Protein tyrosine phosphatase inhibitors and methods of use thereof

Abstract

To provide compounds and compositions for treating cancer, type-2 diabetes, obesity, a metabolic disease, or any other disease, disorder or ailment favorably responsive to PTPN2 or PTPN1 inhibitor treatment, and methods of treating the diseases.SOLUTION: Provided herein are: compounds with an effect of inhibiting PTPN2 and / or PTPN1 illustrated by the compound Y in the figure; pharmaceutically acceptable compositions comprising the compounds and pharmaceutically acceptable carriers; and methods of treatment by administering the compositions.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 818,447, filed March 14, 2019, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] background Cancer immunotherapy regimens that target immune evasion mechanisms, including checkpoint blockade (e.g., PD-1 / PD-L1 and CTLA-4 blocking antibodies), have been shown to be effective in treating a variety of cancers and dramatically improve outcomes in subsets of patients refractory to conventional therapies. However, the patient population in which checkpoint blockade can be effective remains limited due to incomplete clinical responses and the development of intrinsic or acquired resistance.

[0003] Protein tyrosine phosphatase non-receptor type 2 (PTPN2), also known as T-cell protein tyrosine phosphatase (TC-PTP), is an intracellular member of the class 1 subfamily of phospho-tyrosine-specific phosphatases that control multiple cellular regulatory processes by removing phosphate groups from tyrosine substrates. PTPN2 is ubiquitously expressed, with expression highest in hematopoietic and placental cells (Mosinger, B. Jr. et al., Proc Natl Acad Sci USA 89:499-503; 1992). In humans, PTPN2 expression is posttranscriptionally regulated by the existence of two splice variants: a 45-kDa form containing a nuclear localization signal at the C-terminus upstream of the splice junction, and a 48-kDa canonical form with a C-terminal ER retention motif (Tillmann U. et al., Mol Cell Biol 14:3030-3040; 1994). The 45-kDa isoform can passively import into the cytosol under certain conditions of cellular stress. Both isoforms share an N-terminal phosphotyrosine phosphatase catalytic domain. PTPN2 negatively regulates signaling of nonreceptor tyrosine kinases (e.g., JAK1 and JAK3), receptor tyrosine kinases (e.g., INSR, EGFR, CSF1R, and PDGFR), transcription factors (e.g., STAT1, STAT3, and STAT5a / b), and Src family kinases (e.g., Fyn and Lck). As a key negative regulator of the JAK-STAT pathway, PTPN2 functions to directly regulate signaling through cytokine receptors, including IFNγ. The PTPN2 catalytic domain shares 74% sequence identity with PTPN1 (also known as PTP1B) and shares similar enzymatic kinetics (Romsicki Y. et al., Arch Biochem Biophys 414:40-50; 2003).

[0004] Data from a loss-of-function in vivo genetic screen using CRISPR / Cas9 genome editing in a mouse B16F10 transplantable tumor model showed that deletion of the Ptpn2 gene in tumor cells improved response to an immunotherapy regimen consisting of a GM-CSF-secreting vaccine (GVAX) and PD-1 checkpoint blockade (Manguso RT et al., Nature 547:413-418; 2017). Loss of Ptpn2 enhanced IFNγ-mediated effects on antigen presentation and growth suppression, sensitizing tumors to immunotherapy. The same screen revealed that genes known to be involved in immune evasion, including PD-L1 and CD47, were also depleted under the selective pressure of immunotherapy, whereas genes involved in the IFNγ signaling pathway, including IFNGR, JAK1, and STAT1, were enriched. These observations suggest that therapeutic strategies that enhance IFNγ sensing and signaling may play a putative role in enhancing the efficacy of cancer immunotherapy regimens.

[0005] Protein tyrosine phosphatase non-receptor type 1 (PTPN1), also known as protein tyrosine phosphatase-1B (PTP1B), has been shown to play an important role in insulin and leptin signaling and is the primary mechanism for downregulating both insulin and leptin receptor signaling pathways (Kenner KA et al., J Biol Chem 271:19810-19816, 1996 (Non-Patent Document 5)). PTPN1-deficient animals have improved glucose regulation and lipid profiles and are less likely to gain weight when fed a high-fat diet (Elchebly M. et al., Science 283:1544-1548, 1999 (Non-Patent Document 6)). Therefore, PTPN1 inhibitors are expected to be useful for the treatment of type 2 diabetes, obesity, and metabolic syndrome. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Mosinger,B.Jr.et al.,Proc Natl Acad Sci USA 89:499-503;1992 [Non-patent document 2] Tillmann U. et al., Mol Cell Biol 14:3030-3040;1994 [Non-patent document 3] Romsicki Y. et al., Arch Biochem Biophys 414:40-50;2003 [Non-patent document 4] Manguso RTet al.,Nature 547:413-418;2017 [Non-patent document 5] Kenner KA et al., J Biol Chem 271:19810-19816,1996 [Non-patent document 6] Elchebly M. et al.,Science 283:1544-1548,1999 Summary of the Invention

[0007] overview The present disclosure relates, at least in part, to compounds, compositions, and methods for inhibiting protein tyrosine phosphatases, such as protein tyrosine phosphatase non-receptor type 2 (PTPN2) and / or protein tyrosine phosphatase non-receptor type 1 (PTPN1), also known as protein tyrosine phosphatase-1B (PTP1B)). In some embodiments, disclosed herein are inhibitors of protein tyrosine phosphatases, such as PTPN2 and / or PTPN1, including the compounds disclosed herein. In other embodiments, disclosed herein are methods of treating a disease or disorder, such as cancer, type 2 diabetes, obesity, metabolic disease, or any other disease, disorder, or condition that responds well to treatment with a PTPN2 or PTPN1 inhibitor, comprising administering an effective amount of a compound disclosed herein.

[0008] For example, disclosed herein are compounds represented by formula (I), or a pharmaceutically acceptable salt thereof: TIFF2025061064000001.tif27128[in the formula, Z is C(H)(R 3 ), bonds, and N(R 8 ) selected from the group consisting of R 1 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 alkyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 Alkyl is a group having R on one or more available carbons. g optionally substituted with one, two, three or more substituents each independently selected from R 2 is hydrogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -NH2, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-N(R a )(R b ), -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 alkylene-phenyl (where -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C3-6 Cycloalkyl, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 Alkylene-phenyl has R on one or more available carbons. g and optionally substituted with one, two, three or more substituents each independently selected from 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R a )-C1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h and Z is C(H)(R 3 ), then R 2 is not -CH2-CH3), R 2’ is hydrogen, -NR a R b , and -N(R a )-N(R b )—C(O)-phenyl; R 3 is hydrogen, -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 4 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 5 are hydrogen, deuterium, halogens, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 6 is selected from the group consisting of hydrogen and deuterium; R 7 is selected from the group consisting of hydrogen and deuterium; R 8 is hydrogen and C 1-6 is selected from the group consisting of alkyl, R g is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R a R b N-, R a R b NC(O)-, R a R b N-SO w -, R a R b NC(O)-N(R a )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SOw -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SOw -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R P optionally substituted with one, two, three or more substituents each independently selected from R h For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N-SO2- is R Poptionally substituted with one, two, three or more substituents each independently selected from R P For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R a R b N-, R a R b N-carbonyl-, R a R b N-SO2- and R a R b N-carbonyl-N(R a )-, R a and R b For each occurrence, hydrogen and C 1-6 alkyl (wherein C 1-6 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R a and R b together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; R c For each occurrence, hydroxyl, C 1-4 independently selected from the group consisting of alkyl, and phenyl; w is 0, 1, or 2].

[0009] Also disclosed herein is a compound represented by formula (II), or a pharmaceutically acceptable salt thereof: TIFF2025061064000002.tif27128[In the formula, X II1 is O and C(R II1 )(R II1’ ) selected from the group consisting of X II4 is O and C(R II4 )(R II4’ ) selected from the group consisting of (where X II1 and X II4 at least one of which is O), R II1 and R II1’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -C(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C1-6 alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R IIa )-C 1-6 alkylene-phenyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -C(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R IIa )-C 1-6 Alkylene-phenyl has R on one or more available carbons. IIg and optionally substituted with one, two, three or more substituents each independently selected from 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R IIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIh and R II2 Ga-OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, or -N(R IIa )-C 1-6 When X is alkylene-phenyl, II1 is C(R II1 )(R II1’ ) and X II4 is O), R II2’ is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. IIg and 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -C 1-6 alkylene-5-6 membered heteroaryl, or -C 1-6When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIh optionally substituted with R II3 and R II3’ is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II4 and R II4’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II5 are hydrogen, deuterium, halogens, C 1-6 Alkyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II6is selected from the group consisting of hydrogen and deuterium; R II7 is selected from the group consisting of hydrogen and deuterium; R IIg is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R IIa R IIb N-, R IIa R IIb NC(O)-, R IIaIIb N-SO w -, R IIa R IIb NC(O)-N(R IIIa )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIa ), C 1-6 Alkyl-N(R IIa )-C(O)-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-SO w -, C 3-6 Cycloalkyl-N(R IIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIa )-, C 3-6 Cycloalkyl-SO w-N(R IIa )-, C 1-6 Alkoxy-C(O)-N(R IIa )-, C 1-6 Alkyl-C(O)-N(R IIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIa )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIa ), C 1-6 Alkyl-N(R IIa )-C(O)-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-SO w -, C 3-6 Cycloalkyl-N(R IIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIa )-, C 3-6 Cycloalkyl-SO w -N(R IIa )-, C 1-6Alkoxy-C(O)-N(R IIa )-, C 1-6 Alkyl-C(O)-N(R IIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIa )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R IIP optionally substituted with one, two, three or more substituents each independently selected from R IIh For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIa R IIb NC(O)- and R IIa R IIb N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIa R IIb NC(O)- and R IIa R IIb N-SO2- is R IIP optionally substituted with one, two, three or more substituents each independently selected from R IIP For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R IIaR IIb N-, R IIa R IIb N-carbonyl-, R IIa R IIb N-SO2- and R IIa R IIb N-carbonyl-N(R IIa )-, R IIa and R IIb For each occurrence, hydrogen and C 1-3 alkyl (wherein C 1-3 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R IIa and R IIb together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; and w is 0, 1, or 2].

[0010] Also disclosed herein is a compound represented by formula (III), or a pharmaceutically acceptable salt thereof: TIFF2025061064000003.tif28128[in the formula, R III1 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 Alkylene-C 3-8 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-C 1-6 Alkylene-C 3-8 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, -C(O)-N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl, -C=N(R IIIa )-C 1-6 Alkyl, and -S(O)2-C 1-6 alkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 Alkylene-C 3-8 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-C 1-6 Alkylene-C 3-8 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(RIIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, -C(O)-N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl, -C=N(R IIIa )-C 1-6 Alkyl, and -S(O)2-C 1-6 Alkyl is a group having R on one or more available carbons. IIIg and 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, or -C(O)-N(R IIIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIIh optionally substituted with R III3 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III4 is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III4’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III5 is hydrogen, halogen, and C 1-6 is selected from the group consisting of alkyl, R III6is selected from the group consisting of hydrogen and deuterium; R III7 is selected from the group consisting of hydrogen and deuterium; R IIIg is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R IIIa R IIIb N-, R IIIa R IIIb NC(O)-, R IIIaIIIb N-SO w -, R IIIa R IIIb NC(O)-N(R IIIa )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIIa ), C 1-6 Alkyl-N(R IIIa )-C(O)-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-SO w -, C 3-6 Cycloalkyl-N(R IIIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIIa )-, C 3-6 Cycloalkyl-SO w-N(R IIIa )-, C 1-6 Alkoxy-C(O)-N(R IIIa )-, C 1-6 Alkyl-C(O)-N(R IIIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIIa )-C(O)-C 1-6 Alkyl-, C 1-6 Alkoxy-C 1-6 independently selected from the group consisting of alkyl-, and 5- to 6-membered heteroaryl, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIIa ), C 1-6 Alkyl-N(R IIIa )-C(O)-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-SO w -, C 3-6 Cycloalkyl-N(R IIIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIIa )-, C 3-6 Cycloalkyl-SO w -N(R IIIa )-, C1-6 Alkoxy-C(O)-N(R IIIa )-, C 1-6 Alkyl-C(O)-N(R IIIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIIa )-C(O)-C 1-6 Alkyl-, C 1-6 Alkoxy-C 1-6 Alkyl- and 5- to 6-membered heteroaryl are R IIIP optionally substituted with one, two, three or more substituents each independently selected from R IIIh For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIIa R IIIb NC(O)-, R IIIa R IIIb N-SO2- and -C 1-6 alkylene-5-6 membered heteroaryl, 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIIa R IIIb NC(O)-, R IIIa R IIIb N-SO2- and -C 1-6 Alkylene-5-6 membered heteroaryl is R IIIP optionally substituted with one, two, three or more substituents each independently selected from RIIIP For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R IIIa R IIIb N-, R IIIa R IIIb N-carbonyl-, R IIIa R IIIb N-SO2- and R IIIa R IIIb N-carbonyl-N(R IIIa )-, R IIIa and R IIIb For each occurrence, hydrogen and C 1-3 alkyl (wherein C 1-3 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R IIIa and R IIIb together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; and w is 0, 1, or 2].

[0011] Further disclosed herein is a method for producing a semiconductor device comprising: 5-[1-fluoro-3-hydroxy-7-(3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(cyclopropylmethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-Fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(2-cyclopropylethyl)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(2-methoxyethoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(cyclopropylmethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7S)-1-Fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(5-fluoro-7-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-(5-fluoro-7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-6-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1,4-difluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(azetidin-1-yl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3,3,3-trifluoropropyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-difluorocyclobutyl)methoxy]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4-methoxy-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-methoxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({2-[1-(trifluoromethyl)cyclopropyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2,2-difluoro-2-phenylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3-cyclopropyl-2,2-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[methyl(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4-methylpentyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)butyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[4,4,4-trifluoro-3-(trifluoromethyl)butyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2,2-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[2-(pyridin-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-1-fluoro-3-hydroxy-7-[(3RS)-pyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-7-[(3RS)-1-(cyclopropanesulfonyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-1-fluoro-3-hydroxy-7-[(3SR)-pyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-7-[(3SR)-1-(cyclopropanesulfonyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[1-(cyclopropylmethyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[2-(1H-pyrazol-1-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(4,4,4-trifluorobutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methylpentanoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methylpentyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-Fluoro-3-hydroxy-7-({2-[1-(trifluoromethyl)cyclopropyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-ylphenylcarbamate, 4-{[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]amino}-2,2-dimethylbutanenitrile, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3-hydroxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3-methoxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(5,5,5-trifluoropentyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{(3-methylbutyl)[(pyridin-2-yl)methyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[(pyridin-2-yl)methyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-2-hydroxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(difluoromethoxy)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-pentanimidoyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(3-cyclopropylpropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-azaspiro[3.3]heptan-6-yl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(6,6,6-trifluorohexyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,3-difluorocyclobutyl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(azetidin-3-yl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(propan-2-yl)amino]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(azetidin-3-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(azetidin-3-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{(3-methylbutyl)[2-(pyridin-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(spiro[2.3]hexan-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[2-(trifluoromethoxy)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-hydroxy-3-methylbutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 3-Hydroxybutyl 8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-{1-fluoro-3-hydroxy-7-[3-(propan-2-yl)pyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclohexylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-dimethylbutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(butylamino)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopentylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclohexylethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2-hydroxyethyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[2-(propan-2-yl)morpholin-4-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2R)-2-(propan-2-yl)morpholin-4-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(pyrrolidin-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(pyridin-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclobutylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({2-[(propan-2-yl)oxy]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopropyl-2-hydroxyethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[3-(trimethylsilyl)propyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({3-[hydroxy(dimethyl)silyl]propyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(pyridin-2-yl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,3-difluorocyclobutyl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(pyrrolidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-methylbutanimidamide, 5-{8-fluoro-6-hydroxy-2-[3-(oxan-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(3-hydroxy-3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-7-amino-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(4,4-difluorobutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclopentylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclobutylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-7-{[2-(3,3-difluorocyclobutyl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylpentyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(3-ethylpentyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-(3-methylbutyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-methylpropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{8-fluoro-6-hydroxy-2-[3-(pyridin-3-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(pyrimidin-5-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(oxan-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclohexyl-2-hydroxyethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(2-methoxyethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-methoxypropyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(3-aminopropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(piperidin-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-methylbutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl 8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-{8-fluoro-6-hydroxy-2-[(7-oxabicyclo[2.2.1]heptan-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-Fluoro-6-hydroxy-2-{1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]azetidin-3-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(7-oxabicyclo[2.2.1]heptan-2-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(2,2-difluoroethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-{[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]methyl}-3,5-dimethyl-1H-pyrazol-1-yl)-2,2-dimethylpentanenitrile, 5-{8-fluoro-6-hydroxy-2-[(piperidin-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(morpholin-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(piperidin-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(1s,3r)-3-(trifluoromethoxy)cyclobutyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(4-methylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(propan-2-yl)oxy]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-Fluoro-3-hydroxy-7-({2-[(1s,3r)-3-(trifluoromethoxy)cyclobutyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[(1s,3s)-3-(trifluoromethoxy)cyclobutyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-Fluoro-6-hydroxy-2-{2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-2-azaspiro[3.3]heptan-6-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(difluoromethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(bicyclo[2.2.1]heptan-1-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-amino-1-fluoro-3-hydroxy-7-(prop-2-en-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N'-[8-fluoro-6-hydroxy-2-propyl-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzohydrazide, 5-[8-fluoro-6-hydroxy-2-(3-hydroxybutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[1-(trifluoromethyl)cyclopropyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-hydroxypropyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2S)-2-aminopropyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2R)-2-aminopropyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(piperazin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{[rac-(1R,2R)-2-(pyridin-4-yl)cyclopropyl]methyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclopentyl-2-methoxyethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2R)-2-amino-4-cyclohexylbutanoyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{3-[(propan-2-yl)oxy]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(1-methyl-1H-pyrazol-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(2,2-difluoroethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[7-amino-1-fluoro-3-hydroxy-7-(4-methylpentyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-amino-1-fluoro-3-hydroxy-7-propyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1,3-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(cyclopropylmethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{(7S)-7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-[(oxan-4-yl)methyl]-7-(1,1,4-trioxo-1λ) 6,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(3,3-difluorocyclobutyl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(oxolan-2-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-(2-cyclopropylethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{2-[2-(1-tert-butyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(aminomethyl)-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{[bis(3-methylbutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-[(oxolan-3-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(1-methyl-1H-pyrazol-5-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-(2-{2-[3,5-dimethyl-1-(propan-2-yl)-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{[(3-cyclopropylpropyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1-ethyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ6 ,2,5-thiadiazolidine-1,1,3-trione, N-(2,2-dimethylpropyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(3-methoxypropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(3-methoxy-2,2-dimethylpropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[2-(dimethylamino)ethyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[2-(1-methylcyclopropyl)ethyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-methoxyethyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(oxetan-3-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-phenylethyl)-7-(1,1,4-trioxo-1λ) 6,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[3-(dimethylamino)propyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-[2-(3-cyclohexylpropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[3-(2,2-dimethylcyclopropyl)propyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(3S)-5-Fluoro-7-hydroxy-3-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(2R)-4-Fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(2S)-4-Fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methoxybutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{3-[3-(trifluoromethyl)phenyl]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-methyl-3-[4-(propan-2-yl)phenyl]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[4-(5,5-dimethyl-1,3-dioxan-2-yl)butyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(2,6,6-trimethylcyclohex-1-en-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-pentyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-2-[3-(4-fluorophenyl)propyl]-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl [(1r,4r)-4-{2-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}cyclohexyl]carbamate, 5-{2-[3-(4-tert-butylphenyl)propyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3,5,5-trimethylhexyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-2-[3-(2-fluorophenyl)propyl]-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 3-Hydroxybutyl 4,4,8-trifluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-(2-{[(2-cyclobutylethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-fluoro-3-hydroxy-7-{[(3R)-3-hydroxybutyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(4-hydroxy-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-6-(3-hydroxy-3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(cyclopropylmethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{6-[(4,4-difluorobutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(4,4-difluorobutoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-6-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-6-(3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-6-[(3-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl (2-{[5-fluoro-7-hydroxy-6-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]oxy}ethyl)carbamate, 5-(1-fluoro-3-hydroxy-6-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{6-[(cyclopropylmethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(2-aminoethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(cyclohexylmethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide, 5-[1-fluoro-3-hydroxy-7-(4-methylpentyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(3S)-5-Fluoro-7-hydroxy-3-(4-methylpentyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, and pharmaceutically acceptable salts thereof The compound is selected from the group consisting of:

[0012] In some embodiments, the compounds disclosed herein are formulated as pharmaceutically acceptable compositions comprising a compound of the present disclosure and a pharmaceutically acceptable carrier.

[0013] Also disclosed herein are methods of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein in combination with an additional therapeutic agent. In some embodiments, the additional therapeutic agent is an immunotherapeutic agent. For example, in some embodiments, the immunotherapeutic agent is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA-4 antibody.

[0014] For example, disclosed herein is a method of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein.

[0015] Further provided herein is a method of treating type 2 diabetes in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein.

[0016] Disclosed herein are methods for treating and / or controlling obesity, e.g., in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein.

[0017] For example, disclosed herein is a method of inhibiting further weight gain in an overweight or obese patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein.

[0018] Further disclosed herein is a method of treating a metabolic disease in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein.

[0019] In some embodiments, the method comprises treating cancer. In some embodiments, the cancer comprises pancreatic cancer, breast cancer, multiple myeloma, melanoma, or secretory cell carcinoma. In some embodiments, the method comprises treating a metabolic disease. In some embodiments, the metabolic disease comprises non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, type 2 diabetes, heart disease, atherosclerosis, arthritis, cystinosis, phenylketonuria, proliferative retinopathy, metabolic syndrome, or Kearns-Sayre disease.

[0020] Also disclosed herein are compositions for use in treating cancer in a patient in need thereof, the compositions comprising a compound disclosed herein in combination with an additional therapeutic agent. In some embodiments, the additional therapeutic agent is an immunotherapeutic agent. For example, in some embodiments, the immunotherapeutic agent is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA-4 antibody.

[0021] For example, disclosed herein are compositions for use in treating cancer in a patient in need thereof, the compositions comprising a compound disclosed herein.

[0022] Further provided herein is a composition for use in treating type 2 diabetes in a patient in need thereof, the composition comprising a compound disclosed herein.

[0023] Disclosed herein are compositions for use in treating and / or controlling obesity, e.g., in a patient in need thereof, comprising a compound disclosed herein.

[0024] For example, disclosed herein are compositions for use in inhibiting further weight gain in an overweight or obese patient in need thereof, the compositions comprising a compound disclosed herein.

[0025] Further disclosed herein is a composition for use in treating a metabolic disease in a patient in need thereof, the composition comprising a compound disclosed herein.

[0026] In some embodiments, the cancer comprises pancreatic cancer, breast cancer, multiple myeloma, melanoma, or secretory cell carcinoma. In some embodiments, the metabolic disease comprises nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, type 2 diabetes, heart disease, atherosclerosis, arthritis, cystinosis, phenylketonuria, proliferative retinopathy, metabolic syndrome, or Kearns-Sayre disease.

[0027] Brief description of the sequence listing The entire sequence listing entitled "CLS-016WO SEQ ID List_ST25.txt," including SEQ ID NOs: 1 to 3, which contains the amino acid sequences disclosed herein, is incorporated herein by reference. This sequence listing has been submitted herewith by EFS in ASCII text format. This sequence listing was first created on February 19, 2020, and is 7256 bytes in size. [The present invention 1001] A compound represented by formula (I), or a pharmaceutically acceptable salt thereof: TIFF2025061064000004.tif27128[In the formula, Z is C(H)(R 3 ), bonds, and N(R 8 ) selected from the group consisting of R 1 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 alkyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 Alkyl is a group having R on one or more available carbons. g optionally substituted with one, two, three or more substituents each independently selected from R 2 is hydrogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -NH2, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-N(R a )(R b ), -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 alkylene-phenyl (where -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C 3-6Cycloalkyl, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 Alkylene-phenyl has R on one or more available carbons. g and optionally substituted with one, two, three or more substituents each independently selected from 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R a )-C 1-6When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h and Z is C(H)(R 3 ), then R 2 is not -CH2-CH3), R 2’ is hydrogen, -NR a R b , and -N(R a )-N(R b )—C(O)-phenyl; R 3 is hydrogen, -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 4 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 5 are hydrogen, deuterium, halogens, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 6 is selected from the group consisting of hydrogen and deuterium; R 7 is selected from the group consisting of hydrogen and deuterium; R 8 is hydrogen and C 1-6 is selected from the group consisting of alkyl, R g is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R a R b N-, R a R b NC(O)-, R a R b N-SO w -, R a R b NC(O)-N(R a )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SOw -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SOw -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R P optionally substituted with one, two, three or more substituents each independently selected from R h For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N-SO2- is R Poptionally substituted with one, two, three or more substituents each independently selected from R P For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R a R b N-, R a R b N-carbonyl-, R a R b N-SO2- and R a R b N-carbonyl-N(R a )-, R a and R b For each occurrence, hydrogen and C 1-6 alkyl (wherein C 1-6 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R a and R b together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; R c For each occurrence, hydroxyl, C 1-4 independently selected from the group consisting of alkyl, and phenyl; w is 0, 1, or 2]. [The present invention 1002] The compound of the present invention is represented by formula (Ia) or a pharmaceutically acceptable salt thereof: TIFF2025061064000005.tif27128[in the formula, R 1 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6alkyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 Alkyl is a group having R on one or more available carbons. g optionally substituted with one, two, three or more substituents each independently selected from R 2 is hydrogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -NH2, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 alkylene-phenyl (where -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(Ra )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 Alkylene-phenyl has R on one or more available carbons. g and 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R a )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 2’ is hydrogen, -NR a R b , and -N(R a )-N(R b )—C(O)-phenyl; R 3 is hydrogen, -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6alkylene-4- to 6-membered heterocyclyl (where -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 4 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 5 are hydrogen, deuterium, halogens, C1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 6 is selected from the group consisting of hydrogen and deuterium; R 7 is selected from the group consisting of hydrogen and deuterium; R g is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R a R b N-, R a R b NC(O)-, R a R b N-SO w -, R a R b NC(O)-N(R a )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O)w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(Ra )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R P optionally substituted with one, two, three or more substituents each independently selected from R h For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R bN—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N-SO2- is R P optionally substituted with one, two, three or more substituents each independently selected from R P For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R a R b N-, R a R b N-carbonyl-, R a R b N-SO2- and R a R b N-carbonyl-N(R a )-, R a and R b For each occurrence, hydrogen and C 1-6 alkyl (wherein C 1-6 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R a and R b together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; R cFor each occurrence, hydroxyl, C 1-4 independently selected from the group consisting of alkyl, and phenyl; w is 0, 1, or 2]. [The present invention 1003] R 1 The compound of claim 1001 or 1002, wherein is selected from the group consisting of hydrogen and fluorine. [The present invention 1004] R 2 But, -OC 1-6 alkyl, and R 2 But R g The compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1005] R 2 However, fluorine, hydroxyl, C 1-6 Alkoxy, and R a R b The compound of the present invention 1004 optionally substituted with one, two, three or more substituents each independently selected for each occurrence from the group consisting of N-. [The present invention 1006] R 2 But -OCH3, The compound of the present invention 1004 or 1005, selected from the group consisting of TIFF2025061064000006.tif10128. [The present invention 1007] R 2 But -N(R a )-C 1-8 alkyl, and R 2 But R g The compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1008] R 2 fluorine, hydroxyl, cyano, and C 1-6 and optionally substituted with one, two, three or more substituents each independently selected from the group consisting of alkoxy, C1-6 1007. A compound of the present invention wherein the alkoxy is optionally substituted with 1, 2, or 3 fluorines. [The present invention 1009] R 2 but, The compound of the present invention 1007 or 1008, selected from the group consisting of TIFF2025061064000007.tif113152. [The present invention 1010] R 2 But -C 1-6 Alkylene-C 3-6 The compound of any one of 1001 to 1003 of the present invention, which is cycloalkyl. [The present invention 1011] R 2 but, The compound of the present invention 1010 is represented by TIFF2025061064000008.tif10128. [The present invention 1012] R 2 But, -OC 1-6 Alkylene-C 3-6 is cycloalkyl, and R 2 But R g The compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1013] R 2 is optionally substituted with 1, 2, or 3 fluorine atoms. [The present invention 1014] R 2 but, The compound of the present invention 1012 or 1013 selected from the group consisting of TIFF2025061064000009.tif15128. [The present invention 1015] R 2 But -N(R a )-C 1-6 Alkylene-C 3-6 is cycloalkyl, and R 2 But R gThe compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1016] R 2 but, 1015 compounds of the present invention selected from the group consisting of TIFF2025061064000010.tif50129. [The present invention 1017] R 2 But -N(R a )-C 1-6 The compound of any one of 1001 to 1003 of the present invention, which is alkylene-4 to 6-membered heterocyclyl. [The present invention 1018] R 2 but, The compound of the present invention 1017 is represented by TIFF2025061064000011.tif12128. [The present invention 1019] R 2 But -N(R a )-C 1-6 alkylene-phenyl, and R 2 But R g The compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1020] R 2 is optionally substituted with 1, 2, or 3 fluorine atoms. [The present invention 1021] R 2 but, Compound 1019 or 1020 of the present invention represented by TIFF2025061064000012.tif15128. [The present invention 1022] R 2 But -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, R 2 But R gThe compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1023] R 2 but, The compound of the present invention 1022 selected from the group consisting of TIFF2025061064000013.tif44139. [The present invention 1024] R 2 is a 4- to 6-membered heterocyclyl; 4-6 membered heterocyclyl is R g and When the 4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is h optionally substituted with Any of compounds 1001 to 1003 of the present invention. [The present invention 1025] R 2 is pyrrolidinyl, and pyrrolidinyl is R h 1024. A compound of the present invention optionally substituted with [The present invention 1026] R h But C 1-6 Alkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, and C 3-6 The compound of claim 1024 or 1025, selected from the group consisting of cycloalkyl-S(O)2-. [The present invention 1027] R 2 but, Any of the compounds of the present invention 1024 to 1026 selected from the group consisting of TIFF2025061064000014.tif19128. [The present invention 1028] R 2 But -OC(O)-N(R a )-phenyl. [The present invention 1029] R 2 but, The compound of the present invention 1028 is represented by TIFF2025061064000015.tif14128. [The present invention 1030] R 2 But -N(R a )-C 1-6 Alkylene-Si(R c )3. [The present invention 1031] R 2 but, The compound of the present invention 1030 selected from the group consisting of TIFF2025061064000016.tif11128. [The present invention 1032] R 2 But -N(R a )-(C=N(R b ))-C 1-6 The compound of any one of 1001 to 1003 of the present invention, which is alkyl. [The present invention 1033] R 2 but, The compound of the present invention 1032 is represented by TIFF2025061064000017.tif13128. [The present invention 1034] R 2 But -N(R a )-C 3-6 is cycloalkyl, and R 2 But R g The compound of any one of 1001 to 1003 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1035] R 2 but, The compound of the present invention 1034 is represented by TIFF2025061064000018.tif14128. [The present invention 1036] R 2 The compound of any one of 1001 to 1003 of the present invention, wherein is hydrogen. [This invention 1037] R 2’ is selected from the group consisting of hydrogen and -NH2. [The present invention 1038] R 3 The compound of any one of claims 1001 to 1037, wherein is hydrogen. [This invention 1039] R 3 But, -OC 1-6 Alkyl and -OC 1-6 Alkylene-C 3-6 cycloalkyl; R 3 But R g The compound of any one of claims 1001 to 1037 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1040] R 3 But -OCH3, The compound of the present invention 1039 selected from the group consisting of TIFF2025061064000019.tif26152. [This invention 1041] R 3 But -N(R a )-C 1-6 Alkyl and -N(R a )-C 1-6 alkylene-Ccycloalkyl; R 3 But R g The compound of any one of claims 1001 to 1037 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [The present invention 1042] R 3 but, The compound of the present invention 1041 selected from the group consisting of TIFF2025061064000020.tif13128. [This invention 1043] Formula I(c): The compound of the present invention 1001 is represented by TIFF2025061064000021.tif26128. [This invention 1044] R 2 -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C 1-6 Alkylene-N(R a )(R b ), and -C alkylene-N(R a )-C 1-6 Alkylene-C 3-6 cycloalkyl; R 2 But R g 1043. A compound of the present invention optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1045] R 2 but, The compound of the present invention 1044 selected from the group consisting of TIFF2025061064000022.tif37142. [The present invention 1046] Formula I(d): The compound of the present invention 1001 is represented by TIFF2025061064000023.tif26128. [This invention 1047] R 2 C 1-6 The compound of the present invention 1046, which is alkyl. [This invention 1048] R 4 The compound of any one of claims 1001 to 1047, wherein is hydrogen. [This invention 1049] R 5 is selected from the group consisting of hydrogen and fluorine. [The present invention 1050] R 6 The compound of any one of claims 1001 to 1049 of the present invention, wherein is hydrogen. [This invention 1051] R 7 The compound of any one of 1001 to 1050 of the present invention, wherein is hydrogen. [This invention 1052] A compound represented by formula (II), or a pharmaceutically acceptable salt thereof: TIFF2025061064000024.tif27128[in the formula, X II1 is O and C(R II1 )(R II1’ ) selected from the group consisting of X II4 is O and C(R II4 )(R II4’ ) selected from the group consisting of (where X II1 and X II4 at least one of which is O), R II1 and R II1’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -C(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R IIa )-C 1-6 alkylene-phenyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -C(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R IIa )-C 1-6 Alkylene-phenyl has R on one or more available carbons. IIg and optionally substituted with one, two, three or more substituents each independently selected from 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R IIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIh and R II2 Ga-OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, or -N(R IIa )-C 1-6 When X is alkylene-phenyl, II1 is C(R II1 )(R II1’ ) and X II4 is O), R II2’ is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. IIgand 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -C 1-6 alkylene-5-6 membered heteroaryl, or -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIh (optionally substituted with), R II3 and R II3’ is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II4 and R II4’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II5 are hydrogen, deuterium, halogens, C 1-6 Alkyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl and C3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II6 is selected from the group consisting of hydrogen and deuterium; R II7 is selected from the group consisting of hydrogen and deuterium; R IIg is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R IIa R IIb N-, R IIa R IIb NC(O)-, R IIaIIb N-SO w -, R IIa R IIb NC(O)-N(R IIIa )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIa ), C 1-6 Alkyl-N(R IIa )-C(O)-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-SO w -, C 3-6Cycloalkyl-N(R IIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIa )-, C 3-6 Cycloalkyl-SO w -N(R IIa )-, C 1-6 Alkoxy-C(O)-N(R IIa )-, C 1-6 Alkyl-C(O)-N(R IIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIa )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIa ), C 1-6 Alkyl-N(R IIa )-C(O)-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-SO w -, C 3-6 Cycloalkyl-N(R IIa )-SOw -, C 1-6 Alkyl-SO w -N(R IIa )-, C 3-6 Cycloalkyl-SO w -N(R IIa )-, C 1-6 Alkoxy-C(O)-N(R IIa )-, C 1-6 Alkyl-C(O)-N(R IIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIa )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R IIP optionally substituted with one, two, three or more substituents each independently selected from R IIh For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIa R IIb NC(O)- and R IIa R IIb N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIa R IIb NC(O)- and R IIa R IIb N-SO2- is R IIPoptionally substituted with one, two, three or more substituents each independently selected from R IIP For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R IIa R IIb N-, R IIa R IIb N-carbonyl-, R IIa R IIb N-SO2- and R IIa R IIb N-carbonyl-N(R IIa )-, R IIa and R IIb For each occurrence, hydrogen and C 1-3 alkyl (wherein C 1-3 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R IIa and R IIb together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; and w is 0, 1, or 2]. [This invention 1053] R II5 , R II6 , and R II7 The compound of invention 1052, wherein each is hydrogen. [This invention 1054] R II1 and R II1’ or R II4 and R II4’ The compound of invention 1052 or 1053, wherein either of is each hydrogen. [This invention 1055] Any of compounds 1052 to 1054 of the present invention represented by TIFF2025061064000025.tif25128. [This invention 1056] R II2 and R II2’ are each independently selected from the group consisting of hydrogen and -CH3. [This invention 1057] R II3 and R II3’ are each independently selected from the group consisting of hydrogen and -CH3. [This invention 1058] A compound represented by formula (III), or a pharmaceutically acceptable salt thereof: TIFF2025061064000026.tif28128[in the formula, R III1 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 Alkylene-C 3-8 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-C 1-6 Alkylene-C 3-8 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, -C(O)-N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl, -C=N(R IIIa )-C 1-6 Alkyl, and -S(O)2-C 1-6 alkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 Alkylene-C 3-8 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-C 1-6 Alkylene-C 3-8 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, -C(O)-N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl, -C=N(R IIIa )-C 1-6 Alkyl, and -S(O)2-C 1-6 Alkyl is a group having R on one or more available carbons. IIIgand 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, or -C(O)-N(R IIIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIIh (optionally substituted with), R III3 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III4 is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III4’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III5 is hydrogen, halogen, and C 1-6 is selected from the group consisting of alkyl, R III6 is selected from the group consisting of hydrogen and deuterium; R III7 is selected from the group consisting of hydrogen and deuterium; R IIIg is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R IIIa R IIIb N-, R IIIa R IIIb NC(O)-, R IIIaIIIb N-SO w -, R IIIa R IIIbNC(O)-N(R IIIa )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIIa ), C 1-6 Alkyl-N(R IIIa )-C(O)-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-SO w -, C 3-6 Cycloalkyl-N(R IIIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIIa )-, C 3-6 Cycloalkyl-SO w -N(R IIIa )-, C 1-6 Alkoxy-C(O)-N(R IIIa )-, C 1-6 Alkyl-C(O)-N(R IIIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIIa )-C(O)-C 1-6 Alkyl-, C 1-6 Alkoxy-C 1-6independently selected from the group consisting of alkyl-, and 5- to 6-membered heteroaryl, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIIa ), C 1-6 Alkyl-N(R IIIa )-C(O)-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-SO w -, C 3-6 Cycloalkyl-N(R IIIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIIa )-, C 3-6 Cycloalkyl-SO w -N(R IIIa )-, C 1-6 Alkoxy-C(O)-N(R IIIa )-, C 1-6 Alkyl-C(O)-N(R IIIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIIa )-C(O)-C 1-6 Alkyl-, C 1-6 Alkoxy-C 1-6 Alkyl- and 5- to 6-membered heteroaryl are RIIIP optionally substituted with one, two, three or more substituents each independently selected from R IIIh For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIIa R IIIb NC(O)-, R IIIa R IIIb N-SO2- and -C 1-6 alkylene-5-6 membered heteroaryl, 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIIa R IIIb NC(O)-, R IIIa R IIIb N-SO2- and -C 1-6 Alkylene-5-6 membered heteroaryl is R IIIP optionally substituted with one, two, three or more substituents each independently selected from R IIIP For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R IIIa R IIIb N-, R IIIa R IIIb N-carbonyl-, R IIIa R IIIb N-SO2- and R IIIa R IIIb N-carbonyl-N(RIIIa )-, R IIIa and R IIIb For each occurrence, hydrogen and C 1-3 alkyl (wherein C 1-3 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R IIIa and R IIIb together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; and w is 0, 1, or 2]. [This invention 1059] R III5 is selected from the group consisting of hydrogen and fluorine. [The present invention 1060] R III6 and R III7 The compound of claim 1058 or 1059, wherein each is hydrogen. [The present invention 1061] R III4 and R III4’ and each independently selected from the group consisting of hydrogen and fluorine. [The present invention 1062] R III1 , R III3 , R III4 , and R III4’ and each represents hydrogen. [The present invention 1063] Any of compounds 1058 to 1062 of the present invention represented by TIFF2025061064000027.tif21128. [The present invention 1064] R III2 But hydrogen, C 1-6 Alkyl, and -C(O)-C1-6 alkyl; R III2 But R IIIg The compound of any one of claims 1058 to 1063 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1065] R III2 But hydrogen, Any of the compounds of the present invention 1058 to 1064 selected from the group consisting of TIFF2025061064000028.tif58149. [The present invention 1066] R III2 is a 4- to 7-membered heterocyclyl; 4-7 membered heterocyclyl is R at one or more available carbons IIIg and When the 4- to 7-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is IIIh optionally substituted with Any of compounds 1058 to 1063 of the present invention. [This invention 1067] R III2 but, The compound of the present invention 1066 selected from the group consisting of TIFF2025061064000029.tif39128. [The present invention 1068] R III2 is a 5- to 6-membered heteroaryl; The 5-6 membered heteroaryl may have R IIIg and When the 4- to 7-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is IIIh optionally substituted with Any of compounds 1058 to 1063 of the present invention. [The present invention 1069] R III2 but, The compound of the present invention 1068 is represented by TIFF2025061064000030.tif12128. [The present invention 1070] R III2 But -C 1-6 alkylene-5-6 membered heteroaryl; -C 1-6 The alkylene-5-6 membered heteroaryl is bonded to R IIIg and When the 4- to 7-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is IIIh optionally substituted with Any of compounds 1058 to 1063 of the present invention. [This invention 1071] R III2 but, The compound of the present invention 1070 selected from the group consisting of TIFF2025061064000031.tif83147. [This invention 1072] R III2 But -C 1-6 alkylene-phenyl, and R III2 But R IIIg The compound of any one of claims 1058 to 1063 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1073] R III2 but, The compound of the present invention 1072 selected from the group consisting of TIFF2025061064000032.tif34152. [This invention 1074] R III2 But -C 1-6 alkylene-4 to 7 membered heterocyclyl; -C 1-6 alkylene-4 to 7-membered heterocyclyl at one or more available carbons, R IIIgand -C 1-6 When alkylene-4 to 7-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is IIIh optionally substituted with Any of compounds 1058 to 1063 of the present invention. [This invention 1075] R III2 but, 1074 compounds of the present invention selected from the group consisting of TIFF2025061064000033.tif53144. [This invention 1076] R III2 But -C(O)-OC 1-6 alkyl, and R III2 But R IIIg The compound of any one of claims 1058 to 1063 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1077] R III2 but, 1076. A compound of the present invention selected from the group consisting of TIFF2025061064000034.tif12128. [This invention 1078] R III2 But -C(O)-N(R IIIa )-C 1-6 alkyl, and R III2 But R IIIg The compound of any one of claims 1058 to 1063 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1079] R III2 but, 1078 compounds of the present invention selected from the group consisting of TIFF2025061064000035.tif32150. [The present invention 1080] R III2 But -C 1-6 Alkylene-C 3-8is cycloalkyl, and R III2 But R IIIg The compound of any one of claims 1058 to 1063 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1081] R III2 but, 1080 compounds of the present invention selected from the group consisting of TIFF2025061064000036.tif72134. [This invention 1082] R III2 But -C(O)-C 1-6 Alkylene-C 3-8 is cycloalkyl, and R III2 But R IIIg The compound of any one of claims 1058 to 1063 of the present invention, which may be optionally substituted with one, two, three or more substituents each independently selected from: [This invention 1083] R III2 but, The compound of the present invention 1082 is represented by TIFF2025061064000037.tif16128. [This invention 1084] R III2 But -C=N(R IIIa )-C 1-6 The compound of any one of 1058 to 1063 of the present invention, which is alkyl. [This invention 1085] R III2 but, The compound of the present invention 1084 is represented by TIFF2025061064000038.tif11128. [The present invention 1086] R III2 But -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6Alkylene-4 to 7-membered heterocyclyl, and —C(O)—N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl; -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, or -C(O)-N(R IIIa )-C 1-6 The alkylene-5-6 membered heteroaryl is bonded to R IIIg and -C(O)-N(R IIIa )-C 1-6 alkylene-4 to 7-membered heterocyclyl or -C(O)-N(R IIIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIIh optionally substituted with Any of compounds 1058 to 1063 of the present invention. [This invention 1087] R III2 but, 1086 compounds of the present invention selected from the group consisting of TIFF2025061064000039.tif59150. [This invention 1088] 5-[1-fluoro-3-hydroxy-7-(3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(cyclopropylmethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-Fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(2-cyclopropylethyl)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(2-methoxyethoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(cyclopropylmethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7S)-1-Fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(5-fluoro-7-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(5-fluoro-7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-6-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1,4-difluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(azetidin-1-yl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3,3,3-trifluoropropyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-difluorocyclobutyl)methoxy]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4-methoxy-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-methoxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({2-[1-(trifluoromethyl)cyclopropyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2,2-difluoro-2-phenylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3-cyclopropyl-2,2-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[methyl(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4-methylpentyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)butyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[4,4,4-trifluoro-3-(trifluoromethyl)butyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2,2-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[2-(pyridin-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-1-fluoro-3-hydroxy-7-[(3RS)-pyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-7-[(3RS)-1-(cyclopropanesulfonyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-1-fluoro-3-hydroxy-7-[(3SR)-pyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-7-[(3SR)-1-(cyclopropanesulfonyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[1-(cyclopropylmethyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[2-(1H-pyrazol-1-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(4,4,4-trifluorobutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methylpentanoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methylpentyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-Fluoro-3-hydroxy-7-({2-[1-(trifluoromethyl)cyclopropyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-ylphenylcarbamate, 4-{[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]amino}-2,2-dimethylbutanenitrile, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3-hydroxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3-methoxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(5,5,5-trifluoropentyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{(3-methylbutyl)[(pyridin-2-yl)methyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[(pyridin-2-yl)methyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-2-hydroxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(difluoromethoxy)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-pentanimidoyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(3-cyclopropylpropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-azaspiro[3.3]heptan-6-yl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(6,6,6-trifluorohexyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,3-difluorocyclobutyl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(azetidin-3-yl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(propan-2-yl)amino]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(azetidin-3-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(azetidin-3-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{(3-methylbutyl)[2-(pyridin-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(spiro[2.3]hexan-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[2-(trifluoromethoxy)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-hydroxy-3-methylbutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 3-Hydroxybutyl 8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-{1-fluoro-3-hydroxy-7-[3-(propan-2-yl)pyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclohexylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-dimethylbutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(butylamino)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopentylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclohexylethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2-hydroxyethyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[2-(propan-2-yl)morpholin-4-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2R)-2-(propan-2-yl)morpholin-4-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(pyrrolidin-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(pyridin-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclobutylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({2-[(propan-2-yl)oxy]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopropyl-2-hydroxyethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[3-(trimethylsilyl)propyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({3-[hydroxy(dimethyl)silyl]propyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(pyridin-2-yl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,3-difluorocyclobutyl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(pyrrolidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-methylbutanimidamide, 5-{8-fluoro-6-hydroxy-2-[3-(oxan-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(3-hydroxy-3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-7-amino-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(4,4-difluorobutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclopentylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclobutylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-7-{[2-(3,3-difluorocyclobutyl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylpentyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(3-ethylpentyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-(3-methylbutyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-methylpropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{8-fluoro-6-hydroxy-2-[3-(pyridin-3-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(pyrimidin-5-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(oxan-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclohexyl-2-hydroxyethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(2-methoxyethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-methoxypropyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(3-aminopropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(piperidin-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-methylbutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl 8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-{8-fluoro-6-hydroxy-2-[(7-oxabicyclo[2.2.1]heptan-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-Fluoro-6-hydroxy-2-{1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]azetidin-3-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(7-oxabicyclo[2.2.1]heptan-2-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(2,2-difluoroethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-{[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]methyl}-3,5-dimethyl-1H-pyrazol-1-yl)-2,2-dimethylpentanenitrile, 5-{8-fluoro-6-hydroxy-2-[(piperidin-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(morpholin-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(piperidin-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(1s,3r)-3-(trifluoromethoxy)cyclobutyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(4-methylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(propan-2-yl)oxy]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-Fluoro-3-hydroxy-7-({2-[(1s,3r)-3-(trifluoromethoxy)cyclobutyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[(1s,3s)-3-(trifluoromethoxy)cyclobutyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-Fluoro-6-hydroxy-2-{2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-2-azaspiro[3.3]heptan-6-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(difluoromethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(bicyclo[2.2.1]heptan-1-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-amino-1-fluoro-3-hydroxy-7-(prop-2-en-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N'-[8-fluoro-6-hydroxy-2-propyl-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzohydrazide, 5-[8-fluoro-6-hydroxy-2-(3-hydroxybutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[1-(trifluoromethyl)cyclopropyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-hydroxypropyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2S)-2-aminopropyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2R)-2-aminopropyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(piperazin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{[rac-(1R,2R)-2-(pyridin-4-yl)cyclopropyl]methyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclopentyl-2-methoxyethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2R)-2-amino-4-cyclohexylbutanoyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{3-[(propan-2-yl)oxy]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(1-methyl-1H-pyrazol-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(2,2-difluoroethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-amino-1-fluoro-3-hydroxy-7-(4-methylpentyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-amino-1-fluoro-3-hydroxy-7-propyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1,3-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(cyclopropylmethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{(7S)-7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-[(oxan-4-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(3,3-difluorocyclobutyl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(oxolan-2-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-(2-cyclopropylethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{2-[2-(1-tert-butyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(aminomethyl)-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{[bis(3-methylbutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-[(oxolan-3-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(1-methyl-1H-pyrazol-5-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-(2-{2-[3,5-dimethyl-1-(propan-2-yl)-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{[(3-cyclopropylpropyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1-ethyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(2,2-dimethylpropyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(3-methoxypropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(3-methoxy-2,2-dimethylpropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[2-(dimethylamino)ethyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[2-(1-methylcyclopropyl)ethyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-methoxyethyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(oxetan-3-yl)methyl]-7-(1,1,4-trioxo-1λ) 6,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-phenylethyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[3-(dimethylamino)propyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-[2-(3-cyclohexylpropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[3-(2,2-dimethylcyclopropyl)propyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(3S)-5-Fluoro-7-hydroxy-3-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(2R)-4-Fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(2S)-4-Fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methoxybutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{3-[3-(trifluoromethyl)phenyl]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-methyl-3-[4-(propan-2-yl)phenyl]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[4-(5,5-dimethyl-1,3-dioxan-2-yl)butyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(2,6,6-trimethylcyclohex-1-en-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-pentyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-2-[3-(4-fluorophenyl)propyl]-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl [(1r,4r)-4-{2-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}cyclohexyl]carbamate, 5-{2-[3-(4-tert-butylphenyl)propyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3,5,5-trimethylhexyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-2-[3-(2-fluorophenyl)propyl]-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 3-Hydroxybutyl 4,4,8-trifluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-(2-{[(2-cyclobutylethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-fluoro-3-hydroxy-7-{[(3R)-3-hydroxybutyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(4-hydroxy-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-6-(3-hydroxy-3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(cyclopropylmethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{6-[(4,4-difluorobutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(4,4-difluorobutoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-6-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-6-(3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-6-[(3-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl (2-{[5-fluoro-7-hydroxy-6-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]oxy}ethyl)carbamate, 5-(1-fluoro-3-hydroxy-6-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{6-[(cyclopropylmethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(2-aminoethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(cyclohexylmethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide, 5-[1-fluoro-3-hydroxy-7-(4-methylpentyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(3S)-5-Fluoro-7-hydroxy-3-(4-methylpentyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, and pharmaceutically acceptable salts thereof A compound selected from the group consisting of: [This invention 1089] A pharmaceutically acceptable composition comprising any one of the compounds of the present invention 1001 to 1088 and a pharmaceutically acceptable carrier. [The present invention 1090] A composition of the present invention 1089 formulated for oral administration. [This invention 1091] A method for treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of any of the compounds of the present inventions 1001 to 1088 in combination with an additional therapeutic agent. [This invention 1092] A method for treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of a pharmaceutically acceptable composition of invention 1089 or 1090 in combination with an additional therapeutic agent. [This invention 1093] 1093. The method of claim 1091 or 1092, wherein said additional therapeutic agent is an immunotherapeutic agent. [This invention 1094] 1093. The method of claim 1093, wherein said immunotherapeutic agent is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-CTLA-4 antibody. [This invention 1095] A method for treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of any of the compounds of the present inventions 1001 to 1088. [This invention 1096] A method for treating cancer in a patient in need thereof, comprising administering to said patient an effective amount of a pharmaceutically acceptable composition of 1089 or 1090 of the present invention. [This invention 1097] A method for treating type 2 diabetes in a patient in need thereof, comprising administering to the patient an effective amount of any of the compounds of the present invention 1001 to 1088 or the composition of the present invention 1089 or 1090. [This invention 1098] A method for treating and / or controlling obesity in a patient in need thereof, comprising administering to the patient an effective amount of any of the compounds of the present invention 1001 to 1088 or the composition of the present invention 1089 or 1090. [This invention 1099] A method for inhibiting further weight gain in an overweight or obese patient in need thereof, comprising administering to said patient an effective amount of any of the compounds of inventions 1001 to 1088 or the composition of inventions 1089 or 1090. [The present invention 1100] A method for treating a metabolic disease in a patient in need thereof, comprising administering to the patient an effective amount of any of the compounds of the present inventions 1001 to 1088 or the composition of the present invention 1089 or 1090. DETAILED DESCRIPTION OF THE INVENTION

[0028] Detailed Description The present disclosure relates, at least in part, to compounds, compositions, and methods for inhibiting protein tyrosine phosphatases, such as protein tyrosine phosphatase non-receptor type 2 (PTPN2) and / or protein tyrosine phosphatase non-receptor type 1 ((PTPN1), also known as protein tyrosine phosphatase-1B (PTP1B)).

[0029] definition chemical definition Definitions of specific functional groups and chemical terms are detailed below. Chemical elements are listed in the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 th In addition, general principles of organic chemistry, as well as specific functional moieties and reactivities, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5 th Edition, John Wiley & Sons, Inc., New York, 2001, Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989, and Carruthers, Some Modern Methods of Organic Synthesis, 3. rd Edition, Cambridge University Press, Cambridge, 1987.

[0030] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulas depicted herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0031] The compounds described herein may contain one or more asymmetric centers and therefore can exist in various isomeric forms, such as enantiomers and / or diastereomers. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers, or geometric isomers, or may be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts, or preferred isomers can be prepared by asymmetric synthesis. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981), Wilen et al., Tetrahedron 33:2725 (1977), Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962), and Wilen, Tables of Resolving Agents and Optical Resolutions p. 268 (EL Eliel, Ed., University of Notre Dame Press, Notre Dame, IN 1972). The present disclosure further encompasses the compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers.

[0032] As used herein, a pure enantiomer compound is substantially free of other enantiomers or stereoisomers of the compound (i.e., in enantiomeric excess). In other words, the "S" form of a compound is substantially free of the "R" form of the compound and is thus in enantiomeric excess of the "R" form. The terms "enantiomerically pure" or "pure enantiomer" mean that the compound contains more than 75%, more than 80%, more than 85%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, more than 99.5%, or more than 99.9% by weight of an enantiomer. In certain embodiments, the weight is based on the total weight of all enantiomers or stereoisomers of the compound.

[0033] In the compositions provided herein, the enantiomerically pure compound may be present together with other active or inactive ingredients. For example, a pharmaceutical composition containing an enantiomerically pure R compound may contain, for example, about 90% excipients and about 10% enantiomerically pure R compound. In certain embodiments, the enantiomerically pure R compound in such a composition may contain, for example, at least about 95% by weight of the R compound and at most about 5% by weight of the S compound, based on the total weight of the compound. For example, a pharmaceutical composition containing an enantiomerically pure S compound may contain, for example, about 90% excipients and about 10% of the enantiomerically pure S compound. In certain embodiments, the enantiomerically pure S compound in such a composition may contain, for example, at least about 95% by weight of the S compound and at most about 5% by weight of the R compound, based on the total weight of the compound. In certain embodiments, the active ingredient may be formulated with little or no excipients or carriers.

[0034] As used herein, "isotopically enriched variant" refers to a compound of the present disclosure having one or more isotopic substitutions, in which one or more atoms are replaced with an atom having an atomic mass or mass number different from the atomic mass or mass number normally found in nature. Examples of isotopes that may be incorporated into compounds of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, e.g., 2 H, 3 H, 13 C. 14 C. 15 N, 18 O. 17 O. 31 P, 32 P, 35 S, 18 F, and 36 For example, hydrogen (H) is 1 H, 2 H (D or deuterium), and 3 H (T or tritium) and carbon (C) 12 C. 13 C, and 14 C may be in any isotopic form, including oxygen (O) 16 O and 18 and the like. For example, isotopically enriched variants disclosed herein may have one or more hydrogen atoms replaced with deuterium.

[0035] The articles "a" and "an" may be used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an analogue" means one analogue or multiple analogues.

[0036] When a range of values ​​is listed, it is intended to encompass each value and subrange within the range. For example, "C1-C6 alkyl" is intended to include C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6 alkyl.

[0037] The following terms are intended to have the meanings presented below and are useful in understanding the description and intended scope of the present disclosure.

[0038] "Alkyl" refers to the radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms ("C1-C 20 In some embodiments, an alkyl group has 1 to 12 carbon atoms ("C-C 12In some embodiments, an alkyl group has 1 to 8 carbon atoms ("C1-C8 alkyl"). In some embodiments, an alkyl group has 1 to 6 carbon atoms ("C1-C6 alkyl"). In some embodiments, an alkyl group has 1 to 5 carbon atoms ("C1-C5 alkyl"). In some embodiments, an alkyl group has 1 to 4 carbon atoms ("C1-C4 alkyl"). In some embodiments, an alkyl group has 1 to 3 carbon atoms ("C1-C3 alkyl"). In some embodiments, an alkyl group has 1 to 2 carbon atoms ("C1-C2 alkyl"). In some embodiments, an alkyl group has 1 carbon atom ("C1 alkyl"). In some embodiments, an alkyl group has 2 to 6 carbon atoms ("C2-C6 alkyl"). Examples of C1-C6 alkyl groups include methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), iso-butyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), and n-hexyl (C6). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), and the like. Each occurrence of an alkyl group can independently be optionally substituted, i.e., unsubstituted ("unsubstituted alkyl"), or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkyl"). In certain embodiments, an alkyl group can be an unsubstituted C 1-10 In certain embodiments, the alkyl group is a substituted C 1-6 It is alkyl. Common abbreviations for alkyl include Me(-CH), Et(-CHCH), iPr(-CH(CH)), nPr(-CHCHCH), n-Bu(-CHCHCHCHCH), or i-Bu(-CHCH(CH)).

[0039] The term "alkylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkyl, as exemplified but not limited to, -CH2CH2CH2CH2-. Typically, an alkyl (or alkylene) group has from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in this disclosure. The term "alkenylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkene. An alkylene group may be described, for example, as a C1-C6-membered alkylene, where the term "member" refers to an atom within the moiety that is not hydrogen.

[0040] "Alkenyl" refers to the radical of a straight-chain or branched hydrocarbon group having 2 to 20 carbon atoms, one or more carbon-carbon double bonds, and no triple bonds ("C2-C 20 In some embodiments, an alkenyl group has 2 to 10 carbon atoms ("C-C 10 In some embodiments, an alkenyl group has 2 to 8 carbon atoms ("C2-C8 alkenyl"). In some embodiments, an alkenyl group has 2 to 6 carbon atoms ("C2-C6 alkenyl"). In some embodiments, an alkenyl group has 2 to 5 carbon atoms ("C2-C5 alkenyl"). In some embodiments, an alkenyl group has 2 to 4 carbon atoms ("C2-C4 alkenyl"). In some embodiments, an alkenyl group has 2 to 3 carbon atoms ("C2-C3 alkenyl"). In some embodiments, an alkenyl group has 2 carbon atoms ("C2 alkenyl"). The one or more carbon-carbon double bonds can be internal (e.g., 2-butenyl) or terminal (e.g., 1-butenyl). Examples of C2-C4 alkenyl groups include ethenyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), etc. Examples of C2-C6 alkenyl groups include the aforementioned C 2-4Alkenyl groups include pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Each occurrence of an alkenyl group can independently be optionally substituted, e.g., unsubstituted (an "unsubstituted alkenyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent (a "substituted alkenyl"). In certain embodiments, an alkenyl group can be an unsubstituted C 2-10 In certain embodiments, the alkenyl group is a substituted C 2-6 It is alkenyl.

[0041] "Aryl" refers to an aromatic ring system having 6 to 14 ring carbon atoms and 0 heteroatoms ("C6-C 14 "aryl" refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., sharing 6, 10, or 14 π electrons in a cyclic arrangement). In some embodiments, an aryl group has 6 ring carbon atoms ("C6 aryl"; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms ("C 10 aryl"; e.g., naphthyl, such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms ("C 14 aryl"; e.g., anthracyl). Aryl groups include, for example, C-C 10 In certain embodiments, an aryl group may be described as an unsubstituted C-C alkyl group, where the term "membered" refers to a ring atom in the moiety that is not hydrogen. Aryl groups include, but are not limited to, phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Each occurrence of an aryl group may independently be optionally substituted, for example, unsubstituted ("unsubstituted aryl") or substituted with one or more substituents ("substituted aryl"). In certain embodiments, an aryl group is an unsubstituted C-C alkyl group. 14 In certain embodiments, the aryl group is a substituted C-C 14It is aryl.

[0042] In certain embodiments, the aryl group is substituted with one or more groups selected from halo, C1-C8 alkyl, halo-C1-C8 alkyl, haloxy-C1-C8 alkyl, cyano, hydroxy, alkoxyC1-C8 alkyl, and amino.

[0043] Representative examples of substituted aryl are: TIFF2025061064000040.tif17128, where R 56 and R 57 One of R may be hydrogen; 56 and R 57 At least one of C1-C8 alkyl, halo-C1-C8 alkyl, 4- to 10-membered heterocyclyl, alkanoyl, alkoxy-C1-C8 alkyl, heteroaryloxy, alkylamino, arylamino, heteroarylamino, NR 58 COR 59 , N.R. 58 SOR 59 NR 58 SO2R 59 , C(O)O alkyl, C(O)O aryl, CONR 58 R 59 ,CONR 58 OR 59 , N.R. 58 R 59 , SO2NR 58 R 59 , S-alkyl, S(O)-alkyl, S(O)2-alkyl, S-aryl, S(O)-aryl, S(O2)-aryl, or R 56 and R 57 may be linked to form a cyclic ring (saturated or unsaturated) of 5 to 8 atoms, optionally containing one or more heteroatoms selected from the group N, O, or S.

[0044] Other representative aryl groups having a fused heterocyclyl group are: TIFF2025061064000041.tif12128, where each W' is a C(R66 )2, NR 66 , O, and S; each Y' is selected from carbonyl, NR 66 , O, and S; R 66 are independently hydrogen, C1-C8 alkyl, C3-C 10 Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0045] "Arylene" and "heteroarylene," alone or as part of another substituent, mean a divalent radical derived from an aryl and heteroaryl, respectively. Non-limiting examples of heteroaryl groups include pyridinyl, pyrimidinyl, thiophenyl, thienyl, furanyl, indolyl, benzoxadiazolyl, benzodioxolyl, benzodioxanyl, thianaphthalenyl, pyrrolopyridinyl, indazolyl, quinolinyl, quinoxalinyl, pyridopyrazinyl, quinazolinonyl, benzisoxazolyl, imidazopyridinyl, benzofuranyl, benzothienyl, benzothiophenyl, phenyl, naphthyl, biphenyl, and pyrrolopyridinyl. Heteroaryl includes aryl, pyrazolyl, imidazolyl, pyrazinyl, oxazolyl, isoxazolyl, thiazolyl, furylthienyl, pyridyl, pyrimidyl, benzothiazolyl, purinyl, benzimidazolyl, isoquinolyl, thiadiazolyl, oxadiazolyl, pyrrolyl, diazolyl, triazolyl, tetrazolyl, benzothiadiazolyl, isothiazolyl, pyrazolopyrimidinyl, pyrrolopyrimidinyl, benzotriazolyl, benzoxazolyl, or quinolyl. The above examples may be substituted or unsubstituted, and the divalent radical of each of the above heteroaryl examples is a non-limiting example of heteroarylene.

[0046] "Halo" or "halogen," independently or as part of another substituent, means, unless otherwise stated, a fluorine (F), chlorine (Cl), bromine (Br), or iodine (I) atom. The term "halide," alone or as part of another substituent, refers to a fluoride, chloride, bromide, or iodide atom. In certain embodiments, a halo group is either fluorine or chlorine.

[0047] Additionally, terms such as "haloalkyl" are meant to include monohaloalkyl and polyhaloalkyl. For example, the term "halo-C1-C6 alkyl" includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like.

[0048] The term "heteroalkyl," by itself or in combination with another term, means, unless otherwise stated, an acyclic, stable, straight or branched chain, or combination thereof, containing at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, where the nitrogen and sulfur atoms are optionally oxidized and the nitrogen heteroatom is optionally quaternized. The heteroatom(s) O, N, P, S, and Si may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Exemplary heteroalkyl groups include -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -S(O)-CH3, -S(O)-CH3, and -S(O)-CH 3、 Examples of heteroalkyl include, but are not limited to, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, and -O-CH2-CH3. Up to two or three heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. Following the term "heteroalkyl," -CH2O-CH3, -NR BR C When a specific heteroalkyl group is described, such as -CH2O-CH3 or -NR B R C It will be understood that terms such as -CH2O-CH3, -NR3, -N, and -N are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are described for clarity. Thus, the term "heteroalkyl" is used herein to include any of the following: -CH2O-CH3, -NR3, -N ... B R C This should not be construed as excluding specific heteroalkyl groups such as:

[0049] Similarly, the term "heteroalkylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from heteroalkyl, as exemplified, but not limited to, -CHO- and -CHCHO-. A heteroalkylene group may be described, for example, as a 2- to 7-membered heteroalkylene, where the term "member" refers to a non-hydrogen atom within the moiety. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)R'- can represent both -C(O)R'- and -R'C(O)-.

[0050] "Heteroaryl" refers to a radical of a 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., sharing 6 or 10 pi electrons in a cyclic arrangement) comprising ring carbon atoms and 1 to 4 ring heteroatoms in the aromatic ring system, each heteroatom independently selected from nitrogen, oxygen, and sulfur ("5- to 10-membered heteroaryl"). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment can be at a carbon or nitrogen atom, valence permitting. Heteroaryl bicyclic ring systems can contain one or more heteroatoms in one or both rings. "Heteroaryl" also includes ring systems in which a heteroaryl ring, as defined above, is fused to one or more aryl groups, with the point of attachment being at either the aryl or heteroaryl ring; in such cases, the number of ring members designates the number of ring members in the fused (aryl / heteroaryl) ring system. In bicyclic heteroaryl groups in which one ring does not contain heteroatoms (e.g., indolyl, quinolinyl, carbazolyl, etc.), the point of attachment can be in either ring, i.e., the ring with the heteroatom (e.g., 2-indolyl) or the ring without the heteroatom (e.g., 5-indolyl). Heteroaryl groups may be described, for example, as 6- to 10-membered heteroaryl, where the term "member" refers to the non-hydrogen ring atoms in the moiety.

[0051] In some embodiments, heteroaryl groups are 5-10 membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms in the aromatic ring system, each heteroatom being independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl"). In some embodiments, heteroaryl groups are 5-8 membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms in the aromatic ring system, each heteroatom being independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heteroaryl"). In some embodiments, heteroaryl groups are 5-6 membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms in the aromatic ring system, each heteroatom being independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heteroaryl"). In some embodiments, 5-6 membered heteroaryls have 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, 5-6 membered heteroaryls have 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- to 6-membered heteroaryl has one ring heteroatom selected from nitrogen, oxygen, and sulfur. Each occurrence of the heteroaryl group can independently be optionally substituted, i.e., unsubstituted ("unsubstituted heteroaryl") or substituted with one or more substituents ("substituted heteroaryl"). In certain embodiments, the heteroaryl group is an unsubstituted 5- to 14-membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5- to 14-membered heteroaryl.

[0052] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.

[0053] Representative examples of heteroaryls include those of the formula: TIFF2025061064000042.tif64128, wherein each Y is a carbonyl, N, NR 65 , O, and S; R 65 are independently hydrogen, C1-C8 alkyl, C3-C 10Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0054] "Cycloalkyl" means a group of alkyl groups having 3 to 10 ring carbon atoms ("C3-C 10 "Cycloalkyl" refers to the radical of a non-aromatic cyclic hydrocarbon group having 3 to 8 ring carbon atoms ("C3-C8 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5-C 10 Cycloalkyl groups may be described, for example, as C4-C7 membered cycloalkyl, where the term "member" refers to a non-hydrogen ring atom in the moiety. Exemplary C3-C6 cycloalkyl groups include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. Exemplary C3-C8 cycloalkyl groups include, but are not limited to, the aforementioned C3-C6 cycloalkyl groups, as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), cubanyl (C8), bicyclo[1.1.1]pentanyl (C5), bicyclo[2.2.2]octanyl (C8), bicyclo[2.1.1]hexanyl (C6), bicyclo[3.1.1]heptanyl (C7), and the like. 10 The cycloalkyl group includes, but is not limited to, the aforementioned C3-C8 cycloalkyl groups, as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C 10 ), cyclodecenyl (C10 ), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C 10 ), spiro[4.5]decanyl (C 10 ), and the like. As the foregoing examples illustrate, in certain embodiments, a cycloalkyl group is either monocyclic ("monocyclic cycloalkyl") or contains a fused, bridged, or spiro ring system, such as a bicyclic system ("bicyclic cycloalkyl"), and may be saturated or partially unsaturated. "Cycloalkyl" also includes ring systems in which a cycloalkyl ring, as defined above, is fused to one or more aryl groups, and the point of attachment is on the cycloalkyl ring; in such cases, the number of carbons still designates the number of carbons in the cycloalkyl ring system. Each occurrence of a cycloalkyl group may independently be optionally substituted, e.g., unsubstituted ("unsubstituted cycloalkyl") or substituted with one or more substituents ("substituted cycloalkyl"). In certain embodiments, a cycloalkyl group is an unsubstituted C3-C6 10 In certain embodiments, the cycloalkyl group is a substituted C-C 10 It is cycloalkyl.

[0055] In some embodiments, "cycloalkyl" is a monocyclic saturated cycloalkyl group having 3 to 10 ring carbon atoms ("C3-C 10 In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms ("C3-C8 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms ("C5-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5-C 10Examples of C5-C6 cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C5). Examples of C3-C6 cycloalkyl groups include the aforementioned C5-C6 cycloalkyl groups, as well as cyclopropyl (C3) and cyclobutyl (C4). Examples of C3-C8 cycloalkyl groups include the aforementioned C3-C6 cycloalkyl groups, as well as cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise specified, each occurrence of a cycloalkyl group is independently unsubstituted ("unsubstituted cycloalkyl") or substituted with one or more substituents ("substituted cycloalkyl"). In certain embodiments, a cycloalkyl group is an unsubstituted C3-C6 10 In certain embodiments, the cycloalkyl group is a substituted C-C 10 It is cycloalkyl.

[0056] "Heterocyclyl" or "heterocyclic" refers to a radical of a 3- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, each independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3- to 10-membered heterocyclyl"). In heterocyclyl groups containing one or more nitrogen atoms, the point of attachment may be at a carbon or nitrogen atom, valence permitting. Heterocyclyl groups may be monocyclic ("monocyclic heterocyclyl") or fused, bridged, or spiro ring systems, such as bicyclic systems ("bicyclic heterocyclyl"), and may be saturated or partially unsaturated. Heterocyclyl bicyclic ring systems may contain one or more heteroatoms in one or both rings. "Heterocyclyl" also includes ring systems in which a heterocyclyl ring, as defined above, is fused to one or more cycloalkyl groups, with the point of attachment being on either the cycloalkyl or heterocyclyl ring, or in which a heterocyclyl ring, as defined above, is fused to one or more aryl or heteroaryl groups, with the point of attachment being on the heterocyclyl ring; in such cases, the number of ring members still designates the number of ring members in the heterocyclyl ring system. A heterocyclyl group may be described, for example, as a 3- to 7-membered heterocyclyl, where the term "member" refers to the non-hydrogen ring atoms in the moiety, i.e., carbon, nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. Each occurrence of heterocyclyl may independently be optionally substituted, for example, unsubstituted ("unsubstituted heterocyclyl") or substituted with one or more substituents ("substituted heterocyclyl"). In certain embodiments, the heterocyclyl group is an unsubstituted 3- to 10-membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3-10 membered heterocyclyl.

[0057] In some embodiments, a heterocyclyl group is a 5- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, each heteroatom independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon (a "5- to 10-membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5- to 8-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, each heteroatom independently selected from nitrogen, oxygen, and sulfur (a "5- to 8-membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5- to 6-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, each heteroatom independently selected from nitrogen, oxygen, and sulfur (a "5- to 6-membered heterocyclyl"). In some embodiments, a 5- to 6-membered heterocyclyl has 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- to 6-membered heterocyclyl has 1 to 2 ring heteroatoms selected from nitrogen, oxygen, and sulfur, hi some embodiments, the 5- to 6-membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur.

[0058] Exemplary 3-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azirdinyl, oxiranyl, and thiorenyl. Exemplary 4-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, triazinanyl. Exemplary 7-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azocanyl, oxecanyl, and thiocanyl. Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,6-bicyclic heterocyclic rings) fused to a C6 aryl ring include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, etc. Exemplary 6-membered heterocyclyl groups (also referred to herein as 6,6-bicyclic heterocyclic rings) fused to an aryl ring include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, etc.

[0059] Particular examples of heterocyclyl groups are the following illustrative examples: TIFF2025061064000043.tif43128, where each W" is the CR 67 , C(R 67 )2, NR 67 , O, and S, and each Y" is selected from NR 67 , O, and S; R 67 are independently hydrogen, C1-C8 alkyl, C3-C 10 Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 and aryl and 5- to 10-membered heteroaryl. These heterocyclyl rings may be optionally substituted with one or more groups selected from the group consisting of acyl, acylamino, acyloxy, alkoxy, alkoxycarbonyl, alkoxycarbonylamino, amino, substituted amino, aminocarbonyl (e.g., amido), aminocarbonylamino, aminosulfonyl, sulfonylamino, aryl, aryloxy, azido, carboxyl, cyano, cycloalkyl, halogen, hydroxy, keto, nitro, thiol, -S-alkyl, -S-aryl, -S(O)-alkyl, -S(O)-aryl, -S(O)2-alkyl, and -S(O)2-aryl. Substituents include, for example, carbonyl or thiocarbonyl, leading to lactam and urea derivatives.

[0060] A "nitrogen-containing heterocyclyl" group refers to a 4- to 7-membered non-aromatic cyclic group containing at least one nitrogen atom, such as, but not limited to, morpholine, piperidine (e.g., 2-piperidinyl, 3-piperidinyl, and 4-piperidinyl), pyrrolidine (e.g., 2-pyrrolidinyl and 3-pyrrolidinyl), azetidine, pyrrolidone, imidazoline, imidazolidinone, 2-pyrazoline, pyrazolidine, piperazine, and N-alkylpiperazines, such as N-methylpiperazine. Specific examples include azetidine, piperidone, and piperazone.

[0061] "Amino" means -NR 70 R 71 where R refers to the group 70 and R71 are each independently hydrogen, C1-C8 alkyl, C3-C 10 Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 aryl, and 5-10 membered heteroaryl. In some embodiments, amino refers to NH2.

[0062] "Cyano" refers to the radical -CN.

[0063] "Hydroxy" or "hydroxyl" refers to the group --OH.

[0064] In some embodiments, one or more of the nitrogen atoms of the compounds of the present disclosure, if present, is oxidized to the corresponding N-oxide.

[0065] Alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted as defined herein (e.g., "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" cycloalkyl, "substituted" or "unsubstituted" heterocyclyl, "substituted" or "unsubstituted" aryl, or "substituted" or "unsubstituted" heteroaryl groups). In general, the term "substituted," whether preceded by the term "optionally," means that at least one hydrogen present in the group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, e.g., a substituent that, upon substitution, gives rise to a stable compound, e.g., a compound that does not spontaneously transform by rearrangement, cyclization, elimination, or other reaction, etc. Unless otherwise specified, a "substituted" group has a substituent at one or more substitutable positions of the group, and when multiple positions in any given structure are substituted, the substituents are the same or different at each position. The term "substituted" is intended to include substitution with any permissible substituent of organic compounds, for example, any of the substituents described herein, that results in the formation of a stable compound. The present disclosure contemplates all such combinations in order to arrive at stable compounds. For purposes of this disclosure, heteroatoms such as nitrogen can have hydrogen substituents and / or any suitable substituents described herein that satisfy the valence of the heteroatom and result in the formation of a stable moiety.

[0066] Two or more substituents may optionally be bonded to form an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group. Such so-called ring-forming substituents are typically, but not necessarily, found attached to a cyclic base structure. In one embodiment, the ring-forming substituents are attached to adjacent ring members of the base structure. For example, two ring-forming substituents attached to adjacent ring members of a cyclic base structure create a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single ring member of the base structure. For example, two ring-forming substituents attached to a single ring member of a cyclic base structure create a spirocyclic structure. In yet another embodiment, the ring-forming substituents are attached to non-adjacent ring members of the base structure.

[0067] A "counterion" or "anionic counterion" is a negatively charged group that associates with a cationic quaternary amino group to maintain electrical neutrality. Exemplary counterions include halide ions (e.g., F - , Cl - , Br - , I - ), NO3 - , ClO4 - , O.H. - , H2PO4 - , HSO4 - , sulfonate ions (e.g., methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, 10-camphorsulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1-sulfonic acid-5-sulfonic acid, ethane-1-sulfonic acid-2-sulfonic acid, etc.), and carboxylate ions (e.g., acetic acid, ethanoic acid, propanoic acid, benzoic acid, glyceric acid, lactic acid, tartaric acid, glycolic acid, etc.).

[0068] The term "pharmaceutically acceptable salts" is intended to include salts of active compounds prepared using relatively non-toxic acids or bases, depending on the specific substituents found in the compounds described herein.When a compound of the present disclosure contains a relatively acidic functional group, a base addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of the desired base, either directly or in a suitable inert solvent.Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salts, or similar salts.When a compound of the present disclosure contains a relatively basic functional group, an acid addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of the desired acid, either directly or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrogensulfuric acid, hydroiodic acid, or phosphorous acid, and salts derived from relatively non-toxic organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid, etc. Also included are salts of amino acids such as arginic acid, and salts of organic acids such as glucuronic acid or galactunoric acid (see, e.g., Berge et al., Journal of Pharmaceutical Science 66:1-19 (1977)). Certain compounds of the present disclosure contain both basic and acidic functional groups, which allow the compounds to be converted into either base or acid addition salts. Other pharmaceutically acceptable carriers known to those skilled in the art are also suitable for the present disclosure. Salts tend to be more soluble in aqueous or other protic solvents than the corresponding free base forms.In other cases, the preparation may be a lyophilized powder in a first buffer, e.g., 1 mM to 50 mM histidine, 0.1% to 2% sucrose, 2% to 7% mannitol, at a pH range of 4.5 to 5.5, which is combined with a second buffer prior to use.

[0069] Therefore, the compounds of the present disclosure can exist as salts, such as salts with pharmaceutically acceptable acids. The present disclosure includes such salts. Examples of such salts include hydrochloride, hydrobromide, sulfate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate (e.g., (+)-tartrate, (-)-tartrate, or a mixture thereof, including a racemic mixture), succinate, benzoate, and salts with amino acids such as glutamic acid. These salts can be prepared by methods known to those skilled in the art.

[0070] The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents.

[0071] As used herein, the term "salt" refers to the acid or base salt of the compound used in the method of the present disclosure. Illustrative examples of acceptable salts are salts of inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid, etc.), salts of organic acids (such as acetic acid, propionic acid, glutamic acid, citric acid, etc.), and salts of quaternary ammonium (such as methyl iodide, ethyl iodide, etc.).

[0072] Certain compounds of the present disclosure possess asymmetric carbon atoms (optical or chiral centers) or double bonds, and stereoisomeric forms that can be defined in terms of absolute configuration as (R)- or (S)- or (D)- or (L)-amino acids, and individual isomers, are encompassed within the scope of the present disclosure. The compounds of the present disclosure do not include those known in the art to be too unstable to synthesize and / or isolate. The present disclosure is intended to include compounds in racemic and optically pure form. Optically active (R)- and (S)-, or (D)- and (L)-isomers, can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. When a compound described herein contains an olefinic bond or other center of geometric asymmetry, unless otherwise specified, the compound is intended to include both E and Z geometric isomers.

[0073] As used herein, the term "isomers" refers to compounds that have the same number and kinds of atoms, and therefore the same molecular weight, but that differ with respect to the structural arrangement or configuration of the atoms.

[0074] As used herein, the term "tautomer" refers to one of two or more structural isomers that exist in equilibrium and are readily converted from one isomeric form to another.

[0075] It will be apparent to one of ordinary skill in the art that certain compounds of the present disclosure may exist in tautomeric forms, and that all such tautomeric forms of the compounds are within the scope of the present disclosure.

[0076] "Treating" or "treatment" includes preventing or delaying the onset of symptoms, complications, or biochemical signs of a disease; alleviating or ameliorating symptoms; or arresting or inhibiting further progression of a disease, condition, or disorder. "Treating" or "treatment" includes any effect that results in an improvement of a condition, disease, disorder, or the like, e.g., attenuation, reduction, modulation, or elimination. For example, certain methods herein treat cancer by reducing, reducing, or preventing the onset, growth, metastasis, or progression of cancer, or by reducing the symptoms of cancer. The term "treating" and its conjugations include preventing an injury, condition, state, or disease (e.g., preventing the onset of one or more symptoms of a disease, disorder, or condition described herein).

[0077] An "effective amount" is an amount sufficient to achieve a specified purpose (e.g., such that its administration achieves the intended effect, treats a disease, reduces enzyme activity, increases enzyme activity, or reduces one or more symptoms of a disease or condition). An example of an "effective amount" is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which is sometimes referred to as a "therapeutically effective amount." A "prophylactically effective amount" of a drug is an amount of drug that, when administered to a subject, has an intended prophylactic effect, such as preventing or delaying the occurrence (or recurrence) of an injury, disease, symptom, or condition, or reducing the likelihood of the occurrence (or recurrence) of an injury, disease, symptom, or condition, or a symptom thereof. A complete prophylactic effect does not necessarily occur by administration of a single dose, but may occur only after administration of a series of doses. Thus, a prophylactically effective amount can be administered in one or more administrations. The exact amount will depend on the purpose of the treatment, and can be ascertained by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

[0078] "Reduction" of a symptom or symptoms (and grammatical equivalents of this phrase) means a decrease in the severity or frequency of the symptom(s), or the elimination of the symptom(s).

[0079] "Control" or "control experiment" is used according to its plain and ordinary meaning to refer to an experiment in which the experimental subject or agent is treated as in a parallel experiment, except for the omission of an experimental procedure, agent, or variable. In some instances, a control is used as a standard of comparison in evaluating the effectiveness of an experiment.

[0080] "Contacting" is used according to its plain and ordinary meaning to refer to the process of bringing at least two distinct species (e.g., chemical compounds, including biomolecules, or cells) into sufficient proximity so that they react, interact, or are in physical contact. However, it should be understood that the resulting reaction product may be produced directly from the reaction between the added reagents or may be produced from an intermediate derived from one or more of the added reagents that may be produced in the reaction mixture. The term "contacting" can include causing two species to react, interact, or be in physical contact, where the two species can be a compound described herein and a protein or enzyme, e.g., a protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) or protein tyrosine phosphatase non-receptor type 1 (PTPN1).

[0081] As defined herein, the terms "inhibition," "inhibit," "inhibiting," and the like, with respect to the interaction between a protein and an inhibitor (e.g., an antagonist), refer to negatively affecting (e.g., decreasing) the activity or function of the protein compared to the activity or function of the protein in the absence of the inhibitor. In some embodiments, inhibition refers to the reduction of a disease or disease symptoms. In some embodiments, inhibition refers to the reduction of a signal transduction pathway or the activity of a signaling pathway. Thus, inhibition includes, at least in part, partially or totally blocking a stimulus, reducing, preventing, or delaying activation, or inactivating, desensitizing, or downregulating signal transduction or enzymatic activity or the amount of a protein. In some embodiments, inhibition refers to decreasing the activity of a protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) or protein tyrosine phosphatase non-receptor type 1 (PTPN1). Thus, inhibiting can include, at least in part, partially or totally decreasing stimulation, decreasing or reducing activation, or inactivating, desensitizing, or downregulating signaling or enzymatic activity or the amount of a protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) or protein tyrosine phosphatase non-receptor type 1 (PTPN1).

[0082] A "patient" or "subject" in need thereof refers to a living organism suffering from or susceptible to a disease or condition that can be treated by administration of a compound or pharmaceutical composition provided herein. Non-limiting examples include humans, other mammals, bovine, rats, mice, dogs, monkeys, goats, sheep, cows, deer, and other animals that are not mammals. In some embodiments, the patient is a human. In some embodiments, the patient is a domestic animal. In some embodiments, the patient is a dog. In some embodiments, the patient is a parrot. In some embodiments, the patient is a livestock animal. In some embodiments, the patient is a mammal. In some embodiments, the patient is a cat. In some embodiments, the patient is a horse. In some embodiments, the patient is a cow. In some embodiments, the patient is a dog. In some embodiments, the patient is a cat. In some embodiments, the patient is an ape. In some embodiments, the patient is a monkey. In some embodiments, the patient is a mouse. In some embodiments, the patient is a laboratory animal. In some embodiments, the patient is a rat. In some embodiments, the patient is a hamster. In some embodiments, the patient is a test animal. In some embodiments, the patient is a newborn animal. In some embodiments, the patient is a human neonate. In some embodiments, the patient is a newborn mammal. In some embodiments, the patient is an elderly animal. In some embodiments, the patient is an elderly human. In some embodiments, the patient is an elderly mammal. In some embodiments, the patient is a geriatric patient.

[0083] A "disease," "disorder," or "condition" refers to an existing state or state of health of a patient or subject that is treatable with the compounds, pharmaceutical compositions, or methods provided herein. In some embodiments, the compounds and methods described herein include the reduction or elimination of one or more symptoms of a disease, disorder, or condition, e.g., by administration of a compound disclosed herein, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound disclosed herein or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0084] As used herein, the term "signaling pathway" refers to a series of interactions between cellular and optionally extracellular components (e.g., proteins, nucleic acids, small molecules, ions, lipids) that communicate a change in one component to one or more other components, which in turn can communicate the change to additional components, which are optionally propagated to other signaling pathway components.

[0085] "Pharmaceutically acceptable excipient" and "pharmaceutically acceptable carrier" refer to substances that aid in the administration and absorption of an active agent by a subject and that can be included in the compositions of the present disclosure without causing significant adverse toxicological effects to the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, saline, lactated Ringer's solution, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, salt solutions (such as Ringer's solution), alcohols, oils, gelatin, carbohydrates such as lactose, amylose, or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, and coloring agents. Such preparations are sterilized and, if desired, may be mixed with auxiliary substances such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring substances, and / or aromatic substances that do not adversely react with the compounds of the present disclosure. Those skilled in the art will recognize that other pharmaceutical excipients are also useful in the present disclosure.

[0086] The term "preparation" is intended to include a formulation of an active compound with an encapsulating material as a carrier, with or without other carriers, such that the active ingredient is surrounded by, and thus associated with, the carrier, resulting in a capsule. Also included are cachets and lozenges. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.

[0087] As used herein, the term "administering" refers to oral administration, administration as a suppository, topical contact, intravenous, parenteral, intraperitoneal, intramuscular, intralesional, intrathecal, intracranial, intranasal, or subcutaneous administration to a subject, or implantation of a sustained-release device, such as a mini-osmotic pump. Administration can be by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other delivery formats include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, and the like. "Co-administration" means that a compound or composition described herein is administered simultaneously with, immediately before, or immediately after the administration of one or more additional therapies (e.g., anti-cancer, chemotherapeutic, or immunotherapeutic agents). The compounds or compositions described herein can be administered alone or co-administered to a patient. Co-administration is intended to include simultaneous or sequential administration of compounds or compositions, either individually or in combination (multiple compounds or agents). Thus, preparations can also be combined with other active agents, if desired (e.g., to reduce metabolic degradation).

[0088] As used herein, the term "PTPN2" refers to protein tyrosine phosphatase non-receptor type 2. The term "PTPN1" refers to protein tyrosine phosphatase non-receptor type 1 (PTPN1), also known as protein tyrosine phosphatase-1B (PTP1B).

[0089] compound Disclosed herein are, for example, compounds represented by formula (I), or a pharmaceutically acceptable salt thereof: TIFF2025061064000044.tif27128[In the formula, Z is C(H)(R 3 ), bonds, and N(R 8 ) selected from the group consisting of R 1 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 alkyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 Alkyl is a group having R on one or more available carbons. g optionally substituted with one, two, three or more substituents each independently selected from R 2 is hydrogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -NH2, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-N(R a )(R b ), -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 alkylene-phenyl (where -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C3-6 Cycloalkyl, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 Alkylene-phenyl has R on one or more available carbons. g and optionally substituted with one, two, three or more substituents each independently selected from 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R a )-C1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h and Z is C(H)(R 3 ), then R 2 is not -CH2-CH3), R 2’ is hydrogen, -NR a R b , and -N(R a )-N(R b )—C(O)-phenyl; R 3 is hydrogen, -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 4 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 5 are hydrogen, deuterium, halogens, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h (optionally substituted with), R 6 is selected from the group consisting of hydrogen and deuterium; R 7 is selected from the group consisting of hydrogen and deuterium; R 8 is hydrogen and C 1-6 is selected from the group consisting of alkyl, R g is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R a R b N-, R a R b NC(O)-, R a R b N-SO w -, R a R b NC(O)-N(R a )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SOw -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SOw -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R P optionally substituted with one, two, three or more substituents each independently selected from R h For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N-SO2- is R Poptionally substituted with one, two, three or more substituents each independently selected from R P For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R a R b N-, R a R b N-carbonyl-, R a R b N-SO2- and R a R b N-carbonyl-N(R a )-, R a and R b For each occurrence, hydrogen and C 1-6 alkyl (wherein C 1-6 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R a and R b together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; R c For each occurrence, hydroxyl, C 1-4 independently selected from the group consisting of alkyl, and phenyl; w is 0, 1, or 2].

[0090] For example, the compounds disclosed herein can be represented by formula (Ia), or a pharmaceutically acceptable salt thereof: TIFF2025061064000045.tif27128[in the formula, R 1 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC1-6 alkyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl and -OC 1-6 Alkyl is a group having R on one or more available carbons. g optionally substituted with one, two, three or more substituents each independently selected from R 2 is hydrogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -NH2, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 alkylene-phenyl (where -C 1-6 Alkyl, -C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -N(R a )-(C=N(R b ))-C 1-6 Alkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, -OC(O)-N(R a )-C 1-6 Alkyl, -OC(O)-N(R a )-phenyl, -N(R a )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 Alkylene-phenyl has R on one or more available carbons. g and 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -N(R a )-4 to 6-membered heterocyclyl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R a )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 2’ is hydrogen, -NR a R b , and -N(R a )-N(R b )—C(O)-phenyl; R 3 is hydrogen, -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C1-6 alkylene-4- to 6-membered heterocyclyl (where -C 1-6 Alkyl, -OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkyl, -N(R a )-C 1-6 Alkylene-C3-6cycloalkyl, -S(O) w -C 1-6 Alkyl, -C(O)-N(R a )-C 1-6 Alkyl, -N(R a )-C(O)-C 1-6 Alkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 4 is hydrogen, halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 5are hydrogen, deuterium, halogens, C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 3-6 Cycloalkyl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. g and -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h optionally substituted with R 6 is selected from the group consisting of hydrogen and deuterium; R 7 is selected from the group consisting of hydrogen and deuterium; R g is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R a R b N-, R a R b NC(O)-, R a R b N-SO w -, R a R b NC(O)-N(R a )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C1-6 Alkyl-N(R a )-, C 1-6 Alkyl-N(R a )-C(O)-, C 1-6 Alkyl-C(O)-N(R a ), C 1-6 Alkyl-N(R a )-C(O)-N(R a )-, C 1-6 Alkyl-N(R a )-SO w -, C 3-6 Cycloalkyl-N(R a )-SO w -, C 1-6 Alkyl-SO w -N(R a )-, C 3-6 Cycloalkyl-SO w -N(R a )-, C 1-6 Alkoxy-C(O)-N(R a )-, C 1-6 Alkyl-C(O)-N(R a )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R a )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R P optionally substituted with one, two, three or more substituents each independently selected from R h For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a Rb N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R a R b NC(O)- and R a R b N-SO2- is R P optionally substituted with one, two, three or more substituents each independently selected from R P For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R a R b N-, R a R b N-carbonyl-, R a R b N-SO2- and R a R b N-carbonyl-N(R a )-, R a and R b For each occurrence, hydrogen and C 1-6 alkyl (wherein C 1-6 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R a and R b together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; R cFor each occurrence, hydroxyl, C 1-4 independently selected from the group consisting of alkyl, and phenyl; w is 0, 1, or 2].

[0091] In some embodiments, R 1 is selected from the group consisting of hydrogen and fluorine. 1 is hydrogen.

[0092] In certain embodiments, R 2 -OC 1-6 alkyl, and R 2 is R g In some embodiments, R 2 is fluorine, hydroxyl, C 1-6 Alkoxy, and R a R b and optionally substituted with one, two, three or more substituents each independently selected for each occurrence from the group consisting of N-. For example, R 2 is -OCH3, TIFF2025061064000046.tif10128.

[0093] In other embodiments, R 2 is -N(R a )-C 1-8 alkyl, and R 2 is R g In some embodiments, R 2 is fluorine, hydroxyl, cyano, and C 1-6 and optionally substituted with one, two, three or more substituents each independently selected from the group consisting of alkoxy, C 1-6 The alkoxy may be optionally substituted with 1, 2, or 3 fluorines. In some embodiments, R a is hydrogen. In some embodiments, R2 -N(R a )-C5 alkyl. For example, R 2 teeth, TIFF2025061064000047.tif97150.

[0094] In some embodiments, R 2 is -NH2, -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -N(R a )-4 to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6 alkylene-phenyl, which moiety is attached to the tetralin bicycle to form the R-enantiomer; -N(R a )-C 1-8 Alkyl, -N(R a )-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R a )-C 1-6 Alkylene-Si(R c )3, -N(R a )-4 to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R a )-C 1-6Alkylene-phenyl has R on one or more available carbons. g and -N(R a )-4 to 6-membered heterocyclyl, -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R a )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R h may be optionally substituted with

[0095] For example, R 2 teeth, TIFF2025061064000048.tif97147.

[0096] In some embodiments, R 2 teeth TIFF2025061064000049.tif12128. In another embodiment, R 2 teeth The file is TIFF2025061064000050.tif11128.

[0097] In some embodiments, R 2 -C 1-6 Alkylene-C 3-6 Cycloalkyl. For example, R 2 teeth It can be represented by TIFF2025061064000051.tif10128.

[0098] In other embodiments, R 2 -OC 1-6 Alkylene-C 3-6 is cycloalkyl, and R 2 is R g In some embodiments, R 2is optionally substituted with 1, 2, or 3 fluorine atoms. For example, R 2 teeth, TIFF2025061064000052.tif15128.

[0099] In a further embodiment, R 2 is -N(R a )-C 1-6 Alkylene-C 3-6 is cycloalkyl, and R 2 is R g For example, R 2 teeth, TIFF2025061064000053.tif51130.

[0100] For example, R 2 teeth, TIFF2025061064000054.tif49130.

[0101] In still further embodiments, R 2 is -N(R a )-C 1-6 alkylene-4 to 6-membered heterocyclyl. For example, R 2 teeth, It can be represented by TIFF2025061064000055.tif12128.

[0102] For example, R 2 teeth, It can be represented by TIFF2025061064000056.tif11128.

[0103] In certain embodiments, R 2 is -N(R a )-C 1-6 alkylene-phenyl, and R 2 is R gIn some embodiments, R 2 is optionally substituted with 1, 2, or 3 fluorine atoms. For example, R 2 teeth, It can be represented by TIFF2025061064000057.tif15128.

[0104] For example, R 2 teeth, It can be represented by TIFF2025061064000058.tif15128.

[0105] In some embodiments, R 2 is -N(R a )-C 1-6 alkylene-5-6 membered heteroaryl, R 2 is R g For example, R 2 teeth, TIFF2025061064000059.tif44139.

[0106] For example, R 2 teeth, TIFF2025061064000060.tif66141.

[0107] In other embodiments, R 2 is a 4- to 6-membered heterocyclyl, and the 4- to 6-membered heterocyclyl is R g and when the 4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, said ring nitrogen atom is optionally substituted with one, two, three or more substituents each independently selected from R h For example, R 2 may be pyrrolidinyl, where pyrrolidinyl is R h In some embodiments, R h is C 1-6Alkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, and C 3-6 cycloalkyl-S(O)-. For example, R 2 teeth, TIFF2025061064000061.tif19128.

[0108] In a further embodiment, R 2 is -OC(O)-N(R a )-phenyl. For example, R 2 teeth, It can be represented by TIFF2025061064000062.tif14128.

[0109] In some embodiments, R 2 is -N(R a )-C 1-6 Alkylene-Si(R c )3. For example, R 2 teeth, TIFF2025061064000063.tif11128.

[0110] For example, R 2 teeth, TIFF2025061064000064.tif11128.

[0111] In some embodiments, R 2 is -N(R a )-(C=N(R b ))-C 1-6 alkyl. For example, R 2 teeth, It can be represented by TIFF2025061064000065.tif13128.

[0112] In some embodiments, R 2 is -N(R a )-C 3-6 is cycloalkyl, and R 2 is R gFor example, R 2 teeth, TIFF2025061064000066.tif14128. For example, R 2 teeth, It can be represented as TIFF2025061064000067.tif14128.

[0113] In some embodiments, R 2 is hydrogen. In other embodiments, R 2’ is selected from the group consisting of hydrogen and -NH2.

[0114] In some embodiments, R 3 is hydrogen. In other embodiments, R 3 -OC 1-6 Alkyl and -OC 1-6 Alkylene-C 3-6 cycloalkyl; R 3 is R g For example, R 3 is -OCH3, TIFF2025061064000068.tif27148.

[0115] In some embodiments, R 3 is -N(R a )-C 1-6 Alkyl and -N(R a )-C 1-6 alkylene-Ccycloalkyl; R 3 is R g For example, R 3 teeth, TIFF2025061064000069.tif25128.

[0116] Further disclosed herein are compounds of formula I(c): The compound is represented by TIFF2025061064000070.tif26128.

[0117] In some embodiments, R 2 is -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C 1-6 Alkylene-N(R a )(R b ), and -C alkylene-N(R a )-C 1-6 Alkylene-C 3-6 cycloalkyl; R 2 is R g For example, R 2 teeth, TIFF2025061064000071.tif37142.

[0118] Further disclosed herein are compounds of formula I(d): The compound is represented by TIFF2025061064000072.tif26128.

[0119] In some embodiments, R 2 is C 1-6 It is alkyl.

[0120] In other embodiments, R 4 is hydrogen. In a further embodiment, R 5 is selected from the group consisting of hydrogen and fluorine. 6 is hydrogen. In still further embodiments, R 7 is hydrogen.

[0121] Also disclosed herein is a compound represented by formula (II), or a pharmaceutically acceptable salt thereof: TIFF2025061064000073.tif27128[In the formula, X II1 is O and C(R II1 )(R II1’ ) selected from the group consisting of X II4 is O and C(R II4 )(R II4’ ) selected from the group consisting of (where X II1 and X II4 at least one of which is O), R II1 and R II1’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -C(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, C3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R IIa )-C 1-6 alkylene-phenyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -C(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C(O)-OC 1-6 Alkyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-4-6 membered heterocyclyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, and -N(R IIa )-C 1-6 Alkylene-phenyl has R on one or more available carbons. IIg and optionally substituted with one, two, three or more substituents each independently selected from 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4 to 6-membered heterocyclyl, or -N(R IIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIh and R II2 Ga-OC 1-6 Alkyl, -N(R IIa )-C 1-6 Alkyl, -N(R IIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -S(O)2-C 1-6 Alkyl, -N(R IIa )-C(O)-C 1-6 Alkyl, -OC(O)-N(R IIa )-C 1-6 Alkyl, -N(R IIa)-C(O)-OC 1-6 Alkyl, -OC 1-6 Alkylene-C 3-6 Cycloalkyl, -N(R IIa )-4 to 6-membered heterocyclyl, -OC 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-4- to 6-membered heterocyclyl, -N(R IIa )-C 1-6 alkylene-5-6 membered heteroaryl, or -N(R IIa )-C 1-6 When X is alkylene-phenyl, II1 is C(R II1 )(R II1’ ) and X II4 is O), R II2’ is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, and -C 1-6 alkylene-4- to 6-membered heterocyclyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-5-6 membered heteroaryl, and -C 1-6 Alkylene-4 to 6-membered heterocyclyl has R at one or more available carbons. IIg and 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -C 1-6 alkylene-5-6 membered heteroaryl, or -C 1-6 When alkylene-4- to 6-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIh optionally substituted with R II3 and R II3’ is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II4 and R II4’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, and C 3-6 Cycloalkyl has R on one or more available carbons. IIg optionally substituted with one, two, three or more substituents each independently selected from R II5 are hydrogen, deuterium, halogens, C 1-6 Alkyl, and C 3-6 cycloalkyl (where C 1-6 Alkyl and C 3-6 Cycloalkyl has R on one or more available carbons. IIgoptionally substituted with one, two, three or more substituents each independently selected from R II6 is selected from the group consisting of hydrogen and deuterium; R II7 is selected from the group consisting of hydrogen and deuterium; R IIg is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R IIa R IIb N-, R IIa R IIb NC(O)-, R IIaIIb N-SO w -, R IIa R IIb NC(O)-N(R IIIa )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIa ), C 1-6 Alkyl-N(R IIa )-C(O)-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-SO w -, C 3-6 Cycloalkyl-N(R IIa )-SO w -, C 1-6Alkyl-SO w -N(R IIa )-, C 3-6 Cycloalkyl-SO w -N(R IIa )-, C 1-6 Alkoxy-C(O)-N(R IIa )-, C 1-6 Alkyl-C(O)-N(R IIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIa )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 alkyl-, independently selected from the group consisting of 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIa ), C 1-6 Alkyl-N(R IIa )-C(O)-N(R IIa )-, C 1-6 Alkyl-N(R IIa )-SO w -, C 3-6 Cycloalkyl-N(R IIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIa)-, C 3-6 Cycloalkyl-SO w -N(R IIa )-, C 1-6 Alkoxy-C(O)-N(R IIa )-, C 1-6 Alkyl-C(O)-N(R IIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIa )-C(O)-C 1-6 Alkyl- and C 1-6 Alkoxy-C 1-6 Alkyl- is R IIP optionally substituted with one, two, three or more substituents each independently selected from R IIh For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIa R IIb NC(O)- and R IIa R IIb N—SO— (wherein C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIa R IIb NC(O)- and R IIa R IIb N-SO2- is R IIP optionally substituted with one, two, three or more substituents each independently selected from R IIPFor each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R IIa R IIb N-, R IIa R IIb N-carbonyl-, R IIa R IIb N-SO2- and R IIa R IIb N-carbonyl-N(R IIa )-, R IIa and R IIb For each occurrence, hydrogen and C 1-3 alkyl (wherein C 1-3 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R IIa and R IIb together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; and w is 0, 1, or 2].

[0122] In some embodiments, R II5 , R II6 , and R II7 are each hydrogen. In other embodiments, R II1 and R II1’ or R II4 and R II4’ are each hydrogen.

[0123] In certain embodiments, the compounds disclosed herein are Represented by TIFF2025061064000074.tif25128.

[0124] For example, R II2 and R II2’may each independently be selected from the group consisting of hydrogen and —CH. For example, R II3 and R II3’ may each independently be selected from the group consisting of hydrogen and —CH 3 .

[0125] Also disclosed herein is a compound represented by formula (III), or a pharmaceutically acceptable salt thereof: TIFF2025061064000075.tif28128[in the formula, R III1 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 Alkylene-C 3-8 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-C 1-6 Alkylene-C 3-8 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, -C(O)-N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl, -C=N(RIIIa )-C 1-6 Alkyl, and -S(O)2-C 1-6 alkyl (where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, phenyl, 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 Alkylene-C 3-8 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-C 1-6 Alkyl, -C(O)-OC 1-6 Alkyl, -C(O)-C 1-6 Alkylene-C 3-8 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, -C(O)-N(R IIIa )-C 1-6 alkylene-5-6 membered heteroaryl, -C=N(R IIIa )-C 1-6 Alkyl, and -S(O)2-C 1-6 Alkyl is a group having R on one or more available carbons. IIIg and 4- to 7-membered heterocyclyl, 5- to 6-membered heteroaryl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, -C(O)-N(R IIIa )-C 1-6Alkylene-4 to 7-membered heterocyclyl, or -C(O)-N(R IIIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIIh optionally substituted with R III3 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III4 is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III4’ is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, R III5 is hydrogen, halogen, and C 1-6 is selected from the group consisting of alkyl, R III6 is selected from the group consisting of hydrogen and deuterium; R III7 is selected from the group consisting of hydrogen and deuterium; R IIIg is, for each occurrence, hydrogen, halogen, hydroxyl, cyano, nitro, oxo, R IIIa R IIIb N-, R IIIa R IIIb NC(O)-, R IIIaIIIb N-SO w -, R IIIa R IIIb NC(O)-N(R IIIa )-, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyl-C 1-6 Alkylene-, C 1-6 Alkoxy, C 3-6Alkenyloxy, C 3-6 Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIIa ), C 1-6 Alkyl-N(R IIIa )-C(O)-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-SO w -, C 3-6 Cycloalkyl-N(R IIIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIIa )-, C 3-6 Cycloalkyl-SO w -N(R IIIa )-, C 1-6 Alkoxy-C(O)-N(R IIIa )-, C 1-6 Alkyl-C(O)-N(R IIIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIIa )-C(O)-C 1-6 Alkyl-, C 1-6 Alkoxy-C 1-6 independently selected from the group consisting of alkyl-, and 5- to 6-membered heteroaryl, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, C 1-6 Alkoxy, C 3-6 Alkenyloxy, C 3-6Alkynyloxy, C 3-6 Cycloalkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-OC(O)-, C 1-6 Alkyl-C(O)-O-, C 1-6 Alkyl-S(O) w -, C 1-6 Alkyl-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-C(O)-, C 1-6 Alkyl-C(O)-N(R IIIa ), C 1-6 Alkyl-N(R IIIa )-C(O)-N(R IIIa )-, C 1-6 Alkyl-N(R IIIa )-SO w -, C 3-6 Cycloalkyl-N(R IIIa )-SO w -, C 1-6 Alkyl-SO w -N(R IIIa )-, C 3-6 Cycloalkyl-SO w -N(R IIIa )-, C 1-6 Alkoxy-C(O)-N(R IIIa )-, C 1-6 Alkyl-C(O)-N(R IIIa )-C 1-6 Alkyl-, C 1-6 Alkyl-N(R IIIa )-C(O)-C 1-6 Alkyl-, C 1-6 Alkoxy-C 1-6 Alkyl- and 5- to 6-membered heteroaryl are R IIIP optionally substituted with one, two, three or more substituents each independently selected from R IIIh For each existence, C 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIIa R IIIb NC(O)-, R IIIa R IIIb N-SO2- and -C 1-6 alkylene-5-6 membered heteroaryl, 1-6 Alkyl, C 3-6 Alkenyl, C 3-6 Alkynyl, C 3-6 Cycloalkyl, C 1-6 Alkyl-S(O)2-, C 3-6 Cycloalkyl-S(O)2-, C 1-6 Alkyl-C(O)-, C 1-6 Alkoxy-C(O)-, R IIIa R IIIb NC(O)-, R IIIa R IIIb N-SO2- and -C 1-6 Alkylene-5-6 membered heteroaryl is R IIIP optionally substituted with one, two, three or more substituents each independently selected from R IIIP For each occurrence, halogen, hydroxyl, cyano, C 1-6 Alkoxy, C 3-6 Cycloalkyl, R IIIa R IIIb N-, R IIIa R IIIb N-carbonyl-, R IIIa R IIIb N-SO2- and R IIIa R IIIb N-carbonyl-N(R IIIa )-, R IIIa and R IIIb For each occurrence, hydrogen and C 1-3 alkyl (wherein C 1-3 alkyl may be optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or R IIIa and R IIIb together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclyl, which is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, and hydroxyl; and w is 0, 1, or 2].

[0126] In some embodiments, R III5 is selected from the group consisting of hydrogen and fluorine. III6 and R III7 are each hydrogen. In a further embodiment, R III4 and R III4’ are each independently selected from the group consisting of hydrogen and fluorine. III1 , R III3 , R III4 , and R III4’ are each hydrogen.

[0127] For example, disclosed herein are: The compound is represented by TIFF2025061064000076.tif21128.

[0128] In some embodiments, R III2 is hydrogen, C 1-6 Alkyl, and -C(O)-C 1-6 alkyl; R III2 is R IIIg For example, R III2 is hydrogen, TIFF2025061064000077.tif58145.

[0129] In other embodiments, R III2 is a 4- to 7-membered heterocyclyl, which has at one or more available carbons R IIIgand when the 4- to 7-membered heterocyclyl contains a substitutable ring nitrogen atom, said ring nitrogen atom is optionally substituted with one, two, three or more substituents each independently selected from R IIIh For example, R III2 teeth, TIFF2025061064000078.tif39128.

[0130] In certain embodiments, R III2 is a 5-6 membered heteroaryl, which has at one or more available carbons R IIIg and when the 4- to 7-membered heterocyclyl contains a substitutable ring nitrogen atom, said ring nitrogen atom is optionally substituted with one, two, three or more substituents each independently selected from R IIIh For example, R III2 teeth, It can be represented by TIFF2025061064000079.tif12128.

[0131] In some embodiments, R III2 -C 1-6 alkylene-5-6 membered heteroaryl, -C 1-6 Alkylene-5-6 membered heteroaryl has R IIIg and when the 4- to 7-membered heteroaryl contains a substitutable ring nitrogen atom, said ring nitrogen atom is optionally substituted with one, two, three or more substituents each independently selected from R IIIh For example, R III2 teeth, TIFF2025061064000080.tif82147.

[0132] In other embodiments, R III2 -C 1-6 alkylene-phenyl, and R III2 is R IIIgFor example, R III2 teeth, TIFF2025061064000081.tif33143.

[0133] In a further embodiment, R III2 -C 1-6 alkylene-4 to 7 membered heterocyclyl, -C 1-6 Alkylene-4 to 7-membered heterocyclyl has R at one or more available carbons. IIIg and optionally substituted with 1, 2, 3 or more substituents each independently selected from -C 1-6 When alkylene-4 to 7-membered heterocyclyl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIIh For example, R III2 teeth, TIFF2025061064000082.tif53144.

[0134] In some embodiments, R III2 is -C(O)-OC 1-6 alkyl, and R III2 is R IIIg For example, R III2 teeth, TIFF2025061064000083.tif12128.

[0135] In other embodiments, R III2 is -C(O)-N(R IIIa )-C 1-6 alkyl, and R III2 is R IIIg For example, R III2 teeth, TIFF2025061064000084.tif32150.

[0136] In a further embodiment, R III2 -C 1-6 Alkylene-C 3-8 is cycloalkyl, and R III2 is R IIIg For example, R III2 teeth, TIFF2025061064000085.tif65131.

[0137] In some embodiments, R III2 is -C(O)-C 1-6 Alkylene-C 3-8 is cycloalkyl, and R III2 is R IIIg For example, R III2 teeth, It can be represented by TIFF2025061064000086.tif16128.

[0138] In some embodiments, R III2 is -C=N(R IIIa )-C 1-6 alkyl. For example, R III2 teeth, It can be represented by TIFF2025061064000087.tif11128.

[0139] In other embodiments, R III2 is -C(O)-N(R IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, and —C(O)—N(RIIIa )-C 1-6 alkylene-5-6 membered heteroaryl; IIIa )-C 1-6 Alkylene-C 3-6 Cycloalkyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-phenyl, -C(O)-N(R IIIa )-C 1-6 Alkylene-4 to 7-membered heterocyclyl, or -C(O)-N(R IIIa )-C 1-6 Alkylene-5-6 membered heteroaryl has R IIIg and -C(O)-N(R IIIa )-C 1-6 alkylene-4 to 7-membered heterocyclyl or -C(O)-N(R IIIa )-C 1-6 When alkylene-5-6-membered heteroaryl contains a substitutable ring nitrogen atom, the ring nitrogen atom is R IIIh For example, R III2 teeth, TIFF2025061064000088.tif79151.

[0140] Further disclosed herein is a method for producing a semiconductor device comprising: 5-[1-fluoro-3-hydroxy-7-(3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(cyclopropylmethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-Fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(2-cyclopropylethyl)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(2-methoxyethoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(cyclopropylmethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7S)-1-Fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(5-fluoro-7-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(5-fluoro-7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-6-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1,4-difluoro-3-hydroxy-7-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(azetidin-1-yl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3,3,3-trifluoropropyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-difluorocyclobutyl)methoxy]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4-methoxy-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-methoxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({2-[1-(trifluoromethyl)cyclopropyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2,2-difluoro-2-phenylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3-cyclopropyl-2,2-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(3-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[methyl(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4-methylpentyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)butyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[4,4,4-trifluoro-3-(trifluoromethyl)butyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2,2-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-7-[(2-cyclopropylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[2-(pyridin-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-1-fluoro-3-hydroxy-7-[(3RS)-pyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-7-[(3RS)-1-(cyclopropanesulfonyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-1-fluoro-3-hydroxy-7-[(3SR)-pyrrolidin-3-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7RS)-7-[(3SR)-1-(cyclopropanesulfonyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[1-(cyclopropylmethyl)pyrrolidin-3-yl]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[2-(1H-pyrazol-1-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(4,4,4-trifluorobutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methylpentanoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methylpentyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluorobutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-Fluoro-3-hydroxy-7-({2-[1-(trifluoromethyl)cyclopropyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-ylphenylcarbamate, 4-{[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]amino}-2,2-dimethylbutanenitrile, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3-hydroxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3-methoxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(5,5,5-trifluoropentyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{(3-methylbutyl)[(pyridin-2-yl)methyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[(pyridin-2-yl)methyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(4,4,4-trifluoro-2-hydroxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(difluoromethoxy)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-pentanimidoyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(3-cyclopropylpropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-azaspiro[3.3]heptan-6-yl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(6,6,6-trifluorohexyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,3-difluorocyclobutyl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(azetidin-3-yl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(propan-2-yl)amino]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(azetidin-3-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(azetidin-3-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{(3-methylbutyl)[2-(pyridin-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(spiro[2.3]hexan-5-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[2-(trifluoromethoxy)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-hydroxy-3-methylbutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 3-Hydroxybutyl 8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-{1-fluoro-3-hydroxy-7-[3-(propan-2-yl)pyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclohexylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-dimethylbutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-(butylamino)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7S)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-Fluoro-3-hydroxy-7-[(4,4,4-trifluoro-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopentylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclohexylethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2-hydroxyethyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[2-(propan-2-yl)morpholin-4-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2R)-2-(propan-2-yl)morpholin-4-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(pyrrolidin-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(pyridin-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclobutylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({2-[(propan-2-yl)oxy]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-7-[(2-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(2-cyclopropyl-2-hydroxyethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-fluoro-3-hydroxy-7-{[3-(trimethylsilyl)propyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-({3-[hydroxy(dimethyl)silyl]propyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(pyridin-2-yl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,3-difluorocyclobutyl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(pyrrolidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-methylbutanimidamide, 5-{8-fluoro-6-hydroxy-2-[3-(oxan-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-7-(3-hydroxy-3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-7-amino-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(4,4-difluorobutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclopentylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(2-cyclobutylethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-7-{[2-(3,3-difluorocyclobutyl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylpentyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(3-ethylpentyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-(3-methylbutyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-methylpropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{8-fluoro-6-hydroxy-2-[3-(pyridin-3-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(pyrimidin-5-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(oxan-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclohexyl-2-hydroxyethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(2-methoxyethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-methoxypropyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(3-aminopropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(piperidin-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-methylbutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl 8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-{8-fluoro-6-hydroxy-2-[(7-oxabicyclo[2.2.1]heptan-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-Fluoro-6-hydroxy-2-{1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]azetidin-3-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(7-oxabicyclo[2.2.1]heptan-2-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(2,2-difluoroethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-{[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]methyl}-3,5-dimethyl-1H-pyrazol-1-yl)-2,2-dimethylpentanenitrile, 5-{8-fluoro-6-hydroxy-2-[(piperidin-4-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(morpholin-4-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(piperidin-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(1s,3r)-3-(trifluoromethoxy)cyclobutyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[3-(4-methylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[(propan-2-yl)oxy]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-Fluoro-3-hydroxy-7-({2-[(1s,3r)-3-(trifluoromethoxy)cyclobutyl]ethyl}amino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(1-Fluoro-3-hydroxy-7-{[(1s,3s)-3-(trifluoromethoxy)cyclobutyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-Fluoro-6-hydroxy-2-{2-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-2-azaspiro[3.3]heptan-6-yl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(difluoromethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(bicyclo[2.2.1]heptan-1-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[7-amino-1-fluoro-3-hydroxy-7-(prop-2-en-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N'-[8-fluoro-6-hydroxy-2-propyl-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]benzohydrazide, 5-[8-fluoro-6-hydroxy-2-(3-hydroxybutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-[1-(trifluoromethyl)cyclopropyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3-hydroxypropyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2S)-2-aminopropyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2R)-2-aminopropyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(piperazin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{[rac-(1R,2R)-2-(pyridin-4-yl)cyclopropyl]methyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(2-cyclopentyl-2-methoxyethyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[(2R)-2-amino-4-cyclohexylbutanoyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{3-[(propan-2-yl)oxy]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(1-methyl-1H-pyrazol-4-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{2-[1-(2,2-difluoroethyl)-3,5-dimethyl-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-[7-amino-1-fluoro-3-hydroxy-7-(4-methylpentyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-amino-1-fluoro-3-hydroxy-7-propyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1,3-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(cyclopropylmethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{(7S)-7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-7-[(3,3-difluoropropyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-[(oxan-4-yl)methyl]-7-(1,1,4-trioxo-1λ) 6,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(3,3-difluorocyclobutyl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(oxolan-2-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-(2-cyclopropylethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-{2-[2-(1-tert-butyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[2-(aminomethyl)-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{[bis(3-methylbutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 8-Fluoro-6-hydroxy-N-[(oxolan-3-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(1-methyl-1H-pyrazol-5-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-(2-{2-[3,5-dimethyl-1-(propan-2-yl)-1H-pyrazol-4-yl]ethyl}-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(2-{[(3-cyclopropylpropyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(1-ethyl-3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ6 ,2,5-thiadiazolidine-1,1,3-trione, N-(2,2-dimethylpropyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(3-methoxypropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(3-methoxy-2,2-dimethylpropyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[2-(dimethylamino)ethyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[2-(1-methylcyclopropyl)ethyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-methoxyethyl)-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-[(oxetan-3-yl)methyl]-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 8-Fluoro-6-hydroxy-N-(2-phenylethyl)-7-(1,1,4-trioxo-1λ) 6,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[3-(dimethylamino)propyl]-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, 5-[2-(3-cyclohexylpropyl)-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[3-(2,2-dimethylcyclopropyl)propyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(3S)-5-Fluoro-7-hydroxy-3-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(7-{[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]amino}-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(2R)-4-Fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(2S)-4-Fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-inden-5-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(4-methoxybutyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{3-[3-(trifluoromethyl)phenyl]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{2-methyl-3-[4-(propan-2-yl)phenyl]propyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[4-(5,5-dimethyl-1,3-dioxan-2-yl)butyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-6-hydroxy-2-[2-(2,6,6-trimethylcyclohex-1-en-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-pentyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-2-[3-(4-fluorophenyl)propyl]-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl [(1r,4r)-4-{2-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}cyclohexyl]carbamate, 5-{2-[3-(4-tert-butylphenyl)propyl]-8-fluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[8-fluoro-6-hydroxy-2-(3,5,5-trimethylhexyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{8-fluoro-2-[3-(2-fluorophenyl)propyl]-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 3-Hydroxybutyl 4,4,8-trifluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate, 5-(2-{[(2-cyclobutylethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-inden-5-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(7R)-1-fluoro-3-hydroxy-7-{[(3R)-3-hydroxybutyl]amino}-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6,2,5-thiadiazolidine-1,1,3-trione, 5-{(7R)-1-fluoro-3-hydroxy-7-[(4-hydroxy-3,3-dimethylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-6-(3-hydroxy-3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(cyclopropylmethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{6-[(4,4-difluorobutyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(4,4-difluorobutoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-6-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[1-fluoro-3-hydroxy-6-(3-methylbutoxy)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{1-fluoro-3-hydroxy-6-[(3-hydroxy-3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, tert-Butyl (2-{[5-fluoro-7-hydroxy-6-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]oxy}ethyl)carbamate, 5-(1-fluoro-3-hydroxy-6-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{6-[(cyclopropylmethyl)amino]-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[6-(2-aminoethoxy)-1-fluoro-3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-{2-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-4,4,8-trifluoro-6-hydroxy-1,2,3,4-tetrahydroisoquinolin-7-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, N-(cyclohexylmethyl)-8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ) 6 ,2,5-thiadiazolidin-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, N-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1λ 6 ,2,5-thiadiazolidin-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide, 5-[1-fluoro-3-hydroxy-7-(4-methylpentyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-(8-fluoro-6-hydroxy-2-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-1,2,3,4-tetrahydroisoquinolin-7-yl)-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, 5-[(3S)-5-Fluoro-7-hydroxy-3-(4-methylpentyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione, and pharmaceutically acceptable salts thereof The compound is selected from the group consisting of:

[0141] In some embodiments, the compound is 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione or a pharmaceutically acceptable salt thereof.

[0142] In some embodiments, the compound is 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione.

[0143] In some embodiments, the compound is 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ 6 ,2,5-thiadiazolidine-1,1,3-trione is a pharmaceutically acceptable salt thereof.

[0144] In some embodiments, the compound is TIFF2025061064000089.tif20128 or a pharmaceutically acceptable salt thereof.

[0145] In some embodiments, the compound is TIFF2025061064000090.tif20128.

[0146] In some embodiments, the compounds disclosed herein are formulated as pharmaceutically acceptable compositions comprising a compound of the present disclosure and a pharmaceutically acceptable carrier.

[0147] In some embodiments, the compounds disclosed herein are selected from the compounds shown in Table 1.

[0148] Table 1: Exemplary compounds of the present disclosure TIFF2025061064000091.tif196155TIFF2025061064000092.tif213155TIFF2025061064000093.tif219155TIFF2025061064000094.t if217155TIFF2025061064000095.tif208155TIFF2025061064000096.tif216155TIFF2025061064000097.tif210155TIFF20250610640 00098.tif219155TIFF2025061064000099.tif206155TIFF2025061064000100.tif228155TIFF2025061064000101.tif217155TIFF202 5061064000102.tif205155TIFF2025061064000103.tif222155TIFF2025061064000104.tif202155TIFF2025061064000105.tif131155

[0149] Methods of Making Exemplary Compounds The compounds of the present disclosure may be better understood in connection with the following synthetic schemes and methods, which illustrate the means by which the compounds may be prepared. The compounds of the present disclosure may be prepared by a variety of synthetic procedures. Representative synthetic procedures are shown in Schemes 1-19, but are not limited thereto. The variable R 1 , R II1 , R II1’ , RIII1 , R 2 , R 3 , R II3 , R II3’ , R III3 , R 4 , R 5 , R II5 , R III5 , R 6 , R II6 , R III6 ,R 7 , R II7 , R III7 , and R a is defined herein, for example as detailed in the Summary of the Invention.

[0150] Scheme 1: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 1, compounds of formula (1-4) can be prepared from compounds of formula (1-1), where R 5* is R 5 , R II5 , or R III5 and R 6* is R 6 , R II6 , or R III6 and R 7* is R 7 , R II7 , or R III7 Compounds of formula (1-1) (wherein PG 1In the first step, the protecting group PG, such as benzyl, can be reacted with a mixture of chlorosulfonyl isocyanate and tert-butanol in a cooled (-10 to 10°C) solvent, such as, but not limited to, dichloromethane, in the presence of a tertiary amine base, such as triethylamine or diisopropylethylamine. This intermediate can then be treated under acidic conditions, such as trifluoroacetic acid in dichloromethane or hydrochloric acid in dioxane, to give compounds of formula (1-2). Compounds of formula (1-2) can be reacted with an alkoxide base, such as sodium methoxide, in a solvent, such as tetrahydrofuran, at or near ambient temperature to give compounds of formula (1-3). The protecting group PG in compounds of formula (1-3) can be 1 By removing PG, a compound of formula (1-4) can be obtained. 1 When is a benzyl group, deprotection can be achieved by catalytic hydrogenation. Compounds of formula (1-4) are representative compounds of formula (I), formula (II), and formula (III).

[0151] Scheme 2: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 2, compounds of formula (2-4) can be prepared from compounds of formula (2-1), wherein LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (2-1) can be cross-coupled with water under palladium-catalyzed cross-coupling conditions comprising a catalyst or pre-catalyst, a base such as cesium carbonate, and a heated solvent mixture such as N,N-dimethylformamide and water to give compounds of formula (2-2). Compounds of formula (2-2) can be cross-coupled with water to give compounds of formula R in the presence of a base such as cesium carbonate and a solvent such as N,N-dimethylformamide. 2a -LG 1 (In the formula, R 2a is optionally substituted with C 1-6 Alkyl, C 3-6 Cycloalkyl C1-6 Alkylene, or (3- to 6-membered heterocyclyl)C 1-6 alkylene, LG 1 Alkylation with a compound of formula (2-3) (where PG is a leaving group such as chlorine, bromine, iodine, or sulfonic acid) can provide compounds of formula (2-3). Compounds of formula (2-3) can be converted to compounds of formula (2-4) using catalytic hydrogenation (130-150 psi) in a solvent such as 2,2,2-trifluoroethanol for 30-50 hours, freeing the protecting group PG. 1 and the aromatic ring can be reduced. Alternatively, compounds of formula (2-3) can be deprotected using methodology known to those skilled in the art to give compounds of formula (2-5). PG 1 When is benzyl, treatment of compound of formula (2-3) with boron trichloride in the presence of pentamethylbenzene in cold dichloromethane gives compound of formula (2-5). Compound of formula (2-5) can then be converted to compound of formula (2-4) under catalytic hydrogenation conditions in acetic acid. Compound of formula (2-4) is a representative compound of formula (I).

[0152] Scheme 3: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 3, a compound of formula (3-3) can be prepared from a compound of formula (2-1), wherein LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (2-1) can be converted to compounds of formula R under palladium-catalyzed cross-coupling conditions containing a catalyst or pre-catalyst, a ligand, a base such as cesium carbonate, and a heated solvent such as tert-amyl alcohol. 3a -NH2(wherein, R 3a is optionally substituted with C 1-6 Alkyl, optionally substituted C 1-6 Cycloalkyl C 1-6 Alkylene, optionally substituted 4- to 6-membered heterocyclyl, optionally substituted (4- to 6-membered heterocyclyl)C 1-6Alkylene, optionally substituted (5-6 membered heteroaryl)C 1-6 alkylene, or optionally substituted phenyl-C 1-6 Cross-coupling with an amine of formula (3-1), where the amine is an alkylene, can provide compounds of formula (3-1). Compounds of formula (3-1) can be deprotected as described in Scheme 2 to provide compounds of formula (3-2). Compounds of formula (3-2) can be reduced to compounds of formula (3-3) using catalytic hydrogenation conditions in acetic acid or a mixture of methanol and acetic acid. Compounds of formula (3-3) are representative compounds of formula (I).

[0153] Scheme 4: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 4, a compound of formula (4-3) can be prepared from a compound of formula (2-1), wherein LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (2-1) can be deprotected to give compounds of formula (4-1) using methodology known to those skilled in the art. PG 1 When R is benzyl, treatment of compound (2-1) with boron trichloride in the presence of pentamethylbenzene in cold dichloromethane gives compound (4-1). 4a -CH=CH-B(OR 4b ) 2 (wherein -B(OR 4b )2 represents a boronic acid or boronate, and R 4a is optionally substituted with C 3-6 Cross-coupling with a cycloalkyl and optionally substituted 4- to 6-membered heterocyclyl under, for example, Suzuki reaction conditions can provide compounds of formula (4-2). Reduction of compounds of formula (4-2) under catalytic hydrogenation conditions in a solvent such as, but not limited to, 2,2,2-trifluoroethanol can provide compounds of formula (4-3). Compounds of formula (4-3) are representative compounds of formula (I).

[0154] Scheme 5: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 5, compounds of formula (5-6) can be prepared from compounds of formula (5-1), wherein LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (5-1) can be reacted with a base such as lithium 2,2,6,6-tetramethylpiperidin-1-ide in the presence of N,N,N',N'-tetramethylethylenediamine in a solvent such as cold tetrahydrofuran, followed by treatment with allyl bromide (5-2) to give compounds of formula (5-3). Compounds of formula (5-3) can be treated with a three-step hydroboration-oxidation procedure to give compounds of formula (5-4). Compounds of formula (5-4) can then be reacted under appropriate palladium-catalyzed cross-coupling reaction conditions to give chromans of formula (5-5). Compounds of formula (5-5) can be deprotected using methodology known to those skilled in the art to give compounds of formula (5-6). PG 1 When is benzyl, treatment of compounds of formula (5-5) with boron trichloride in the presence of pentamethylbenzene in cold dichloromethane gives compounds of formula (5-6), which are representative compounds of formula (II).

[0155] Scheme 6: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 6, compounds of formula (6-4) can be prepared from compounds of formula (6-1), where LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 1is a protecting group such as, but not limited to, benzyl. Compounds of formula (6-1) are prepared similarly to compounds of formula (5-3) in Scheme 5 and can be cross-coupled with water to give compounds of formula (6-2). Compounds of formula (6-2) can be reacted with boron trichloride in the presence of pentamethylbenzene in cold dichloromethane to give compounds of formula (6-3). Compounds of formula (6-3) can be cyclized in the presence of a silver salt such as silver trifluoromethanesulfonate to give compounds of formula (6-4). Compounds of formula (6-4) are representative compounds of formula (II).

[0156] Scheme 7: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 7, compounds of formula (7-5) can be prepared from compounds of formula (7-1), where LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 2 is a protecting group such as, but not limited to, (methoxyethoxy)methyl. Compounds of formula (7-1) can be cross-coupled with H2NCH2CO2-t-Bu in the presence of a palladium catalyst, a ligand, and a base to give compounds of formula (7-2). Compounds of formula (7-2) can then be reacted with a mixture of chlorosulfonyl isocyanate and tert-butanol in a chilled solvent such as, but not limited to, dichloromethane in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine to give compounds of formula (7-3). Compounds of formula (7-3) can then be reacted with Mg(OCH3)2 in methanol in a heated solvent such as 2-methyltetrahydrofuran to give cyclized compounds of formula (7-4). The protecting group PG can then be reacted under conditions known to those skilled in the art and dependent on the particular protecting group. 2 Compounds of formula (7-4) can be converted to compounds of formula (7-5) by removing PG 2When is (methoxyethoxy)methyl, treatment with an acid such as 4M HCl in dioxane provides compounds of formula (7-5), which are representative compounds of formula (II).

[0157] Scheme 8: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 8, compounds of formula (8-5) can be prepared from compounds of formula (8-1), where LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 2 is a protecting group such as, but not limited to, (methoxyethoxy)methyl. Thus, compounds of formula (8-1) can be converted to amines, HNC(R 6 )(R 7 )CO2-t-Bu. Subsequent treatment with a mixture of chlorosulfonyl isocyanate and allylic alcohol in a chilled solvent such as dichloromethane gives compounds of formula (8-2). Treatment of compounds of formula (8-2) with tetrakis(triphenylphosphine)palladium(0) in the presence of a base such as sodium methoxide gives the corresponding 1λ 6 The dioxolane moiety can then be removed by treatment under acidic conditions, such as, but not limited to, formic acid, to afford compounds of formula (8-3). Compounds of formula (8-3) can be converted to amines, (R 3a )(R a )NH(wherein, R 3a (as described in Scheme 3) to give compounds of formula (8-4). 3a and R a and the nitrogen to which they are attached may be linked to form a 4- to 8-membered heterocycle, which may be used in the reductive amination of compounds of formula (8-3). 2 is removed in a manner known to those skilled in the art and dependent on the particular protecting group to give compounds of formula (8-5).2 When is (methoxyethoxy)methyl, treatment with an acid such as 4M HCl in dioxane provides compounds of formula (8-5), which are representative compounds of formula (I).

[0158] Scheme 9: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 9, compounds of formula (9-4) can be prepared from compounds of formula (2-1), where LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate, and PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (2-1) can be converted to compounds of formula (9-1) (wherein -B(OR 4b )2 represents a boronic acid or boronate, and PG 3 Cross-coupling with a compound of formula (9-2) (where "het" is an amine protecting group such as tert-butoxycarbonyl, and "het" is a heterocyclyl containing a ring nitrogen) provides compounds of formula (9-2). Treatment under catalytic hydrogenation conditions saturates the heterocyclyl ring, removing the protecting group PG 1 The protecting group PG is removed to give a compound of formula (9-3). Compounds of formula (9-3) may be further reduced under catalytic hydrogenation conditions to give a compound of formula (9-3). 3 In a second step, PG is removed to give compounds of formula (9-4). 3 When is tert-butoxycarbonyl, treatment with an acid such as trifluoroacetic acid in dichloromethane is suitable for removing the protecting group. Compounds of formula (9-4) are representative of compounds of formula (I). Compounds of formula (9-4) can be further modified, such as by alkylation or acylation, to provide additional compounds of formula (I).

[0159] Scheme 10: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 10, compounds of formula (10-8), formula (10-10), and formula (10-11) can be prepared from compounds of formula (10-1), where LG 2 is a leaving group such as chlorine, bromine, or iodine, and PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (10-1) can be reacted with compounds of formula (10-2) under reductive amination conditions. Subsequent protection of the formed amine with a nitrogen protecting group such as, but not limited to, tert-butoxycarbonyl provides compounds of formula (10-3). Compounds of formula (10-3) can be cyclized by treatment with n-butyllithium to give compounds of formula (10-4). The amide nitrogen of compounds of formula (10-4) can be converted to bromoacetic acid, BrC(R) in the presence of a base such as, but not limited to, 1,2,2,6,6-pentamethylpiperidine in a heated solvent such as heated N,N-dimethylformamide. III6 )(R III7Alkylation with 1H-CO2CH3 affords compounds of formula (10-5). The carbonyl can be reduced to the corresponding methylene in a three-step process. In the first step, treatment with a reducing agent such as sodium borohydride affords the corresponding alcohol. In the second step, treatment with 1,1'-thiocarbonyldiimidazole (TCDI) in the presence of base affords the corresponding 1H-imidazole-1-carbothioate. In the third step, treatment of the 1H-imidazole-1-carbothioate with tributyltin hydride and triethylborane affords the tetrahydroisoquinoline of formula (10-6). Compounds of formula (10-6) can be treated with sodium methoxide in warm methanol to remove the trifluoroacetyl moiety. Subsequent treatment with a mixture of chlorosulfonyl isocyanate and allyl alcohol in a cold solvent such as dichloromethane affords the alloc-sulfonylurea. Treatment of alloc-sulfonylurea with tetrakis(triphenylphosphine)palladium(0) in the presence of a base such as sodium methoxide affords the corresponding 1λ 6 ,2,5-thiadiazolidine-1,1,3-trione moiety can be obtained. 1 and P.G. 3 By simultaneously removing PG, compounds of formula (10-8) are obtained. 1 is benzyl and PG 3 When is tert-butoxycarbonyl, treatment with boron trichloride in the presence of 1,2,3,4,5-pentamethylbenzene in cold dichloromethane removes both the benzyl and tert-butoxycarbonyl groups. Alternatively, the protecting group PG 3 can also be selectively removed from compounds of formula (10-7) to give compounds of formula (10-9). PG 3 When is tert-butoxycarbonyl, treatment with an acid such as trifluoroacetic acid in dichloromethane gives compounds of formula (10-9). Compounds of formula (10-9) can be converted to compounds of formula R under amide bond forming conditions. 10a -CO2H (in the formula, R 10ais optionally substituted with C 1-6 carboxylic acid (which is alkyl), followed by PG 1 Subsequent removal of PG affords compounds of formula (10-10). One set of amide bond-forming conditions involves treatment with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU) in the presence of a tertiary amine base such as diisopropylethylamine in a solvent such as dichloromethane. 1 When is benzyl, treatment with boron trichloride in the presence of 1,2,3,4,5-pentamethylbenzene in cold dichloromethane removes the benzyl protecting group. 10b -LG 1 (In the formula, R 10b is optionally substituted with C 1-6 Alkyl, optionally substituted -C 1-6 Alkylene-C 3-6 Cycloalkyl, optionally substituted C 1-6 Alkylene-phenyl, optionally substituted C 1-6 Alkylene-(4-6 membered)heterocyclyl and optionally substituted C 1-6 alkylene-(5-6 membered)heteroaryl, LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonic acid), followed by deprotection to give compounds of formula (10-11). One set of alkylation conditions involves converting compounds of formula (10-9) to compounds of formula R in the presence of a base such as cesium carbonate in warm acetonitrile. 10b -LG 1 Then, PG 1 When is benzyl, treatment with boron trichloride in the presence of 1,2,3,4,5-pentamethylbenzene in cold dichloromethane removes the benzyl protecting group to give compounds of formula (10-11). Compounds of formula (10-8), formula (10-10), and formula (10-11) are representative compounds of formula (III).

[0160] Scheme 11: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 11, compounds of formula (11-2) can be prepared from compounds of formula (10-9), where PG 1 is a protecting group such as, but not limited to, benzyl. Compounds of formula (10-9) can be prepared by reacting compounds of formula R 11a Reaction of the aryl group with a .dbd.O under reductive amination conditions gives compounds of formula (11-1). 11a is optionally substituted with C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-7 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4-6 membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, 4-8 membered heterocycle, -(4-7 membered heterocycle)-C 1-6 alkylene-5-6 membered heteroaryl. 11a is R III2 R may be optionally substituted as described for 11a =O is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, HC 1-6 Alkylene-C 3-7 Cycloalkyl, HC 1-6 Alkylene-phenyl, HC 1-6 Alkylene-4-6 membered heterocyclyl, HC 1-6 Alkylene-5-6 membered heteroaryl, 4-8 membered heterocycle, H-(4-7 membered heterocycle)-C 1-6 The corresponding aldehyde or ketone of alkylene-5-6 membered heteroaryl is known to those skilled in the art. 1 Compounds of formula (11-1) can be deprotected using methods that depend on the nature of PG to give compounds of formula (11-1). 1When PG is benzyl, treatment with boron trichloride in the presence of 1,2,3,4,5-pentamethylbenzene in cold dichloromethane removes the benzyl protecting group to give compounds of formula (11-2). 1 When is benzyl, treatment under catalytic or transfer hydrogenation conditions removes the benzyl protecting group to afford compounds of formula (11-2). Compounds of formula (11-1) and formula (11-2) can be further modified using methodology known to those skilled in the art. Compounds of formula (11-2) are representative compounds of formula (III).

[0161] Scheme 12: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 12, compounds of formula (12-5) can be prepared from compounds of formula (12-1), where R 10b is optionally substituted with C 1-6 Alkyl, optionally substituted -C 1-6 Alkylene-C 3-6 Cycloalkyl, optionally substituted C 1-6 Alkylene-phenyl, optionally substituted C 1-6 Alkylene-(4-6 membered)heterocyclyl and optionally substituted C 1-6 The compound of formula (12-1) (wherein PG 1 is a protecting group such as benzyl) can be converted to compounds of formula (12-2) in a three-step process. The dioxolane in compounds of formula (12-1) can be removed under acidic conditions known to those skilled in the art. Reductive amination can introduce the amine moiety, -NH2. Reductive amination can be carried out under conditions known to those skilled in the art. One set of stereoselective conditions involves treatment with monobasic sodium phosphate, hydrochloric acid, sec-butylamine, pyridoxal-5-phosphate, and Codexis® ATA-025. The resulting amine can be converted to a compound of formula (12-3) using a benzyloxycarbonyl (PG 3The thiadiazolidine-trione formation procedure described in Scheme 8 can then be used to convert compounds of formula (12-2) to compounds of formula (12-3). Compounds of formula (12-2) can be converted to compounds of formula (12-3) by the addition of R as described in Scheme 10. 10b -LG 1 Alkylation with PG gives compounds of formula (12-4). 1 and P.G. 3 Depending on the reaction, the protecting groups of compounds of formula (12-4) can be removed stepwise or simultaneously to give compounds of formula (12-5). For example, PG 1 is benzyl and PG 3 When is benzyloxycarbonyl, treatment with boron trichloride in the presence of pentamethylbenzene in cold dichloromethane simultaneously removes both protecting groups. Compounds of formula (12-5) are representative of compounds of formula (I).

[0162] Scheme 13: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 13, compounds of formula (13-2) can be prepared from compounds of formula (10-9). Compounds of formula (10-9) can be reacted with triphosgene in the presence of a base, such as, but not limited to, a tertiary amine. The amine, R 10b -NH2(wherein, R 10b is optionally substituted with C 1-6 Alkyl, optionally substituted -C 1-6 Alkylene-C 3-6 Cycloalkyl, optionally substituted C 1-6 Alkylene-phenyl, optionally substituted C 1-6 Alkylene-(4-6 membered)heterocyclyl and optionally substituted C 1-6 Subsequent treatment with alkylene-(5-6 membered)heteroaryl provides compounds of formula (13-1). 1 The removal of PG is known to those skilled in the art.1 This is achieved using a methodology that depends on PG 1 When is benzyl, treatment with boron trichloride in the presence of 1,2,3,4,5-pentamethylbenzene in cold dichloromethane removes the benzyl protecting group to give compounds of formula (13-2), which are representative of compounds of formula (III).

[0163] Scheme 14: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 14, compounds of formula (14-1) can be prepared from compounds of formula (10-8). 11a Reaction of the aryl group with ═O under reductive amination conditions gives compounds of formula (14-1). 11a is optionally substituted with C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-7 Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4-6 membered heterocyclyl, -C 1-6 Alkylene-5-6 membered heteroaryl, 4-8 membered heterocycle, -(4-7 membered heterocycle)-C 1-6 alkylene-5-6 membered heteroaryl. 11a is R III2 R may be optionally substituted as described for 11a =O is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, HC 1-6 Alkylene-C 3-7 Cycloalkyl, HC 1-6 Alkylene-phenyl, HC 1-6 Alkylene-4-6 membered heterocyclyl, HC 1-6Alkylene-5-6 membered heteroaryl, 4-8 membered heterocycle, H-(4-7 membered heterocycle)-C 1-6 The corresponding aldehyde or ketone of alkylene-5-6-membered heteroaryl is used. Reductive amination can be carried out using conventional reagents such as sodium cyanoborohydride or sodium borohydride or solid-supported equivalents. Compounds of formula (14-1) can be further modified using methodologies known to those skilled in the art. Compounds of formula (14-1) are representative compounds of formula (III).

[0164] Scheme 15: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 15, compounds of formula (15-4) can be prepared from compounds of formula (15-1). Compounds of formula (15-1) can be cross-coupled with water under palladium-catalyzed cross-coupling conditions containing a catalyst or pre-catalyst, an optional ligand, a base such as cesium carbonate, and a heated solvent such as N,N-dimethylacetamide to give compounds of formula (15-2). Compounds of formula (15-2) can be converted to compounds of formula R 15a -LG 1 (In the formula, R 15a is optionally substituted with C 1-6 Alkyl, optionally substituted -C 1-6 Alkylene-C 3-6 Cycloalkyl, optionally substituted C 1-6 Alkylene-phenyl, optionally substituted C 1-6 Alkylene-(4-6 membered)heterocyclyl and optionally substituted C 1-6 alkylene-(5-6 membered)heteroaryl, LG 1 is a leaving group such as chlorine, bromine, iodine, or sulfonate), followed by deprotection, gives compounds of formula (15-3). One set of alkylation conditions involves the conversion of compounds of formula (15-2) to compounds of formula R in the presence of a base such as cesium carbonate in N,N-dimethylformamide. 15a -LG 1 Then, PG1 When is benzyl, treatment with ammonium formate in ethanol in the presence of 10% palladium on carbon removes the benzyl protecting group to give compounds of formula (15-3). Compounds of formula (15-3) can be reduced with hydrogen (approximately 120 psi) in the presence of 10% palladium on carbon in a solvent such as trifluoroethanol to give compounds of formula (15-4). Compounds of formula (15-4) are representative of compounds of formula (I).

[0165] Scheme 16: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 16, compounds of formula (16-3) can be prepared from compounds of formula (15-1). Compounds of formula (15-1) can be converted to amines, R, under palladium-catalyzed cross-coupling conditions containing a catalyst or pre-catalyst, an optional ligand, a base such as cesium carbonate, and a heated solvent mixture such as N,N-dimethylacetamide. 16a Cross-coupling with -NH2 gives compounds of formula (16-1). 1 can be removed under conditions known to those skilled in the art and dependent on the particular protecting group used. 1 When is benzyl, the protecting group is removed by treatment with boron trichloride in the presence of pentamethylbenzene in cold dichloromethane or under transfer hydrogenation conditions to give compounds of formula (16-2). Compounds of formula (16-2) can be reduced with hydrogen (approximately 120 psi) in the presence of 10% palladium on carbon in a solvent such as trifluoroethanol to give compounds of formula (16-3). Compounds of formula (16-3) are representative of compounds of formula (I).

[0166] Scheme 17: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 17, compounds of formula (17-7) can be prepared from compounds of formula (17-1).2 is a leaving group such as chloro, bromo, or iodo, and PG 1 is a protecting group such as benzyl) with a base such as lithium diisopropylamide, followed by the formation of a compound of formula (17-2) (where Boc is tert-butoxycarbonyl and R 17a is an optionally substituted alkyl, an optionally substituted -C 1-6 Alkylene-C 3-6 cycloalkyl, or optionally substituted -C 1-6 Treatment with oxathiazolidine 2,2-dioxide of alkylene-4-6-membered heterocyclyl (alkylene-4-6-membered heterocyclyl) affords compounds of formula (17-3). Compounds of formula (17-3) can be alkylated with methyl bromoacetate in the presence of base and potassium iodide. Cross-coupling with potassium vinyltrifluoroborate then provides compounds of formula (17-4). Compounds of formula (17-4) can be oxidized to the corresponding aldehyde using potassium osmate dihydrate in the presence of N-methylmorpholine N-oxide and sodium metaperiodate. Cyclization of the intermediate aldehyde with triethylsilane in the presence of boron trifluoride diethyl etherate affords compounds of formula (17-5). The trifluoroacetamide group can be removed from compounds of formula (17-5) by treatment with sodium methoxide. Thiadiazolidine-trione formation can be achieved by following the steps described in Scheme 8 to afford compounds of formula (17-6). The protecting groups Boc and PG are reacted using conditions known to those skilled in the art. 1 from the compound of formula (17-6), PG 1 The simultaneous or stepwise removal of PG affords compounds of formula (17-7). 1 When is benzyl, transfer hydrogenation gives PG 1 is selectively removed. Subsequent exposure to hydrochloric acid in dioxane removes the tert-butoxycarbonyl protecting group. Compounds of formula (17-7) are representative of compounds of formula (I).

[0167] Scheme 18: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 18, compounds of formula (18-7) and (18-8) can be prepared from compounds of formula (18-1). 1 (wherein 1 is a protecting group such as benzyl) can be converted to compounds of formula (18-2) in a three-step process. Compounds of formula (18-1) can be treated under cross-coupling reaction conditions to form bicyclic structures. The benzyl group can be selectively removed from the tetrahydroisoquinoline nitrogen by treatment with 1-chloroethyl chloroformate and 8-bis(dimethylamino)naphthalene in a solvent such as 1,2-dichloroethane. The exposed amine can be protected as a tert-butoxycarbonyl by treatment with di-tert-butyl dicarbonate in the presence of a base such as sodium bicarbonate in a solvent such as a mixture of tetrahydrofuran and water. Compounds of formula (18-2) can be oxidized with osmium tetroxide and sodium periodate to give the corresponding ketone, compounds of formula (18-3). Compounds of formula (18-3) can be treated with diethylaminosulfur trifluoride (DAST) to convert the ketone to the corresponding difluoromethylene. Subsequent treatment with potassium carbonate in methanol removes the trifluoroacetyl moiety to give compounds of formula (18-4). Compounds of formula (18-4) can be treated as described in Scheme 8 to assemble the thiadiazolidine-trione to give compounds of formula (18-5). The tert-butoxycarbonyl protecting group can be removed from compounds of formula (18-5) by treatment under acidic conditions, such as with trifluoroacetic acid in dichloromethane, to give compounds of formula (18-6). Reductive amination of compounds of formula (18-6) followed by deprotection using procedures known to those skilled in the art can give compounds of formula (18-7), where R 18a is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, 4- to 7-membered heterocyclyl, -C 1-6 Alkylene-C 3-8Cycloalkyl, -C 1-6 Alkylene-phenyl, -C 1-6 alkylene-4 to 7-membered heterocyclyl, or -C 1-6 Alkylene-5-6-membered heteroaryl. Compounds of formula (18-6) can also be converted to compounds of formula (18-8). Compounds of formula (18-6) can be treated with 4-nitrophenyl carbonochloridate in the presence of a tertiary amine base. The alcohol R can then be reacted with a base such as potassium tert-butoxide to afford the aryl group. 18b -OH(in the formula, R 18b is optionally substituted with C 1-6 alkyl), followed by PG 1 Removal of the protecting group gives compounds of formula (18-8): Compounds of formula (18-7) and (18-8) are representative compounds of formula (III).

[0168] Scheme 19: Representative scheme for the synthesis of exemplary compounds of the present disclosure As shown in Scheme 19, compounds of formula (19-2) can be obtained from compounds of formula (19-1). Compounds of formula (19-1) can be prepared as described in the Examples. Compounds of formula (19-1) can be converted to aldehydes or ketones (R 19a Reductive amination with 2-( ... 19a -C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkyl, -C1-6 alkylene-N(R a )-C 1-6 Alkylene-C 3-6 Cycloalkyl, C 3-6 Cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkyl, or -C 1-6 alkylene-4 to 6-membered heterocyclyl, each moiety being optionally substituted. Compounds of formula (19-2) are representative compounds of formula (I).

[0169] Pharmaceutical Composition The present disclosure provides pharmaceutical compositions comprising a compound disclosed herein, for example, a compound of Formula (I), Formula (II), or Formula (III). In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient. In some embodiments, the compound disclosed herein, for example, a compound of Formula (I), Formula (II), or Formula (III), is provided in an effective amount in the pharmaceutical composition. In some embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount.

[0170] The pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. Generally, such preparation methods include the step of bringing a compound of the present disclosure (the "active ingredient") into association with a carrier and / or one or more other accessory ingredients, and then, if necessary and / or desirable, shaping and / or packaging the product into a desired single or multiple dosage unit. Pharmaceutical compositions can be prepared, packaged, and / or sold in bulk, as a single unit dose, and / or as a plurality of single unit doses. As used herein, a "unit dose" is a discrete amount of a pharmaceutical compo...

Claims

1. A pharmaceutical composition for treating cancer in a patient in need thereof, comprising an effective amount of a compound represented by the formula:

2. 1. A pharmaceutical composition for treating cancer in a patient in need thereof, comprising an effective amount of a compound, wherein the compound is 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ ６ ,2,5-thiadiazolidine-1,1,3-trione, or a pharmaceutically acceptable salt thereof.

3. The compound is 5-{(7R)-1-fluoro-3-hydroxy-7-[(3-methylbutyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}-1λ ６ 3. The pharmaceutical composition according to claim 2, wherein the compound is a pharmaceutically acceptable salt of 2,5-thiadiazolidine-1,1,3-trione.

4. 4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is selected from solid tumors and lymphatic cancers, kidney cancer, breast cancer, lung cancer, bladder cancer, colon cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, brain cancer, head and neck cancer, skin cancer, uterine cancer, testicular cancer, glioma, esophageal cancer, liver cancer such as liver cancer, lymphoma such as acute B lymphoblastic lymphoma, non-Hodgkin's lymphoma (e.g., Burkitt's lymphoma, small cell lymphoma, and large cell lymphoma), Hodgkin's lymphoma, leukemia (e.g., AML, ALL, and CML), and multiple myeloma.

5. 4. The pharmaceutical composition of any one of claims 1 to 3, wherein the cancer is selected from lung cancer, breast cancer, ovarian cancer, epithelial ovarian cancer, leukemia, lymphoma, melanoma, pancreatic cancer, sarcoma, bladder cancer, bone cancer, brain cancer, cervical cancer, colon cancer, esophageal cancer, gastric cancer, liver cancer, head and neck cancer, kidney cancer, myeloma, thyroid cancer, prostate cancer, metastatic cancer, or carcinoma.

6. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is selected from leukemia, lymphoma, carcinoma, or sarcoma.

7. The cancer is selected from the group consisting of lymphoma, sarcoma, bladder cancer, bone cancer, brain cancer, cervical cancer, colon cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, myeloma, thyroid cancer, leukemia, prostate cancer, breast cancer (e.g., ER positive, ER negative, chemotherapy resistant, Herceptin resistant, HER2 positive, doxorubicin resistant, tamoxifen resistant, ductal carcinoma, lobular carcinoma, primary, metastatic), ovarian cancer, pancreatic cancer, liver cancer (e.g., hepatocellular carcinoma), lung cancer (e.g., non-small cell lung cancer, squamous cell lung carcinoma, adenocarcinoma, large cell lung carcinoma, small cell lung carcinoma, carcinoid, sarcoma), glioblastoma multiforme, glioma, and melanoma, thyroid cancer, endocrine system cancer, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, liver cancer, kidney cancer, lung cancer, non-small cell lung cancer, melanoma, mesothelioma, ovarian cancer, sarcoma, gastric cancer, uterine cancer, or 4. The pharmaceutical composition of any one of claims 1 to 3, wherein the cancer is selected from medulloblastoma, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, primary thrombocytosis, primary macroglobulinemia, primary brain tumor, cancer, malignant pancreatic insulinoma, malignant carcinoid, bladder cancer, premalignant skin lesion, testicular cancer, lymphoma, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary cancer, malignant hypercalcemia, uterine cancer, adrenocortical carcinoma, neoplasms of the endocrine or exocrine pancreas, medullary thyroid carcinoma, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid carcinoma, hepatocellular carcinoma, Paget's disease of the nipple, phyllodes tumor, lobular carcinoma, ductal carcinoma, pancreatic stellate cell carcinoma, hepatic stellate cell carcinoma, or prostate cancer.

8. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is a solid tumor.

9. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is leukemia.

10. Leukemia includes acute nonlymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, nonleukemic leukemia, leukemic leukemia, basophilic leukemia, blast cell leukemia, bovine leukemia, chronic myelocytic leukemia, leukemia cutis, fetal leukemia, eosinophilic leukemia, gross leukemia, hairy cell leukemia, hemoblastic leukemia, hemoblastic leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, leukopenic leukemia, lymphocytic leukemia, lymphoblastic leukemia 10. The pharmaceutical composition of claim 9, wherein the leukemia is selected from myeloid leukemia, lymphocytic leukemia, lymphocytic leukemia, lymphoid leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocytic leukemia, small myeloblastic leukemia, monocytic leukemia, myeloblastic leukemia, myelocytic leukemia, myelogranulocytic leukemia, myelomonocytic leukemia, Naegeli leukemia, plasma cell leukemia, multiple myeloma, plasma cell leukemia, promyelocytic leukemia, Leder cell leukemia, Schilling leukemia, stem cell leukemia, subleukemic leukemia, or undifferentiated cell leukemia.

11. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is a sarcoma.

12. Sarcomas include chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy's sarcoma, liposarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, green sarcoma, choriocarcinoma, embryonal sarcoma, Wilms' tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, and granulocytic sarcoma.

12. The pharmaceutical composition of claim 11, wherein the tumor is selected from Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer's astrocytic sarcoma, angiosarcoma, leukemia sarcoma, malignant mesenchymal sarcoma, paraperiosteal sarcoma, reticulocyte sarcoma, Rous sarcoma, serous bursal sarcoma, synovial sarcoma, or telangiectasia sarcoma.

13. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is melanoma.

14. 14. The pharmaceutical composition of claim 13, wherein the melanoma is selected from acral lentigo melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman melanoma, S91 melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo melanoma, malignant melanoma, nodular melanoma, subungual melanoma, or superficial widespread melanoma.

15. The pharmaceutical composition according to any one of claims 1 to 3, wherein the cancer is carcinoma.

16. Carcinomas include medullary thyroid carcinoma, familial medullary thyroid carcinoma, acinar carcinoma, acinic cell carcinoma, adenocystic carcinoma, adenoid cystic carcinoma, adenomatous carcinoma, adrenocortical carcinoma, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, basaloid carcinoma, basal squamous cell carcinoma, bronchoalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebral carcinoma, cholangiocarcinoma, choriocarcinoma, colloid carcinoma, comedocarcinoma, corpus carcinoma, cribriform carcinoma, armor carcinoma, skin cancer, columnar carcinoma, columnar cell carcinoma, ductal carcinoma, ductal carcinoma, scirrhous carcinoma, embryonal carcinoma, cerebrocarcinoma, epidermoid carcinoma, epithelial adenoid carcinoma, exophytic carcinoma, ulcer carcinoma, fibrocarcinoma, colloid carcinoma, colloid carcinoma, giant cell carcinoma, glandular adenocarcinoma carcinoma), granulosa cell carcinoma, hair matrix carcinoma, blood-like carcinoma, hepatocellular carcinoma, Hürthle cell carcinoma, hyaline carcinoma, adrenal-like carcinoma, infantile embryonal carcinoma, carcinoma in situ, carcinoma in situ in epidermis, carcinoma in situ, Krompecher carcinoma, Kulchitzky cell carcinoma, large cell carcinoma, lenticular carcinoma, lenticular carcinoma, lipomatous carcinoma, lobular carcinoma, lymphoepithelial carcinoma, medullary carcinoma, melanoma, soft carcinoma, mucinous carcinoma, mucosecreting carcinoma, mucous cell carcinoma, mucoepidermoid carcinoma, mucinous carcinoma, mucinous carcinoma, myxomatous carcinoma, nasopharyngeal carcinoma, oat cell carcinoma, ossifying carcinoma, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, squamous cell carcinoma, medullary carcinoma, renal cell carcinoma, sarcomatoid carcinoma sarcomatodes), Schneiderian carcinoma, scirrhous carcinoma, scrotal carcinoma, signet ring cell carcinoma, simplex carcinoma, small cell carcinoma, potato-like carcinoma, spheroid cell carcinoma, spindle cell carcinoma, cavernous carcinoma, squamous cell carcinoma, squamous cell carcinoma, cord-like carcinoma, telangiectatic carcinoma, telangiectatic-like carcinoma, transitional cell carcinoma, nodular carcinoma, tubular carcinoma, nodular carcinoma, warty carcinoma, or choriocarcinoma.