Heterocyclic compounds and their uses

Abstract

The present disclosure provides compounds and pharmaceutical compositions comprising the same. The compounds, their pharmaceutical compositions, and methods of using them have a variety of applications as therapeutic, diagnostic, and research tools. The subject compositions and methods are particularly useful for enhancing immune responses and / or treating cancer and other diseases. In some embodiments, the compounds described herein are provided in at least 99% enantiomeric excess. In certain aspects, the present disclosure provides pharmaceutical compositions comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

Description

[Technical Field]

[0001] cross reference This application claims the benefit of U.S. Provisional Application No. 63 / 504,147, filed May 24, 2023, and U.S. Provisional Application No. 63 / 517,046, filed August 1, 2023, each of which is incorporated herein by reference in its entirety. [Background technology]

[0002] PTPN2 encodes a protein tyrosine phosphatase involved in multiple intracellular signaling pathways in immune cells. PTPN2 can negatively regulate signaling from the T cell receptor (TCR), αβ TCR, by dephosphorylating and activating Src family kinases, including LCK. Additionally, PTPN2 can antagonize growth factor- or cytokine-mediated signaling required for T cell function, homeostasis, and / or differentiation by dephosphorylating and inactivating JAK family kinases, such as JAK-1 and JAK-3, and / or target substrates of JAK family kinases, such as STAT-1, STAT-3, and STAT-5.

[0003] Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) in PTPN2 are associated with the development of several human autoimmune diseases, including, but not limited to, type 1 diabetes, rheumatoid arthritis, Crohn's disease, and celiac disease. For example, the PTPN2 variant rs1893217(C) is associated with a 40% decrease in PTPN2 mRNA expression in CD4+ T cells and the development of type 1 diabetes. Additionally, PTPN2 mRNA expression levels in lung cancer tissue have been shown to be higher than those in normal lung tissue or adjacent normal tissue, and such overexpression promotes lung cancer cell proliferation. Furthermore, two PTPN2 SNPs, rs2847297 and rs2847282, have been associated with reduced PTPN2 mRNA expression and lung cancer risk, particularly squamous cell carcinoma risk.

[0004] Cancer is the second leading cause of human death. In 2020, there were nearly 10 million cancer deaths worldwide, with over 18 million new cases diagnosed. In the United States alone, cancer causes the deaths of over 500,000 people annually, with approximately 1.9 million new cases diagnosed per year (excluding basal and squamous cell skin cancer). Worldwide, lung, liver, stomach, and intestinal cancers account for more than 4 in 10 of all cancer deaths.

[0005] Adoptive transfer of genetically modified lymphoid cells, particularly T cells (i.e., ACT), is an emerging cancer treatment. While its efficacy has been demonstrated in a range of hematological cancers, including ALL, CLL, DLBCL, FL, and multiple myeloma, its effectiveness in the treatment of solid tumors has yet to be established. Current immune cell therapies (e.g., CAR-T therapy) suffer from a number of serious drawbacks. T cell production and clonal expansion are highly inefficient and costly. The antitumor activity and numbers of T cells can be reduced in the immunosuppressive microenvironment often found in tumors once introduced into patients. Additionally, CAR-T therapy is limited by life-threatening toxicity in over 30% of patients. Toxicity primarily manifests as cytokine release syndrome (CRS), characterized by an early phase with fever, hypotension, and elevated levels of various cytokines, and a later phase associated with fatal neurological events. Summary of the Invention

[0006] In view of the above, there exists a significant need for alternative compositions and methods for treating cancer and / or performing immunotherapy. The compositions and methods of the present disclosure address this need while also providing additional advantages. The ability of PTPN2 to act as a negative regulator of immune receptor-related pathways (e.g., TCR signaling) and promote cancer cell proliferation can be utilized in the treatment of cancer and tumors. Various aspects of the present disclosure provide compositions and methods for inducing lymphoid cell activity.

[0007] In certain aspects, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W 1 is C, C(R 8 ), and N; W 2 is C, C(R 8 ), and N; W 4 is N and C(R 4 ) and W 5 is N and C(R 5 ) and W 6 is N and C(R 6 ) and J 1 is N, C, and C(R 8 ) and J 2 is N, N(R 7 ), C(R 8 ), C(R 8 )2, and C(O), J 3 is N(R 7 ) and C(R 8 )2 is selected, L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 9 is C3~12 carbocycle and 3- to 12-membered heterocycle, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 optionally substituted with R 4 , R 5 , R 6 , and R 8 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 7 is, in each occurrence, independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OR 12 , -C(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23)-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, [ka] indicates a single or double bond where all valences are satisfied, R 9 , W 1 , W 2 , W4 , W 5 , W 6 , J 2 , or J 3 At least one of the groups is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -OC(O)N(R 12 )(R 13 ), -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 is replaced by .

[0008] In some embodiments, for compounds of formula (I), W 4 is C(R 4 ) and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W 1 is C and W 2 is C(R 8 In some embodiments, J 3 is N(R 7 In some embodiments, R 9 is a 4- to 7-membered heterocyclic ring, and the 4- to 7-membered heterocyclic ring is selected from the group consisting of (i) one, two, or three R 20 and (ii) -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R is a 4- to 7-membered heterocycle containing a ring nitrogen atom substituted with 9 -OR 15 or O-(C 1~6 alkyl)-OR 15 The ring carbon atoms are substituted by:

[0009] In some embodiments, for compounds of formula (I), R 9 teeth, [ka] where: W is C(R 2 )2, n is 0, 1, or 2; R 1 is halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12)(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R 20 is optionally substituted with

[0010] In certain aspects, the present disclosure provides a compound of formula (II): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J1 is C and J 2 is CH, R 1 is a halogen, -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C3 carbocyclic), -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2) R bonded to the same carbon atom 1 and R 2together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or (3) R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 (4) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, -C 0~6 Alkyl-(C3 carbocycle) is a ring structure consisting of one, two, or three R 20 is replaced by -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 )2, (2) two R bonded to the same carbon atom 2 together with the carbon atoms to which they are attached, C 3~12 (3) forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring; and (4) two vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22)(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0011] In certain aspects, the present disclosure provides a compound of formula (III) or (IV): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12)(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23)-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0012] In some embodiments, the compound is a compound of formula (III) provided in at least 98% enantiomeric excess. In some embodiments, the compound is a compound of formula (IV) provided in at least 98% enantiomeric excess.

[0013] In some embodiments, for compounds of formula (I), (II), (III), or (IV), R 4 is hydrogen, halogen, C 1~6 Alkyl, C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, -OR 12 , and -N(R 12 )(R 13 ) and C 1~6 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 4 is selected from hydrogen, halogen, and —OH. In some embodiments, R 4 is hydrogen. In some embodiments, R 5 is halogen, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, R 5 is —OH. In some embodiments, R 5 -OR 15 and -O-(C 1~6 alkyl)-OR 15 In some embodiments, R 6 is halogen, -OR 12 , and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, R 6 is halogen. In some embodiments, R6 is selected from fluorine and chlorine. In some embodiments, R 4 is hydrogen and R 5 is -OH and R 6 is fluorine.

[0014] In some embodiments, in compounds of Formula (I), (II), (III), or (IV), J 1 is N and J 2 is CH. In some embodiments, R 7 is hydrogen and -(C 1~6 alkyl)-OR 15 In some embodiments, R 7 is hydrogen. In some embodiments, R 7 is -(C 1~6 alkyl)-OR 15 is.

[0015] In some embodiments, for compounds of formula (I), (II), (III), or (IV), L 1 does not exist or is C 1~6 Alkylene, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )S(O)2-, -C(O)-, -C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)-, -S(O)2-, and -S(O)2N(R 12 In some embodiments, L 1 does not exist or is C 1~3 Alkylene, -O-, and -C(O)N(R 12 In some embodiments, L 1 does not exist.

[0016] In some embodiments, for compounds of Formula (II), (III), or (IV), W is CH. In some embodiments, n is 0 or 1, e.g., n is 0. In some embodiments, R 1is a halogen, C 2~6 Alkyl, C 2~6 Alkenyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and 3- to 12-membered heterocycle may have one, two, or three R 20 In some embodiments, R 1 is C 2~6 Alkyl and -C 0~6 Alkyl-(C 3~8 carbocyclic rings), each of which is selected from one, two, or three R 20 In some embodiments, R 1 is C 2~6 Alkyl and -C 0~3 Alkyl-(C 3~6 In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] is selected from.

[0017] In some embodiments, for compounds of formula (II), (III), or (IV), R 2 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, -OR 12 , and -N(R 12 )(R 13 ), or two R bonded to the same carbon atom 2 together, oxo, =NR 12 , or =C(R 14 )2, and C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, each R 2 is hydrogen. In some embodiments, R 3 is hydrogen, C 1~6 Alkyl, -C 0~6 Alkyl-(3-12 membered heterocycle), -C(O)OR 12 , and -C(O)O-(C 1~6 alkyl)-OR 15 Selected from C 1~6 Alkyl and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is -C2 alkyl-(5-6 membered heterocycle) and -C(O)O-(C 1~6 alkyl)-OR 15 -C alkyl-(5-6 membered heterocycle) is independently selected from C 1~3 It is substituted with 1, 2, or 3 substituents selected from alkyl and oxo.

[0018] In some embodiments, for compounds of formula (I), (II), (III), or (IV), R 15 is -C(O)R 12 and -P(O)(XR16 )(YR 17 In some embodiments, R 12 is C optionally substituted with -NH 1~6 In some embodiments, X and Y are each -O-. In some embodiments, R 16 and R 17 At least one of the groups is independently a halogen, -OR 12 , -SSR 12 , -SC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , and -P(O)(OR 12 C optionally substituted in each occurrence with one or more substituents selected from 1~6 In some embodiments, R 16 and R 17 are independently halogen, -OR 12 , -SSR 12 , -SC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , and -P(O)(OR 12 C optionally substituted in each occurrence with one or more substituents selected from 1~6 In some embodiments, R 16 and R 17 are independently hydrogen, and independently halogen, -OR 12 , -SSR 12 , -SC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , and -P(O)(OR 12 C optionally substituted in each occurrence with one or more substituents selected from 1~6 In some embodiments, R 16 and R 17 are independently hydrogen, -CH2OC(O)R 12 , and -CH2OC(O)OR 12 In some embodiments, R16 and R 17 is independently selected from —CH2OC(O)C(CH3)3, —CH2OC(O)OCH(CH3)2, —CH2OC(O)CH3, —CH2CH2-SS-(CH2)2OH, and —CH2CH2-SC(O)CH3. In some embodiments, R 15 is -P(O)(OH)2.

[0019] In certain aspects, the present disclosure provides compounds of the following formula: [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein W is CH, n is 0, and R 1 teeth, [ka] and R 3 is hydrogen and -C(O)OCH(CH3)OC(O)R 12 Selected from R 5 is -OH and R 6 is fluorine and R 7 is hydrogen and R 12 is C 1~6 Alkyl and C 3~6 selected from carbocycles, [ka] indicates a double bond. In certain aspects, the present disclosure provides [ka] or a pharmaceutically acceptable salt or solvate thereof.

[0020] In certain aspects, the disclosure provides a compound selected from Table 1, or a pharmaceutically acceptable salt or solvate thereof.

[0021] In certain aspects, the present disclosure provides a compound of formula DL DE-E, wherein D is a monovalent form of a compound described herein, and L DE is a covalent linker attached to D and E, and E is a monovalent form of a degradation-promoting agent. In some embodiments, the degradation-promoting agent is selected from the group consisting of E3A, mdm2, APC, EDD1, SOCS / BC-box / eloBC / CUL5 / RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von Hippel-Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperone-mediated autophagy), SCFb-TRCP (Skip-Cullin-F box (beta-TRCP) ubiquitin complex), b-TRCP (b-transduction repeat-containing protein), cIAP1 (cellular inhibitor of apoptosis protein 1), APC / C (anaphase-promoting complex / cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4 CRBN) is capable of binding to a protein selected from ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885. In some embodiments, the degradation-promoting agent is capable of binding to a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1. DE -L DE1 -L DE2 -L DE3 -L DE4 -L DE5 - and L DE1 , L DE2 , L DE3 , L DE4 , and L DE5 are independently a bond, -O-, -N(R 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 12 )-, -S(O)N(R 12 )-, -N(R 12 )S(O)-, -N(R 12 )S(O)2-, C 1~6 Alkylene, (-OC 1~6 alkyl) z -, (-C 1~6 Alkyl-O)z - 、 C 2~6 Alkenylene, C 2~6 Alkynylene, C 1~6 Haloalkylene, C 3~12 Cycloalkylene, C 1~11 Heterocycloalkylene, C 6~12 Arylene, or C 1~11 Heteroarylene, C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, C 1~6 Haloalkylene, C 3~12 Cycloalkylene, C 1~11 Heterocycloalkylene, C 6~12 Arylene, or C 1~11 Heteroarylene can be one, two, or three R 20 Optionally replaced by (-OC 1~6 alkyl) z - and (-C 1~6 Alkyl-O) z -Each C 1~6 Alkyl can be one, two, or three R 20 and z is independently an integer from 0 to 10. In some embodiments, L DE is -(O-C2 alkyl) z - and z is an integer from 1 to 10. In some embodiments, L DE is -(C2 alkyl-O-) z - and z is an integer from 1 to 10. In some embodiments, L DE is -(CH2) zz1 L DE2 (CH2O) zz2 - and L DE2 is a bond, 5- or 6-membered heterocycloalkylene or heteroarylene, phenylene, -C 2~4 alkynylene, -SO2-, or -NH-, and zz1 and zz2 are independently integers from 0 to 10. In some embodiments, L DE is -(CH2) zz1 (CH2O) zz2-, and zz1 and zz2 are each independently an integer from 0 to 10. In some embodiments, L DE is a PEG linker. In some embodiments, E is [ka] is a monovalent form of a compound selected from

[0022] In some embodiments, the compounds described herein are provided in an enantiomeric excess of at least 99%. In certain aspects, the present disclosure provides a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

[0023] In certain aspects, the present disclosure provides a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof. In certain aspects, the present disclosure provides a method of enhancing cellular immunity, the method comprising: (a) contacting a cell with a compound described herein, thereby enhancing cellular immunity, wherein the cell comprises (i) a chimeric T cell receptor sequence encoding a T cell receptor fusion protein (TFP), and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and the CAR exhibits specific binding to an antigen.

[0024] In certain aspects, the present disclosure provides methods for enhancing the immunity of a cell, the methods comprising: (a) contacting the cell with a compound described herein; and (b) introducing into the cell (i) a chimeric T cell receptor sequence encoding a T cell receptor fusion protein (TFP) and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and CAR exhibits specific binding to an antigen, thereby enhancing the immunity of the cell. In some embodiments, (a) is performed before, simultaneously with, or after (b). In some embodiments, the cell retains PTPN2 expression or activity before (a). In some embodiments, the cell is a lymphoid cell. In some embodiments, the methods described herein further comprise administering the cell to a subject in need thereof. In some embodiments, the methods described herein further comprise administering to the subject a compound described herein before, simultaneously with, or after administering the cell. In some embodiments, the subject's cells exhibit PTPN2 expression or activity before administering a compound described herein.

[0025] In certain aspects, the present disclosure provides methods of treating cancer in a subject in need thereof, comprising: (a) administering a compound described herein; and (b) administering, concurrently with, before, or after step (a), a second agent or second therapy, wherein the second agent or second therapy (1) retains PTPN2 expression or activity prior to exposure to the compound, and (2) comprises lymphoid cells expressing (i) a chimeric T cell receptor (TCR) sequence encoding a T cell receptor fusion protein (TFP) and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and CAR exhibits specific binding to a tumor antigen. In some embodiments, the compound is administered systemically and / or transiently to a subject in need thereof, and the second agent or second therapy comprises (1) lymphoid cells that retain PTPN2 expression or activity prior to exposure to the compound, and (2) a chimeric antigen receptor (CAR) sequence encoding a CAR that exhibits specific binding to a tumor antigen. In some embodiments, the compounds described herein are administered systemically and transiently to a subject in need thereof. In some embodiments, prior to exposure to the compound, the lymphoid cells retain at least about 90% of PTPN2 expression or activity compared to a control. In some embodiments, the second agent or second therapy comprises a subtherapeutic amount of lymphoid cells. In some embodiments, the compound (i) does not modulate site-specific recombination of the gene encoding PTPN2 and (ii) does not affect editing of the gene encoding PTPN2. In some embodiments, the lymphoid cells are immune effector cells. In some embodiments, the lymphoid cells are selected from the group consisting of T cells, B cells, NK cells, KHYG cells, T helper cells, regulatory T cells, memory T cells, tumor-infiltrating T cells (TILs), antigen-presenting cells, and dendritic cells. In some embodiments, the lymphoid cells are selected from the group consisting of CD4+ T cells, CD8+ T cells, and CD4+ and CD8+ T cells. In some embodiments, the subject is afflicted with a cancer selected from cancer of the bladder, bone, brain, breast, cervix, colon, lung, esophagus, head and neck, ovary, prostate, uterus, stomach, skin, and renal tissue.In some embodiments, the compound has an IC of 500 nM or less for PTPN2 as determined in a phosphatase assay utilizing DiFMUP as a substrate. 50 In some embodiments, the compound exhibits (i) an IC of less than 5 nM as determined in a phosphatase assay utilizing DiFMUP as a substrate. 50 , and (ii) an EC of less than 10 μM in the pSTAT1 assay. 50 In some embodiments, the compound exhibits (i) an IC of less than 5 nM as determined in a phosphatase assay utilizing DiFMUP as a substrate. 50 , (ii) an EC of less than 5 μM in the pSTAT1 assay 50 and (iii) an EC of less than 1 μM when tested in the CD25 assay. 50 In some embodiments, the compounds exhibit an IC of 500 nM or less for PTP1B as determined in a phosphatase assay utilizing DiFMUP as a substrate. 50 In some embodiments, PTPN2 expression or activity is transiently downregulated by intermittent administration of the compound to lymphoid cells. In some embodiments, the method further comprises monitoring one or more inflammatory biomarkers present in the subject selected from the group consisting of antibodies, cytokines, radicals, and coagulation factors, concurrently with or following administration of the compound and / or lymphoid cells. In some embodiments, the cytokine comprises IL-1, IL-6, TNF-α, IL-10, or IL-1RR.

[0026] In some embodiments, the methods of the present disclosure further comprise administering to the subject another agent selected from the group consisting of a chemotherapeutic agent, a radioactive agent, an anti-tumor marker inhibitor, and a checkpoint inhibitor, hi some embodiments, the methods of the present disclosure further comprise administering an additional therapeutic agent in conjunction with the compound.

[0027] In certain aspects, the present disclosure provides methods of enhancing the immunity of a subject in need thereof, comprising administering (e.g., systemically or locally) to the subject a PTPN2 inhibitor, such as a compound of Formula (I), (II), (II-a), (III), or (IV), thereby enhancing the immunity of the subject. In another aspect, the present disclosure provides methods of enhancing the immunity of a subject in need thereof, comprising using one or more compounds described herein, such as a compound of Formula (I), (II), (II-a), (III), or (IV), to downregulate (e.g., transiently) PTPN2 expression or activity in vivo in the subject's cells, thereby enhancing the immunity of the subject. In yet another aspect, the present disclosure provides a method for enhancing immunity in a subject in need thereof, comprising systemically and transiently downregulating PTPN2 expression or activity in vivo in cells of the subject using one or more compounds described herein, such as a compound of Formula (I), (II), (II-a), (III), or (IV), thereby enhancing the immunity of the subject.

[0028] In certain aspects, the present disclosure provides modified lymphoid cells comprising (i) a chimeric T cell receptor (TCR) sequence encoding a T cell receptor fusion protein (TFP), and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and CAR exhibits specific binding to an antigen, and the lymphoid cells comprise a compound described herein. In some embodiments, the compound has (i) an IC of less than 5 nM as determined in a phosphatase assay utilizing DiFMUP as a substrate. 50 , (ii) an EC of less than 10 μM in the pSTAT1 assay 50 and / or (iii) an EC of less than 1 μM when tested in a CD25 assay. 50 Shows.

[0029] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0030] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also herein "Figures and FIG."). [Brief explanation of the drawings]

[0031] [Figure 1] 1 shows the results of a study in which MC38 tumor-bearing mice were treated with (i) a PTPN2 inhibitor of the present disclosure (eg, Compound A at various concentrations) or (ii) vehicle.

[0032] [Figure 2]

[0023] Figure 1 shows the results of a study in which mice cured of MC38 tumors by a PTPN2 inhibitor of the present disclosure (e.g., Compound B) were re-challenged with MC38 cells 30 days after the last dose of the PTPN2 inhibitor without any further treatment. Naive mice challenged with MC38 cells were used as controls. DETAILED DESCRIPTION OF THE INVENTION

[0033] 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 to which this disclosure belongs. In the event of a plurality of definitions for terms herein, those in this section prevail. All patents, patent applications, publications, and published nucleotide and amino acid sequences (e.g., sequences available in GenBank or other databases) mentioned herein are incorporated by reference. Chemical structures are named herein according to IUPAC conventions as implemented in ChemDraw® software (Perkin Elmer, Inc., Cambridge, MA). Section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described. As used in the specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Furthermore, the use of the term "including," as well as other forms such as "include," "includes," and "included," is not limiting. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0034] "C x~y " or "C x ~C y The term "alkyl," when used in conjunction with a chemical moiety such as alkyl, alkenyl, or alkynyl, is intended to include groups containing x to y carbons in the chain. For example, "C x~y The term "alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain and branched-chain alkyl groups containing x to y carbon atoms in the chain.

[0035] "Alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain and branched-chain alkyl groups. An alkyl group contains 1 to 8 carbon atoms (C 1~8 alkyl) or 1 to 6 carbon atoms (C 1~6alkyl) and the like, 1 to 12 carbon atoms (e.g., C 1~12 The alkyl group may include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, septyl, octyl, nonyl, and decyl. The alkyl group is attached to the remainder of the molecule by a single bond. Unless otherwise stated herein, the alkyl group is optionally substituted with one or more substituents, such as those described herein.

[0036] "Haloalkyl" refers to an alkyl group substituted by one or more halogens. Exemplary haloalkyl groups include trifluoromethyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, and 1,2-dibromoethyl.

[0037] "Alkenyl" refers to a substituted or unsubstituted hydrocarbon group, including straight- and branched-chain alkenyl groups, containing at least one double bond. Alkenyl groups are groups containing 2 to 8 carbon atoms (C 2~8 alkenyl) or 2 to 6 carbon atoms (C 2~6 alkenyl) and the like, 2 to 12 carbon atoms (e.g., C 2~12 Exemplary alkenyl groups include ethenyl (i.e., vinyl), prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless stated otherwise in the specification, alkenyl groups are optionally substituted with one or more substituents, such as those described herein.

[0038] "Alkynyl" refers to a substituted or unsubstituted hydrocarbon group, including straight- and branched-chain alkynyl groups, containing at least one triple bond. Alkynyl groups are groups of 2 to 8 carbon atoms (C 2~8 alkynyl) or 2 to 6 carbon atoms (C 2~6 alkynyl) and other 2-12 carbon atoms (e.g., C2~12 alkynyl). Exemplary alkynyl groups include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, alkynyl groups are optionally substituted with one or more substituents, such as those described herein.

[0039] An "alkylene" or "alkylene chain" is an alkylene group having 1 to 8 carbon atoms (C 1~8 alkylene) or 1 to 6 carbon atoms (C 1~6 alkylene) and the like, 1~12 "Alkylene" refers to a substituted or unsubstituted divalent saturated hydrocarbon group, including straight-chain alkylene and branched-chain alkylene groups, including alkylene (methylene, ethylene, propylene, and n-butylene). Exemplary alkylene groups include methylene, ethylene, propylene, and n-butylene. Similarly, "alkenylene" and "alkynylene" refer to an alkylene group, as defined above, that contains one or more carbon-carbon double or triple bonds, respectively. The point of attachment of the alkylene, alkenylene, or alkynylene chain to the rest of the molecule can be through one or any two carbons of the chain. Unless stated otherwise herein, alkylene, alkenylene, or alkynylene groups are optionally substituted with one or more substituents, such as those described herein.

[0040] "Heteroalkyl," "heteroalkenyl," and "heteroalkynyl" refer to substituted or unsubstituted alkyl, alkenyl, and alkynyl groups, respectively, in which one or more, such as 1, 2, or 3, of the carbon atoms are replaced with a heteroatom such as O, N, P, Si, S, or a combination thereof. Any nitrogen, phosphorus, and sulfur heteroatoms present in the chain can be optionally oxidized, and any nitrogen heteroatom can be optionally quaternized. When a numerical range is specified, it refers to the total chain length. For example, a 3- to 8-membered heteroalkyl group has a chain length of 3 to 8 atoms. Connection to the remainder of the molecule can be through either a heteroatom or a carbon in the heteroalkyl, heteroalkenyl, or heteroalkynyl chain. Unless otherwise stated herein, a heteroalkyl, heteroalkenyl, or heteroalkynyl group is optionally substituted with one or more substituents, such as those described herein.

[0041] "Heteroalkylene," "heteroalkenylene," and "heteroalkynylene" refer to substituted or unsubstituted alkylene, alkenylene, and alkynylene groups, respectively, in which one or more, such as 1, 2, or 3, of the carbon atoms are replaced with a heteroatom such as O, N, P, Si, S, or a combination thereof. Any nitrogen, phosphorus, and sulfur heteroatoms present in the chain can be optionally oxidized, and any nitrogen heteroatom can be optionally quaternized. When a numerical range is specified, it refers to the total chain length. For example, a 3- to 8-membered heteroalkylene group has a chain length of 3 to 8 atoms. The points of attachment of the heteroalkylene, heteroalkenylene, or heteroalkynylene chain to the rest of the molecule can be through either one heteroatom or one carbon, or any two heteroatoms, any two carbons, or any one heteroatom and any one carbon in the heteroalkylene, heteroalkenylene, or heteroalkynylene chain. Unless stated otherwise specifically in the specification, heteroalkylene, heteroalkenylene, or heteroalkynylene groups are optionally substituted with one or more substituents, such as those described herein.

[0042] "Carbocycle" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is a carbon atom. 3~10 Monocyclic ring, C 5~12 Bicyclic ring, C 5~18 polycyclic ring, C 5~12 Spirocyclic rings, and C 5~12 It may contain bridged rings. Each ring of a bicyclic or polycyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. A polycyclic carbocycle contains a number or rings equal to the minimum number of cleavages required to convert the carbocycle into an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). In some embodiments, a carbocycle is a C 6~10 C such as aryl 6~12 In some embodiments, the carbocycle is a C 3~12 In some embodiments, the carbocycle is a C 5~12A carbocycle is a cycloalkenyl group. In an exemplary embodiment, an aromatic ring, such as phenyl, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic rings, valence permitting, is included in the definition of a carbocycle. A carbocycle can include fused rings, bridged rings, spirocyclic rings, saturated rings, unsaturated rings, aromatic rings, or any combination thereof. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantine, phenyl, indanyl, and naphthyl. Unless otherwise specified herein, a carbocycle is optionally substituted with one or more substituents, such as those described herein.

[0043] "Heterocycle" refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms, e.g., 1, 2, 3, or 4 heteroatoms selected from O, S, P, and N. Heterocycles can include 3- to 10-membered monocyclic rings, 5- to 12-membered bicyclic rings, 5- to 18-membered polycyclic rings, 5- to 12-membered spirocyclic rings, and 5- to 12-membered bridged rings. Each ring in a bicyclic or polycyclic heterocycle can be selected from saturated, unsaturated, and aromatic rings. Polycyclic heterocycles contain a number or rings equal to the minimum number of cleavages required to convert the heterocycle into an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). A heterocycle can be attached to the remainder of the molecule through any atom of the heterocycle, such as a carbon or nitrogen atom of the heterocycle, as valence allows. In some embodiments, the heterocycle is a 5- to 10-membered heteroaryl group, such as a 5- or 6-membered heteroaryl. In some embodiments, the heterocycle is a 3- to 12-membered heterocycloalkyl group. The heterocycle can include fused rings, bridged rings, spirocyclic rings, saturated rings, unsaturated rings, aromatic rings, or any combination thereof. In an exemplary embodiment, a heterocycle, such as pyridyl, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, benzothienyl, benzoxazolyl, and quinolinyl. Unless otherwise specified herein, the heterocycle is optionally substituted with one or more substituents, such as those described herein.

[0044] "Heteroaryl" refers to an aromatic ring containing at least one heteroatom, e.g., 1, 2, 3, or 4 heteroatoms selected from O, S, and N. Heteroaryls can include 5-10-membered monocyclic rings, 6-12-membered bicyclic rings, 6-18-membered polycyclic rings, 5-12-membered spirocyclic rings, and 6-12-membered bridged rings. As used herein, heteroaryl rings can be selected from monocyclic, bicyclic, or polycyclic rings (including fused, spirocyclic, and bridged ring systems), in which at least one of the rings in the ring system is aromatic and contains at least one heteroatom. Polycyclic heteroaryls contain a number or rings equal to the minimum number of cleavages required to convert the heteroaryl to an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). The heteroatom(s) in a heteroaryl can be optionally oxidized. One or more nitrogen atoms, if present, can be optionally quaternized. The heteroaryl may be attached to the remainder of the molecule through any atom of the heteroaryl, such as a carbon or nitrogen atom of the heteroaryl, valence permitting. Examples of heteroaryl groups include, but are not limited to, azepinyl, benzimidazolyl, benzisothiazolyl, benzisoxazolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, purinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridazolyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydroquinolinyl, thiadiazolyl, thiazolyl, and thienyl groups. Unless stated otherwise specifically in the specification, a heteroaryl is optionally substituted with one or more substituents such as those described herein.

[0045] Unless otherwise stated, hydrogen atoms are implicit in structures depicted herein where necessary to satisfy valence requirements.

[0046] Wavy lines drawn across or at the ends of bonds [ka] or dashed bond [ka] are used interchangeably herein to indicate where a bond break or bond occurs. For example, the structure [ka] So, R 1 but [ka] When R is cyclobutyl, 1 teeth, [ka] It can be depicted as:

[0047] The term "substituted" refers to moieties having substituents replacing a hydrogen on one or more carbon or heteroatoms of the structure. It is understood that "substituted" or "substituted with" includes the implicit meaning, provided that such substitution is in accordance with the permissible valences of the replacing atom and substituent, and that the substitution results in a stable compound that does not spontaneously undergo transformation, for example, by rearrangement, cyclization, elimination, and the like. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, heteroatoms, such as nitrogen, can have any permissible substituent of organic compounds described herein that satisfies the valence of the heteroatom.

[0048] The compounds disclosed herein, such as compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), Halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, and -S(=O)(=NR 22 )N(R 22 )(R 23and wherein two substituents attached to the same or adjacent atoms are optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), -C 0~6 Alkyl-(C 3~12 Carbocyclic) and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently selected from halogen and C 1~6 optionally substituted with 1, 2, or 3 groups selected from alkyl; R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocycle.

[0049] In some embodiments, a compound disclosed herein, such as a compound of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), Halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , and -S(O)N(R 22 )(R 23 )-, optionally substituted by one or more, such as 1, 2, or 3, substituents selected from C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , and =C(R 21 ) optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, and C 1~6 haloalkyl; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), -C 0~6 Alkyl-(C 3~12 Carbocyclic) and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently selected from halogen and C 1~6 optionally substituted with 1, 2, or 3 groups selected from alkyl; R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R23 forms a 3- to 10-membered heterocycle.

[0050] In some embodiments, the compounds disclosed herein, such as compounds of Formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), may contain a halogen, oxo, ═NH, —CN, —NO, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycle, -CH2-(C 3~10 carbocyclic ring), a 3- to 10-membered heterocyclic ring, -CH2- (a 3- to 10-membered heterocyclic ring), -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, and -NHCH2CH3; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycle, -CH2-(C 3~10 -carbocycle), 3- to 10-membered heterocycle, and -CH2- (3- to 10-membered heterocycle) are optionally substituted with 1, 2, or 3 groups independently selected from halogen, oxo, =NH, -CN, -NO2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, and -NHCH2CH3.

[0051] Those skilled in the art will understand that the substituents themselves can be substituted, if appropriate. Unless specifically specified as "unsubstituted," reference to a chemical moiety herein is understood to include substituted variants. For example, reference to a "heteroaryl" group or moiety implicitly includes both substituted and unsubstituted variants.

[0052] When divalent substituents are identified herein by their conventional chemical formula written from left to right, they are intended to encompass the isomers resulting from writing the structure from right to left, e.g., -CHO- is also intended to encompass -OCH-.

[0053] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not occur. For example, an "optionally substituted" group can be either unsubstituted or substituted.

[0054] The compounds of the present disclosure also include crystalline and amorphous forms of the compounds, pharmaceutically acceptable salts, and active metabolites having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, non-solvated polymorphs (including anhydrates), conformational polymorphs, amorphous forms, and mixtures thereof of the compounds.

[0055] The compounds described herein may exhibit their natural isotopic abundance, or one or more of the atoms may be artificially enriched in a particular isotope, which has the same atomic number but an atomic mass or mass number different from the atomic mass or mass number predominantly found in nature.All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are included within the scope of the present disclosure.For example, hydrogen is: 1 H (protium), 2 H (deuterium), and 3 H (tritium). Protium is the most abundant hydrogen isotope in nature. Enrichment with deuterium may provide certain therapeutic benefits, such as increased in vivo half-life and / or exposure, or may provide compounds useful for investigating in vivo pathways of drug elimination and metabolism. Examples of isotopes that may be incorporated into compounds of the present disclosure include: 2 H, 3 H, 13 C. 14 C. 15 N,18 O. 17 O. 35 S, 36 Cl, and 18 Of particular note are compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1) that are enriched with tritium or carbon-14, which can be used, for example, in tissue distribution studies, particularly compounds of the present disclosure that are enriched with deuterium at metabolic sites, resulting in compounds with, for example, greater metabolic stability, and compounds that can be used in positron emission topography (PET) studies. 11 C. 18 F, 15 O, and 13 A compound of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1) enriched in a positron-emitting isotope such as N. Isotopically enriched compounds may be prepared by conventional techniques well known to those skilled in the art.

[0056] As used herein, the phrases "of the formula," "having the formula," or "having the structure" are not intended to be limiting and are used in the same manner as the term "comprising" is generally used. For example, when a structure is depicted, it is understood that all stereoisomeric and tautomeric forms are encompassed unless otherwise specified.

[0057] Certain compounds described herein contain one or more asymmetric centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, which can be defined in terms of absolute stereochemistry as (R)- or (S)-. In some embodiments, to optimize the therapeutic activity of the compounds of the present disclosure, e.g., for treating cancer, it may be desirable for the carbon atoms to have a particular configuration (e.g., (R,R), (S,S), (S,R), or (R,S)), or to be enriched in stereoisomeric forms having such configurations. Compounds of the present disclosure can be provided as racemic mixtures. Thus, the present disclosure relates to racemic mixtures, pure stereoisomers (e.g., enantiomers and diastereomers), stereoisomer-enriched mixtures, and the like, unless otherwise indicated. When chemical structures are depicted herein without any stereochemistry, it is understood that all possible stereoisomers are encompassed by such structures. Similarly, when a particular stereoisomer is shown or designated herein, unless otherwise indicated, it will be understood by those skilled in the art that minor amounts of such other isomers may be present in the composition, provided that the overall utility of the disclosed composition is not precluded by the presence of other stereoisomers. Individual stereoisomers can be obtained by a number of methods known in the art, including preparation using chiral synthons or chiral reagents, resolution using chiral chromatography using a suitable chiral stationary phase or chiral support, or by chemically converting them to diastereomers, separating the diastereomers by conventional means such as chromatography or recrystallization, and then regenerating the original stereoisomers.

[0058] Additionally, where applicable and unless otherwise specified, all cis-trans or E / Z isomers (geometric isomers), tautomeric forms, and topoisomeric forms of the compounds described herein are included within the scope of the disclosure.

[0059] The term "tautomer," as used herein, refers to each of two or more isomers of a compound that exist in equilibrium and are readily interconvertible. For example, one skilled in the art will recognize that 1,2,3-triazole exists in two tautomeric forms. [ka] Unless otherwise specified, chemical compounds described herein are intended to encompass all possible tautomers, even when the structure depicts only one tautomer. For example, for clarity, even though a single tautomer of the following compound may be depicted herein, the present disclosure is intended to encompass all possible tautomers, including: [ka]

[0060] The term "pharmaceutically acceptable" refers to a substance that is biologically or otherwise acceptable when used in the subject compositions and methods. For example, the term "pharmaceutically acceptable carrier" refers to a substance such as an adjuvant, excipient, fluidizer, sweetener, diluent, preservative, dye, colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonicity agent, solvent, or emulsifier that can be introduced into a composition and administered to a patient without causing unacceptable biological effects or interacting with other components of the composition in an unacceptable manner. Such pharmaceutically acceptable substances typically have met the required standards of toxicological and manufacturing testing and include substances identified as suitable inactive ingredients by the U.S. Food and Drug Administration.

[0061] The terms "salt" and "pharmaceutically acceptable salt" refer to a salt prepared from a base or an acid. A pharmaceutically acceptable salt is suitable for administration to a patient, such as a mammal (e.g., a salt that has acceptable mammalian safety for a given dosing regimen). Salts can be formed from inorganic bases, organic bases, inorganic acids, and organic acids. In addition, when a compound contains both a basic moiety, such as an amine, pyridine, or imidazole, and an acidic moiety, such as a carboxylic acid or tetrazole, zwitterions can be formed, and zwitterions are included in the term "salt" as used herein. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0062] "Pharmaceutically acceptable acid addition salts" refer to salts which are not biologically or otherwise undesirable and which retain the biological effectiveness and properties of the free bases formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts formed with organic acids such as aliphatic monocarboxylic and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, including, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Thus, exemplary salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, malate, tartrate, methanesulfonate, and the like. Also contemplated are amino acid salts such as arginate, gluconate, and galacturonate (see, e.g., Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt according to methods and techniques familiar to those skilled in the art.

[0063] "Pharmaceutically acceptable base addition salts" refer to salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from the addition of inorganic or organic bases to the free acids. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. See Berge et al., supra.

[0064] "Prodrug" is intended to refer to a compound that can be converted under physiological conditions or by solvation into a biologically active compound as described herein. That is, the term "prodrug" refers to a pharmaceutically acceptable precursor of a biologically active compound. In some embodiments, a prodrug is inactive when administered to a subject, but is converted to an active compound in vivo, for example, by hydrolysis. Prodrug compounds often offer advantages of solubility, tissue compatibility, or delayed release in mammals (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam); Higuchi, T., et al., "Prodrugs as Novel Delivery Systems," (1987) ACS Symposium Series, Vol. 14; and Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, each of which is incorporated herein by reference in its entirety). The term "prodrug" is also intended to include any covalently bonded carrier that releases an active compound in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the active compounds described herein are typically prepared by modifying functional groups present in the active compound such that the modifications are cleaved to the parent active compound either by routine manipulation or in vivo. Prodrugs include compounds in which a hydroxy group, an amino group, or a mercapto group is bonded to any group that is cleaved to form a free hydroxy group, a free amino group, or a free mercapto group, respectively, when the prodrug of the active compound is administered to a mammalian subject. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of hydroxy functional groups in the active compound, and acetamide, formamide, and benzamide derivatives of amine functional groups.

[0065] The term "in vivo" refers to events that occur within a subject's body. The term "ex vivo" refers to events that occur initially outside a subject's body for subsequent in vivo application within the subject's body. For example, ex vivo preparation can involve preparing cells outside a subject's body with the intent of introducing the prepared cells into the body of the same or a different subject. The term "in vitro" refers to events that occur outside a subject's body. For example, an in vitro assay encompasses any assay performed outside a subject's body. In vitro assays encompass cell-based assays in which live or dead cells are used. In vitro assays also encompass cell-free assays in which intact cells are not used.

[0066] The present disclosure is also intended to encompass in vitro metabolic products of the compounds of the present disclosure. Such products may result, for example, from oxidation, reduction, hydrolysis, amidation, esterification, etc. of the administered compound, primarily by enzymatic processes. Accordingly, the present disclosure includes compounds produced by a process comprising administering a compound disclosed herein to a mammal for a period of time sufficient to yield a metabolic product thereof. Such products are typically identified by administering a detectable dose of a radiolabeled compound of the present disclosure to an animal, such as a rat, mouse, guinea pig, monkey, or human, allowing sufficient time for metabolism to occur, and isolating the conversion product from urine, blood, or other biological sample.

[0067] The terms "administer," "administering," "administration," and derivatives thereof refer to methods that can be used to enable delivery of an agent or composition to a desired site of biological action. These methods include, but are not limited to, parenteral administration (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular, intrathecal, intranasal, intravitreal injection, and local injection), transmucosal injection, oral administration, administration as a suppository, and topical administration. Administration may be by any route, including parenteral. Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, implantation, and the like. Those skilled in the art will know additional methods for administering a therapeutically effective amount of a composition of the present disclosure to prevent or alleviate one or more symptoms associated with a disease.

[0068] The term "systemic administration" refers to administering an agent or composition such that the agent or composition is distributed throughout the subject's body. Distribution of the agent or composition throughout the subject's body can be uniform. Alternatively, distribution can be selective, resulting in higher localization of the agent or composition at one or more desired sites. The desired sites can be the blood or another site accessible by the vascular system. Non-limiting examples of systemic routes of administration include (1) administration by introducing the agent directly into the vascular system, or (2) oral, pulmonary, or intramuscular administration, in which the agent is adsorbed, enters the vascular system, and is carried via the blood to one or more desired site(s) of action. In contrast, "non-systemic administration" refers to administering an agent or composition such that the agent or composition is administered locally to a desired target site in the subject's body to affect a primarily local effect.

[0069] The terms "co-administration," "administered in combination with," and their grammatical equivalents include administering two or more agents and / or their metabolites to a subject so that both agents can perform their respective functions. Co-administration includes simultaneous administration in separate compositions, administration at different times in separate compositions, or administration in a composition in which both agents are present.

[0070] The term "effective amount" or "therapeutically effective amount" refers to an amount of an agent sufficient to produce a beneficial or desired result. A therapeutically effective amount may vary depending on one or more of the subject and condition being treated, the subject's weight and age, the severity of the condition, the mode of administration, etc., which can be readily determined by one of ordinary skill in the art. An effective amount of an active agent may be administered in a single dose or multiple doses. A component may be described herein as having at least an effective amount, or at least an effective amount, such as those associated with a particular goal or objective, such as any described herein. The term "effective amount" also applies to a dose that provides an image for detection by an appropriate imaging method. Specific doses may vary depending on one or more of the particular agent selected, the dosing regimen to be followed, whether the agent is administered in combination with other compounds, the timing of administration, the tissue to be imaged, and the physical delivery system in which the agent is delivered.

[0071] As used herein, "treating" or "treatment" refers to an approach for achieving a beneficial or desired result with respect to a disease, disorder, or condition (such as cancer) in a subject, including, but not limited to, (a) preventing a disease or condition from occurring, e.g., preventing the recurrence of a disease or condition, or prophylactic treatment of a subject predisposed to a disease or condition; (b) ameliorating a disease or condition, e.g., eliminating or causing a remission of a disease or condition in a subject; (c) inhibiting a disease or condition, e.g., slowing or arresting the onset of a disease or condition in a subject; or (d) alleviating the symptoms of a disease or condition in a subject. For example, "treating cancer" includes preventing cancer from occurring, ameliorating cancer, inhibiting cancer, and alleviating the symptoms of cancer. A therapeutic benefit is also achieved by eradicating or ameliorating one or more physiological symptoms associated with the underlying disorder, such that an improvement is observed in a subject, even though the subject may still suffer from the underlying disorder.

[0072] A "therapeutic effect," as that term is used herein, encompasses the therapeutic and / or prophylactic benefits described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0073] The terms "antagonist" and "inhibitor" are used interchangeably and refer to compounds that have the ability to inhibit the biological function (e.g., activity, expression, binding, protein-protein interaction) of a target protein (e.g., PTPN2). Thus, the terms "antagonist" and "inhibitor" are defined in the context of the biological role of the target protein. Preferred antagonists herein specifically interact (e.g., bind) with the target, but specifically included within this definition are compounds that inhibit the biological activity of the target protein by interacting with other members of a signaling pathway of which the target protein is a member.

[0074] The term "selective inhibition" or "selectively inhibiting" refers to the ability of a bioactive agent to preferentially reduce target signaling activity relative to off-target signaling activity, through direct or indirect interaction with the target.

[0075] The terms "subject" and "patient" refer to an animal, such as a mammal, e.g., a human. The methods described herein can be useful for both human therapy and veterinary applications. In some embodiments, the subject is a mammal, such as a human. "Mammal" includes both humans and domestic animals, such as laboratory animals and household pets (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits), as well as non-domestic animals, such as wildlife.

[0076] The terms "therapeutic agent," "therapeutic agent," or "treatment agent" are used interchangeably and refer to a molecule or compound that, when administered to a subject, produces some beneficial effect. Beneficial effects include enabling a diagnostic determination, ameliorating a disease, symptom, disorder, or condition, reducing or preventing the onset of a disease, symptom, disorder, or condition, and generally counteracting a disease, symptom, disorder, or condition.

[0077] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymers may be linear or branched, may comprise modified amino acids, and may be interrupted by non-amino acids. These terms also encompass amino acid polymers that have been modified, for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. As used herein, the term "amino acid" refers to either natural amino acids and / or unnatural or synthetic amino acids, including glycine and both D- or L-optical isomers, as well as amino acid analogs and peptidomimetics.

[0078] The terms "polynucleotide," "nucleotide sequence," "nucleic acid," and "oligonucleotide" are used interchangeably. These terms refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides can have any three-dimensional structure and can perform any function, known or unknown. Coding or non-coding regions of a gene or gene fragment, locus(s) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, small interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers are non-limiting examples of polynucleotides. A polynucleotide may contain one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acids (PNAs), morpholino nucleic acids, locked nucleic acids (LNAs), glycol nucleic acids (GNAs), threose nucleic acids (TNAs), 2'-fluoro, 2'-OMe, and phosphorothioated DNA. Modifications to the nucleotide structure, if present, may be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. Polynucleotides may be further modified after polymerization, such as by conjugation with a labeling component or other conjugation target.

[0079] As used herein, "expression" refers to the process by which a polynucleotide is transcribed from a DNA template (such as into mRNA or other RNA transcript) and / or the process by which the transcribed mRNA is subsequently translated into a peptide, polypeptide, or protein. The transcript and the encoded polypeptide may be collectively referred to as a "gene product." If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0080] "Aberrantly expressed" or "aberrant expression," when applied to a nucleotide sequence (e.g., a gene) or polypeptide sequence in a subject, refers to the abnormal production of mRNA transcribed and / or translated from the nucleotide sequence or the protein product encoded by the nucleotide sequence. A differentially expressed sequence can be overexpressed (or abnormally high expression) or underexpressed (or abnormally low expression) compared to the expression level of a reference sample (i.e., reference level). As used herein, overexpression is an increase in expression of at least 1.25-fold, or alternatively at least 1-fold, at least 2-fold, at least 3-fold, at least 4-fold, or at least 10-fold, etc., above that detected in the reference sample. As used herein, underexpression is a decrease in expression of at least 1.25-fold, or alternatively at least 1-fold, at least 2-fold, at least 3-fold, at least 4-fold, or at least 10-fold, etc., above that detected in the reference sample. Underexpression also encompasses the lack of expression of a particular sequence evidenced by the lack of detectable expression in a test subject when compared to a reference sample.

[0081] The term "reference level" refers to a control level used to evaluate the test level. In some examples, the reference level can be a control. For example, a biomarker can be considered underexpressed when its expression level is lower than the reference level. The reference level can be determined by multiple methods, provided that the resulting reference level accurately represents the biomarker level and there is a first control group whose level, when exceeded, has a different likelihood of showing a clinically beneficial response to treatment with a PTPN2 inhibitor than the likelihood of a second patient group whose biomarker level is below the reference level. The reference level can be determined, for example, by measuring the expression level of the biomarker in tumorous or non-tumorous cancer cells from the same tissue as the tissue of the cancer cells being tested. In some examples, the reference level can be the level of the biomarker determined in vivo. The reference level can be determined by comparing biomarker levels in a population of subjects with the same cancer. Two or more separate subject groups can be determined by identifying subsets of a cohort population with the same or similar levels of a biomarker. The reference level can then be determined based on the level that distinguishes these separate groups. The reference level can be a single number that is equally applicable to all subjects, or the reference level can vary depending on the specific subpopulation of subjects. For example, elderly men may have a different reference level for the same cancer than young men, and women may have a different reference level for the same cancer than men. Furthermore, the reference level can be any level determined individually for each subject. For example, the reference level can be the ratio of the biomarker level in cancer cells of the same subject to the biomarker level in normal cells of the same subject. In some embodiments, the reference level is a numerical range of gene expression obtained from statistical sampling from a population of individuals with cancer. The sensitivity of individuals with cancer to treatment with a PTPN2 inhibitor can be determined.In certain embodiments, the reference level is derived by comparing gene expression with a control gene (e.g., a housekeeping gene such as actin) that is expressed at a relatively stable level in the same cellular environment. Comparison with the reference level can be a qualitative assessment or a quantitative determination.

[0082] The terms "determining," "measuring," "evaluating," "assessing," "assaying," "testing," and "analyzing" are used interchangeably herein to refer to any form of measurement, including determining whether an analyte is present (e.g., detecting). These terms can include both quantitative and / or qualitative determinations. Assessment can be relative or absolute. A relative amount can be, for example, high, medium, or low. An absolute amount can reflect the measured intensity of a signal, or converting this signal intensity to another quantitative form, such as micrograms / mL. "Detecting the presence of" can include determining the amount of something present, as well as determining whether it is present or absent.

[0083] "Signal transduction" is the process by which stimulatory or inhibitory signals are transmitted into or within a cell to elicit an intracellular response. A molecule can mediate its signaling effect through direct or indirect interaction with downstream molecules in the same pathway or related pathway(s). For example, PTPN2 signaling can involve a number of downstream molecules, including, but not limited to, PI3-kinase and AKT.

[0084] The term "downregulating PTPN2 activity," as used herein, refers to slowing down, reducing, altering, inhibiting, and completely eliminating and / or preventing PTPN2 activity.

[0085] The term "effector function" refers to a specialized function of a cell. An effector function of a T cell can be, for example, cytolytic activity or helper activity, including secretion of cytokines. Thus, the term "intracellular signaling domain" refers to the portion of a protein that transmits an effector function signal and instructs the cell to carry out a specialized function.

[0086] The term "autologous" refers to any material derived from the same individual that is subsequently reintroduced into the individual. The term "allogeneic" refers to any material derived from a different animal of the same species as the individual to which the material is introduced. Two or more individuals are said to be allogeneic to one another when the genes at one or more loci are not identical. In some embodiments, allogeneic material from individuals of the same species may be sufficiently genetically different to interact antigenically.

[0087] The term "costimulatory molecule" refers to a cognate binding partner on a T cell that specifically binds to a costimulatory ligand, thereby mediating a costimulatory response by the T cell, such as, but not limited to, proliferation. Costimulatory molecules are cell surface molecules other than antigen receptors or their ligands that contribute to an efficient immune response. Costimulatory molecules include, but are not limited to, MHC class I molecules, BTLA and Toll ligand receptors, as well as OX40, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a / CD18), ICOS (CD278), and 4-1BB (CD137). Further examples of such costimulatory molecules include CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, CD4, CD8 alpha, CD8 beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, L Examples of ligands that specifically bind to costimulatory molecules include FA-1, ITGB7, NKG2D, NKG2C, TNFR2, TRANCE / RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, ​​LAT, GADS, SLP-76, PAG / Cbp, CD19a, and CD83. The costimulatory intracellular signaling domain can be the intracellular portion of a costimulatory molecule. Costimulatory molecules can be represented in the following protein families: TNF receptor proteins, immunoglobulin-like proteins, cytokine receptors, integrins, signaling lymphocyte activation molecules (SLAM proteins), and activating NK cell receptors.Examples of such molecules include ligands that specifically bind to CD27, CD28, 4-1BB (CD137), OX40, GITR, CD30, CD40, ICOS, BAFFR, HVEM, ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), CD2, CDS, CD7, CD287, LIGHT, NKG2C, NKG2D, SLAMF7, NKp80, NKp30, NKp44, NKp46, CD160, B7-H3, and CD83. The intracellular signaling domain can comprise the entire intracellular portion or entire native intracellular signaling domain of the molecule from which it is derived, or a functional fragment or derivative thereof.

[0088] The terms "immune effector cell" and "effector cell" are used interchangeably herein. These terms refer to cells that are involved in an immune response, e.g., promoting an immune effector response. Examples of immune effector cells include T cells, e.g., alpha / beta T cells and gamma / delta T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells, and bone marrow-derived phagocytes.

[0089] The terms "immunity" and "immune response" are used interchangeably herein. When applied to a subject, these terms refer to the ability of the subject to mount an immune response, via its immune cells, to an antigen, including, but not limited to, a tumor antigen, a viral antigen, a bacterial antigen, or a neoantigen. When applied to a cell, these terms refer to the ability of the cell to generate a cellular response, directly or indirectly, to an antigen, including, but not limited to, a tumor antigen, a viral antigen, a bacterial antigen, or a neoantigen.

[0090] The term "lymphoid cell(s)" refers to any of the cells responsible for the generation of immunity (or immune response) mediated by cells or antibodies, including lymphocytes, lymphoblasts, and plasma cells. Lymphoid cells include granulocytes such as basophils, eosinophils, and neutrophils, mast cells, monocytes that can evolve into macrophages, antigen-presenting cells such as dendritic cells, and lymphocytes such as natural killer cells (NK cells), B cells, and T cells (including activated T cells). In some examples, T cells include both naive and memory cells (e.g., central memory or T cells). CM , Effector Memory or T EM , and effector memory RA or T EMRA ), effector cells (e.g., cytotoxic T cells or CTL cells or Tc cells), helper cells (e.g., Thl, Th2, Th3, Th9, Th7, TfH), regulatory cells (e.g., Treg and Trl cells), natural killer T cells (NKT cells), tumor-infiltrating lymphocytes (TIL), lymphocyte-activated killer cells (LAK), αβT cells, γδT cells, and similar unique classes of T cell lineages.

[0091] The terms "tumor marker," "tumor antigen," and "tumor-associated antigen" are used interchangeably herein and refer to a molecule or fragment thereof expressed on or inside a cancer cell, or another molecule or fragment thereof (e.g., circulating tumor DNA or circulating tumor RNA) derived from a cancer cell, that is useful for detecting cancer cells or preferentially targeting drugs to cancer cells. A tumor antigen can be a marker expressed by both normal and cancer cells, such as a lineage marker, e.g., CD19 on B cells. A tumor antigen can also be a cell surface molecule that is overexpressed or underexpressed on cancer cells compared to normal cells. A tumor antigen can also be a cell surface molecule that is inappropriately synthesized on cancer cells, e.g., a molecule that contains deletions, additions, or mutations compared to molecules expressed on normal cells. A tumor antigen can be expressed exclusively on the cell surface of cancer cells, either completely or as fragments (e.g., MHC / peptides), and is not synthesized or expressed on the surface of normal cells. Tumor antigens include neoantigens encoded by tumor-specific mutated genes.

[0092] The term "transiently downregulated," as used herein, generally refers to a non-permanent downregulation of the expression or activity of a target molecule (e.g., PTPN2). Transient downregulation may not be a permanent downregulation. In some cases, transient downregulation may involve downregulating (e.g., reducing) the expression or activity of a target molecule over a period of time, followed by maintaining at least a portion of the expression or activity level of the target molecule that was previously downregulated. Transient downregulation may involve intermittent downregulation of a target molecule (e.g., PTPN2).

[0093] The term "intermittent" is used herein to describe a process that is not continuous. An intermittent process can be followed by a break or cessation. Multiple intermittent processes can involve alternating starting and stopping of the same or different processes. In some embodiments, the term "intermittent dosing regimen," as used herein, refers to a dosing regimen that includes administering a pharmaceutical composition followed by a rest period.

[0094] The term "side effect," as used herein, refers to any complication that is an unwanted or pathological outcome of a therapy (e.g., cell therapy, immunotherapy, etc.) that occurs in addition to, or instead of, the desired therapeutic outcome of the therapy. Examples of side effects may include, but are not limited to, (i) off-target cytotoxicity, (ii) on-target off-tumor toxicity, and / or (iii) autoimmunity (e.g., chronic autoimmunity). In one example, a side effect of cell therapy involving a T cell receptor fusion protein (TFP) and / or a chimeric antigen receptor (CAR) may include graft-versus-host disease. In another example, a side effect of cell therapy involving a TFP and / or a CAR may include the death of cells configured to express the TFP and / or the CAR.

[0095] Other examples of side effects of cell therapy may include, but are not limited to, disorders mediated by phagocytes, including macrophages and neutrophilic granulocytes (polymorphonuclear leukocytes, PMNs), and / or T cells. Examples include inflammatory skin diseases including psoriasis, responses associated with inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), adult respiratory distress syndrome, dermatitis, CNS inflammatory disorders such as multiple sclerosis, allergic conditions such as uveal disorders, eczema, and asthma, as well as other conditions involving T cell infiltration and chronic inflammatory responses, cutaneous hypersensitivity reactions including poison ivy and poison oak, rheumatoid arthritis, systemic lupus erythematosus (SLE), diabetes, multiple sclerosis, Raynaud's syndrome, autoimmune thyroid disease, and other conditions involving T cell infiltration and chronic inflammatory responses. autoimmune diseases such as adenitis, Sjogren's syndrome, juvenile-onset diabetes, and immune responses associated with cytokine- and T-lymphocyte-mediated delayed hypersensitivity typically found in tuberculosis, sarcoidosis, polymyositis, granulomatosis, and vasculitis; pernicious anemia, multiple organ dysfunction syndrome secondary to sepsis or trauma; autoimmune hemolytic anemia, myasthenia gravis, antigen-antibody complex-mediated diseases; and / or transplant rejection of any kind, including graft-versus-host disease or host-versus-graft disease.

[0096] The term "effectiveness" of a treatment or method, as used herein, can be measured based on the course of a disease or condition in response to such treatment or method. For example, the effectiveness of a treatment or method of the present disclosure can be measured by its effect on the signs or symptoms of a subject's disease or condition, e.g., a subject's tumor or cancer. A response can be achieved when a subject with a disease or condition experiences partial or complete alleviation of the disease or condition, or a reduction in one or more symptoms of the disease or condition. In one example, a response can be achieved when a subject suffering from a tumor exhibits a reduction in tumor size after a treatment or method provided in the present disclosure. In some examples, efficacy can be measured by assessing cancer cell death, tumor shrinkage (e.g., as evidenced by a reduction in tumor size), and / or inhibition of tumor growth, progression, and dissemination.

[0097] An "antigen" is a moiety or molecule that contains an epitope and therefore also specifically binds to an antibody. An "antigen-binding unit" can be the whole or fragment(s) of a full-length antibody, a structural variant thereof, a functional variant thereof, or a combination thereof. Full-length antibodies can be, for example, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized antibodies, humanized antibodies, and human antibodies. Examples of fragments of full-length antibodies include variable heavy chains (VH), variable light chains (VL), heavy chains (VHH or VL) found in camelids, such as camels, llamas, and alpacas. H H), heavy chains found in sharks (V-NAR domains), single domain antibodies (sdAbs, e.g., "nanobodies") comprising a single antigen-binding domain, Fv, Fd, Fab, Fab', F(ab')2, and "r IgG" (or half antibodies). Examples of modified antibody fragments may include, but are not limited to, scFv, di-scFv, or bi(s)-scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabodies, single-chain diabodies, tandem diabodies (Tandab's), tandem di-scFv, tandem tri-scFv, minibodies (e.g., (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3), ((scFv)2-CH3) or (scFv-CH3-scFv)2), and multibodies (e.g., triabodies or tetrabodies).

[0098] The term "antibody(s)" encompasses any antigen-binding unit, including, but not limited to, monoclonal antibodies, human antibodies, humanized antibodies, camelized antibodies, chimeric antibodies, and any other epitope-binding fragment.

[0099] The practice of some embodiments disclosed herein will employ, unless otherwise indicated, conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics, and recombinant DNA that are within the skill of one in the art. See, e.g., Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4th Edition (2012), the series Current Protocols in Molecular Biology (F.M.A.usubel, et al. eds.), the series Methods in Enzymology (Academic Press, Inc.), PCR 2: A Practical Approach (M.J. MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th Edition (R.I. Freshney, ed. (2010)).

[0100] compound The compounds disclosed herein, including compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), and (IV-1), or pharmaceutically acceptable salts or solvates thereof, are PTPN2 inhibitors and have a wide range of applications in therapy, diagnosis, and other biomedical research.

[0101] In certain aspects, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W 1 is C, C(R 8 ), and N; W 2 is C, C(R 8 ), and N; W 4 is N and C(R 4 ) and W 5 is N and C(R 5 ) and W 6 is N and C(R 6 ) and J 1 is N, C, and C(R 8 ) and J 2 is N, N(R 7 ), C(R 8 ), C(R 8 )2, and C(O), J 3 is N(R 7 ) and C(R 8 )2 is selected, L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 9 is C 3~12 carbocycle and 3- to 12-membered heterocycle, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 optionally substituted with R 4 , R 5 , R 6 , and R 8 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 7 is, in each occurrence, independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are substituted with one, two, or three R 20optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, [ka] indicates a single or double bond where all valences are satisfied, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of the groups is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -OR 15 , -O-(C 1~6alkyl)-OR 15 , -OC(O)N(R 12 )(R 13 ), -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 is replaced by .

[0102] In certain aspects, the present disclosure provides a compound of formula (I-1): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W 1 is C, C(R 8 ), and N; W 2 is C, C(R 8 ), and N; W 4 is N and C(R 4 ) and W 5 is N and C(R 5 ) and W 6 is N and C(R 6 ) and J 1 is N, C, and C(R 8 ) and J 2 is N, N(R 7 ), C(R 8 ), C(R 8 )2, and C(O), J 3 is N(R 7 ) and C(R 8 )2 is selected, L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 9 is C 3~12 carbocycle and 3- to 12-membered heterocycle, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 and each C 1~6 Alkyl can be one, two, or three R 20 optionally substituted with R 4 , R 5 , R 6 , and R 8 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 7 is, in each occurrence, independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 optionally substituted with 1, 2, or 3 substituents selected from R 13 is, in each occurrence, independently hydrogen, C 1~6Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12, -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, [ka] indicates a single or double bond where all valences are satisfied, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of the groups is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -OC(O)N(R 12 )(R 13 ), -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 is replaced by .

[0103] In some embodiments, for compounds of formula (I) or (I-1), W 4 is C(R 4 ) and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W 4 is C(R 4 In some embodiments, W 4 is N. In some embodiments, W 5is C(R 5 In some embodiments, W 6 is C(R 6 In some embodiments, W 4 is N and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W 1 is C and W 2 is C(R 8 In some embodiments, W 1 is C(R 8 ) and W 2 is C. In some embodiments, W 1 is C and W 2 is C(R 8 ) and W 4 is C(R 4 ) and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W 1 is C(R 8 ) and W 2 is C and W 4 is C(R 4 ) and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W 1 is C and W 2 is CH and W 4 is CH and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W 1 is CH and W 2 is C and W 4 is CH and W 5 is C(R 5 ) and W 6 is C(R 6 In some embodiments, W1 is C and W 2 is CH and W 4 is CH and W 5 is C(R 5 ) and W 6 is CF. In some embodiments, W 1 is CH and W 2 is C and W 4 is CH and W 5 is C(R 5 ) and W 6 is CF. In some embodiments, W 1 is C and W 2 is CH and W 4 is CH and W 5 is C(OH) and W 6 is CF. In some embodiments, W 1 is CH and W 2 is C and W 4 is CH and W 5 is C(OH) and W 6 is CF.

[0104] In some embodiments, for compounds of formula (I) or (I-1), J 1 is selected from N and C, and J 2 is C(R 8 ) and C(R 8 )2, and J 3 is N(R 7 In some embodiments, J 1 is selected from N and C, and J 2 is C(R 8 ) and C(R 8 In some embodiments, J 1 is N. In some embodiments, J 2 is C(R 8 )2. In some embodiments, J 3 is N(R 7 In some embodiments, J 1 is N and J 2 is C(R 8)2. In some embodiments, J 1 is N and J 2 is C(R 8 )2 and J 3 is N(R 7 In some embodiments, J 1 is C. In some embodiments, J 2 is C(R 8 In some embodiments, J 1 is C and J 2 is C(R 8 In some embodiments, J 1 is C and J 2 is C(R 8 ) and J 3 is N(R 7 In some embodiments, J 1 is selected from N and C, and J 2 is selected from CH and CH2, J 3 is N(R 7 In some embodiments, J 1 is selected from N and C, and J 2 is selected from CH and CH2, J 3 is NH. In some embodiments, J 1 is selected from N and C, and J 2 is selected from CH and CH. In some embodiments, J 2 is CH. In some embodiments, J 3 is N(R 7 In some embodiments, J 3 is NH. In some embodiments, J 1 is N and J 2 is CH. In some embodiments, J 1 is N and J 2 is CH2 and J 3 is N(R 7 In some embodiments, J 1 is N and J 2 is CH2 and J 3 is NH. In some embodiments, J2 is CH. In some embodiments, J 1 is C and J 2 is CH. In some embodiments, J 1 is C and J 2 is CH and J 3 is N(R 7 In some embodiments, J 1 is C and J 2 is CH and J 3 is NH.

[0105] In some embodiments, for compounds of formula (I) or (I-1), R 9 is C 3~8 carbocycle and 3- to 8-membered heterocycle, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is a 4- to 7-membered heterocyclic ring, and the 4- to 7-membered heterocyclic ring is selected from the group consisting of (i) one, two, or three R 20 and (ii) -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is a 4- to 7-membered heterocyclic ring, and the 4- to 7-membered heterocyclic ring is selected from the group consisting of (i) one, two, or three R 20 and (ii) -OR 15 , -O-(C 1~6 alkyl)-OR 15, -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 and (iii) contains one carbon-carbon double bond. In some embodiments, R 9 is C 3~8 carbocycle and 3- to 8-membered heterocycle, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 optionally substituted with C 3~8 The carbocycles and 3- to 8-membered heterocycles are saturated or partially unsaturated. 3~8 The carbocyclic and 3- to 8-membered heterocyclic rings are saturated. 3~8 The carbocycle and 3- to 8-membered heterocycle are partially unsaturated. 3~8 Carbocycles and 3- to 8-membered heterocycles contain one carbon-carbon double bond. In some embodiments, R 9 is selected from pyrrolidine, 2,5-dihydro-1H-pyrrole, piperidine, and 1,2,3,6-tetrahydropyridine, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9is selected from pyrrolidin-3-yl, 2,5-dihydro-1H-pyrrol-3-yl, piperidin-3-yl, and 1,2,3,6-tetrahydropyridin-3-yl, each of which is selected from (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is pyrrolidin-3-yl, which is selected from the group consisting of (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is 2,5-dihydro-1H-pyrrol-3-yl, which is selected from the group consisting of (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is piperidin-3-yl, which is selected from the group consisting of (i) one, two, or three R20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is 1,2,3,6-tetrahydropyridin-3-yl, which is selected from the group consisting of (i) one, two, or three R 20 and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R 9 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 In some embodiments, R is a 4- to 7-membered heterocycle containing a ring nitrogen atom substituted with 9 -OR 15 or O-(C 1~6 alkyl)-OR 15The ring carbon atoms are substituted by:

[0106] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] where: W is C(R 2 )2, n is 0, 1, or 2; R 1 is halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12, -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R 20 is optionally substituted with

[0107] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] [ka] [ka] In some embodiments, R 9 teeth, [ka] is.

[0108] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] is.

[0109] In some embodiments, for compounds of formula (I) or (I-1), R 9 is C 1~6 Alkyl, [ka] In some embodiments, R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] In some embodiments, R 9 is substituted with -CN.

[0110] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] In some embodiments, R 9 teeth, [ka] is replaced by .

[0111] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] is substituted with a substituent selected from:

[0112] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] is substituted with a substituent selected from:

[0113] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] is substituted with a substituent selected from:

[0114] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] is substituted with a substituent selected from:

[0115] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] is substituted with a substituent selected from:

[0116] In some embodiments, for compounds of formula (I) or (I-1), R 9 teeth, [ka] is substituted with a substituent selected from:

[0117] In some embodiments, for compounds of Formula (I) or (I-1), (i) R 9 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , or -C(O)O-(C 1~6 alkyl)-OR 15 or (ii) W 1 , W 2 , W 4 , W 5 , or W 6 -OR 15 , -O-(C 1~6 alkyl)-OR 15 , or -OC(O)N(R 12 )(R 13 ) or (iii) J 2 Or J 3 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)O-(C 1~6 alkyl)-OR 15 , or -(C 1~6 alkyl)-OR 15 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of the is -OR 15 , -O-(C 1~6alkyl)-OR 15 , -OC(O)N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 9 is -C(O)OR12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 9 is -C(O)OCH2OC(O)R 12 or -C(O)OCH(CH3)OC(O)R 12 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3At least one of -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH) or —CHP(O)(OH). In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12, -P(O)(OH)2, or -CH2P(O)(OH)2, and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(OH)2, or -CH2P(O)(OH)2, and R 12 is C 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3at least one of -OC(O)N(CH3)2, -OC(O)N(CH3)(CH2CH2OCH3), -OC(O)NHCH2CH3, -OC(O)(pyrrolidin-1-yl), -OC(O)CH(CH3)OC(O)CH3, -OC(O)CH(CH3)OC(O)CH(CH3)2, -OC(O)CH(CH3)2, methyleneoxy(4-methyl-1,3-dioxol-2-one), -OCH2OC(O)CH2CH2CH3, -OCH2OP(O)(OCH2OC(O)OCH(CH3)2)2, -OC(O)CH(NH2)CH(CH3)2, -OCH2OP(O)(OH)2, -C(O)OCH(CH3)OC(O)CH(CH3)2, -C(O)OCH(CH3)OC( and substituted with -O)CH3, -C(O)OCH(CH3)OC(O)CH2CH2CH3, -C(O)OCH(CH3)2, -C(O)OCH2CH(CH3)2, -C(O)O(CH2)3CH3, ((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)(oxo)methyl, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OCH(CH3)OC(O)CH(NH2)(CH(CH3)2), -C(O)OCH2OC(O)(4-(phosphonooxy)phenyl)methyl, -CH2OP(O)(OH)(OCH2OC(O)OCH(CH3)2), -C(O)OCH(CH3)OP(O)(OH)2, or -CH2OP(O)(OH2). In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3At least one of -OC(O)N(CH3)2, -OC(O)N(CH3)(CH2CH2OCH3), -OC(O)NHCH2CH3, -OC(O)(pyrrolidin-1-yl), -OC(O)CH(CH3)OC(O)CH3, -OC(O)CH(CH3)OC(O)CH(CH3)2, -OC(O)CH(CH3)2, methyleneoxy(4-methyl-1,3-dioxol-2-one), -OCH2OC(O)CH2CH2CH3, -OCH2OP(O) substituted with (OCH2OC(O)OCH(CH3)2), -OC(O)CH(NH2)CH(CH3)2, -OCH2OP(O)(OH), -CH2OP(O)(OH), -CH(CH3)OP(O)(OH), -CH2OP(O)(OCH2OC(O)OCH(CH3)2), -CH2OC(O)CH(NH2)(CH(CH3)2), -CH(CH3)OC(O)CH(NH2)(CH(CH3)2), or -CH2OC(O)CH(CH3)2.

[0118] In some embodiments, for compounds of formula (I) or (I-1), R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) in which R 12 is C 1~6 Alkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), each of which is optionally and independently selected from —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR16 )(YR 17 ) and R 12 are independently -N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 C optionally substituted with 1, 2, or 3 substituents selected from 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) and R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 9 , W 1, W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) and R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(XR 16 )(YR 17 ), -OCH2OP(O)(XR 16 )(YR 17 ), -OC(O)N(R12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), or -CH2P(O)(XR 16 )(YR 17 ) and R 12 is optionally substituted with -NHC(O)CH(CH3)NH2, -NHC(O)CH(CH3)N(CH3)2, -NHC(O)CH(CH(CH3)2)NH2, or -NHC(O)CH(CH(CH3)2)N(CH3)2 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12, -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(OH)2, or -CH2P(O)(OH)2, and R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 9 , W 1 , W 2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(OH)2, or -CH2P(O)(OH)2, and R 12 is a C substituted with -NHC(O)CH(CH3)NH2, -NHC(O)CH(CH3)N(CH3)2, -NHC(O)CH(CH(CH3)2)NH2, or -NHC(O)CH(CH(CH3)2)N(CH3)2. 1~6 In some embodiments, R 9 , W 1 , W2 , W 4 , W 5 , W 6 , J 2 , or J 3 At least one of -OC(O)N(CH3)2, -OC(O)N(CH3)(CH2CH2OCH3), -OC(O)NHCH2CH3, -OC(O)(pyrrolidin-1-yl), -OC(O)CH(CH3)OC(O)CH3, -OC(O)CH(CH3)OC(O)CH(CH3)2, -OC(O)CH(CH3)2, methyleneoxy(4-methyl-1,3-dioxol-2-one), -OCH2OC(O)CH 2CH2CH3, -OCH2OP(O)(OCH2OC(O)OCH(CH3)2)2, -OC(O)CH(NH2)CH(CH3)2, -OCH2OP(O)(OH)2, -C(O)OCH(CH3)OC(O)CH(CH3)2, -C( O)OCH(CH3)OC(O)CH3, -C(O)OCH(CH3)OC(O)CH2CH2CH3, -C(O)OCH(CH3)2, -C(O)OCH2CH(CH3)2, -C(O)O(CH2)3CH3, ((5-methyl-2-oxo -1,3-dioxol-4-yl)methoxy)(oxo)methyl, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OCH(CH3)OC(O)CH(NH2)(CH(CH3)2), -C(O)OCH(CH3)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)NH2, -C(O)OCH(CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)NH2, -C(O)OCH(CH3)OC(O) CH(CH(CH3)2)NHC(O)CH(CH(CH3)2)NH2, -C(O)OCH(CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH(CH3)2)NH2, -C(O)OCH(CH3)OC(O )CH(CH(CH3)2)NHC(O)CH(CH3)N(CH3)2, -C(O)OCH(CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)N(CH3)2, -C(O)OCH(CH3)OC(O)C Substituted with H(CH(CH3)2)NHC(O)CH(CH(CH3)2)N(CH3)2, -C(O)OCH(CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH(CH3)2)N(CH3)2, -C(O)OCH2OC(O)(4-(phosphonooxy)phenyl)methyl, -CH2OP(O)(OH)(OCH2OC(O)OCH(CH3)2), -C(O)OCH(CH3)OP(O)(OH)2, or -CH2OP(O)(OH2).

[0119] In some embodiments, the compound of formula (I) or (I-1) is [ka] or a pharmaceutically acceptable salt or solvate thereof. The embodiments disclosed herein that refer to compounds of formula (I) or (I-1) are also intended to apply to compounds of any formula depicted in this paragraph. Any provision of an embodiment that refers to formula (I) or (I-1) may be omitted if the compound contains a substituent or variable not depicted (e.g., W 1 ) is to be considered as separable and unaffected by the missing substituent or variable.

[0120] In certain aspects, the present disclosure provides a compound of formula (II): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is a halogen, -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C3 carbocyclic), -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2) R bonded to the same carbon atom 1 and R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or (3) R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 (4) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, -C 0~6 Alkyl-(C3 carbocycle) is a ring structure consisting of one, two, or three R 20 is replaced by -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR12 , or =C(R 14 )2, (2) two R bonded to the same carbon atom 2 together with the carbon atoms to which they are attached, C 3~12 (3) forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring; and (4) two vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12)S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23)-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0121] In certain aspects, the present disclosure provides a compound of formula (II-a) [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2) R bonded to the same carbon atom 1 and R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or (3) R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 (4) R 1 and R 3 form, together with the carbon atoms to which they are attached, a 3- to 12-membered heterocyclic ring, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 )2, (2) two R bonded to the same carbon atom 2 together with the carbon atoms to which they are attached, C 3~12 (3) forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring; and (4) two vicinal R 2 together with the carbon atoms to which they are attached, C 3~12forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence independently, -C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied; During the ceremony, (1) n is 0, and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, ethyl, propyl, isopropyl, butyl, isobutyl, isopentyl, hydroxymethyl, methoxymethyl, methoxy(oxo)methyl, (difluoromethoxy)methyl, 2,2-difluoroethan-1-yl, 2-methoxyethan-1-yl, 2-phenylethan-1-yl, 3,3-difluoropropan-1-yl, but-3-en-1-yl, 3,3-dimethylbutan-1-yl, cyclopropyl, cyclopropylmethyl, 2-cyclopropylethan-1-yl, or 2,2-difluorocyclopropan-1-yl; (2) n is 0 and three R 2 group is hydrogen, and R 1 The remaining R bonded to the same carbon as 2 is methyl and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, (3) n is 0, and each R 2 is hydrogen and R 3 is -C(=NH)NH2 or -C(=NH)NHCN, and the left [ka] is a double bond, and J 1 and J2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, (4) n is 0, and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -CHF2, and R 6 If is -F, then R 1 is not cyclopropylmethyl, (5) n is 0, and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a single bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1is not methyl or hydroxymethyl, (6) n is 1 and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, propyl, or isobutyl, (7) n is 1 and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -CHF2, and R 6 If is -F, then R 1 is not isobutyl.

[0122] In certain aspects, the present disclosure provides a compound of formula (II-1): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is a halogen, -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C3 carbocyclic), -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2together, oxo, =NR 12 , or =C(R 14 )2 or (2) R bonded to the same carbon atom 1 and R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or (3) R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 (4) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, -C 0~6 Alkyl-(C3 carbocycle) is a ring structure consisting of one, two, or three R 20 is replaced by -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12)(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 )2, (2) two R bonded to the same carbon atom 2 together with the carbon atoms to which they are attached, C 3~12 (3) forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring; and (4) two vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 optionally substituted with 1, 2, or 3 substituents selected from R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12)(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0123] In certain aspects, the present disclosure provides a compound of formula (II-a1) [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2) R bonded to the same carbon atom 1 and R 2 together with the carbon atoms to which they are attached, C3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or (3) R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 (4) R 1 and R 3 form, together with the carbon atoms to which they are attached, a 3- to 12-membered heterocyclic ring, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12, -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 )2, (2) two R bonded to the same carbon atom 2 together with the carbon atoms to which they are attached, C 3~12 (3) forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring; and (4) two vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 optionally substituted with 1, 2, or 3 substituents selected from R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence independently, -C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22)(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied; During the ceremony, (1) n is 0, and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1is not methyl, ethyl, propyl, isopropyl, butyl, isobutyl, isopentyl, hydroxymethyl, methoxymethyl, methoxy(oxo)methyl, (difluoromethoxy)methyl, 2,2-difluoroethan-1-yl, 2-methoxyethan-1-yl, 2-phenylethan-1-yl, 3,3-difluoropropan-1-yl, but-3-en-1-yl, 3,3-dimethylbutan-1-yl, cyclopropyl, cyclopropylmethyl, 2-cyclopropylethan-1-yl, or 2,2-difluorocyclopropan-1-yl; (2) n is 0 and three R 2 group is hydrogen, and R 1 The remaining R bonded to the same carbon as 2 is methyl and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, (3) n is 0, and each R 2 is hydrogen and R 3 is -C(=NH)NH2 or -C(=NH)NHCN, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, (4) n is 0, and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -CHF2, and R 6 If is -F, then R 1 is not cyclopropylmethyl, (5) n is 0, and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a single bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl or hydroxymethyl, (6) n is 1 and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -OH and R 6 If is -F, then R 1 is not methyl, propyl, or isobutyl, (7) n is 1 and each R 2 is hydrogen and R 3 is hydrogen, and the left [ka] is a double bond, and J 1 and J 2 Between [ka] is a single bond, and J 1 is N and J 2 is CH2 and R 4 is hydrogen and R 5 is -CHF2, and R 6 If is -F, then R 1 is not isobutyl.

[0124] In some embodiments, for compounds of Formula (II), (II-1), (II-a), or (II-a1), R 1 is a halogen, -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C3 carbocyclic), -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -N(R12 )(R 13 ), -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), and -N(R 12 )C(O)R 12 Selected from -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C3 carbocyclic), -C 0~6 Alkyl-(C 4~5 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are substituted with one, two, or three R 20 In some embodiments, R 1 -C 0~6 Alkyl-CN, -C 0~6 Alkyl-(C3 carbocyclic), and -C 0~6 Alkyl-(C 4~5 carbocyclic ring), -C 0~6 Alkyl-(C3 carbocycle) is a ring structure consisting of one, two, or three R 20 is replaced by -C 0~6 Alkyl-CN and -C 0~6 Alkyl-(C 4~5 Carbocyclic rings can have one, two, or three R 20 In some embodiments, R 1 is -C, such as -CH2CN, -CH2CH2CN, or -CH2CH2CH2CN 0~6 In some embodiments, R 1 can be one, two, or three R 20 -C optionally substituted with 0~6 Alkyl-(C 4~5 carbocyclic ring), e.g., R 1are cyclobutyl, methylcyclobutan-1-yl, 2-methylcyclobutan-1-yl, 2,2-dimethylcyclobutan-1-yl, cyclobutylmethyl, (1-methylcyclobutyl)methyl, (2-methylcyclobutyl)methyl, (2,2-dimethylcyclobutyl)methyl, cyclobutylethyl, 2-(1-methylcyclobutyl)ethan-1-yl, 2-(2-methylcyclobutyl)ethan-1-yl, 2-(2,2-dimethylcyclobutyl)ethan-1-yl, cyclopentyl In some embodiments, R is methylcyclopentan-1-yl, 2-methylcyclopentan-1-yl, 2,2-dimethylcyclopentan-1-yl, cyclopentylmethyl, (1-methylcyclopentyl)methyl, (2-methylcyclopentyl)methyl, (2,2-dimethylcyclopentyl)methyl, cyclopentyl, 2-(1-methylcyclopentyl)ethan-1-yl, 2-(2-methylcyclopentyl)ethan-1-yl, or 2-(2,2-dimethylcyclopentyl)ethan-1-yl. 1 is -C such as cyclobutylethyl 0~6 Alkyl-(C 4~5 In some embodiments, R 1 can be one, two, or three R 20 -C optionally substituted with 0~6 alkyl-(C carbocycle), e.g., R 1 is methylcyclopropan-1-yl, 2-methylcyclopropan-1-yl, 2,2-dimethylcyclopropan-1-yl, (1-methylcyclopropyl)methyl, (2-methylcyclopropyl)methyl, (2,2-dimethylcyclopropyl)methyl, 2-(1-methylcyclopropyl)ethan-1-yl, 2-(2-methylcyclopropyl)ethan-1-yl, or 2-(2,2-dimethylcyclopropyl)ethan-1-yl. In some embodiments, R 1 and R 2 together form an oxo group such as =NH, =NCN, =CH2, =CHF, or =CF2, 12 , or =C(R 14 In some embodiments, R 2 bonded to the same carbon atom form1 and R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which is substituted with one, two, or three R 20 In some embodiments, R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which is substituted with one, two, or three R 20 In some embodiments, R 1 and R 3 can be one, two, or three R's along with the atoms to which they are attached. 20 to form a 3- to 12-membered heterocycle optionally substituted with

[0125] In some embodiments, for compounds of Formula (II), (II-1), (II-a), or (II-a1), R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] is selected from.

[0126] In some embodiments, the compound of formula (II), (II-1), (II-a), or (II-a1) is [ka] or a pharmaceutically acceptable salt or solvate thereof. Embodiments disclosed herein that refer to compounds of Formula (II), (II-1), (II-a), or (II-a1) are also intended to apply to compounds of any formula depicted in this paragraph. Any provision of an embodiment that refers to Formula (II), (II-1), (II-a), or (II-a1) may be omitted if the compound does not contain a substituent or variable (e.g., J 1 ) is to be considered as separable and unaffected by the missing substituent or variable.

[0127] In certain aspects, the present disclosure provides a compound of formula (III): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12)C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl;1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0128] In certain aspects, the present disclosure provides a compound of formula (IV): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0129] In certain aspects, the present disclosure provides a compound of formula (III-1): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15, -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12, -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12)C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 optionally substituted with 1, 2, or 3 substituents selected from R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R 12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12, -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12 or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22, -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 )-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0130] In certain aspects, the present disclosure provides a compound of formula (IV-1): [ka] or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R 2 )2, n is 0, 1, or 2; J 1 is N and J 2 is CH2 or J 1 is C and J 2 is CH, R 1 is halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12)C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), or (1) R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or (2)R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12 (3) R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 2is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), and -S(O)(NR 12 )N(R 12 )(R 13 ), optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 3 and R 7 are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 optionally substituted with R 4 , R 5 , and R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclic ring, 3-10 membered heterocyclic ring, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13), and -S(O)(NR 12 )N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocycles and 3- to 10-membered heterocycles may contain one, two, or three R 20 optionally substituted with L 1 does not exist or is C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )C(NR 12 )-, -C(NR 12 )N(R 12 )-, -N(R 12 )C(NR 12 )N(R 12 )-, -C(O)O-, -OC(O)O-, -OC(O)N(R 12 )-, -N(R 12 )C(O)N(R 12 )-, -N(R 12 )C(O)O-, -C(O)N(R 12 )C(O)-, -C(O)N(R 12 )C(O)N(R 12 )-, -N(R 12 )S(O)2-, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R 12 )-, -C(O)C(O)N(R 12 )-, -N(R 12)C(O)-, -S(O)2-, -OS(O)-, -S(O)O-, -OS(O)2-, -S(O)2O-, -S(O)(NR 12 )-, -S(O)2N(R 12 )-, -S(O)(NR 12 )N(R 12 )-, -N(R 12 )S(O)-, -S(O)N(R 12 )-, -N(R 12 )S(O)2N(R 12 )-, -N(R 12 )S(O)N(R 12 )-, -P(O)(OR 12 )- and -P(O)(R 12 )- is selected from C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 optionally substituted with R 12 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is independently —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R20 )N(R 22 )2, and R 20 optionally substituted with 1, 2, or 3 substituents selected from R 13 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R attached to the same nitrogen atom 12 and R 13 is one, two, or three R 20 forming a 3- to 10-membered heterocycle optionally substituted with R 14 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 14 together with the carbon atoms to which they are attached, form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3-12 membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 optionally substituted with R 15 is, in each occurrence, independently (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and X and Y, in each occurrence, independently represent -O- and -N(R12 )-selected from R 16 and R 17 is, in each occurrence, independently hydrogen, C 1~6 alkyl, and phenyl; 1~6 Alkyl and phenyl are independently selected from halogen, -NO2, -CN, C 3~12 Carbocyclic ring, 3-12 membered heterocyclic ring, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -N(R 12 )S(O)2N(R 12 )(R 13 ), -SSR 12 , -SC(O)R 12 , -C(O)R 12 , -S(O)R 12 , -OC(O)R 12 , -OC(O)OR 12 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 , -S(O)2R 12 , -S(O)(NR 12 )R 12 , -S(O)2N(R 12 )(R 13 ), -S(O)(NR 12 )N(R 12 )(R 13 ), -P(O)(OR 12 )2, -P(O)(R 12 )2, -OP(O)(OR 12 )2, =O, =S, and =NR 12or R 16 and R 17 together with the atoms to which they are attached, can be one, two, or three R 20 forming a 3- to 12-membered heterocycle optionally substituted with R 20 is, in each occurrence, independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23)-, -S(=O)(=NR 22 )N(R 22 )(R 23 ), and -OCH2C(O)OR 22 and two R attached to the same or adjacent atoms are selected from 20 is optionally joined to form C 3~12 Forms a carbocyclic ring or a 3- to 12-membered heterocyclic ring, 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles are independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 , -OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 , -S(O)R 22 , -OC(O)R 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R22 , -S(O)2R 22 , -S(O)(NR 22 )R 22 , -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 Optionally substituted with one or more substituents selected from R 21 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or two R 21 together with the carbon atoms to which they are attached, form C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R 22 is, in each occurrence, independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle); R 23 is, in each occurrence, independently hydrogen and C 1~6 alkyl or R attached to the same nitrogen atom 22 and R 23 forms a 3- to 10-membered heterocyclic ring, each [ka] independently represent a single or double bond such that all valences are satisfied.

[0131] In some embodiments, the compound of formula (III) is provided with an enantiomeric excess of at least 98%. In some embodiments, the compound of formula (III) is provided with an enantiomeric excess of at least 80%, such as an enantiomeric excess of at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.9%. In some embodiments, the compound of formula (III-1) is provided with an enantiomeric excess of at least 98%. In some embodiments, the compound of formula (III-1) is provided with an enantiomeric excess of at least 80%, such as an enantiomeric excess of at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.9%. In some embodiments, the compound of formula (IV) is provided with an enantiomeric excess of at least 98%. In some embodiments, the compound of formula (IV) is provided in an enantiomeric excess of at least 80%, such as an enantiomeric excess of at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.9%. In some embodiments, the compound of formula (IV-1) is provided in an enantiomeric excess of at least 98%. In some embodiments, the compound of formula (IV-1) is provided in an enantiomeric excess of at least 80%, such as an enantiomeric excess of at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.9%.

[0132] In some embodiments, for compounds of formula (III), (III-1), (IV), or (IV-1), R 1 is halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)R 12 , -C(O)N(R 12 )(R 13 ), and -N(R 12 )C(O)R 12 Selected from C 2~6 Alkyl, C 2~6 Alkenyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are substituted with one, two, or three R 20 In some embodiments, R 1 is halogen, -CN, C 2~6 Alkyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , and -N(R 12 )(R 13 ) and C 2~6 Alkyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are substituted with one, two, or three R 20 In some embodiments, R 1 is C 2~6 Alkyl and -C 0~6 Alkyl-(C3~12 carbocyclic rings), each of which is selected from one, two, or three R 20 In some embodiments, R 1 is C 2~6 Alkyl and -C 0~6 Alkyl-(C 3~12 carbocyclic rings), each of which is independently selected from -CN and C 1~6 Optionally substituted with 1, 2, or 3 substituents selected from alkyl.

[0133] In some embodiments, for compounds of formula (III), (III-1), (IV), or (IV-1), R 1 is -C such as -CH2CH2CN or -CH2CH2CH2CN 2~6 In some embodiments, R 1 can be one, two, or three R 20 -C optionally substituted with 0~6 Alkyl-(C 3~12 carbocyclic ring), e.g., R 1are cyclopropyl, methylcyclopropan-1-yl, 2-methylcyclopropan-1-yl, 2,2-dimethylcyclopropan-1-yl, cyclopropylmethyl, (1-methylcyclopropyl)methyl, (2-methylcyclopropyl)methyl, (2,2-dimethylcyclopropyl)methyl, cyclopropylethyl, 2-(1-methylcyclopropyl)ethan-1-yl, 2-(2-methylcyclopropyl)ethan-1-yl, 2-2,2-dimethylcyclopropyl)ethan-1-yl, cyclobutyl, methylcyclobutan-1-yl, 2-methylcyclobutan-1-yl, 2,2-dimethylcyclobutan-1-yl, cyclobutylmethyl, (1-methylcyclobutyl)methyl, (2-methylcyclobutyl)methyl, (2 ,2-dimethylcyclobutyl)methyl, cyclobutylethyl, 2-(1-methylcyclobutyl)ethan-1-yl, 2-(2-methylcyclobutyl)ethan-1-yl, 2-(2,2-dimethylcyclobutyl)ethan-1-yl, cyclopentyl, methylcyclopentan-1-yl, 2-methylcyclopentan-1-yl, 2,2-dimethylcyclopentan-1-yl, cyclopentylmethyl, (1-methylcyclopentyl)methyl, (2-methylcyclopentyl)methyl, (2,2-dimethylcyclopentyl)methyl, cyclopentylethyl, 2-(1-methylcyclopentyl)ethan-1-yl, 2-(2-methylcyclopentyl)ethan-1-yl, or 2-(2,2-dimethylcyclopentyl)ethan-1-yl. 1 is cyclobutylethyl. In some embodiments, R 1 is selected from cyclopropyl, methylcyclopropan-1-yl, 2-methylcyclopropan-1-yl, 2,2-dimethylcyclopropan-1-yl, cyclopropylmethyl, (1-methylcyclopropyl)methyl, (2-methylcyclopropyl)methyl, (2,2-dimethylcyclopropyl)methyl, cyclopropylethyl, 2-(1-methylcyclopropyl)ethan-1-yl, 2-(2-methylcyclopropyl)ethan-1-yl, and 2-(2,2-dimethylcyclopropyl)ethan-1-yl. 1is cyclopropylethyl. In some embodiments, R 1 is selected from cyclobutyl, methylcyclobutan-1-yl, 2-methylcyclobutan-1-yl, 2,2-dimethylcyclobutan-1-yl, cyclobutylmethyl, (1-methylcyclobutyl)methyl, (2-methylcyclobutyl)methyl, (2,2-dimethylcyclobutyl)methyl, cyclobutylethyl, 2-(1-methylcyclobutyl)ethan-1-yl, 2-(2-methylcyclobutyl)ethan-1-yl, and 2-(2,2-dimethylcyclobutyl)ethan-1-yl. 1 is selected from cyclopentyl, methylcyclopentan-1-yl, 2-methylcyclopentan-1-yl, 2,2-dimethylcyclopentan-1-yl, cyclopentylmethyl, (1-methylcyclopentyl)methyl, (2-methylcyclopentyl)methyl, (2,2-dimethylcyclopentyl)methyl, cyclopentylethyl, 2-(1-methylcyclopentyl)ethan-1-yl, 2-(2-methylcyclopentyl)ethan-1-yl, and 2-(2,2-dimethylcyclopentyl)ethan-1-yl.

[0134] In some embodiments, for compounds of formula (III), (III-1), (IV), or (IV-1), R 1 is a halogen, C 2~6 Alkyl, C 2~6 Alkenyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), or R bonded to the same carbon atom 1 and R 2 together, oxo, =NR 12 , or =C(R 14 )2 or R 1 and R 3 form, together with the atoms to which they are attached, a 3- to 12-membered heterocyclic ring, C 2~6 Alkyl, C 2~6 Alkenyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle) and 3- to 12-membered heterocycle may have one, two, or three R 20 In some embodiments, R 1 is C 2~6 Alkyl and -C 0~6 Alkyl-(C 3~8 carbocyclic rings), each of which is selected from one, two, or three R 20 In some embodiments, R 1 is C 2~6 Alkyl and -C 0~3 Alkyl-(C 3~6 In some embodiments, R 1 is -CH2CH2CH(CH3)2.

[0135] In some embodiments, for compounds of formula (III), (III-1), (IV), or (IV-1), R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] is.

[0136] In some embodiments, for compounds of formula (III), (III-1), (IV), or (IV-1), R 1 and R 2 together form an oxo group such as =NH, =NCN, =CH2, =CHF, or =CF2, 12 , or =C(R 14 )2. In some embodiments, R 1 and R 2 C, along with the atom(s) to which they are attached. 3~12forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which is substituted with one, two, or three R 20 In some embodiments, R 1 and Vicinal R 2 together with the carbon atoms to which they are attached, C 3~12 forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which is substituted with one, two, or three R 20 In some embodiments, R 1 and R 3 can be one, two, or three R's along with the atoms to which they are attached. 20 to form a 3- to 12-membered heterocycle optionally substituted with

[0137] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 4 , R 5 , and R 6 are independently hydrogen, halogen, C 1~3 Alkyl, -OR 12 , -OR 15 , and -O-(C 1~6 alkyl)-OR 15 Selected from C 1~3 Alkyl can be one, two, or three R 20 In some embodiments, R 4 , R 5 , and R 6 are independently hydrogen, halogen, C 1~6 Alkyl, C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, -OR 12 , and -N(R 12 )(R 13 ) and C 1~6 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 4 , R 5 , and R 6are independently hydrogen, halogen, -OR 12 , -OR 15 , and -O-(C 1~6 alkyl)-OR 15 In some embodiments, R 4 , R 5 , and R 6 is independently selected from hydrogen, —Cl, —F, and —OH. In some embodiments, R 4 , R 5 , and R 6 is independently selected from hydrogen, —F, and —OH.

[0138] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 4 are independently hydrogen, halogen, C 1~3 Alkyl, -OR 12 , -OR 15 , and -O-(C 1~6 alkyl)-OR 15 Selected from C 1~3 Alkyl can be one, two, or three R 20 In some embodiments, R 4 are independently hydrogen, halogen, C 1~6 Alkyl, C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, -OR 12 , and -N(R 12 )(R 13 ) and C 1~6 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 4 is selected from hydrogen, halogen, and —OH. In some embodiments, R 4 is hydrogen.

[0139] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 5 are independently hydrogen, halogen, C 1~3 Alkyl, -OR 12 , -OR 15 , and -O-(C 1~6 alkyl)-OR 15 Selected from C 1~3 Alkyl can be one, two, or three R 20 In some embodiments, R 5 are independently hydrogen, halogen, C 1~6 Alkyl, C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, -OR 12 , and -N(R 12 )(R 13 ) and C 1~6 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 5 is halogen, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, R 5 is -OH.

[0140] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 5 -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and -OC(O)N(R 12 )(R 13In some embodiments, R 5 -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and -OC(O)N(R 12 )(R 13 ) and R 15 is -C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 5 -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and -OC(O)N(R 12 )(R 13 ) and R 15 is -C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 5 -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and -OC(O)N(R 12 )(R 13 ) and R 15 is -C(O)R 12 , -C(O)OR 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R5 are -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 In some embodiments, R 5 are -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 Selected from R 12 is optionally followed by one, two, or three R 20 C replaced with 1~6 alkyl, and R 13 is hydrogen and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, R 5 are -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH(R 20 )OC(O)OR 12 , -OC(O)CH(R 20 )NH2, -OCH(R 20 )OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 Selected from R 12 is C 1~6 alkyl, and R 13 is hydrogen and C1~6 In some embodiments, R 5 are -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 In some embodiments, R 5 are -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 Selected from R 12 can be one, two, or three R 20 C optionally substituted with 1~6 alkyl, and R 13 is hydrogen and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, R 5 are -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OC(O)N(R 12 )(R 13 ), -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OC(O)CH2NH2, -OC(O)CH(CH3)NH2, -OCH2OC(O)R 12, -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 Selected from R 12 is C 1~6 alkyl, and R 13 is hydrogen and C 1~6 In some embodiments, R 5 is -OP(O)(OH)2, -OCH2OP(O)(OH)2, -OCH2OC(O)OR 12 , -OCH(CH3)OC(O)OR 12 , -OCH2OC(O)R 12 , -OCH(CH3)OC(O)R 12 , -OC(O)R 12 , and -OC(O)OR 12 Selected from R 12 is C 1~6 In some embodiments, R 5 is selected from -OC(O)N(CH), -OC(O)N(CH)(CHCHOCH), -OC(O)NHCHCH, -OC(O)(pyrrolidin-1-yl), -OC(O)CH(CH)OC(O)CH, -OC(O)CH(CH)OC(O)CH(CH), -OC(O)CH(CH), methyleneoxy(4-methyl-1,3-dioxol-2-one), -OCHOC(O)CHCHCH, -OCHOP(O)(OCHOC(O)OCH(CH)), -OC(O)CH(NH)CH(CH), and -OCHOP(O)(OH). In some embodiments, R 5 -OR 15 and -O-(C 1~6 alkyl)-OR 15 In some embodiments, R 5 -OR 15 and -O-(C 1~6 alkyl)-OR 15 wherein R 15 is -C(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR16 )(YR 17 ) is selected.

[0141] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 6 are independently hydrogen, halogen, C 1~3 Alkyl, -OR 12 , -OR 15 , and -O-(C 1~6 alkyl)-OR 15 Selected from C 1~3 Alkyl can be one, two, or three R 20 In some embodiments, R 6 are independently hydrogen, halogen, C 1~6 Alkyl, C 3~6 Carbocyclic ring, 3- to 6-membered heterocyclic ring, -OR 12 , and -N(R 12 )(R 13 ) and C 1~6 Alkyl, C 3~6 Carbocycles and 3- to 6-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 6 is halogen, -OR 12 , and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, R 6 is a halogen, such as fluorine or chlorine. In some embodiments, R 6 is fluorine. In some embodiments, R 6 is chlorine.

[0142] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 4is selected from hydrogen, halogen, and —OH; R 5 is halogen, -OR 12 , -OR 15 , -O-(C 1~6 alkyl)-OR 15 , and C 1~6 alkyl, C 1~6 Alkyl can be one, two, or three R 20 optionally substituted with R 6 is halogen. In some embodiments, R 4 is hydrogen and R 5 -OR 15 and -O-(C 1~6 alkyl)-OR 15 Selected from R 6 is halogen. In some embodiments, R 4 is hydrogen and R 5 -OR 15 and -O-(C 1~6 alkyl)-OR 15 Selected from R 6 is fluorine. In some embodiments, R 4 is hydrogen and R 5 is -OH and R 6 is halogen. In some embodiments, R 4 is hydrogen and R 5 is -OH and R 6 is fluorine.

[0143] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 7 is hydrogen, C 1~6 Alkyl, 2- to 6-membered heteroalkyl, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , and -(C 1~6 alkyl)-OR 15 Selected from C 1~6Alkyl and 2-6 membered heteroalkyl may have one, two, or three R 20 In some embodiments, R 7 is hydrogen and -(C 1~6 alkyl)-OR 15 In some embodiments, R 7 is hydrogen.

[0144] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 7 is -(C 1~6 alkyl)-OR 15 In some embodiments, R 7 is -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 7 is -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 7 is -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R 7 is -CH2OC(O)R12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 7 is -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 7 is -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R 7 is -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH) and —CHP(O)(OH). In some embodiments, R 7 is -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH)2, and —CH2P(O)(OH)2; R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 7 is -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12, —P(O)(OH)2, and —CH2P(O)(OH)2; R 12 is C 1~6 In some embodiments, R 7 is selected from —CH2OP(O)(OH)2, —CH(CH3)OP(O)(OH)2, —CH2OP(O)(OCH2OC(O)OCH(CH3)2), —CH2OC(O)CH(NH2)(CH(CH3)2), —CH(CH3)OC(O)CH(NH2)(CH(CH3)2), and —CH2OC(O)CH(CH3)2.

[0145] In some embodiments, for a compound of Formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), J 1 [ka] J 2 is N-CH. In some embodiments, J 1 [ka] J 2 is C=CH. In some embodiments, J 1 is N and J 2 is CH. In some embodiments, J 1 is C and J 2 is CH.

[0146] In some embodiments, for compounds of formula (I), (I-1), (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), L 1 does not exist or is C 1~6 Alkylene, 2-6 membered heteroalkylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -N(R 12 )-, -C(O)-, -C(O)N(R 12 )- and -N(R 12 )C(O)-, C 1~6 Alkylene, 2-6 membered heteroalkylene, -C 0~6 Alkyl-(C 3~12 Carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle)-, -C 0~6 Alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are substituted with one, two, or three R 20 In some embodiments, L 1 does not exist or is C 1~6 Alkylene, -O-, -S-, -N(R 12 )-, -C(NR 12 )-, -N(R 12 )S(O)2-, -C(O)-, -C(O)N(R 12 )-, -N(R 12 )C(O)-, -S(O)-, -S(O)2-, and -S(O)2N(R 12 In some embodiments, L 1 does not exist or is C 1~3 Alkylene, -O-, -N(R 12 )- and -C(O)N(R 12 In some embodiments, L 1 does not exist or is C 1~3 Alkylene, -O-, and -C(O)N(R 12 In some embodiments, L 1 is absent. In some embodiments, L 1 can be one, two, or three R 20 C optionally substituted with 1~3 In some embodiments, L is alkylene. 1 is —O—. In some embodiments, L 1 is -C(O)N(R 12)-.

[0147] In some embodiments, for compounds of formula (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), W is C(R 2 )2, where R 2 is hydrogen, halogen, C 1~3 Alkyl, C 1~3 In some embodiments, W is selected from haloalkyl, —OH, —OCH 3 , —NH 2 , —NHCH 3 , and —N(CH 3 ) 2 . In some embodiments, W is selected from CHR 2 In some embodiments, W is CH2.

[0148] In some embodiments, for compounds of Formula (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), n ​​is 0 or 1. In some embodiments, n is 1 or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.

[0149] In some embodiments, for compounds of formula (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 2 is, in each occurrence, independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)R 12 , -OC(O)R 12 , -C(O)N(R 12 )(R13 ), and -N(R 12 )C(O)R 12 and optionally, (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 2~6 Alkenyl, 2-6 membered heteroalkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 2 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, -OR 12 , and -N(R 12 )(R 13 ) (1) two R 2 together, oxo, =NR 12 , or =C(R 14 ) forming two R 2 together with the atom(s) to which they are attached, C 3~12 forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, or both, 1~6 Alkyl, C 3~12 Carbocycles and 3- to 12-membered heterocycles may contain one, two, or three R 20 In some embodiments, R 2 is, in each occurrence, independently hydrogen, halogen, C 1~6 Alkyl, -OR 12 , and -N(R12 )(R 13 ), or two R bonded to the same carbon atom 2 together, oxo, =NR 12 , or =C(R 14 )2, wherein C 1~6 Alkyl can be one, two, or three R 20 In some embodiments, each R 2 is hydrogen.

[0150] In some embodiments, for compounds of formula (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, -C 0~6 Alkyl-(C 3~12 carbocycle), -C 0~6 Alkyl-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -C(O)R 12 , and -C(O)N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 In some embodiments, R 3 is hydrogen, C 1~6 Alkyl, -C 0~6 Alkyl-(3-12 membered heterocycle), -C(O)OR 12 , and -C(O)O-(C 1~6 alkyl)-OR 15 Selected from C 1~6 Alkyl and -C0~6 Alkyl-(3- to 12-membered heterocycle) is a heterocyclic ring having one, two, or three R 20 In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is -C2 alkyl-(5-6 membered heterocycle) and -C(O)O-(C 1~6 alkyl)-OR 15 -C alkyl-(5-6 membered heterocycle) is independently selected from C 1~3 In some embodiments, R is substituted with 1, 2, or 3 substituents selected from alkyl and oxo. 3 is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl.

[0151] In some embodiments, for compounds of formula (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 3 is -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 3 is -C(O)OCH(R 20 )OC(O)R 12 In some embodiments, R 3is -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is C 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH) and —CHP(O)(OH). In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH)2, and —CH2P(O)(OH)2; R 12 can be one, two, or three R 20 C optionally substituted with 1~6 In some embodiments, R 3 is -C(O)OCH(CH3)OC(O)R 12 In some embodiments, R 3is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH)2, and —CH2P(O)(OH)2; R 12 is C 1~6 In some embodiments, R 3 is -C(O)OCH(CH3)OC(O)CH(CH3)2, -C(O)OCH(CH3)OC(O)CH3, -C(O)OCH(CH3)OC(O)CH2CH2CH3, -C(O)OCH(CH3)2, -C(O)OCH2CH(CH3)2, -C(O)O(CH2)3CH3, ((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)(oxo)methyl, (5-methyl- In some embodiments, R is selected from 2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OCH(CH)OC(O)CH(NH)(CH(CH)), —C(O)OCHOC(O)(4-(phosphonooxy)phenyl)methyl, —CHOP(O)(OH)(OCHOC(O)OCH(CH)), —C(O)OCH(CH)OP(O)(OH), and —CHOP(O)(OH). 3 is —C(O)OCH(CH)OC(O)CH(CH). In some embodiments, R 3 is —C(O)OCH(CH)OC(O)-cyclopentyl. In some embodiments, R 3 is -C(O)OCH(CH3)OC(O)R 12 where R 12 is cyclopentyl. In some embodiments, R 3 is selected from —CH2OP(O)(OH)2, —CH(CH3)OP(O)(OH)2, —CH2OP(O)(OCH2OC(O)OCH(CH3)2), —CH2OC(O)CH(NH2)(CH(CH3)2), —CH(CH3)OC(O)CH(NH2)(CH(CH3)2), and —CH2OC(O)CH(CH3)2.

[0152] In some embodiments, for compounds of formula (II), (II-1), (II-a), (II-a1), (III), (III-1), (IV), or (IV-1), R 3 is -C(O)OR 12 , -C(O)O-(C 1~6 alkyl)-OR 15 , -(C 1~6 alkyl)-OR 15 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) wherein R 12 is C 1~6 Alkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), each of which is independently selected from —N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) wherein R 12 is C 1~6 Alkyl, -C 0~6 Alkyl-(C 3~12 carbocyclic ring), and -C 0~6 alkyl-(3- to 12-membered heterocycle), each of which is independently selected from —N(R 22 )C(O)CH(R 20 )N(R22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 are independently -N(R 22 )C(O)CH(R 20 )N(R 22 )2, -C(O)CH(R 20 )N(R 22 )2, and R 20 C optionally substituted with 1, 2, or 3 substituents selected from 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH(R 20 )OC(O)R 12 , -CH(R 20 )OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12, -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 In some embodiments, R 3 is -C(O)OCH2OC(O)R 12 and -C(O)OCH(CH3)OC(O)R 12 In some embodiments, R 3 is -C(O)R 12 and R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 3 is -C(O)R 12 and R 12 is optionally substituted with -NHC(O)CH(CH3)NH2, -NHC(O)CH(CH3)N(CH3)2, -NHC(O)CH(CH(CH3)2)NH2, or -NHC(O)CH(CH(CH3)2)N(CH3)2 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , -P(O)(XR 16 )(YR 17 ), and -CH2P(O)(XR 16 )(YR 17 ) and R 12 is optionally substituted with -NHC(O)CH(CH3)NH2, -NHC(O)CH(CH3)N(CH3)2, -NHC(O)CH(CH(CH3)2)NH2, or -NHC(O)CH(CH(CH3)2)N(CH3)2 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH)2, and —CH2P(O)(OH)2; R 12 is -N(R 22 )C(O)CH(R 20 )N(R 22 )2 substituted C 1~6 In some embodiments, R 3 is -C(O)OR 12 , -C(O)OCH2OC(O)R 12 , -C(O)OCH(CH3)OC(O)R 12 , -CH2OC(O)R 12 , -CH(CH3)OC(O)R 12 , —P(O)(OH)2, and —CH2P(O)(OH)2; R 12 is optionally substituted with -NHC(O)CH(CH3)NH2, -NHC(O)CH(CH3)N(CH3)2, -NHC(O)CH(CH(CH3)2)NH2, or -NHC(O)CH(CH(CH3)2)N(CH3)2 1~6 In some embodiments, R 3are -C(O)OCH(CH3)OC(O)CH(CH3)2, -C(O)OCH(CH3)OC(O)CH3, -C(O)OCH(CH3)OC(O)CH2CH2CH3, -C(O)OCH(CH3)2, -C(O)OCH2CH(CH3)2, -C(O)O(CH2)3CH3, ((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)(oxo)methyl, (5-methyl-2-oxo-1,3-dioxol-4 -yl)methyl, -C(O)OCH(CH3)OC(O)CH(NH2)(CH(CH3)2), -C(O)OCH(CH3)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)NH2, -C(O)OCH (CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)NH2, -C(O)OCH(CH3)OC(O)CH(CH(CH3)2)NHC(O)CH(CH(CH3)2)NH2, -C( O)OCH(CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH(CH3)2)NH2, -C(O)OCH(CH3)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)N (CH3)2, -C(O)OCH(CH(CH3)2)OC(O)CH(CH(CH3)2)NHC(O)CH(CH3)N(CH3)2, -C(O)OCH(CH3)OC(O)CH(CH(CH3)2)NHC(O) and -CHOP(O)(OH).

[0153] In some embodiments, for compounds of fo...

Claims

1. Compounds of formula (I): 【Chemistry 181】 or a pharmaceutically acceptable salt or solvate thereof, wherein: W １ But C, C(R ８ ), and N; W ２ But C, C(R ８ ), and N; W ４ is N and C(R ４ ) are selected from W ５ is N and C(R ５ ) are selected from W ６ is N and C(R ６ ) are selected from J １ is N, C, and C(R ８ ) are selected from J ２ But N, N(R ７ ), C(R ８ ), C(R ８ ) ２ and C(O); J ３ But N(R ７ ) and C(R ８ ) ２ is selected from L １ does not exist or C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, —C ０～６ Alkyl-(C ３～１２ carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle) -, -C ０～６ Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R １２ ) -, -C(NR １２ ) -, -N(R １２ ) C (NR １２ ) -, -C(NR １２ ) N (R １２ ) -, -N(R １２ ) C (NR １２ ) N (R １２ )-, -C(O)O-, -OC(O)O-, -OC(O)N(R １２ ) -, -N(R １２ )C(O)N(R １２ ) -, -N(R １２ )C(O)O-, -C(O)N(R １２ )C(O)-, -C(O)N(R １２ )C(O)N(R １２ ) -, -N(R １２ ) S (O) ２ -, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R １２ )-, -C(O)C(O)N(R １２ ) -, -N(R １２ )C(O)-,-S(O) ２ -, -OS(O)-, -S(O)O-, -OS(O) ２ -, -S(O) ２ O-, -S(O)(NR １２ ) -, -S(O) ２ N (R １２ )-,-S(O)(NR １２ ) N (R １２ ) -, -N(R １２ )S(O)-, -S(O)N(R １２ ) -, -N(R １２ ) S (O) ２ N (R １２ ) -, -N(R １２ ) S ( O ) N ( R １２ )-,-P(O)(OR １２ )-, and -P(O)(R １２ )-, and C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, —C ０～６ Alkyl-(C ３～１２ carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle)-,-C ０～６ alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are present in one, two, or three R ２０ optionally substituted with R ９ But C ３～１２ carbocycle and 3- to 12-membered heterocycle, each of which is selected from (i) one, two, or three R ２０ and (ii) (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR １５ , —O—(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , or —C(O)O—(C １～６ alkyl)-OR １５ optionally substituted with R ４ , R ５ , R ６ , and R ８ is, in each occurrence, independently hydrogen, halogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ Carbocycle, 3- to 10-membered heterocycle, —OR １２ , -OR １５ , —O—(C １～６ alkyl)-OR １５ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ Carbocycles and 3- to 10-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ７ is, in each occurrence, independently hydrogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OR １２ , -C(O)O-(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , -C(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(═O)(═NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle) are present in one, two, or three R ２０ optionally substituted with R １２ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ optionally substituted with R １３ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, and C １～６ haloalkyl or R bonded to the same nitrogen atom １２ and R １３ But one, two, or three R ２０ forming a 3- to 10-membered heterocycle optionally substituted with R １５ is, independently in each occurrence, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OR １２ , -C(O)R １２ , -P(O)(X-R １６ ) (Y-R １７ ), and -CH ２ P(O)(X-R １６ ) (Y-R １７ ) are selected from X and Y, in each occurrence, are independently —O— and —N(R １２ ) - is selected from R １６ and R １７ may, in each occurrence, independently be hydrogen, C １～６ alkyl, and phenyl; １～６ The alkyl and phenyl are independently selected from halogen, —NO ２ , -CN,C ３～１２ Carbocycle, 3- to 12-membered heterocycle, —OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -N(R １２ ) S (O) ２ N (R １２ ) (R １３ ), -S-S-R １２ , -S-C(O)R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -OC(O)OR １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), -S(O)(NR １２ ) N (R １２ ) (R １３ ), -P(O)(OR １２ ) ２ , -P(O)(R １２ ) ２ , -OP(O)(OR １２ ) ２ , =O, =S, and =NR １２ or R １６ and R １７ together with the atoms to which they are attached, can be one, two, or three R ２０ forming a 3- to 12-membered heterocycle optionally substituted with R ２０ is, in each occurrence, independently selected from halogen, oxo, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR ２２ , -SR ２２ , -N(R ２２ ) (R ２３ ), =NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)OR ２２ , -N(R ２２ ) S (O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (R ２３ ), -C(O)C(O)N(R ２２ ) (R ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N (R ２２ ) (R ２３ )-, -S(=O)(=NR ２２ ) N (R ２２ ) (R ２３ ), and -OCH ２ C(O)OR ２２ and two R attached to the same or adjacent atoms are selected from ２０ is optionally joined to form C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ The carbocycle and the 3- to 12-membered heterocycle are independently selected from halogen, oxo, —CN, C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ haloalkoxy, -OR ２２ , -SR ２２ , -N(R ２２ ) (R ２３ ), =NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)OR ２２ , -N(R ２２ ) S (O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (R ２３ ), -C(O)C(O)N(R ２２ ) (R ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N (R ２２ ) (R ２３ ), and —S(═O)(═NR ２２ ) N (R ２２ ) (R ２３ Optionally substituted with one or more substituents selected from R ２１ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, C １～６ Haloalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or two R ２１ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently contains halogen, C １～３ Alkyl, C １～３ optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R ２２ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle); R ２３ is, in each occurrence, independently hydrogen and C １～６ alkyl or R bonded to the same nitrogen atom ２２ and R ２３ form a 3- to 10-membered heterocyclic ring, 【Chemistry 182】 represents a single or double bond such that all valences are satisfied, R ９ , W １ , W ２ , W ４ , W ５ , W ６ , J ２ , or J ３ At least one of the groups is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR １５ , —O—(C １～６ alkyl)-OR １５ , -OC(O)N(R １２ ) (R １３ ), -(C １～６ alkyl)-OR １５ , or —C(O)O—(C １～６ alkyl)-OR １５ or a pharmaceutically acceptable salt or solvate thereof, wherein:

2. W ４ But C(R ４ ) and W ５ But C(R ５ ) and W ６ But C(R ６ 2. The compound, salt, or solvate of claim 1, wherein

3. W １ is C and W ２ But C(R ８ 3. The compound, salt, or solvate of claim 1, wherein

4. J ３ But N(R ７ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein:

5. R ９ is a 4- to 7-membered heterocycle, and the 4- to 7-membered heterocycle is ２０ and (ii) -OR １５ , —O—(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , or —C(O)O—(C １～６ alkyl)-OR １５ 10. A compound, salt, or solvate according to any one of the preceding claims, optionally substituted with:

6. R ９ (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —OR １５ , —O—(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , or —C(O)O—(C １～６ alkyl)-OR １５ 10. A compound, salt, or solvate according to any one of the preceding claims, substituted with:

7. R ９ (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, -(C １～６ alkyl)-OR １５ , or —C(O)O—(C １～６ alkyl)-OR １５ 10. A compound, salt, or solvate according to any one of the preceding claims, which is a 4- to 7-membered heterocycle containing a ring nitrogen atom substituted by:

8. R ９ But, -OR １５ or O-(C １～６ alkyl)-OR １５ 7. The compound, salt, or solvate of any one of claims 1 to 6, comprising a ring carbon atom substituted by:

9. R ９ but, 【Chemistry 183】 and W is C(R ２ ) ２ and n is 0, 1, or 2; R １ But halogen, -CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) or (1) R １ and R ２ together, oxo, =NR １２ , or = C(R １４ ) ２ or (2) R １ and R ２ together with the atom(s) to which they are attached, C ３～１２ (3) R １ and R ３ together with the atoms to which they are attached form a 3- to 12-membered heterocyclic ring, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ２ is, in each occurrence, independently hydrogen, halogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) and optionally, (1) two R ２ together, oxo, =NR １２ , or =C(R １４ ) ２ and (2) forming two R ２ together with the atom(s) to which they are attached, C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ３ is hydrogen, -CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OR １２ , -C(O)O-(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , -C(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(═O)(═NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ optionally substituted with R １４ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or two R １４ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ 10. A compound, salt, or solvate according to any one of the preceding claims, optionally substituted with:

10. Compound of formula (II): 【Chemistry 184】 or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R ２ ) ２ and n is 0, 1, or 2; J １ is N and J ２ But CH ２ or J １ is C and J ２ is CH, R １ But halogen, -C ０～６ Alkyl-CN, -C ０～６ Alkyl-(C ３ carbocycle), -C ０～６ Alkyl-(C ４～５ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR １２ , -SR １２ , -N(R １２ ) (R １３ ), -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) or (1) R １ and R ２ together, oxo, =NR １２ , or = C(R １４ ) ２ or (2) R １ and R ２ together with the carbon atoms to which they are attached, C ３～１２ (3) R １ and Vicinal R ２ together with the carbon atoms to which they are attached, C ３～１２ (4) R １ and R ３ together with the atoms to which they are attached form a 3- to 12-membered heterocyclic ring, ０～６ Alkyl-(C ３ carbocyclic ring) is one, two, or three R ２０ is substituted with -C ０～６ Alkyl-CN, -C ０～６ Alkyl-(C ４～５ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ２ is, in each occurrence, independently hydrogen, halogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) and optionally, (1) two R ２ together, oxo, =NR １２ , or =C(R １４ ) ２ (2) forming two R ２ together with the carbon atoms to which they are attached, C ３～１２ (3) forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring; and (4) two vicinal R ２ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ３ and R ７ are independently hydrogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OR １２ , -C(O)O-(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , -C(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(═O)(═NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ optionally substituted with R ４ , R ５ , and R ６ are independently hydrogen, halogen, -CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ Carbocycle, 3- to 10-membered heterocycle, —OR １２ , -OR １５ , —O—(C １～６ alkyl)-OR １５ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ Carbocycles and 3- to 10-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with L １ does not exist or C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, —C ０～６ Alkyl-(C ３～１２ carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle)-,-C ０～６ Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R １２ ) -, -C(NR １２ ) -, -N(R １２ ) C (NR １２ ) -, -C(NR １２ ) N (R １２ ) -, -N(R １２ ) C (NR １２ ) N (R １２ )-, -C(O)O-, -OC(O)O-, -OC(O)N(R １２ ) -, -N(R １２ )C(O)N(R １２ ) -, -N(R １２ )C(O)O-, -C(O)N(R １２ )C(O)-, -C(O)N(R １２ )C(O)N(R １２ ) -, -N(R １２ ) S (O) ２ -, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R １２ )-, -C(O)C(O)N(R １２ ) -, -N(R １２ )C(O)-,-S(O) ２ -, -OS(O)-, -S(O)O-, -OS(O) ２ -, -S(O) ２ O-, -S(O)(NR １２ ) -, -S(O) ２ N (R １２ )-,-S(O)(NR １２ ) N (R １２ ) -, -N(R １２ )S(O)-, -S(O)N(R １２ ) -, -N(R １２ ) S (O) ２ N (R １２ ) -, -N(R １２ ) S ( O ) N ( R １２ )-,-P(O)(OR １２ )-, and -P(O)(R １２ )-, and C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, —C ０～６ Alkyl-(C ３～１２ carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle) -, -C ０～６ alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are present in one, two, or three R ２０ optionally substituted with R １２ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ optionally substituted with R １３ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, and C １～６ haloalkyl or R bonded to the same nitrogen atom １２ and R １３ But one, two, or three R ２０ forming a 3- to 10-membered heterocycle optionally substituted with R １４ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or two R １４ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R １５ is, independently in each occurrence, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R １２ , -C(O)OR １２ , -P(O)(X-R １６ ) (Y-R １７ ), and -CH ２ P(O)(X-R １６ ) (Y-R １７ ) are selected from X and Y, in each occurrence, are independently —O— and —N(R １２ ) - is selected from R １６ and R １７ may, in each occurrence, independently be hydrogen, C １～６ alkyl, and phenyl; １～６ The alkyl and phenyl are independently selected from halogen, —NO ２ , -CN,C ３～１２ Carbocycle, 3- to 12-membered heterocycle, —OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -N(R １２ ) S (O) ２ N (R １２ ) (R １３ ), -S-S-R １２ , -S-C(O)R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -OC(O)OR １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), -S(O)(NR １２ ) N (R １２ ) (R １３ ), -P(O)(OR １２ ) ２ , -P(O)(R １２ ) ２ , -OP(O)(OR １２ ) ２ , =O, =S, and =NR １２ or R １６ and R １７ together with the atoms to which they are attached, can be one, two, or three R ２０ forming a 3- to 12-membered heterocycle optionally substituted with R ２０ is, in each occurrence, independently selected from halogen, oxo, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR ２２ , -SR ２２ , -N(R ２２ ) (R ２３ ), =NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)OR ２２ , -N(R ２２ ) S (O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (R ２３ ), -C(O)C(O)N(R ２２ ) (R ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N (R ２２ ) (R ２３ )-, -S(=O)(=NR ２２ ) N (R ２２ ) (R ２３ ), and -OCH ２ C(O)OR ２２ and two R attached to the same or adjacent atoms are selected from ２０ is optionally joined to form C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ The carbocycle and the 3- to 12-membered heterocycle are independently selected from halogen, oxo, —CN, C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ haloalkoxy, -OR ２２ , -SR ２２ , -N(R ２２ ) (R ２３ ), =NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)OR ２２ , -N(R ２２ ) S (O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (R ２３ ), -C(O)C(O)N(R ２２ ) (R ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N (R ２２ ) (R ２３ ), and —S(═O)(═NR ２２ ) N (R ２２ ) (R ２３ Optionally substituted with one or more substituents selected from R ２１ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, C １～６ Haloalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or two R ２１ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently contains halogen, C １～３ Alkyl, C １～３ optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R ２２ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle); R ２３ is, in each occurrence, independently hydrogen and C １～６ alkyl or R bonded to the same nitrogen atom ２２ and R ２３ form a 3- to 10-membered heterocyclic ring, each 【Chemistry 185】 are independently a single or double bond such that all valences are satisfied, or a pharmaceutically acceptable salt or solvate thereof.

11. Compounds of formula (III) or (IV): 【Chemistry 186】 or a pharmaceutically acceptable salt or solvate thereof, wherein: W is C(R ２ ) ２ and n is 0, 1, or 2; J １ is N and J ２ But CH ２ or J １ is C and J ２ is CH, R １ But halogen, -CN, C ２～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) or (1) R １ and R ２ together, oxo, =NR １２ , or = C(R １４ ) ２ or (2) R １ and R ２ together with the atom(s) to which they are attached, C ３～１２ (3) R １ and R ３ together with the atoms to which they are attached form a 3- to 12-membered heterocyclic ring, C ２～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ２ is, in each occurrence, independently hydrogen, halogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) and optionally, (1) two R ２ together, oxo, =NR １２ , or =C(R １４ ) ２ and (2) forming two R ２ together with the atom(s) to which they are attached, C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R ３ and R ７ are independently hydrogen, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ Alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)OR １２ , -C(O)O-(C １～６ alkyl)-OR １５ , -(C １～６ alkyl)-OR １５ , -C(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(═O)(═NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ optionally substituted with R ４ , R ５ , and R ６ are independently hydrogen, halogen, -CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ Carbocycle, 3- to 10-membered heterocycle, —OR １２ , -OR １５ , —O—(C １～６ alkyl)-OR １５ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), and —S(O)(NR １２ ) N (R １２ ) (R １３ ) and C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１０ Carbocycles and 3- to 10-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with L １ does not exist or C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, —C ０～６ Alkyl-(C ３～１２ carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle)-,-C ０～６ Alkyl-(3- to 12-membered heterocyclic ring)-, -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic ring)-, -O-, -S-, -N(R １２ ) -, -C(NR １２ ) -, -N(R １２ ) C (NR １２ ) -, -C(NR １２ ) N (R １２ ) -, -N(R １２ ) C (NR １２ ) N (R １２ )-, -C(O)O-, -OC(O)O-, -OC(O)N(R １２ ) -, -N(R １２ )C(O)N(R １２ ) -, -N(R １２ )C(O)O-, -C(O)N(R １２ )C(O)-, -C(O)N(R １２ )C(O)N(R １２ ) -, -N(R １２ ) S (O) ２ -, -C(O)-, -S(O)-, -OC(O)-, -C(O)N(R １２ )-, -C(O)C(O)N(R １２ ) -, -N(R １２ )C(O)-,-S(O) ２ -, -OS(O)-, -S(O)O-, -OS(O) ２ -, -S(O) ２ O-, -S(O)(NR １２ ) -, -S(O) ２ N (R １２ )-,-S(O)(NR １２ ) N (R １２ ) -, -N(R １２ )S(O)-, -S(O)N(R １２ ) -, -N(R １２ ) S (O) ２ N (R １２ ) -, -N(R １２ ) S ( O ) N ( R １２ )-,-P(O)(OR １２ )-, and -P(O)(R １２ )-, and C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, 2- to 6-membered heteroalkylene, 3- to 6-membered heteroalkenylene, 3- to 6-membered heteroalkynylene, —C ０～６ Alkyl-(C ３～１２ carbocyclic)-, -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle) -, -C ０～６ alkyl-(3- to 12-membered heterocycle)- and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle)- are present in one, two, or three R ２０ optionally substituted with R １２ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ optionally substituted with R １３ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, and C １～６ haloalkyl or R bonded to the same nitrogen atom １２ and R １３ But one, two, or three R ２０ forming a 3- to 10-membered heterocycle optionally substituted with R １４ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or two R １４ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, —C ０～６ Alkyl-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), C ３～１２ Carbocycles and 3- to 12-membered heterocycles may be substituted with one, two, or three R ２０ optionally substituted with R １５ is, independently in each occurrence, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl, —C(O)R １２ , -C(O)OR １２ , -P(O)(X-R １６ ) (Y-R １７ ), and -CH ２ P(O)(X-R １６ ) (Y-R １７ ) are selected from X and Y, in each occurrence, are independently —O— and —N(R １２ ) - is selected from R １６ and R １７ may, in each occurrence, independently be hydrogen, C １～６ alkyl, and phenyl; １～６ The alkyl and phenyl are independently selected from halogen, —NO ２ , -CN,C ３～１２ Carbocycle, 3- to 12-membered heterocycle, —OR １２ , -SR １２ , -N(R １２ ) (R １３ ), —C(O)OR １２ , -OC(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)N(R １２ ) (R １３ ), -N(R １２ )C(O)OR １２ , -N(R １２ ) S (O) ２ R １２ , -N(R １２ ) S (O) ２ N (R １２ ) (R １３ ), -S-S-R １２ , -S-C(O)R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -OC(O)OR １２ , -C(O)N(R １２ ) (R １３ ), -C(O)C(O)N(R １２ ) (R １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N (R １２ ) (R １３ ), -S(O)(NR １２ ) N (R １２ ) (R １３ ), -P(O)(OR １２ ) ２ , -P(O)(R １２ ) ２ , -OP(O)(OR １２ ) ２ , =O, =S, and =NR １２ or R １６ and R １７ together with the atoms to which they are attached, can be one, two, or three R ２０ forming a 3- to 12-membered heterocycle optionally substituted with R ２０ is, in each occurrence, independently selected from halogen, oxo, —CN, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), -OR ２２ , -SR ２２ , -N(R ２２ ) (R ２３ ), =NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)OR ２２ , -N(R ２２ ) S (O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (R ２３ ), -C(O)C(O)N(R ２２ ) (R ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N (R ２２ ) (R ２３ )-, -S(=O)(=NR ２２ ) N (R ２２ ) (R ２３ ), and -OCH ２ C(O)OR ２２ and two R attached to the same or adjacent atoms are selected from ２０ is optionally joined to form C ３～１２ forming a carbocyclic ring or a 3- to 12-membered heterocyclic ring, １～６ Alkyl, C ２～６ Alkenyl, C ２～６ alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), -(2- to 6-membered heteroalkyl)-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C ３～１２ The carbocycle and the 3- to 12-membered heterocycle are independently selected from halogen, oxo, —CN, C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ haloalkoxy, -OR ２２ , -SR ２２ , -N(R ２２ ) (R ２３ ), =NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)N(R ２２ ) (R ２３ ), -N(R ２２ )C(O)OR ２２ , -N(R ２２ ) S (O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (R ２３ ), -C(O)C(O)N(R ２２ ) (R ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N (R ２２ ) (R ２３ ), and —S(═O)(═NR ２２ ) N (R ２２ ) (R ２３ Optionally substituted with one or more substituents selected from R ２１ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, C １～６ Haloalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or two R ２１ together with the carbon atoms to which they are attached, C ３～１２ forming a carbocyclic or 3- to 12-membered heterocyclic ring, each of which independently contains halogen, C １～３ Alkyl, C １～３ optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and —OH; R ２２ may, in each occurrence, independently be hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle); R ２３ is, in each occurrence, independently hydrogen and C １～６ alkyl or R bonded to the same nitrogen atom ２２ and R ２３ form a 3- to 10-membered heterocyclic ring, each 【Chemistry 187】 are independently a single or double bond such that all valences are satisfied, or a pharmaceutically acceptable salt or solvate thereof.

12. 12. The compound, salt, or solvate of claim 11, wherein the compound is a compound of formula (III) provided in an enantiomeric excess of at least 98%.

13. 12. The compound, salt, or solvate of claim 11, wherein the compound is a compound of formula (IV) provided in an enantiomeric excess of at least 98%.

14. R ４ But hydrogen, halogen, C １～６ Alkyl, C ３～６ Carbocyclic ring, 3- to 6-membered heterocyclic ring, -OR １２ , and −N(R １２ ) (R １３ ) and C １～６ Alkyl, C ３～６ Carbocycles and 3- to 6-membered heterocycles may be formed by one, two, or three R ２０ 10. A compound, salt, or solvate according to any one of the preceding claims, optionally substituted with:

15. R ４ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein is selected from hydrogen, halogen, and -OH.

16. R ４ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein is hydrogen.

17. R ５ is halogen, -OR １２ , -OR １５ , —O—(C １～６ alkyl)-OR １５ , and C １～６ alkyl, C １～６ The alkyl may be one, two, or three R ２０ 10. A compound, salt, or solvate according to any one of the preceding claims, optionally substituted with:

18. R ５ The compound, salt, or solvate of any one of claims 1 to 17, wherein is -OH.

19. R ５ But, -OR １５ and —O—(C １～６ alkyl)-OR １５ 18. The compound, salt, or solvate of any one of claims 1 to 17, selected from:

20. R ６ is halogen, -OR １２ , and C １～６ alkyl, C １～６ The alkyl may be one, two, or three R ２０ 10. A compound, salt, or solvate according to any one of the preceding claims, optionally substituted with:

21. R ６ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein is halogen.

22. R ６ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein is selected from fluorine and chlorine.

23. R ４ is hydrogen, and R ５ is —OH, and R ６ The compound, salt, or solvate according to any one of claims 1 to 13, wherein is fluorine.

24. J １ is N and J ２ But CH ２ 10. A compound, salt, or solvate according to any one of the preceding claims, which is

25. R ７ is hydrogen and -(C １～６ alkyl)-OR １５ 10. A compound, salt, or solvate according to any one of the preceding claims selected from:

26. R ７ 26. The compound, salt, or solvate of any one of claims 1 to 25, wherein is hydrogen.

27. R ７ But -(C １～６ alkyl)-OR １５ 26. The compound, salt, or solvate of any one of claims 1 to 25, wherein:

28. L １ does not exist or C １～６ Alkylene, —O—, —S—, —N(R １２ ) -, -C(NR １２ ) -, -N(R １２ ) S (O) ２ -, -C(O)-, -C(O)N(R １２ ) -, -N(R １２ )C(O)-, -S(O)-, -S(O) ２ - and -S(O) ２ N (R １２ 2. A compound, salt, or solvate according to any one of the preceding claims, selected from:

29. L １ does not exist or C １～３ Alkylene, —O—, and —C(O)N(R １２ 2. A compound, salt, or solvate according to any one of the preceding claims, selected from:

30. L １ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein is absent.

31. W is CH ２ 31. The compound, salt, or solvate of any one of claims 9 to 30, wherein:

32. 32. The compound, salt, or solvate of any one of claims 9 to 31, wherein n is 0 or 1.

33. 33. The compound, salt, or solvate of claim 32, wherein n is 0.

34. R １ But halogen, C ２～６ Alkyl, C ２～６ alkenyl, 2- to 6-membered heteroalkyl, —C ０～６ Alkyl-(C ３～１２ carbocyclic ring), and -C ０～６ alkyl-(3- to 12-membered heterocycle), or R bonded to the same carbon atom １ and R ２ together, oxo, =NR １２ , or = C(R １４ ) ２ or R １ and R ３ together with the atoms to which they are attached form a 3- to 12-membered heterocyclic ring, C ２～６ Alkyl, C ２～６ alkenyl, 2- to 6-membered heteroalkyl, —C ０～６ Alkyl-(C ３～１２ carbocycle), -C ０～６ alkyl-(3- to 12-membered heterocycle), and 3- to 12-membered heterocycles are selected from the group consisting of 1, 2, or 3 R ２０ 34. The compound, salt, or solvate of any one of claims 9 to 33, optionally substituted with:

35. R １ But C ２～６ Alkyl and -C ０～６ Alkyl-(C ３～８ carbocyclic rings), each of which is selected from one, two, or three R ２０ 35. The compound, salt, or solvate of any one of claims 9 to 34, optionally substituted with:

36. R １ But C ２～６ Alkyl and -C ０～３ Alkyl-(C ３～６ 36. The compound, salt, or solvate of any one of claims 9 to 35, wherein the compound is selected from the group consisting of:

37. R １ but, 【Chemical 188】 34. The compound, salt, or solvate of any one of claims 9 to 33, selected from:

38. R １ but, 【Chemical 189】 34. The compound, salt, or solvate of any one of claims 9 to 33, selected from:

39. R １ but, 【Chemistry 190】 34. The compound, salt, or solvate of any one of claims 9 to 33, selected from:

40. R ２ may, in each occurrence, independently be hydrogen, halogen, C １～６ Alkyl, -OR １２ , and −N(R １２ ) (R １３ ) or two R bonded to the same carbon atom ２ together, oxo, =NR １２ , or =C(R １４ ) ２ Forming C １～６ The alkyl may be one, two, or three R ２０ 40. The compound, salt, or solvate of any one of claims 9 to 39, optionally substituted with:

41. Each R ２ The compound, salt, or solvate of any one of claims 9 to 40, wherein is hydrogen.

42. R ３ But hydrogen, C １～６ Alkyl, —C ０～６ alkyl-(3- to 12-membered heterocycle), —C(O)OR １２ , and —C(O)O—(C １～６ alkyl)-OR １５ is selected from C １～６ Alkyl and -C ０～６ alkyl-(3- to 12-membered heterocycle) is present in one, two, or three R ２０ 42. The compound, salt, or solvate of any one of claims 9 to 41, optionally substituted with:

43. R ３ 43. The compound, salt, or solvate of any one of claims 9 to 42, wherein is hydrogen.

44. R ３ But, -C ２ Alkyl-(5- to 6-membered heterocycle) and —C(O)O—(C １～６ alkyl)-OR １５ -C ２ alkyl-(5- to 6-membered heterocycle) is independently C １～３ 43. The compound, salt, or solvate of any one of claims 9 to 42, substituted with 1, 2, or 3 substituents selected from alkyl and oxo.

45. R １５ But -C(O)R １２ and -P(O)(X-R １６ ) (Y-R １７ 10. A compound, salt, or solvate according to any one of the preceding claims, selected from:

46. R １２ But -NH ２ C optionally substituted with １～６ 10. A compound, salt, or solvate according to any one of the preceding claims, wherein: R is alkyl.

47. 10. A compound, salt, or solvate according to any one of the preceding claims, wherein X and Y are each -O-.

48. R １６ and R １７ At least one of the groups is independently a halogen, —OR １２ , -S-S-R １２ , -S-C(O)R １２ , -OC(O)R １２ , -OC(O)OR １２ , and -P(O)(OR １２ ) ２ C optionally substituted in each occurrence with one or more substituents selected from １～６ 48. The compound, salt, or solvate of any one of claims 1 to 47, wherein: R is alkyl.

49. Independently, R １６ and R １７ are independently halogen, -OR １２ , -S-S-R １２ , -S-C(O)R １２ , -OC(O)R １２ , -OC(O)OR １２ , and -P(O)(OR １２ ) ２ C optionally substituted in each occurrence with one or more substituents selected from １～６ 48. The compound, salt, or solvate of any one of claims 1 to 47, wherein: R is alkyl.

50. R １６ and R １７ are independently hydrogen, and independently halogen, —OR １２ , -S-S-R １２ , -S-C(O)R １２ , -OC(O)R １２ , -OC(O)OR １２ , and -P(O)(OR １２ ) ２ C optionally substituted in each occurrence with one or more substituents selected from １～６ 48. The compound, salt, or solvate of any one of claims 1 to 47, wherein the alkyl is selected from the group consisting of:

51. R １６ and R １７ are independently hydrogen, —CH ２ O.C.(O.)R. １２ , and -CH ２ OC(O)OR １２ 48. The compound, salt, or solvate of any one of claims 1 to 47, selected from:

52. R １６ and R １７ are independently -CH ２ OC(O)C(CH ３ ) ３ , -CH ２ OC(O)OCH(CH ３ ) ２ , -CH ２ OC(O)CH ３ , -CH ２ CH ２ -S-S-(CH ２ ) ２ OH, and -CH ２ CH ２ —S—C(O)CH ３ 48. The compound, salt, or solvate of any one of claims 1 to 47, selected from:

53. R １５ But -P(O)(OH) ２ 48. The compound, salt, or solvate of any one of claims 1 to 47, wherein:

54. A compound of the formula: 【Chemistry 191】 or a pharmaceutically acceptable salt or solvate thereof, wherein: W is CH ２ and n is 0, R １ but, 【Chemistry 192】 and R ３ is hydrogen and -C(O)OCH(CH ３ )OC(O)R １２ is selected from R ５ is —OH, R ６ is fluorine, R ７ is hydrogen, R １２ But C １～６ Alkyl and C ３～６ selected from carbocycles, 【Chemistry 193】 represents a double bond, or a pharmaceutically acceptable salt or solvate thereof. 【Request Item 55】 【Chemistry 194】 or a pharmaceutically acceptable salt or solvate thereof.

56. A compound selected from Table 1, or a pharmaceutically acceptable salt or solvate thereof.

57. Formula DL ＤＥ -E, wherein D is a monovalent form of a compound of any one of claims 1 to 56; L ＤＥ is a covalent linker attached to D and E, The compound wherein E is a monovalent form of the decomposition accelerator.

58. The degradation promoter is selected from the group consisting of E3A, mdm2, APC, EDD1, SOCS / BC-box / eloBC / CUL5 / RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, and HERC 3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A , UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von Hippel-Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperone-mediated autophagy), SCFb-TRCP (Skip-Cullin-F box (beta-TRCP) ubiquitin complex), b-TRCP (b-transduction repeat-containing protein), cIAP1 (cellular inhibitor of apoptosis protein 1), APC / C (anaphase-promoting complex / cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4) ＣＲＢＮ 58. The compound of claim 57, wherein the compound is capable of binding to a protein selected from ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885.

59. The decomposition accelerator is UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L 58. The compound of claim 57, which is capable of binding to a protein selected from: UBE2L1, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1.

60. L ＤＥ But, -L ＤＥ１ -L ＤＥ２ -L ＤＥ３ -L ＤＥ４ -L ＤＥ５ - and L ＤＥ１ , L ＤＥ２ , L ＤＥ３ , L ＤＥ４ , and L ＤＥ５ are independently a bond, —O—, —N(R １２ )-, -C(O)-, -N(R １２ )C(O)-, -C(O)N(R １２ )-, -S-, -S(O) ２ -, -S(O)-, -S(O) ２ N (R １２ )-,-S(O)N(R １２ ) -, -N(R １２ )S(O)-,-N(R １２ ) S (O) ２ -, C １～６ Alkylene, (—O—C １～６ alkyl) ｚ -, (-C １～６ alkyl-O) ｚ - 、 C ２～６ Alkenylene, C ２～６ Alkynylene, C １～６ Haloalkylene, C ３～１２ Cycloalkylene, C １～１１ Heterocycloalkylene, C ６～１２ Arylene, or C １～１１ heteroarylene, C １～６ Alkylene, C ２～６ Alkenylene, C ２～６ Alkynylene, C １～６ Haloalkylene, C ３～１２ Cycloalkylene, C １～１１ Heterocycloalkylene, C ６～１２ Arylene, or C １～１１ The heteroarylene may be one, two, or three R ２０ optionally substituted with (—O—C １～６ alkyl) ｚ - and (-C １～６ alkyl-O) ｚ -Each C １～６ The alkyl may be one, two, or three R ２０ optionally substituted with 60. The compound of any one of claims 57 to 59, wherein z is independently an integer from 0 to 10.

61. L ＤＥ But -(O-C ２ alkyl) ｚ - and z is an integer from 1 to 10.

62. L ＤＥ But -(C ２ alkyl-O-) ｚ - and z is an integer from 1 to 10.

63. L ＤＥ But -(CH ２ ) ｚｚ１ L ＤＥ２ (CH ２ O) ｚｚ２ - and L ＤＥ２ is a bond, 5- or 6-membered heterocycloalkylene or heteroarylene, phenylene, —C ２～４ Alkynylene, —SO ２ -, or -NH-, and zz1 and zz2 are independently an integer of 0 to 10. The compound according to any one of claims 57 to 60,

64. L ＤＥ But -(CH ２ ) ｚｚ１ (CH ２ O) ｚｚ２ - and zz1 and zz2 are each independently an integer from 0 to 10.

65. L ＤＥ The compound of any one of claims 57 to 60, wherein is a PEG linker.

66. E, 【Chemistry 195】 66. The compound of any one of claims 57 to 65, which is a monovalent form of a compound selected from:

67. 10. The compound, salt, or solvate of any one of the preceding claims, wherein the compound is provided in an enantiomeric excess of at least 99%.

68. 68. A pharmaceutical composition comprising a compound according to any one of claims 1 to 67, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

69. 100. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 67, or a pharmaceutically acceptable salt or solvate thereof.

70. 1. A method for enhancing cellular immunity, comprising:

68. A method comprising: (a) contacting said cell with a compound of any one of claims 1 to 67, thereby immune-enhancing said cell, wherein said cell comprises (i) a chimeric T cell receptor sequence encoding a T cell receptor fusion protein (TFP), and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and CAR exhibits specific binding to an antigen.

71. 1. A method for enhancing cellular immunity, comprising: (a) contacting the cell with a compound of any one of claims 1 to 67; (b) introducing into the cells (i) a chimeric T cell receptor sequence encoding a T cell receptor fusion protein (TFP), and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, each of the TFP and CAR exhibiting specific binding to an antigen, thereby enhancing the immunity of the cells.

72. 72. The method of claim 71, wherein (a) is performed before, simultaneously with, or after (b).

73. 73. The method of any one of claims 70-72, wherein the cells retain PTPN2 expression or activity prior to (a).

74. 74. The method of any one of claims 70 to 73, wherein the cell is a lymphoid cell.

75. 75. The method of any one of claims 70 to 74, further comprising administering the cells to a subject in need thereof.

76. 76. The method of claim 75, further comprising administering to the subject a compound of any one of claims 1 to 67 prior to, simultaneously with, or after administering the cells.

77. 77. The method of claim 76, wherein cells of the subject exhibit PTPN2 expression or activity prior to administering the compound of any one of claims 1-67.

78. 100. A method of treating cancer in a subject in need thereof, comprising: (a) administering a compound of any one of claims 1-67; and (b) administering, concurrently with, before, or after step (a), a second agent or second therapy, wherein the second agent or second therapy (1) retains PTPN2 expression or activity prior to exposure to the compound, and (2) comprises lymphoid cells expressing (i) a chimeric T cell receptor (TCR) sequence encoding a T cell receptor fusion protein (TFP), and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and CAR exhibits specific binding to a tumor antigen.

79. 79. The method of claim 78, wherein the compound is administered systemically and / or transiently to the subject in need thereof, and the second agent or therapy comprises (1) lymphoid cells that retain PTPN2 expression or activity prior to exposure to the compound, and (2) a chimeric antigen receptor (CAR) sequence encoding a CAR that exhibits specific binding to a tumor antigen.

80. 80. The method of claim 78 or 79, wherein the lymphoid cells retain at least about 90% of the PTPN2 expression or activity compared to a control prior to exposure to the compound.

81. 81. The method of any one of claims 78-80, wherein the second agent or therapy comprises a sub-therapeutic amount of the lymphoid cells.

82. 82. The method of any one of claims 78-81, wherein the compound (i) does not modulate site-specific recombination of the gene encoding PTPN2, and (ii) does not affect editing of the gene encoding PTPN2.

83. 83. The method of any one of claims 78 to 82, wherein the lymphoid cells are immune effector cells.

84. The method of any one of claims 78 to 83, wherein the lymphoid cells are selected from the group consisting of T cells, B cells, NK cells, KHYG cells, T helper cells, regulatory T cells, memory T cells, tumor-infiltrating T cells (TIL), antigen-presenting cells, and dendritic cells.

85. 85. The method of claim 84, wherein the lymphoid cells are selected from the group consisting of CD4+ T cells, CD8+ T cells, and CD4+ and CD8+ T cells.

86. 86. The method of any one of claims 78-85, wherein the subject is afflicted with a cancer selected from cancer of the bladder, bone, brain, breast, cervix, colon, lung, esophagus, head and neck, ovary, prostate, uterus, stomach, skin, and renal tissue.

87. The compound has an IC50 of 500 nM or less for PTPN2 as determined in a phosphatase assay utilizing DiFMUP as a substrate. ５０ The method according to any one of claims 78 to 86, wherein

88. The compound has (i) an IC of less than 5 nM as determined in a phosphatase assay utilizing DiFMUP as the substrate. ５０ , and (ii) an EC of less than 10 μM in the pSTAT1 assay. ５０ The method according to any one of claims 78 to 86, wherein

89. The compound has (i) an IC of less than 5 nM as determined in a phosphatase assay utilizing DiFMUP as the substrate. ５０ , (ii) an EC of less than 5 μM in the pSTAT1 assay ５０ and (iii) an EC of less than 1 μM when tested in the CD25 assay. ５０ The method according to any one of claims 78 to 86, wherein

90. The compound has an IC of 500 nM or less for PTP1B as determined in a phosphatase assay utilizing DiFMUP as a substrate. ５０ The method according to any one of claims 78 to 89, wherein

91. 91. The method of any one of claims 78-90, wherein PTPN2 expression or activity is transiently downregulated by intermittent administration of said compound to said lymphoid cells.

92. 92. The method of any one of claims 78-91, further comprising monitoring one or more inflammatory biomarkers present in the subject selected from the group consisting of antibodies, cytokines, radicals, and coagulation factors, concurrently with or following administration of the compound and / or the lymphoid cells.

93. 93. The method of claim 92, wherein the cytokine comprises IL-1, IL-6, TNF-α, IL-10, or IL-1RR.

94. 94. The method of any one of claims 78-93, further comprising administering to the subject another agent selected from the group consisting of a chemotherapeutic agent, a radioactive agent, an anti-tumor marker inhibitor, and a checkpoint inhibitor.

95. 95. The method of any one of claims 69 to 94, further comprising administering an additional therapeutic agent in conjunction with the compound of any one of claims 1 to 67.

96. 68. A modified lymphoid cell comprising (i) a chimeric T cell receptor (TCR) sequence encoding a T cell receptor fusion protein (TFP), and / or (ii) a chimeric antigen receptor (CAR) sequence encoding a CAR, wherein each of the TFP and the CAR exhibits specific binding to an antigen, and wherein the lymphoid cell comprises a compound of any one of claims 1 to 67.

97. The compound has (i) an IC of less than 5 nM as determined in a phosphatase assay utilizing DiFMUP as the substrate. ５０ , (ii) an EC of less than 10 μM in the pSTAT1 assay ５０ and / or (iii) an EC of less than 1 μM when tested in a CD25 assay. ５０ 97. The modified lymphoid cell of claim 96, which exhibits:

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