Compounds for modulating HUR (ELAVL1)

Abstract

The present invention relates to compounds of formula (I) that degrade HuR, or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers thereof, pharmaceutical compositions comprising compounds of formula (I), and methods for treating or preventing diseases in which HuR is involved. JPEG2025539873000326.jpg3661

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of PCT Application No. PCT / CN2022 / 134645, filed November 28, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Post-transcriptional gene regulation occurs at the level of pre-mRNA splicing and maturation, and at the level of mRNA transport, editing, storage, stability, and translation. This level of gene regulation is essential for normal development, but when dysregulated, it has many effects on disease states, including cancer. These functions are mediated by RNA-binding proteins (RBPs).

[0003] RBPHu antigen R ("HuR") is a member of the embryonic lethal abnormalities in vision ("ELAV") family that binds to adenine- and uridine-rich elements (collectively referred to as "AREs") located in the 3'- or 5'-untranslated regions ("UTRs") of target mRNAs. HuR is elevated in a wide range of cancer tissues compared with corresponding normal tissues. Initial reports indicated that upregulation of HuR in brain and colon cancers was associated with increased expression of COX-2, VEGF, TGF-β, IL-8, and other cancer-related proteins. Subsequent studies revealed that HuR is widely overexpressed in almost all malignant tumors tested, including colon, prostate, breast, brain, ovarian, pancreatic, and lung cancers. Elevated cytoplasmic accumulation of HuR is associated with high-grade tumors and serves as a prognostic factor for poor clinical outcomes in these cancers. Furthermore, HuR is thought to play a causal role in tumor development / progression. In a mouse xenograft model, cancer cells with elevated HuR produced tumors significantly larger than those produced by controls, whereas reduced HuR levels resulted in a decrease in tumor size.

[0004] Although there are many examples of compounds that specifically disrupt protein-protein interactions, drug discovery for protein-RNA interactions (particularly HuR) has had limited success. Summary of the Invention [Means for solving the problem]

[0005] The present application provides a novel HuR degrading agent that regulates HuR activity by degrading HuR, and the degrading agent can be used to treat diseases or disorders in which HuR is involved.

[0006] A first aspect of the present application is a compound of formula I: With respect to JPEG2025539873000002.jpg4063 or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, the variables in Formula I are as described herein.

[0007] Another aspect of the present application relates to a pharmaceutical composition comprising a compound described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable diluent, excipient, or carrier.

[0008] Another aspect of the present application relates to a method of treating or preventing a disease or disorder described herein (e.g., a HuR-mediated disease or disorder or a disease or disorder in which HuR is implicated), such as a disease or disorder described herein (e.g., bladder cancer, brain cancer, breast cancer, colorectal cancer, cervical cancer, gastrointestinal cancer, genitourinary system cancer, glioma, head and neck cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, skin cancer, or testicular cancer). The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a therapeutically effective amount of a pharmaceutical composition described herein.

[0009] Another aspect of the present application pertains to a compound, as described herein, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a pharmaceutical composition, as described herein, for use in a method for treating or preventing a disease or disorder, or for modulating (e.g., inactivating or degrading) HuR.

[0010] Another aspect of the present application relates to the use of a compound as described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a pharmaceutical composition as described herein, in the manufacture of a medicament for treating or preventing a disease or disorder, or for modulating (e.g., inactivating or degrading) HuR.

[0011] The present application provides degraders of HuR that are therapeutic agents for treating diseases or disorders associated with the regulation of HuR.

[0012] The present application further provides compounds and compositions with improved therapeutic properties (e.g., efficacy, pharmacodynamics, safety) compared to known HuR degraders and alternative routes of administration for treating HuR-associated diseases. DETAILED DESCRIPTION OF THE INVENTION

[0013] Compounds used This application relates to compounds and compositions thereof that can degrade HuR. This application describes methods for treating, preventing, or ameliorating a disease or disorder in which HuR is involved by administering to a subject in need thereof a therapeutically effective amount of a compound or composition described herein. The compounds or compositions of this application can be used to treat various HuR-mediated diseases and disorders by degrading HuR.

[0014] According to one aspect, the present application provides a compound of formula I: JPEG2025539873000003.jpg3760 or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof,

[0015] X is N or CRX and Y4 is N or CR4; Y5 is N or CR5; Y7 is N or CR7, with the proviso that not more than one of Y4, Y5, and Y7 is N; R X , R4, R5 and R7 are each independently H, a C1-C6 alkyl group, a C1-C6 haloalkyl group or halogen; m is 0, 1, 2, 3 or 4; each R3 is independently a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, OH, or halogen; R N is H or a C1-C6 alkyl group, R6 is R6' or (CH2) 1-3 -R6',

[0016] R6' is a heterocyclyl group containing a 4- to 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O and S, C6-C 10 an aryl group, a heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, or a fused-ring heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S and a 5- or 6-membered ring containing optionally 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group, aryl group, heteroaryl group, or fused-ring heteroaryl group optionally comprises one or more R 61 is replaced by, and

[0017] Each R 61 is independent, C1-C6 alkyl group, which may optionally independently be selected from C1-C6 alkylamino group, di-C1-C6 alkylamino group, halogen, OH, amino group, C6-C 10an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C6 alkylamino group, di-C1-C6 alkylamino group, OH, amino group, NO2, halogen, CN, ═O, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , L-C6-C 10 and substituted with one or more groups selected from the group consisting of an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, an L-C3-C6 carbocyclyl group, or an L-heterocyclyl group containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the aryl group, heteroaryl group, carbocyclyl group, or heterocyclyl group is optionally and independently selected from (CH2) optionally substituted with one or more substituents selected from a C1-C6 alkyl group, a C1-C6 haloalkyl group, a halogen atom, a C1-C6 alkylamino group, a di-C1-C6 alkylamino group, and a C1-C6 alkoxy group; 0-3 -C1-C6 alkoxy group, O-(CH2) 0-3 -C3-C6 carbocyclyl group, O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 -heterocyclyl group, O-(CH2) 0-3 -C6-C 10 O-(CH2) containing an aryl group, one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S 0-3-substituted with one or more groups selected from the group consisting of heteroaryl groups, C1-C6 alkylamino groups, and C1-C6 alkylamino groups, wherein the alkyl groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups, di-C1-C6 alkylamino groups and C1-C6 alkoxy groups, di-C1-C6 alkylamino groups, wherein each alkyl group is optionally and independently selected from the group consisting of C1-C6 alkylamino groups, di-C1-C6 alkylamino groups and C1-C6 alkoxy groups, OH, amino group, NO2, halogen, CN, ═O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, a C3-C6 carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, a C6-C 10 aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and 1 to 2 heteroatoms selected from N, O, and S, and the carbocyclyl or heterocyclyl group optionally can be substituted with one or more R A and one or more hydrogen atoms of the substituents may be replaced by one or more deuterium atoms,

[0018] Among them, L is absent or O, (CR L1 R L2 ) n , O-(CR L1 R L2 ) n , (CR L1 R L2 ) n is a linker selected from —O and S(O)2; Each R L1 and each R L2 are independently H, CH, CHCH, or CH(CH), or R L1 and R L2 can be taken together with the carbon atoms to which they are attached to form a C(O), a C-C cycloalkyl group, or a heterocyclyl group containing a 4- to 6-membered ring and 1-3 heteroatoms selected from N, O, and S; R L1 and R L2 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms,

[0019] Each R A are independently halogen, OH, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkylamino group, or a di-C1-C6 alkylamino group, and n is 1, 2 or 3; or The Two R's 61 together with the carbon atoms to which they are attached form C4-C 10 It can form a carbocyclyl group, a heterocyclyl group containing one 4- to 6-membered ring and 1-3 heteroatoms selected from N, O, and S, a spiroheterocyclyl group or fused heterocyclyl group containing two 4- to 6-membered rings each containing 1-4 heteroatoms selected from N, O, and S, or a C6 aryl group, wherein the carbocyclyl group, heterocyclyl group, spiroheterocyclyl group, fused heterocyclyl group, or aryl group is optionally independently substituted with one or more groups selected from the group consisting of a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylamino group, a di-C1-C6 alkylamino group, OH, an amino group, a halogen atom, CN, and =O, and Each R 62 , each R 63 and each R 64 are independently H, a C1-C6 alkyl group, or a C1-C6 haloalkyl group.

[0020] In some embodiments, the compound of formula I has any one of formulas II-IX: JPEG2025539873000004.jpg163147 or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof.

[0021] In some embodiments, the compound of formula I is a compound of formula II or formula III: JPEG2025539873000005.jpg40132 or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof.

[0022] In some embodiments, the compound of Formula I is a compound of Formula Ia: JPEG2025539873000006.jpg4670 or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, wherein:

[0023] X is N or CR X and R X , R4, R5 and R7 are each independently H, a C1-C6 alkyl group, a C1-C6 haloalkyl group or halogen; R 61 'teeth H, C1-C6 alkyl group, which may optionally independently be selected from C1-C6 alkylamino group, di-C1-C6 alkylamino group, halogen, OH, amino group, C6-C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C-6 alkylamino group, di-C1-C6 alkylamino group, OH, amino group, NO2, halogen, CN, C(O)R 62 , C(O)OR 62 , or C(O)NR 63 R 64 and substituted with one or more groups selected from the group consisting of

[0024] R 62 , R 63 and R 64 are each independently H, a C1-C6 alkyl group, or a C1-C6 haloalkyl group; R L1 and each R L2 are each independently H, CH, CHCH, or CH(CH), or R L1 and R L2 can be taken together with the carbon atoms to which they are attached to form a C(O), a C-C cycloalkyl group, or a heterocyclyl group containing a 4- to 6-membered ring and 1-3 heteroatoms selected from N, O, and S; R L1 and R L2 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms,

[0025] X1 is N or CR X1 and X2 is N or CR X2 and X3 is N or CR X3 and X4 is N or CR X4 and X5 is N or CR X5 where no more than four of X1, X2, X3, X4, and X5 are N;

[0026] R X1 , R X2 , R X3 , R X4 and R X5are each independently substituted with one or more substituents selected from H, a C-C alkyl group, a C-C haloalkyl group, optionally a halogen, a C-C alkylamino group, a di-C-C alkylamino group, and a C-C alkoxy group (CH). 0-3 -C1-C6 alkoxy group, O-(CH2) 0-3 -C3-C6 carbocyclyl group, O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 -heterocyclyl group, O-(CH2) 0-3 -C6-C 10 O-(CH2) containing an aryl group, one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S 0-3 -heteroaryl group, C1-C6 alkylamino group, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino group, di-C1-C6 alkylamino group and C1-C6 alkoxy group, di-C1-C6 alkylamino group, each alkyl group is optionally independently selected from the group consisting of C1-C6 alkylamino group, di-C1-C6 alkylamino group and C1-C6 alkoxy group, OH, amino group, NO2, halogen, CN, ═O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, a C3-C6 carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, a C6-C 10aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; X1 , R X2 , R X3 , R X4 and R X5 Any two of these can be taken together with the carbon atoms to which they are attached to form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and R X1 , R X2 , R X3 , R X4 and R X5 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms,

[0027] Each R A are independently halogen, OH, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkylamino group, or a di-C1-C6 alkylamino group.

[0028] In some embodiments, the compound of formula I is a compound of formula Ib: JPEG2025539873000007.jpg5776 or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, wherein:

[0029] X is N or CR X and R X , R4, R5 and R7 are each independently H, a C1-C6 alkyl group, a C1-C6 haloalkyl group or halogen;

[0030] Each R 61 " is independent, H, C1-C6 alkyl group, which may optionally independently be selected from C1-C6 alkylamino group, di-C1-C6 alkylamino group, halogen, OH, amino group, C6-C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C-6 alkylamino group, di-C1-C6 alkylamino group, OH, amino group, NO2, halogen, CN, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , L-C6-C 10 and substituted with one or more groups selected from the group consisting of an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, an L-C3-C6 carbocyclyl group, or an L-heterocyclyl group containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the aryl group, heteroaryl group, carbocyclyl group, or heterocyclyl group is optionally and independently selected from (CH2) optionally substituted with one or more substituents selected from a C1-C6 alkyl group, a C1-C6 haloalkyl group, a halogen atom, a C1-C6 alkylamino group, a di-C1-C6 alkylamino group, and a C1-C6 alkoxy group; 0-3 -C1-C6 alkoxy group, O-(CH2) 0-3 -C3-C6 carbocyclyl group, O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 -heterocyclyl group, O-(CH2) 0-3 -C6-C 10 O-(CH2) containing an aryl group, one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S 0-3-substituted with one or more groups selected from the group consisting of heteroaryl groups, C1-C6 alkylamino groups, and C1-C6 alkylamino groups, wherein the alkyl groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups, di-C1-C6 alkylamino groups and C1-C6 alkoxy groups, di-C1-C6 alkylamino groups, wherein each alkyl group is optionally and independently selected from the group consisting of C1-C6 alkylamino groups, di-C1-C6 alkylamino groups and C1-C6 alkoxy groups, OH, amino group, NO2, halogen, CN, ═O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, a C3-C6 carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, a C6-C 10 aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and 1 to 2 heteroatoms selected from N, O, and S, and the carbocyclyl or heterocyclyl group optionally contains one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms,

[0031] Each R 61 is independent, C1-C6 alkyl group, which may optionally independently be selected from C1-C6 alkylamino group, di-C1-C6 alkylamino group, halogen, OH, amino group, C6-C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C6 alkylamino group, di-C1-C6 alkylamino group, OH, amino group, NO2, halogen, CN, ═O, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , L-C6-C 10 and substituted with one or more groups selected from the group consisting of an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, an L-C3-C6 carbocyclyl group, or an L-heterocyclyl group containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the aryl group, heteroaryl group, carbocyclyl group, or heterocyclyl group is optionally and independently selected from (CH2) optionally substituted with one or more substituents selected from a C1-C6 alkyl group, a C1-C6 haloalkyl group, a halogen atom, a C1-C6 alkylamino group, a di-C1-C6 alkylamino group, and a C1-C6 alkoxy group; 0-3 -C1-C6 alkoxy group, O-(CH2) 0-3 -C3-C6 carbocyclyl group, O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 -heterocyclyl group, O-(CH2) 0-3 -C6-C 10 O-(CH2) containing an aryl group, one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S 0-3-substituted with one or more groups selected from the group consisting of heteroaryl groups, C1-C6 alkylamino groups, and C1-C6 alkylamino groups, wherein the alkyl groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups, di-C1-C6 alkylamino groups and C1-C6 alkoxy groups, di-C1-C6 alkylamino groups, wherein each alkyl group is optionally and independently selected from the group consisting of C1-C6 alkylamino groups, di-C1-C6 alkylamino groups and C1-C6 alkoxy groups, OH, amino group, NO2, halogen, CN, ═O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, a C3-C6 carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, a C6-C 10 aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and 1 or 2 heteroatoms selected from N, O, and S, and the carbocyclyl or heterocyclyl group optionally can be substituted with one or more R A and one or more hydrogen atoms of the substituents may be replaced by one or more deuterium atoms,

[0032] Among them, L is absent or O, (CR L1 R L2 ) n , O-(CR L1 R L2 ) n , (CR L1 R L2 ) n is a linker selected from —O and S(O)2; Each R L1 and each R L2 are independently H, CH, CHCH, or CH(CH), or R L1 and R L2 can be taken together with the carbon atoms to which they are attached to form a C(O), a C-C cycloalkyl group, or a heterocyclyl group containing a 4- to 6-membered ring and 1-3 heteroatoms selected from N, O, and S; R L1 and R L2 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms,

[0033] Each R A are independently halogen, OH, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkylamino group, or a di-C1-C6 alkylamino group, and n is 1, 2 or 3; or The Two R's 61 together with the carbon atoms to which they are attached form C4-C 10 It can form a carbocyclyl group, a heterocyclyl group containing one 4- to 6-membered ring and 1-3 heteroatoms selected from N, O, and S, a spiroheterocyclyl group or fused heterocyclyl group containing two 4- to 6-membered rings each containing 1-4 heteroatoms selected from N, O, and S, or a C6 aryl group, wherein the carbocyclyl group, heterocyclyl group, spiroheterocyclyl group, fused heterocyclyl group, or aryl group is optionally independently substituted with one or more groups selected from the group consisting of a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkylamino group, a di-C1-C6 alkylamino group, OH, an amino group, a halogen atom, CN, and =O, and Each R 62 , each R 63 and each R 64 are independently H, a C1-C6 alkyl group, or a C1-C6 haloalkyl group.

[0034] For the above formula, if applicable, the variables (e.g., X, Y, Y, Y, R) in any formula described herein (e.g., Formulas I-IX, Formula Ia, or Formula Ib) may be X , R4, R5, R7) are described below.

[0035] In some embodiments, X is N. In some embodiments, X is CR X is. In some embodiments, Y4 is N. In some embodiments, Y4 is CR4. In some embodiments, Y5 is N. In some embodiments, Y5 is CR5. In some embodiments, Y7 is N. In some embodiments, Y7 is CR7. In some embodiments, X is CR X and Y4 is CR4, Y5 is CR5, and Y7 is CR7.

[0036] In some embodiments, X is CR X wherein Y4 is N, Y5 is CR5, and Y7 is CR7. In some embodiments, X is CR X wherein Y4 is CR4, Y5 is N, and Y7 is CR7. In some embodiments, X is CR X and Y4 is CR4, Y5 is CR5, and Y7 is N. In some embodiments, X is N, Y4 is CR4, Y5 is CR5, and Y7 is CR7.

[0037] In some embodiments, X is N, Y4 is N, Y5 is CR5, and Y7 is CR7. In some embodiments, X is N, Y4 is CR4, Y5 is N, and Y7 is CR7. In some embodiments, X is N, Y4 is CR4, Y5 is CR5, and Y7 is N. In some embodiments, R X is H.

[0038] In some embodiments, R X is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, R X is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I).

[0039] In some embodiments, R X is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R X is F or Cl. In some embodiments, R4 is H. In some embodiments, R4 is a C1-C6 alkyl group (eg, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl).

[0040] In some embodiments, R4 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R4 is halogen (eg, F, Cl, Br, or I).

[0041] In some embodiments, R4 is F or Cl. In some embodiments, R5 is H. In some embodiments, R5 is a C1-C6 alkyl group (eg, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). In some embodiments, R5 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0042] In some embodiments, R5 is halogen (eg, F, Cl, Br, or I). In some embodiments, R5 is F or Cl. In some embodiments, R7 is H. In some embodiments, R7 is a C1-C6 alkyl group (eg, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl).

[0043] In some embodiments, R7 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)). In some embodiments, R7 is halogen (eg, F, Cl, Br, or I). In some embodiments, R7 is F or Cl. In some embodiments, m is 0.

[0044] In some embodiments, m is 1, 2, 3, or 4. In some embodiments, m is 1. In some embodiments, at least one R3 is a C1-C6 alkyl group (eg, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl).

[0045] In some embodiments, at least one R3 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0046] In some embodiments, at least one R3 is a C1-C6 alkoxy group (eg, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0047] In some embodiments, at least one R3 is a C1-C6 haloalkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0048] In some embodiments, at least one R3 is OH. In some embodiments, at least one R3 is halogen (eg, F, Cl, Br, or I). In some embodiments, at least one R3 is F or Cl. In some embodiments, R N is H.

[0049] In some embodiments, R N is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, R6 is R6'. In some embodiments, R6 is (CH2) 1-3 -R6'. In some embodiments, R6 is (CH2)-R6'. In some embodiments, R6 is (CH2)2-R6'. In some embodiments, R6 is (CH2)3-R6'.

[0050] In some embodiments, R6' is a heterocyclyl group (e.g., a heterocyclyl group described herein) comprising a 4-6 membered ring containing one nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0051] In some embodiments, R6' is a heterocyclyl group (e.g., a 4-membered heterocyclyl group described herein) comprising a 4-membered ring containing one nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0052] In some embodiments, R6' is a heterocyclyl group (e.g., a 5-membered heterocyclyl group described herein) comprising a 5-membered ring containing one nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R61 is replaced by

[0053] In some embodiments, R6' is a heterocyclyl group (e.g., a 6-membered heterocyclyl group described herein) comprising a 6-membered ring containing one nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0054] In some embodiments, R6' is C6-C 10 an aryl group (e.g., phenyl or naphthyl), which optionally contains one or more R 61 is replaced by In some embodiments, R6' is phenyl, which optionally has one or more R 61 is replaced by

[0055] In some embodiments, R6' is a heteroaryl group (e.g., a heteroaryl group described herein) comprising a 5- or 6-membered ring containing one nitrogen atom and, optionally, 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0056] In some embodiments, R6' is a heteroaryl group (e.g., a 5-membered heteroaryl group described herein) comprising a 5-membered ring containing one nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0057] In some embodiments, R6' is a heteroaryl group (e.g., a 5-membered heteroaryl group described herein) comprising a 5-membered ring containing one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0058] In some embodiments, R6' is a heteroaryl group (e.g., a 5-membered heteroaryl group described herein) comprising a 5-membered ring containing one nitrogen atom and optionally one additional N atom, which optionally includes one or more R 61 is replaced by

[0059] In some embodiments, R6' is a heteroaryl group (e.g., a 6-membered heteroaryl group described herein) comprising a 6-membered ring containing one nitrogen atom and, optionally, 1-3 additional heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0060] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5- or 6-membered ring containing a nitrogen atom and, optionally, 1-3 additional heteroatoms selected from N, O, and S, and a 5- or 6-membered ring containing, optionally, 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0061] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5-membered ring containing a nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, and a 5-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0062] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 5-membered ring containing one nitrogen atom and a 5-membered ring containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0063] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 5-membered ring containing a nitrogen atom and a 5-membered ring containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0064] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5-membered ring containing one nitrogen atom and, optionally, one additional heteroatom selected from N, O, and S, and a 5-membered ring containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0065] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5-membered ring containing one nitrogen atom and, optionally, one additional heteroatom selected from N, O, and S, and a 5-membered ring containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0066] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5-membered ring containing a nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, and a 6-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0067] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 5-membered ring containing a nitrogen atom and, optionally, a 6-membered ring containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0068] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 5-membered ring containing a nitrogen atom and, optionally, a 6-membered ring containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0069] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) including 5- and 6-membered rings containing one nitrogen atom, which optionally includes one or more R 61 is replaced by

[0070] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5-membered ring containing one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, and a 6-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0071] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 5-membered ring containing one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, and a 6-membered ring optionally containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0072] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) including 5- and 6-membered rings containing one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0073] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 6-membered ring containing a nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, and a 6-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0074] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 6-membered ring containing one nitrogen atom and, optionally, a 6-membered ring containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0075] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 6-membered ring containing a nitrogen atom and, optionally, a 6-membered ring containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0076] In some embodiments, R6' is a 6-membered ring containing one nitrogen atom and a fused ring heteroaryl group comprising a 6-membered ring (e.g., a fused ring heteroaryl group described herein), which optionally includes one or more R 61 is replaced by

[0077] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 6-membered ring containing one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, and a 6-membered ring optionally containing 1 to 4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0078] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 6-membered ring containing one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, and a 6-membered ring optionally containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0079] In some embodiments, R6' is a fused ring heteroaryl group containing a 6-membered ring (e.g., a fused ring heteroaryl group described herein) that contains one nitrogen atom and optionally one additional heteroatom selected from N, O, and S, and that optionally contains one or more R 61 is replaced by

[0080] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) that includes a 6-membered ring containing a nitrogen atom and optionally 1-3 additional heteroatoms selected from N, O, and S, and a 5-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0081] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 6-membered ring containing a nitrogen atom and a 5-membered ring containing 1-4 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0082] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 6-membered ring containing a nitrogen atom and a 5-membered ring containing 1-2 heteroatoms selected from N, O, and S, which optionally includes one or more R 61 is replaced by

[0083] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 6-membered ring containing one nitrogen atom and, optionally, one additional heteroatom selected from N, O, and S, and a 5-membered ring containing 1-4 heteroatoms selected from N, O, and S, which optionally comprises one or more R 61 is replaced by

[0084] In some embodiments, R6' is a fused ring heteroaryl group (e.g., a fused ring heteroaryl group described herein) comprising a 6-membered ring containing one nitrogen atom and, optionally, one additional heteroatom selected from N, O, and S, and a 5-membered ring containing 1-2 heteroatoms selected from N, O, and S, which optionally comprises one or more R 61 is replaced by

[0085] In some embodiments, at least one R 61 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0086] In some embodiments, at least one R 61 are independently a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), which can be a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a halogen (e.g., F, Cl, Br, or I), OH, an amino group, a C6-C 10and substituted with one or more groups selected from the group consisting of aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heteroaryl groups described herein).

[0087] In some embodiments, at least one R 61 is a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0088] In some embodiments, at least one R 61 is a C1-C6 haloalkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0089] In some embodiments, at least one R 61 is OH. In some embodiments, at least one R 61 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, at least one R 61 is F or Cl.

[0090] In some embodiments, at least one R 61 is a C1-C6 alkylamino group (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) or a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl).

[0091] In some embodiments, at least one R 61 is OH, an amino group, NO2, a halogen, or CN. In some embodiments, at least one R 61 is =O. In some embodiments, at least one R 61 is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is.

[0092] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl), which optionally independently represents: C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0093] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0094] In some embodiments, at least one R 61 is L-C6-C 10It is an aryl group (e.g., phenyl or naphthyl) substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br or I)).

[0095] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0096] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains at least one O—(CH2) 0-3- a C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0097] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, and at least one O—(CH) 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally comprises one or more R A is replaced by

[0098] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains at least one O—(CH2) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0099] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, and at least one O—(CH) 0-3 -substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0100] In some embodiments, at least one R 61 is L-C6-C 10an aryl group (e.g., phenyl or naphthyl) substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0101] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that is substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl); and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0102] In some embodiments, at least one R 61 is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl), which is substituted with at least one OH.

[0103] In some embodiments, at least one R 61 is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl) that is substituted with at least one amino group.

[0104] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (eg, phenyl or naphthyl) that is substituted with at least one NO2.

[0105] In some embodiments, at least one R 61 is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl) that is substituted with at least one halogen (eg, F, Cl, Br, or I).

[0106] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (eg, phenyl or naphthyl) which is substituted with at least one CN.

[0107] In some embodiments, at least one R 61 is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl) that is substituted with at least one =0.

[0108] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(RN )C(O)R 62 is replaced by .

[0109] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )C(O)OR 62 is replaced by .

[0110] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0111] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by

[0112] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl group), where C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0113] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0114] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0115] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one C(O)R 62 is replaced by .

[0116] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one C(O)OR 62 is replaced by .

[0117] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one C(O)NR 63 R 64 is replaced by .

[0118] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one P(=O)(OR 62 )2.

[0119] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group optionally contains one or more R A is replaced by

[0120] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group optionally contains one or more R A is replaced by

[0121] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one C-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0122] In some embodiments, at least one R 61 is L-C6-C 10An aryl group (e.g., phenyl or naphthyl) that is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S.

[0123] In some embodiments, at least one R 61 is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl), wherein the aryl group is substituted and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group optionally contains one or more R A is replaced by

[0124] In some embodiments, at least one R 61 is L-C6-C 10 An aryl group (eg, phenyl or naphthyl), wherein the aryl group is substituted, and one or more hydrogen atoms in the substituent may be replaced by one or more deuterium atoms.

[0125] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) comprising one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which independently and optionally are selected from a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0126] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0127] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group described herein) comprising one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0128] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which has at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0129] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0130] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), said heterocyclyl group optionally comprising one or more R A is replaced by

[0131] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0132] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which contains at least one O—(CH) 0-3-substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0133] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally substituted with a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0134] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with a C1-C6 alkylamino group (wherein the alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0135] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one OH.

[0136] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one amino group.

[0137] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one NO.

[0138] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one halogen (e.g., F, Cl, Br, or I).

[0139] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one CN.

[0140] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one ═O.

[0141] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )C(O)R 62 is replaced by .

[0142] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )C(O)OR 62 is replaced by .

[0143] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0144] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by

[0145] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2It is substituted with NH(C1-C6 alkyl), where C1-C6 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0146] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0147] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0148] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one C(O)R 62 is replaced by .

[0149] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is selected from at least one C(O)OR 62 is replaced by .

[0150] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is at least one C(O)NR 63 R 64 is replaced by .

[0151] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one P(═O)(OR 62 )2.

[0152] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is optionally substituted with one or more R A is replaced by

[0153] In some embodiments, at least one R 61is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group is optionally substituted with one or more R A is replaced by

[0154] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one C-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0155] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S.

[0156] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group as described herein) comprising one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group is substituted, and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group comprising a 5- or 6-membered ring and 1 or 2 heteroatoms selected from N, O, and S, and the carbocyclyl or heterocyclyl group optionally comprises one or more RA is replaced by

[0157] In some embodiments, at least one R 61 is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group is substituted and one or more hydrogen atoms in the substituents are optionally replaced with one or more deuterium atoms.

[0158] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is independently and optionally C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0159] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0160] In some embodiments, at least one R 61is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0161] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and a C1-C6 alkoxy group (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0162] In some embodiments, at least one R 61is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one O—(CH2) 0-3 - a C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0163] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that contains one or two 3- to 6-membered rings and one to four heteroatoms selected from N, O, and S, and at least one O—(CH2) 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group is optionally substituted with one or more R A is replaced by

[0164] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one O—(CH2) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0165] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that contains one or two 5- or 6-membered rings and one to four heteroatoms selected from N, O, and S, and at least one O—(CH2) 0-3 -substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0166] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0167] In some embodiments, at least one R 61is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein each alkyl group is optionally independently a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0168] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one OH.

[0169] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one amino group.

[0170] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one NO2.

[0171] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one halogen (e.g., F, Cl, Br, or I).

[0172] In some embodiments, at least one R 61 is a L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one CN.

[0173] In some embodiments, at least one R 61 is a L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one =0.

[0174] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one N(R N )C(O)R 62 is replaced by .

[0175] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one N(R N )C(O)OR 62 is replaced by .

[0176] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one N(R N)S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0177] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by

[0178] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl), where C1-C6 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0179] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0180] In some embodiments, at least one R 61is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0181] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which is substituted with at least one C(O)R 62 is replaced by .

[0182] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one C(O)OR 62 is replaced by .

[0183] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one C(O)NR 63 R 64 is replaced by .

[0184] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one P(=O)(OR 62 )2.

[0185] In some embodiments, at least one R 61is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is optionally substituted with one or more R A is replaced by

[0186] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group optionally contains one or more R A is replaced by

[0187] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that has at least one C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0188] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S.

[0189] In some embodiments, at least one R 61is substituted with an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is substituted and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S, and wherein the carbocyclyl group or heterocyclyl group optionally contains one or more R A is replaced by

[0190] In some embodiments, at least one R 61 is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is substituted and one or more hydrogen atoms in the substituent may be replaced by one or more deuterium atoms.

[0191] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is independently and optionally: C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0192] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0193] In some embodiments, at least one R 61is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0194] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which contains at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0195] In some embodiments, at least one R 61is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0196] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group is optionally substituted with one or more R A is replaced by

[0197] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0198] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one O—(CH) 0-3-substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0199] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally selected from a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0200] In some embodiments, at least one R 61is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein each alkyl group is optionally independently selected from C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0201] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one OH.

[0202] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one amino group.

[0203] In some embodiments, at least one R 61is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one NO.

[0204] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one halogen (e.g., F, Cl, Br, or I).

[0205] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one CN.

[0206] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one ═O.

[0207] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )C(O)R 62 is replaced by .

[0208] In some embodiments, at least one R 61is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )C(O)OR 62 is replaced by .

[0209] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0210] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by

[0211] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl), where C1-C6 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0212] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0213] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0214] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C(O)R 62 is replaced by .

[0215] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is selected from at least one C(O)OR 62 is replaced by .

[0216] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is at least one C(O)NR 63 R 64 is replaced by .

[0217] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one P(═O)(OR 62 )2.

[0218] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4-6 membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is optionally substituted with one or more R A is replaced by

[0219] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group is optionally substituted with one or more R A is replaced by

[0220] In some embodiments, at least one R 61is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0221] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S.

[0222] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) comprising one or two 4- to 6-membered rings and one to four heteroatoms selected from N, O, and S, wherein the heterocyclyl group is substituted, and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group comprising a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S, and wherein the carbocyclyl or heterocyclyl group optionally comprises one or more R A is replaced by

[0223] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group is substituted and one or more hydrogen atoms in the substituents are optionally replaced with one or more deuterium atoms.

[0224] In some embodiments, L is absent. In some embodiments, L is O. In some embodiments, L is (CR L1 R L2 ) n is. In some embodiments, L is O—(CR L1 R L2 ) n is. In some embodiments, L is (CR L1 R L2 ) n -O. In some embodiments, L is S(O)2. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.

[0225] In some embodiments, R L1 and R L2 are each independently H, CH3, CH2CH3, or CH(CH3)2. In some embodiments, each R L1 and each R L2 is H. In some embodiments, each R L1 is H and at least one R L2 is CH3, CH2CH3 or CH(CH3)2. In some embodiments, R L1 at least one of R is CH3, CH2CH3 or CH(CH3)2, and at least one of R L2 is CH3, CH2CH3 or CH(CH3)2. In some embodiments, R L1 and R L2 together with the carbon atoms to which they are attached to form C(O). In some embodiments, R L1 and R L2together with the carbon atom to which they are attached form a C3-C6 cycloalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl).

[0226] In some embodiments, R L1 and R L2 together with the carbon atoms to which they are attached form a heterocyclyl group containing a 4- to 6-membered ring and 1-3 heteroatoms selected from N, O, and S (e.g., a heterocyclyl group described herein). In some embodiments, at least one R A is a halogen (e.g., F, Cl, Br, or I). In some embodiments, at least one R A is OH. In some embodiments, at least one R A is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0227] In some embodiments, at least one R A is a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy). In some embodiments, at least one R A is a C1-C6 alkylamino group (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) or a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl).

[0228] In some embodiments, two R 61together with the carbon atoms to which they are attached form C4-C 10 forming a carbocyclyl group (e.g., cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl), which independently and optionally can be selected from the group consisting of a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I), a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy), a C1- C6 haloalkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I)), C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), OH, amino groups, halogens (e.g., F, Cl, Br, or I), CN, and =O.

[0229] In some embodiments, two R 61together with the carbon atoms to which they are attached form a heterocyclyl group (e.g., a heterocyclyl group described herein) containing a 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S, which independently and optionally can be selected from a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I), a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy), C1-C6 haloalkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I)), C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), OH, amino groups, halogens (e.g., F, Cl, Br, or I), CN, and =O.

[0230] In some embodiments, two R 61 together with the carbon atoms to which they are attached form a heterocyclyl group containing four members and one to three heteroatoms selected from N, O, and S (e.g., a four-membered heterocyclyl group described herein), which is optionally substituted as described herein.

[0231] In some embodiments, two R61 together with the carbon atoms to which they are attached form a heterocyclyl group containing 5 members and 1 to 3 heteroatoms selected from N, O, and S (e.g., a 5-membered heterocyclyl group described herein), which is optionally substituted as described herein.

[0232] In some embodiments, two R 61 together with the carbon atoms to which they are attached form a heterocyclyl group containing 6 members and 1 to 3 heteroatoms selected from N, O, and S (e.g., a 6-membered heterocyclyl group described herein), which is optionally substituted as described herein.

[0233] In some embodiments, two R 61together with the carbon atoms to which they are attached form a spiroheterocyclyl group or a fused heterocyclyl group (e.g., a spiroheterocyclyl group or a fused heterocyclyl group described herein) encompassing two 4- to 6-membered rings containing 1-4 heteroatoms selected from N, O, and S, which independently and optionally can be selected from the group consisting of a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I), a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, , tert-butoxy, pentoxy or hexoxy), C1-C6 haloalkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy or hexoxy, each of which is substituted with one or more halogens (e.g., F, Cl, Br or I)), C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl), di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl), OH, amino group, halogen (e.g., F, Cl, Br or I), CN and =O.

[0234] In some embodiments, two R 61together with the carbon atoms to which they are attached form a spiroheterocyclyl group or a fused heterocyclyl group containing two 5- to 6-membered rings containing 1-4 heteroatoms selected from N, O, and S (e.g., a spiroheterocyclyl group or a fused heterocyclyl group described herein), which is optionally substituted as described herein.

[0235] In some embodiments, two R 61 together with the carbon atoms to which they are attached form a C6 aryl group, which independently and optionally can be selected from the group consisting of a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I), a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy), a C1-C6 haloalkoxy group (e.g., and substituted with one or more groups selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each substituted with one or more halogens (e.g., F, Cl, Br, or I), a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), OH, an amino group, a halogen (e.g., F, Cl, Br, or I), CN, and =O.

[0236] In some embodiments, each R 62 is H. In some embodiments, at least one R 62 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, at least one R 62 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, each R 63 is H.

[0237] In some embodiments, at least one R 63 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, at least one R 63 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, each R 64 is H. In some embodiments, at least one R 64 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0238] In some embodiments, at least one R 64is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R 61 ' is H. In some embodiments, R 61 ' is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0239] In some embodiments, R 61 ' is independently a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), which can be a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a halogen (e.g., F, Cl, Br, or I), OH, an amino group, a C6 ... 10 and substituted with one or more groups selected from the group consisting of aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heteroaryl groups described herein).

[0240] In some embodiments, R 61 ' is a C1-C6 alkoxy group (for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy or hexoxy).

[0241] In some embodiments, R 61is a C1-C6 haloalkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each substituted with one or more halogens (e.g., F, Cl, Br, or I)). In some embodiments, R 61 ' is OH. In some embodiments, R 61 ' is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R 61 ' is F or Cl.

[0242] In some embodiments, R 61 is a C1-C6 alkylamino group (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) or a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). In some embodiments, R 61 ' is OH, an amino group, NO2, a halogen, or CN. In some embodiments, R 61 ' is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is.

[0243] In some embodiments, R 61 ' is H or halogen. In some embodiments, X 1 is N. In some embodiments, X1 is CR X1 is. In some embodiments, X2 is N. In some embodiments, X2 is CR X1 is. In some embodiments, X3 is N. In some embodiments, X3 is CR X1 is. In some embodiments, X4 is N. In some embodiments, X4 is CR X1 is. In some embodiments, X5 is N. In some embodiments, X5 is CR X1 is.

[0244] In some embodiments, one of X1, X2, X3, X4, and X5 is N. In some embodiments, two of X1, X2, X3, X4, and X5 are N. In some embodiments, three of X1, X2, X3, X4, and X5 are N. In some embodiments, four of X1, X2, X3, X4, and X5 are N. In some embodiments, R X1 is H. In some embodiments, R X1 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl).

[0245] In some embodiments, R X1 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R X1 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R X1 is F or Cl.

[0246] In some embodiments, R X1 is (CH2) 0-3 - a C1-C6 alkoxy group, wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy group is optionally halogen (e.g., F, Cl, Br, or I), a C1-C6 alkylamino group, wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl; and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0247] In some embodiments, R X1 is O-(CH2) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A (which is replaced by ). In some embodiments, R X1 is O—(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally includes one or more R A is replaced by

[0248] In some embodiments, R X1 is O-(CH2) 0-3 -C6-C 10It is an aryl group (eg, phenyl or naphthyl). In some embodiments, R X1 is O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -a heteroaryl group (eg, a heteroaryl group described herein).

[0249] In some embodiments, R X1is a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino group is optionally selected from C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy) or di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0250] In some embodiments, R X1 is OH, an amino group, NO2, a halogen, CN, or =O. In some embodiments, R X1 is N(R N)C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2 or S(O) 0-2 -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, and wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and optionally one or more R A is replaced by

[0251] In some embodiments, R X1 is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is. In some embodiments, R X1 is P(=O)(OR 62 )2. In some embodiments, R X1 is a C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which optionally contains one or more R A , substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, the heterocyclyl group optionally containing one or more R A , C6-C 10 It is substituted with an aryl group (e.g., phenyl or naphthyl) or a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., a heteroaryl group described herein).

[0252] In some embodiments, R X2 is H. In some embodiments, R X2 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, R X2 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R X2 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R X2 is F or Cl.

[0253] In some embodiments, R X2 is (CH2) 0-3 - a C1-C6 alkoxy group, wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy group is optionally halogen (e.g., F, Cl, Br, or I), a C1-C6 alkylamino group, wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl; ), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0254] In some embodiments, R X2 is O-(CH2) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A (which is replaced by ). In some embodiments, R X2 is O—(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally includes one or more R A is replaced by

[0255] In some embodiments, R X2 is O-(CH2) 0-3 -C6-C 10 It is an aryl group (eg, phenyl or naphthyl). In some embodiments, R X2 is O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -a heteroaryl group (eg, a heteroaryl group described herein).

[0256] In some embodiments, R X2is a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino group is optionally selected from C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy) or di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0257] In some embodiments, R X2 is OH, an amino group, NO2, a halogen, CN, or =O. In some embodiments, R X2 is N(R N)C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2 or S(O) 0-2 -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, and wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and optionally one or more R A is replaced by

[0258] In some embodiments, R X2 is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is. In some embodiments, R X2 is P(=O)(OR 62 )2. In some embodiments, R X2 is a C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which optionally contains one or more R A , substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, the heterocyclyl group optionally containing one or more R A , C6-C 10 It is substituted with an aryl group (e.g., phenyl or naphthyl) or a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., a heteroaryl group described herein).

[0259] In some embodiments, R X3 is H. In some embodiments, R X3 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, R X3 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R X3 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R X3 is F or Cl.

[0260] In some embodiments, R X3 is (CH2) 0-3 -C1-C6 alkoxy group, wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy group is optionally halogen (e.g., F, Cl, Br, or I), a C1-C6 alkylamino group, wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0261] In some embodiments, R X3 is O-(CH2) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A (which is replaced by ). In some embodiments, R X3 is O—(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally includes one or more R A is replaced by

[0262] In some embodiments, R X3 is O-(CH2) 0-3 -C6-C 10 It is an aryl group (eg, phenyl or naphthyl). In some embodiments, R X3 is O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -a heteroaryl group (eg, a heteroaryl group described herein).

[0263] In some embodiments, R X3is a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino group is optionally selected from C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy) or di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0264] In some embodiments, R X3 is OH, an amino group, NO2, a halogen, CN, or =O. In some embodiments, R X3 is N(R N)C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2 or S(O) 0-2 -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, and wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and optionally one or more R A is replaced by

[0265] In some embodiments, R X3 is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is. In some embodiments, R X3 is P(=O)(OR 62 )2. In some embodiments, R X3 is a C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which optionally contains one or more R A , substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, the heterocyclyl group optionally containing one or more R A , C6-C 10 It is substituted with an aryl group (e.g., phenyl or naphthyl) or a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., a heteroaryl group described herein).

[0266] In some embodiments, R X4 is H. In some embodiments, R X4 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, R X4 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R X4 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R X4 is F or Cl.

[0267] In some embodiments, R X4 is (CH2) 0-3 -C1-C6 alkoxy group, wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy group is optionally halogen (e.g., F, Cl, Br, or I), a C1-C6 alkylamino group, wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0268] In some embodiments, R X4 is O-(CH2) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A (which is replaced by ). In some embodiments, R X4 is O—(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally includes one or more R A is replaced by

[0269] In some embodiments, R X4 is O-(CH2) 0-3 -C6-C 10 It is an aryl group (eg, phenyl or naphthyl). In some embodiments, R X4 is O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -a heteroaryl group (eg, a heteroaryl group described herein).

[0270] In some embodiments, R X4is a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino group is optionally selected from C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy) or di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0271] In some embodiments, R X4 is OH, an amino group, NO2, a halogen, CN, or =O. In some embodiments, R X4 is N(R N)C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2 or S(O) 0-2 -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, and wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and optionally one or more R A is replaced by

[0272] In some embodiments, R X4 is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is. In some embodiments, R X4 is P(=O)(OR 62 )2. In some embodiments, R X4 is a C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which optionally contains one or more R A , substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, the heterocyclyl group optionally containing one or more R A , C6-C 10 It is substituted with an aryl group (e.g., phenyl or naphthyl) or a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., a heteroaryl group described herein).

[0273] In some embodiments, R X5 is H. In some embodiments, R X5 is a C1-C6 alkyl group (for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl). In some embodiments, R X5 is a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I). In some embodiments, R X5 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, R X5 is F or Cl.

[0274] In some embodiments, R X5 is (CH2) 0-3 -C1-C6 alkoxy group, wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy group is optionally halogen (e.g., F, Cl, Br, or I), a C1-C6 alkylamino group, wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0275] In some embodiments, R X5 is O-(CH2) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A (which is replaced by ). In some embodiments, R X5 is O—(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally includes one or more R A is replaced by

[0276] In some embodiments, R X5 is O-(CH2) 0-3 -C6-C 10 It is an aryl group (eg, phenyl or naphthyl). In some embodiments, R X5 is O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -a heteroaryl group (eg, a heteroaryl group described herein).

[0277] In some embodiments, R X5is a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino group is optionally selected from C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy) or di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkylamino groups are optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0278] In some embodiments, R X5 is OH, an amino group, NO2, a halogen, CN, or =O. In some embodiments, R X5 is N(R N)C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2 or S(O) 0-2 -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, and wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and optionally one or more R A is replaced by

[0279] In some embodiments, R X5 is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is. In some embodiments, R X5 is P(=O)(OR 62 )2. In some embodiments, R X5 is a C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which optionally contains one or more R A , substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, the heterocyclyl group optionally containing one or more R A , C6-C 10 It is substituted with an aryl group (e.g., phenyl or naphthyl) or a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., a heteroaryl group described herein).

[0280] In some embodiments, R X1 , R X2 , R X3 , R X4 and R X5 two of which bonded to adjacent carbon atoms can be taken together with the carbon atoms to which they are bonded to form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, wherein the carbocyclyl group or heterocyclyl group is optionally substituted with one or more halogens, and wherein R X1 , R X2 , R X3 , R X4 and R X5 One or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms. In some embodiments, each R 61 " is H. In some embodiments, at least one R 61 " is H. In some embodiments, at least one R 61 " is a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl).

[0281] In some embodiments, at least one R 61" is a C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), which is independently selected from C1-C6 alkylamino groups (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), halogen (e.g., F, Cl, Br, or I), OH, amino groups, C6-C 10 It is substituted with one or more groups selected from the group consisting of aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heteroaryl groups described herein).

[0282] In some embodiments, at least one R 61 " is a C1-C6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy). In some embodiments, at least one R 61 " is a C1-C6 haloalkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, each substituted with one or more halogens (e.g., F, Cl, Br, or I)). In some embodiments, at least one R 61 " is OH. In some embodiments, at least one R 61 " is a halogen (e.g., F, Cl, Br, or I). In some embodiments, at least one R 61 " is F or Cl.

[0283] In some embodiments, at least one R 61 " is a C1-C6 alkylamino group (wherein the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) or a di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). In some embodiments, at least one R 61 " is OH, an amino group, NO2, a halogen, or CN. In some embodiments, at least one R 61 " is C(O)R 62 , C(O)OR 62 or C(O)NR 63 R 64 is.

[0284] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl), which optionally is C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0285] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0286] In some embodiments, at least one R 61 " is L-C6-C 10It is an aryl group (e.g., phenyl or naphthyl) substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br or I)).

[0287] In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0288] In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains at least one O—(CH2) 0-3- a C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0289] In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, and at least one O—(CH) 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group optionally comprises one or more R A is replaced by

[0290] In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains at least one O—(CH2) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0291] In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that contains one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, and at least one O—(CH) 0-3 -substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0292] In some embodiments, at least one R 61 " is L-C6-C 10an aryl group (e.g., phenyl or naphthyl) substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0293] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that is substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl); and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0294] In some embodiments, at least one R 61 " is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl), which is substituted with at least one OH. In some embodiments, at least one R 61 " is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl) that is substituted with at least one amino group. In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (eg, phenyl or naphthyl) that is substituted with at least one NO2.

[0295] In some embodiments, at least one R 61 " is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl) that is substituted with at least one halogen (eg, F, Cl, Br, or I). In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (eg, phenyl or naphthyl) which is substituted with at least one CN. In some embodiments, at least one R 61 " is L-C6-C 10 It is an aryl group (eg, phenyl or naphthyl) that is substituted with at least one =0.

[0296] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is L-C6-C10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )C(O)OR 62 is replaced by . In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0297] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl group), where C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0298] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one S(O) 1-2Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0299] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that contains at least one C(O)OR 62 is replaced by . In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one C(O)NR 63 R 64 is replaced by .

[0300] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one P(=O)(OR 62 )2. In some embodiments, at least one R 61 " is L-C6-C10 an aryl group (e.g., phenyl or naphthyl) that is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group optionally contains one or more R A is replaced by

[0301] In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group optionally contains one or more R A is replaced by In some embodiments, at least one R 61 " is L-C6-C 10 an aryl group (e.g., phenyl or naphthyl) that has at least one C-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl). In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (e.g., phenyl or naphthyl) that is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S.

[0302] In some embodiments, at least one R 61 " is L-C6-C 10an aryl group (e.g., phenyl or naphthyl), wherein the aryl group is substituted and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group optionally contains one or more R A is replaced by In some embodiments, at least one R 61 " is L-C6-C 10 An aryl group (eg, phenyl or naphthyl), wherein the aryl group is substituted, and one or more hydrogen atoms in the substituent may be replaced by one or more deuterium atoms.

[0303] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which independently and optionally: C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0304] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0305] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C-C alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C-C haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I)). In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which has at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0306] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one O—(CH) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0307] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which contains at least one O-(CH2) group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S. 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), said heterocyclyl group optionally comprising one or more R A is replaced by

[0308] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one O—(CH) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0309] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one O-(CH) group containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S.0-3 -substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0310] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally substituted with a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl). butyl, sec-butyl, tert-butyl, pentyl or hexyl), di-C1-C6 alkylamino group (each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl), and C1-C6 alkoxy group (alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy or hexoxy).

[0311] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one di-C1-C6 alkylamino group (each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with a C1-C6 alkylamino group (the alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, and C1-C6 alkoxy groups (wherein the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0312] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one OH. In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one amino group.

[0313] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one NO. In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one halogen (e.g., F, Cl, Br, or I).

[0314] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one CN. In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one =0.

[0315] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )C(O)OR 62is replaced by .

[0316] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0317] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by

[0318] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl), where C1-C6 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0319] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0320] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which includes at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0321] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is substituted with at least one C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which is selected from at least one C(O)OR 62 is replaced by .

[0322] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which has at least one C(O)NR 63 R 64 is replaced by . In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which may contain at least one P(=O)(OR 62 )2.

[0323] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is optionally substituted with one or more R A is replaced by In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group optionally contains one or more R A is replaced by

[0324] In some embodiments, at least one R 61" is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two five- or six-membered rings and one to four heteroatoms selected from N, O, and S, which has at least one C-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl). In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S.

[0325] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group as described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group is substituted, and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and 1 or 2 heteroatoms selected from N, O, and S, and the carbocyclyl or heterocyclyl group optionally contains one or more R A is replaced by

[0326] In some embodiments, at least one R 61 " is an L-heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group is substituted and one or more hydrogen atoms in the substituents are optionally replaced with one or more deuterium atoms.

[0327] In some embodiments, at least one R 61" is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which independently and optionally is C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N )S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0328] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R Aand one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0329] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), a C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0330] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and a C1-C6 alkoxy group (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0331] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one O-(CH2) 0-3 - a C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ). In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that contains one or two 3- to 6-membered rings and one to four heteroatoms selected from N, O, and S, and at least one O-(CH2) 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group is optionally substituted with one or more R A is replaced by

[0332] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one O-(CH2) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl). In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that contains one or two 5- or 6-membered rings and one to four heteroatoms selected from N, O, and S, and at least one O-(CH2) 0-3 -substituted with a heteroaryl group (eg, a heteroaryl group described herein);

[0333] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0334] In some embodiments, at least one R 61" is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein each alkyl group is optionally independently a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and is substituted with one or more substituents selected from the group consisting of di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0335] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one OH. In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one amino group.

[0336] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one NO2. In some embodiments, at least one R 61" is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one halogen (e.g., F, Cl, Br, or I).

[0337] In some embodiments, at least one R 61 " is a L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), which is substituted with at least one CN. In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which is substituted with at least one =0.

[0338] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one N(R N )C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one N(R N )C(O)OR 62 is replaced by .

[0339] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one N(R N)S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0340] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by

[0341] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl), where C1-C6 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0342] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0343] In some embodiments, at least one R 61" is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0344] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one C(O)OR 62 is replaced by .

[0345] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one C(O)NR 63 R 64 is replaced by . In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one P(=O)(OR 62 )2.

[0346] In some embodiments, at least one R 61" is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) that is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is optionally substituted with one or more R A is replaced by

[0347] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group optionally contains one or more R A is replaced by

[0348] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) which has at least one C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl). In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S.

[0349] In some embodiments, at least one R 61" is substituted with an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is substituted and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S, and wherein the carbocyclyl group or heterocyclyl group optionally contains one or more R A is replaced by

[0350] In some embodiments, at least one R 61 " is an L-C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group is substituted and one or more hydrogen atoms in the substituent may be replaced by one or more deuterium atoms.

[0351] In some embodiments, at least one R 61 is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is independently and optionally: C1-C6 alkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl groups (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each substituted with one or more halogens (e.g., F, Cl, Br, or I)), (CH2) 0-3-C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with one or more groups selected from the group consisting of halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl) and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); O-(CH2) 0-3 -C3-C6 carbocyclyl group (wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl); O-(CH2) containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heterocyclyl group (e.g., a heterocyclyl group described herein), O-(CH2) 0-3 -C6-C 10 an aryl group (e.g., phenyl or naphthyl); O—(CH2) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S 0-3 a heteroaryl group (e.g., a heteroaryl group described herein), C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and the alkyl group is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and each alkyl group is optionally independently substituted with one or more substituents selected from the group consisting of C1-C6 alkylamino groups (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy); OH, amino group, NO2, halogen (e.g., F, Cl, Br, or I), CN, =O, N(R N )C(O)R 62 , N(R N )C(O)OR 62 , N(R N )S(O)2-C1-C6 alkyl group, N(R N)S(O)2-C3-C6 cycloalkyl group, S(O) 1-2 NH(C1-C6 alkyl group), S(O) 1-2 N(C1-C6 alkyl group)2, S(O) 0-2 -C1-C6 alkyl groups, wherein the C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, and wherein the C3-C6 carbocyclyl groups are cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 )2, C3-C6 carbocyclyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), heterocyclyl groups containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S (e.g., heterocyclyl groups described herein), C6-C 10 an aryl group (e.g., phenyl or naphthyl) and a heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S;

[0352] wherein two of the substituents, together with the carbon atoms to which they are attached, can form a C5-C6 carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O and S, and the carbocyclyl or heterocyclyl group can optionally be one or more R A and one or more hydrogen atoms of the substituents may be replaced with one or more deuterium atoms.

[0353] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), C1-C6 haloalkyl group (e.g., methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, each of which is substituted with one or more halogens (e.g., F, Cl, Br, or I)).

[0354] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which contains at least one (CH2) 0-3 -C1-C6 alkoxy groups, where the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy, and the alkoxy groups are optionally substituted with halogen (e.g., F, Cl, Br, or I), C1-C6 alkylamino groups, where the alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl. and di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0355] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one O—(CH) 0-3 - a C3-C6 carbocyclyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by ).

[0356] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one O-(CH2) group containing one or two 3- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S. 0-3 -substituted with a heterocyclyl group (e.g., a heterocyclyl group described herein), wherein said heterocyclyl group is optionally substituted with one or more R A is replaced by

[0357] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one O—(CH) 0-3 -C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl).

[0358] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which contains at least one O-(CH2) group containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S. 0-3-substituted with a heteroaryl group a (eg, a heteroaryl group described herein);

[0359] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein the alkyl group is optionally substituted with a C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, , sec-butyl, tert-butyl, pentyl, or hexyl), di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0360] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one di-C1-C6 alkylamino group (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), wherein each alkyl group is optionally independently selected from C1-C6 alkylamino group (wherein the alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, and is substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl, di-C1-C6 alkylamino groups (wherein each alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl), and C1-C6 alkoxy groups (wherein the alkoxy group is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, or hexoxy).

[0361] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one OH. In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one amino group.

[0362] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one NO.

[0363] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one halogen (e.g., F, Cl, Br, or I). In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one CN.

[0364] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one =0. In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which has at least one N(R N )C(O)R 62 is replaced by .

[0365] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which has at least one N(R N )C(O)OR62 is replaced by . In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which has at least one N(R N )S(O)2-C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0366] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which has at least one N(R N )S(O)2-C3-C6 cycloalkyl group, wherein the C3-C6 carbocyclyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and optionally one or more R A is replaced by In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 It is substituted with NH(C1-C6 alkyl), where C1-C6 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0367] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one S(O) 1-2 Substituted with N(C1-C6 alkyl)2, wherein each C1-C6 alkyl group is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, or hexyl.

[0368] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one S(O) 0-2 It is substituted with a -C1-C6 alkyl group, wherein the C1-C6 alkyl group is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl.

[0369] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is selected from at least one C(O)R 62 is replaced by . In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is selected from at least one C(O)OR 62 is replaced by .

[0370] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which has at least one C(O)NR 63 R 64 is replaced by . In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which may contain at least one P(=O)(OR 62 )2.

[0371] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which is substituted with at least one C3-C6 carbocyclyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), wherein the carbocyclyl group optionally contains one or more R A is replaced by

[0372] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 3- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group optionally contains one or more R A is replaced by

[0373] In some embodiments, at least one R 61" is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, which includes at least one C6-C 10 It is substituted with an aryl group (eg, phenyl or naphthyl). In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1-4 heteroatoms selected from N, O, and S, which is substituted with at least one heteroaryl group (e.g., a heteroaryl group described herein) containing one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S.

[0374] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) comprising one or two 4- to 6-membered rings and one to four heteroatoms selected from N, O, and S, wherein the heterocyclyl group is substituted, and two of the substituents, together with the carbon atoms to which they are attached, form a C5-C6 carbocyclyl group or a heterocyclyl group comprising a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S, and wherein the carbocyclyl or heterocyclyl group optionally comprises one or more R A is replaced by

[0375] In some embodiments, at least one R 61 " is an L-heterocyclyl group (e.g., a heterocyclyl group described herein) containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group is substituted and one or more hydrogen atoms in the substituents are optionally replaced with one or more deuterium atoms.

[0376] In some embodiments, the compound of the present application is selected from Table A or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the compound of the present application is selected from Table B or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the compound of the present application is selected from Table C or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof. In another aspect, this application relates to a pharmaceutical composition comprising a compound described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable diluent, carrier, or excipient.

[0377] In another aspect, the present application relates to compounds and compositions thereof that can degrade HuR (e.g., compounds and compositions described herein, such as compounds of a formula described herein or compounds listed in the Tables). In some embodiments, the present application's compounds and compositions thereof can selectively degrade HuR, i.e., more efficiently, e.g., with a lower IC, compared to the degradation of other targets (e.g., Wee1 and / or GSPT1). 50 In some embodiments, the IC of HuR and other targets can be 50 can be assessed by the methods described herein and by commonly used methods.

[0378] In another aspect, this application relates to a method of treating or preventing a disease or disorder as described herein (e.g., a HuR-mediated disease or disorder, or a disease or disorder in which HuR is implicated), the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a therapeutically effective amount of a pharmaceutical composition described herein.

[0379] In another aspect, this application relates to a compound described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a pharmaceutical composition described herein, for use in a method for treating or preventing a disease or disorder, or for modulating (e.g., inactivating or degrading) HuR.

[0380] In another aspect, this application relates to the use of a compound described herein or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a pharmaceutical composition described herein, in the manufacture of a medicament for treating or preventing a disease or disorder, or for modulating (e.g., inactivating or degrading) HuR.

[0381] In some embodiments, the disease or disorder is a cell proliferative disease or disorder. In some embodiments, the cell proliferative disease or disorder is cancer. In some embodiments, the cancer is selected from bladder cancer, brain cancer, breast cancer, colorectal cancer, cervical cancer, gastrointestinal cancer, genitourinary system cancer, glioma, head and neck cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, skin cancer, and testicular cancer.

[0382] Any moiety herein described with respect to any one of the variables in the formulas herein can be combined with any moiety described with respect to one or more of the remaining variables in the formulas herein.

[0383] Non-limiting exemplary compounds of the present application are listed in Tables A-C. As indicated in Tables A-C, and throughout the compounds, examples, solutions, and other tables of compounds of the present application, "or 1" (or "or 1") and "or 2" (or "or 2") represent a single stereoisomeric configuration, and "&1" represents a mixture of stereoisomers of the indicated chiral carbon atom, even though the absolute stereochemistry of the indicated chiral carbon atom has not been determined.

[0384] Table A. Non-limiting exemplary compounds of the present application JPEG2025539873000008.jpg185151

[0385] JPEG2025539873000009.jpg226151

[0386] JPEG2025539873000010.jpg226151

[0387] JPEG2025539873000011.jpg226151

[0388] JPEG2025539873000012.jpg226151

[0389] JPEG2025539873000013.jpg226151

[0390] JPEG2025539873000014.jpg226151

[0391] JPEG2025539873000015.jpg226151

[0392] JPEG2025539873000016.jpg226151

[0393] JPEG2025539873000017.jpg239164

[0394] JPEG2025539873000018.jpg231164

[0395] JPEG2025539873000019.jpg226151

[0396] JPEG2025539873000020.jpg226151

[0397] JPEG2025539873000021.jpg226151

[0398] JPEG2025539873000022.jpg226151

[0399] JPEG2025539873000023.jpg226151

[0400] JPEG2025539873000024.jpg226151

[0401] JPEG2025539873000025.jpg226151

[0402] JPEG2025539873000026.jpg226151

[0403] JPEG2025539873000027.jpg226151

[0404] JPEG2025539873000028.jpg226164

[0405] JPEG2025539873000029.jpg226151

[0406] JPEG2025539873000030.jpg226151

[0407] JPEG2025539873000031.jpg226151

[0408] JPEG2025539873000032.jpg226151

[0409] JPEG2025539873000033.jpg226151

[0410] JPEG2025539873000034.jpg226151

[0411] JPEG2025539873000035.jpg226151

[0412] JPEG2025539873000036.jpg226151

[0413] JPEG2025539873000037.jpg226151

[0414] JPEG2025539873000038.jpg226151

[0415] JPEG2025539873000039.jpg226151

[0416] JPEG2025539873000040.jpg229163

[0417] JPEG2025539873000041.jpg226151

[0418] JPEG2025539873000042.jpg226164

[0419] JPEG2025539873000043.jpg230164

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[0430] JPEG2025539873000054.jpg226151

[0431] Table B. Non-limiting selected compounds of the present application JPEG2025539873000055.jpg226151

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[0433] JPEG2025539873000057.jpg226151

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[0441] JPEG2025539873000065.jpg226151

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[0443] JPEG2025539873000067.jpg226151

[0444] JPEG2025539873000068.jpg103142

[0445] Table C. Non-limiting selected compounds of the present application JPEG2025539873000069.jpg127142

[0446] JPEG2025539873000070.jpg226151

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[0451] Details of the present application are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, exemplary methods and materials are described herein. Other features, objects, and advantages of the present application will be apparent from the specification and claims. In the specification and appended claims, the singular forms "a," "an," and "the" include the plural unless the context clearly dictates otherwise. 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. All patents and publications cited herein are incorporated by reference in their entirety.

[0452] definition The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" refers to one element or to more than one element.

[0453] Unless otherwise stated, the term "and / or" as used herein means "and" or "or." The present application further includes pharmaceutical compositions comprising an effective amount of a compound of the present application (e.g., a compound of any formula or any individual compound disclosed herein) and a pharmaceutically acceptable carrier.

[0454] As used herein, the term "alkyl group" refers to a saturated, straight- or branched-chain hydrocarbon radical, which in some embodiments contains 1 to 6 carbon atoms. Examples of C1-C8 alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl, n-heptyl, and n-octyl. Examples of C1-C6 alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, and n-hexyl.

[0455] As used herein, the term "alkenyl group" refers to a monovalent group derived from a hydrocarbon moiety, which in certain embodiments contains 2 to 6 carbon atoms and at least one carbon-carbon double bond. The double bond may or may not be the point of attachment to another group. Examples of alkenyl groups include, but are not limited to, vinyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, and the like. The term "alkoxy" refers to an --O-alkyl radical. As used herein, "hal," "halo," and "halogen" refer to an atom selected from fluoro, chloro, bromo, and iodo.

[0456] As used herein, the term "aryl group" refers to a monocyclic or polycyclic carbocyclic ring system having one or more aromatic rings (fused or unfused), including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl, and the like. As used herein, the term "aralkyl group" refers to an alkyl residue attached to an aromatic ring. Examples include, but are not limited to, benzyl, phenethyl, and the like.

[0457] As used herein, the term "cycloalkyl group" or "carbocyclyl group" refers to a monovalent group derived from a monocyclic or polycyclic saturated or partially unsaturated carbocyclic ring compound (fused, bridged, or spiro). Examples of C3-C8 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentyl, and cyclooctyl, and C3-C8 cycloalkyl groups are substituted or unsubstituted C3-C8 cycloalkyl groups. 12 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[2.2.1]heptyl, and bicyclo[2.2.2]octyl. Monovalent groups derived from monocyclic or polycyclic carbocyclic ring compounds having at least one carbon-carbon double bond by removing a single hydrogen atom are also contemplated. Examples of such groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like.

[0458] As used herein, the term "heteroaryl group" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic or higher) fused or non-fused radical or ring system having at least one aromatic ring having 5 to 10 ring atoms, of which one ring atom is selected from S, O, and N, 0, 1, or 2 ring atoms are additional heteroatoms independently selected from S, O, and N, and the remaining ring atoms are carbon. Heteroaryl groups include, but are not limited to, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thienyl, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolyl, quinoxalinyl, and the like.

[0459] As used herein, the term "heteroaralkyl group" refers to an alkyl residue attached to a heteroaromatic ring. Examples include, but are not limited to, pyridylmethyl, pyrimidinylethyl, and the like.

[0460] As used herein, the terms "heterocyclyl group" or "heterocycloalkyl group" refer to a saturated or unsaturated non-aromatic 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic (fused, bridged, or spiro), or 11-, 12-, 13-, or 14-membered tricyclic system (fused, bridged, or spiro), in which (i) each ring contains 1 to 3 heteroatoms independently selected from oxygen, sulfur, and nitrogen, (ii) each 5-membered ring has 0 to 1 double bond and each 6-membered ring has 0 to 2 double bonds, (iii) the nitrogen and sulfur heteroatoms may optionally be oxidized, and (iv) the nitrogen heteroatom may optionally be quaternized.Representative heterocycloalkyl groups include [1,3]dioxolanyl, pyrrolidinyl, pyrazolidinyl, pyrazolinyl, imidazolinyl, imidazolyldinyl, piperidinyl, piperazinyl, 2-pyridinone, oxazolinyl, isoxazolinyl, morpholinyl, tetrahydropyranyl, thiazolidinyl, isothiazolidinyl, tetrahydrofuryl, dioxanyl, oxetanyl, azetidinyl, thietanyl, oxiranyl, aziridinyl, thiiranyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, and 2-oxa-6-azaspiro[3.3]heptyl. butyl, 2,6-diazaspiro[3.3]heptyl, 1,4-dioxa-8-azaspiro[4.5]decyl, 2-azaspiro[3.3]heptan-5-amine, 1-azaspiro[3.3]heptan-5-amine, 1-oxa-6-azaspiro[3.3]heptan-3-amine, 2-azaspiro[3.3]heptan-6-amine, 1-azaspiro[3.3]heptan-6-amine, 6-azaspiro[3.4]octan-2-amine, 5-azaspiro[3.4]octan-2-amine, 6-azaspiro[3.4]octan-1-amine, 5-azaspiro[3.4]octan-1-amine, 5-oxa-2-azaspiro[3.4]octan-7-amine, 7- The compound may be, but is not limited to, amino-5-thia-2-azaspiro[3.4]octane 5,5-dioxide, 5-oxa-2-azaspiro[3.4]octan-8-amine, 8-amino-5-thia-2-azaspiro[3.4]octane 5,5-dioxide, and the like.

[0461] The term "alkylamino group" refers to a group having the structure (eg, NH(C1-C6 alkyl group)), where C1-C6 alkyl group is as defined above. The term "dialkylamino group" refers to a group having the structure (eg, N(C1-C6 alkyl group)2), in which the C1-C6 alkyl group is as defined above. According to the present application, any of the aryl, substituted aryl, heteroaryl, and substituted heteroaryl groups described herein may be any aromatic group, which may be substituted or unsubstituted.

[0462] The compounds of the present application described herein may be optionally substituted with one or more substituents, as generally described above or as exemplified by specific classes, subclasses, and species of the present application. The phrase "optionally substituted" is understood to be used interchangeably with "substituted or unsubstituted." In general, the term "substituted," whether preceded by the term "optionally," refers to the replacement of a hydrogen radical in a given structure with the radical of a specified substituent. Unless otherwise specified, an optionally substituted group may have a substituent at each substitutable position in the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituents at each position may be the same or different. As used herein, the terms "optionally substituted," "optionally substituted alkyl group," "optionally substituted alkenyl group," "optionally substituted cycloalkyl group," "optionally substituted cycloalkenyl group," "optionally substituted aryl group," "optionally substituted heteroaryl group," "optionally substituted aralkyl group," "optionally substituted heteroaralkyl group," "optionally substituted heterocyclyl group," and any other optionally substituted group refer to a group that is substituted or unsubstituted by independently replacing one, two, or three or more hydrogen atoms thereon with substituents, wherein said substituents are -F, -CI, -Br, -I, -OH, protected hydroxyl, -NO2, -CN, -NH2, protected amino, -NH-C1-C 12 -Alkyl, -NH-C2-C 12 -Alkenyl, -NH-C2-C 12 -Alkenyl, -NH-C3-C 12-cycloalkyl, -NH-aryl, -NH-heteroaryl, -NH-heterocycloalkyl, -dialkylamino, -diarylamino, -diheteroarylamino, -O-C1-C 12 -Alkyl, -O-C2-C 12 -Alkenyl, -O-C2-C 12 -Alkenyl, -O-C3-C 12 -Cycloalkyl, -O-aryl, -O-heteroaryl, -O-heterocycloalkyl, -C(O)-C1-C 12 -Alkyl, -C(O)- C2-C 12 -alkenyl, -C(O)-C-C 12 -alkenyl, -C(O)-C-C 12 -Cycloalkyl, -C(O)-aryl, -C(O)-heteroaryl, -C(O)-heterocycloalkyl, -C(O)NH2, -C(O)NH-C1-C 12 -Alkyl, -C(O)NH-C2-C 12 -alkenyl, -C(O)NH-C2-C 12 -alkenyl, -C(O)NH-C3-C 12 -cycloalkyl, -C(O)NH-aryl, -C(O)NH-heteroaryl, -C(O)NH-heterocycloalkyl, -OCO2-C1-C 12 -Alkyl, -OCO2-C2-C 12 -Alkenyl, -OCO2-C2-C 12 -Alkenyl, -OCO2-C3-C 12 -cycloalkyl, -OCO2-aryl, -OCO2-heteroaryl, -OCO2-heterocycloalkyl, -OC(O)NH2, -OC(O)NH-C1-C 12 -Alkyl, -OC(O)NH- C2-C 12 -Alkenyl, -OC(O)NH- C2-C 12 -Alkenyl, -OC(O)NH-C3-C 12 -cycloalkyl, -OC(O)NH-aryl, -OC(O)NH-heteroaryl, -OC(O)NH-heterocycloalkyl, -NHC(O)-C1-C 12 -Alkyl, -NHC(O)-C2-C 12-Alkenyl, -NHC(O)-C-C 12 -Alkenyl, -NHC(O)-C3-C 12 -cycloalkyl, -NHC(O)-aryl, -NHC(O)-heteroaryl, -NHC(O)-heterocycloalkyl, -NHCO2-C1-C 12 -Alkyl, -NHCO2-C2-C 12 -Alkenyl, -NHCO2-C2-C 12 -Alkenyl, -NHCO2-C3-C 12 -cycloalkyl, -NHCO2-aryl, -NHCO2-heteroaryl, -NHCO2-heterocycloalkyl, -NHC(O)NH2, -NHC(O)NH-C1-C 12 -Alkyl, -NHC(O)NH-C2-C 12 -Alkenyl, -NHC(O)NH-C2-C 12 -Alkenyl, -NHC(O)NH-C3-C 12 -cycloalkyl, -NHC(O)NH-aryl, -NHC(O)NH-heteroaryl, NHC(O)NH-heterocycloalkyl, -NHC(S)NH2, -NHC(S)NH-C1-C 12 -Alkyl, -NHC(S)NH-C2-C 12 -Alkenyl, -NHC(S)NH-C2-C 12 -Alkenyl, -NHC(S)NH-C3-C 12 -Cycloalkyl, -NHC(S)NH-aryl, -NHC(S)NH-heteroaryl, -NHC(S)NH-heterocycloalkyl, -NHC(NH)NH2, -NHC(NH)NH- C1-C 12 -Alkyl, -NHC(NH)NH-C2-C 12 -Alkenyl, -NHC(NH)NH-C2-C 12 -Alkenyl, -NHC(NH)NH-C3-C 12 -cycloalkyl, -NHC(NH)NH-aryl, -NHC(NH)NH-heteroaryl, -NHC(NH)NHheterocycloalkyl, -NHC(NH)-C1-C 12 -Alkyl, -NHC(NH)-C2-C 12 -Alkenyl, -NHC(NH)-C-C 12-Alkenyl, -NHC(NH)-C3-C 12 -cycloalkyl, -NHC(NH)-aryl, -NHC(NH)-heteroaryl, -NHC(NH)-heterocycloalkyl, -C(NH)NH-C1-C 12 -Alkyl, -C(NH)NH-C2-C 12 -alkenyl, -C(NH)NH-C-C 12 -Alkenyl, C(NH)NH-C3-C 12 -cycloalkyl, -C(NH)NH-aryl, -C(NH)NH-heteroaryl, -C(NH)NHheterocycloalkyl, -S(O)-C1-C 12 -Alkyl, - S(O)-C2-C 12 -Alkenyl, -S(O)-C2-C 12 -alkenyl, -S(O)-C3-C 12 -Cycloalkyl, -S(O)-aryl, -S(O)-heteroaryl, -S(O)-heterocycloalkyl-SO2NH2, -SO2NH-C1-C 12 -Alkyl, -SO2NH-C2-C 12 -Alkenyl, -SO2NH-C2-C 12 -Alkenyl, -SO2NH-C3-C 12 -cycloalkyl, -SO2NH-aryl, -SO2NH-heteroaryl, -SO2NH-heterocycloalkyl, -NHSO2-C1-C 12 -Alkyl, -NHSO2-C2-C 12 -Alkenyl, -NHSO2-C2-C 12 -Alkenyl, -NHSO2-C3-C 12 -cycloalkyl, -NHSO2-aryl, -NHSO2-heteroaryl, -NHSO2-heterocycloalkyl, -CH2NH2, -CH2SO2CH3, -aryl, -arylalkyl, -heteroaryl, -heteroarylalkyl, -heterocycloalkyl, -C3-C 12 -Cycloalkyl, polyalkoxyalkyl, polyalkoxy, -methoxymethoxy, -methoxyethoxy, -SH, -S-C1-C 12 -Alkyl, -S-C2-C 12 -Alkenyl, -S-C2-C 12-Alkenyl, -S-C3-C 12 Examples include, but are not limited to, -S-cycloalkyl, -S-aryl, -S-heteroaryl, -S-heterocycloalkyl, or methylthiomethyl.

[0463] The term "carrier" as used herein encompasses carriers, excipients, and diluents, and refers to a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, that is involved in carrying or transporting a drug from one organ or body part of a subject to another. The compounds of the present application can form salts, which are also within the scope of the present application, and unless otherwise stated, reference to a compound herein should be understood to include reference to its salts.

[0464] Representative "pharmaceutically acceptable salts" include, for example, acetate, sulfamate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzoate, bicarbonate, hydrogensulfate, bitartrate, borate, bromide, butyrate, calcium, calcium ethylenediaminetetraacetate, camphorsulfonate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, ethanedisulfonate, estolate, ethanesulfonate, fumarate, fiunarate, glucoheptonate, gluconate, glutamate, glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydrabamine, hydroxybenzoate ... Roxinaphthoate, iodide, isothiosulfate, lactate, lactosate, laurate, magnesium, malate, maleate, mandelate, methanesulfonate, methyl bromide, methyl nitrate, methyl sulfate, mucate, naphthalenesulfonate, nitrate, N-methylglucosamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (1,1-methylene-bis-2-hydroxyl 3- Examples of water-soluble and water-insoluble salts include naphthoate, einbonate, pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, diacetate, succinate, sulfate, sulfosalicylate, suramate, tannate, tartrate, chlorate, tosylate, triethyl iodide, and pentanoate.

[0465] For example, the compounds of the present application, including pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers of said compounds, may exist in unsolvated or solvated forms or in solvated forms with other solvent molecules.

[0466] "Solvate" refers to a solvent addition form containing a stoichiometric or non-stoichiometric amount of solvent. Some compounds or salts tend to capture a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. When the solvent is water, the solvate formed is a hydrate; when the solvent is alcohol, the solvate formed is an alcoholate. A hydrate is formed by the combination of one or more water molecules with a substance molecule, where the water retains its molecular state as HO.

[0467] All stereoisomers (e.g., geometric isomers, optical isomers, etc.) of the compounds of the present invention (including salts, solvates, esters, and prodrugs of the compounds, and salts, solvates, and esters of the prodrugs), including enantiomeric forms (which may exist even when no asymmetric carbon atom is present), rotamer forms, atropisomers, and diastereomeric forms, as well as positional isomers (e.g., 4-pyridyl and 3-pyridyl groups), are contemplated within the scope of the present application. Individual stereoisomers of the compounds of the present application may, for example, be substantially free of other isomers or may be mixed, e.g., as racemates, or mixed with all or selected other stereoisomers. Chiral centers of the present application may have the S or R configuration as defined by the IUPAC 1974 Recommendations. Use of the terms "salts," "solvates," "esters," "prodrugs," and the like is intended to apply equally to salts, solvates, esters, and prodrugs of the enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates, or prodrugs of the compounds of the invention.

[0468] The term "isomer" refers to compounds that have the same composition and molecular weight but differ in physical and / or chemical properties. The structural difference can be in constitution (geometric isomers) or in ability to rotate the plane of polarized light (stereoisomers). With respect to stereoisomers, the compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound) may have one or more asymmetric carbon atoms and may exist in the form of a racemate, a racemic mixture, or individual enantiomers or diastereomers.

[0469] In this specification, the structural formula of a compound may, in some cases, conveniently represent a specific isomer, but the present application includes all isomers such as geometric isomers, optical isomers based on asymmetric carbons, stereoisomers, tautomers, etc. "Isomerism" means compounds that have the same molecular formula but differ in the sequence of bonding of their atoms or the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are called "stereoisomers." Stereoisomers that are not mirror images of one another are called "diastereomers," and stereoisomers that are non-superimposable mirror images of each other are called "enantiomers" or sometimes optical isomers. A mixture containing equal amounts of individual enantiomeric forms of opposite chirality is called a "racemic mixture."

[0470] The compounds of the present application may contain asymmetric or chiral centers and therefore exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of the present application and mixtures thereof, including racemic mixtures, are intended to form part of the present application. Furthermore, the present application encompasses all geometric and positional isomers. For example, if a compound of the present application incorporates a double bond or a fused ring, both the cis- and trans-forms and mixtures thereof are encompassed within the scope of the present application. Each compound disclosed herein includes all enantiomers consistent with the general structure of the compound. The compounds may be in racemic or pure enantiomeric form, or any other stereochemical form. Measurement results may reflect data collected from racemic forms, pure enantiomeric forms, or any other stereochemical form.

[0471] A carbon atom bonded to four different substituents is called a "chiral center." "Chiral isomer" means a compound having at least one chiral center. Compounds having more than one chiral center may exist as individual diastereomers or as a mixture of diastereomers, termed a "diastereomeric mixture." When one chiral center is present, a stereoisomer may be characterized by the absolute configuration (R or S) of said chiral center. Absolute configuration refers to the arrangement in space of the substituents attached to the chiral center. The substituents attached to the chiral center under consideration are ordered according to the Sequence Rules of Cahn, Ingold and Prelog (Cahn et al., Angew. Chem. Inter. Edit. 1966, 5, 385; Erratum 511; Cahn et al., Angew. Chem. 1966, 78, 413; Cahn and Ingold, J. Chem. Soc. 1951 (London), 612; Cahn et al., Experientia 1956, 12, 81; Cahn, J. Chem. Educ. 1964, 41, 116).

[0472] "Geometric isomers" refer to diastereomers that exist due to hindered rotation about a double bond. These configurations are distinguished in their names by the prefixes cis and trans or Z and E, which indicate that the groups are located on the same or opposite sides of the double bond in the molecule, based on the Cahn-Ingold-Prelog rules.

[0473] In another embodiment of the present application, the compounds of the present application (e.g., compounds of any formula disclosed herein or any individual compound) are enantiomers. In some embodiments, the compounds are (S)-enantiomers. In some embodiments, the compounds are (R)-enantiomers. In other embodiments, the compounds of the present application (e.g., compounds of any formula disclosed herein or any individual compound) may be (+) or (-) enantiomers. The compounds may contain more than one stereocenter.

[0474] In another embodiment of the present application, the compound of the present application (e.g., a compound of any formula disclosed herein or any single compound) is a diastereomer. In some embodiments, the compound is a cis diastereomer. In other embodiments, the compound is a trans diastereomer.

[0475] Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences via well-known methods (e.g., chromatography and / or fractional crystallization). Enantiomers can also be separated by converting the enantiomeric mixture to a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., a chiral auxiliary such as a chiral alcohol, Mosher's acid chloride, etc.), separating the diastereomers, and converting the individual diastereomers to the corresponding pure enantiomers (e.g., by hydrolysis). Enantiomers can also be separated using a chiral HPLC column.

[0476] It is also possible that the compounds of the present application may exist in different tautomeric forms, and all such forms are embraced within the scope of the present application. Further, for example, all keto-enol and imine-enamine forms of the compounds are included herein.

[0477] A "tautomer" is one of two or more structural isomers that exist in equilibrium and are readily converted from one isomeric form to another. This conversion results in the formal migration of a hydrogen atom accompanied by the switching of adjacent conjugated double bonds. Tautomers exist as mixtures of tautomeric series in solution. In solid form, one tautomer generally predominates. In solutions where tautomerization is possible, a chemical equilibrium of the tautomers is reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent, and pH. The concept of tautomers that are interconvertible by tautomerization is called tautomerism.

[0478] Of each type of possible tautomerism, two are commonly observed: keto-enol tautomerism, which involves the simultaneous migration of an electron and a hydrogen atom; and ring-chain tautomerism, which occurs when an aldehyde group (-CHO) in a sugar molecule reacts with one of the hydroxyl groups (-OH) in the same molecule to give a cyclic (ring-shaped) form, such as that exhibited by glucose.

[0479] Common tautomeric pairs are keto-enol, amide-nitrile, lactam-lactim, amide-imidic acid tautomers in heterocycles (e.g., in nucleobases such as guanine, thymine, and cytosine), amine-enamine, and enamine-imine.

[0480] The compounds of the present application can be converted to N-oxides by treatment with an oxidizing agent (e.g., 3-chloroperbenzoic acid (m-CPBA) and / or hydrogen peroxide) to provide other compounds of the present application. Thus, where valence and structure permit, all of the nitrogen-containing compounds shown and claimed are equivalent to the compounds shown and their N-oxide derivatives (N→O or N + -O -(which may be depicted as N-hydroxyl or N-alkoxy). Additionally, in other cases, nitrogen in the compounds of the present application may be converted to N-hydroxyl or N-alkoxy compounds. For example, N-hydroxyl compounds can be prepared by oxidizing the parent amine with an oxidizing agent (such as m-CPBA). Where valence and structure permit, all depicted and desired nitrogen-containing compounds are considered to include both the depicted compound and its N-hydroxyl (i.e., N—OH) and N-alkoxy (i.e., N—OR, where R is a substituted or unsubstituted C1-C6 alkyl group, C1-C6 alkenyl group, C1-C6 alkynyl group, 3- to 14-membered carbocyclic ring, or 3- to 14-membered heterocyclic ring) derivatives.

[0481] The term "prodrug," as used herein, means a compound that may be converted in vivo by metabolic means (eg, by hydrolysis) to a disclosed compound. Because prodrugs are known to enhance various desirable properties of drugs (e.g., solubility, bioavailability, manufacturing, etc.), the compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound) or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers thereof may be delivered in prodrug form. Accordingly, the present application is intended to encompass prodrugs of the compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound) or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers thereof, methods of delivering the same, and compositions containing the same. "Prodrugs" are intended to include any covalently bonded carriers that release the active parent drug of the present application in vivo when the prodrug is administered to a mammalian subject. Prodrugs are prepared by modifying functional groups present in the compound such that they are cleaved into the parent compound by conventional procedures or in vivo. Prodrugs include compounds of the present application in which a hydroxyl or amino group is bonded to a group that cleaves to form the free hydroxyl or free amino group, respectively, when the prodrug is administered to a mammalian subject. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohol and amine functional groups in the compounds of each formula described herein or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers thereof.

[0482] The terms "crystalline polymorph," "polymorph," or "crystalline form" refer to crystalline structures in which a compound (or a salt or solvate thereof) can crystallize in different crystal packing arrangements, all of which have the same elemental composition. Generally, different crystalline forms have different X-ray diffraction patterns, infrared spectra, melting points, density hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, crystallization rate, storage temperature, and other factors may cause one crystalline form to predominate.

[0483] As used herein, the term "analog" refers to a compound that is structurally similar to another compound but has a slightly different composition (e.g., one atom is replaced with an atom of a different element, or a particular functional group is present, or one functional group is replaced with another functional group). Thus, an analog is a compound that is similar or equivalent in function and appearance to the reference compound, but differs in structure or origin.

[0484] The present application further includes isotopically labeled compounds that are identical to those described in each formula set forth herein, but in practice, one or more atoms are replaced by an atom of an atomic mass or mass number different from the atomic mass or mass number most frequently found in nature. Examples of isotopes that can be incorporated into the compounds of the present application include isotopes of hydrogen, carbon, nitrogen, fluorine, e.g. 3 H, 11 C. 14 C. 2 H and 18 F is one example.

[0485] Any compound of the present application (e.g., a compound of any formula disclosed herein or any single compound) or pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof that contains said isotopes and / or other isotopes of other atoms is within the scope of the present application. Isotopically labeled compounds of the present application, e.g., compounds containing radioactive isotopes ( 3 H, 14 Compounds incorporating tritiated (i.e., C) can be used to measure drug and / or substrate tissue distribution. 3 H) and carbon-14 (i.e., 14 C) Isotopes can be used because they are easily prepared and detectable. 11 C and 18 F isotopes can be used in PET (positron emission tomography). PET can be used for brain imaging. Additionally, heavier isotopes, such as deuterium (i.e. 2H) can provide certain therapeutic advantages resulting from greater metabolic stability, such as increased biological half-life or reduced dosage requirements; therefore, in certain circumstances, it may be preferable to generally prepare isotopically labeled compounds of the present application (e.g., compounds of any formula disclosed herein or any individual compound) or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers thereof by carrying out the procedures disclosed in the solutions and / or examples herein by replacing the non-isotopically labeled reagent with a readily available isotopically labeled reagent. In one embodiment, the compounds of the present application (e.g., compounds of any formula disclosed herein or any individual compound) or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers thereof are not isotopically labeled.

[0486] As used herein, the terms "administer," "administering," or "administration" refer to the direct administration of a disclosed compound or a pharmaceutically acceptable salt or composition of said disclosed compound to a subject, or the administration of a prodrug, derivative, or analog of said compound or a pharmaceutically acceptable salt or composition of said compound that is capable of forming an equivalent amount of the active compound in the subject's body.

[0487] A "patient" or "subject" is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate such as a monkey, chimpanzee, baboon, or rhesus monkey. An "effective amount" or "therapeutically effective amount" when used in reference to a compound or pharmaceutical composition is an amount effective to treat or prevent a disease in a subject as described herein.

[0488] The term "treatment," with respect to a subject, refers to improving at least one symptom of the subject's disorder. Treatment includes curing, ameliorating, or at least partially alleviating the disorder. The compounds of the present application, or pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers thereof, can further be used to prevent a disease, condition, or disorder. As used herein, "preventing" or "prevent" refers to reducing or eliminating the onset of symptoms or complications of a disease, condition, or disorder.

[0489] Unless otherwise explained, the term "disorder" is used herein to mean, and is used interchangeably with, the terms disease, condition, or illness.

[0490] As used herein, the terms "HuR-mediated" disease or disorder or "HuR-involving" or "HuR-associated" disease or disorder refer to any disease or other deleterious condition in which HuR or a variant thereof is known to be involved. Accordingly, another embodiment of the present application relates to treating or lessening the severity of one or more diseases in which HuR or a variant thereof is known to be involved. Specifically, the present application relates to treating a disease or reducing the severity of a disorder selected from cell proliferative diseases or disorders, such as cancer (e.g., bladder cancer, brain cancer, breast cancer, colorectal cancer, cervical cancer, gastrointestinal cancer, genitourinary system cancer, glioma, head and neck cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, skin cancer, or testicular cancer) by using a compound of the present application (e.g., a compound of any formula disclosed herein or any compound alone) or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a composition according to the present application.

[0491] Methods for preparing compounds The compounds of the present application can be prepared by a variety of methods, including standard chemical methods. Suitable synthetic routes are set out in the Solution below. The compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound) can be prepared by methods known in the art of organic synthesis, as shown in the synthetic procedures section below. In the procedures described below, protecting groups for sensitive or reactive groups are used where necessary, as will be understood, in accordance with general or chemical principles. Protecting groups are manipulated according to standard methods of organic synthesis (T.W. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis", 3rd ed., Wiley, New York 1999). These groups are removed at a convenient stage in the compound synthesis, using methods apparent to those skilled in the art. The methods selected, as well as the reaction conditions and order of their execution, should be consistent with the preparation of the compounds of the present application.

[0492] Those skilled in the art will recognize whether a stereocenter exists in the compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound). Accordingly, the present application includes both possible stereoisomers (unless otherwise stated in the synthesis), including not only racemates but also individual enantiomers and / or diastereomers. When a compound is desired as a single enantiomer or diastereomer, it can be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. Isolation of the final product, intermediate, or starting material may be effected by any suitable method known in the art. See, for example, "Stereochemistry of Organic Compounds" by EL Eliel, SH Wilen, and LN Mander (Wiley-Interscience, 1994). The compounds described herein may be prepared from commercially available starting materials or may be synthesized using known organic, inorganic and / or enzymatic methods.

[0493] The compounds of the present application can be prepared by a variety of methods well known to those skilled in the art of organic synthesis. For example, the compounds of the present application may be synthesized by combining the methods described below with synthetic methods known in the art of synthetic organic chemistry or variations thereof as understood by those skilled in the art. Preferred methods include, but are not limited to, the methods described below. The compounds of the present application (i.e., compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound)) are synthesized by following the steps outlined in the examples, procedures, processes, and / or syntheses described herein (e.g., in the Examples). Starting materials are commercially available or prepared by reported literature or known processes as illustrated.

[0494] The mixtures of enantiomers, diastereomers, cis / trans isomers obtained by the above methods can be separated into their single components by chiral salt techniques, chromatography using normal phase, reverse phase or chiral columns (depending on the nature of the separation).

[0495] The present application relates to methods for synthesizing the compounds of the present application or their pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers or tautomers. The following procedures and descriptions show general routes for preparing the compounds of the present application. For example, the compounds of the present application can be synthesized by following the steps outlined in Procedure 1 or Procedure 2. Starting materials are commercially available or prepared by reported literature or known processes as shown.

[0496] General Method 1 JPEG2025539873000075.jpg92164

[0497] According to general procedure 1, compound I is converted through several steps to an intermediate such as a 6-halo-benzofuran-3-one or its azo counterpart II or a 7-halo-substituted-4-hydroxy-chroman-2-one or its azo counterpart III, which is then converted to a substituted acetate IV. Key intermediate VI is obtained by alkylation of IV (with or without isolation of V). Coupling of intermediate VI with an organoboron or tin reagent in the presence of an appropriate selected transition metal catalyst provides target compound VIII. Alternatively, intermediate VI can first be converted to its corresponding organoboron or tin reagent VII, followed by coupling with an appropriate substituted ArBr to provide target compound VIII.

[0498] Additional measures such as general measure 2 may also be used. General Method 2 JPEG2025539873000076.jpg57164

[0499] The mixtures of enantiomers, diastereomers, cis / trans isomers obtained by the above methods can be separated into their single components by chiral salt techniques, chromatography using normal phase, reverse phase or chiral columns (depending on the nature of the separation).

[0500] Analytical methods, materials and equipment Unless otherwise stated, reagents and solvents were used as obtained from the supplier. Proton nuclear magnetic resonance (NMR) spectra were obtained at 400 MHz on a Bruker or Varian spectrometer. Spectra are given in ppm (δ) and coupling constants J are reported in Hertz.

[0501] Abbreviations frequently used in the art or herein are as follows: JPEG2025539873000077.jpg7398 JPEG2025539873000078.jpg105131

[0502] Biological Testing The biological activity of the compounds of the present application can be assessed using methods and assays known in the art, exemplary methods of which are described in the Examples.

[0503] How to use the compound The compounds of the present application can be used to degrade HuR, and therefore can be used to treat or prevent diseases or disorders associated with HuR. One aspect of the present application relates to a method for treating, preventing, inhibiting, or eliminating a disease or disorder associated with HuR (e.g., overexpression or dysregulation of HuR), the method comprising administering to a subject in need of treatment for a disease or disorder associated with HuR an effective amount of a compound of the present application (e.g., a compound of any formula disclosed herein or any single compound) or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, or a pharmaceutical composition of a compound of the present application (e.g., a compound of any formula disclosed herein or any single compound).

[0504] Another aspect of the present application relates to a compound of the present application (e.g., a compound of any formula or any single compound disclosed herein), or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, for use in a method of treating or preventing a HuR-mediated disease or disorder. In another aspect, this application relates to a pharmaceutical composition of a compound of this application (e.g., a compound of any formula disclosed herein or any single compound) or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, for use in a method of treating or preventing a HuR-mediated disease or disorder.

[0505] Another aspect of the present application relates to the use of a compound of the present application (e.g., a compound of any formula disclosed herein or any single compound) or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof in the manufacture of a medicament for treating or preventing a HuR-mediated disease or disorder. In another aspect, this application relates to the use of a pharmaceutical composition of a compound of this application (e.g., a compound of any formula disclosed herein or any single compound) or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof in the manufacture of a medicament for treating or preventing a HuR-mediated disease or disorder.

[0506] The presently disclosed compounds can be administered in an effective amount to treat or prevent a disorder in a subject and / or to prevent its onset. In some embodiments, the disease or disorder is one in which there is overexpression or dysregulation of HuR. In some embodiments, the disease or disorder having overexpression or dysregulation of HuR is cancer.

[0507] In some embodiments, the cancer is adrenocortical carcinoma, AIDS-related cancer, AIDS-related lymphoma, anal cancer, anorectal cancer, anal canal cancer, appendiceal cancer, pediatric cerebellar astrocytoma, pediatric astrocytoma, basal cell tumor, basal cell tumor (non-melanoma), biliary tract cancer, extrahepatic bile duct cancer, intrahepatic bile duct cancer, bladder cancer, urethral cancer, bone tumor, osteosarcoma, and malignant fibrous histiocytoma, malignant brain tumor, brain tumor, brain stem glioma, cerebellar astrocytoma, cerebral astrocytoma / malignant neuroblastoma. Glioma, Ependymoma, Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, Visual Pathway and Hypothalamic Glioma, Breast Cancer, Bronchogenic Adenoma / Carcinoid, Carcinoid, Nervous System Cancer, Nervous System Lymphoma, Central Nervous System Cancer, Central Nervous System Lymphoma, Cervical Cancer, Childhood Cancer, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, Chronic Myelogenous Disease, Colon Cancer, Colorectal Cancer, Cutaneous T-Cell Lymphoma, Lymph Node Tumor, Mycosis Fungoides, Sezary Syndrome Syndrome), endometrial cancer, esophageal cancer, extracranial germ cell tumor, extragonadal germ cell tumor, eye cancer, intraocular melanoma, retinoblastoma, gallbladder cancer, gastric / stomach cancer, gastrointestinal carcinoid, gastrointestinal stromal tumor (GIST), germ cell tumor, ovarian tumor, gestational chorioglioma, head and neck cancer, hepatocellular (liver) cancer, Hodgkin lymphoma, hypopharyngeal cancer, eye tumor, pancreatic islet cell tumor (pancreatic endocrine gland), Kaposi's sarcoma, kidney cancer, renal cancer cancer, pharyngeal cancer, acute lymphocytic leukemia, acute myeloid leukemia, hairy cell leukemia, lip and oral cavity cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, non-Hodgkin's lymphoma, primary central nervous system lymphoma, Waldenstroem macroglobulinemia, melanoma, Merkel cell tumorcarcinoma), malignant mesothelioma, mesothelioma, metastatic squamous cell cervical cancer, oral cavity cancer, tongue cancer, multiple endocrine neoplasia syndrome, myelodysplastic syndrome, myelodysplastic / myeloproliferative disorders, multiple myeloma, nasopharyngeal carcinoma, neuroblastoma, oral cavity cancer, oropharyngeal cancer, ovarian cancer, epithelial ovarian cancer, low-grade ovarian tumors, pancreatic cancer, pancreatic islet cell tumors, paranasal sinus and nasal cavity cancer, parathyroid carcinoma, penile cancer, pharyngeal cancer, pheochromocytoma, pineoblastoma and supratentorial primitive neuroectodermal tumor, pituitary tumor, plasmacytoma, pleural sarcoma, prostate cancer, rectal cancer, renal pelvis and ureter, transitional cell carcinoma, rhabdomyosarcoma, salivary gland cancer, Ewing family of sarcomas tumors), soft tissue sarcoma, synovial sarcoma, uterine cancer, uterine sarcoma, skin cancer (non-melanoma), Merkel cell tumor, small intestine cancer, squamous cell carcinoma, testicular cancer, laryngeal and pharyngeal cancer, thymoma, thymic carcinoma, thyroid cancer, transitional cell carcinoma of the renal pelvis and ureter and other urinary tract, gestational choriocarcinoma, urethral cancer, endometrial cancer, uterine cancer, vaginal cancer, vulvar cancer, Wilms' tumor, lymphoma or diffuse large B-cell lymphoma (DLBCL).

[0508] In some embodiments, the cancer is bladder cancer, brain cancer, breast cancer, colorectal cancer, cervical cancer, gastrointestinal cancer, genitourinary system cancer, glioma, head and neck cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, skin cancer, or testicular cancer.

[0509] The compounds of the present application can be administered in a therapeutically effective amount in combination with a therapy or treatment regimen (e.g., non-drug therapy) using one or more therapeutic agents (drug combinations). For example, synergistic effects can be produced with other antiproliferative, anticancer, immunomodulatory, or anti-inflammatory substances. In some embodiments, the compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound) are administered in combination with an additional therapeutic agent selected from anti-inflammatory agents, immunomodulatory agents, chemotherapeutic agents, drugs for treating cardiovascular disease, drugs for treating liver disease, drugs for treating lung disease, drugs for treating kidney disease, drugs for treating eye disease, drugs for treating skin disease, antiviral agents, drugs for treating blood disorders, drugs for treating diabetes, and drugs for treating immune deficiencies. When the compounds of the present application are administered in combination with other therapies, the dose of the co-administered compound will naturally vary depending on the type of co-drug used, the specific drug used, the disease being treated, etc.

[0510] Combination therapy includes administering the subject compounds in further combination with other biologically active ingredients (e.g., but not limited to, anti-inflammatory agents, immunomodulators, chemotherapeutic agents, drugs for treating cardiovascular disease, drugs for treating liver disease, antiviral agents, drugs for treating blood disorders, drugs for treating diabetes, drugs for treating immune deficiencies, and drugs for treating pain) and non-drug therapies (e.g., but not limited to, surgery or radiation therapy). For example, the compounds of the present application can be preferably used in combination with other pharmaceutically active compounds that can enhance the effects of the compounds of the present application. The compounds of the present application can be administered simultaneously with other drug therapies or treatment methods (as a single formulation or in separate formulations), or sequentially. Generally, combination therapy contemplates the administration of two or more drugs in a single treatment cycle or treatment period.

[0511] Pharmaceutical Composition The present application further provides pharmaceutical compositions comprising a compound of the present application (e.g., a compound of any formula disclosed herein or any single compound) or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof in combination with at least one pharmaceutically acceptable excipient or carrier.

[0512] A "pharmaceutical composition" is a formulation containing a compound of the present application in a form suitable for administration to a subject. In one embodiment, the pharmaceutical composition is in bulk or unit dosage form. The unit dosage form may be in any of a variety of forms, including, for example, a capsule, an IV bag, a tablet, a single pump of an aerosol inhaler, or a vial. The content of the active ingredient (e.g., a formulation of the disclosed compound or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof) in a unit dose composition is an effective amount that varies depending on the specific treatment. As will be understood by those skilled in the art, routine variations in dosage may be required depending on the age and condition of the patient. The dosage further depends on the route of administration. Various routes are contemplated, including oral, pulmonary, enteral, parenteral, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalation, buccal, sublingual, intrapleural, intrathecal, nasal, etc. Dosage forms for topical or transdermal administration of the compounds of the present application include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. In one embodiment, the active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers, or propellants.

[0513] As used herein, the term "pharmaceutically acceptable" refers to compounds, materials, compositions, carriers, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, and are commensurate with a reasonable benefit / risk ratio.

[0514] A "pharmaceutically acceptable excipient" refers to an excipient that is generally safe, non-toxic, and without biologically or otherwise undesirable effects for preparing pharmaceutical compositions, and includes excipients that are acceptable for use in veterinary medicine and human medicine. As used in the specification and claims, "pharmaceutically acceptable excipient" includes both one and more than one such excipient.

[0515] The pharmaceutical compositions of the present application are prepared to be compatible with their intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), and transmucosal administration. Solutions or suspensions for parenteral, intradermal, or subcutaneous use may contain, as ingredients, a sterile diluent such as water for injection, saline, fixed oils, polyethylene glycol, glycerol, propylene glycol, or other synthetic solvents; antibacterial agents such as benzyl alcohol or methylparabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates, or phosphates; and agents for adjusting tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases (e.g., hydrochloric acid or sodium hydroxide). Parenteral formulations can be enclosed in glass or plastic ampoules, disposable syringes, or multiple-dose vials.

[0516] The compound or pharmaceutical composition of the present application can be administered to a subject by many well-known methods currently used in chemotherapy treatment. The selected dose should be sufficient to constitute an effective treatment, but not so high as to cause unacceptable side effects. The patient's disease state and health status should be carefully monitored during and for a reasonable period after treatment.

[0517] As used herein, the term "therapeutically effective amount" refers to an amount of an agent that treats, ameliorates, or prevents an identified disease or condition, or that exhibits a detectable therapeutic or modulating effect. The effect can be detected according to any measurement method known in the art. The precise effective amount to be used in a subject will depend on the subject's weight, size, and health, the nature and extent of the condition, and the treatment or combination of treatments selected to be administered. The therapeutically effective amount for a given situation can be determined by routine experimentation that is within the skill and judgment of the clinician. In one embodiment, the disease or disorder is a disease or disorder described herein.

[0518] For any compound, the therapeutically effective amount can be estimated initially by cell culture assays (e.g., tumor cells) or animal models (commonly rats, mice, rabbits, dogs, or pigs). Animal models can also be used to determine appropriate concentration ranges and routes of administration. This information can then be used to determine useful doses and routes of administration in humans. Therapeutic / prophylactic efficacy and toxicity can be assessed by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., ED 50 (therapeutic effective dose in 50% of the population) and LD 50 The dose ratio between toxic and therapeutic effects is the therapeutic index, and the LD 50 / ED 50 Pharmaceutical compositions that exhibit large therapeutic indices are preferred. The dosage may vary within this range depending upon the dosage form used, sensitivity of the patient, and the route of administration.

[0519] Dosage and administration are adjusted to maintain sufficient levels of the active agent or the desired effect. Factors to be considered include the severity of the disease state, the subject's general health, the subject's age, weight, and sex, diet, time and frequency of administration, drug combinations, reaction sensitivities, and tolerance / response to therapy. Long-acting pharmaceutical compositions can be administered every 3-4 days, every week, or every other week, depending on the half-life and clearance rate of the particular formulation.

[0520] Pharmaceutical compositions containing the active compounds of the present application (i.e., compounds of the present application (e.g., compounds of any formula disclosed herein or any single compound)) can be manufactured by generally known methods, such as conventional mixing, dissolving, granulating, dragee-making, pulverizing, emulsifying, encapsulating, embedding, or lyophilizing processes. Pharmaceutical compositions can be formulated in a conventional manner using one or more pharmaceutically acceptable carriers, including excipients and / or auxiliaries that facilitate processing of the active compound into pharmaceutically usable preparations. Of course, appropriate formulations depend upon the chosen route of administration.

[0521] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL TM (BASF, Parsippany, NJ) or phosphate-buffered saline (PBS). In all cases, the composition must be sterile and should be fluid in an easily syringable amount. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. Prevention of the action of microorganisms may be achieved by various antibacterial and antifungal agents (e.g., parahydroxybenzoates, chlorobutanol, phenol, ascorbic acid, thimerosal). Often, preferred compositions include isotonic agents, for example, sugars, polyalcohols (mannitol, sorbitol, and the like), and sodium chloride. Prolonged absorption of the injectable compositions can be achieved by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0522] Sterile injection solution can be prepared by incorporating the required amount of active compound into a suitable solvent with the above-listed ingredients or a combination thereof, and then filter sterilization as needed.Generally, dispersion is prepared by incorporating active compound into a sterile vehicle that contains a basic dispersion medium and the other ingredients listed above that are required.For the preparation of sterile powder for sterile injection solution, the preparation method is vacuum drying or freeze-drying, which method obtains the powder of active ingredient and any other desired ingredients from its previously sterile-filtered solution.

[0523] Oral compositions generally contain an inert diluent or an edible pharmaceutically acceptable carrier. They may be enclosed in gelatin capsules or made into tablets. For oral therapeutic administration, the active compound may be combined with an excipient and used in the form of tablets, lozenges or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, where the compound in the fluid carrier is taken orally and swished in the mouth, expectorated, or swallowed. Pharmaceutically compatible binding agents and / or adjuvant materials may also be included as part of the composition. The tablets, pills, capsules, troches and the like may contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, tragacanth or gelatin; a filler such as starch or lactose; a disintegrating agent such as alginic acid, Primogel or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silica; a sweetener such as sucrose or saccharin; or a flavoring such as mint, methyl salicylate or orange flavoring.

[0524] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant (e.g., a gas such as carbon dioxide) or a nebulizer. Systemic administration can also be carried out via transmucosal or transdermal routes. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art and include, for example, detergents, bile salts, and fusidic acid derivatives for transmucosal administration. Transmucosal administration can also be achieved by using nasal sprays or suppositories. For transdermal administration, the active compound is formulated into ointments, salves, gels, or creams commonly known in the art.

[0525] The active compounds can be prepared with pharmaceutically acceptable carriers that protect the compound from rapid elimination from the body, such as controlled-release formulations, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparing such formulations will be clear to those of ordinary skill in the art. Materials are commercially available from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including infected-cell-targeted liposomes bearing monoclonal antibodies against viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared by methods known to those of ordinary skill in the art, such as those described in U.S. Pat. No. 4,522,811.

[0526] For ease of administration and uniformity of dosage, it is particularly advantageous to formulate oral and parenteral compositions in dosage unit form.As used herein, dosage unit form refers to a physically separate unit suitable as a unit dose for the treatment subject, each unit containing a predetermined amount of active compound calculated to produce desired therapeutic effect in association with required pharmaceutical carrier.The specification for dosage unit form of this application is determined by and directly depends on the unique characteristics of active compound and the specific therapeutic effect to be achieved.

[0527] For therapeutic applications, the dosage of the pharmaceutical composition used for each application will vary depending on the drug, the age, weight, and clinical condition of the patient, the experience and judgment of the clinician or practitioner administering the treatment, and other factors that may influence the selected dosage. The dosage range may be from about 0.01 mg / kg to about 5000 mg / kg per day. An effective amount of a drug is an amount that provides an objectively identifiable improvement as noted by a clinician or other qualified observer. As used herein, the term "dosage-effective regimen" refers to the amount of active compound that produces the desired biological effect in a subject or cell. The pharmaceutical compositions may be included in a container, pack, or dispenser together with instructions for administration.

[0528] As used herein, "pharmaceutically acceptable salts" refers to derivatives of the compounds of the present application in which the parent compound has been modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues (such as amines), alkali metal or organic salts of acidic residues (such as carboxylic acids), etc. Pharmaceutically acceptable salts include the conventional non-toxic salts or quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, conventional non-toxic salts include 2-acetoxybenzoic acid, 2-hydroxyethanesulfonic acid, acetic acid, ascorbic acid, benzenesulfonic acid, benzoic acid, bicarbonate, carbonic acid, citric acid, ethylenediaminetetraacetic acid, ethanedisulfonic acid, 1,2-ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, glycolyl-p-aminobenzoic acid, hexylresorcinol, hydrabamic acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, hydroxymaleic acid, hydroxynaphthoic acid, isethionic acid, lactic acid, lactobionic acid, These include, but are not limited to, salts derived from inorganic and organic acids selected from the group consisting of laurylsulfonic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, naphthalenesulfonic acid, nitric acid, oxalic acid, pamoic acid, pantothenic acid, phenylacetic acid, phosphoric acid, polygalacturonic acid, propionic acid, salicylic acid, stearic acid, subacetic acid, succinic acid, sulfamic acid, sulfanilic acid, sulfuric acid, tannic acid, tartaric acid, toluenesulfonic acid, and common amino acids such as glycine, alanine, phenylalanine, and arginine.

[0529] Other examples of pharmaceutically acceptable salts include hexanoic acid, cyclopentanepropanoic acid, pyruvic acid, malonic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo-[2.2.2]-oct-2-ene-1-carboxylic acid, 3-phenylpropanoic acid, pivalic acid, tert-butylmuconic acid, etc. The present application also encompasses salts formed when an acidic proton present in the parent compound is replaced with a metal ion (e.g., an alkali metal ion, an alkaline earth metal ion, or an aluminum ion) or when coordinated with an organic base (ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, etc.).

[0530] It will be understood that all references to pharmaceutically acceptable salts include solvent addition forms (solvates) or crystal forms (polymorphs) of the same salt as defined herein. The compounds of the present application may also be prepared as esters, e.g., pharmaceutically acceptable esters. For example, a carboxylic acid functional group in a compound may be converted to its corresponding ester, e.g., a methyl, ethyl, or other ester. Furthermore, an alcohol group in a compound may be converted to its corresponding ester, e.g., an acetate, propionate, or other ester.

[0531] The compounds of the present application may also be prepared as prodrugs, e.g., pharmaceutically acceptable prodrugs. The terms "pro-drug" and "prodrug" are used interchangeably herein and refer to any compound that releases an active parent drug in vivo. Because prodrugs are known to enhance many desirable properties of drugs (e.g., solubility, bioavailability, manufacturing, etc.), the compounds of the present application may be delivered in prodrug form. Accordingly, the present application is intended to encompass prodrugs of the compounds protected by the present claims, methods of delivering such prodrugs, and compositions containing such prodrugs. "Prodrugs" are intended to include any covalently bonded carriers that release the active parent drug of the present application in vivo when the prodrug is administered to a subject. The prodrugs of the present application are prepared by modifying functional groups present in the compound such that they are cleaved into the parent compound by conventional procedures or in vivo. Prodrugs include compounds of the present application in which a hydroxyl, amino, sulfhydryl, carboxyl, or carbonyl is bonded to any group that is cleavable in vivo to form a free hydroxyl, free amino, free sulfhydryl, free carboxyl, or free carbonyl, respectively.

[0532] Examples of prodrugs include, but are not limited to, esters (e.g., acetate, dialkylaminoacetate, formate, phosphate, sulfate, and benzoate derivatives) and carbamates (e.g., dimethylaminocarbonyl) of hydroxyl functional groups in the compounds of the present application; esters (e.g., ethyl ester, morpholine ethanol ester); N-acyl derivatives (e.g., N-acetyl) of carboxyl functional groups; N-Mannich bases, Schiff bases, and enamine ketones of amino functional groups; and oxime, acetal, ketal, and enol esters of ketone and aldehyde functional groups in the compounds of the present application. See Bundegaard, H., Design of Prodrugs, pp. 1-92, Elsevier, New York-Oxford (1985).

[0533] The compound or its pharmaceutically acceptable salt, tautomer, prodrug, solvate, metabolite, polymorph, analog, or derivative may be administered orally, intranasally, transdermally, pulmonary, inhalation, buccal, sublingually, intraperitoneally, subcutaneously, intramuscularly, intravenously, enterally, intrapleurally, intrathecally, and parenterally. In one embodiment, the compound or its pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer is administered orally. Those skilled in the art will recognize the advantages of certain routes of administration.

[0534] Dosage regimens utilizing the compounds are selected according to a variety of factors, including the type, species, age, weight, sex, and medical condition of the patient, the severity of the condition being treated, the route of administration, the patient's renal and hepatic function, and the particular compound or its pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer used. A clinician or veterinarian of ordinary skill can readily determine and prescribe the effective amount of the drug required to prevent, counter, or inhibit the progress of the condition.

[0535] Techniques for formulating and administering the compounds disclosed herein can be found in Remington: The Science and Practice of Pharmacy, 19th Edition, Mack Publishing Co., Easton, PA (1995). In embodiments, the compounds described herein and their pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers are used in drug formulations in combination with a pharmaceutically acceptable carrier or diluent. Suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions. The compound or its pharmaceutically acceptable salts, solvates, prodrugs, stereoisomers, or tautomers are present in such pharmaceutical compositions in an amount sufficient to provide the desired dosage within the range described herein.

[0536] Unless otherwise stated, all percentages and ratios used herein are by weight. Other features and advantages of the present application will be apparent from the different examples. The examples provided illustrate different assemblies and methods useful in practicing the present application. These examples do not limit the claimed application. Based on the present application, one skilled in the art will be able to identify and adopt other assemblies and methods that can be used to practice the present application. [Example]

[0537] The present application is further illustrated by the following examples and synthetic procedures, which should not be construed as limiting the scope or spirit of the present application to the particular sequences described herein. It should be understood that these examples are provided to illustrate particular embodiments and are therefore not intended to limit the scope of the present application. Moreover, those skilled in the art may envision various other embodiments, modifications, and equivalents without departing from the spirit of the present application and / or the scope of the appended claims.

[0538] Part I: Synthesis of intermediates Synthesis of 3-(6-bromobenzofuran-3-yl)piperidinyl-2,6-dione (Int 1-A) and 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-yl)piperidinyl-2,6-dione (Int 1-A and Int 1-B) JPEG2025539873000079.jpg61164

[0539] Step 1: Under N2, to a solution of 1-(4-bromo-2-hydroxy-phenyl)ethanone (10 g, 46.50 mmol, 1 eq) in CHCl3 (250 mL) and ethyl acetate (250 mL) was added CuBr2 (25.97 g, 116.26 mmol, 5.44 mL, 2.5 eq). The mixture was stirred at 100 °C for 16 h. The mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The reaction mixture was filtered. The filtrate was directly concentrated to give crude 2-bromo-1-(4-bromo-2-hydroxy-phenyl)ethanone 1.1 (45 g, 153.09 mmol, 82.30% yield) as a yellow solid.

[0540] Step 2: To a solution of 1.1 (45 g, 153.09 mmol, 1 eq) in DCM (500 mL) under N at 0 °C, EtN (18.59 g, 183.71 mmol, 25.57 mL, 1.2 eq) was added. The mixture was stirred at 20 °C for 2 h. The mixture was poured into water and extracted with DCM. The combined organic layers were washed with brine, dried over NaSO, filtered, and concentrated. The crude compound 6-bromobenzofuran-3-one 1.2 (44 g, 103.27 mmol, 67.46% yield, 50% purity) was obtained as a red solid.

[0541] Step 3: To a solution of 1.2 (44 g, 103.27 mmol, 50% purity, 1 eq) in toluene (500 mL) under N2, 2-(triphenyl-λ5-phosphanylidene)acetate (43.17 g, 123.93 mmol, 1.2 eq) was added. The mixture was stirred at 120 °C for 16 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography to give 2-(6-bromobenzofuran-3-yl)acetate 1.3 (6 g, 21.19 mmol, 20.52% yield) as a white solid.

[0542] Step 4: To a solution of 1.3 (5 g, 12.36 mmol, 70% purity, 1 eq) in DMF (10 mL) under N2 at 0 °C, t-BuOK (1.53 g, 13.60 mmol, 1.1 eq) and prop-2-enamide (1.76 g, 24.72 mmol, 1.71 mL, 2 eq) were added. The mixture was stirred at 0 °C for 2 h. The mixture was poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried, filtered, and concentrated to give a residue. The residue was purified by column chromatography to give Int 1-A (3.3 g, 10.71 mmol, 86.63% yield) as a yellow solid. 1 H NMR (400MHz, d6-DMSO) δ 10.91 (s, 1H), 7.94 (s, 1H), 7.89 (d, J = 1.2Hz, 1H), 7.57 (d, J = 8.0Hz, 1H), 7.42 (dd, J = 2.0, 8.0Hz, 1H), 4.15 (dd, J = 4.8, 12.0Hz, 1H), 2.79 - 2.72 (m, 1H), 2.63 - 2.54 (m, 1H), 2.37 - 2.25 (m, 1H), 2.11 (m, 1H). MS:(ESI) m / z C 13 H 10 BrNO3[M+H] + Calculated value: 307.9, measured value: 307.9.

[0543] Step 5: A solution of Int 1-A (500 mg, 1.62 mmol, 1 eq), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (494.48 mg, 1.95 mmol, 1.2 eq), and KOAc (477.77 mg, 4.87 mmol, 3 eq) in dioxane (10 mL) and HO (2 mL) was purged with N three times, followed by the addition of Pd(dppf)Cl (66.26 mg, 81.14 μmol, 0.05 eq). The mixture was stirred under N at 100 °C for 16 h. The mixture was poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried, filtered, and concentrated. The residue was purified by column chromatography to give 3-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-yl]piperidinyl-2,6-dione Int 1-B (420 mg, 1.18 mmol, 72.87% yield). LCMS: C 19 H 22 Calculated value for BNO5: 355.2, Measured value: No desired MS signal. 1 H NMR (400MHz, DMSO-d6) δ 10.91 (s, 1H), 7.98 (s, 1H), 7.78 (s, 1H), 7.60 (d, J = 8.0Hz, 1H), 7.54 (d, J = 7.6Hz, 1H),, 4.12-4.21 (m, 1H), 2.69-2.82 (m, 1H), 2.55-2.61 (m, 1H), 2.27-2.36 (m, 1H), 2.06-2.20 (m, 1H), 1.31 (s, 12H).

[0544] Synthesis of 3-(6-bromo-5-fluorobenzofuran-3-yl)piperidinyl-2,6-dione (Int 2-A) JPEG2025539873000080.jpg55164

[0545] Step 1: To a solution of 3-bromo-4-fluorophenol (50 g, 261.78 mmol, 1 eq) in DCM (500 mL) was added acetyl ethyl ester (32.07 g, 314.14 mmol, 29.42 mL, 1.2 eq) and pyridyl (51.77 g, 654.46 mmol, 52.82 mL, 2.5 eq). The mixture was stirred at 20 °C for 16 h. The reaction mixture was adjusted to pH = 3 with aqueous AcOH (1 M). The resulting mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give 2.1 (61 g, 261.76 mmol, 99.99% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ 7.34 (dd, J = 2.8, 5.6Hz, 1H), 7.17 - 7.11 (m, 1H), 7.04 (m, 1H), 2.30 (s, 3H).

[0546] Step 2: At 0 °C, TfOH (183.54 g, 1.22 mol, 107.97 mL, 5 eq) was added to a solution of (3-bromo-4-fluoro-phenyl)acetate (57 g, 244.60 mmol, 1 eq). The mixture was stirred at 60 °C for 3.5 h. The mixture was poured into cold water and extracted with CHCl. ​​The combined organic phases were washed with water, dried over anhydrous NaSO, filtered and concentrated. A yellow solid, 1-(4-bromo-5-fluoro-2-hydroxy-phenyl)ethanone (2.2, 50 g, 214.56 mmol, 87.72% yield), was obtained. 1 H NMR (400MHz, d6-DMSO) δ 11.64 (br d, J= 1.6Hz, 1H), 7.79 (d, J= 9.2Hz, 1H), 7.33 (d, J= 6.0Hz, 1H), 2.61 (s, 3H).

[0547] Step 3: To a solution of 1-(4-bromo-5-fluoro-2-hydroxy-phenyl)ethanone (43 g, 184.52 mmol, 1 eq) in CHCl3 (250 mL) and EtOAc (250 mL) under N2, CuBr2 (103.03 g, 461.31 mmol, 21.60 mL, 2.5 eq) was added. The mixture was stirred at 100 °C for 16 h. The mixture was filtered and the filtrate was concentrated. A red solid, 2-bromo-1-(4-bromo-5-fluoro-2-hydroxy-phenyl)ethanone (2.3, 65 g, crude) was obtained. 1 H NMR (400MHz, d6-DMSO) δ 11.33 (s, 1H), 7.67 (d, J = 9.2Hz, 1H), 7.31 (d, J = 5.6Hz, 1H), 4.85 (s, 2H).

[0548] Step 4: To a solution of 2-bromo-1-(4-bromo-5-fluoro-2-hydroxy-phenyl)ethanone (25 g, 80.15 mmol, 1 eq) in DCM (250 mL) was added TEA (9.73 g, 96.18 mmol, 13.39 mL, 1.2 eq) under N atmosphere at 0 °C. The mixture was stirred at 20 °C for 2 h, poured into water and extracted with DCM. The combined organic layers were washed with brine, dried over Na SO , filtered and concentrated to give 6-bromo-5-fluoro-benzofuran-3-one (2.4, 18.5 g, 80.08 mmol, 99.92% yield) as a red solid. 1 H NMR (400MHz, d6-DMSO) δ 7.83 (d, J=4.8Hz, 1H), 7.67 (d, J=7.2Hz, 1H), 4.87 (s, 2H).

[0549] Step 5: Under N2, to a solution of 6-bromo-5-fluoro-benzofuran-3-one (6 g, 15.58 mmol, 60% purity, 1 eq) in toluene (40 mL) was added 2-(triphenyl-λ5-phosphanylidene)acetate (6.51 g, 18.70 mmol, 1.2 eq). The mixture was stirred at 130 °C for 16 h. The reaction mixture was directly concentrated in vacuo. The residue was purified by flash silica gel chromatography. A yellow solid, 2-(6-bromo-5-fluoro-benzofuran-3-yl)acetate (2.5 g, 6.64 mmol, 42.62% yield), was obtained. 1 H NMR (400MHz, d6-DMSO) δ 8.04 - 8.00 (m, 2H), 7.62 (d, J =8.8Hz, 1H), 4.11 (q, J =7.2Hz, 2H), 3.79 (s, 2H), 1.19 (t, J =7.2Hz, 3H)

[0550] Step 6: To a solution of 2-(6-bromo-5-fluoro-benzofuran-3-yl)acetate (5 g, 16.61 mmol, 1 eq) in DMF (50 mL) was added t-BuOK (2.05 g, 18.27 mmol, 1.1 eq) over 0.5 h at 0 °C under N2. Then, at 0 °C, prop-2-enamide (2.36 g, 33.21 mmol, 2.29 mL, 2 eq) was added dropwise. The mixture was stirred at 0 °C for 1.5 h. The mixture was poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by 20% ethanol with PE:EA = 10:1. ℃ for 1 hour to give Int 2-A (2.8 g, 8.59 mmol, 51.71% yield) as a yellow solid. 1H NMR (400MHz, d6-DMSO) δ 10.92 (s, 1H), 8.06 (d, J=5.6Hz, 1H), 8.03 (s, 1H), 7.68 (d, J=8.8Hz, 1H), 4.13 (dd, J=4.8, 12.4Hz, 1H), 2.77 - 2.67 (m, 1H), 2.57 - 2.53 (m, 1H), 2.42 - 2.30 (m, 1H), 2.13 - 2.05 (m, 1H).

[0551] Synthesis of 3-[5...

Claims

1. A compound of formula I, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, X is N or CR X and Y 4 is N or CR 4 and Y 5 is N or CR 5 and Y 7 is N or CR 7 where Y 4 , Y 5 and Y 7 at most one of is N, R X , R 4 , R 5 and R 7 are each independently H, C 1 -C 6 Alkyl group, C 1 -C 6 is a haloalkyl group or a halogen, m is 0, 1, 2, 3 or 4; Each R 3 is independent, C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 haloalkoxy group, OH or halogen; R N is H or C 1 -C 6 is an alkyl group, R 6 is R 6 ' or (CH 2 ) 1-3 -R 6 ' and R 6 C' is a heterocyclyl group containing a 4- to 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O and S; 6 -C 10 an aryl group, a heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, or a fused-ring heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S and optionally 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclyl group, aryl group, heteroaryl group, or fused-ring heteroaryl group optionally comprises one or more R 61 is replaced by, and Each R 61 is independent, C 1 -C 6 alkyl group, which optionally independently comprises 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, halogen, OH, amino group, C 6 -C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, OH, amino group, NO 2 , halogen, CN, ═O, C(O)R 62 、C(O)OR 62 、C(O)NR 63 R 64 、 L-C 6 -C 10 an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, L-C 3 -C 6 and one or more groups selected from the group consisting of carbocyclyl groups or L-heterocyclyl groups containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, wherein the aryl, heteroaryl, carbocyclyl or heterocyclyl groups are optionally and independently selected from: C 1 -C 6 Alkyl group, C 1 -C 6 haloalkyl group, optionally halogen, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 substituted with one or more substituents selected from alkoxy groups (CH 2 ) 0-3 -C 1 -C 6 Alkoxy group, O—(CH 2 ) 0-3 -C 3 -C 6 a carbocyclyl group, an O—(CH ) group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heterocyclyl group, O—(CH 2 ) 0-3 -C 6 -C 10 aryl groups, O—(CH ) groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heteroaryl group, C 1 -C 6 alkylamino groups, wherein the alkyl groups are optionally substituted with one or more groups selected from the group consisting of 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, di-C 1 -C 6 alkylamino groups, wherein each alkyl group is optionally and independently substituted with one or more substituents selected from the group consisting of: 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, OH, amino group, NO 2 , halogen, CN, ═O, N(R N ) C(O)R 62 , N(R N )C(O)OR 62 , N(R N ) S (O) 2 -C 1 -C 6 alkyl group, N(R N ) S (O) 2 -C 3 -C 6 Cycloalkyl group, S(O) 1-2 NH (C 1 -C 6 alkyl group), S(O) 1-2 N (C 1 -C 6 alkyl group) 2 , S(O) 0-2 -C 1 -C 6 Alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 ) 2 , C 3 -C 6 a carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 6 -C 10 and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein two of the substituents together with the carbon atoms to which they are attached form a C 5 -C 6 A carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S can be formed, and the carbocyclyl or heterocyclyl group can optionally be one or more R A wherein one or more hydrogen atoms in said substituents may be replaced by one or more deuterium atoms; Among them, L is absent or O, (CR L1 R L2 ) n , O-(CR L1 R L2 ) n , (CR L1 R L2 ) n -O and S(O) 2 is a linker selected from Each R L1 and each R L2 are independently H, CH 3 , C.H. 2 CH 3 or CH(CH 3 ) 2 or R L1 and R L2 together with the carbon atoms to which they are attached, form C(O), C 3 -C 6 can form a cycloalkyl group or a heterocyclyl group containing a 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S; R L1 and R L2 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms, Each R A are independently halogen, OH, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Alkylamino group or di-C 1 -C 6 an alkylamino group, and n is 1, 2 or 3; or Two R's 61 together with the carbon atoms to which they are attached form C 4 -C 10 a carbocyclyl group, a heterocyclyl group containing one 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O and S, a spiroheterocyclyl group or a fused heterocyclyl group containing two 4- to 6-membered rings each containing 1 to 4 heteroatoms selected from N, O and S, or C 6 and aryl groups, wherein the carbocyclyl, heterocyclyl, spiroheterocyclyl or fused heterocyclyl or aryl groups are optionally independently selected from the group consisting of: 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 substituted with one or more groups selected from the group consisting of alkylamino, OH, amino, halogen, CN, and ═O; Each R 62 , each R 63 and each R 64 are independently H, C 1 -C 6 Alkyl group or C 1 -C 6 A compound that is a haloalkyl group.

2. A compound of any one of formulas II to IX: or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof.

3. a compound of formula II or formula III, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof.

4. R X The compound according to any one of claims 1 to 3, wherein is H.

5. The compound according to any one of claims 1 to 4, wherein m is 0.

6. R N The compound of any one of claims 1 to 5, wherein is H.

7. R 6 (CH 2 ) 1-3 -R 6 7. The compound according to any one of claims 1 to 6, wherein

8. R 6 is R 6 7. The compound according to any one of claims 1 to 6, wherein

9. R 6 ' is a heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, or a fused-ring heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, and a 5- or 6-membered ring containing optionally 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group or fused-ring heteroaryl group optionally comprises one or more R 61 The compound of any one of claims 1 to 8, substituted with

10. R 6 ' is a heteroaryl group comprising a 5-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O and S, said heteroaryl group optionally containing one or more R 61 The compound of any one of claims 1 to 9, substituted with

11. R 6 ' is a fused ring heteroaryl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, and a 5- or 6-membered ring optionally containing 1 to 4 heteroatoms selected from N, O, and S, said fused ring heteroaryl group optionally containing one or more R 61 The compound of any one of claims 1 to 9, substituted with

12. R 6 ' is a fused ring heteroaryl group comprising a 5-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, and a 5- or 6-membered ring optionally containing 1 to 4 heteroatoms selected from N, O, and S, said fused ring heteroaryl group optionally containing one or more R 61 12. The compound of any one of claims 1 to 9 and 11, substituted with:

13. R 6 ' is a fused ring heteroaryl group comprising a 5-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O, and S, and a 6-membered ring optionally containing 1 to 4 heteroatoms selected from N, O, and S, said fused ring heteroaryl group optionally containing one or more R 61 13. The compound of any one of claims 1 to 9, 11 and 12, substituted with:

14. R 6 ' optionally represents one or more R 61 C substituted with 6 -C 10 The compound according to any one of claims 1 to 9, which is an aryl group.

15. R 6 ' is a heterocyclyl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O and S, said heterocyclyl group optionally containing one or more R 61 The compound of any one of claims 1 to 9, substituted with

16. R 6 ' is a heterocyclyl group comprising a 5- or 6-membered ring containing one nitrogen atom and optionally 1 to 3 additional heteroatoms selected from N, O and S, said heterocyclyl group optionally containing one or more R 61 and the heterocyclyl group is fully saturated or partially saturated.

17. At least one R 61 teeth, C 1 -C 6 alkyl group, which optionally independently comprises 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, halogen, OH, amino group, C 6 -C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, OH, amino group, NO 2 , halogen, CN, ═O, C(O)R 62 、C(O)OR 62 、C(O)NR 63 R 64 、 L-C 6 -C 10 an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, L-C 3 -C 6 17. The compound of any one of claims 1 to 16, substituted with one or more groups selected from the group consisting of carbocyclyl groups or L-heterocyclyl groups containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, wherein the aryl, heteroaryl, carbocyclyl or heterocyclyl groups are optionally substituted.

18. At least one R 61 teeth, C 1 -C 6 alkyl group, which optionally independently comprises 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, halogen, OH, amino group, C 6 -C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, OH, amino group, NO 2 , halogen, CN, ═O, C(O)R 62 , C(O)OR 62 , or C(O)NR 63 R 64 18. The compound of any one of claims 1 to 17, substituted with one or more groups selected from the group consisting of:

19. At least one R 61 is L-C 6 -C 10 an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, L-C 3 -C 6 18. The compound according to any one of claims 1 to 17, which is a carbocyclyl group or an L-heterocyclyl group containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, wherein the aryl, heteroaryl, carbocyclyl or heterocyclyl group is optionally substituted.

20. At least one R 61 is L-C 6 -C 10 18. The compound according to any one of claims 1 to 17, which is an aryl group or an L-heteroaryl group comprising one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, wherein the aryl or heteroaryl group is optionally substituted.

21. R 6 ' is two or more R 61 and at least two R 61 together with the carbon atoms to which they are attached form C 4 -C 10 a carbocyclyl group, a heterocyclyl group containing one 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O and S, a spiroheterocyclyl group or a fused heterocyclyl group containing two 4- to 6-membered rings each containing 1 to 4 heteroatoms selected from N, O and S, or C 6 and optionally independently form an aryl group, wherein the carbocyclyl group, heterocyclyl group, spiroheterocyclyl group, or fused heterocyclyl group, or aryl group, is selected from the group consisting of: 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 18. The compound of any one of claims 1 to 17, substituted with one or more groups selected from the group consisting of alkylamino groups, OH, amino groups, halogens, CN and =0.

22. R 5 The compound of any one of claims 1 to 21, wherein is H.

23. R 5 The compound of any one of claims 1 to 21, wherein is halogen.

24. R 5 is F.

25. R 5 is C 1 -C 6 Alkyl group or C 1 -C 6 The compound of any one of claims 1 to 21, which is a haloalkyl group.

26. R 4 The compound of any one of claims 1 to 25, wherein is H.

27. R 4 The compound of any one of claims 1 to 25, wherein is a halogen.

28. R 4 is F.

29. R 4 is C 1 -C 6 Alkyl group or C 1 -C 6 The compound of any one of claims 1 to 25, which is a haloalkyl group.

30. R 7 The compound of any one of claims 1 to 29, wherein is H.

31. R 7 The compound of any one of claims 1 to 29, wherein is a halogen.

32. R 7 is F.

33. R 7 is C 1 -C 6 Alkyl group or C 1 -C 6 The compound of any one of claims 1 to 29, which is a haloalkyl group.

34. A compound of formula Ia, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, wherein: X is N or CR X and R X , R 4 , R 5 and R 7 are each independently H, C 1 -C 6 Alkyl group, C 1 -C 6 is a haloalkyl group or a halogen, R 61 'teeth H. C 1 -C 6 alkyl group, which optionally independently comprises 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, halogen, OH, amino group, C 6 -C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C- 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, OH, amino group, NO 2 , halogen, CN, C(O)R 62 , C(O)OR 62 , or C(O)NR 63 R 64 and is substituted with one or more groups selected from the group consisting of R 62 , R 63 and R 64 are each independently H, C 1 -C 6 Alkyl group or C 1 -C 6 is a haloalkyl group, R L1 and each R L2 are each independently H, CH 3 , C.H. 2 CH 3 or CH(CH 3 ) 2 or R L1 and R L2 together with the carbon atoms to which they are attached, form C(O), C 3 -C 6 A cycloalkyl group or a heterocyclyl group containing a 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S can be formed, of which R L1 and R L2 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms, X 1 is N or CR X1 and X 2 is N or CR X2 and X 3 is N or CR X3 and X 4 is N or CR X4 and X 5 is N or CR X5 where X 1 , X 2 , X 3 , X 4 and X 5 Four or fewer of them are N, R X1 , R X2 , R X3 , R X4 and R X5 are each independently H, C 1 -C 6 Alkyl group, C 1 -C 6 haloalkyl group, optionally halogen, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 substituted with one or more substituents selected from alkoxy groups (CH 2 ) 0-3 -C 1 -C 6 Alkoxy group, O—(CH 2 ) 0-3 -C 3 -C 6 a carbocyclyl group, an O—(CH ) group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heterocyclyl group, O—(CH 2 ) 0-3 -C 6 -C 10 aryl groups, O—(CH ) groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heteroaryl group, C 1 -C 6 alkylamino groups, wherein the alkyl group is optionally selected from the group consisting of C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, di-C 1 -C 6 alkylamino groups, each alkyl group optionally independently selected from the group consisting of: 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, OH, amino group, NO 2 , halogen, CN, ═O, N(R N ) C(O)R 62 , N(R N )C(O)OR 62 , N(R N ) S (O) 2 -C 1 -C 6 alkyl group, N(R N ) S (O) 2 -C 3 -C 6 Cycloalkyl group, S(O) 1-2 NH (C 1 -C 6 alkyl group), S(O) 1-2 N (C 1 -C 6 alkyl group) 2 , S(O) 0-2 -C 1 -C 6 Alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 ) 2 , C 3 -C 6 a carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 6 -C 10 aryl groups and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, of which R X1 , R X2 , R X3 , R X4 and R X5 Any two of these, together with the carbon atoms to which they are attached, form C 5 -C 6 A carbocyclyl group or a heterocyclyl group containing one or two heteroatoms selected from N, O and S together with a 5- or 6-membered ring can be formed, and the carbocyclyl group or heterocyclyl group can optionally be one or more R A and R X1 , R X2 , R X3 , R X4 and R X5 one or more hydrogen atoms in any one of Each R A are independently halogen, OH, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Alkylamino group or di-C 1 -C 6 The compound of claim 1 which is an alkylamino group.

35. R 61 35. The compound of claim 34, wherein ' is H or halogen.

36. R L1 and R L2 are each independently H, CH 3 , C.H. 2 CH 3 or CH(CH 3 ) 2 36. The compound of claim 34 or 35, wherein:

37. X 1 , X 2 and X 3 The compound of any one of claims 34 to 36, wherein each is CH.

38. X 1 and X 2 are N, and X 3 The compound of any one of claims 34 to 36, wherein is CH.

39. X 2 and X 3 are N, and X 1 The compound of any one of claims 34 to 36, wherein is CH.

40. R 4 and R 7 are each H, and R 5 is H or F.

41. R 4 is F and R 5 and R 7 are each independently H or F.

42. A compound of formula Ib, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, wherein: X is N or CR X and R X , R 4 , R 5 and R 7 are each independently H, C 1 -C 6 Alkyl group, C 1 -C 6 is a haloalkyl group or a halogen, Each R 61 " is independent, H. C 1 -C 6 alkyl group, which optionally independently comprises 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, halogen, OH, amino group, C 6 -C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C- 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, OH, amino group, NO 2 , halogen, CN, C(O)R 62 、C(O)OR 62 、C(O)NR 63 R 64 、 L-C 6 -C 10 an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, L-C 3 -C 6 and one or more groups selected from the group consisting of a carbocyclyl group or an L-heterocyclyl group containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, wherein the aryl, heteroaryl, carbocyclyl or heterocyclyl groups are optionally and independently selected from: C 1 -C 6 Alkyl group, C 1 -C 6 haloalkyl group, optionally halogen, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 substituted with one or more substituents selected from alkoxy groups (CH 2 ) 0-3 -C 1 -C 6 Alkoxy group, O—(CH 2 ) 0-3 -C 3 -C 6 a carbocyclyl group, an O—(CH ) group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heterocyclyl group, O—(CH 2 ) 0-3 -C 6 -C 10 aryl groups, O—(CH ) groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heteroaryl group, C 1 -C 6 alkylamino groups, wherein the alkyl groups are optionally substituted with one or more groups selected from the group consisting of 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, di-C 1 -C 6 alkylamino groups, wherein each alkyl group is optionally and independently substituted with one or more substituents selected from the group consisting of: 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, OH, amino group, NO 2 , halogen, CN, ═O, N(R N ) C(O)R 62 , N(R N )C(O)OR 62 , N(R N ) S (O) 2 -C 1 -C 6 alkyl group, N(R N ) S (O) 2 -C 3 -C 6 Cycloalkyl group, S(O) 1-2 NH (C 1 -C 6 alkyl group), S(O) 1-2 N (C 1 -C 6 alkyl group) 2 , S(O) 0-2 -C 1 -C 6 Alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 ) 2 , C 3 -C 6 a carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 6 -C 10 and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein two of the substituents together with the carbon atoms to which they are attached form a C 5 -C 6 A carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S can be formed, and the carbocyclyl or heterocyclyl group can optionally be one or more R A wherein one or more hydrogen atoms in said substituents may be replaced by one or more deuterium atoms; Each R 61 is independent, C 1 -C 6 alkyl group, which optionally independently comprises 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, halogen, OH, amino group, C 6 -C 10 an aryl group and a heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S; C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group, OH, amino group, NO 2 , halogen, CN, ═O, C(O)R 62 、C(O)OR 62 、C(O)NR 63 R 64 、 L-C 6 -C 10 an aryl group, an L-heteroaryl group containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, L-C 3 -C 6 and one or more groups selected from the group consisting of carbocyclyl groups or L-heterocyclyl groups containing one or two 4- to 6-membered rings and 1 to 4 heteroatoms selected from N, O and S, wherein the aryl, heteroaryl, carbocyclyl or heterocyclyl groups are optionally and independently selected from: C 1 -C 6 Alkyl group, C 1 -C 6 haloalkyl group, optionally halogen, C 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 substituted with one or more substituents selected from alkoxy groups (CH 2 ) 0-3 -C 1 -C 6 Alkoxy group, O—(CH 2 ) 0-3 -C 3 -C 6 a carbocyclyl group, an O—(CH ) group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heterocyclyl group, O—(CH 2 ) 0-3 -C 6 -C 10 aryl groups, O—(CH ) groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 2 ) 0-3 -heteroaryl group, C 1 -C 6 alkylamino groups, wherein the alkyl groups are optionally substituted with one or more groups selected from the group consisting of 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, di-C 1 -C 6 alkylamino groups, wherein each alkyl group is optionally and independently substituted with one or more substituents selected from the group consisting of: 1 -C 6 Alkylamino group, di-C 1 -C 6 Alkylamino group and C 1 -C 6 Alkoxy group, OH, amino group, NO 2 , halogen, CN, ═O, N(R N ) C(O)R 62 , N(R N )C(O)OR 62 , N(R N ) S (O) 2 -C 1 -C 6 alkyl group, N(R N ) S (O) 2 -C 3 -C 6 Cycloalkyl group, S(O) 1-2 NH (C 1 -C 6 alkyl group), S(O) 1-2 N (C 1 -C 6 alkyl group) 2 , S(O) 0-2 -C 1 -C 6 Alkyl group, C(O)R 62 , C(O)OR 62 , C(O)NR 63 R 64 , P(=O)(OR 62 ) 2 , C 3 -C 6 a carbocyclyl group, a heterocyclyl group containing one or two 3- to 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S; 6 -C 10 and heteroaryl groups containing one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, wherein two of the substituents together with the carbon atoms to which they are attached form a C 5 -C 6 A carbocyclyl group or a heterocyclyl group containing a 5- or 6-membered ring and one or two heteroatoms selected from N, O, and S can be formed, and the carbocyclyl or heterocyclyl group can optionally be one or more R A wherein one or more hydrogen atoms in said substituents may be replaced by one or more deuterium atoms; Among them, L is absent or O, (CR L1 R L2 ) n , O-(CR L1 R L2 ) n , (CR L1 R L2 ) n -O and S(O) 2 is a linker selected from Each R L1 and each R L2 are independently H, CH 3 , C.H. 2 CH 3 or CH(CH 3 ) 2 or R L1 and R L2 together with the carbon atoms to which they are attached, form C(O), C 3 -C 6 can form a cycloalkyl group or a heterocyclyl group containing a 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S; R L1 and R L2 one or more hydrogen atoms in any one of may be replaced with one or more deuterium atoms, Each R A are independently halogen, OH, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Alkylamino group or di-C 1 -C 6 an alkylamino group, and n is 1, 2 or 3; or Two R's 61 together with the carbon atoms to which they are attached form C 4 -C 10 a carbocyclyl group, a heterocyclyl group containing one 4- to 6-membered ring and 1 to 3 heteroatoms selected from N, O and S, a spiroheterocyclyl group or a fused heterocyclyl group containing two 4- to 6-membered rings each containing 1 to 4 heteroatoms selected from N, O and S, or C 6 and aryl groups, wherein the carbocyclyl, heterocyclyl, spiroheterocyclyl or fused heterocyclyl or aryl groups are optionally independently selected from the group consisting of: 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxy group, C 1 -C 6 Alkylamino group, di-C 1 -C 6 substituted with one or more groups selected from the group consisting of alkylamino, OH, amino, halogen, CN, and ═O; Each R 62 , each R 63 and each R 64 are independently H, C 1 -C 6 Alkyl group or C 1 -C 6 The compound of claim 1 which is a haloalkyl group.

43. Each R 61 43. The compound of claim 42, wherein " is H.

44. R 4 and R 7 are each H, and R 5 is H or F.

45. Each R 61 is independent, C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 The compound of any one of claims 42 to 44, wherein the haloalkoxy group is OH or halogen.

46. A compound selected from Table A or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof.

47. 47. The compound of claim 46, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, selected from Table B.

48. 47. The compound of claim 46, or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer or tautomer thereof, selected from Table C.

49. 49. A pharmaceutical composition comprising a compound according to any one of claims 1 to 48, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or excipient.

50. 49. A method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt or solvate thereof.

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