- to 7-membered heterocyclyl optionally substituted with one or two R 4a In some embodiments, the heterocyclyl is optionally substituted with one R 4a is optionally substituted with

[0158] In some embodiments, compounds of the present disclosure include R x5 However, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 alkyl)2, or -O(C 1~3 alkyl), where each alkyl is independently selected from one or two R 4a In some embodiments, each alkyl is optionally substituted with one R 4a is optionally substituted with

[0159] In some embodiments, compounds of the present disclosure include R x5 is methyl, or a pharmaceutically acceptable salt thereof.

[0160] In some embodiments, compounds of the present disclosure include compounds in which each R 4a But independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6 haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, where each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 4b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or two R 4b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one R 4b is optionally substituted with

[0161] In some embodiments, compounds of the present disclosure include compounds in which each R 4a But independently, C 1~6 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 4b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 4a But independently, C 1~3alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one or two R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one R 4b is optionally substituted with

[0162] In some embodiments, compounds of the present disclosure comprise at least one R 4a But C 1~6 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 4b In some embodiments, the compounds of the present disclosure are compounds having at least one R 4a But independently, C 1~3 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one or two R 4b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one R 4b is optionally substituted with

[0163] In some embodiments, compounds of the present disclosure include compounds in which each R 4a are independently selected from halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1~6alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl), or -C(O)N(C1-C6 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 4b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 4a are independently chloro, fluoro, -C(O)(C1-C3 alkyl), -OH, -O(C 1~3 alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 4b is optionally substituted with

[0164] In some embodiments, compounds of the present disclosure comprise at least one R 4a is halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1~6 alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl), or -C(O)N(C1-C6 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 4b In some embodiments, the compounds of the present disclosure are compounds having at least one R 4a Chloro, fluoro, -C(O)(C1-C3 alkyl), -OH, -O(C 1~3 alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 4bIn some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 4b is optionally substituted with

[0165] In some embodiments, compounds of the present disclosure include compounds in which each R 4a However, independently, -O(C 1~3 alkyl), 5-7 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 4b is optionally substituted with

[0166] In some embodiments, compounds of the present disclosure comprise at least one R 4a But -O(C 1~3 alkyl), 5-7 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 4b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 4b is optionally substituted with

[0167] In some embodiments, compounds of the present disclosure include compounds in which each R 4aare independently halogen or —C(O)(C1-C6 alkyl), where alkyl is selected from 1 to 3 R 4b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 4a is independently halogen or —C(O)(C1-C3 alkyl), or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds wherein each R 4a is independently chloro, fluoro, or —C(O)(methyl), or a pharmaceutically acceptable salt thereof.

[0168] In some embodiments, compounds of the present disclosure comprise at least one R 4a is halogen or —C(O)(C1-C6 alkyl), where alkyl is selected from 1 to 3 R 4b In some embodiments, the compounds of the present disclosure are compounds having at least one R 4a is halogen or —C(O)(C1-C3 alkyl), or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure have at least one R 4a is chloro, fluoro, or —C(O)(methyl), or a pharmaceutically acceptable salt thereof.

[0169] In some embodiments, compounds of the present disclosure include compounds in which each R 4a are independently -OH or -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each R 4a is independently -OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0170] In some embodiments, compounds of the present disclosure comprise at least one R 4a -OH or -O(C 1~3In some embodiments, the compounds of the present disclosure are compounds having at least one R 4a is —OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0171] In some embodiments, compounds of the present disclosure include R 4a is O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R 4a is methoxy, or a pharmaceutically acceptable salt thereof.

[0172] In some embodiments, compounds of the present disclosure comprise at least one R 4a -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds having at least one R 4a is methoxy, or a pharmaceutically acceptable salt thereof.

[0173] In some embodiments, compounds of the present disclosure include compounds in which each R 4a is independently halogen or —OH, or a pharmaceutically acceptable salt thereof. 4a is independently chloro, fluoro, or —OH, or a pharmaceutically acceptable salt thereof.

[0174] In some embodiments, compounds of the present disclosure comprise at least one R 4a is halogen or —OH, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure have at least one R 4a is chloro, fluoro, or —OH, or a pharmaceutically acceptable salt thereof.

[0175] In some embodiments, compounds of the present disclosure include compounds in which each R 4b But independently, C1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5-10 membered heterocyclyl), -O(C6 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, or a pharmaceutically acceptable salt thereof.

[0176] In some embodiments, compounds of the present disclosure include compounds in which each R 4b are independently halogen, -O(C 1~6 alkyl), or -O(C 1~6In some embodiments, the compounds of the present disclosure are compounds wherein each R 4b are independently fluoro, chloro-O(C 1~3 alkyl), or -O(C 1~3 haloalkyl), or a pharmaceutically acceptable salt thereof.

[0177] In some embodiments, compounds of the present disclosure comprise at least one R 4b But halogen, -O(C 1~6 alkyl), or -O(C 1~6 haloalkyl), or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure have at least one R 4b Where halogens are independently fluoro, chloro-O(C 1~3 alkyl), or -O(C 1~3 haloalkyl), or a pharmaceutically acceptable salt thereof.

[0178] In some embodiments, the compounds of the present disclosure each L 3 However, independently, the bond, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 alkyl)C(O)N(R L )(C 1~6 alkyl)-, -(C 1~6 alkyl), -(C 1~6 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~6 alkyl)C(O)-, or -N(R L )C(O)—, where R Lor a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds in which each L 3 However, independently, the bond, -(C 1~3 alkyl)O-, -(C 1~3 alkyl)N(R L )C(O)-, -(C 1~3 alkyl)C(O)N(R L )-, -(C 1~3 alkyl)N(R L )C(O)(C 1~3 alkyl)-, -(C 1~3 alkyl)C(O)N(R L )(C 1~3 alkyl)-, -(C 1~3 alkyl), -(C 1~3 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~3 alkyl)C(O)-, or -N(R L )C(O)—, where R L is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0179] In some embodiments, the compounds of the present disclosure each L 3 However, independently, -(C 1~6 alkyl)O-, -(C 1~6 alkyl)N(R L )C(O)-, -(C 1~6 alkyl)C(O)N(R L )-, -(C 1~6 alkyl)N(R L )C(O)(C 1~6 alkyl)-, -(C 1~6 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 is a compound described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 3 However, independently, -(C 1~3 alkyl)O-, -(C 1~3 alkyl)N(R L )C(O)-, -(C 1~3 alkyl)C(O)N(R L )-, -(C 1~3 alkyl)N(R L )C(O)(C 1~3 alkyl)-, -(C 1~3 alkyl)C(O)N(R L )(C 1~3 alkyl)-, -(C 1~3 alkyl), -(C 1~3 alkyl)N(R L )S(O)2-, -N(R L )S(O)2-, -C(O)-, -(C 1~3 alkyl)C(O)-, or -N(R L )C(O)—, where R L is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0180] In some embodiments, the compounds of the present disclosure include L 3 is a bond or N(R L )S(O)2-, where R L is as defined herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 3 But N(R L )S(O)2-, where R L is as defined herein, or a pharmaceutically acceptable salt thereof.

[0181] In some embodiments, the compounds of the present disclosure include L 3 is a bond, or a pharmaceutically acceptable salt thereof.

[0182] In some embodiments, compounds of the present disclosure include compounds in which each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -O(C 1~6 alkyl), or -OC 3~8 cycloalkyl, where each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 3a In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 3 are independently a bond, halogen, hydroxy, -CN, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Alkoxy, C 3~8 Cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 alkyl)2, -O(C 1~3 alkyl), or -OC 3~8 cycloalkyl, where each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R 3a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with 1 to 3 R 3a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one or two R 3a In some embodiments, each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one R 3a is optionally substituted with

[0183] In some embodiments, compounds of the present disclosure include compounds in which each R 3 are independently a bond, C1-C6 alkyl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl)2, C 1~6 alkoxy, C3-C8 cycloalkyl, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R 3a In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 3 are independently a bond, C1-C3 alkyl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3 Alkyl)2, C 1~3 alkoxy, C3-C8 cycloalkyl, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R 3a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one or two R 3a In some embodiments, each alkyl, alkoxy, cycloalkyl, and heterocyclyl is optionally substituted with one R 3a is optionally substituted with

[0184] In some embodiments, compounds of the present disclosure include R 3 is a C3-C8 cycloalkyl, and the cycloalkyl ... 3a In some embodiments, the cycloalkyl is a compound optionally substituted with one R 3a is optionally substituted with

[0185] In some embodiments, compounds of the present disclosure comprise at least one R 3is a C3-C8 cycloalkyl, where the cycloalkyl is selected from the group consisting of one or two R 3a In some embodiments, the cycloalkyl is a compound optionally substituted with one R 3a is optionally substituted with

[0186] In some embodiments, compounds of the present disclosure include R 3 C 1~6 alkoxy, wherein the alkoxy is selected from one or two R 3a In some embodiments, the alkoxy is a compound optionally substituted with one R 3a In some embodiments, the alkoxy is methoxy.

[0187] In some embodiments, compounds of the present disclosure comprise at least one R 3 But C 1~6 alkoxy, wherein the alkoxy is selected from one or two R 3a In some embodiments, the alkoxy is a compound optionally substituted with one R 3a In some embodiments, the alkoxy is methoxy.

[0188] In some embodiments, compounds of the present disclosure include compounds in which each R 3 are independently C1 to C6 alkyl, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 Alkyl)2, C 1~6 alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R 3a In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 3 are independently C1 to C3 alkyl, -NH2, -NH(C 1~3 alkyl), -N(C 1~3Alkyl)2, C 1~3 alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R 3a In some embodiments, each alkyl, alkoxy, and heterocyclyl is optionally substituted with one or two R 3a In some embodiments, each alkyl, alkoxy, and heterocyclyl is optionally substituted with one R 3a is optionally substituted with

[0189] In some embodiments, compounds of the present disclosure include R 3 However, 1 to 3 R 3a In some embodiments, the heterocyclyl is a 5- to 7-membered heterocyclyl optionally substituted with one or two R 3a In some embodiments, the heterocyclyl is optionally substituted with one R 3a is optionally substituted with

[0190] In some embodiments, compounds of the present disclosure comprise at least one R 3 However, 1 to 3 R 3a In some embodiments, the heterocyclyl is a 5- to 7-membered heterocyclyl optionally substituted with one or two R 3a In some embodiments, the heterocyclyl is optionally substituted with one R 3a is optionally substituted with

[0191] In some embodiments, compounds of the present disclosure include compounds in which each R 3 are independently -NH2, -NH(C 1~3 alkyl), -N(C 1~3 alkyl)2, or -O(C 1~3 alkyl), where each alkyl is independently selected from one or two R 3aIn some embodiments, each alkyl is optionally substituted with one R 3a is optionally substituted with

[0192] In some embodiments, compounds of the present disclosure include R 3 is methyl, or a pharmaceutically acceptable salt thereof.

[0193] In some embodiments, compounds of the present disclosure comprise at least one R 3 is methyl, or a pharmaceutically acceptable salt thereof.

[0194] In some embodiments, compounds of the present disclosure comprise at least one R 3 is halogen. In some embodiments, the compounds of the present disclosure have at least one R 3 is fluoro or chloro, or a pharmaceutically acceptable salt thereof.

[0195] In some embodiments, compounds of the present disclosure include compounds in which each R 3a But independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 3~8 Cycloalkyl, 5-10 membered heterocyclyl, C6 aryl, 5-10 membered heteroaryl, oxo, -OH, -CN, -NH2, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C 3~8 cycloalkyl), -NH(5-10 membered heterocyclyl), -NH(C6 aryl), -NH(5-10 membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 1~6haloalkyl)2, -N(C 3~8 cycloalkyl)2, -N(C 1~6 Alkyl)(C 1~6 haloalkyl), -N(C 1~6 Alkyl)(C 3~8 cycloalkyl), -N(C 1~6 alkyl)(5-10 membered heterocyclyl), -N(C 1~6 alkyl)(C6 aryl), -N(C 1~6 alkyl)(5-10 membered heteroaryl), -C(O)(5-10 membered heterocyclyl), -C(O)(5-10 membered heteroaryl), -C(O)NH2, -C(O)NH(C 1~6 alkyl), -C(O)NH(C 1~6 haloalkyl), -C(O)NH(C 3~8 cycloalkyl), -C(O)NH(5-10 membered heterocyclyl), -C(O)NH(C6 aryl), -C(O)NH(5-10 membered heteroaryl), -C(O)N(C 1~6 alkyl)2, -C(O)N(C 1~6 haloalkyl)2, -C(O)N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(C6 aryl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(C6 aryl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), -NHC(O)NH(C 1~6 haloalkyl), -NHC(O)NH(C 3~8 Cycloalkyl), -NHC(O)NH(5-10 membered heterocyclyl), -NHC(O)NH(C6 aryl), -NHC(O)NH(5-10 membered heteroaryl), -S(O)2(C1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, where each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R 3b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or two R 3b In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one R 3b is optionally substituted with

[0196] In some embodiments, compounds of the present disclosure include compounds in which each R 3a But independently, C 1~6 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 3b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 3a But independently, C 1~3 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one or two R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one R 3bis optionally substituted with

[0197] In some embodiments, compounds of the present disclosure comprise at least one R 3a But C 1~6 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 3b In some embodiments, the compounds of the present disclosure are compounds having at least one R 3a But independently, C 1~3 alkyl, -C(O)(5-10 membered heterocyclyl), or -O(C 3~8 cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one or two R 3b In some embodiments, each alkyl, heterocyclyl, and cycloalkyl is optionally substituted with one R 3b is optionally substituted with

[0198] In some embodiments, compounds of the present disclosure include compounds in which each R 3a are independently selected from halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1~6 alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl), or -C(O)N(C1-C6 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 3b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 3a are independently chloro, fluoro, -C(O)(C1-C3 alkyl), -OH, -O(C 1~3alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 3b is optionally substituted with

[0199] In some embodiments, compounds of the present disclosure comprise at least one R 3a is halogen, -C(O)(C1-C6 alkyl), -OH, -O(C 1~6 alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C6 alkyl), or -C(O)N(C1-C6 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 3b In some embodiments, the compounds of the present disclosure are compounds having at least one R 3a Chloro, fluoro, -C(O)(C1-C3 alkyl), -OH, -O(C 1~3 alkyl), 5-10 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 3b is optionally substituted with

[0200] In some embodiments, compounds of the present disclosure include compounds in which each R 3a However, independently, -O(C1~3 alkyl), 5-7 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 3b is optionally substituted with

[0201] In some embodiments, compounds of the present disclosure comprise at least one R 3a But -O(C 1~3 alkyl), 5-7 membered heterocyclyl, -C(O)NH2, -C(O)N(H)(C1-C3 alkyl), or -C(O)N(C1-C3 alkyl)2, where each alkyl and heterocyclyl is selected from 1 to 3 R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one or two R 3b In some embodiments, each alkyl and heterocyclyl is optionally substituted with one R 3b is optionally substituted with

[0202] In some embodiments, compounds of the present disclosure include compounds in which each R 3a are independently halogen or —C(O)(C1-C6 alkyl), where alkyl is selected from 1 to 3 R 3b In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein each R 3a is independently halogen or —C(O)(C1-C3 alkyl), or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds wherein each R 3ais independently chloro, fluoro, or —C(O)(methyl), or a pharmaceutically acceptable salt thereof.

[0203] In some embodiments, compounds of the present disclosure comprise at least one R 3a is halogen or —C(O)(C1-C6 alkyl), where alkyl is selected from 1 to 3 R 3b In some embodiments, the compounds of the present disclosure are compounds having at least one R 3a is halogen or —C(O)(C1-C3 alkyl), or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure have at least one R 3a is chloro, fluoro, or —C(O)(methyl), or a pharmaceutically acceptable salt thereof.

[0204] In some embodiments, compounds of the present disclosure include compounds in which each R 3a are independently -OH or -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each R 3a is independently -OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0205] In some embodiments, compounds of the present disclosure comprise at least one R 3a -OH or -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds having at least one R 3a is —OH or methoxy, or a pharmaceutically acceptable salt thereof.

[0206] In some embodiments, compounds of the present disclosure include R 3a -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R 3ais methoxy, or a pharmaceutically acceptable salt thereof.

[0207] In some embodiments, compounds of the present disclosure comprise at least one R 3a But -O(C 1~3 In some embodiments, the compounds of the present disclosure are compounds having at least one R 3a is methoxy, or a pharmaceutically acceptable salt thereof.

[0208] In some embodiments, compounds of the present disclosure include compounds in which each R 3a is independently halogen or —OH, or a pharmaceutically acceptable salt thereof. 3a is independently chloro, fluoro, or —OH, or a pharmaceutically acceptable salt thereof.

[0209] In some embodiments, compounds of the present disclosure comprise at least one R 3a is halogen or —OH, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure have at least one R 3a is chloro, fluoro, or —OH, or a pharmaceutically acceptable salt thereof.

[0210] In some embodiments, compounds of the present disclosure include compounds in which each R 3b But independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, halogen, oxo, -OH, -NH2, CO2H, -O(C 1~6 alkyl), -O(C 1~6 haloalkyl), -O(C 3~8 cycloalkyl), -O(5- to 10-membered heterocyclyl), -O(C 6~10 aryl), -O(5-10 membered heteroaryl), -NH(C 1~6 alkyl), -NH(C 1~6 haloalkyl), -NH(C3~8 cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(5- to 10-membered heteroaryl), -N(C 1~6 alkyl)2, -N(C 3~8 cycloalkyl)2, -NHC(O)(C 1~6 alkyl), -NHC(O)(C 1~6 haloalkyl), -NHC(O)(C 3~8 cycloalkyl), -NHC(O)(5-10 membered heterocyclyl), -NHC(O)(5-10 membered heteroaryl), -NHC(O)O(C 1~6 alkyl), -NHC(O)O(C 1~6 haloalkyl), -NHC(O)O(C 3~8 cycloalkyl), -NHC(O)O(5-10 membered heterocyclyl), -NHC(O)O(5-10 membered heteroaryl), -NHC(O)NH(C 1~6 alkyl), S(O)2(C 1~6 alkyl), -S(O)2(C 1~6 haloalkyl), -S(O)2(C 3~8 cycloalkyl), -S(O)(NH)(C 1~6 alkyl), -S(O)2NH(C 1~6 alkyl), or -S(O)N(C 1~6 alkyl)2, or a pharmaceutically acceptable salt thereof.

[0211] In some embodiments, compounds of the present disclosure include compounds in which each R 3b are independently halogen, -O(C 1~6 alkyl), or -O(C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein each R 3b are independently fluoro, chloro-O(C 1~3 alkyl), or -O(C 1~3 haloalkyl), or a pharmaceutically acceptable salt thereof.

[0212] In some embodiments, compounds of the present disclosure include compounds in which each R L are independently hydrogen, C 1~6 Alkyl, C1~6 Haloalkyl, or C 3~8 In some embodiments, the compounds of the present disclosure are compounds wherein each R is cycloalkyl, or a pharmaceutically acceptable salt thereof. L are independently hydrogen or C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein each R is alkyl, or a pharmaceutically acceptable salt thereof. L are independently hydrogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. L is hydrogen, or a pharmaceutically acceptable salt thereof. L is methyl, or a pharmaceutically acceptable salt thereof.

[0213] In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is an integer from 0 to 3. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is an integer from 0 to 2. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is 0. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is 1 or 2. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is 0. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is 1. In some embodiments, the compound of the present disclosure is a compound, or a pharmaceutically acceptable salt thereof, where n is 2.

[0214] In some embodiments, the compounds of the present disclosure include X 6 is N or CH, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds wherein X 6 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 6is CH, or a pharmaceutically acceptable salt thereof.

[0215] In some embodiments, the compounds of the present disclosure include X 7 is N or CH, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are compounds wherein X 7 is N, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 7 is CH, or a pharmaceutically acceptable salt thereof.

[0216] In some embodiments, the compounds of the present disclosure include X 6 and X 7 is CH, or a pharmaceutically acceptable salt thereof.

[0217] In some embodiments, the compounds of the present disclosure include X 4 , X 5 , X 6 , and X 7 or a pharmaceutically acceptable salt thereof, wherein no more than two of X are N. In some embodiments, the compounds of the present disclosure are 4 , X 5 , X 6 , and X 7 or a pharmaceutically acceptable salt thereof, wherein two of X are N. In some embodiments, the compounds of the present disclosure are 4 , X 5 , X 6 , and X 7 or a pharmaceutically acceptable salt thereof, wherein one of X is N. In some embodiments, the compounds of the present disclosure are 4 , X 5 , X 6 , and X 7 wherein none of the groups is N, or a pharmaceutically acceptable salt thereof.

[0218] In some embodiments, the compounds of the present disclosure include L 2 is a bond, C1-6 alkyl, -(C 1~6alkyl)O-, -(C 1~6 alkyl)O(C 1~6 alkyl)-, -(C 1~6 alkyl)(R L2 )NC(O)-, -(C 1~6 alkyl)C(O)N(R L2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, or -(C 1~6 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-, where R L2 or a pharmaceutically acceptable salt thereof, wherein: 2 is a bond, C1-3 alkyl, -(C 1~3 alkyl)O-, -(C 1~3 alkyl)O(C 1~3 alkyl)-, -(C 1~3 alkyl)(R L2 )NC(O)-, -(C 1~3 alkyl)C(O)N(R L2 )-, -(C 1~3 alkyl)S(O)2N(R L2 )-, -(C 1~3 alkyl)N(R L2 )S(O)2-, or -(C 1~3 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-, where R L2 is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0219] In some embodiments, the compounds of the present disclosure include L 2 is C1-6 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(RL2 )-, -(C 1~6 alkyl)S(O)2N(R L2 )-, -(C 1~6 alkyl)N(R L2 )S(O)2-, or -(C 1~6 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-, where R L2 or a pharmaceutically acceptable salt thereof, wherein: 2 is C1-3 alkyl, -(C 1~3 alkyl)O-, -(C 1~3 alkyl)O(C 1~3 alkyl)-, -(C 1~3 alkyl)(R L2 )NC(O)-, -(C 1~3 alkyl)C(O)N(R L2 )-, -(C 1~3 alkyl)S(O)2N(R L2 )-, -(C 1~3 alkyl)N(R L2 )S(O)2-, or -(C 1~3 alkyl)S(O)2N(R L2 )(C 1~6 alkyl)-, where R L2 is a compound described herein, or a pharmaceutically acceptable salt thereof.

[0220] In some embodiments, the compounds of the present disclosure include L 2 is a bond, or a pharmaceutically acceptable salt thereof.

[0221] In some embodiments, the compounds of the present disclosure include L 2 is C1-C3 alkyl, or a pharmaceutically acceptable salt thereof. 2 is methyl. In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein L 2is ethyl. In some embodiments, the compounds of the present disclosure are compounds, or pharmaceutically acceptable salts thereof, wherein L 2 is propyl, or a pharmaceutically acceptable salt thereof.

[0222] In some embodiments, compounds of the present disclosure include R L2 is hydrogen or C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. L2 is hydrogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. L2 is hydrogen, or a pharmaceutically acceptable salt thereof. L2 is methyl, or a pharmaceutically acceptable salt thereof.

[0223] In some embodiments, compounds of the present disclosure include R 5 is hydrogen, -CN, -OR 5a , -C(O)NR 5a 2, -NR 5a 2、 C 3~8 cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b In some embodiments, each cycloalkyl, aryl, heterocyclyl, and heteroaryl is optionally substituted with one R 5b is optionally substituted with

[0224] In some embodiments, compounds of the present disclosure include R 5 is hydrogen, or a pharmaceutically acceptable salt thereof.

[0225] In some embodiments, compounds of the present disclosure include R 5is -CN, or a pharmaceutically acceptable salt thereof.

[0226] In some embodiments, compounds of the present disclosure include R 5 But C 3~8 cycloalkyl, C6 aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b In some embodiments, each cycloalkyl, aryl, heterocyclyl, and heteroaryl is optionally substituted with one R 5b is optionally substituted with

[0227] In some embodiments, compounds of the present disclosure include R 5 But C 5~6 cycloalkyl, C aryl, 5- to 7-membered heterocyclyl, or 5- to 9-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R 5b In some embodiments, each cycloalkyl, aryl, heterocyclyl, and heteroaryl is optionally substituted with one R 5b is optionally substituted with

[0228] In some embodiments, compounds of the present disclosure include compounds in which each R 5a are independently hydrogen or C 1~6 In some embodiments, the compounds of the present disclosure are compounds wherein each R is alkyl, or a pharmaceutically acceptable salt thereof. 5a are independently hydrogen or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein R is alkyl, or a pharmaceutically acceptable salt thereof. 5a is hydrogen, or a pharmaceutically acceptable salt thereof. 5a is methyl, or a pharmaceutically acceptable salt thereof.

[0229] In some embodiments, compounds of the present disclosure include compounds in which each R 5b are independently selected from halogen, cyclopropyl, hydroxy, -CN, C 1~3 Alkyl, C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each R is alkoxy, -OCF, or -OCFH, or a pharmaceutically acceptable salt thereof. 5b is independently fluoro, chloro, cyclopropyl, hydroxy, —CN, methyl, methoxy, —OCF 3 , or —OCF 2 H, or a pharmaceutically acceptable salt thereof.

[0230] In some embodiments, compounds of the present disclosure include compounds in which each R 5b But independently, C 1~3 Alkyl or C 1~3 In some embodiments, the compounds of the present disclosure are compounds wherein each R is alkoxy, or a pharmaceutically acceptable salt thereof. 5b is independently methyl or methoxy, or a pharmaceutically acceptable salt thereof. 5b is independently methyl, or a pharmaceutically acceptable salt thereof. In some embodiments, the compounds of the present disclosure are 5b is independently methoxy, or a pharmaceutically acceptable salt thereof.

[0231] In some embodiments, the compounds of the disclosure are compounds, or pharmaceutically acceptable salts thereof, where Z is O or S. In some embodiments, the compounds of the disclosure are compounds, or pharmaceutically acceptable salts thereof, where Z is O. In some embodiments, the compounds of the disclosure are compounds, or pharmaceutically acceptable salts thereof, where Z is S.

[0232] In some embodiments, a compound of the present disclosure is a compound having the structure shown in Scheme A, or a pharmaceutically acceptable salt thereof: Scheme A:

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[0233] In some embodiments, the compound of the present disclosure is a compound having the structure shown in Scheme B: or a pharmaceutically acceptable salt thereof: Scheme B [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0234] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0235] In some embodiments, the compounds of the present disclosure are [ka] [ka] or a pharmaceutically acceptable salt thereof.

[0236] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0237] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0238] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0239] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0240] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0241] In some embodiments, the compounds of the present disclosure are [ka] or a pharmaceutically acceptable salt thereof.

[0242] In some embodiments, the compound of the present disclosure is a compound selected from any one of Examples 1-1102, or a pharmaceutically acceptable salt thereof.

[0243] In vivo metabolic products of the compounds described herein are also within the scope of the present invention, so long as such products are novel and unobvious over the prior art. Such products may result, for example, from the oxidation, reduction, hydrolysis, amidation, esterification, etc., of the administered compound, primarily through enzymatic processes. Thus, included are novel and unobvious compounds produced by a process comprising contacting a compound with a mammal for a period of time sufficient to yield metabolic products. Such products are typically radioisotopes (e.g., 14 C or 3 Compounds labeled with H are prepared and parenterally administered to animals, such as rats, mice, guinea pigs, monkeys, or humans, at detectable doses (e.g., greater than about 0.5 mg / kg), allowing sufficient time for metabolism to occur (usually about 30 seconds to about 30 hours), and then isolating the conversion products from urine, blood, or other biological samples. These products are easily isolated because they are labeled (others are isolated by using antibodies capable of binding to epitopes surviving in the metabolites). Metabolite structures are determined in conventional manner, for example, by MS or NMR analysis. Metabolite analysis is generally performed similarly to conventional drug metabolism studies known to those skilled in the art.

[0244] The compounds of the present disclosure can be prepared by various methods. For example, Schemes 1-11 show representative syntheses of compounds of the present disclosure. The variables shown in the following schemes are for illustrative purposes only and are independent of those described elsewhere herein.

[0245] General Reaction Scheme 1: [ka]

[0246] Intermediate 1.1 (wherein X is -OTf, -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to provide intermediate 1.2. Condensation of intermediate 1.2 with intermediate 1.3 in the presence of a base with heating provides intermediate 1.4. Metal-mediated cross-coupling with a suitable coupling partner, BM (wherein B is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si, or -Mg), in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (1.a).

[0247] General Reaction Scheme 2: [ka]

[0248] Palladium-mediated boronation of intermediate 1.4 with bis(pinacolato)diboron and a suitable Pd catalyst can be used to provide intermediate 2.1. Metal-mediated cross-coupling with a suitable coupling partner BX (where B is aryl or heteroaryl and X is -Cl, -Br, -I, or OTf) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (1.a).

[0249] General Reaction Scheme 3: [ka]

[0250] Intermediate 3.1 (wherein X is -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 3.2. Condensation of intermediate 3.2 with intermediate 1.3 in the presence of a base with heating gives intermediate 3.3. Metal-mediated cross-coupling with a suitable coupling partner, BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg), in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to give compounds of formula (1.b).

[0251] General Reaction Scheme 4: [ka]

[0252] Intermediate 4.1 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 4.2. Condensation of intermediate 4.2 with intermediate 1.3 in the presence of a base with heating gives intermediate 4.3. Intermediate 4.3 can be reacted with NBS to give intermediate 4.4. Metal-mediated cross-coupling with a suitable coupling partner BM (where B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to give compounds of formula (1.c).

[0253] General Reaction Scheme 5: [ka]

[0254] Intermediate 5.1 can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 5.2. Condensation of intermediate 5.2 with intermediate 1.3 in the presence of a base with heating gives intermediate 5.3. Metal-mediated C-H arylation with a suitable coupling partner BX (where B is aryl, heteroaryl, and X is -Cl, -Br, -I, or OTf) in the presence of a suitable catalyst (i.e., Pd) can be used to give compounds of formula (1.d).

[0255] General Reaction Scheme 6: [ka]

[0256] Intermediate 6.1 (wherein X is -OTf, -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) with heating to provide intermediate 6.2. Condensation of intermediate 6.2 with intermediate 1.3 in the presence of a base with heating provides intermediate 6.3. Metal-mediated cross-coupling with a suitable coupling partner, BM (wherein B is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si, or -Mg), in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to provide compounds of formula (1.e).

[0257] General Reaction Scheme 7: [ka]

[0258] Intermediate 7.1 (wherein X is -OTf, -Cl, Br, or -I) can be reacted with phenyl chloroformate in the presence of a suitable base (e.g., DIPEA) and heated to give intermediate 7.2. Condensation of intermediate 7.2 with intermediate 1.3 in the presence of a base with heating gives intermediate 7.3. Metal-mediated cross-coupling with a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to give compounds of formula (1.f).

[0259] General Reaction Scheme 8: [ka]

[0260] Metal-mediated cross-coupling of intermediate 1.1 (wherein X is -OTf, -Cl, Br, or -I) with a suitable coupling partner BM (wherein B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to generate intermediate 8.1. Intermediate 8.1 can be reacted with intermediate 8.2 in the presence of a suitable base (e.g., DIPEA) with heating to provide intermediate 8.3. Condensation of intermediate 8.3 with intermediate 1.3 in the presence of a base with heating can be used to provide compounds of formula (1.g).

[0261] General Reaction Scheme 9: [ka]

[0262] Metal-mediated cross-coupling of intermediate 3.1 (where X is -OTf, -Cl, Br, or -I) and a suitable coupling partner BM (where B is aryl, heteroaryl, and M is -B, -Sn, -Zn, -Si, or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to generate intermediate 9.1. Intermediate 9.1 can be reacted with intermediate 8.2 in the presence of a suitable base (e.g., DIPEA) with heating to provide intermediate 9.2. Condensation of intermediate 9.2 with intermediate 1.3 in the presence of a base with heating can be used to provide compounds of formula (1.h).

[0263] General Reaction Scheme 10: [ka]

[0264] Metal-mediated cross-coupling of compounds of formula 1.a (wherein X is -OTf, -Cl, Br or -I) with a suitable coupling partner Ar-M (wherein Ar is aryl or heteroaryl and M is -B, -Sn, -Zn, -Si or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to generate compounds of formula (1.i).

[0265] General Reaction Scheme 11: [ka]

[0266] Metal-mediated cross-coupling of compounds of formula 1.b (wherein X is -OTf, -Cl, -Br or -I) with a suitable coupling partner Ar-M (wherein Ar is aryl, heteroaryl and M is -B, -Sn, -Zn, -Si or -Mg) in the presence of a suitable catalyst (i.e., Pd or Ni) can be used to generate compounds of formula (1.j). Pharmaceutical preparations

[0267] In some embodiments, the present disclosure provides a pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Also provided herein are pharmaceutical formulations comprising a pharmaceutically effective amount of a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0268] In some embodiments, the pharmaceutical composition is for use in treating a virus.

[0269] In some embodiments, the pharmaceutical composition further comprises one or more additional therapeutic agents. Any suitable additional therapeutic agent or combination therapy, such as those described herein, can be used with a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof.

[0270] In some embodiments, the pharmaceutical composition comprises a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb) and an additional therapeutic agent, wherein the additional therapeutic agent is as described herein under the heading "Combination Therapy."

[0271] In some embodiments, the compounds disclosed herein are formulated with conventional carriers and excipients, which may be selected according to ordinary practice. Tablets may contain excipients, glidants, fillers, binders, etc. Aqueous formulations may be prepared in sterile form and may be isotonic, for example, if intended for delivery by a route other than oral administration. In some embodiments, formulations 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, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, and stearic acid. The pH of the formulation ranges from about 3 to about 11, e.g., from about 7 to about 10.

[0272] In some embodiments, a compound disclosed herein is administered alone. In some embodiments, a compound disclosed herein is administered in a pharmaceutical formulation. In some embodiments, formulations for veterinary and / or human use comprise at least one compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof, together with one or more acceptable carriers and optionally other therapeutic ingredients, such as additional therapeutic ingredients discussed herein. In some embodiments, the carrier(s) are "acceptable" in the sense of being compatible with the other ingredients of the formulation and physiologically innocuous to the recipient thereof.

[0273] In some embodiments, formulations of the present disclosure include those suitable for the aforementioned routes of administration. In some embodiments, the formulations are provided in unit dosage form. The formulations may be prepared by methods known in the art of pharmacy. Techniques and formulations may be found, for example, in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA). Such methods include, for example, the step of bringing into association the active ingredient with the carrier(s) which may include one or more accessory ingredients. In some embodiments, the formulations are prepared by bringing into association the active ingredient(s) with liquid carriers or finely divided solid carriers, or both, and then, in some embodiments, shaping the product.

[0274] In some embodiments, the pharmaceutical formulation is for subcutaneous, intramuscular, intravenous, oral, or inhaled administration.

[0275] Formulations suitable for oral administration may be presented as discrete units such as capsules, cachets, or tablets, each containing a predetermined amount of the active ingredient, e.g., a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water or water-in-oil liquid emulsion. In some embodiments, the active ingredient is administered as a bolus, electuary, or paste.

[0276] Tablets can be made, for example, by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient in a free-flowing form, such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surfactant, or dispersing agent. Molded tablets can be produced, for example, by molding in a suitable machine a mixture of the powdered active ingredient moistened with an inert liquid diluent. Tablets can optionally be coated or scored. In some embodiments, tablets are formulated to provide sustained or controlled release of the active ingredient therefrom.

[0277] For infections of the eye or other external tissues, e.g., mouth and skin, the compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb) may be formulated in an amount of, for example, about 0.075 to about 20% w / w (including about 0.1% w / w increments of about 0.1% to about 20%, e.g., about 0.6% w / w, about 0.7% w / w, etc., of the active ingredient(s)), for example, about 0.2 to about 15% w / w, and for example, about 0.5 to about 10% w / w. When formulated in an ointment, the compounds of Formula (I), (II-a), (II-b), (II-c), (III-a), or (III-b) may be used with either a paraffinic or a water-miscible ointment base. Alternatively, the compounds of Formula (I), (II-a), (II-b), (II-c), (III-a), or (III-b) may be formulated in a cream with an oil-in-water cream base.

[0278] Optionally, the aqueous phase of the cream base may contain, for example, at least about 30% w / w of a polyhydric alcohol, i.e., an alcohol having two or more hydroxyl groups, such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol, and polyethylene glycol (including PEG 400), and mixtures thereof. In some embodiments, the topical formulation may include a compound that enhances 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.

[0279] The oily phase of the emulsion can be composed of known ingredients in a known manner. The phase can contain only an emulsifier (also known as an emulsifier (emulgent)), but can also contain, for example, a mixture of at least one emulsifier with a fat or oil, or a mixture of both a fat and an oil. In some embodiments, a hydrophilic emulsifier is included together with a lipophilic emulsifier that functions as a stabilizer. In some embodiments, the emulsion contains both an oil and a fat. Together, the emulsifier, with or without a stabilizer, constitutes a so-called emulsifying wax, which, together with the oil and fat, constitutes a so-called emulsifying ointment base that forms the oily dispersed phase of a cream formulation.

[0280] Suitable emulsifiers and emulsion stabilizers for use in the formulation include, for example, Tween® 60, Span® 80, cetostearyl alcohol, benzyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate. Additional suitable emulsifiers and emulsion stabilizers for use in the formulation include TWEEN® 80.

[0281] The selection of suitable oils or fats for the formulation is based on achieving the desired properties. The cream can be a non-greasy, non-staining, and washable product with a suitable consistency to avoid leakage from tubes or other containers. Linear or branched, mono- or dibasic alkyl esters, such as diisoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acid, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or a blend of branched esters known as Crodamol CAP, can be used. These can be used alone or in combination depending on the required properties. Alternatively, high-melting point lipids such as white soft paraffin and / or liquid paraffin or other mineral oils can be used.

[0282] The pharmaceutical formulation according to the present invention comprises a compound according to the present invention together with one or more pharmaceutically acceptable carriers or excipients and optionally other therapeutic agents.The pharmaceutical formulation containing the active ingredient can be in any form suitable for the intended method of administration.For example, when used for oral use, tablets, troches, lozenges, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups, or elixirs can be prepared.Compositions intended for oral use can be prepared according to any method known in the art for the manufacture of pharmaceutical compositions, and such compositions can contain one or more agents, including sweeteners, flavoring agents, coloring agents, and preservatives, to provide a palatable preparation.Tablets containing the active ingredient in a mixture with non-toxic pharmaceutically acceptable excipients suitable for the manufacture of tablets are acceptable. These excipients may be, for example, inert diluents such as calcium or sodium carbonate, lactose, calcium or sodium phosphate; granulating and disintegrating agents such as corn starch or alginic acid; binders such as starch, gelatin, or acacia; and lubricants such as magnesium stearate, stearic acid, or talc. Tablets may be uncoated or may be coated by known techniques, including microencapsulation, to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be used alone or with a wax.

[0283] Formulations for oral use may also be presented as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium phosphate or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil.

[0284] Aqueous suspensions of the present invention contain the active ingredient in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, and gum acacia, as well as dispersing or wetting agents such as naturally occurring phosphatides (e.g., lecithin), condensation products of alkylene oxides with fatty acids (e.g., polyoxyethylene stearates), condensation products of ethylene oxide with long-chain aliphatic alcohols (e.g., heptadecaethyleneoxycetanol), condensation products of ethylene oxide with partial esters derived from fatty acids, and hexitol anhydrides (e.g., polyoxyethylene sorbitan monooleate). Aqueous suspensions may also contain one or more preservatives, such as ethyl or n-propyl p-hydroxybenzoates, one or more colorants, one or more flavoring agents, and one or more sweeteners, such as sucrose or saccharin. Further non-limiting examples of suspending agents include cyclodextrins. In some examples, the suspending agent is sulfobutyl ether β-cyclodextrin (SEB-β-CD), such as Captisol®.

[0285] Oil suspensions can be prepared by suspending the active ingredient in vegetable oils such as peanut oil, olive oil, sesame oil or coconut oil, or in mineral oils such as liquid paraffin.Oral suspensions can contain thickening agents such as beeswax, hard paraffin or cetyl alcohol.Sweeteners and flavoring agents such as those mentioned above can be added to provide a palatable oral preparation.These compositions can be preserved by adding antioxidants such as ascorbic acid.

[0286] Dispersible powders and granules of the present invention suitable for preparation of an aqueous suspension by adding water provide the active ingredient in admixture with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersing 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.

[0287] The pharmaceutical composition of the present invention can also be in the form of an oil-in-water emulsion. The oil phase can be a vegetable oil such as olive oil or peanut oil, a mineral oil such as liquid paraffin, or a mixture thereof. Suitable emulsifiers include naturally occurring gums such as acacia gum and tragacanth gum, naturally occurring phosphatides such as soybean lecithin, esters or partial esters derived from fatty acids, and hexitol anhydrides such as sorbitan monooleate, and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. Emulsions can also contain sweeteners and flavoring agents. Syrups and elixirs can be formulated with sweeteners such as glycerol, sorbitol, or sucrose. Such formulations can also contain demulcents, preservatives, flavorings, or coloring agents.

[0288] The pharmaceutical compositions of the present invention may be in the form of a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. These suspensions may be formulated according to known techniques using suitable dispersing or wetting agents and suspending agents as described above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,3-butanediol, or may be prepared as a lyophilized powder. Among the acceptable vehicles and solvents that may be used are water, Ringer's solution, and isotonic sodium chloride solution. Additionally, sterile fixed oils are conventionally used as solvents or suspending media. For this purpose, any solvent-free fixed oil, including synthetic monoglycerides or diglycerides, may be used. Additionally, fatty acids such as oleic acid may also be used in the preparation of injectables. Among the acceptable vehicles and solvents that may be used are water, Ringer's solution, isotonic sodium chloride solution, and hypertonic sodium chloride solution.

[0289] The amount of active ingredient that may be combined with a carrier material to produce a single dosage form will vary depending on the host treated and the particular mode of administration. For example, a sustained-release formulation intended for oral administration to humans may contain about 1 to 1000 mg of active ingredient combined with an appropriate and convenient amount of carrier material, which may vary from about 5 to about 95% (weight:weight) of the total composition. Pharmaceutical compositions can be prepared to provide easily measurable amounts for administration. For example, an aqueous solution intended for intravenous infusion may contain about 3 to 500 mg of active ingredient per milliliter of solution to allow infusion of a suitable volume at a rate of about 30 mL / hour.

[0290] Formulations suitable for topical administration to the eye also include eye drops wherein the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient. The active ingredient is preferably present in such formulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10%, especially about 1.5% w / w.

[0291] Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavored base, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.

[0292] Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate.

[0293] In some embodiments, the compounds disclosed herein are administered by inhalation. In some embodiments, formulations suitable for pulmonary or nasal administration have particle sizes ranging from, for example, 0.1 to 500 micrometers, e.g., 0.5, 1, 30, 35, etc., and are administered by rapid inhalation through the nasal passage or by inhalation through the mouth to reach the alveoli. 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 may be delivered 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 spray 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 tent.

[0294] Another embodiment provides an inhalable composition comprising a compound of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt, including hydrochloride, hydrobromide, sulfate, or phosphate. For example, such salts may be less likely to cause pulmonary irritation compared to other salts. In some embodiments, the inhalable composition is delivered to the endobronchial space in an aerosol comprising particles having a mass median aerodynamic diameter (MMAD) of about 1 to about 5 μm. In some embodiments, the compounds of Formula (I), (II), (II-a), (II-b), (II-c), (II-d), (III), (III-a), (III-b), (III-c), (III-d), (IV), (IV-a), (IV-b), (V), (Va), and (Vb), or pharmaceutically acceptable salts thereof, are formulated for aerosol delivery using a nebulizer, a pressurized metered dose inhaler (pMDI), or a dry powder inhaler (DPI).

[0295] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulations containing, in addition to the active ingredient, such carriers as are known in the art to be appropriate.

[0296] Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.

[0297] The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of a sterile liquid carrier, for example, water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules, and tablets of the kind described above. Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as herein above recited, of the active ingredient, or an appropriate fraction thereof.

[0298] It will be understood that in addition to the ingredients specifically mentioned above, the formulations of the present invention may include other agents conventional in the art having regard to the type of formulation in question; for example, those suitable for oral administration may include flavoring agents.

[0299] The present invention further provides veterinary compositions comprising at least one active ingredient as defined above together with a veterinary carrier therefor.

[0300] A veterinary carrier may be a solid, liquid, or gaseous substance that is useful for the purpose of administering the composition and is otherwise inert or acceptable in veterinary art and compatible with the active ingredient. These veterinary compositions may be administered orally, parenterally, or by any other desired route.

[0301] The compounds of the present invention are used to provide controlled-release pharmaceutical formulations ("controlled-release formulations") containing one or more compounds of the present invention as the active ingredient, in which release of the active ingredient is controlled and regulated to allow less frequent administration or to improve the pharmacokinetic or toxicity profile of a given active ingredient.

[0302] The effective dose of the active ingredient depends at least on the nature of the condition being treated, toxicity, delivery method, and pharmaceutical formulation, and can be determined by a clinician using conventional dose-escalation studies. This can be expected to be about 0.0001 to about 100 mg / kg body weight per day, typically about 0.01 to about 10 mg / kg body weight per day, more typically about 0.01 to about 5 mg / kg body weight per day, and most typically about 0.05 to about 0.5 mg / kg body weight per day. For example, the candidate daily dose for an adult human weighing about 70 kg can range from about 1 mg to about 1000 mg, e.g., about 5 mg to about 500 mg, and can take the form of a single dose or multiple doses. How to use

[0303] The present disclosure also provides a method of treating or preventing a viral infection in a subject (e.g., a human) in need thereof, comprising administering to the subject a compound described herein.

[0304] In some embodiments, the disclosure provides a method of treating or preventing a viral infection in a subject (e.g., a human) in need thereof, comprising administering to the subject in need thereof a compound described herein.

[0305] In some embodiments, the compounds described herein are administered to humans via oral, intramuscular, intravenous, subcutaneous, or inhaled administration.

[0306] In some embodiments, the present disclosure provides a method of treating or preventing a viral infection in a subject (e.g., a human) in need thereof, comprising administering to the subject a compound disclosed herein and at least one additional active therapeutic or prophylactic agent.

[0307] In some embodiments, the present disclosure provides a method of treating a viral infection in a subject (e.g., a human) in need thereof, the method comprising administering to the subject a compound disclosed herein and at least one additional active therapeutic or prophylactic agent.

[0308] In one embodiment, the present disclosure provides a method of inhibiting a viral polymerase in a cell, comprising contacting a virally infected cell with a compound disclosed herein, thereby inhibiting the viral polymerase.

[0309] In one embodiment, the present disclosure provides a method of inhibiting a viral polymerase in a cell, comprising contacting a virally infected cell with a compound disclosed herein and at least one additional active therapeutic agent, thereby inhibiting the viral polymerase.

[0310] Also provided herein is the use of a compound disclosed herein for use in treating or preventing a viral infection in a subject in need thereof. For example, provided herein is the use of a compound disclosed herein for use in treating a viral infection in a subject in need thereof.

[0311] In some embodiments, the viral infection is a coronavirus infection. Accordingly, in some embodiments, provided herein are methods of treating a coronavirus infection in a human in need thereof, the method comprising administering a compound provided herein to the human. In some embodiments, the coronavirus infection is a severe acute respiratory syndrome (SARS-CoV) infection, a Middle East respiratory syndrome (MERS) infection, a SARS-CoV-2 infection, another human coronavirus (229E, NL63, OC43, HKU1, or WIV1) infection, or a zoonotic coronavirus (PEDV or HKU CoV isolate, e.g., HKU3, HKU5, or HKU9) infection. In some embodiments, the viral infection is a severe acute respiratory syndrome (SARS) infection. In some embodiments, the viral infection is a Middle East respiratory syndrome (MERS) infection. In some embodiments, the viral infection is a SARS-CoV-2 infection. In some embodiments, the viral infection is a zoonotic coronavirus infection. In some embodiments, the viral infection is caused by a virus having at least 70% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, the viral infection is caused by a virus having at least 80% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, the viral infection is caused by a virus having at least 90% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2. In some embodiments, the viral infection is caused by a virus having at least 95% sequence homology to a viral polymerase selected from the group consisting of SARS-CoV polymerase, MERS-CoV polymerase, and SARS-CoV-2.

[0312] In some embodiments, the viral infection is caused by a SARS-CoV-2 variant, such as the B.1.1.7 variant (UK variant), the B.1.351 variant (South African variant), the P.1 variant (Brazilian variant), the B.1.1.7 with the E484K mutation, the B.1.1.207 variant, the B.1.1.317 variant, the B.1.1.318 variant, the B.1.429 variant, the B.1.525 variant, or the P.3 variant. In some embodiments, the viral infection is caused by the B.1.1.7 variant of SARS-CoV-2. In some embodiments, the viral infection is caused by the B.1.351 variant of SARS-CoV-2. In some embodiments, the viral infection is caused by the P.1 variant of SARS-CoV-2.

[0313] In some embodiments, the disclosure provides compounds for use in treating a coronavirus infection in a human in need thereof. In some embodiments, the coronavirus infection is a severe acute respiratory syndrome (SARS) infection, a Middle East respiratory syndrome (MERS) infection, a SARS-CoV-2 infection, another human coronavirus (229E, NL63, OC43, HKU1, or WIV1) infection, or a zoonotic coronavirus (PEDV or HKUCoV isolate, e.g., HKU3, HKU5, or HKU9) infection. In some embodiments, the viral infection is a severe acute respiratory syndrome (SARS) infection. In some embodiments, the viral infection is a Middle East respiratory syndrome (MERS) infection. In some embodiments, the viral infection is a SARS-CoV-2 infection (COVID19).

[0314] As described more fully herein, the compounds described herein can be administered to an individual (e.g., a human) infected with a viral infection along with one or more additional therapeutic agents. The additional therapeutic agents can be administered to the infected individual simultaneously with the compounds of the present disclosure, or before or after administration of the compounds of the present disclosure. Administration

[0315] One or more compounds of the present invention can be administered by any route appropriate to the condition to be treated. Suitable routes include oral, rectal, inhalation, pulmonary, topical (including buccal and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural), etc. In some embodiments, the compounds disclosed herein are administered by inhalation or intravenously. In some embodiments, the compounds disclosed herein are administered orally. It will be understood that the preferred route may vary depending, for example, on the condition of the recipient.

[0316] In the method of the present invention for treating a viral infection, the compound of the present invention can be administered at any time to a person who may have come into contact with the virus or who is already suffering from the viral infection. In some embodiments, the compound of the present invention can be administered prophylactically to a person who comes into contact with a person suffering from a viral infection or who is at risk of coming into contact with a person suffering from a viral infection, such as a healthcare provider. In some embodiments, the compound of the present invention can be administered to a person who has tested positive for a viral infection but has not yet shown symptoms of the viral infection. In some embodiments, the compound of the present invention can be administered to a person at the onset of symptoms of the viral infection.

[0317] In some embodiments, the methods disclosed herein include event-driven administration of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, to a subject.

[0318] As used herein, the term "event-driven" or "event-driven administration" refers to administration of a compound described herein, e.g., a compound of the present disclosure, or a pharmaceutically acceptable salt thereof: (1) before an event (e.g., 2 hours, 1 day, 2 days, 5 days, or 7 days or more before the event) that exposes an individual to a virus (or otherwise increases the individual's risk of contracting a viral infection); and / or (2) during an event (or two or more recurring events) that exposes an individual to a virus (or otherwise increases the individual's risk of being infected with the virus), and / or (3) after an event (or after the last event in a series of recurring events) that exposes an individual to a virus (or otherwise increases the individual's risk of being infected with the virus). In some embodiments, event-driven administration occurs before the subject's exposure to the virus. In some embodiments, event-driven administration occurs after the subject's exposure to the virus. In some embodiments, event-driven administration occurs before the subject's exposure to the virus and after the subject's exposure to the virus.

[0319] In certain embodiments, the methods disclosed herein involve administration before and / or after an event that exposes an individual to the virus or that otherwise increases the individual's risk of becoming infected with the virus, e.g., as pre-exposure prophylaxis (PrEP) and / or post-exposure prophylaxis (PEP). In some embodiments, the methods disclosed herein involve pre-exposure prophylaxis (PrEP). In some embodiments, the methods disclosed herein involve post-exposure prophylaxis (PEP).

[0320] In some embodiments, the compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is administered prior to the subject's exposure to the virus.

[0321] In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is administered before and after exposure of the subject to the virus.

[0322] In some embodiments, the compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is administered after the subject's exposure to the virus.

[0323] An example of an event-driven dosing regimen includes administering a compound of the disclosure, or a pharmaceutically acceptable salt thereof, within 24 hours to 2 hours prior to the virus, followed by administration of a compound of the disclosure, or a pharmaceutically acceptable salt thereof, every 24 hours for the duration of exposure, followed by another administration of a compound of the disclosure, or a pharmaceutically acceptable salt thereof, after the final exposure, and finally another administration of a compound of Formula A or Formula B, or a pharmaceutically acceptable salt thereof, 24 hours later.

[0324] A further example of an event-driven dosing regimen includes administering a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, within 24 hours before exposure to the virus, followed by daily dosing for the duration of exposure, followed by a final dose (which may be an increased dose, such as a double dose) about 24 hours after the last exposure.

[0325] The specific dose level of a compound of the present disclosure for any particular subject will depend on a variety of factors, including the activity of the specific compound used, age, body weight, general health, sex, diet, time of administration, route of administration, and rate of excretion, drug combinations, and the severity of the particular disease in the subject receiving therapy. For example, dosages may be expressed as milligrams of a compound described herein per kilogram of subject body weight (mg / kg). Doses of about 0.1 to 150 mg / kg may be appropriate. In some embodiments, doses of about 0.1 and 100 mg / kg may be appropriate. In other embodiments, doses of 0.5 to 60 mg / kg may be appropriate. Normalizing by subject body weight is particularly useful when adjusting dosages between subjects of widely different sizes, such as occurs when using drugs in both pediatric and adult humans, or when converting effective dosages in non-human subjects, such as dogs, to dosages suitable for human subjects.

[0326] The daily dose may also be described as the total amount of the compound described herein administered per administration or per day. The daily dose of the compound of the present disclosure, or a pharmaceutically acceptable salt thereof, may be about 1 mg to 4,000 mg, about 2,000 to 4,000 mg / day, about 1 to 2,000 mg / day, about 1 to 1,000 mg / day, about 10 to 500 mg / day, about 20 to 500 mg / day, about 50 to 300 mg / day, about 75 to 200 mg / day, or about 15 to 150 mg / day.

[0327] The dosage or frequency of administration of a compound of the present disclosure may be adjusted over the course of treatment, based on the judgment of the administering physician.

[0328] The compounds of the present disclosure can be administered to an individual (e.g., a human) in a therapeutically effective amount. In some embodiments, the compounds are administered once daily.

[0329] The compounds provided herein can be administered by any useful route and means, such as oral or parenteral (e.g., intravenous) administration. A therapeutically effective amount of a compound can include from about 0.00001 mg / kg body weight per day to about 10 mg / kg body weight per day, e.g., from about 0.0001 mg / kg body weight per day to about 10 mg / kg body weight per day, or from about 0.001 mg / kg body weight per day to about 1 mg / kg body weight per day, or from about 0.01 mg / kg body weight per day to about 1 mg / kg body weight per day, or from about 0.05 mg / kg body weight per day to about 0.5 mg / kg body weight per day. In some embodiments, a therapeutically effective amount of a compound provided herein includes from about 0.3 mg to about 30 mg per day, or from about 30 mg to about 300 mg per day, or from about 0.3 mg to about 30 mg per day, or from about 30 mg to about 300 mg per day.

[0330] The compounds of the present disclosure can be combined with one or more additional therapeutic agents at any dosage of the compound of the present disclosure (e.g., 1 mg to 1000 mg of compound). Therapeutically effective amounts may include from about 0.1 mg per dose to about 1000 mg per dose, such as from about 50 mg per dose to about 500 mg per dose, or from about 100 mg per dose to about 400 mg per dose, or from about 150 mg per dose to about 350 mg per dose, or from about 200 mg per dose to about 300 mg per dose, or from about 0.01 mg per dose to about 1000 mg per dose, or from about 0.01 mg per dose to about 100 mg per dose, or from about 0.1 mg per dose to about 100 mg per dose, or from about 1 mg per dose to about 100 mg per dose, or from about 1 mg per dose to about 10 mg per dose, or from about 1 mg per dose to about 1000 mg per dose. Other therapeutically effective amounts of a compound of the present disclosure are about 1 mg per dose, or about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or about 100 mg per dose. Other therapeutically effective amounts of compounds of the present disclosure are about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or about 1000 mg per dose.

[0331] In some embodiments, the method includes administering to a subject an initial daily dose of about 1 to 500 mg of a compound provided herein, and increasing the dose incrementally until clinical efficacy is achieved. Increments of about 5, 10, 25, 50, or 100 mg can be used to increase the dose. The dose can be increased daily, daily, twice weekly, weekly, every two weeks, every three weeks, or monthly.

[0332] When administered orally, the total daily dosage for a human subject may be about 1-4,000 mg / day, about 1-3,000 mg / day, 1-2,000 mg / day, about 1-1,000 mg / day, about 10-500 mg / day, about 50-300 mg / day, about 75-200 mg / day, or about 100-150 mg / day. In some embodiments, the total daily dosage for a human subject can be about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject can be about 200, 300, 400, 500, 600, 700, or 800 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 300, 400, 500, or 600 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, or 4000 mg / day.In some embodiments, the total daily dosage for a human subject is about 100-200, 100-300, 100-400, 100-500, 100-600, 100-700, 100-800, 100-900, 100-1000, 500-1100, 500-1200, 500-1300, 500-1400, 500-1500, 500-1600, 500-1700, 500-1800, 500-1900, 500-2000, 1500-2100, It may be 1500 to 2200, 1500 to 2300, 1500 to 2400, 1500 to 2500, 2000 to 2600, 2000 to 2700, 2000 to 2800, 2000 to 2900, 2000 to 3000, 2500 to 3100, 2500 to 3200, 2500 to 3300, 2500 to 3400, 2500 to 3500, 3000 to 3600, 3000 to 3700, 3000 to 3800, 3000 to 3900, or 3000 to 4000 mg / day.

[0333] In some embodiments, the total daily dosage for a human subject may be about 100 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 150 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 200 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 250 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 300 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 350 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 400 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 450 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 500 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 550 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 600 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 650 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 700 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 750 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 800 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 850 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 900 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 950 mg / day administered in a single dose.In some embodiments, the total daily dosage for a human subject may be about 1000 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 1500 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 2000 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 2500 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 3000 mg / day administered in a single dose. In some embodiments, the total daily dosage for a human subject may be about 4000 mg / day administered in a single dose.

[0334] A single dose can be administered hourly, daily, weekly, or monthly. For example, a single dose can be administered once every 1, 2, 3, 4, 6, 8, 12, 16 hours, or once every 24 hours. A single dose can also be administered once every 1, 2, 3, 4, 5, 6 days, or once every 7 days. A single dose can also be administered once every 1, 2, 3 weeks, or once every 4 weeks. In certain embodiments, a single dose can be administered once weekly. A single dose can also be administered once monthly. In some embodiments, a compound disclosed herein is administered once daily in a method disclosed herein. In some embodiments, a compound disclosed herein is administered twice daily in a method disclosed herein. In some embodiments, a compound disclosed herein is administered three times daily in a method disclosed herein.

[0335] In some embodiments, the compounds disclosed herein are administered once daily at a total daily dose of 100-4000 mg / day. In some embodiments, the compounds disclosed herein are administered twice daily at a total daily dose of 100-4000 mg / day. In some embodiments, the compounds disclosed herein are administered three times daily at a total daily dose of 100-4000 mg / day.

[0336] The frequency of administration of the compounds of the present disclosure is determined by the needs of each individual patient and can be, for example, once a day or twice a day or more. Administration of the compounds continues as long as necessary to treat the viral infection. For example, the compounds can be administered to a human infected with a virus for a period of 20 to 180 days, or for example, for a period of 20 to 90 days, or for example, for a period of 30 to 60 days.

[0337] Administration can be intermittent, with the patient receiving a daily dose of a compound of the present disclosure for a period of several days or more, followed by a period of several days or more during which the patient does not receive a daily dose of the compound. For example, the patient can receive a dose of the compound every other day or three times per week. As a further example, the patient can receive a dose of the compound daily for a period of 1 to 14 days, followed by a period of 7 to 21 days during which the patient does not receive a dose of the compound, followed by a subsequent period (e.g., 1 to 14 days) during which the patient again receives a daily dose of the compound. The alternating periods of compound administration followed by non-compound administration can be repeated as clinically needed to treat the patient.

[0338] The compounds of the present disclosure or pharmaceutical compositions thereof may be administered once, twice, three times, or four times daily using any suitable method described above. Administration or treatment with the compounds may continue for several days; for example, treatment typically lasts at least 7, 14, or 28 days per treatment cycle. Treatment cycles may alternate with rest periods of about 1 to 28 days, typically about 7 days or about 14 days, between cycles. Treatment cycles may also be continuous in other embodiments. Combination therapy

[0339] The compounds described herein can also be used in combination with one or more additional therapeutic agents. Accordingly, also provided herein is a method for treating a viral infection in a subject in need thereof, the method comprising administering to the subject a compound disclosed herein and a therapeutically effective amount of one or more additional therapeutic or prophylactic agents.

[0340] In some embodiments, the additional therapeutic agent comprises an antiviral agent. Any suitable antiviral agent can be used in the methods described herein.

[0341] In some embodiments, the additional therapeutic agent is a 2,5-oligoadenylate synthetase stimulator, 5-HT 2a receptor antagonists, 5-lipoxygenase inhibitors, ABL family tyrosine kinase inhibitors, Abl tyrosine kinase inhibitors, acetaldehyde dehydrogenase inhibitors, acetyl-CoA carboxylase inhibitors, actin antagonists, actin modulators, activity-dependent neuroprotective modulators, adenosine A3 receptor agonists, adrenergic receptor antagonists, adrenomedullin ligands, adrenomedullin ligand inhibitors, advanced glycosylation product receptor antagonists, advanced glycosylation product receptor modulators, AKT protein kinase inhibitors, alanine-proline-rich secretory protein stimulators, aldose reductase inhibitors, alkaline phosphatase stimulators, alpha 2 adrenergic receptor antagonists, alpha 2B adrenergic receptor agonists, AMP-activated protein kinase stimulators, AMPA receptor modulators, amyloid protein deposition inhibitors, androgen receptor antagonists, angiotensin II AT-1 receptor antagonist, angiotensin II AT-2 receptor agonist, angiotensin II receptor modulator, angiotensin converting enzyme 2 inhibitor, angiotensin converting enzyme 2 modulator, angiotensin converting enzyme 2 stimulator, angiotensin receptor modulator, annexin A5 stimulator, anoctamin 1 inhibitor, anticoagulant, antihistamine, antihypoxic agent, antithrombotic agent, AP1 transcription factor modulator, apelin receptor agonist, APOA1 gene stimulator, apolipoprotein A1 agonist, apolipoprotein B antagonist, apolipoprotein B modulator, apolipoprotein C3 antagonist, Aryl hydrocarbon receptor agonists, aryl hydrocarbon receptor antagonists, ATP-binding cassette transporter B5 modulators, Axl tyrosine kinase receptor inhibitors, bactericidal permeability protein inhibitors, Basigin inhibitors, Basigin modulators, BCL2 gene inhibitors, BCL2L11 gene stimulators, Bcr protein inhibitors, beta 1 adrenergic receptor modulators, beta 2 adrenergic receptor agonists, beta adrenergic receptor agonists, beta-arrestin stimulators, blood coagulation regulators, BMP10 gene inhibitors, BMP15 gene inhibitors,Bone morphogenetic protein-10 ligand inhibitor, bone morphogenetic protein-15 ligand inhibitor, bradykinin B2 receptor antagonist, brain-derived neurotrophic factor ligand, bromodomain-containing protein 2 inhibitor, bromodomain-containing protein 4 inhibitor, Btk tyrosine kinase inhibitor, C-reactive protein modulator, Ca2+ release-activated Ca2+ channel 1 inhibitor, cadherin-5 modulator, calcium-activated chloride channel inhibitor, calcium channel modulator, calpain-I inhibitor, calpain-II inhibitor, calpain-IX inhibitor, cannabinoid CB2 receptor receptor agonists, cannabinoid receptor modulators, casein kinase II inhibitors, CASP8-FADD-like modulator inhibitors, caspase inhibitors, catalase stimulators, CCL26 gene inhibitors, 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 antigen 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 transfer protein inhibitors, collagen modulators, complement C1s accessory component inhibitors, complement C3 inhibitors, complement factor C5 inhibitors, complement factor C5a inhibitors, complement factor H stimulators, complement cascade inhibitors, complement factor C2 inhibitors, complement factor D inhibitors, connective tissue growth factor ligand inhibitors, coronavirus nucleoprotein modulators, Ronavirus small envelope protein modulators, coronavirus spike glycoprotein inhibitors, coronavirus spike glycoprotein modulators, COVID19 envelope small membrane protein modulators, COVID19 nonstructural protein 8 modulators, COVID19 nucleoprotein modulators, COVID19 protein 3a inhibitors, COVID19 replicase polyprotein 1a inhibitors, COVID19 replicase polyprotein 1a modulators, COVID19 replicase polyprotein 1ab inhibitors, COVID19 replicase polyprotein 1ab modulators,COVID19 spike glycoprotein inhibitors, COVID19 spike glycoprotein modulators, COVID19 structural glycoprotein modulators, CRF-2 receptor agonists, CSF-1 agonists, CSF-1 antagonists, CX3CR1 chemokine antagonists, CXC10 chemokine ligand inhibitors, CXC5 chemokine ligand inhibitors, CXCL1 gene modulators, CXCL2 gene modulators, CXCL3 gene modulators, CXCR1 chemokine antagonists, CXCR2 chemokine antagonists, CXCR4 chemokine antagonists, cyclin D1 inhibitors, cyclin E inhibitors, cyclin-dependent kinase 1 inhibitors, cyclin-dependent kinase 2 inhibitors, cyclin-dependent kinase 5 inhibitors, cyclin-dependent kinase 7 inhibitors, cyclin-dependent kinase 9 inhibitors, cyclooxygenase 2 inhibitors, cyclooxygenase inhibitors, cysteine protease inhibitors, cytochrome 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 delta 4 desaturase inhibitors, dihydroorotate dehydrogenase inhibitors, dipeptidyl peptidase I inhibitors, dipeptidyl peptidase III inhibitors, diuretics, DNA binding protein inhibitors, DNA methyltransferase inhibitors, dopamine transporter inhibitors, E-selectin antagonists, Ecto NOX disulfide thiol exchanger 2 inhibitors, EGFR gene inhibitors, elongation factor 1 alpha 2 modulators, endoplasmin modulators, endoribonuclease DICER modulators, endothelin ET-A receptor antagonists, epidermal growth factor receptor antagonists, estrogen receptor beta agonists, estrogen receptor modulators, eukaryotic initiation factor 4A-I inhibitors, exo-alpha sialidase modulators, exportin 1 inhibitors, factor Ia modulators, factor IIa modulators, factor VII antagonists, factor Xa antagonists, factor XIa antagonists, FGF receptor antagonists, FGF-1 ligands,FGF-1 ligand inhibitor, FGF-2 ligand inhibitor, FGF1 receptor antagonist, FGF2 receptor antagonist, FGF3 receptor antagonist, Flt3 tyrosine kinase inhibitor, fractalkine ligand inhibitor, free fatty acid receptor 2 agonist, free fatty acid receptor 3 agonist, furin inhibitor, Fyn tyrosine kinase inhibitor, FYVE finger phosphoinositide kinase inhibitor, G protein-coupled bile acid receptor 1 agonist, GABA A receptor modulators, galectin-3 inhibitors, gamma-secretase inhibitors, GDF agonists, gelsolin stimulators, glial neurotrophic factor ligands, glucocorticoid receptor agonists, glutathione peroxidase stimulators, GM-CSF ligand inhibitors, GM-CSF receptor agonists, GM-CSF receptor modulators, Griffithsin modulators, growth regulatory protein alpha ligand inhibitors, Grp78 calcium binding protein inhibitors, heat shock protein HSP90 alpha inhibitors, heat shock protein HSP90 beta inhibitors, heat shock block protein inhibitors, heat shock protein stimulators, hemagglutinin regulators, hemoglobin regulators, hemolysin alpha 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 protein B1 inhibitors, histamine H1 receptor antagonists, histamine H2 receptor antagonists, histone deacetylase-6 inhibitors, histone inhibitors, HIV protease inhibitors, HIV-1 gp120 protein inhibitors, HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HLA class I antigen modulators, HLA class II antigen modulators, host cell factor modulators, Hsp 90 inhibitors, human papillomavirus E6 protein modulators, human papillomavirus E7 protein modulators, hypoxia-inducible factor inhibitor gene inhibitors, hypoxia-inducible factor-2 alpha modulators, I-kappa B kinase inhibitors, I-kappa B kinase modulators, ICAM-1 stimulators, IgG receptor FcRn large subunit p51 modulators, IL-12 receptor antagonists, IL-15 receptor agonists, IL-15 receptor modulators, IL-17 antagonists,IL-18 receptor accessory protein antagonist, IL-2 receptor agonist, IL-22 agonist, IL-23 antagonist, IL-6 receptor agonist, IL-6 receptor antagonist, IL-6 receptor modulator, IL-7 receptor agonist, IL-8 receptor antagonist, IL12 gene stimulator, IL8 gene modulator, immunoglobulin G modulator, immunoglobulin G1 agonist, immunoglobulin G1 modulator, immunoglobulin agonist, immunoglobulin gamma Fc receptor I modulator , immunoglobulin kappa modulators, inosine monophosphate dehydrogenase inhibitors, insulin sensitizers, integrin agonists, integrin alpha-4 / beta-7 antagonists, integrin alpha-V / beta-1 antagonists, integrin alpha-V / beta-6 antagonists, interferon agonists, interferon alpha 14 ligands, interferon alpha 2 ligands, interferon alpha 2 ligand modulators, interferon alpha ligands, Interferon alpha ligand inhibitors, interferon alpha ligand modulators, interferon beta ligands, interferon gamma ligand inhibitors, interferon gamma receptor agonists, interferon gamma receptor antagonists, interferon receptor modulators, interferon type I receptor agonists, interleukin-17A ligand inhibitors, interleukin-17F ligand inhibitors, interleukin-18 ligand inhibitors, interleukin-22 ligands, interleukin-1 beta ligand inhibitors, interleukin-1 beta ligand modulators, interleukin-1 ligand inhibitors, interleukin-2 ligands, interleukin-29 ligands, interleukin-6 ligand inhibitors, interleukin-7 ligands, interleukin-8 ligand inhibitors, IRAK-4 protein kinase inhibitors, JAK tyrosine kinase inhibitors, Jak1 tyrosine kinase inhibitors, Jak2 tyrosine kinase inhibitors, Jak3 tyrosine kinase inhibitors, Jun N-terminal kinase inhibitors, Jun N-terminal kinase regulators, kallikrein regulators, Kelch-like ECH-associated protein 1 regulators, Kit tyrosine kinase inhibitors, KLKB1 gene inhibitors, lactoferrin stimulators,Lanosterol-14 demethylase inhibitors, Lck kinase inhibitors, leukocyte Ig-like receptor A4 modulators, leukocyte elastase inhibitors, leukotriene BLT receptor antagonists, leukotriene D4 antagonists, leukotriene receptor antagonists, listeriocin stimulators, liver X receptor antagonists, low molecular weight heparins, lung fields, Surfactant-associated protein B stimulators, Pulmonary surfactant-associated protein D modulators, Lyn tyrosine kinase inhibitors, Lyn tyrosine kinase stimulators, Lysine-specific histone demethylase 1 inhibitors, Macrophage migration inhibitory factor inhibitors, Mannan-binding lectin serine protease inhibitors, Mannan-binding lectin serine protease 2 inhibitors, MAO B inhibitors, MAP kinase inhibitors, MAPK gene modulators, Matrix metalloproteinase modulators, Maxi K potassium channel inhibitors, MCL1 gene inhibitors, MEK protein kinase inhibitors, MEK-1 protein kinase inhibitors, melanocortin MC1 receptor agonists, melanocortin MC3 receptor agonists, metalloproteinase-12 inhibitors, METTL3 gene inhibitors, moesin inhibitors, moesin modulators, monocyte chemoattractant protein 1 ligand inhibitors, monocyte differentiation antigen CD14 inhibitors, mRNA cap guanine N7 methyltransferase modulators, mTOR complex 1 inhibitors, mTOR complex 2 inhibitors, mTOR inhibitors, mucolipin modulators, muscarinic receptor antagonists, myeloperoxidase inhibitors, NACHT LRR PYD domain protein 3 inhibitors, NAD synthase modulators, NADPH oxidase inhibitors, neuropilin 2 modulators, neuroplastin inhibitors, NFE2L2 gene stimulators, NK cell receptor agonists, NK1 receptor antagonists, NMDA receptor antagonists, NMDA receptor epsilon 2 subunit inhibitors, non-receptor tyrosine kinase TYK2 antagonists, non-nucleoside reverse transcriptase inhibitors, nuclear erythroid 2-related factor 2 stimulators, nuclear factor kappa B inhibitors, nuclear factor kappa B modulators, nuclease stimulators, nucleolin inhibitors, nuclear protein inhibitors, nuclear protein modulators, nucleoside reverse transcriptase inhibitors, opioid receptor agonists, opioid receptor antagonists, opioid receptor mu modulators, opioid receptor sigma antagonists 1, ornithine decarboxylase inhibitors, outer membrane protein inhibitors, OX40 ligands, p38 MAP kinase alpha inhibitors, p38 MAP kinase inhibitors, p38 MAP kinase modulators, p53 tumor suppressor protein stimulators, palmitoyl protein thioesterase 1 inhibitors, papain inhibitors, PARP inhibitors, PARP modulators, PDE 10 inhibitors,PDE 3 inhibitors, PDE 4 inhibitors, PDGF receptor alpha antagonists, PDGF receptor antagonists, PDGF receptor beta antagonists, peptidyl prolyl cis-trans isomerase A inhibitors, peroxiredoxin 6 modulators, PGD2 antagonists, PGI2 agonists, P-glycoprotein inhibitors, phosphoinositide 3 kinase inhibitors, phosphoinositide-3 kinase delta inhibitors, phosphoinositide-3 kinase gamma inhibitors, phospholipase A2 inhibitors, plasma kallikrein inhibitors, plasminogen activator inhibitor-1 inhibitors, platelet inhibitors anti-inflammatory agents, 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, PPAR alpha agonists, progesterone receptor agonists, programmed cell death protein 1 regulators, prolyl hydroxylase inhibitors, prostaglandin E synthase-1 inhibitors, protease inhibitors, proteasome inhibitors, protein arginine deiminase IV inhibitors, protein tyrosine kinase inhibitors, protein tyrosine phosphatase inhibitors Tyrase beta inhibitors, protein tyrosine phosphatase-2C inhibitors, proto-oncogene Mas agonists, purinergic receptor antagonists, Raf protein kinase inhibitors, RANTES ligands, Ras gene inhibitors, retinoic acid receptor response 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-CoV-3C protease-like inhibitors, serine protease inhibitors protease inhibitors, serine threonine protein kinase ATR inhibitors, serine threonine protein kinase TBK1 inhibitors, serum amyloid A protein modulators, signal transduction CD24 stimulators, sodium channel stimulators, sodium glucose transporter-2 inhibitors, sphingosine kinase 1 inhibitors, sphingosine kinase 2 inhibitors, sphingosine kinase inhibitors, sphingosine-1-phosphate receptor-1 agonists, sphingosine-1-phosphate receptor-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, stimulators of interferon gene proteins, 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 modulators, tankyrase-1 inhibitors, tankyrase-2 inhibitors, Tek tyrosine kinase receptor stimulators, telomerase modulators, tetanus toxin modulators, TGF beta receptor antagonists, TGFB2 gene inhibitors, thymosin beta 4 ligands, thyroid hormone receptor beta agonists, tissue factor inhibitors, tissue plasminogen activator modulators, tissue plasminogen activator stimulators, TLR agonists, TLR modulators, 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 R-9 agonists, TMPRSS2 gene inhibitors, TNF alpha ligand inhibitors, TNF alpha ligand modulators, TNF binders, TNF gene inhibitors, topoisomerase inhibitors, transcription factor EB stimulators, transferrin modulators, transketolase inhibitors, translocation-associated protein inhibitors, transmembrane serine protease 2 inhibitors, transthyretin 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 alpha inhibitors, tubulin beta inhibitors, tumor necrosis factor 14 ligand inhibitors, TYK2 gene inhibitors, type I IL-1 receptor antagonists, tyrosine protein kinase ABL1 inhibitors, ubiquinol cytochrome C reductase 14kDa inhibitors,Ubiquitin ligase modulators, non-specific GPCR agonists, non-specific cytokine receptor modulators, non-specific enzyme stimulators, non-specific gene inhibitors, non-specific 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 inhibitors of inhibitor of apoptosis protein, xanthine oxidase inhibitors, or zonulin inhibitors.

[0342] In some embodiments, the compounds and compositions of the disclosure may be administered in combination with Sars-Cov-2 treatments such as parenteral fluids (including dextrose saline and lactated Ringer's solution), nutrition, antibiotics (including azithromycin, metronidazole, amphotericin B, amoxicillin / clavulanate, trimethoprim / sulfamethoxazole, R-327 and cephalosporin antibiotics such as ceftriaxone and cefuroxime), antifungal prophylaxis, fever and pain medications, antiemetics (e.g., metoclopramide) and / or antidiarrheal agents, vitamin and mineral supplements (including vitamin K, vitamin D, cholecalciferol, vitamin C and zinc sulfate), anti-inflammatory agents (e.g., ibuprofen or steroids), corticosteroids such as dexamethasone, methylprednisolone, prednisone, mometasone, immunomodulators (e.g., interferons), vaccines, and analgesics.

[0343] In some embodiments, the additional therapeutic agent is an Abl tyrosine kinase inhibitor (such as, for example, radotinib or imatinib).

[0344] In some embodiments, the additional therapeutic agent is an acetaldehyde dehydrogenase inhibitor, such as ADX-629.

[0345] In some embodiments, the additional therapeutic agent is an adenosine A3 receptor agonist, such as piclidenoson.

[0346] In some embodiments, the additional therapeutic agent is an adrenomedullin ligand, such as adrenomedullin.

[0347] In some embodiments, the additional therapeutic agent is a p38 MAPK+PPAR gamma agonist / insulin sensitizer, such as KIN-001.

[0348] In some embodiments, the additional therapeutic agent is an aldose reductase inhibitor, such as cafficlestat.

[0349] In some embodiments, the additional therapeutic agent is an AMPA receptor modulator, such as traneurosin.

[0350] In some embodiments, the additional therapeutic agent is an annexin A5 stimulator, such as AP-01 or SY-005.

[0351] In some embodiments, the additional therapeutic agent is an anticoagulant such as heparin (heparin and low molecular weight heparin), aspirin, apixaban, dabigatran, edoxaban, argatroban, enoxaparin, or fondaparinux.

[0352] In some embodiments, the additional therapeutic agent is an androgen receptor antagonist, such as bicalutamide, enzalutamide, or purselutamide (procultamide).

[0353] In some embodiments, the additional therapeutic agent is an antihypoxic agent, such as trans-sodium crocetinate.

[0354] In some embodiments, the additional therapeutic agent is an antithrombotic agent such as defibrotide, rivaroxaban, alteplase, tirofiban, clopidogrel, prasugrel, bemiparin, bivalirudin, sulodexide, or tenecteplase.

[0355] In some embodiments, the additional therapeutic agent is an antihistamine such as chloroperastine or clemastine.

[0356] In some embodiments, the additional therapeutic agent is an apolipoprotein A1 agonist, eg, CER-001.

[0357] In some embodiments, the additional therapeutic agent is a phospholipase A2 inhibitor, such as ethyl icosapentate.

[0358] In some embodiments, the additional therapeutic agent is an axl tyrosine kinase receptor inhibitor, such as bemcentinib.

[0359] In some embodiments, the additional therapeutic agent is a corticosteroid / beta 2 adrenergic receptor agonist such as budesonide plus formoterol fumarate.

[0360] In some embodiments, the additional therapeutic agent is a BET bromodomain inhibitor / APOA1 gene stimulator, e.g., apabetalone.

[0361] In some embodiments, the additional therapeutic agent is a blood coagulation modulating agent, such as lanadelumab.

[0362] In some embodiments, the additional therapeutic agent is a bradykinin B2 receptor antagonist, eg, icatiban.

[0363] In some embodiments, the additional therapeutic agent is an EGFR gene inhibitor / Btk tyrosine kinase inhibitor, e.g., abivertinib.

[0364] In some embodiments, the additional therapeutic agent is a Btk tyrosine kinase inhibitor (such as, for example, ibrutinib or zanubrutinib).

[0365] In some embodiments, the additional therapeutic agent is a calpain-I / II / IX inhibitor, eg, BLD-2660.

[0366] In some embodiments, the additional therapeutic agent is a Ca2+ release-activated Ca2+ channel 1 inhibitor, for example, zegoculactin (CM-4620).

[0367] In some embodiments, the additional therapeutic agent is a cadherin-5 modulating agent, such as FX-06.

[0368] In some embodiments, the additional therapeutic agent is a casein kinase II inhibitor, such as silmitasertib.

[0369] In some embodiments, the additional therapeutic agent is a caspase inhibitor, such as emricasan.

[0370] In some embodiments, the additional therapeutic agent is a catalase / superoxide dismutase stimulator, such as MP-1032.

[0371] In some embodiments, the additional therapeutic agent is a CCR2 / CCR5 chemokine antagonist (such as, for example, cenicriviroc).

[0372] In some embodiments, the additional therapeutic agent is a CCR5 chemokine antagonist, eg, maraviroc.

[0373] In some embodiments, the additional therapeutic agent is a CD122 agonist / IL-2 receptor agonist, eg, bempegaldeleukin.

[0374] In some embodiments, the additional therapeutic agent is a CD73 agonist / interferon beta ligand (eg, FP-1201).

[0375] In some embodiments, the additional therapeutic agent is a cholesterol ester transfer protein inhibitor, such as dalcetrapib.

[0376] In some embodiments, the additional therapeutic agent is a mannan-binding lectin serine protease / complement C1s subcomponent inhibitor / myeloperoxidase inhibitor, such as RLS-0071.

[0377] In some embodiments, the additional therapeutic agent is a complement factor C5 inhibitor / leukotriene BLT receptor antagonist, e.g., nomacopan.

[0378] In some embodiments, the additional therapeutic agent is a complement factor C5 inhibitor, eg, zilucoplan.

[0379] In some embodiments, the additional therapeutic agent is a CXCR4 chemokine antagonist, eg, motixafortide.

[0380] In some embodiments, the additional therapeutic agent is a cytochrome P450 3A4 inhibitor / peptidyl-prolyl cis-trans isomerase A inhibitor, such as alisporivir.

[0381] In some embodiments, the additional therapeutic agent is a cysteine protease inhibitor, such as SLV-213.

[0382] In some embodiments, the additional therapeutic agent is a dihydroorotate dehydrogenase inhibitor, such as brequinar, RP-7214, or emvodostat.

[0383] In some embodiments, the additional therapeutic agent is a dehydropeptidase-1 modulator, eg, Metablok.

[0384] In some embodiments, the additional therapeutic agent is a dihydroorotate dehydrogenase inhibitor / IL-17 antagonist, such as bidofurzimus.

[0385] In some embodiments, the additional therapeutic agent is a diuretic, such as an aldosterone antagonist, such as spironolactone.

[0386] In some embodiments, the additional therapeutic agent is a desoxyribonuclease I stimulator, such as GNR-039 or dornase alfa.

[0387] In some embodiments, the additional therapeutic agent is a NET inhibitor, such as NTR-441.

[0388] In some embodiments, the additional therapeutic agent is a dihydroceramide delta 4 desaturase inhibitor / sphingosine kinase 2 inhibitor, e.g., opaganib.

[0389] In some embodiments, the additional therapeutic agent is a DNA methyltransferase inhibitor, for example, azacytidine.

[0390] In some embodiments, the additional therapeutic agent is an LXR antagonist (such as, for example, larscosterol).

[0391] In some embodiments, the additional therapeutic agent is a dipeptidyl peptidase I inhibitor, such as brenosertib.

[0392] In some embodiments, the additional therapeutic agent is an elongation factor 1 alpha 2 modulator, eg, plitidepsin.

[0393] In some embodiments, the additional therapeutic agent is a eukaryotic initiation factor 4A-I inhibitor, such as zotatifine.

[0394] In some embodiments, the additional therapeutic agent is an exo-alpha sialidase modulator, such as DAS-181.

[0395] In some embodiments, the additional therapeutic agent is an exportin 1 inhibitor, such as selinexor.

[0396] In some embodiments, the additional therapeutic agent is a fractalkine ligand inhibitor, such as KAND-567.

[0397] In some embodiments, the additional therapeutic agent is a FYVE finger phosphoinositide kinase inhibitor / IL-12 receptor antagonist / IL-23 antagonist, e.g., apilimod dimesylate.

[0398] In some embodiments, the additional therapeutic agent is a GABA A receptor modulator, such as brexanolone.

[0399] In some embodiments, the additional therapeutic agent is a glucocorticoid receptor agonist, eg, ciclesonide, hydrocortisone, dexamethasone, dexamethasone phosphate, or 101-PGC-005.

[0400] In some embodiments, the additional therapeutic agent is a GM-CSF receptor agonist, such as sargramostim.

[0401] In some embodiments, the additional therapeutic agent is a GPCR agonist, such as esveraprost sodium.

[0402] In some embodiments, the additional therapeutic agent is a Griffithin modulator, eg, Q-Griffithin.

[0403] In some embodiments, the additional therapeutic agent is a leukotriene D4 antagonist, such as montelukast.

[0404] In some embodiments, the additional therapeutic agent is a histamine H1 receptor antagonist, such as ebastine, tranilast, or levocetirizine dihydrochloride.

[0405] In some embodiments, the additional therapeutic agent is a histamine H2 receptor antagonist, such as famotidine.

[0406] In some embodiments, the additional therapeutic agent is a heat shock protein stimulator such as BGP-15 / insulin sensitizer / PARP inhibitor.

[0407] In some embodiments, the additional therapeutic agent is a histone inhibitor, such as STC-3141.

[0408] In some embodiments, the additional therapeutic agent is a histone deacetylase-6 inhibitor, eg, CKD-506.

[0409] In some embodiments, the additional therapeutic agent is a HIF prolyl hydroxylase-2 inhibitor, eg, desidustat.

[0410] In some embodiments, the additional therapeutic agent is a HIF prolyl hydroxylase inhibitor (such as, for example, vadadustat).

[0411] In some embodiments, the additional therapeutic agent is an IL-8 receptor antagonist (such as, for example, reparixin).

[0412] In some embodiments, the additional therapeutic agent is an IL-7 receptor agonist, such as CYT-107.

[0413] In some embodiments, the additional therapeutic agent is an IL-7 receptor agonist / interleukin-7 ligand, eg, efyneptakine alfa.

[0414] In some embodiments, the additional therapeutic agent is an IL-22 agonist, such as efmarodocoquin alfa.

[0415] In some embodiments, the additional therapeutic agent is an IL-22 agonist / interleukin 22 ligand, such as F-652.

[0416] In some embodiments, the additional therapeutic agent is an integrin alpha-V / beta-1 antagonist / integrin alpha-V / beta-6 antagonist, such as bexotegrast.

[0417] In some embodiments, the additional therapeutic agent is an interferon alpha-2 ligand, eg, interferon alpha-2b or virafin.

[0418] In some embodiments, the additional therapeutic agent is an interferon beta ligand, eg, interferon beta-1a follow-on biologic, interferon beta-1b, or SNG-001.

[0419] In some embodiments, the additional therapeutic agent is an interferon receptor modulator, such as pegylated interferon lambda-1a.

[0420] In some embodiments, the additional therapeutic agent is an interleukin-2 ligand, eg, aldesleukin.

[0421] In some embodiments, the additional therapeutic agent is an IRAK-4 protein kinase inhibitor, eg, dimlobicertib.

[0422] In some embodiments, the additional therapeutic agent is a JAK inhibitor, for example, the additional therapeutic agent is baricitinib, filgotinib, jactinib, tofacitinib, or nedulcitinib (TD-0903).

[0423] In some embodiments, the additional therapeutic agent is a neutrophil elastase inhibitor, eg, alberestat.

[0424] In some embodiments, the additional therapeutic agent is a pulmonary surfactant-associated protein D modulator, eg, AT-100.

[0425] In some embodiments, the additional therapeutic agent is a plasma kallikrein inhibitor, e.g., donidalorsen.

[0426] In some embodiments, the additional therapeutic agent is a lysine-specific histone demethylase 1 / MAO B inhibitor, such as bafidemstat.

[0427] In some embodiments, the additional therapeutic agent is a mannan-binding lectin serine protease inhibitor, e.g., conestat alfa.

[0428] In some embodiments, the additional therapeutic agent is a maximum K potassium channel inhibitor, such as ENA-001.

[0429] In some embodiments, the additional therapeutic agent is a MEK protein kinase inhibitor (such as, for example, zapnometinib).

[0430] In some embodiments, the additional therapeutic agent is a MEK-1 protein kinase inhibitor / Ras gene inhibitor, eg, antroquinonol.

[0431] In some embodiments, the additional therapeutic agent is a melanocortin MC1 receptor agonist, eg, PL-8177.

[0432] In some embodiments, the additional therapeutic agent is a matrix metalloproteinase-12 inhibitor, eg, FP-025.

[0433] In some embodiments, the additional therapeutic agent is a NACHT LRR PYD domain protein 3 inhibitor, such as dapanstril, DFV-890, or ZYIL-1.

[0434] In some embodiments, the additional therapeutic agent is an NADPH oxidase inhibitor, for example, isquinaxib.

[0435] In some embodiments, the additional therapeutic agent is a neuropilin 2 modulator, such as efzofitimod.

[0436] In some embodiments, the additional therapeutic agent is an NK1 receptor antagonist, such as aprepitant or tradipitant.

[0437] In some embodiments, the additional therapeutic agent is an NMDA receptor antagonist, such as translocetin or ifenprodil.

[0438] In some embodiments, the additional therapeutic agent is a nuclear factor kappa B inhibitor / p38 MAP kinase inhibitor (such as, for example, Zenuzolac).

[0439] In some embodiments, the additional therapeutic agent is an ornithine decarboxylase inhibitor, such as eflornithine.

[0440] In some embodiments, the additional therapeutic agent is an opioid receptor sigma antagonist 1, such as MR-309.

[0441] In some embodiments, the additional therapeutic agent is a PGD2 antagonist, e.g., asapiprant.

[0442] In some embodiments, the additional therapeutic agent is a PDGF receptor antagonist / TGFβ receptor antagonist / p38 MAP kinase inhibitor (such as, for example, deupirfenidone).

[0443] In some embodiments, the additional therapeutic agent is a phospholipase A2 inhibitor, such as varespladib methyl.

[0444] In some embodiments, the additional therapeutic agent is a phosphoinositide 3-kinase inhibitor / mTOR complex inhibitor, such as ductolisib.

[0445] In some embodiments, the additional therapeutic agent is a phosphoinositide-3 kinase delta / gamma inhibitor (such as, for example, duvelisib).

[0446] In some embodiments, the additional therapeutic agent is a plasminogen activator inhibitor-1 inhibitor, such as TM-5614.

[0447] In some embodiments, the additional therapeutic agent is a protein tyrosine phosphatase beta inhibitor, e.g., razuprotafib.

[0448] In some embodiments, the additional therapeutic agent is a RIP-1 kinase inhibitor (such as, for example, DNL-758 or SIR-0365).

[0449] In some embodiments, the additional therapeutic agent is a Rev protein modulator, such as obefagimod.

[0450] In some embodiments, the additional therapeutic agent is an S-phase kinase-associated protein 2 inhibitor, e.g., niclosamide or DWRX-2003.

[0451] In some embodiments, the additional therapeutic agent is a signal transducer CD24 stimulator, such as EXO-CD24.

[0452] In some embodiments, the additional therapeutic agent is a sodium glucose transporter-2 inhibitor, such as dapagliflozin propanediol.

[0453] In some embodiments, the additional therapeutic agent is a calcium channel stimulator, such as solnatide.

[0454] In some embodiments, the additional therapeutic agent is a sphingosine-1-phosphate receptor-1 agonist / sphingosine-1-phosphate receptor-5 agonist, such as ozanimod.

[0455] In some embodiments, the additional therapeutic agent is a nonsteroidal anti-inflammatory drug, such as Ampion.

[0456] In some embodiments, the additional therapeutic agent is a superoxide dismutase stimulator, such as avasopasem manganese.

[0457] In some embodiments, the additional therapeutic agent is a Syk tyrosine kinase inhibitor, such as fostamacitinib sodium hydrate.

[0458] In some embodiments, the additional therapeutic agent is a Tie2 tyrosine kinase receptor agonist, such as AV-001.

[0459] In some embodiments, the additional therapeutic agent is a TGFB2 gene inhibitor, e.g., travedersen.

[0460] In some embodiments, the additional therapeutic agent is a tissue factor inhibitor, such as AB-201.

[0461] In some embodiments, the additional therapeutic agent is a TLR-3 agonist, such as lintatolimod.

[0462] In some embodiments, the additional therapeutic agent is a TLR-4 antagonist, such as ApTLR-4FT, EB-05, or erythrolan.

[0463] In some embodiments, the additional therapeutic agent is a TLR-7 / 8 antagonist (such as, for example, empatran).

[0464] In some embodiments, the additional therapeutic agent is a TLR-2 / 6 agonist, such as INNA-051.

[0465] In some embodiments, the additional therapeutic agent is a TLR-7 antagonist, such as PRTX-007.

[0466] In some embodiments, the additional therapeutic agent is a TLR agonist such as, for example, PUL-042.

[0467] In some embodiments, the additional therapeutic agent is a TLR-4 agonist, such as REVTx-99.

[0468] In some embodiments, the additional therapeutic agent is a TLR-2 / 4 antagonist, such as VB-201.

[0469] In some embodiments, the additional therapeutic agent is a TNFα ligand inhibitor, such as pezipanelmin.

[0470] In some embodiments, the additional therapeutic agent is a type I IL-1 receptor antagonist, such as anakinra.

[0471] In some embodiments, the additional therapeutic agent is a TREM receptor 1 antagonist, eg, nangibotide.

[0472] In some embodiments, the additional therapeutic agent is a trypsin inhibitor, such as urinastatin.

[0473] In some embodiments, the additional therapeutic agent is a tubulin inhibitor such as sabizabrin, CCI-001, PCNT-13, CR-42-24, albendazole, entasobrin, SAR-132885, or ON-24160.

[0474] In some embodiments, the additional therapeutic agent is a VIP receptor agonist, such as aviptadil.

[0475] In some embodiments, the additional therapeutic agent is a xanthine oxidase inhibitor, such as oxypurinol.

[0476] In some embodiments, the additional therapeutic agent is a vasodilator, e.g., iloprost, epoprostenol (VentaProst), zavegepant, TXA-127, USB-002, ambrisentan, nitric oxide nasal spray (NORS), pentoxifylline, propranolol, RESP301, sodium nitrite, or dipyridamole.

[0477] In some embodiments, the additional therapeutic agent is a vitamin D3 receptor agonist, such as cholecalciferol.

[0478] In some embodiments, the additional therapeutic agent is a zonulin inhibitor, such as larazotide acetate.

[0479] In some embodiments, the additional therapeutic agent is a synthetic retinoid derivative, such as fenretinide.

[0480] In some embodiments, the additional therapeutic agent is a glucose metabolism inhibitor, eg, WP-1122.

[0481] In some embodiments, the additional therapeutic agent is AT-H201, 2-deoxy-D-glucose, AD-17002, AIC-649, Astodrimer, AZD-1656, Bitespiramicin, Bucillamine, Budesonide, CNM-AgZn-17, Codevir, Didodecylmethotrexate, DW-2008S (DW-2008), EDP-1815, EG-009A, Fabencov, Gamunex, Genistein, GLS-1200, hzVSF-v13, Imidazolylethaneamide Pentanedioic Acid, IMM-101, MAS-825, MRG-001, Nasitrol, Nylexa, OP-101, OPN-019, Orynotide rhesus theta defensin-1 defensin-1), pyronaridine plus artesunate, dapsone, RPH-104, sodium pyruvate, sulfoladex, tafenoquine, TB-006, telasevec, Tempol, TL-895, thimesol, trimodulin, XC-221, XC-7, duncemtinib, metformin glycinate, lucinactant, EOM-613, mosdipimode, ivermectin, leflunomide, ibudilast, RBT-9, raloxifene, prothion, gemcabene, or idronoxyl.

[0482] In some embodiments, the additional therapeutic agent is a CD73 antagonist, such as AK-119.

[0483] In some embodiments, the additional therapeutic agent is a CD95 protein fusion, such as asnercept.

[0484] In some embodiments, the additional therapeutic agent is a complement factor C2 modulator, eg, ARGX-117.

[0485] In some embodiments, the additional therapeutic agent is a complement C3 inhibitor, eg, NGM-621.

[0486] In some embodiments, the additional therapeutic agent is a CXC10 chemokine ligand inhibitor (such as, for example, EB-06).

[0487] In some embodiments, the additional therapeutic agent is a cytotoxic T-lymphocyte protein-4 fusion protein, such as abatacept.

[0488] In some embodiments, the additional therapeutic agent is an anti- S. aureus antibody (e.g., tosatocumab, etc.).

[0489] In some embodiments, the additional therapeutic agent is an anti-LPS antibody, such as IMM-124-E.

[0490] In some embodiments, the additional therapeutic agent is an adrenomedullin ligand inhibitor (such as, for example, enivalcimab).

[0491] In some embodiments, the additional therapeutic agent is a basigin inhibitor, such as meplasmab.

[0492] In some embodiments, the additional therapeutic agent is a CD3 antagonist, such as foralaumab.

[0493] In some embodiments, the additional therapeutic agent is a connective tissue growth factor ligand inhibitor, e.g., pamrevlumab.

[0494] In some embodiments, the additional therapeutic agent is a complement factor C5a inhibitor, such as BDB-1 or vilobelimab.

[0495] In some embodiments, the additional therapeutic agent is a complement factor C5 inhibitor, e.g., ravulizumab.

[0496] In some embodiments, the additional therapeutic agent is a mannan-binding lectin serine protease-2 inhibitor (such as, for example, narsoplimab).

[0497] In some embodiments, the additional therapeutic agent is a GM-CSF modulator, for example, gimsilumab, namilumab, brommallimab, otolimab, or lenzilumab.

[0498] In some embodiments, the additional therapeutic agent is a heat shock protein inhibitor / IL-6 receptor antagonist (such as, for example, siltuximab).

[0499] In some embodiments, the additional therapeutic agent is an IL-6 receptor antagonist, such as clazakizumab, revilimab, olokizumab, tocilizumab, or sirukumab.

[0500] In some embodiments, the additional therapeutic agent is an IL-8 receptor antagonist (such as, for example, BMS-986253).

[0501] In some embodiments, the additional therapeutic agent is an interleukin-1 beta ligand inhibitor, such as canakinumab.

[0502] In some embodiments, the additional therapeutic agent is an interferon gamma ligand inhibitor, such as emapalumab.

[0503] In some embodiments, the additional therapeutic agent is an anti-ILT7 antibody, such as daxzilimab.

[0504] In some embodiments, the additional therapeutic agent is a monocyte differentiation antigen CD14 inhibitor, such as atibuclimab.

[0505] In some embodiments, the additional therapeutic agent is a plasma kallikrein inhibitor, such as lanadelumab.

[0506] In some embodiments, the additional therapeutic agent is a platelet glycoprotein VI inhibitor (such as, for example, glenzocimab).

[0507] In some embodiments, the additional therapeutic agent is a T-cell differentiation antigen CD6 inhibitor, such as itolizumab.

[0508] In some embodiments, the additional therapeutic agent is a TNFα ligand inhibitor / TNF binder (such as, for example, infliximab).

[0509] In some embodiments, the additional therapeutic agent is an anti-LIGHT antibody, such as AVTX-002.

[0510] In some embodiments, the additional therapeutic agent is COVID-HIG.

[0511] In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is co-administered with one or more agents useful in the treatment and / or prevention of COVID-19.

[0512] 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 sarilumab; Janus kinase (JAK) inhibitors, such as baricitinib, ruxolitinib, or tofacitinib; and antiviral agents, such as molnupiravir, sotrovimab, or remdesivir.

[0513] In further embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is co-administered with two or more agents useful in the treatment of COVID-19, including, but not limited to, a compound of the present disclosure and two additional therapeutic agents, such as nilmatrervir and ritonavir, casirivimab and imdevimab, or ruxolitinib and tofacitinib.

[0514] In some embodiments, the additional therapeutic agent comprises 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 additional therapeutic agent is an RNA-dependent RNA polymerase (RdRp) inhibitor.

[0515] In some embodiments, the antiviral agent is an angiotensin converting enzyme 2 inhibitor, an angiotensin converting enzyme 2 modulator, an angiotensin converting enzyme 2 stimulator, an angiotensin II AT-2 receptor agonist, an angiotensin II AT-2 receptor antagonist, an angiotensin II receptor modulator, a coronavirus nucleoprotein modulator, a coronavirus small envelope protein modulator, a coronavirus spike glycoprotein inhibitor, a coronavirus spike glycoprotein modulator, a COVID19 envelope small membrane protein inhibitor, a COVID19 envelope small membrane protein modulator, a COVID19 MPro inhibitors, COVID19 nonstructural protein 8 modulators, COVID19 nucleoprotein inhibitors, COVID19 nucleoprotein modulators, COVID19 protein 3a inhibitors, COVID19 replicase polyprotein 1a modulators, COVID19 replicase polyprotein 1a inhibitors, COVID19 replicase polyprotein 1ab modulators, COVID19 replicase polyprotein 1ab modulators, COVID19 spike glycoprotein inhibitors, COVID19 spike glycoprotein modulators, COVID19 structural glycoprotein modulators, papain inhibitors, protease inhibitors The inhibitor is selected from a protease inhibitor, a protease modulator, an RNA polymerase inhibitor, an RNA polymerase modulator, an RNA-dependent RNA polymerase (RdRp) inhibitor, a SARS coronavirus 3C protease-like inhibitor, a 3CLpro / Mpro inhibitor, a serine protease inhibitor, a transmembrane serine protease 2 inhibitor, a transmembrane serine protease 2 modulator, a viral envelope protein inhibitor, a viral protease inhibitor, a viral protease modulator, a viral protein target modulator, a viral ribonuclease inhibitor, and a viral structural protein modulator.

[0516] In some embodiments, the additional therapeutic agent is an entry inhibitor, e.g., in some embodiments, the additional therapeutic agent is an ACE2 inhibitor, a fusion inhibitor, or a protease inhibitor.

[0517] In some embodiments, the additional therapeutic agent is an angiotensin-converting enzyme 2 inhibitor, eg, SBK-001.

[0518] In some embodiments, the additional therapeutic agent is an angiotensin-converting enzyme 2 modulator, such as Numifil or JN-2019.

[0519] In some embodiments, the additional therapeutic agent is an entry inhibitor, such as MU-UNMC-1.

[0520] In some embodiments, the additional therapeutic agent is an angiotensin-converting enzyme 2 stimulator, such as alnasidase alfa.

[0521] In some embodiments, the additional therapeutic agent is an angiotensin II AT-2 receptor agonist, eg, VP-01.

[0522] In some embodiments, the additional therapeutic agent is an ACE II receptor antagonist, eg, DX-600.

[0523] In some embodiments, the additional therapeutic agent is an angiotensin II receptor modulator, such as TXA-127.

[0524] In some embodiments, the additional therapeutic agent is a transmembrane serine protease 2 modulator, eg, BC-201.

[0525] In some embodiments, the additional therapeutic agent is a viral envelope protein inhibitor, such as MXB-9 or MXB-004.

[0526] In some embodiments, the additional therapeutic agent is a vaccine. For example, in some embodiments, the additional 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 cellular vaccine, or a dendritic cell vaccine.

[0527] In some embodiments, the additional therapeutic agent is Tosinameran, NVX-CoV2373, Elasomeran, KD-414, Janssen COVID-19 vaccine, Bakiszebria, 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, 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 Virion, 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.These vaccines include 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, and BNT162b5.

[0528] In some embodiments, the additional therapeutic agent is a protease inhibitor. For example, in some embodiments, the additional therapeutic agent is a 3C-like cysteine protease inhibitor (3CL (also called main protease, M)), a papain-like protease inhibitor (PL), a serine protease inhibitor, or a transmembrane serine protease 2 inhibitor (TMPRSS2).

[0529] In some embodiments, the additional therapeutic agent 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, nilmatrervir, ensitrervir, ASC-11, EDDC-2214, SIM-0417, CDI-45205, COR-803, ALG-097111, TJC-642, CVD-0013943, eravacycline, cynarin, or prexasertib.

[0530] In some embodiments, the additional therapeutic agent is a papain-like protease inhibitor (PLpro), e.g., SBFM-PL4 or GRL-0617.

[0531] In some embodiments, the additional therapeutic agent is a SARS-CoV-2 helicase Nsp13 inhibitor, such as EIS-4363.

[0532] In some embodiments, the additional therapeutic agent is a SARS-CoV-2 spike (S) and a protease modulator, e.g., ENU-200.

[0533] In some embodiments, t...

Claims

1. Compounds of formula (I): 【Hua747】 or a pharmaceutically acceptable salt thereof [wherein: ring 【Chemical 748】 is C ６～１０ aryl or 5-10 membered heteroaryl; Each L １ are independently a bond, —O—, —(C １～６ alkyl)O—, —O(C １～６ alkyl)-, -C １～６ Alkyl-O(C １～６ alkyl)-, -C(O)-, -N(R Ｌ )C(O)-, -C(O)N(R Ｌ ) -, -(C １～６ alkyl) (R Ｌ )NC(O)-,-(C １～６ alkyl)C(O)N(R Ｌ ) -, -N(R Ｌ )C(O)(C １～６ alkyl)-, -C(O)N(R Ｌ ) (C １～６ alkyl)-, -(C １～６ alkyl)N(R Ｌ )C(O)(C １～６ alkyl)-, -(C １～６ alkyl)C(O)N(R Ｌ ) (C １～６ alkyl)-, -S(O) ２ -, -S(O) ２ N (R Ｌ ) -, -N(R Ｌ )-S(O) ２ -, -(C １～６ alkyl)S(O) ２ N (R Ｌ ) -, -(C １～６ alkyl)N(R Ｌ ) S (O) ２ -, -S(O) ２ N (R Ｌ ) (C １～６ alkyl)-, -N(R Ｌ ) S (O) ２ (C １～６ alkyl)-, -(C １～６ alkyl)S(O) ２ N (R Ｌ ) (C １～６ alkyl)- or -(C １～６ alkyl)N(R Ｌ ) S (O) ２ (C １～６ alkyl)-; Each R １ are independently halogen, —OH, —CN, C １～６ Alkyl, —CN, —C(O)NH ２ , C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, C ３～８ Cycloalkyl, C ６ aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R １ａ optionally substituted with; Or, two R １ are the rings to which they are attached. 【Chemical 749】 together with the atom(s) form a 5- to 10-membered heterocyclyl; Each R １ａ are independently １～６ Alkyl, halogen, C ３～８ cycloalkyl, 4- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, oxo, —OH, —CN, —NH ２ , -O(C １～６ alkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C ３～８ cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C ３～８ cycloalkyl) ２ , —N(5- to 10-membered heterocyclyl) ２ , -N(C ６ aryl) ２ , —N(5- to 10-membered heteroaryl) ２ , -N(C １～６ alkyl) (C ３～８ cycloalkyl), -N(C １～６ alkyl)(5- to 10-membered heterocyclyl), —N(C １～６ alkyl) (C ６ aryl), -N(C １～６ alkyl)(5- to 10-membered heteroaryl), —C(O)(5- to 10-membered heterocyclyl), —C(O)(5- to 10-membered heteroaryl), —C(O)O(C １～６ alkyl), —C(O)O(C ３～８ cycloalkyl), —C(O)O(5- to 10-membered heterocyclyl), —C(O)O(C ６ aryl), —C(O)O (5- to 10-membered heteroaryl), —C(O)NH ２ , -C(O)NH(C １～６ alkyl), —C(O)NH(C ３～８ cycloalkyl), —C(O)NH(5- to 10-membered heterocyclyl), —C(O)NH(C ６ aryl), —C(O)NH (5- to 10-membered heteroaryl), —C(O)N(C １～６ alkyl) ２ , -C(O)N(C ３～８ cycloalkyl) ２ , —C(O)N(5- to 10-membered heterocyclyl) ２ , -C(O)N(C ６ aryl) ２ , —C(O)N(5- to 10-membered heteroaryl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), -NHC(O)NH(C ３～８ cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C ６ aryl), -NHC(O)NH (5- to 10-membered heteroaryl), -NHS(O)(C １～６ alkyl), -N(C １～６ alkyl)(S(O)(C １～６ alkyl), -S(O) ２ (C １～６ alkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O) ２ (5- to 10-membered heterocyclyl), —S(O) ２ (C ６ aryl), -S(O) ２ (5- to 10-membered heteroaryl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R １ｂ optionally substituted with; Each R １ｂ are independently １～６ Alkyl, C １～６ Haloalkyl, halogen, oxo, —OH, —NH ２ , CO ２ H, —O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ２～６ alkynyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６－ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O) ２ (5- to 10-membered heterocyclyl), —S(O) ２ (C ６ aryl), -S(O) ２ (5- to 10-membered heteroaryl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and m is an integer from 0 to 3; R ２ is hydrogen, C １～３ Alkyl, C １～３ Haloalkyl, cyclopropyl, C １～３ Alkoxy, —O(C １～３ haloalkyl), —O(cyclopropyl), halogen, or —CN; X １ is S, N, or C(R ｘ１ ) and X ２ is S, N, or C(R ｘ２ ) and X ３ is N or C(R ｘ３ ) where X １ and X ２ is not S; Or, X ３ is a bond, where X １ and X ２ one of which is S; Each R ｘ１ , R ｘ２ , and R ｘ３ are independently hydrogen, halogen, C １～３ Alkyl, C １～３ Haloalkyl, O C １～３ Haloalkyl, C １～３ alkoxy, cyclopropyl, or O-cyclopropyl; X ４ and X ５ Tamaki who became friends with 【Chemistry 750】 is C ６ Aryl, 5- to 6-membered heteroaryl, C ５～１０ cycloalkyl, or 5- to 10-membered heterocyclyl; Here, each X ４ and X ５ is independently N or C; Or, ring 【Chemistry 751】 does not exist, where X ４ is N or CL ｘ４ -R ｘ４ and X ５ is N or CL ｘ５ -R ｘ５ and Each L ｘ４ and L ｘ５ are independently a bond, -(C １～６ alkyl)O-, -(C １～６ alkyl)N(R Ｌ )C(O)-,-(C １～６ alkyl)C(O)N(R Ｌ ) -, -(C １～６ alkyl)N(R Ｌ )C(O)(C １～６ alkyl)-, -(C １～６ alkyl)C(O)N(R Ｌ ) (C １～６ alkyl)-, -(C １～６ alkyl), -(C １～６ alkyl)N(R Ｌ ) S (O) ２ -, -N(R Ｌ ) S (O) ２ -, -C(O)-, -(C １～６ alkyl)C(O)-, or -N(R Ｌ )C(O)—; Each R ｘ４ and R ｘ５ are independently hydrogen, halogen, hydroxy, —CN, C １～６ Alkyl, C ２～６ Alkynyl, C １～６ Alkoxy, C ３～８ cycloalkyl, 4- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -O(C １～６ alkyl), or —OC ３～８ is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R ４ａ optionally substituted with; Each R ４ａ are independently １～６ Alkyl, C １～６ Haloalkyl, halogen, C ３～８ cycloalkyl, 4- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, oxo, —OH, —CN, —NH ２ , -O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６～１０ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), —NH(5- to 10-membered heterocyclyl), —NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C １～６ haloalkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -N(C １～６ alkyl) (C １～６ haloalkyl), -N(C １～６ alkyl) (C ３～８ cycloalkyl), -N(C １～６ alkyl)(5- to 10-membered heterocyclyl), —N(C １～６ alkyl) (C ６ aryl), -N(C １～６ alkyl)(5- to 10-membered heteroaryl), —C(O)(5- to 10-membered heterocyclyl), —C(O)(5- to 10-membered heteroaryl), —C(O)NH ２ , -C(O)NH(C １～６ alkyl), —C(O)NH(C １～６ haloalkyl), —C(O)NH(C ３～８ cycloalkyl), —C(O)NH(5- to 10-membered heterocyclyl), —C(O)NH(C ６ aryl), —C(O)NH (5- to 10-membered heteroaryl), —C(O)N(C １～６ alkyl) ２ , -C(O)N(C １～６ haloalkyl) ２ , -C(O)N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), -NHC(O)NH(C １～６ haloalkyl), -NHC(O)NH(C ３～８ cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C ６ aryl), —NHC(O)NH (5- to 10-membered heteroaryl), —S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R ４ｂ optionally substituted with; Each R ４ｂ are independently １～６ Alkyl, C １～６ Haloalkyl, C ３～６ Cycloalkyl, halogen, oxo, —OH, —NH ２ , CO ２ H, —O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), —NH(5- to 10-membered heterocyclyl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(5- to 10-membered heteroaryl), —NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ３～８ cycloalkyl), —NHC(O)O(5- to 10-membered heterocyclyl), —NHC(O)O(5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and Each L ３ are independently a bond, -(C １～６ alkyl)O-, -(C １～６ alkyl)N(R Ｌ )C(O)-,-(C １～６ alkyl)C(O)N(R Ｌ ) -, -(C １～６ alkyl)N(R Ｌ )C(O)(C １～６ alkyl)-, -(C １～６ alkyl)C(O)N(R Ｌ ) (C １～６ alkyl)-, -(C １～６ alkyl), -(C １～６ alkyl)N(R Ｌ ) S (O) ２ -, -N(R Ｌ ) S (O) ２ -, -C(O)-, -(C １～６ alkyl)C(O)-, or -N(R Ｌ )C(O)—; Each R ３ are independently a bond, halogen, hydroxy, —CN, C １～６ Alkyl, C ２～６ Alkynyl, C １～６ Alkoxy, C ３～８ cycloalkyl, 4- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , or -OC ３～８ is cycloalkyl; wherein each alkyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 4 R ３ａ optionally substituted with; Each R ３ａ are independently １～６ Alkyl, C １～６ Haloalkyl, halogen, C ３～８ cycloalkyl, 4- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, oxo, —OH, —CN, —NH ２ , -O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６～１０ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), —NH(5- to 10-membered heterocyclyl), —NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C １～６ haloalkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -N(C １～６ alkyl) (C １～６ haloalkyl), -N(C １～６ alkyl) (C ３～８ cycloalkyl), -N(C １～６ alkyl)(5- to 10-membered heterocyclyl), —N(C １～６ alkyl) (C ６ aryl), -N(C １～６ alkyl)(5- to 10-membered heteroaryl), —C(O)(5- to 10-membered heterocyclyl), —C(O)(5- to 10-membered heteroaryl), —C(O)NH ２ , -C(O)NH(C １～６ alkyl), —C(O)NH(C １～６ haloalkyl), —C(O)NH(C ３～８ cycloalkyl), —C(O)NH(5- to 10-membered heterocyclyl), —C(O)NH(C ６ aryl), —C(O)NH (5- to 10-membered heteroaryl), —C(O)N(C １～６ alkyl) ２ , -C(O)N(C １～６ haloalkyl) ２ , -C(O)N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), -NHC(O)NH(C １～６ haloalkyl), -NHC(O)NH(C ３～８ cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C ６ aryl), —NHC(O)NH (5- to 10-membered heteroaryl), —S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R ３ｂ optionally substituted with; Each R ３ｂ are independently １～６ Alkyl, C １～６ Haloalkyl, C ３～６ Cycloalkyl, halogen, oxo, —OH, —NH ２ , CO ２ H, —O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６～１０ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), —NH(5- to 10-membered heterocyclyl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(5- to 10-membered heteroaryl), —NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ３～８ cycloalkyl), —NHC(O)O(5- to 10-membered heterocyclyl), —NHC(O)O(5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and Each R Ｌ are independently hydrogen, C １～６ Alkyl, C １～６ haloalkyl, or C ３～８ is cycloalkyl; n is an integer from 0 to 3; Each X ６ and X ７ are independently N, CH, or CF; Here, X ４ , X ５ , X ６ , and X ７ no more than two of are N; L ２ is a bond, C １ ~C 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) ２ N (R Ｌ２ ) -, -(C １～６ alkyl)N(R Ｌ２ ) S (O) ２ -, -(C １～６ alkyl)S(O) ２ N (R Ｌ２ ) (C １～６ alkyl)- or -(C １～６ alkyl)S(O) ２ -(C １～６ alkyl)-; R Ｌ２ is hydrogen or C １～６ is alkyl; R ５ represents 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, C ６ aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R ５ｂ optionally substituted with; Each R ５ａ are independently hydrogen or C １～６ is alkyl; Each R ５ｂ are independently halogen, cyclopropyl, hydroxy, —CN, C １～３ Alkyl, C １～３ Alkoxy, -OCF ３ , or -OCF ２ H; and Z is O or S.

2. or a pharmaceutically acceptable salt thereof, wherein each R ３ are independently a bond, halogen, hydroxy, —CN, C １～６ Alkyl, C ２～６ Alkynyl, C １～６ Alkoxy, C ３～８ cycloalkyl, 4- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , or -OC ３～８ is cycloalkyl; Each alkyl, alkynyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 4 R ３ａ optionally substituted with; Each X ６ and X ７ is independently N or CH; Here, X ４ , X ５ , X ６ , and X ７ no more than two of are N; L ２ is bond, C １ ~C 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) ２ N (R Ｌ２ ) -, -(C １～６ alkyl)N(R Ｌ２ ) S (O) ２ -, or - (C １～６ alkyl)S(O) ２ N (R Ｌ２ ) (C １～６ alkyl)-; and R ５ is hydrogen, -CN, -OR ５ａ , —C(O)NR ５ａ ２ , -NR ５ａ C(O)R ５ａ , -NR ５ａ ２、 C ３～８ Cycloalkyl, C ６ aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R ５ｂ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, optionally substituted with:

3. or a pharmaceutically acceptable salt thereof; Each R １ are independently selected from halogen, —OH, —CN, C １～６ Alkyl, —CN, —C(O)NH ２ , C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, C ３～８ Cycloalkyl, C ６ aryl, 5- to 12-membered heteroaryl, or 4- to 10-membered heterocyclyl; wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, and heterocyclyl is selected from 1 to 4 R １ａ optionally substituted with; Each R １ａ But independently, C １～６ Alkyl, halogen, C ３～８ Cycloalkyl, 5- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, oxo, —OH, —CN, —NH ２ , -O(C １～６ alkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C ３～８ cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C ３～８ cycloalkyl) ２ , —N(5- to 10-membered heterocyclyl) ２ , -N(C ６ aryl) ２ , —N(5- to 10-membered heteroaryl) ２ , -N(C １～６ alkyl) (C ３～８ cycloalkyl), -N(C １～６ alkyl)(5- to 10-membered heterocyclyl), —N(C １～６ alkyl) (C ６ aryl), -N(C １～６ alkyl)(5- to 10-membered heteroaryl), —C(O)(5- to 10-membered heterocyclyl), —C(O)(5- to 10-membered heteroaryl), —C(O)O(C １～６ alkyl), —C(O)O(C ３～８ cycloalkyl), —C(O)O(5- to 10-membered heterocyclyl), —C(O)O(C ６ aryl), —C(O)O (5- to 10-membered heteroaryl), —C(O)NH ２ , -C(O)NH(C １～６ alkyl), —C(O)NH(C ３～８ cycloalkyl), —C(O)NH(5- to 10-membered heterocyclyl), —C(O)NH(C ６ aryl), —C(O)NH (5- to 10-membered heteroaryl), —C(O)N(C １～６ alkyl) ２ , -C(O)N(C ３～８ cycloalkyl) ２ , —C(O)N(5- to 10-membered heterocyclyl) ２ , -C(O)N(C ６ aryl) ２ , —C(O)N(5- to 10-membered heteroaryl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), -NHC(O)NH(C ３～８ cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C ６ aryl), -NHC(O)NH (5- to 10-membered heteroaryl), -NHS(O)(C １～６ alkyl), -N(C １～６ alkyl)(S(O)(C １～６ alkyl), -S(O) ２ (C １～６ alkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O) ２ (5- to 10-membered heterocyclyl), —S(O) ２ (C ６ aryl), -S(O) ２ (5- to 10-membered heteroaryl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R １ｂ optionally substituted with; Each R ４ａ But independently, C １～６ Alkyl, C １～６ Haloalkyl, halogen, C ３～８ Cycloalkyl, 5- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, oxo, —OH, —CN, —NH ２ , -O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６～１０ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C １～６ haloalkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -N(C １～６ alkyl) (C １～６ haloalkyl), -N(C １～６ alkyl) (C ３～８ cycloalkyl), -N(C １～６ alkyl)(5- to 10-membered heterocyclyl), —N(C １～６ alkyl) (C ６ aryl), -N(C １～６ alkyl)(5- to 10-membered heteroaryl), —C(O)(5- to 10-membered heterocyclyl), —C(O)(5- to 10-membered heteroaryl), —C(O)NH ２ , -C(O)NH(C １～６ alkyl), —C(O)NH(C １～６ haloalkyl), —C(O)NH(C ３～８ cycloalkyl), —C(O)NH(5- to 10-membered heterocyclyl), —C(O)NH(C ６ aryl), —C(O)NH (5- to 10-membered heteroaryl), —C(O)N(C １～６ alkyl) ２ , -C(O)N(C １～６ haloalkyl) ２ , -C(O)N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), -NHC(O)NH(C １～６ haloalkyl), -NHC(O)NH(C ３～８ cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C ６ aryl), —NHC(O)NH (5- to 10-membered heteroaryl), —S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R ４ｂ optionally substituted with; Each R ３ａ But independently, C １～６ Alkyl, C １～６ Haloalkyl, halogen, C ３～８ Cycloalkyl, 5- to 10-membered heterocyclyl, C ６ Aryl, 5- to 10-membered heteroaryl, oxo, —OH, —CN, —NH ２ , -O(C １～６ alkyl), —O(C １～６ haloalkyl), —O(C ３～８ cycloalkyl), —O(5- to 10-membered heterocyclyl), —O(C ６～１０ aryl), —O(5- to 10-membered heteroaryl), —NH(C １～６ alkyl), -NH(C １～６ haloalkyl), -NH(C ３～８ cycloalkyl), -NH(5- to 10-membered heterocyclyl), -NH(C ６ aryl), —NH(5- to 10-membered heteroaryl), —N(C １～６ alkyl) ２ , -N(C １～６ haloalkyl) ２ , -N(C ３～８ cycloalkyl) ２ , -N(C １～６ alkyl) (C １～６ haloalkyl), -N(C １～６ alkyl) (C ３～８ cycloalkyl), -N(C １～６ alkyl)(5- to 10-membered heterocyclyl), —N(C １～６ alkyl) (C ６ aryl), -N(C １～６ alkyl)(5- to 10-membered heteroaryl), —C(O)(5- to 10-membered heterocyclyl), —C(O)(5- to 10-membered heteroaryl), —C(O)NH ２ , -C(O)NH(C １～６ alkyl), —C(O)NH(C １～６ haloalkyl), —C(O)NH(C ３～８ cycloalkyl), —C(O)NH(5- to 10-membered heterocyclyl), —C(O)NH(C ６ aryl), —C(O)NH (5- to 10-membered heteroaryl), —C(O)N(C １～６ alkyl) ２ , -C(O)N(C １～６ haloalkyl) ２ , -C(O)N(C ３～８ cycloalkyl) ２ , -NHC(O)(C １～６ alkyl), -NHC(O)(C １～６ haloalkyl), —NHC(O)(C ３～８ cycloalkyl), —NHC(O)(5- to 10-membered heterocyclyl), —NHC(O)(C ６ aryl), -NHC(O)(5- to 10-membered heteroaryl), -NHC(O)O(C １～６ alkyl), -NHC(O)O(C １～６ haloalkyl), -NHC(O)O(C ３～８ cycloalkyl), -NHC(O)O(5- to 10-membered heterocyclyl), -NHC(O)O(C ６ aryl), —NHC(O)O (5- to 10-membered heteroaryl), —NHC(O)NH(C １～６ alkyl), -NHC(O)NH(C １～６ haloalkyl), -NHC(O)NH(C ３～８ cycloalkyl), -NHC(O)NH(5- to 10-membered heterocyclyl), -NHC(O)NH(C ６ aryl), —NHC(O)NH (5- to 10-membered heteroaryl), —S(O) ２ (C １～６ alkyl), -S(O) ２ (C １～６ haloalkyl), -S(O) ２ (C ３～８ cycloalkyl), —S(O)(NH)(C １～６ alkyl), -S(O) ２ NH (C １～６ alkyl), or —S(O) ２ N (C １～６ alkyl) ２ and wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from 1 to 3 R ３ｂ and R ５ is hydrogen, -CN, -OR ５ａ , —C(O)NR ５ａ ２ , -NR ５ａ ２、 C ３～８ Cycloalkyl, C ６ aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R ５ｂ 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, optionally substituted with:

4. Structure of formula (I-1): 【Chemical 752】 The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, having the formula:

5. Structure of Formula (II): 【Chemical 753】 5. The compound according to claim 1, wherein the compound has the formula:

6. Structure of formula (II-a): 【Chemical 754】 6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, having the formula:

7. Structure of formula (II-b): 【Chemistry 755】 6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, having the formula:

8. Structure of formula (II-c): 【Chemical 756】 6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, having the formula:

9. Structure of formula (II-d): 【Chemical 757】 6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, having the formula:

10. Structure of formula (III): 【Chemical 758】 5. The compound according to claim 1, wherein the compound has the formula:

11. Structure of formula (III-a): 【Chemical 759】 11. The compound of any one of claims 1 to 4 and 10, or a pharmaceutically acceptable salt thereof, having the formula:

12. Structure of formula (III-b): 【Hua760】 11. The compound of any one of claims 1 to 4 and 10, or a pharmaceutically acceptable salt thereof, having the formula:

13. Structure of formula (III-c): 【Chemical 761】 11. The compound of any one of claims 1 to 4 and 10, or a pharmaceutically acceptable salt thereof, having the formula:

14. Structure of formula (III-d): 【Chemical 762】 11. The compound of any one of claims 1 to 4 and 10, or a pharmaceutically acceptable salt thereof, having the formula:

15. X ６ and X ７ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is CH.

16. X ４ and X ５ 5. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each is C.

17. ring 【Chemical 763】 is C ６ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is aryl.

18. Structure of formula (IV): 【Chemical 764】 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, having the formula:

19. X ４ , X ５ , X ６ and X ７ A ring containing a ring 【Chemical 765】 10. The compound of any one of the preceding claims, wherein:

20. Structure of formula (IV-a): 【Chemical 766】 5. The compound according to claim 1, wherein the compound has the formula:

21. Structure of formula (IV-b): 【Chemical 767】 5. The compound according to claim 1, wherein the compound has the formula:

22. ring 【Chemical 768】 The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein is a 5-membered heteroaryl.

23. X ４ , X ５ , X ６ , and X ７ A ring containing a ring 【Chemical Formula 769】 23. The compound of claim 22, wherein:

24. L ３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is a bond.

25. At least one R ３ But 1 to 3 R ３ａ 10. A compound according to any one of the preceding claims, wherein R is 5 to 7 membered heterocyclyl optionally substituted with R, or a pharmaceutically acceptable salt thereof.

26. At least one R ３ is one or two R ３ａ C optionally substituted with １～６ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is alkoxy.

27. At least one R ３ But -NH ２ , —NH(C １～３ alkyl), -N(C １～３ alkyl) ２ , or —O(C １～３ alkyl), where each alkyl is independently selected from one or two R ３ａ 10. A compound according to any one of the preceding claims, optionally substituted with: or a pharmaceutically acceptable salt thereof.

28. At least one R ３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is methyl.

29. Each R ３ But independently, C １ ~C ６ Alkyl, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , C １～６ alkoxy, or 5- to 10-membered heterocyclyl, wherein each alkyl, alkoxy, and heterocyclyl is selected from 1 to 3 R ３ａ 10. A compound according to any one of the preceding claims, optionally substituted with: or a pharmaceutically acceptable salt thereof.

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

31. Each R ３ａ are independently halogen, —C(O)(C １ ~C ６ alkyl), —OH, —O(C １～６ alkyl), 5- to 10-membered heterocyclyl, —C(O)NH ２ , -C(O)N(H)(C １ ~C ６ alkyl), or —C(O)N(C １ ~C ６ alkyl) ２ 10. The compound of any one of the preceding claims, wherein:

32. At least one R ３ａ But -O(C １～３ alkyl), 5- to 7-membered heterocyclyl, —C(O)NH ２ , -C(O)N(H)(C １ ~C ３ alkyl), or —C(O)N(C １ ~C ３ alkyl) ２ 10. The compound of any one of the preceding claims, wherein:

33. At least one R ３ａ is halogen or —C(O)(C １ ~C ６ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R is 1 or 2;

34. At least one R ３ａ is —OH or —O(C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R is 1 or 2;

35. At least one R ３ａ But -O(C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R is 1 or 2;

36. At least one R ３ａ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is halogen or -OH.

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

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

39. ring 【Chemical 770】 16. The compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt thereof, wherein:

40. Structure of formula (V): 【Chemical 771】 40. The compound of claim 39, or a pharmaceutically acceptable salt thereof, having the formula:

41. Structure of formula (Va): 【Chemical 772】 41. The compound of claim 39 or 40, or a pharmaceutically acceptable salt thereof, having the formula:

42. Structure of formula (V-b): 【Chemical 773】 41. The compound of claim 39 or 40, or a pharmaceutically acceptable salt thereof, having the formula:

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

44. L ｘ４ 44. The compound of any one of claims 39 to 43, or a pharmaceutically acceptable salt thereof, wherein is a bond.

45. L ｘ５ 45. The compound of any one of claims 39 to 44, or a pharmaceutically acceptable salt thereof, wherein is a bond.

46. Each R ｘ４ and R ｘ５ are independently hydrogen, C １ ~C ６ Alkyl, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , C １～６ Alkoxy, C ３ ~C ８ cycloalkyl, or 5- to 10-membered heterocyclyl, where each alkyl, alkoxy, cycloalkyl, and heterocyclyl is selected from 1 to 3 R ４ａ 43. The compound of any one of claims 39 to 42, or a pharmaceutically acceptable salt thereof, optionally substituted with:

47. R ｘ４ and R ｘ５ One of them is C ３ ~C ８ cycloalkyl, and the other is hydrogen, and said cycloalkyl is one or two R ４ａ 47. The compound of any one of claims 39 to 42 and 46, or a pharmaceutically acceptable salt thereof, optionally substituted with:

48. R ｘ４ and R ｘ５ One of them is C １～６ and the other is hydrogen, and the alkoxy is one or two R ４ａ 47. The compound of any one of claims 39 to 42 and 46, or a pharmaceutically acceptable salt thereof, optionally substituted with:

49. Each R ４ａ are independently １～６ alkyl, —C(O)(5- to 10-membered heterocyclyl), or —O(C ３～８ cycloalkyl), where each alkyl, heterocyclyl, and cycloalkyl is selected from 1 to 3 R ４ｂ 49. The compound of any one of claims 39 to 48, or a pharmaceutically acceptable salt thereof, optionally substituted with:

50. Each R ４ｂ are independently halogen, —O(C １～６ alkyl), or —O(C １～６ 50. The compound of any one of claims 39 to 42 and 49, or a pharmaceutically acceptable salt thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 2

51. ring 【Chemical 774】 is C ６ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is aryl.

52. ring 【Chemical 775】 10. The compound of any one of the preceding claims, wherein:

53. ring 【Chemical 776】 10. The compound of any one of the preceding claims, wherein:

54. ring 【Chemical 777】 51. The compound of any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof, wherein is 5-10 membered heteroaryl.

55. L １ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is a bond.

56. Each L １ are independently -(C １～６ alkyl)O—, —O(C １～６ alkyl)- or -C １～６ Alkyl-O(C １～６ 55. The compound of any one of claims 1 to 54, wherein R is 1 or 2; R is 2 or 3; R is 3 or 4; R is 4 or 5; R is 5 or 6 ...7; R is 5 or 8; R is 5 or 9; R is 5 or 10; R is 5 or 11;

57. Each L １ are independently -(C １～６ alkyl)O—, or —O(C １～６ 55. The compound of any one of claims 1 to 54, wherein R is 1 or 2; R is 2 or 3; R is 3 or 4; R is 4 or 5; R is 5 or 6 ...7; R is 5 or 8; R is 5 or 9; R is 5 or 10; R is 5 or 11;

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

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

60. Each R １ are independently halogen, —CN, or C １～６ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is alkoxy.

61. Each R １ are independently halogen or C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is alkoxy.

62. Each R １ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is independently fluoro, chloro, or methoxy.

63. Each R １ａ are independently halogen, —OH, —CN, —C(O)NH ２ , C １～６ Alkyl, C １～６ Alkoxy, C ３～８ Cycloalkyl, C ６ aryl, or 5- to 10-membered heteroaryl, or a pharmaceutically acceptable salt thereof.

64. Each R １ａ are independently halogen, —OH, —C(O)NH ２ , C １～６ Alkyl, C １～６ Alkoxy, or C ６ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is aryl.

65. At least one R １ａ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is halogen.

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

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

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

69. ring 【Chemical 778】 51. The compound of any one of claims 1 to 50, wherein: 【Request 70】 【Chemical 779】 51. The compound of any one of claims 1 to 50, wherein:

71. R ２ But hydrogen, halogen, C １～３ Alkyl, or C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is alkoxy.

72. R ２ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

73. R ２ 72. The compound of any one of claims 1 to 71, or a pharmaceutically acceptable salt thereof, wherein is halogen.

74. R ｘ１ is halogen or C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein:

75. R ｘ１ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

76. R ｘ２ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

77. R ｘ３ But halogen, C １～３ Alkyl, or C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is alkoxy.

78. R ｘ３ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

79. L ２ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is a bond.

80. L ２ is C １ ~C ３ 79. The compound of any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof, wherein:

81. R ５ 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

82. R ５ 81. The compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, wherein is -CN.

83. R ５ But C ３～８ Cycloalkyl, C ６ aryl, 4- to 10-membered heterocyclyl, or 5- to 10-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from the group consisting of one or two R ５ｂ 81. The compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, optionally substituted with:

84. R ５ But C ５～６ Cycloalkyl, C ６ aryl, 5- to 7-membered heterocyclyl, or 5- to 9-membered heteroaryl, wherein each cycloalkyl, aryl, heterocyclyl, and heteroaryl is selected from one or two R ５ｂ 81. The compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, optionally substituted with:

85. Each R ５ｂ But independently, C １～３ Alkyl or C １～３ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, which is alkoxy.

86. R ５ｂ 10. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein is methyl.

87. 10. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Z is O. 【Request 88】 【Chemical 780】 【Chemical 781】 【Chemical 782】 【Chemical 783】 【Chemical 784】 【Chemical 785】 【Chemical 786】 【Chemical 787】 【Hua788】 【Chemical 789】 【Chemical 790】 【Chemical 791】 【Chemical 792】 【Chemical 793】 【Chemical 794】 【Chemical Formula 795】 【Chemical 796】 【Chemical 797】 【Chemical 798】 【Chemical 799】 【Hua800】 【Chemistry 801】 【Chemical 802】 【Chemistry 803】 【Chemistry 804】 【Chemistry 805】 【Chemistry 806】 【Chemical 807】 【Chemical 808】 【Chemistry 809】 【Chemical 810】 【Hua 811】 【Hua 812】 【Hua 813】 【Hua 814】 【Chemical 815】 【Hua 816】 【Hua 817】 【Hua 818】 【Hua 819】 【Hua 820】 【Hua 821】 【Hua 822】 【Hua 823】 【Hua 824】 【Hua 825】 【Hua 826】 【Hua 827】 【Hua 828】 【Hua 829】 【Chemical 830】 【Hua 831】 【Hua 832】 【Hua 833】 【Chemical 834】 【Chemistry 835】 【Hua 836】 【Hua 837】 【Hua 838】 【Chemical 839】 【Chemistry 840】 【Hua 841】 【Chemical 842】 【Hua 843】 【Chemical 844】 【Chemistry 845】 【Hua 846】 【Hua 847】 【Hua 848】 【Chemical 849】 【Chemical 850】 【Chemistry 851】 【Hua 852】 【Hua 853】 【Hua 854】 【Chemistry 855】 【Hua 856】 【Hua 857】 【Hua 858】 【Hua 859】 【Chemical 860】 【Hua 861】 【Hua 862】 【Hua 863】 【Hua 864】 or a pharmaceutically acceptable salt thereof.

89. 【Chemical 865】 or a pharmaceutically acceptable salt thereof. 【Request 90】 【Chemical 866】 or a pharmaceutically acceptable salt thereof.

91. A compound of the formula: 【Hua 867】 or a pharmaceutically acceptable salt thereof.

92. A compound of the formula: 【Hua868】 or a pharmaceutically acceptable salt thereof.

93. A compound of the formula: 【Hua 869】 or a pharmaceutically acceptable salt thereof.

94. A compound of the formula: 【Hua 870】 or a pharmaceutically acceptable salt thereof.

95. A compound of the formula: 【Hua 871】 or a pharmaceutically acceptable salt thereof.

96. A compound of the formula: 【Hua 872】 or a pharmaceutically acceptable salt thereof.

97. A compound of the formula: 【Hua 873】 or a pharmaceutically acceptable salt thereof.

98. A compound of the formula: 【Chemical 874】 or a pharmaceutically acceptable salt thereof.

99. A compound of the formula: 【Chemistry 875】 or a pharmaceutically acceptable salt thereof.

100. A compound of the formula: 【Hua 876】 or a pharmaceutically acceptable salt thereof.

101. A compound of the formula: 【Hua 877】 or a pharmaceutically acceptable salt thereof.

102. A compound of the formula: 【Hua 878】 or a pharmaceutically acceptable salt thereof.

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

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

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

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

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

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

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

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

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

112. 104. Use of a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 103, for the manufacture of a medicament for the treatment or prevention of a viral infection in a human being in need thereof.

113. 104. A composition comprising a compound according to any one of claims 1 to 102, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 103, for use in treating or preventing a viral infection in a human in need thereof.

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