INIBIDORES DE DPP1 COM LIGANTES POLICÍCLICOS E SEUS USOS

Abstract

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts or deuterated forms thereof, wherein R0 , L and R1 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt or deuterated form thereof, e.g., in the treatment of a disease that is treatable by administration of a DPP1 inhibitor.

Description

“DPP1 INHIBITORS WITH POLYCYCLIC LIGANDS AND THEIR USES” CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 452,636, filed March 16, 2023, and U.S. Provisional Application No. 63 / 546,686, filed October 31, 2023, the contents of which are incorporated by reference into their entities for all purposes. BACKGROUND

[0002] Dipeptidyl peptidase 1 (DPP1; EC 3.4.14.1), also known as cathepsin C, is a lysosomal cysteine ​​protease belonging to the papain family, with a molecular weight of 200 kDa. DPP1 was first discovered by Gutman and Fruton in 1948 (J Biol Chem, 174, 851-858); however, the cDNA of the human enzyme was first described in 1995 (Paris et al. 1995, FEBS Lett, 369, 326-330). DPP1 is the only member of the papain family that functions as a tetramer, composed of four identical subunits. Each subunit is composed of an N-terminal fragment, a heavy chain, and a light chain (Dolenc et al. 1995, J Biol Chem, 270, 21626-21631).

[0003] DPP1 is constitutively expressed in many tissues, with the highest levels in the lung, kidney, liver, and spleen. DPP1 catalyzes the removal of dipeptides from the N-terminal end of polypeptide substrates with broad specificity. Recent data suggest that, in addition to being an important enzyme in the degradation of lysosomal proteins, DPP1 also functions as an essential enzyme in the activation of serine proteases in cytotoxic T lymphocytes and natural killer cells (granzymes A and B), mast cells (chymase and tryptase), and neutrophils (cathepsin G, neutrophil elastase, and proteinase-3).

[0004] Mast cells are found in many tissues, but are present in greater numbers along the epithelial linings of the body, such as the skin, respiratory tract, and gastrointestinal tract. In humans, two types of mast cells have been identified: the T type, which expresses only tryptase, and the MC type, which expresses both tryptase and chymase. In humans, T-type mast cells are located primarily in alveolar tissue and mucosa. Petition 870250103180, dated 11 / 11 / 2025, page 9 / 393 2 / 383 intestinal, while TC-type cells predominate in the skin and conjunctiva. Tryptase and chymase appear to be important mediators of allergic diseases, being involved in processes of inflammation, bronchoconstriction, and mucus secretion.

[0005] Neutrophils play a fundamental role in host defense against the invasion of pathogens. Neutrophils are produced in the bone marrow and are fully mature when released into circulation to assume their role as the first line of cellular defense. Pro-inflammatory mediators and chemotactic attractants activate neutrophils and attract them to the site of infection, where they act to engulf bacteria by phagocytosis, attacking them with an arsenal of antibacterial compounds that use oxidative and non-oxidative attack methods. The powerful serine protease, neutrophil elastase, is one such antibacterial compound that is clearly involved in the destruction of bacteria. Neutrophil elastase is released into the phagolysosome that engulfs the microorganism, which is then destroyed.Neutrophil elastase is capable of attacking the outer membrane protein, OmpA, in Gram-negative bacteria, helping to directly kill the pathogen by degrading its membrane, and allowing other antibacterial compounds to access the pathogen. Furthermore, neutrophil elastase can help process other antibacterial compounds, converting them from inactive propeptides into their active states, such as cathelicidin.

[0006] However, neutrophil elastase can also cause problems for its host. It is one of the most destructive enzymes in the body, with the ability to degrade extracellular matrix proteins (including collagens, proteoglycans, fibronectin, platelet receptors, complement receptors, thrombomodulin, pulmonary surfactant, and cadherins) and major plasma proteins (including coagulation and complement factors, immunoglobulin, various proteases, and protease inhibitors). Under physiological conditions, endogenous protease inhibitors, such as α1-antitrypsin, tightly regulate neutrophil elastase activity. However, in inflammatory sites, elastase Petition 870250103180, dated 11 / 11 / 2025, page 10 / 393 3 / 383 of neutrophils is capable of escaping regulation and, once dysregulated, can induce the release of pro-inflammatory cytokines, such as interleukin-6 and interleukin-8, leading to acute lung injury. It can even impair host defense against infection by degrading phagocyte surface receptors and opsonins. Its negative function is illustrated by its involvement in tissue destruction and inflammation that characterize several diseases, including hereditary emphysema, chronic obstructive pulmonary disease, cystic fibrosis, adult respiratory distress syndrome, ischemia-reperfusion injury, and rheumatoid arthritis.

[0007] Thus, there is a need in the literature to provide new DPP1 inhibitors to treat the diseases mentioned above and others associated with DPP1 and neutrophil elastase. SUMMARY

[0008] In some respects, the present disclosure provides a compound of Formula (I), (I)

[0009] or a pharmaceutically acceptable salt or deuterated form thereof,

[0010] where:

[0011] R0é

[0012] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R(I) * * * * * * 8, or

[0013] • 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8, Petition 870250103180, dated 11 / 11 / 2025, page 11 / 393 4 / 383

[0014] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0015] L is a polycyclic cycloalkylene, polycyclic arylene, or polycyclic heteroarylene, in which a first atom of a first ring of the polycyclic arylene or polycyclic heteroarylene is bonded to and a second atom of a second ring of polycyclic arylene or heteroarylene is connected to R1;

[0016] where L is independently replaced by 0-4 R10;

[0017] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl, or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1-3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0018] R1é

[0019] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0020] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0021] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0022] • 5- to 12-membered monocyclic heteroaryl Petition 870250103180, dated 11 / 11 / 2025, page 12 / 393 5 / 383 containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0023] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0024] • 7- to 20-membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0025] each R is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(Ci-6 alkyl)2, -COC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(Ci-6 alkyl)2, NHCOCi-6 alkyl, -NHCOC3-5 cycloalkyl, -P(O)(Ci—6 alkyl), -S(O)Ci—6alkyl, S(O)2C1-6 alkyl, -S(O)2 C3-6 cycloalkyl, -SO2 3- to 7-membered heterocycle, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2 -C1-6 alkyl, C1-6-alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen,or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from O, halogen, cyano, C1-6 alkyl, and C1-6 haloalkyl.

[0026] In some embodiments, the present disclosure provides a compound of Formula (II): Petition 870250103180, dated 11 / 11 / 2025, page 13 / 393 6 / 383 (II)

[0027] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0028] R0é

[0029] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0030] • 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0031] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0032] R1é

[0033] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0034] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0035] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0036] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg, Petition 870250103180, dated 11 / 11 / 2025, page 14 / 393 7 / 383

[0037] · 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0038] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0039] each Rg is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C26alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(Ci-6 alkyl)2, -COCi-6alkyl, -COOC1-6 alkyl, -CONH2, -CONHCi-6 alkyl, -CONHC3-6 cycloalkyl, -CON(Ci-6 alkyl)2, NHCOCi-6 alkyl, -NHCOC3—5cycloalkyl, -P(O)(Ci-6 alkyl), -S(O)Ci—6alkyl, S(O)2C1-6 alkyl, -S(O)2 C3-6 cycloalkyl, -SO2 3- to 7-membered heterocycle, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2 -C1-6 alkyl, C1-6-alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen,or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from O, halogen, cyano, C1-6 alkyl, and C1-6 haloalkyl.

[0040] In some embodiments, the present disclosure provides a compound of Formula (III): (III),

[0041] or a pharmaceutically acceptable salt or form Petition 870250103180, dated 11 / 11 / 2025, page 15 / 393 8 / 383 deuterated from the same, in which

[0042] R0é

[0043] · 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0044] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0045] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0046] R1é

[0047] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0048] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0049] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0050] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0051] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0052] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0053] each Rgé selected independently of Petition 870250103180, dated 11 / 11 / 2025, page 16 / 393 9 / 383 hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(Ci-6 alkyl)2, -COC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(Ci-6 alkyl)2, NHCOC1-6 alkyl, -NHCOC3-5 cycloalkyl, -P(O)(Ci-6 alkyl), -S(O)Ci-6 alkyl, S(O)2Ci-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3- to 7-membered heterocyclyl, S(O)NH2, -S(O)NHCi-6 alkyla, -S(O)N(Ci-6 alkyla)2, -S(O)2NH2, -OSO2-C1-6 alkyla, Ci—6alkylene-O-Ci—6alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3-7 heterocycle Members containing 1 to 3 heteroatoms selected from N, S and O, or Rgé optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6 -alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogenium,or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from O, halogen, cyano, C1-6 alkyl, and C1-6 haloalkyl.

[0054] In some embodiments, the present disclosure provides a compound of Formula (IV): (IV),

[0055] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0056] R0é

[0057] · 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0058] • 5- to 12-membered polycyclic heterocyclyl Petition 870250103180, dated 11 / 11 / 2025, page 17 / 393 10 / 383 containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0059] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0060] R1é

[0061] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0062] • 6 to 18 member cage optionally replaced by 1 to 3 Rg,

[0063] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0064] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0065] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0066] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0067] each R is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(C1-6 alkyl)2, NHCOC1-6alkyl, -NHCOC^cycloalkyl, -P(O)(C1-6 alkyl), -S(O)C1-6alkyl, S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3- to 7-membered heterocyclyl, Petition 870250103180, dated 11 / 11 / 2025, p. 18 / 393 11 / 383 S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2-C1-6 alkyl, C16-alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, a 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and the Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl and C1-6 haloalkyl.

[0068] In some embodiments, the present disclosure provides a compound of Formula (V), (V)

[0069] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0070] R0é

[0071] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0072] • 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0073] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0074] R1é Petition 870250103180, dated 11 / 11 / 2025, page 19 / 393 12 / 383

[0075] · 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0076] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0077] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0078] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0079] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0080] • 7- to 20-membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0081] each R is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(Ci-6 alkyl)2, -COC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHCi-6 alkyl, -CONHC3-6 cycloalkyl, -CON(Ci-6 alkyl)2, NHCOCi—6alkyl, -NHCOC^cycloalkyl, -P(O)(Ci—6 alkyl), -S(O)Ci—6alkyl, S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3- to 7-membered heterocycle, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2 -C1-6 alkyl, C1-6-alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen,or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein the 5- to 7-membered heterocycle is optionally, Petition 870250103180, dated 11 / 11 / 2025, page 20 / 393 13 / 383 replaced by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl and C1-6 haloalkyl.

[0082] n is 0 or 1;

[0083] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0084] In some embodiments, the present disclosure provides a compound of formula (VI), (VI)

[0085] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0086] R0é

[0087] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0088] • 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0089] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-e-alkyl), N(C1-e-alkyl)2, COOH, alkyl Petition 870250103180, dated 11 / 11 / 2025, page 21 / 393 14 / 383 C1-6, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-alkoxy, C1-6halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0090] R1é

[0091] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0092] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0093] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0094] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0095] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0096] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0097] each R is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(C1-6 alkyl)2, NHCOC1-6 alkyl, -NHCOC3-5cycloalkyl, -P(O)(C1-6 alkyl), -S(O)C1-6alkyl, S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3- to 7-membered heterocycle, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2 -C1-6 alkyl, C1-6 alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and the Rg e optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 Petition 870250103180, dated 11 / 11 / 2025, p. 22 / 393 15 / 383 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl and C1-6 haloalkyl.

[0098] n is 0 or 1;

[0099] each R10 is independently =O, halogen, C116 alkyl, C116 alkoxy, S-C116 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C116 alkyl, N(C116 alkyl)2, COOH, COC116 alkyl, COOC116 alkyl, CON116 alkyl, CON(C116 alkyl)2, NHCOC116 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0100] In some embodiments, the present disclosure provides a compound of formula (VII), (VII)

[0101] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0102] R0é

[0103] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0104] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the heterocycle Petition 870250103180, dated 11 / 11 / 2025, page 23 / 393 The 16 / 383 polycyclic is optionally replaced by 1 to 3 R8.

[0105] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0106] R1é

[0107] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0108] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0109] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0110] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0111] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0112] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0113] each R is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(C1-6 alkyl)2, NHCOC1-6alkyl, -NHCOC^cycloalkyl, -P(O)(C1-6 alkyl), -S(O)C1-6alkyl, S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3- to 7-membered heterocyclyl, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2 -C1-6 alkyl, Petition 870250103180, dated 11 / 11 / 2025, page 24 / 393 17 / 383 C1-6-alkylene-O-C1-6-alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, a 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and the Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl and C1-6 haloalkyl.

[0114] n is 0 or 1;

[0115] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-e alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-e alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0116] In some embodiments, the present disclosure provides a compound of formula (XIV),

[0117] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0118] R0é

[0119] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or Petition 870250103180, dated 11 / 11 / 2025, page 25 / 393 18 / 383

[0120] · 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0121] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0122] R1é

[0123] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0124] • 6 to 18 member aril optionally replaced by 1 to 3 Rg,

[0125] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0126] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0127] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0128] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg groups,

[0129] each Rg is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(C1-6 alkyl)2, NHCOC1-6alkyl, -NHCOC^cycloalkyl, -P(O)(C1-6 alkyl), -S(O)C1-6alkyl, Petition 870250103180, dated 11 / 11 / 2025, page 26 / 393 19 / 383 S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3- to 7-membered heterocycle, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2-C1-6 alkyl, C1-6 alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, wherein the 5- to 7-membered heterocycle is optionally replaced by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl and C1-6 haloalkyl.

[0130] n is 0 or 1;

[0131] each R10 is independently =O, halogen, C1-6alkyl, C1-6alkoxy, S-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-ealkyl, N(C1-ealkyl)2, COOH, COC1-6alkyl, COOC1-6alkyl, CON1-6alkyl, CON(C1-ealkyl)2, NHCOC1-ealkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0132] In some embodiments, the present disclosure provides a compound of formula (VIII), (VIII)

[0133] or a pharmaceutically acceptable salt or deuterated form thereof, wherein Petition 870250103180, dated 11 / 11 / 2025, p. 27 / 393 20 / 383

[0134] R0é

[0135] · 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0136] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0137] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0138] R1é

[0139] • 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg,

[0140] • 6 to 18 member cage optionally replaced by 1 to 3 Rg,

[0141] • 5- to 12-membered monocyclic heterocycline containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally replaced by 1-3 Rg,

[0142] • 5- to 12-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally replaced by 1-3 Rg,

[0143] • 7- to 14-membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the bicyclic heteroaryl group is optionally replaced by 1-4 Rg, or

[0144] • 7 to 20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, in which the tricyclic heteroaryl group is optionally replaced by 1-5 Rg,

[0145] each Rg independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 Petition 870250103180, dated 11 / 11 / 2025, page 28 / 393 21 / 383 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(Ci-6 alkyl)2, -COCi-6alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -CON(Ci-6 alkyl)2, NHCOCi-6alkyl, -NHCOC^cycloalkyl, -P(O)(Ci-6 alkyl), -S(O)Ci-6alkyl, S(O)2Ci-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 heterocyclyl of 3 to 7 members, S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2-C1-6 alkyl, C16-alkylene-O-C1-6 alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, a 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, and the Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, -COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, wherein the 5- to 7-membered heterocycle is optionally replaced by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl and C1-6 haloalkyl.

[0146] n is 0 or 1;

[0147] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH.

[0148] In some embodiments, the present disclosure provides a compound of formula (IX), Petition 870250103180, dated 11 / 11 / 2025, p. 29 / 393 22 / 383 (IX)

[0149] or a pharmaceutically acceptable salt or deuterated form thereof,

[0150] R0é

[0151] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0152] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0153] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0154] each R6 is selected independently from H, C1-alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0155] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH.

[0156] In some embodiments, the present disclosure provides a compound of formula (X), Petition 870250103180, dated 11 / 11 / 2025, page 30 / 393 23 / 383 (X)

[0157] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0158] R0é

[0159] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0160] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0161] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0162] each R6 is selected independently from H, C1-alkyl, C2-6-COC1-6 alkyl, C2-6-alkenyl, C2-6-alkynyl and C3-6-cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0163] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein Petition 870250103180, dated 11 / 11 / 2025, page 31 / 393 24 / 383 the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH.

[0164] In some embodiments, the present disclosure provides a compound of Formula (XI), (XI)

[0165] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0166] R0é

[0167] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0168] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0169] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0170] each R6 is selected independently of H, Ci- 6-alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl groups are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0171] each R7 is selected independently of H, Petition 870250103180, dated 11 / 11 / 2025, page 32 / 393 25 / 383 halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0172] n is 0 or 1;

[0173] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0174] In some embodiments, the present disclosure provides a compound of Formula (XII), (XII)

[0175] or a pharmaceutically acceptable salt or deuterated form thereof, wherein R0 is

[0176] • monocyclic heterocycline of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the heterocycle Petition 870250103180, dated 11 / 11 / 2025, page 33 / 393 The 26 / 383 monocyclic is optionally replaced by 1 to 3 R8, or

[0177] • 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0178] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0179] each R6 is selected independently from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0180] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0181] n is 0 or 1;

[0182] each R10 is independently =O, halogen, C16alkyl, C1-6alkoxy, S-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6alkyl, N(C1-6alkyl)2, COOH, COC1-6alkyl, COOC1-6alkyl, CON1-6alkyl, CON(C1-6alkyl)2, NHCOC1-6alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0183] In some forms, the present disclosure Petition 870250103180, dated 11 / 11 / 2025, p. 34 / 393 27 / 383 provides a compound of Formula (XIII),

[0184] or a pharmaceutically acceptable salt or deuterated form thereof, wherein R0 is

[0185] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0186] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0187] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0188] each R6 is selected independently from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0189] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4 to 7 membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are Petition 870250103180, dated 11 / 11 / 2025, page 35 / 393 28 / 383 optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0190] n is 0 or 1;

[0191] each R10 is independently =O, halogen, C16 alkyl, C16 alkoxy, S-C16 alkyl, C26 alkenyl, C26 alkynyl, C36 cycloalkyl, cyano, hydroxyl, NH2, -NH-C16 alkyl, N(C16 alkyl)2, COOH, COC16 alkyl, COOC16 alkyl, CON16 alkyl, CON(C16 alkyl)2, NHCOC16 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0192] In some embodiments, the present disclosure provides a compound of Formula (XV), N (R10)n / / / / V ς / ΐίπr6 R°Á0r7 X^O (XV)

[0193] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0194] R0é

[0195] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0196] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0197] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(Ci-6alkyl), N(Ci-6alkyl)2, COOH, Ci-6 alkyl, Ci-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, Ci-6 alkoxy, Ci-6 alkoxy Petition 870250103180, dated 11 / 11 / 2025, page 36 / 393 29 / 383 halogenated, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0198] each R6 is selected independently from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0199] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0200] n is 0 or 1;

[0201] each R10 is independently =O, halogen, C16 alkyl, C16 alkoxy, S-C16 alkyl, C26 alkenyl, C26 alkynyl, C36 cycloalkyl, cyano, hydroxyl, NH2, -NH-C16 alkyl, N(C16 alkyl)2, COOH, COC16 alkyl, COOC16 alkyl, CON16 alkyl, CON(C16 alkyl)2, NHCOC16 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

[0202] In some embodiments, the present disclosure provides a compound of Formula (XVI), Petition 870250103180, dated 11 / 11 / 2025, p. 37 / 393 30 / 383

[0203] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0204] R0é

[0205] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0206] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0207] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0208] each R6 is selected independently from H, C16 alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0209] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0210] each of rings E and F is a 5-membered heteroarylene ring;

[0211] n is 0 or 1;

[0212] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, Petition 870250103180, dated 11 / 11 / 2025, page 38 / 393 31 / 383 hydroxyl, NH2, -NH-C1-ealkyl, N(C1-ealkyl)2, COOH, COC1-6alkyl, COOC1-6alkyl, CON1-6alkyl, CON(C1-6alkyl)2, NHCOC1-ealkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R0 is substituted on ring E or ring F.

[0213] In some embodiments, the present disclosure provides a compound of Formula (XVII),

[0214] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0215] R0é

[0216] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0217] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0218] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-e alkoxy, C1-e alkoxy halogenated, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0219] each R6 is selected independently from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; Petition 870250103180, dated 11 / 11 / 2025, pp. 39 / 393 32 / 383

[0220] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0221] X' is O, S, NH or N(Ci-6 alkyl);

[0222] n is 0 or 1;

[0223] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-alkyl, N(C1-alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or on the ring of 5 . / ^^-X' ''Wv members of > .

[0224] In some embodiments, the present disclosure provides a compound of Formula (XVIII), (XVIII)

[0225] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0226] R0é Petition 870250103180, dated 11 / 11 / 2025, p. 40 / 393 33 / 383

[0227] · 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0228] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0229] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0230] each R6 is selected independently from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0231] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHCl-6 alkyl, N(C1-6 alkyl)2, COOH, COCl-6 alkyl, COOCl-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0232] X' is O, S, NH or N(Ci-6 alkyl);

[0233] n is 0 or 1;

[0234] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, Petition 870250103180, dated 11 / 11 / 2025, p. 41 / 393 34 / 383 cyano, hydroxyl, NH2 and COOH, and R10 is substituted in the phenyl ring or in the 5-membered ring of

[0235] In embodiments, the present disclosure provides a compound of Formula (XIX), (19)

[0236] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0237] R0é

[0238] • 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0239] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0240] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0241] each R6 is selected independently from H, C1-alkyl, C2-6-alkyl, C2-6-alkenyl, C2-6-alkynyl and C3-6-cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0242] each R7 is selected independently of H, Petition 870250103180, dated 11 / 11 / 2025, page 42 / 393 35 / 383 halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0243] n is 0 or 1;

[0244] each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or thiophene ring of 'I A

[0245] In some embodiments, the present disclosure provides a compound of Formula (XX), (XX)

[0246] or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0247] R0é

[0248] • 5- to 12-membered monocyclic heterocyclyl Petition 870250103180, dated 11 / 11 / 2025, p. 43 / 393 36 / 383 containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8, or

[0249] • polycyclic heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8,

[0250] each R8 is selected independently from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl;

[0251] each R6 is selected independently from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0252] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH,

[0253] n is 0 or 1;

[0254] each R10 is independently =O, halogen, C16alkyl, C1-6alkoxy, S-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6alkyl, N(C1-6alkyl)2, COOH, COC1-6alkyl, COOC1-6alkyl, CON1-6alkyl, CON(C1-6alkyl)2, NHCOC1-6alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH, and R10 is substituted on the phenyl ring or thiophene ring of Petition 870250103180, dated 11 / 11 / 2025, p. 44 / 393 37 / 383

[0255] In embodiments, the present disclosure provides a pharmaceutical composition comprising a compound disclosed in this document (for example, a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or a pharmaceutically acceptable salt or deuterated form thereof), and a pharmaceutically acceptable adjuvant, diluent or carrier.

[0256] In another aspect of the disclosure, a method of treatment is provided. The method of treatment, in modalities, comprises administering to an individual in need thereof, a composition comprising an effective amount of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or a pharmaceutically acceptable salt or deuterated form thereof.

[0257] The treatment method, in modalities, is a treatment method for an obstructive airway disease, for example, cystic fibrosis (CF), asthma, or bronchiectasis (e.g., non-CF bronchiectasis). In another modality, the treatment method is a method for treating chronic rhinosinusitis (CRS).

[0258] In some modalities, the treatment method is a method for treating hidradenitis suppurativa (HS).

[0259] In some modalities, the treatment method is a method for treating cancer.

[0260] In some modalities, the treatment method is a treatment method for lupus nephritis.

[0261] In some modalities, the treatment method is a rheumatoid arthritis treatment method.

[0262] In some modalities, the treatment method is a treatment method for inflammatory bowel disease (IBD). Petition 870250103180, dated 11 / 11 / 2025, page 45 / 393 38 / 383 DETAILED DESCRIPTION

[0263] Throughout this disclosure, various patents, patent applications, and publications are referenced. The disclosures of these patents, patent applications, and publications in their entirety are incorporated into this disclosure by reference for all purposes in order to describe more fully the state of the art, as known to those qualified in the subject matter, at the date of this disclosure. This disclosure shall prevail in the event of any inconsistency between the patents, patent applications, and publications cited and this disclosure. DEFINITIONS

[0264] Listed below are definitions of various terms used in the descriptive report and claims to describe this disclosure.

[0265] Unless defined otherwise, all technical and scientific terms used in this disclosure have the same meanings commonly understood by one skilled in the art to which this disclosure pertains.

[0266] The term “about”, when immediately preceding a numerical value, means a range encompassing the said numerical value plus or minus an acceptable amount of variation in the art (e.g., plus or minus 10% of that value). For example, “about 50” may mean from 45 to 55, “about 25,000” may mean from 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise or is inconsistent with such interpretation. For example, in a list of numerical values ​​such as “about 49, about 50, about 55, ...”, “about 50” means a range extending to less than half the range(s) between the preceding and subsequent values, for example, more than 49.5 to less than 50.5. Furthermore, the phrases “less than about” a value or “greater than about” a value should be understood in light of the definition of the term “about” provided in this document.Similarly, the term "about" when preceding a series of numerical values ​​or a range of values ​​(for example, "about. Petition 870250103180, dated 11 / 11 / 2025, p. 46 / 393 39 / 383 "10, 20, 30" or "approximately 10 to 30") refers, respectively, to all values ​​in the series or to the endpoints of the interval.

[0267] The terms below, as used in this document, have the following meanings, unless otherwise indicated:

[0268] “Cyan” refers to the root -CN.

[0269] “Hydroxy” or “hydroxyl” refers to the radical -OH.

[0270] “Oxo” refers to the substituent =O.

[0271] “Alkyl” or “alkyl group” refers to a fully saturated, linear or branched hydrocarbon chain radical with one to twelve carbon atoms and which is linked to the rest of the molecule by a single bond. Alkyls comprising any number of carbon atoms from 1 to 12 are included. An alkyl comprising up to 12 carbon atoms is a C1-C12 alkyl, an alkyl comprising up to 10 carbon atoms is a C1-C10 alkyl, an alkyl comprising up to 6 carbon atoms is a C1-C6 alkyl, and an alkyl comprising up to 5 carbon atoms is a C1-C5 alkyl. A C1-C5 alkyl includes C5 alkyls, C4 alkyls, C3 alkyls, C2 alkyls and C1 alkyls. A C1-C6 alkyl includes all the chemical moieties described above for C1-C5 alkyls, but also includes C6 alkyls. A C1-C6 alkyl includes all the chemical moieties described above for C1-C5 alkyls and C1-C6 alkyls, but also includes C7, C8, C9, and C10 alkyls.Similarly, a C1-C12 alkyl includes all the previous chemical moieties, but also includes C11 and C12 alkyls. Non-limiting examples of C1-C12 alkyl include methyl, ethyl, n-propyl, i-propyl, sec-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, t-amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, and n-dodecyl. Unless otherwise specifically indicated in the descriptive report, an alkyl group may optionally be substituted.

[0272] “Alkylene” or “alkylene chain” refers to a divalent, linear or branched, fully saturated hydrocarbon chain radical with one to twelve carbon atoms. Non-limiting examples of C1-C12 alkylenes include methylene, ethylene, propylene, n-butylene, ethenylene, propenylene, n-butenylene, propynylene, n-butynylene, and the like. The alkylene chain is linked to the rest of the Petition 870250103180, dated 11 / 11 / 2025, p. 47 / 393 40 / 383 molecule by means of a single bond and to the radical group by means of a single bond. The attachment points of the alkylene chain to the rest of the molecule and to the radical group may be through any one or two carbons within the chain. Unless otherwise specifically indicated in the descriptive report, an alkylene chain may optionally be substituted.

[0273] “Alkenyl” or “alkenyl group” refers to a linear or branched hydrocarbon chain radical with two to twelve carbon atoms and with one or more carbon-carbon double bonds. Each alkenyl group is linked to the rest of the molecule by a single bond. The alkenyl group comprising any number of carbon atoms from 2 to 12 is included. An alkenyl group comprising up to 12 carbon atoms is a C2-C12 alkenyl, an alkenyl comprising up to 10 carbon atoms is a C2-C10 alkenyl, an alkenyl group comprising up to 6 carbon atoms is a C2-C6 alkenyl, and one comprising up to 5 carbon atoms is a C2-C5 alkenyl. A C2-C5 alkenyl includes C5 alkenyls, C4 alkenyls, C3 alkenyls, and C2 alkenyls. A C2-C6 alkenyl group includes all the chemical moieties described above for C2-C5 alkenyls, but also includes C6 alkenyls.A C2-C6 alkenyl group includes all the chemical moieties described above for C2-C5 alkenyl groups, but also includes C7, C8, C9, and C10 alkenyl groups. Similarly, a C2-C12 alkenyl group includes all the previous chemical moieties, but also includes C11 and C12 alkenyl groups.Non-limiting examples of C2-C12 alkenyl include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), iso-propenyl, 2-methyl-1propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenila, 3nonenila, 4-none, 5-none, 6-none, 7-none, 8-none, 1-none, 2-none, 3-none, 4-none, 5-none, 6-none, 7-none, 8-none, 9-none, 1-none, 2-none, 3-none, 4-undervalued, 5-undervalued, 6-undervalued, 7-undervalued, 8-undervalued, 9-undervalued, 10-undervalued, 1-undervalued, 2-undervalued, 3-undervalued, 4-undervalued, 5-undervalued, 6-undervalued, 7-undervalued,. Petition 870250103180, de 11 / 11 / 2025, pag. 48 / 393 41 / 383 8-dodecenyl, 9-dodecenyl, 10-dodecenyl and 11-dodecenyl. Unless otherwise specifically indicated in the descriptive report, an alkenyl group may optionally be substituted.

[0274] “Alkenylene” or “alkenylene chain” refers to a linear or branched divalent hydrocarbon chain radical having from two to twelve carbon atoms and having one or more carbon-carbon double bonds. Non-limiting examples of C2-C12 alkenylene include ethene, propene, butene, and the like. The alkenylene chain is linked to the rest of the molecule by a single bond and to the radical group by a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group may be via one carbon or any two carbons within the chain. Unless otherwise specifically indicated in the descriptive report, an alkenylene chain may optionally be substituted.

[0275] “Alkynyl” or “alkynyl group” refers to a linear or branched hydrocarbon chain radical with two to twelve carbon atoms and one or more carbon-carbon triple bonds. Each alkynyl group is linked to the rest of the molecule by a single bond. An alkynyl group comprising any number of carbon atoms from 2 to 12 is included. An alkynyl group comprising up to 12 carbon atoms is a C2-C12 alkynyl, an alkynyl group comprising up to 10 carbon atoms is a C2-C10 alkynyl, an alkynyl group comprising up to 6 carbon atoms is a C2-C6 alkynyl, and one comprising up to 5 carbon atoms is a C2-C5 alkynyl. A C2-C5 alkynyl includes C5 alkynyls, C4 alkynyls, C3 alkynyls, and C2 alkynyls. A C2-C6 alkynyl group includes all the chemical moieties described above for C2-C5 alkynyl groups, but also includes C6 alkynyl groups.A C2-C10 alkynyl group includes all the chemical moieties described above for C2-C5 and C2-C6 alkynyl groups, but also includes C7, C8, C9, and C10 alkynyl groups. Similarly, a C2-C12 alkynyl group includes all the previous chemical moieties, but also includes C11 and C12 alkynyl groups. Non-limiting examples of C2-C12 alkynyl groups include ethinyl, propynyl, butynyl, pentinyl, and the like. Unless otherwise specifically indicated in the descriptive report, an alkynyl group may be... Petition 870250103180, dated 11 / 11 / 2025, p. 49 / 393 42 / 383 optionally replaced.

[0276] “Alkynylene” or “alkynylene chain” refers to a linear or branched divalent hydrocarbon chain radical with two to twelve carbon atoms and one or more carbon-carbon triple bonds. Non-limiting examples of C2-C12 alkynylene include ethynylene, propargylene, and the like. The alkynylene chain is linked to the rest of the molecule by a single bond and to the radical group by a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group may be through any one or two carbons within the chain. Unless otherwise specifically indicated in the descriptive report, an alkynylene chain may optionally be substituted.

[0277] “Alkoxy” refers to a radical of the formula -ORa where Ra is an alkyl, alkenyl or alkynyl radical, as defined above, containing from one to twelve carbon atoms. Unless otherwise specifically indicated in the descriptive report, an alkoxy group may optionally be substituted.

[0278] “Alkylamino” refers to a radical of the formula NHRa or -NRaRa where each Ra is independently an alkyl, alkenyl or alkynyl radical, as defined above, containing from one to twelve carbon atoms. Unless otherwise specifically indicated in the descriptive report, an alkylamino group may optionally be substituted.

[0279] “Aryl” refers to a radical hydrocarbon ring system comprising hydrogen, 6 to 18 carbon atoms, and at least one aromatic ring. For purposes of this invention, the aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused, spiro, or bridging ring systems. Aryl radicals include, but are not limited to, aryl radicals derived from aceantrylene, acenaphthylene, acephenantrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. Unless otherwise specifically indicated in the descriptive report, the term “aryl” shall include aryl radicals that are optionally substituted. Petition 870250103180, dated 11 / 11 / 2025, page 50 / 393 43 / 383

[0280] “Aralkyl” or “arylalkyl” refers to a radical of the formula -Rb-Rc where Rb is an alkylene group, as defined above, and Rc is one or more aryl radicals as defined above, for example, benzyl, diphenylmethyl and the like. Unless otherwise specifically indicated in the descriptive report, an aralkyl group may optionally be substituted.

[0281] “Carbocyclyl”, “carbocyclic ring” or “carbocycle” refers to a non-aromatic, saturated and unsaturated ring structure in which the atoms forming the ring are each carbon. Carbocyclic rings may comprise from 3 to 20 carbon atoms in the ring. Carbocyclic rings include cycloalkyl, cycloalkenyl and cycloalkynyl, as defined in this document. Unless otherwise specifically indicated in the descriptive report, a carbocyclyl group may optionally be substituted.

[0282] “Cycloalkyl” refers to a fully saturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which may include fused, spiro or bridging ring systems, having from three to twenty carbon atoms, for example, having from three to ten carbon atoms, and which is linked to the rest of the molecule by a single bond. Monocyclic cycloalkyl radicals include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl, decalinyl, 7,7-dimethylbicyclo[2.2.1]heptanyl and the like. Unless otherwise specifically indicated in the descriptive report, a cycloalkyl group may optionally be substituted.

[0283] “Polycyclic” refers to ring systems comprising 2 or more rings, for example 2, 3 or 4 rings. Polycyclic rings can be fused, spiral or bridge ring systems.

[0284] “Polycyclic cycloalkylene” refers to a fully saturated divalent non-aromatic polycyclic hydrocarbon ring consisting solely of carbon and hydrogen atoms, having from four to twenty carbon atoms, for example, having from four to ten carbon atoms, and which is linked Petition 870250103180, dated 11 / 11 / 2025, page 51 / 393 44 / 383 to the rest of the molecule (e.g., as shown in Formula I) by two single bonds. The polycyclic cycloalkylene may include fused, spiro, or bridging ring systems. The polycyclic cycloalkylene may include, for example, bicyclo[2.2.2]octanylene, cubanylene, bicyclo(1.1.1)pentylene, adamantylene, norbornylene, decalynylene, 7,7-dimethyl-bicyclo[2.2.1]heptanylene, and the like. Unless otherwise specifically indicated in the descriptive report, a cycloalkylene group may optionally be substituted.

[0285] “Haloalkyl refers to an alkyl radical, as defined above, which is substituted by one or more halo radicals, as defined above, for example, trifluoromethyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl and the like. Unless otherwise specifically indicated in the descriptive report, a haloalkyl group may optionally be substituted.

[0286] “Haloalkenyl” refers to an alkenyl radical, as defined above, which is replaced by one or more halo radicals, as defined above, for example, 1-fluoropropenyl, 1,1-difluorobutenyl and the like. Unless otherwise specifically indicated in the descriptive report, a haloalkenyl group may optionally be substituted.

[0287] “Haloalkynyl” refers to an alkynyl radical, as defined above, which is replaced by one or more halo radicals, as defined above, for example, 1-fluoropropynyl, 1-fluorobutynyl and the like. Unless otherwise specifically indicated in the descriptive report, a haloalkynyl group may optionally be substituted.

[0288] “Heterocyclyl”, “heterocyclic ring” or “heterocycle” refers to a non-aromatic, saturated or unsaturated radical of 3 to 20 members, consisting of two to twelve carbon atoms and one to six heteroatoms selected from nitrogen, oxygen or sulfur. Unless otherwise specifically indicated in the descriptive report, the heterocyclyl radical may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused, spiro or bridging ring systems; and the nitrogen, carbon or sulfur atoms Petition 870250103180, dated 11 / 11 / 2025, page 52 / 393 45 / 383 sulfur in the heterocyclyl radical can be optionally oxidized; the nitrogen atom can be optionally quaternized; and the heterocyclyl radical can be partially or fully saturated. Examples of such heterocyclic radicals include, but are not limited to, dioxolanyl, tienyl[1,3]ditianyl, decahydroisoquinoline, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidinyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tritianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl and 1,1-dioxo-thiomorpholinyl. Unless otherwise specifically indicated in the descriptive report, a heterocyclyl group may optionally be substituted.

[0289] “Heterocycloalkyl” refers to a radical of the formula -Rb-Re where Rb is an alkylene group as defined above and Re is a heterocyclyl radical as defined above. Unless otherwise specifically indicated in the descriptive report, a heterocycloalkyl group may optionally be substituted.

[0290] “N-heterocyclyl” refers to a heterocyclyl radical as defined above, containing at least one nitrogen and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom in the heterocyclyl radical. Unless otherwise specifically indicated in the descriptive report, an N-heterocyclyl group may optionally be substituted.

[0291] “Heteroaryl” refers to a radical ring system of 5 to 20 members comprising hydrogen atoms, one to thirteen carbon atoms, one to six heteroatoms selected from nitrogen, oxygen, and sulfur, and at least one aromatic ring. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused or bridging ring systems; the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may optionally be oxidized; and the nitrogen atom may optionally be quaternized. Examples include, but are not limited to, azepinyl, Petition 870250103180, dated 11 / 11 / 2025, page 53 / 393 46 / 383 acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzo-oxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophene), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophene, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidine, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl,quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thienyl. Unless otherwise specifically indicated in the descriptive report, a heteroaryl group may optionally be substituted.

[0292] “Heteroarylene” refers to a 5- to 20-membered divalent radical ring system comprising hydrogen atoms, one to thirteen carbon atoms, one to six heteroatoms selected from nitrogen, oxygen, and sulfur, and at least one aromatic ring comprising at least one heteroatom selected from nitrogen, oxygen, and sulfur. For purposes of this disclosure, the heteroarylene radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused or bridging ring systems; the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may optionally be oxidized; the nitrogen atom may optionally be quaternized.Examples include, but are not limited to, azepinylene, acridinylene, benzimidazolylene, benzothiazolylene, benzindolylene, benzodioxolylene, benzofuranylene, benzo-oxazolylene, benzothiazolylene, benzothiadiazolylene, benzo[b][1,4]dioxepinylene, 1,4-benzodioxanylene, benzonaphthofuranylene, benzoxazolylene, benzodioxolylene, benzodioxylene, benzopyranylene, benzopyranonylene, benzofuranylene, benzofuranonylene, benzothienylene (radical). Petition 870250103180, dated 11 / 11 / 2025, page 54 / 393 47 / 383 benzothiophene divalent), benzotriazolylene, benzo[4,6]imidazo[1,2-a]pyridinylene, carbazolylene, cinnolinylene, dibenzofuranylene, dibenzothiophene, furanylene, furanonylene, isothiazolylene, imidazolylene, indazolylene, indazolylene, indazolylene, isoindolylene, indolinylene, isoindolylene, indolinylene, isoindolylene, isoquinolylene, indolizinylene, isoxazolylene, naphthyridinylene, oxadiazolylene, 2-oxoazepinylene, oxazolylene, oxiranylene, 1oxidopyridinylene, 1-oxidopyrimidinylene, 1-oxidopyrazinylene, 1-oxidopyridazinylene, 1-phenyl-1H-pyrrolylene, phenazinylene, phenothiazinylene, phenoxazinylene, phthalazinylene, pteridinylene, purinylene, pyrrolylene, pyrazolylene, pyridinylene, pyrazinylene, pyrimidinylene, pyridazinylene, quinazolinylene, quinoxalinylene, quinolinylene, quinuclidinylene, isoquinolinylene, tetrahydroquinolinylene, thiazolylene, thiadiazolylene, triazolylene, tetrazolylene, triazinylene and thiophene (for example, thienylene).Unless otherwise specifically indicated in the descriptive report, a heteroarylene group may optionally be substituted.

[0293] “N-heteroaryl” refers to a heteroaryl radical as defined above, containing at least one nitrogen and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. Unless otherwise specifically indicated in the descriptive report, an N-heteroaryl group may be optionally substituted.

[0294] “Heteroarylalkyl” refers to a radical of the formula -Rb-Rf where Rb is an alkylene chain as defined above and Rf is a heteroaryl radical as defined above. Unless otherwise specifically indicated in the descriptive report, a heteroarylalkyl group may optionally be substituted.

[0295] “Thioalkyl” refers to a radical of the formula -SRa where Ra is an alkyl, alkenyl or alkynyl radical, as defined above, containing from one to twelve carbon atoms. Unless otherwise specifically indicated in the descriptive report, a thioalkyl group may optionally be substituted.

[0296] The term “replaced” used in this document Petition 870250103180, dated 11 / 11 / 2025, p. 55 / 393 48 / 383 means any of the above groups (for example, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, carbocyclyl, cycloalkyl, cycloalkylene, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, haloalkyl, heterocyclyl, N-heterocyclyl, heterocyclylalkyl, heteroaryl, N-heteroaryl and / or heteroarylalkyl) in which at least one hydrogen atom is replaced by a bond to non-hydrogen atoms, such as, but not limited to: a halogen atom, such as F, Cl, Br and I; an oxygen atom in groups such as hydroxyl groups, alkoxy groups and ester groups; a sulfur atom in groups such as thiol groups, thioalkyl groups, sulfone groups, sulfonyl groups and sulfoxide groups; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides and enamines;a silicon atom in groups such as trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups and triarylsilyl groups; and other heteroatoms in various other groups.

[0297] “Substituted” also means any of the above groups in which one or more hydrogen atoms are replaced by a higher-order bond (e.g., a double or triple bond) to a heteroatom, such as oxygen in oxo, carbonyl, carboxyl, and ester groups; and nitrogen in groups such as imines, oximes, hydrazones, and nitriles. For example, “substituted” includes any of the above groups in which one or more hydrogen atoms are replaced by -NRgRh, -NRgC(=O)Rh, -NRgC(=O)NRgRh, -NRgC(=O)ORh, -NRgSO2Rh, -OC(=O)NRgRh, -ORg, -SRg, -SORg, -SO2Rg, -OSO2Rg, -SO2ORg, =NSO2Rg, and -SO2NRgRh. “Replaced” also means any of the above groups in which one or more hydrogen atoms are replaced by -C(=O)Rg, -C(=O)ORg, -C(=O)NRgRh, -CH2SO2Rg, -CH2SO2NRgRh.In the above, Rg and Rh are the same or different and independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclyl, N-heterocyclyl, heterocyclylalkyl, heteroaryl, N-heteroaryl and / or heteroarylalkyl. “Substituted” also includes any of the above groups in which. Petition 870250103180, dated 11 / 11 / 2025, p. 56 / 393 49 / 383 One or more hydrogen atoms are replaced by a bond to an amino, cyano, hydroxyl, imino, nitro, oxo, thioxo, halo, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclyl, N-heterocyclyl, heterocyclylalkyl, heteroaryl, N-heteroaryl and / or heteroarylalkyl group. In addition, each of the preceding substituents may also be optionally replaced by one or more of the above substituents.

[0298] As used in this document, the symbol “ ” (hereinafter referred to as a “fixing point linkage”) denotes a linkage that is a point linkage between two chemical entities, one of which is represented as being linked to the fixing point linkage and the other is not represented as being linked to the fixing point linkage. For example, “1” indicates that the chemical entity “XY” is linked to another chemical entity by means of the fixing point linkage. Furthermore, the specific point linkage to the unrepresented chemical entity can be specified by inference. For example, the compound CH3-RL, where RL is H or “ infers that when RL is “XY”, the fixing point linkage is the same linkage by which RL is represented as being linked to CH3.

[0299] In this descriptive report, unless otherwise indicated, the term “pharmaceutically acceptable” is used to characterize a chemical portion (e.g., a salt, dosage form, or excipient) as being appropriate for use according to medical common sense. In general, a pharmaceutically acceptable chemical portion has one or more benefits that outweigh any deleterious effects the chemical portion may have. Deleterious effects may include, for example, excessive toxicity, irritation, allergic response, and other problems and complications.

[0300] The term “pharmaceutically acceptable salt” includes Petition 870250103180, dated 11 / 11 / 2025, page 57 / 393 50 / 383 Acid and base addition salts. Pharmaceutically acceptable salts include those obtained by reacting the active compound that functions as a base with an inorganic or organic acid to form a salt, for example, salts of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, camphorsulfonic acid, oxalic acid, maleic acid, succinic acid, citric acid, formic acid, hydrobromic acid, benzoic acid, tartaric acid, fumaric acid, salicylic acid, mandelic acid, carbonic acid, etc. Those skilled in the art will further recognize that acid addition salts can be prepared by reacting the compounds with the appropriate inorganic or organic acid by any one of several known methods.

[0301] The compounds of the invention, or their pharmaceutically acceptable salts, may contain one or more asymmetric centers and may therefore give rise to enantiomers, diastereomers and other stereoisomeric forms which may be defined, in terms of absolute stereochemistry, as (R)- or (S)- or as (D)- or (L)- for amino acids. The present disclosure is intended to include all such possible isomers, as well as their racemic and optically pure forms, whether or not they are specifically described in this document. The optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, for example, chromatography and fractional crystallization.Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high-performance liquid chromatography (HPLC). When the compounds described in this document contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, the compounds are intended to include both E and Z geometric isomers. Similarly, all tautomeric forms should also be included.

[0302] A “stereoisomer” refers to a compound made of the same atoms linked by the same bonds, but with different three-dimensional structures that are not interchangeable. The present disclosure Petition 870250103180, dated 11 / 11 / 2025, page 58 / 393 51 / 383 contemplates various stereoisomers and mixtures thereof and includes "enantiomers," which refers to two stereoisomers whose molecules are non-superimposable mirror images of each other.

[0303] The term “treat,” as used in this document in relation to a patient, refers to the improvement of at least one symptom of the patient’s disorder. Treating may mean improving or at least partially alleviating a disorder or a symptom associated with a disorder.

[0304] An “effective amount” means the amount of a compound or pharmaceutical formulation that, when administered to a patient to treat a state, disorder or condition, is sufficient to effect such treatment.

[0305] The term “therapeutically effective” as applied to dose or quantity refers to the amount of a compound or pharmaceutical formulation that is sufficient to result in a desired clinical benefit after administration to a patient who needs it. A “therapeutically effective quantity,” in some embodiments, is a dose or quantity of a compound or pharmaceutical formulation that is sufficient to result in prophylaxis after administration to a patient who needs it.

[0306] The terms “subject”, “individual” and “patient” are used interchangeably in this document to refer to a vertebrate, such as a mammal. The mammal may be, for example, a mouse, a rat, a rabbit, a cat, a dog, a pig, a sheep, a horse, a non-human primate (e.g., cynomolgus monkey, chimpanzee) or a human. COMPOUNDS

[0307] In several embodiments, disclosure provides DPP1 inhibitor of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or Table 1. FORMULAS

[0308] In some embodiments, the present disclosure provides a compound of formula (I), Petition 870250103180, dated 11 / 11 / 2025, p. 59 / 393 52 / 383 XR1

[0309] (I), or a pharmaceutically acceptable salt or deuterated form thereof.

[0310] In some embodiments, the present disclosure provides a compound of Formula (II): _ H R1

[0311] (II), or a pharmaceutically acceptable salt or deuterated form thereof.

[0312] In some embodiments, the present disclosure provides a compound of Formula (III):

[0313] (III), or a pharmaceutically acceptable salt or deuterated form thereof, wherein

[0314] In some embodiments, the present disclosure provides a compound of Formula (IV):

[0315] (IV), or a pharmaceutically acceptable salt or deuterated form thereof, wherein Petition 870250103180, dated 11 / 11 / 2025, p. 60 / 393 53 / 383

[0316] In some embodiments, the present disclosure provides a compound of Formula (V),

[0317] (V), or a pharmaceutically acceptable salt or deuterated form thereof.

[0318] In some embodiments, the present disclosure provides a compound of formula (VI),

[0319] (VI), or a pharmaceutically acceptable salt or deuterated form thereof.

[0320] In some embodiments, the present disclosure provides a compound of formula (VII),

[0321] (VII), or a pharmaceutically acceptable salt or deuterated form thereof.

[0322] In some embodiments, the present disclosure provides a compound of formula (XIV), Petition 870250103180, dated 11 / 11 / 2025, p. 61 / 393 54 / 383

[0323] or a pharmaceutically acceptable salt or deuterated form thereof.

[0324] In some embodiments, the present disclosure provides a compound of formula (VIII),

[0325] (VIII), or a pharmaceutically acceptable salt or deuterated form thereof.

[0326] In some embodiments, the present disclosure provides a compound of formula (IX),

[0327] (IX), or a pharmaceutically acceptable salt or deuterated form thereof.

[0328] In some embodiments, the present disclosure provides a compound of formula (X), Petition 870250103180, dated 11 / 11 / 2025, p. 62 / 393 55 / 383

[0329] (X), or a pharmaceutically acceptable salt or deuterated form thereof.

[0330] In some embodiments, the present disclosure provides a compound of Formula (XI),

[0331] (XI), or a pharmaceutically acceptable salt or deuterated form thereof.

[0332] In some embodiments, the present disclosure provides a compound of Formula (XII),

[0333] (XII), or a pharmaceutically acceptable salt or deuterated form thereof.

[0334] In some embodiments, the present disclosure provides a compound of Formula (XIII), Petition 870250103180, dated 11 / 11 / 2025, p. 63 / 393 56 / 383

[0335] (XIII), or a pharmaceutically acceptable salt or deuterated form thereof.

[0336] In some embodiments, the present disclosure provides a compound of Formula (XV),

[0337] (XV), or a pharmaceutically acceptable salt or deuterated form thereof.

[0338] In some embodiments, the present disclosure provides a compound of Formula (XVI),

[0339] (XVI), or a pharmaceutically acceptable salt or deuterated form thereof.

[0340] In some embodiments, the present disclosure provides a compound of Formula (XVII), Petition 870250103180, dated 11 / 11 / 2025, p. 64 / 393 57 / 383

[0341] (XVII), or a pharmaceutically acceptable salt or deuterated form thereof.

[0342] In some embodiments, the present disclosure provides a compound of Formula (XVIII),

[0343] deuterated form of the same.

[0344] compound of Formula (XIX), (XVIII), or a pharmaceutically acceptable salt or In terms of modalities, this disclosure provides a

[0345] deuterated form of the same,

[0346] (XIX), or a pharmaceutically acceptable salt or In some embodiments, the present disclosure provides a compound of Formula (XX), Petition 870250103180, dated 11 / 11 / 2025, p. 65 / 393 58 / 383

[0347] (XX), or a pharmaceutically acceptable salt or deuterated form thereof.

[0348] R0, L, R1, R6, R7, R8, Rg, R10, n, X, X', X1, X2, X3, X4, RA, RB, ring B, ring C, ring D, ring E and ring F of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) are described in this document. R0

[0349] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or a deuterated form thereof, R0 is a 5 to 12 membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8 groups, or a 5 to 12 membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8 groups. In some embodiments, each R8 is independently selected from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6alkyl)2, N(C1-6alkyl)2, COOH, C1-6 alkyl, C1-6alkylOH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl.

[0350] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, each R8 is independently selected from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6alkyl)2, N(C1-6alkyl)2, COOH, C1-6 alkyl, C16alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 Petition 870250103180, dated 11 / 11 / 2025, p. 66 / 393 59 / 383 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl.

[0351] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R8 is H, OH, halogen, NH2, COOH, C1-6 alkyl, C1-6 alkylOH, C1-6 alkoxy or C1-6 alkoxy halogenated.

[0352] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R8 is H, OH, halogen, NH2, COOH, unsubstituted C1-6 alkyl, C1-6 alkyl-OH, unsubstituted C1-6 alkoxy or halogenated C1-6 alkoxy.

[0353] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R8 is hydrogen, methoxy or hydroxy.

[0354] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R8 is methoxy.

[0355] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R8 is OH.

[0356] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R8 is hydrogen.

[0357] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or a form Petition 870250103180, dated 11 / 11 / 2025, p. 67 / 393 60 / 383 deuterated from the same, R0 is a 5- to 12-membered monocyclic heterocycle containing 3 heteroatoms selected from N, S, O, wherein the monocyclic heterocycle is optionally substituted by 1 to 3 R8 groups. In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0e

[0358] or in what

[0359] Xi and X2 are independently O, S, NH, N(C-alkyl) or CR12R13, wherein at least one of Xi and X2 is not CR12R13;

[0360] X3 is O, S, NH or N(Ci-6 alkyl);

[0361] R8 is H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-e-alkyl), N(C1-e-alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, S(O)2NH2, C1-6 alkoxy or C1-6 halogenated alkoxy;

[0362] Ri2e H, halogen, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, S(O)2NH2, C1-6 alkoxy or C1-6 halogenated alkoxy

[0363] Ri3 is independently H, halogen or C1-C6 alkyl;

[0364] RA is H, C1-ealkyl, C1-6 alkylene-carbocyclyl or C16 alkylene-heteroaryl; and

[0365] RBé C1-ealkyl, C2-ealkenyl, C1-ealkylenecarbocyclyl or C1-6-alkyleneheteroaryl, or

[0366] RAe RBsão taken together to form a heterocyclyl; and Petition 870250103180, dated 11 / 11 / 2025, p. 68 / 393 61 / 383

[0367] m is 0, 1, 2 or 3.

[0368] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R13 is independently H, F, Cl, Br, I or C1-C6 alkyl. In some embodiments, R13 is independently H, F or C1-C6 alkyl. In some embodiments, R13 is H.

[0369] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R12 is H, OH, halogen, NH2, COOH, unsubstituted C1-4 alkyl, C1-4 alkyl-OH, unsubstituted C1-4 alkoxy or halogenated C1-4 alkoxy.

[0370] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R12 is hydrogen.

[0371] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI) or a pharmaceutically acceptable salt thereof or deuterated form thereof, X is O, S CHF or CF2.

[0372] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or deuterated form thereof, X is O, S or CF2.

[0373] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or deuterated form thereof, X is O.

[0374] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), Petition 870250103180, dated 11 / 11 / 2025, p. 69 / 393 62 / 383 (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or deuterated form thereof, X is S.

[0375] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or deuterated form thereof, X is CF2.

[0376] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, Xi and X2 are independently O, S, NH, N(C1-6 alkyl), or CR12R13, wherein at least one of Xi and X2 is not CR12R13. In some embodiments, at least Xi is O, S, NH, N(C1-6 alkyl).

[0377] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, Xi and X2 are independently O, S or NH, N(C1-6 alkyl).

[0378] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, Xi and X2 are independently O or NH.

[0379] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, X3 is O, S, NH or N(C1-6 alkyl).

[0380] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, X3 is O, S, NH.

[0381] In embodiments of compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), Petition 870250103180, dated 11 / 11 / 2025, p. 70 / 393 63 / 383 (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, X3 is O.

[0382] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é:HN z z.

[0383] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RAe H, C1-6 alkyl, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl.

[0384] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof,

[0385] RA is H, Ci-6alkyl, Ci-6alkylene-carbocyclyl or Ci— 6-alkylene-heteroaryl; and

[0386] RBe C1-6 alkyl, C2-6 alkenyl, C1-6 alkylenecarbocyclyl or C1-6 alkyleneheteroaryl; or

[0387] RAe RBsão taken together to form a heterocyclyl.

[0388] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RAeH or C1-6 alkyl.

[0389] In one embodiment of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), Petition 870250103180, dated 11 / 11 / 2025, p. 71 / 393 64 / 383 (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RAé H.

[0390] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RAe C1-6 alkyl.

[0391] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RAe -CH3.

[0392] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RBé C1-6 alkyl, C2-6 alkenyl, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl.

[0393] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RBé C1-6 alkyl, C2-6 alkenyl, C1-6 alkylene-carbocyclyl or C1-6 alkylene-heteroaryl.

[0394] In embodiments of compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RBé C1-6 alkyl, C1-6 alkylene-aryl or C1-6 heteroaryl-alkylene of 5 to 6 members.

[0395] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, RBé Ci-6alkyl.

[0396] In embodiments of the compounds of Formula (I), (II), Petition 870250103180, dated 11 / 11 / 2025, p. 72 / 393 65 / 383 (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), RA and RB are taken together to form a heterocyclyl.

[0397] Another modality is a product obtained by any of the processes or examples disclosed in this document.

[0398] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é r® r® __ReaRbrçR£ z R8_C_£ z r8_^£ Z X2'' ,X2'' ,X2'' , or .

[0399] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0 is . In some embodiments, m is 2 or 3.

[0400] In some modalities, m is 2. In modalities R8 C of the compounds, R0ex2 . R8 Chi, I Jr

[0401] In modalities of, R0 is X2 where Xi is O, X2 is NH and R8 is Ci-e alkoxy. r® í I / 1...... . ..... ,

[0402] In some modalities, R0éH. Petition 870250103180, dated 11 / 11 / 2025, p. 73 / 393 66 / 383

[0403] In some forms, R0 is h or

[0404] In some modalities, R0 is h

[0405] In some modalities, R0éH.

[0406] In an embodiment of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof or a deuterated form thereof, R0 is or

[0407] In some modalities, R0 or

[0408] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a form Petition 870250103180, dated 11 / 11 / 2025, p. 74 / 393 67 / 383 deuterada do mesmo, R0é R8

[0409] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0 is —nh, wherein each R8 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy or halogenated C1-6 alkoxy. or

[0410] In some modes, R0 is:HN

[0411] In some modalities, R0éHN

[0412] In some modes, R0 is:HN

[0413] In some modalities, R0é /

[0414] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a form Petition 870250103180, dated 11 / 11 / 2025, p. 75 / 393 68 / 383 deuterated from the same, R0é

[0415] In some sports, R0 is

[0416] In some modalities, R0éHN

[0417] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é

[0418] In some sports, R0 is

[0419] In some modalities, R0éHN

[0420] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é Petition 870250103180, dated 11 / 11 / 2025, p. 76 / 393 69 / 383

[0421] In some sports, R0 is

[0422] In some disciplines, R0 is HN

[0423] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é

[0424] In some sports, R0 is

[0425] In some sports, R0 is

[0426] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é

[0427] In some sports, R0 is Petition 870250103180, dated 11 / 11 / 2025, p. 77 / 393 70 / 383

[0428] In some sports, R0 is

[0429] In some sports, R0 is

[0430] In some sports, R0 is

[0431] In embodiments of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é: In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a Xr. (CH2)n2(CH2)n1*2\ '' (OH2)n^ν , , where each n1, n2 and n3 is a deuterated form of them, R0é Petition 870250103180, dated 11 / 11 / 2025, p. 78 / 393 71 / 383 independently an integer from 0 to 3, and the total sum of n1, n2 and n3 is < 4, Xi and X2 are independently O, S, NR6 or CR12R13, wherein at least one of Xi and X2 is not CR12R13; each R6, R12 and R13 is independently H, halo or C1-C6 alkyl. In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R 0é OH or , where R8 is H, F, OH, CH3, OCH3, OCHF2, OCF3, OCH2 CH3 or -CH2 OCH3.

[0434] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é or

[0435] In some sports, R0 is or Petition 870250103180, dated 11 / 11 / 2025, p. 79 / 393 72 / 383

[0436] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0 is a 5 to 12 membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8. In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, the 5 to 12 membered polycyclic heterocycle is

[0437] (i) 5 to 12 membered spiro heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the spiro heterocycle is optionally replaced by 1 to 3 R8,

[0438] (ii) fused heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, O, wherein the fused heterocycle is optionally replaced by 1 to 3 R8, or

[0439] (iii) 7 to 12 membered bridging heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the bridging heterocycle is optionally replaced by 1 to 3 R8.

[0440] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0 is a 5 to 12 membered spiro heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the spiro heterocycle is optionally replaced by 1 to 3 R8.

[0441] In some forms, the 5-spiro-heterocycle Petition 870250103180, dated 11 / 11 / 2025, p. 80 / 393 73 / 383 with 12 members is , ml and m2 are each independently 0, 1 or 2, provided that m1 and m2 are not 0, or m1 and m2 are not 2, and e is 1 or 2.

[0442] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0 is a 5 to 12 membered fused heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the fused heterocycle is optionally replaced by 1 to 3 R8.

[0443] In some embodiments, the fused heterocycle of 12 members is in 5,

[0444] m4 is 0 or 1,

[0445] m5 is 1 or 2,

[0446] X2 is O, S, NH, N(Ci-ealkyl) or CRI2RI3,

[0447] R12 is selected from H, halogen, cyano, hydroxyl, NH2, NH(C1-e-alkyl), N(C1-e-alkyl)2, COOH, C1-6-alkyl, -CONH2, S(=O)NH2, -S(O)2NH2, C1-6-alkoxy or halogenated C1-6-alkoxy;

[0448] Ri3 is independently H, F, Cl, Br, I or Ci-C6 alkyl.

[0449] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a Petition 870250103180, dated 11 / 11 / 2025, p. 81 / 393 74 / 383 m5 is deuterated form of the same, • , or

[0450] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é

[0451] or, in which

[0452] X2 is O, S, NH, N (Ci-ealkyl) or CRI2RI3

[0453] R12 is H, halogen, cyano, hydroxyl, NH2, NH(C16alkyl), N(C1-6alkyl)2, COOH, C1-6alkyl, -CONH2, -S(=O)NH2, -S(O)2NH2, C16alkoxy or C16alkoxy halogenated;

[0454] Ri3é H, halogen or Ci-C6 alkyl;

[0455] each me m' is independently an integer from 0 to 3, and the total sum of me m' is < 3.

[0456] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a their deuterated form, R0é Ά .

[0457] In forms of the compounds of Formula (I), (II), Petition 870250103180, dated 11 / 11 / 2025, p. 82 / 393 75 / 383 (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é1, wherein X2é NH, O or St.

[0458] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a hn y-f deuterated form of them, R0é1ou

[0459] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0é or NH

[0460] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a >CH2)mx2\ m'(H2C) their deuterated form, R0é

[0461] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a NH their deuterated form, R0é

[0462] In embodiments of the compounds of Formula (I), (II), Petition 870250103180, dated 11 / 11 / 2025, p. 83 / 393 76 / 383 (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R0 is a 7 to 12 membered bridging heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the bridging heterocycle is optionally replaced by 1 to 3 R8.

[0463] In some modalities, the 7- to 12-member bridge heterocycle is HN B—A or each of which is optionally replaced by 1 to 4 R8, where

[0464] A is a linkage, -O-, -O-CH2-, -CH2-O-CH2-, CH2OCH2CH2-, -CH2-, -CH2CH2-, or -CH2NH-,

[0465] B is N or CH,

[0466] m4 is 0 or 1,

[0467] p1 is 0, 1 or 2,

[0468] q1 is 1, 2 or 3.

[0469] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a their deuterated form, R0é or

[0470] In embodiments of compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), Petition 870250103180, dated 11 / 11 / 2025, p. 84 / 393 77 / 383 (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R is selected from or NH NH

[0471] a pharmaceutical salt In embodiments of the compounds of Formula (I), or an acceptable form thereof, or a deuterated form thereof, L is polycyclic cycloalkylene, polycyclic arylene or polycyclic heteroarylene.

[0472] In some embodiments, the polycyclic cycloalkylene is connected to R1 on a first quaternary carbon of the cycloalkylene nHR° .N The polycyclic group is independently connected to the quaternary carbon of the polycyclic cycloalkylene. through a second

[0473] In some embodiments, a first atom of a first ring of polycyclic arylene or polycyclic heteroarylene is connected to nHR° .N THE ee a second atom of a second ring of the polycyclic arylene or heteroarylene is connected to R1.

[0474] In some forms, L is independently replaced by 0 to 4 R10.

[0475] In embodiments, each R10 is independently =O, halogen, C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3 Petition 870250103180, dated 11 / 11 / 2025, p. 85 / 393 78 / 383 6cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6alkyl, N(C1-6alkyl)2, COOH, COC16alkyl, COOC1-6alkyl, CON1-6alkyl, CON(C1-6alkyl)2, NHCOC1-6alkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH.

[0476] In some embodiments, L is a polycyclic cycloalkylene.

[0477] In some embodiments, the polycyclic cycloalkylene comprises from 4 to 10 carbon atoms.

[0478] In some embodiments, the polycyclic cycloalkylene is connected to R1 on a first quaternary carbon of the polycyclic cycloalkylene°YRY^N 0w and independently connected to »' via a second quaternary carbon of the polycyclic cycloalkylene.

[0479] In embodiments of the compounds of Formula (I), either a pharmaceutically acceptable salt thereof, or a deuterated form thereof Petition 870250103180, dated 11 / 11 / 2025, page 86 / 393 79 / 383

[0481]

[0482] In modalities, L is In modalities, L is

[0483] In modalities, L is

[0484] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is polycyclic heteroarylene substituted by 0 to 4 R10. In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is a polycyclic heteroarylene comprising 8 to 12 ring atoms and is substituted by 0 to 4 R10. In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is a polycyclic heteroarylene comprising 9 to 10 ring atoms and is substituted by 0 to 4 R10. In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, the polycyclic heteroarylene comprises 8 to 10 ring atoms and is substituted by 0 to 4 R10.In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, the polycyclic heteroarylene comprises 8 to 9 ring atoms and is substituted by 0 to 4 R10. In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is a polycyclic heteroarylene comprising 9 ring atoms and 1 or 2 heteroatoms selected from O, N or S, and the polycyclic heteroarylene is substituted by 0 to 4 R10. In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is a polycyclic heteroarylene comprising 8 ring atoms and 1 to 3 heteroatoms selected from O, N or S, and the polycyclic heteroarylene is substituted by 0 to 4 R10. In forms of the compounds of Formula (I), or a salt. Petition 870250103180, dated 11 / 11 / 2025, p. 87 / 393 80 / 383 pharmaceutically acceptable thereof, or a deuterated form thereof, L is polycyclic heteroarylene substituted by zero (0) R10. In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is polycyclic heteroarylene substituted by one (1) R10.

[0485] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, L is BH-'—s is replaced by 0 to 4 R10, where ring B is a heteroaryl ring. When L is polycyclic heteroarylene, the polycyclic heteroarylene can have any -lL TBXI- -:4b orientation (for example, or ).

[0486] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, the polycyclic heteroarylene is substituted by 0 to 4 R10, wherein X' is O, S, NH or N(C1-6 alkyl). In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, the polycyclic heteroarylene is benzothienylene, indolylene or benzofuranylene substituted by 0 to 4 R10.

[0487] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, the polycyclic heteroarylene is either1, each of which is substituted by 0 to 4 R10.

[0488] In embodiments of the compounds of Formula (I), either a pharmaceutically acceptable salt thereof, or a deuterated form thereof Petition 870250103180, dated 11 / 11 / 2025, p. 88 / 393 81 / 383 same, polycyclic heteroarylene is replaced by 0 to 4 R10.

[0489] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, polycyclic heteroarylene is replaced by 0 to 4 R10.

[0490] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, L is benzothienylene substituted by 0 to 4 R10. / XV / '

[0491] In some forms, L is replaced by 0 to 4 R10. _;_L

[0492] In some forms, L is l'o^''' / or

[0493] In embodiments of the compounds of Formula (I), either a pharmaceutically acceptable salt thereof, or a deuterated form thereof They themselves, and are linked to the phenyl ring of, R1 is connected to the 5-member ring of in what Petition 870250103180, dated 11 / 11 / 2025, p. 89 / 393 82 / 383 I •I I is replaced by 0 to 4 R10.

[0494] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, wherein are connected to the 5-member ring of , and R1 is attached to the phenyl ring of replaced by 0 to 4 R10.

[0495] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, heteroarylene / polycyclic is

[0496] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, L is II I replaced by 1 to 4 R10.

[0497] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, L is III replaced by an R10. Petition 870250103180, dated 11 / 11 / 2025, p. 90 / 393 83 / 383

[0498] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, R10 is halo.

[0499] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, L is or

[0500] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, L is the polycyclic heteroarylene comprising 8 ring atoms and 1 or 2 heteroatoms selected from O, N or S, and the polycyclic heteroarylene is substituted by 0 to 4 R10.

[0501] In embodiments of the compounds of Formula (I), or a pharmaceutically acceptable salt or deuterated form thereof, L is F

[0502] In embodiments of the compounds of Formula (I) or (XVI), or a pharmaceutically acceptable salt or deuterated form thereof, L is ' ' ' , wherein each of the rings E and F is a heteroaryl or heterocyclyl of members comprising 1 to 3 heteroatoms selected from O, N or S.

[0503] In embodiments of the compounds of Formula (I) or (XVI), or a pharmaceutically acceptable salt or deuterated form thereof, L is '1, wherein each of rings E and F is a 5-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N or S.

[0504] In embodiments of the compounds of Formula (I) or Petition 870250103180, dated 11 / 11 / 2025, p. 91 / 393 84 / 383 (XVI), or a pharmaceutically acceptable salt or deuterated form thereof, where L is

[0505] In embodiments of the compounds of Formula (I) or (XVI), or a pharmaceutically acceptable salt or deuterated form thereof, in -i / TH that L is.

[0506] In embodiments of compounds of Formula (I), where L is polycyclic arylene.

[0507] In the forms of the compounds of Formula (I), in । íí η 1 । that L is .

[0508] In the modalities of the compounds of Formula (I), in XYYque L is '' .

[0509] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R10 is independently oxo, halogen, C1-6 alkyl, C1-6 alkoxy, -S-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, -N(C1-4 alkyl)2, -COOH, -COC1-6 alkyl, -COOC1-6 alkyl, CON1-6 alkyl, -CON(C1-6 alkyl)2, -NHCOC1-6 alkyl, or a heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and -COOH.

[0510] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), or a pharmaceutically acceptable salt thereof, or a Petition 870250103180, dated 11 / 11 / 2025, p. 92 / 393 85 / 383 deuterated form thereof, R10 is independently oxo, halogen, Ci-6 alkyl, Ci6 alkoxy, -SCi-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, -NH-Ci-6 alkyl, -N(Ci-4 alkyl)2, -COOH, -COC1-6 alkyl, -COOC1-6 alkyl, CON1—6 alkyl, -CON(Ci-6 alkyl)2, -NHCOCi-6 alkyl, or 4 to 7 membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are independently optionally substituted by 1-3 substituents selected from halogen, cyano, hydroxyl, NH2 and -COOH.

[0511] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R10 is independently halogen, C1-4 alkyl, C1-6 alkoxy, -SC1-6 alkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, -N(C1-6 alkyl)2, -COOH, -COC1-6 alkyl, -COOC1-6 alkyl, -CON1-6 alkyl, -CON(C1-6 alkyl)2, or -NHCOC1-6 alkyl; wherein each alkyl and alkoxy are independently substituted optionally with 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and -COOH.

[0512] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R10 is a halogen.

[0513] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R10 is fluoro.

[0514] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, n is 0.

[0515] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, n is 1. Petition 870250103180, dated 11 / 11 / 2025, p. 93 / 393 86 / 383

[0516] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, n is 2.

[0517] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, n is 1 and R10 is fluoro.

[0518] In embodiments of compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, n is 1 and the substituent R10 is located on the phenyl ring of L, for example,

[0519] In embodiments of the compounds of Formula (I), (V), (VI), (VII), (XI), (XII), (XIII), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, n is 1 and the substituent R10 is located on the thiophene ring of L, for example, r10 R1

[0520] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is (i) a 5- to 12-membered carbocyclyl optionally substituted by 1 to 3 Rg; (ii) a 6- to 18-membered aryl optionally substituted by 1 to 3 Rg; (iii) a 5- to 12-membered monocyclic heterocyclyl containing 1 to 3 heteroatoms selected from N, S or O, wherein the monocyclic heterocyclyl is optionally substituted by 1 to 3 Rg; (iv) a 5- to 12-membered monocyclic heteroaryl containing 1 to 3 heteroatoms selected from N, S or O, wherein the monocyclic heteroaryl is optionally substituted by 1 to 3 Rg; (v) Bicyclic heteroaryl of 7 to 14 members containing 1-3 heteroatoms selected from N, S or Petition 870250103180, dated 11 / 11 / 2025, p. 94 / 393 87 / 383 O, wherein the bicyclic heteroaryl is optionally replaced by 1 to 4 Rg; or (vi) a 7 to 20 membered tricyclic heteroaryl containing 1 to 3 heteroatoms selected from N, S, or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg. In some embodiments, R1 is a 5 to 12 membered carbocyclyl optionally replaced by 1 to 3 Rg. In some embodiments, R1 is a 6 to 18 membered aryl optionally replaced by 1 to 3 Rg. In some embodiments, R1 is a 5 to 12 membered monocyclic heterocyclyl containing 1 to 3 heteroatoms selected from N, S, or O, wherein the monocyclic heterocyclyl is optionally replaced by 1 to 3 Rg. In some embodiments, R1 is a 5- to 12-membered monocyclic heteroaryl containing 1 to 3 heteroatoms selected from N, S, or O, wherein the monocyclic heteroaryl is optionally replaced by 1 to 3 Rg. In some embodiments, R1 is a 7- to 14-membered bicyclic heteroaryl containing 1 to 3 heteroatoms selected from N, S, or O.in which the bicyclic heteroaryl is optionally replaced by 1 to 4 Rg. In some embodiments, R1 is a tricyclic heteroaryl of 7 to 20 members containing 1 to 3 heteroatoms selected from N, S, or O, in which the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg. In embodiments, each R is independently selected from hydrogen, SF5, =O, halogen, cyano, hydroxyl, nitro, NH2, COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6 alkenyloxy, C2-6 alkynyloxy, C36 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl, -N(C1-6 alkyl)2, -COC1-6 alkyl, -COOC1-6 alkyl, -CONH2, -CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, CON(C1-6 alkyl)2, -NHCOC1-6 alkyl, -NHCOC3-5 cycloalkyl, -P(O)(C1-6 alkyl), S(O)C1-ealkyl, -S(O)2C1-6 alkyl, -S(O)2 C3-6 cycloalkyl, -SO2 3- to 7-membered heterocyclyl, -S(O)NH2, -S(O)NHC1-6 alkyl, -S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2 C1-6 alkyl, C1-6alkylene-O-C1-6alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl,A 3- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, and the Rg is optionally substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6 alkoxy, hydroxyl, COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, and O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from =O, halogen, cyano, C1-6 alkyl, and Petition 870250103180, dated 11 / 11 / 2025, page 95 / 393 88 / 383 C1-6 haloalkyl.

[0521] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, Rg is selected from R6, R7, R11, R14 or R15, wherein

[0522] each R6 and R11 is independently selected from H, C1-6 alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0523] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0524] R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C16 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 a 3- to 7-membered heterocycle and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH;

[0525] Alternatively, R14e R15forma =O.

[0526] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a 5 to 12 membered carbocyclyl Petition 870250103180, dated 11 / 11 / 2025, p. 96 / 393 89 / 383 optionally replaced by 1 to 3 Rg groups. In modalities, R1 is or , each of which is optionally replaced by 1 to 3 Rg.

[0527] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is an aryl of 6 to 18 members optionally replaced by 1 to 3 Rg groups.

[0528] In modalities, R1 is or , where L is linked to R1 by the substitution of any hydrogen atom of R1, and where each R1 is optionally replaced by 1 to 3 Rg.

[0529] In modalities, R1 is

[0530]

[0531] In modalities, R1 is In modalities, R1 is o / —ç II / \ S—NN— II / The '—' the HN P II O N or Petition 870250103180, dated 11 / 11 / 2025, p. 97 / 393 90 / 383

[0532]

[0533]

[0534] In embodiments of compounds of formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a 5- to 12-membered monocyclic heterocycline containing heteroatoms selected from N, S, or O, wherein the monocyclic heterocycline is optionally substituted by 1 to 3 Rg groups. In embodiments, R1 is or । , where each one de R1é opcional se por 1 a 3 Rg.

[0535] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a 5- to 12-membered monocyclic heteroaryl containing heteroatoms selected from N, S, or O, wherein each of the monocyclic heteroaryl is optionally substituted by 1 to 3 Rg groups. In embodiments, R1 is N^, N--^, ', J or , each of which is optionally substituted by 1 to 3 Rg groups. In embodiments, R is independently H, halogen, C1-C6 alkyl, OSO2C1-C6 alkyl, or CN. In In modalities, R1 is, Petition 870250103180, dated 11 / 11 / 2025, p. 98 / 393 91 / 383

[0536] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a 7 to 14 membered bicyclic heteroaryl containing heteroatoms selected from N, S or O, wherein the bicyclic heteroaryl is optionally replaced by 1 to 4 Rg groups. In modalities, R1 is each of which is optionally replaced by 1 to 3 Rg groups. In modalities, R1 is or In modalities, R1 is

[0538] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is or R6, in which

[0539] Y is independently O, S, CHR6 or NR6; and

[0540] R6 is optionally substituted C1-6 alkyl with 1, 2 or 3 F, or with OH, O-C1-6 alkyl, N(C1-6 alkyl)2, cycloalkyl or heterocyclyl.

[0541] In some sports, Rié or

[0542] In embodiments of the compounds of Formula (I), (II), Petition 870250103180, dated 11 / 11 / 2025, p. 99 / 393 92 / 383 (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1é what

[0543] X4é NR6, O, CR7, CR14R15, S, S(O) or S(O)2,

[0544] Q is CH or N,

[0545] each R6 is selected independently from H, C16 alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0546] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0547] R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C16 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 a 3- to 7-membered heterocycle and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH;

[0548] Alternatively, R14e R15forma =O. Petition 870250103180, dated 11 / 11 / 2025, p. 100 / 393 93 / 383 R7 X / X^^N'X) '' I

[0549] In modalities, R1 is R6. R7 X / X^^N'X) ...... _ . ''' I

[0550] In some modes, R1 is R

[0551] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, R7 YVx4, R6. / 1X4 t 1 > / v\n ' YT >0 [II YYN or a deuterated form thereof, R1ér6, ,r > ?7,r6' / YY^-n ' XX oux, where

[0552] each X4 is independently NR6, O, CR14R15, S, S(O) or S(O)2,

[0553] each R6 is selected independently from H, C16 alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0554] each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O; wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; Petition 870250103180, dated 11 / 11 / 2025, page 101 / 393 94 / 383

[0555] R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 heterocycle of 3 to 7 members and a heterocycle of 4 to 7 members containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle groups are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH; alternatively, R14 and R15 form =O. In modalities, it is

[0556]

[0557] O, S, NR6 or CR14R15.

[0558] In some modes, X4 is independent. In embodiments, R6 is C1-6 alkyl, wherein C16 alkyl is optionally replaced by 1, 2 or 3 F, OH, OC1-6 alkyl, N(C1-6 alkyl)2, cycloalkyl or heterocyclyl.

[0559] In embodiments, cycloalkyl is cyclopropyl.

[0560] In embodiments, the heterocycline is tetrahydropyran. In embodiments R6é C1-6alkyl wherein said C1-6alkyl is optionally replaced by 1, 2 or 3 F.

[0561]

[0562]

[0563]

[0564]

[0565] In embodiments, R6 is methyl or ethyl. In embodiments, R6 is CH3. In some embodiments, R7 is H, F, Cl, or CH3. In embodiments, R7 is H. In some embodiments, R7 is H, halo, or C1- 6alkyl, R14 and R15 are independently H, halo or C1-6alkyl.

[0566] In modalities, each X4 is independently NH, O, S, CHF or CHF2.

[0567] In some modes, X4 is O. Petition 870250103180, dated 11 / 11 / 2025, p. 102 / 393 95 / 383 N

[0570] In modalities, R1 is o >o N

[0571]

[0572] In modalities, R1 is \ . In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, Petition 870250103180, dated 11 / 11 / 2025, p. 103 / 393 96 / 383 or a deuterated form thereof, R1 is optionally replaced by 1 to 4 Rg groups, wherein the C ring is a 7 to 8 membered heterocycle comprising 1 to 3 heteroatoms selected from O, S and N. the

[0573] In some forms, R1é0ou 'o, each of which is optionally replaced by 1 to 4 Rg groups.

[0574] In some sports, R1 is

[0575] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a 7 to 20 membered tricyclic heteroaryl containing heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg groups.

[0576] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a 7 to 20 membered tricyclic spiro heteroaryl containing heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg groups. Petition 870250103180, dated 11 / 11 / 2025, p. 104 / 393 97 / 383

[0577] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, in what

[0578] each R6 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or alkyleneO-alkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; and,

[0579] R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 heterocycle of 3 to 7 members and a heterocycle of 4 to 7 members containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH;

[0580] Alternatively, R14e R15forma =O.

[0581] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, Petition 870250103180, dated 11 / 11 / 2025, p. 105 / 393 98 / 383 x4xw or a deuterated form thereof, R1éD^EJ, where

[0582] W, X4 and Y2 are each independently CH or N, provided that at most one of W, X4 and Y2 can be N;

[0583] DE is N(H)-C(=O), N(G1-alkyl)-C(=O), CH2CH2, C(=O)-O or CH2-O;

[0584] R11 is H, C1-6 alkyl, alkylene-O-alkyl or heterocyclyl; and

[0585] iej are each independently 1, 2 or 3; provided that the sum of i+j is 2, 3 or 4.

[0586] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, W, X4 and Y2 are selected independently of CH and N, provided that at most one of W, X4 and Y2 may be N.

[0587] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, DE is selected from N(H)-C(O), N(C1-3-alkyl)-C(O), CH2CH2, C(O)-O and CH2-O.

[0588] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, DE is N(H)-C(O), N(CH3)-C(O), CH2CH2, C(O)-O or CH2-O.

[0589] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, DE is CH2-O; Petition 870250103180, dated 11 / 11 / 2025, p. 106 / 393 99 / 383

[0590] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R11 is H, alkylene-O-alkyl, or heterocyclyl.

[0591] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R11 is H, CH3OCH2CH2, or heterocyclyl.

[0592] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R11 is H, alkylene-O-alkyl, or oxetanyl, tetrahydrofuranyl, 4-tetrahydropyranyl or 3-tetrahydropyranyl.

[0593] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R11 is H, C1-3 alkyl, CH3OCH2CH2, oxetanyl, tetrahydrofuranyl, 4-tetrahydropyranyl or 3-tetrahydropyranyl.

[0594] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R11 is H, CH3- or oxetanyl.

[0595] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, i and j are each independently 1, 2 or 3; provided that the sum of i+j is 2, 3 or 4.

[0596] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, Petition 870250103180, dated 11 / 11 / 2025, p. 107 / 393 100 / 383 R11 is H, CH3, or oxetanyl; W is CH or N; X4 is CH or N; Y2 is CH; provided that at most one of W, X, and Y can be N; DE is selected from N(CH3)-C(O), CH2CH2, C(O)-O and CH2-O; i is 1 or 2 and j is 1 or 2, provided that the sum of i+j is 2, 3 or 4.

[0597] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof,

[0598]

[0599] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, R1 is a fused tricyclic heteroaryl of 7 to 20 members containing heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg groups.

[0600] In embodiments of the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (XIV), or a pharmaceutically acceptable salt thereof, Petition 870250103180, dated 11 / 11 / 2025, p. 108 / 393 101 / 383 , each of which is optionally replaced by 1 to 5 Rg, where R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, S(O)2C3-6 cycloalkyl, -SO2 heterocycle of 3 to 7 members and a heterocycle of 4 to 7 members containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0601] each R6 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or alkyleneO-alkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;

[0602] Ring D is selected from an 8-membered aryl and heteroaryl ring containing 1 to 3 heteroatoms, wherein the aryl and said heteroaryl ring are 5 to 8 members containing 1 to 3 heteroatoms, each independently Petition 870250103180, dated 11 / 11 / 2025, p. 109 / 393 102 / 383 optionally replaced by 1 to 3 Rg. In some embodiments, the D-ring is x''N'A^N, or '', each of which is optionally replaced by 1 to 3 FFF,, Petition 870250103180, dated 11 / 11 / 2025, p. 110 / 393 103 / 383

[0603] In embodiments, a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, is provided in this document.

[0604] In embodiments, a pharmaceutically acceptable salt of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or Petition 870250103180, dated 11 / 11 / 2025, p. 111 / 393 104 / 383 (XX). Other embodiments of the invention relate to a deuterated compound of (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX) or a pharmaceutically acceptable salt thereof, or a deuterated form thereof.

[0605] In some embodiments, a compound from Table 1 is provided in this document, or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, or a stereoisomer thereof. TABLE 1. N° of Compound Structure of Compound 101 n NI 101a / z IZ ° zoo 101b ~ N ™ -\ j? 1 rVo \ fRV Ν'-Vs / / S—< / °\ HI 101c o οΛ I z— oz^. θ ZX z / XX—J 101d N ΗΝ~Λ J? / / Γ— ( / °\ H X--S / 2^-q N υ Petition 870250103180, 11 / 11 / 2025, pág. 112 / 393 105 / 383 Petition 870250103180, 11 / 11 / 2025, pág. 113 / 393 106 / 383 103a N 0 '1' hn-xA J / r; J23 / / (S;rn H 103b Z / °X o M A- / N0 '1' 43 ΗΝ-'Χ .A ,.us; J23 / / fRH Ν' 103c N ΑΧ NN \ ο II / rz| HN^X ,AJ / R) 123 / / (R) INH 103d .. . (r ,.Qs; yy / ÍS?[ Ν' Petition 870250103180, 11 / 11 / 2025, pág. 114 / 393 107 / 383 Petition 870250103180, 11 / 11 / 2025, pág. 115 / 393 108 / 383 105b 105c 105d 105e 106 106a 106b Petition 870250103180, dated 11 / 11 / 2025, p. 116 / 393 109 / 383 106c Λη0 / (ΤΑ—0 HN—\(R) T \ i ys F 106d H n ax>° 0^—0 HN—\(R) J \ i \-7 ys F 106e H n A / / -XA>0 (TX--0 HN<ÍSJ J \ i ys F 107 H XJW / χτ°>° 107a H / ΧΥ°>° 0' Petition 870250103180, dated 11 / 11 / 2025, p. 117 / 393 110 / 383 Petition 870250103180, dated 11 / 11 / 2025, p. 118 / 393 111 / 383 109 109a 109b 109c 109d 109e 110 110a Petition 870250103180, dated 11 / 11 / 2025, p. 119 / 393 112 / 383 110b H ^^0 O^X-0 HN<fs; / Γ~ζ | \ । v11 F 110c H n AH j s Λ > ° (A-0 ΗΝ·φ II \ F 110d A / jn> O^XO HN—Jl \ F 110e H n A / / XzttZ0 O^V-0 HN <fs; r—( |T \ i F 111 |_| aa 111a H n Ax° / 'v-rOA o' X— ο ηνΆ / \ । \_4 As 111b H o Ah? —Ο ηνΆ 1 \ । \—4 ys Petition 870250103180, dated 11 / 11 / 2025, p. 120 / 393 113 / 383 Petition 870250103180, dated 11 / 11 / 2025, p. 121 / 393 114 / 383 Petition 870250103180, dated 11 / 11 / 2025, p. 122 / 393 115 / 383 115b H 116 H Qw° J XX°>° ^0 HN—Ç 116a HO^° f HN < HÍJ ξ 116b CJA >° h —ÇJl^l ξ 117 H 117a Òín...^0XX>° 117b N / =\ Z=\ Cn) ha H Petition 870250103180, dated 11 / 11 / 2025, p. 123 / 393 116 / 383 118 í T A0 n s. 0 1 1 rv ' OH 118a r 0 1 hn^A' OH o <A^ CO co 118b N 0 1 A J. o í N H o o ω \ ω 119 r o । O H O oAz. to 119a 0 1 hn^AnO H o (0 120 r 0 1 hn^V O H V i-A 'zy° o Petition 870250103180, dated 11 / 11 / 2025, p. 124 / 393 117 / 383 120a h 0 1 OHV 'zy° o 121 0 1H,N^Ar OH o Petition 870250103180, of 11 / 11 / 2025, p. 125 / 393 118 / 383 Petition 870250103180, of 11 / 11 / 2025, p. 126 / 393 119 / 383 126a H V-0 HN< F 127 CH / ^Xx^· 127a H CH.-^qXX>° 128 H CW / h xx>° \— Ο Η N ( NN nXr ' 128a HO^° fh χχο>° 128b HO^° x>-29 HJ KI° QÍnH^qXX^0 H Petition 870250103180, of 11 / 11 / 2025, p. 127 / 393 120 / 383 129a iX Z f TZ^Yy z OY o 129b í / f Γ >o η ΜΊ J \ H 130 °<γ° Z'Y 7 Zx T Ox ZT °'A> / ZI 130a ' JN^\ / —QP zN / L z° [ (só·^ f|^ H|J N^ H 1 H 1 1 H zx ? of 'V o 131 o O w \sz^__) o \ Petition 870250103180, of 11 / 11 / 2025, p. 128 / 393 121 / 383 ​131a Λ NH r? 4o 131b N θ Ψ rAA--S HN—AL II )>l . n \_J) H \ _ZN^O ° 132 y~N ΝΞΞ—< JI s UOx í •A Η 132a f <Z)A z=\ z 'NH ΟΆ. «A Η 133 o H ^y^A-NH 1 ° 133a o H f} .ΝγΑχ^ΝΗ 1 ° J Petition 870250103180, of 11 / 11 / 2025, p. 129 / 393 122 / 383 133b H (O | | 0 °AJJN 134 |_| 134a H Λ rw µ A>0 X^O HNÇ )~(j \ 134b H n 0-x° 134c / ~C> θ N ΑΓ°Χα C}'< HN^ W f \ H x 134> OX 7° H X^O HN^ Jj \ 135 OH Η N -XXf N ° h XV-» ML Petition 870250103180, of 11 / 11 / 2025, p. 130 / 393 123 / 383 135a OH 0 135b OH HN^TN' 0 . N ML 136 H LV' 0 \\ N 136a H / y N*“ HN— 0 \\ N 136b H / y N HN— 0 \\ N 137 ? H ΜγΝγ 0 II N / '^Víí\ saX V ^XjO 137a N \\ s \\ s \ ™\ N \ 0 λ== / / HV^NH Petition 870250103180, of 11 / 11 / 2025, p. 131 / 393 124 / 383 Petition 870250103180, of 11 / 11 / 2025, p. 132 / 393 125 / 383 139a 1 H πΑγΑ 0 II NO Ao A / 139b 1 H ΗΝ->γΝγ 0 II N o Ao Az yX 139c Γ x? h ΗΝ->γΝγ ° II N o Ao ω - / yX 141 . CJ H °A / ;on ;;......ÁA N 141a ^~NH X°V0^yN ÁA N 141b Π H ° A AA N Petition 870250103180, dated 11 / 11 / 2025, p. 133 / 393 126 / 383 141c / —NH „…..άΑ N 142 / ^NH ° 1 l· O Ao Ay 142a / —NH ° o Ao Ay Aí 142b yNH x° aa 0 1 o Ao Ay Aí 142c y' NH VXXK-· 0 O Ao HΓ3 NH W-Aí / ,4 \__ / / Tf η , h —\ II A / HL JX Kíí^O Petition 870250103180, dated 11 / 11 / 2025, p. 134 / 393 127 / 383 143a 0. / A / ° / hnA H o Λ z OY zx z^\ J 143b / ^9 ,° \ )·< / SY hn.-< H Al! / HT JT y=Q 143c 0. / A ,o \ / SA hnH H Γ °Y^ o 144 —\ T ? H HN-AyN\ 0 1 I* o Λ z OA / 144a / °v / —\ ( 9 H hnANx0 1 ro A zo (Y 144b / °vz—\ T ? H hiAA 0 1 / Y ^-Οί o. zY o Petition 870250103180, dated 11 / 11 / 2025, p. 135 / 393 128 / 383 144c of ΞΕ / —( z \ °Y ZI o . Λ z OY ?— z 145 0 1 <Y NH 1 । jlX ? Vs ξ Z--- 145a ZI oA / — o— y~w Ύ o 145b 0 1 VXY K cr NH 1 Υω OT^~Z. O Y o 145c r 0 1 λ°\Λ J XY M CT NH 1 Yco OT_^Z o Y o Petition 870250103180, dated 11 / 11 / 2025, p. 136 / 393 129 / 383 146 ho 1 aX J / YN ( ; Hx—NH . x χ >0 LX / Se 146a h O 1 Λ J / VN ( ) Hx—NH . xx >0 _ / ζ ·ζΝ Se AI \ Ϊ VSe 146b h O 1 Λ H' ) X γ v / YA ( 146c h O 1 Λ J / YN^ ( ; H x—NH γχΡΧ' COMPOSITIONS

[0606] Compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or Table 1, or pharmaceutically acceptable salts thereof, or deuterated versions thereof, may be used alone, but will generally be administered in the form of a pharmaceutical composition in which the compound / salt (active ingredient) of Formula (I), (II) or (III), (III-A), (III-B) or Table 1 is associated with pharmaceutically acceptable adjuvant(s), diluent(s) or carrier(s). Conventional procedures for selecting and preparing suitable pharmaceutical formulations are described by Petition 870250103180, dated 11 / 11 / 2025, p. 137 / 393 130 / 383 example, in “Pharmaceuticals - The Science of Dosage Form Designs”, ME Aulton, Churchill Livingstone, 2ndEd. 2002.

[0607] In embodiments, the present disclosure provides pharmaceutical composition(s) comprising a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or Table 1 or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, as defined above, in association with pharmaceutically acceptable adjuvant(s), diluent(s) or carrier(s).

[0608] The disclosure further provides a process for preparing a pharmaceutical composition of the disclosure comprising mixing a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI), or Table 1 or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, as defined above, with pharmaceutically acceptable adjuvant(s), diluent(s) or carrier(s).

[0609] Pharmaceutical compositions can be administered topically (e.g., on the skin or in the lungs and / or airways) in the form of, for example, creams, solutions, suspensions, heptafluoroalkane (HFA) aerosols and dry powder formulations, for example, formulations in the inhaler device known as Turbuhaler®; or systemically, for example, by oral administration in the form of tablets, capsules, syrups, powders or granules; or by parenteral administration in the form of a sterile solution, suspension or emulsion for injection (including intravenous, subcutaneous, intramuscular, intravascular or infusion); or by rectal administration in the form of suppositories.

[0610] For oral administration, the disclosure compound may be mixed with adjuvant(s), diluent(s) or carrier(s), for example, lactose, sucrose, sorbitol, mannitol; starch, for example, potato starch, corn starch or amylopectin; cellulose derivative; binder, for example, gelatin or polyvinylpyrrolidone; disintegrant, for example, cellulose derivative, and / or lubricant, for example, magnesium stearate, calcium stearate, polyethylene glycol, wax, Petition 870250103180, dated 11 / 11 / 2025, page 138 / 393 131 / 383 paraffin and similar materials, and then compressed into tablets. If coated tablets are required, the cores, prepared as described above, may be coated with a suitable polymer dissolved or dispersed in water or readily volatile organic solvent(s). Alternatively, the tablet may be coated with a concentrated sugar solution which may contain, for example, gum arabic, gelatin, talc and titanium dioxide.

[0611] For the preparation of soft gelatin capsules, the disclosure compound can be mixed with, for example, a vegetable oil or polyethylene glycol. Hard gelatin capsules can contain granules of the compound using pharmaceutical excipients such as the aforementioned excipients for tablets. In addition, liquid or semi-solid formulations of the disclosure compound can be placed in hard gelatin capsules.

[0612] Liquid preparations for oral application may be in the form of syrups, solutions, or suspensions. Solutions, for example, may contain the disclosure compound, the remainder being sugar and a mixture of ethanol, water, glycerol, and propylene glycol. Optionally, such liquid preparations may contain coloring agents, flavoring agents, saccharin, and / or carboxymethylcellulose as a thickening agent. In addition, other excipients known to those skilled in the art may be used in the preparation of formulations for oral use. THERAPEUTIC USE

[0613] In embodiments, the compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or Table 1 and the pharmaceutically acceptable salts thereof, are DPP1 inhibitors and therefore can be used in any disease area where DPP1 plays a role. Thus, in one aspect of the invention, a treatment method is provided. The treatment method, in one modality, comprises administering to an individual in need, a composition comprising an effective amount of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or Table 1 or a pharmaceutically acceptable salt of Formula (I), (II), (III), Petition 870250103180, dated 11 / 11 / 2025, p. 139 / 393 132 / 383 (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or Table 1. In some embodiments, the composition is administered to the patient for a period of administration.

[0614] In embodiments, a compound or composition of the present disclosure is administered to a patient in a method to treat an obstructive airway disease; chronic rhinosinusitis (CRS); hidradenitis suppurativa (HS); cancer (e.g., cancer metastasis); granulomatosis with polyangiitis (GPA); microscopic polyangiitis (MPA); giant cell arteritis; polyarteritis nodosa; anti-GBM (Goodpasture) disease; rheumatoid arthritis; lupus nephritis; systemic lupus erythematosus; systemic scleroderma; inflammatory bowel disease (IBD) (e.g., ulcerative colitis; Crohn's disease); diabetic nephropathy; diabetic neuropathy; diabetic retinopathy; diabetic ulcers; Duchenne muscular dystrophy; bronchiolitis obliterans; long covid) - IBD prophylaxis; atopic dermatitis; pyoderma gangrenosum; Sweet's syndrome; dermatomyositis / polymyositis; neutrophilic dermatoses; uveitis; Behçet's disease; thrombosis; bronchopulmonary dysplasia; amyotrophic lateral sclerosis;Sickle cell anemia; psoriasis; ventilator-induced lung injury.

[0615] In embodiments, a compound or composition of the present disclosure is administered to a patient in a method for treating an obstructive airway disease.Obstructive airway disease, in one modality, is asthma (e.g., bronchial, allergic, intrinsic, extrinsic, exercise-induced, drug-induced (including aspirin- and NSAID-induced asthma and dust-induced, both intermittent and persistent and of all severities), airway hyperresponsiveness, chronic obstructive pulmonary disease (COPD), bronchitis (e.g., infectious bronchitis, eosinophilic bronchitis), emphysema, cystic fibrosis (CF), bronchiectasis (e.g., non-CF bronchiectasis (NCFBE) and CF-associated bronchiectasis), cystic fibrosis; sarcoidosis; alpha-1 antitrypsin (A1AT) deficiency, farmer's lung and related diseases, hypersensitivity pneumonitis, interstitial lung disease, pulmonary fibrosis (including idiopathic pulmonary fibrosis, cryptogenic fibrosing alveolitis, etc.). Petition 870250103180, dated 11 / 11 / 2025, page 140 / 393 133 / 383 idiopathic interstitial pneumonias, fibrosis complicating antineoplastic therapy and chronic infection, including tuberculosis and aspergillosis and other fungal infections), lung transplant complications, vasculitic and thrombotic disorders of the pulmonary vasculature, pulmonary hypertension (e.g., pulmonary arterial hypertension), antitussive activity, including treatment of chronic cough associated with inflammatory and secretory conditions of the airways, iatrogenic cough, acute and chronic rhinitis, including rhinitis medicamentosa and vasomotor rhinitis; perennial and seasonal allergic rhinitis, including nervous rhinitis (hay fever), nasal polyposis;Acute viral infection, including the common cold and infection due to a respiratory virus (e.g., respiratory syncytial virus, influenza, coronavirus (including SARS), and adenovirus), acute lung injury, acute respiratory distress syndrome (ARDS), as well as exacerbations of each of the aforementioned respiratory tract disease states.

[0616] Cystic fibrosis (CF) is caused by abnormalities in the CF transmembrane conductance regulatory protein, leading to chronic lung infections (particularly Pseudomonas aeruginosa) and excessive inflammation, resulting in bronchiectasis, declining lung function, respiratory failure, and reduced quality of life. The inflammatory process is dominated by neutrophils that produce NE, as well as other destructive NSPs, including CatG and PR3, which act directly on extracellular matrix proteins and play a role in the host response to inflammation and infection (Dittrich et al., Eur Respir J. 2018;51(3)). The methods provided in this document employ reversible DPP1 inhibitors.Without wanting to get bogged down in theory, it is believed that compounds of Formula (I), (II) or (III), administered by means of the methods provided in this document, have beneficial effects by inhibiting the activation of NSPs and decreasing inflammation, which in turn leads to a decrease in pulmonary exacerbations, a decrease in the rate of pulmonary exacerbations and / or an improvement in pulmonary function (e.g., forced expiratory volume in 1 second [FEV1]) in patients with CF.

[0617] In one embodiment, a method is provided for Petition 870250103180, dated 11 / 11 / 2025, page 141 / 393 134 / 383 treat CF, comprising administering to a patient with CF who needs treatment, a composition comprising an effective amount of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof.

[0618] In a method of treating CF, a composition comprising an effective amount of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, is administered to a patient with CF requiring treatment for a period of administration. The method comprises improving the patient's lung function during the administration period, compared with the patient's lung function before the administration period. The improvement in lung function in a modality is measured by spirometry.

[0619] Improving the patient's lung function, in one embodiment, comprises increasing the patient's forced expiratory volume in 1 second (FEVi), increasing the patient's forced vital capacity (FVC), increasing the patient's peak expiratory flow rate (PEFR), or increasing the patient's forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)), compared to the respective value prior to the administration period. The increase, in one embodiment, is approximately 5%, approximately 10%, approximately 15%, approximately 20%, approximately 25%, approximately 30%, approximately 35%, approximately 40%, approximately 45%, or approximately 50% of the respective value. The increase, in one modality, is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50%.In another scenario, the increase is from about 5% to about 50%, from about 5% to about 40%, from about 5% to about 30%, or from about 5% to about 20%. In another scenario, the increase is from about 10% to about 50%, from about 15% to about 50%, from about 20% to about 50%, or from about 25% to about 50%. Petition 870250103180, dated 11 / 11 / 2025, page 142 / 393 135 / 383 of 50%.

[0620] In one embodiment of a method provided in this document, a composition comprising an effective amount of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX) or (XX), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof, is administered to a patient with bronchiectasis requiring treatment for a period of administration. Bronchiectasis is considered a pathological outcome resulting from many pathological processes and is a persistent or progressive condition characterized by dilated, thick-walled bronchi. Symptoms range from intermittent episodes of expectoration and infection localized in the affected lung region to persistent daily expectoration, usually of large volumes of purulent sputum. Bronchiectasis may be associated with other nonspecific respiratory symptoms.The underlying pathological process of bronchiectasis, without delving into theory, has been described as airway damage resulting from an event or series of events where inflammation is central to the process (Guideline for non-CF Bronchiectasis, Thorax, July 2010, Vol. 65(Suppl 1), incorporated by reference herein in its entirety for all purposes).

[0621] Bronchiectasis is considered a pathological outcome resulting from many pathological processes and is a persistent or progressive condition characterized by dilated, thickened bronchi. Symptoms range from intermittent episodes of expectoration and infection localized in the affected lung region to persistent daily expectoration, usually of large volumes of purulent sputum. Bronchiectasis may be associated with other nonspecific respiratory symptoms. The underlying pathological process of bronchiectasis, without delving into theory, has been reported as airway damage resulting from an event or series of events where inflammation is central to the process (Guideline for non-CF Bronchiectasis, Thorax, July 2010, Vol. 65(Suppl 1), incorporated by reference herein in its entirety for all purposes).

[0622] The methods provided in this document employ Petition 870250103180, dated 11 / 11 / 2025, page 143 / 393 136 / 383 reversible DPP1 inhibitors. Without delving into theory, it is believed that the compounds of Formula (I), (II), or (III), administered using the methods provided in this document, have beneficial effects by reducing inflammation and mucus hypersecretion, which, in some modalities, leads to a decrease in pulmonary exacerbations, a decrease in the rate of pulmonary exacerbations, and / or an improvement in pulmonary function (cough, sputum production, and forced expiratory volume in 1 second [FEVi]) in patients with bronchiectasis. Without delving into theory, it is believed that the methods provided in this document modify the progression of bronchiectasis by reducing the accelerated rate of decline in pulmonary function or destruction of lung tissue.

[0623] In one form, bronchiectasis is bronchiectasis unrelated to CF.

[0624] In one embodiment, the method for treating bronchiectasis comprises improving the patient's lung function during the administration period, compared with the patient's lung function before the administration period.

[0625] A pulmonary exacerbation, in one embodiment, is characterized by three or more of the following symptoms exhibited for at least 48 hours by the patient: (1) increased cough; (2) increased sputum volume or change in sputum consistency; (3) increased sputum purulence; (4) increased shortness of breath and / or decreased exercise tolerance; (5) fatigue and / or malaise; (6) hemoptysis. In another embodiment, the three or more symptoms result in the physician's decision to prescribe one or more antibiotics to the symptomatic patient.

[0626] In one embodiment of a method for treating bronchiectasis, the method comprises decreasing the rate of pulmonary exacerbation in the individual, compared with the rate of pulmonary exacerbation experienced by the individual before the period of administration of the composition, or compared with a control individual with bronchiectasis who is not subject to the treatment method. In another embodiment, bronchiectasis is non- Petition 870250103180, dated 11 / 11 / 2025, page 144 / 393 137 / 383 related to the CF.

[0627] In another aspect, a method is provided for treating chronic rhinosinusitis (CRS) in an individual who needs it. The method comprises, in one embodiment, administering to the individual, for a period of administration, a pharmaceutical composition comprising an effective amount of a compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof.

[0628] Chronic rhinosinusitis is chronic rhinosinusitis without nasal polyps (CRSsNP) or chronic rhinosinusitis with nasal polyps (CRSwNP). In some modalities, chronic rhinosinusitis is chronic rhinosinusitis without nasal polyps (CRSsNP). In some modalities, chronic rhinosinusitis is chronic rhinosinusitis with nasal polyps (CRSwNP). In some modalities, chronic rhinosinusitis is refractory chronic rhinosinusitis. In some modalities, refractory chronic rhinosinusitis is refractory chronic rhinosinusitis without nasal polyps (CRSsNP). In some modalities, refractory chronic rhinosinusitis is refractory chronic rhinosinusitis with nasal polyps (CRSwNP).

[0629] In some modalities, the individual presents one or more symptoms of CRS. In some modalities, one or more symptoms of CRS are: (a) nasal congestion; (b) nasal obstruction; (c) nasal discharge; (d) postnasal drip; (e) facial pressure; (f) facial pain; (g) facial swelling; (h) reduced sense of smell; (i) depression; (j) mucosal edema; (k) mucopurulent discharge; (l) middle meatus obstruction; (m) mucosal changes within the ostiomeatal complex and sinuses; (n) rhinorrhea; or (o) any combination thereof. In some modalities, middle meatus obstruction is mucosal obstruction, edematous obstruction, or a combination thereof.

[0630] In some embodiments, administration of the pharmaceutical composition reduces, diminishes the severity, delays the onset, or eliminates one or more symptoms of CRS. In some embodiments, one or more symptoms of CRS are: (a) nasal congestion; (b) nasal obstruction; (c) nasal discharge; (d) postnasal drip; (e) facial pressure; (f) facial pain; (g) facial fullness; (h) reduced sense of smell; (i) Petition 870250103180, dated 11 / 11 / 2025, page 145 / 393 138 / 383 depression; (j) mucosal edema; (k) mucopurulent discharge; (l) middle meatus obstruction; (m) mucosal changes within the ostiomeatal complex and sinuses; (n) rhinorrhea; (o) or any combination thereof. In some modalities, administration of the pharmaceutical composition improves sinus drainage.

[0631] In some embodiments, the methods comprise the reduction of a composite severity score of one or more CRS symptoms. As used in this document, the “compound severity score” is a quantitative measure of all CRS symptoms exhibited by the individual. In some embodiments, the compound severity score is a total sum of all daily symptoms exhibited by the individual. In some embodiments, the compound severity score is reduced during or after the administration period compared to the compound severity score measured before the administration period. In some embodiments, one or more CRS symptoms exhibited by the individual may be any symptoms described herein or known in the art as associated with CRS. In some embodiments, one or more CRS symptoms are: nasal congestion, reduced sense of smell, rhinorrhea, or any combination thereof. In some embodiments, rhinorrhea is anterior rhinorrhea.In some disciplines, rhinorrhea is posterior rhinorrhea.

[0632] In some modalities, the methods comprise decreasing the individual’s Sino-Nasal Outcome Test-22 (SNOT-22) score during or after the administration period, compared to the individual’s SNOT-22 score before the administration period. As used in this document, “SNOT-22” is a patient-reported outcome measure developed for use in CRS with or without nasal polyps and contains 22 individual questions. The questions cover a wide range of health problems and health-related quality of life, including physical problems, functional limitations, and emotional consequences. The theoretical range of the SNOT-22 score is 0 to 110, with lower scores implying better health-related quality of life. More details on SNOT22 are provided in Hopkins, et al., Clin. Otolaryngol. 2009, 34, 447-454, and Kennedy, Petition 870250103180, dated 11 / 11 / 2025, page 146 / 393 139 / 383 et al., Ann Allergy Asthma Immunol. October 2013; 111 (4): 246-251, the content of which is incorporated herein by reference in its entirety.

[0633] Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory disease. Symptoms include skin lesions that are usually associated with hair follicles and may be painful, inflamed, and / or swollen. In some cases, when the skin lesions heal, they may reappear and lead to tunneling under the skin and progressive scarring. Because HS is a chronic condition, it can persist for many years and also worsen over time, with serious effects on quality of life and psychological and emotional well-being. In fact, patients with HS have higher rates of anxiety and depression, with a two-and-a-half times higher risk of suicide than the general population.

[0634] Patients with HS are categorized according to the severity of the disease, called Hurley staging, as mild (stage I), moderate (stage II), or severe (stage III). Although more than 200,000 cases of HS are diagnosed in the US each year, this disease can be difficult to diagnose and requires specialized care. HS can be confused with an infection, an ingrown hair, or other conditions. Furthermore, current treatment options are limited and lack effectiveness.

[0635] In one aspect, a method of treating HS in an individual who needs it is provided. The method comprises, in one embodiment, administering to the individual, for a period of administration, a pharmaceutical composition comprising an effective amount of a compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof. In another embodiment, the method of treating HS comprises reducing neutrophilic inflammation in the individual.

[0636] A HS in a discipline is HS in Hurley Stage I, HS in Hurley Stage II, or HS in Hurley Stage III. In some disciplines, the HS is HS in Hurley Stage I. In some disciplines, the HS is HS in Hurley Stage II. In some disciplines, the HS is HS in Hurley Stage III. Petition 870250103180, dated 11 / 11 / 2025, page 147 / 393 140 / 383 Hurley.

[0637] The disclosure provides methods of treating cancer in an individual in need thereof, comprising administering to the individual a pharmaceutical composition comprising an effective amount of any of the compounds disclosed herein. The disclosure provides methods of treating cancer-induced pain in an individual with cancer, comprising administering to the individual for a period of administration a pharmaceutical composition comprising an effective amount of any of the compounds disclosed herein. In some embodiments, cancer-induced pain is cancer-induced bone pain. The disclosure also provides methods of treating cancer-induced bone pain in an individual with cancer, comprising administering to the individual for a period of administration a pharmaceutical composition comprising an effective amount of any of the compounds disclosed herein.

[0638] In some modalities, cancer comprises a primary solid tumor. In some modalities, cancer is bladder cancer, lung cancer, brain cancer, ovarian cancer, pancreatic cancer, colorectal cancer, prostate cancer, liver cancer, hepatocellular carcinoma, kidney cancer, stomach cancer, skin cancer, uterine fibroids, lymphoma, virus-induced cancer, oropharyngeal cancer, testicular cancer, thymus cancer, thyroid cancer, melanoma, or bone cancer.

[0639] In some modalities, the cancer is bladder cancer. In some modalities, the cancer is lung cancer. In some modalities, the cancer is brain cancer. In some modalities, the cancer is ovarian cancer. In some modalities, the cancer is pancreatic cancer. In some modalities, the cancer is colorectal cancer. In some modalities, the cancer is prostate cancer. In some modalities, the cancer is liver cancer. In some modalities, the cancer is hepatocellular carcinoma. In some modalities, the cancer is kidney cancer. In some modalities, the cancer is stomach cancer. In some modalities, the cancer is skin cancer. In some Petition 870250103180, dated 11 / 11 / 2025, page 148 / 393 In 141 / 383 modalities, the cancer is a fibroid cancer. In some modalities, the cancer is lymphoma. In some modalities, the cancer is virus-induced. In some modalities, the cancer is oropharyngeal cancer. In some modalities, the cancer is testicular cancer. In some modalities, the cancer is thymus cancer. In some modalities, the cancer is thyroid cancer. In some modalities, the cancer is melanoma. In some modalities, the cancer is bone cancer. In some modalities, the fibroid cancer is leiomyosarcoma.

[0640] In some forms, breast cancer includes ductal carcinoma, lobular carcinoma, medullary carcinoma, colloid carcinoma, tubular carcinoma, or inflammatory breast cancer. In some forms, breast cancer includes ductal carcinoma. In some forms, breast cancer includes lobular carcinoma. In some forms, breast cancer includes medullary carcinoma. In some forms, breast cancer includes colloid carcinoma. In some forms, breast cancer includes tubular carcinoma. In some forms, breast cancer includes inflammatory breast cancer.

[0641] In some forms, breast cancer is triple-negative breast cancer. In some forms, breast cancer does not respond to hormone therapy or treatments that target HER2 protein receptors.

[0642] In some forms, the lymphoma is Hodgkin lymphoma, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, immunoblastic B-cell lymphoma, Natural Killer cell lymphoma, T-cell lymphoma, Burkitt lymphoma, or Kaposi's sarcoma. In some forms, the lymphoma is Hodgkin lymphoma. In some forms, the lymphoma is non-Hodgkin lymphoma. In some forms, the lymphoma is diffuse large B-cell lymphoma. In some forms, the lymphoma is immunoblastic B-cell lymphoma. In some forms, the lymphoma is Natural Killer cell lymphoma. In some forms, the lymphoma is T-cell lymphoma. In some forms, the lymphoma is Burkitt lymphoma. In some forms, the lymphoma is Kaposi's sarcoma. Petition 870250103180, dated 11 / 11 / 2025, page 149 / 393 142 / 383

[0643] In some modalities, brain cancer is astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, oligodendroglioma, ependymoma, meningioma, schwannoma, or medulloblastoma. In some modalities, brain cancer is astrocytoma. In some modalities, brain cancer is anaplastic astrocytoma. In some modalities, brain cancer is glioblastoma multiforme. In some modalities, brain cancer is oligodendroglioma. In some modalities, brain cancer is ependymoma. In some modalities, brain cancer is meningioma. In some modalities, brain cancer is schwannoma. In some modalities, brain cancer is medulloblastoma.

[0644] In some modalities, the cancer is a liquid tumor. In some modalities, the liquid tumor is acute myeloid leukemia (AML), acute lymphoblastic leukemia, acute lymphocytic leukemia, acute promyelocytic leukemia, chronic myeloid leukemia, hairy cell leukemia, a myeloproliferative disorder, Natural Killer cell leukemia, blastic plasmacytoid dendritic cell neoplasm, chronic myeloid leukemia (CML), mastocytosis, chronic lymphocytic leukemia (CLL), multiple myeloma (MM), or myelodysplastic syndrome (MDS). In some modalities, the liquid tumor is acute myeloid leukemia (AML). In some modalities, the liquid tumor is acute lymphoblastic leukemia. In some modalities, the liquid tumor is acute lymphocytic leukemia. In some modalities, the liquid tumor is acute promyelocytic leukemia. In some forms, the liquid tumor is chronic myeloid leukemia. In some forms, the liquid tumor is hairy cell leukemia.In some modalities, the liquid tumor is a myeloproliferative disorder. In some modalities, the liquid tumor is Natural Killer cell leukemia. In some modalities, the liquid tumor is a blastic plasmacytoid dendritic cell neoplasm. In some modalities, the liquid tumor is chronic myeloid leukemia (CML). In some modalities, the liquid tumor is mastocytosis. In some modalities, the liquid tumor is chronic lymphocytic leukemia (CLL). In some modalities, the liquid tumor is multiple myeloma (MM). In some modalities, the liquid tumor is myelodysplastic syndrome (MDS). Petition 870250103180, dated 11 / 11 / 2025, page 150 / 393 143 / 383

[0645] In some modalities, the cancer is pediatric cancer. In some modalities, pediatric cancer is neuroblastoma, Wilms' tumor, rhabdomyosarcoma, retinoblastoma, osteosarcoma, or Ewing's sarcoma. In some modalities, pediatric cancer is neuroblastoma. In some modalities, pediatric cancer is Wilms' tumor. In some modalities, pediatric cancer is rhabdomyosarcoma. In some modalities, pediatric cancer is retinoblastoma. In some modalities, pediatric cancer is osteosarcoma. In some modalities, pediatric cancer is Ewing's sarcoma.

[0646] In some forms, cancer is metastatic. In some forms, the individual is at risk of developing metastatic cancer. In some forms, metastatic cancer includes metastasis from breast cancer to the brain, bone, pancreas, lymph nodes, and / or liver. In some forms, metastatic cancer includes metastasis from bone cancer to the lung. In some forms, metastatic cancer includes metastasis from colorectal cancer to the peritoneum, pancreas, stomach, lung, liver, kidney, and / or spleen. In some forms, metastatic cancer includes metastasis from stomach cancer to the mesentery, spleen, pancreas, lung, liver, adrenal gland, and / or ovary. In some forms, metastatic cancer includes metastasis from leukemia to the lymph nodes, lung, liver, hind limb, brain, kidney, and / or spleen.In some forms, metastatic cancer includes metastasis from liver cancer to the intestine, spleen, pancreas, stomach, lung, and / or kidney. In some forms, metastatic cancer includes metastasis from lymphoma to the kidney, ovary, liver, bladder, and / or spleen.

[0647] In some forms, metastatic cancer includes metastasis of hematopoietic cancer to the intestine, lung, liver, spleen, kidney, and / or stomach. In some forms, metastatic cancer includes metastasis of melanoma to the lymph nodes and / or lung. In some forms, metastatic cancer includes metastasis of pancreatic cancer to the mesentery, ovary, kidney, spleen, lymph nodes, stomach, and / or the Petition 870250103180, dated 11 / 11 / 2025, page 151 / 393 144 / 383 liver. In some forms, metastatic cancer includes metastasis from prostate cancer to the lung, pancreas, kidney, spleen, intestine, liver, bone, and / or lymph nodes. In some forms, metastatic cancer includes metastasis from ovarian cancer to the diaphragm, liver, intestine, stomach, lung, pancreas, spleen, kidney, lymph nodes, and / or uterus. In some forms, metastatic cancer includes metastasis from myeloma to the bone.

[0648] In some modalities, metastatic cancer comprises metastasis from lung cancer to the bone, brain, lymph nodes, liver, ovary, and / or intestine. In some modalities, metastatic cancer comprises metastasis from kidney cancer to the liver, lung, pancreas, stomach, brain, and / or spleen. In some modalities, metastatic cancer comprises metastasis from bladder cancer to the bone, liver, and / or lung. In some modalities, metastatic cancer comprises metastasis from thyroid cancer to the bone, liver, and / or lung.

[0649] In some embodiments, the methods disclosed in this document comprise the treatment of cancer-induced bone pain (CIBP) in an individual with metastatic bone cancer. In some embodiments, the individual has metastasis of prostate cancer, breast cancer, lung cancer, or myeloma in the bone. In some embodiments, the individual is identified as having bone metastasis using any of the following methods: plain radiography, computed tomography, technetium-99m bone scintigraphy, magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, fluorine positron emission tomography, and / or choline positron emission tomography, but does not yet experience cancer-induced bone pain. In some embodiments, the individual suffers from cancer-induced bone pain, which is indicative of metastasis from a previously treated or untreated primary tumor in the bone.In some forms, the cancer has metastasized to the vertebrae, pelvis, long bones, or ribs.

[0650] In some modalities, the administration of Petition 870250103180, dated 11 / 11 / 2025, page 152 / 393 The 145 / 383 composition reduces the severity, delays the onset, or eliminates a symptom of cancer. In some modalities, the symptom of cancer is cancer-induced bone pain (CIBP). In some modalities, CIBP is neuropathic pain. In some modalities, CIBP is inflammatory pain. In some modalities, CIBP is spontaneous pain. In some modalities, the symptom of cancer is nociceptive hypersensitivity. In some modalities, the symptom of cancer is allodynia. In some modalities, allodynia is tactile allodynia. In some modalities, tactile allodynia is static mechanical allodynia. In some modalities, tactile allodynia is dynamic mechanical allodynia. In some modalities, the individual has bone cancer or bone metastasis.

[0651] In another embodiment of the present invention, a method is provided for treating lupus nephritis (LN) in an individual in need thereof. The method comprises administering to the individual, for a period of administration, a pharmaceutical composition comprising an effective amount of a compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof.

[0652] Rheumatoid arthritis (RA) is characterized by inflammation and thickening of the joint capsule, along with an effect on the underlying bone and cartilage. Currently, the cause of RA is unknown and there is no satisfactory cure available. Although several therapeutic agents have been developed and used to alleviate the pain and inflammation associated with the disease, such as disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs), they often produce intolerable side effects. To address this and other needs, the present invention, in one embodiment, provides a method for treating RA using reversible DPP1 inhibitors of Formula (I), (II) or (III).In one embodiment, a method is provided for treating RA in an individual who needs it, comprising administering to the individual, for a period of administration, a pharmaceutical composition comprising an effective amount of a compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof. Petition 870250103180, dated 11 / 11 / 2025, page 153 / 393 146 / 383 same. In another modality, the method involves reducing neutrophilic inflammation in the individual.

[0653] Inflammatory bowel disease (IBD) is a group of inflammatory conditions affecting the colon and small intestine. The most common IBDs are Crohn's disease and ulcerative colitis. The present invention, in one embodiment, addresses the need for novel therapies for IBD. Specifically, in one embodiment, a method is provided for treating inflammatory bowel disease (IBD) in an individual in need thereof. The method comprises administering to the individual, for a period of administration, a pharmaceutical composition comprising an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a deuterated form thereof.

[0654] In another modality, IBD is Crohn's disease or ulcerative colitis. In another modality, the method involves reducing neutrophilic inflammation in the individual.

[0655] The duration of the course of treatment in any given case may depend on the nature and severity of the condition being treated and / or prevented and be determined by the physician. In one modality, the course of treatment begins approximately at the time of diagnosis of the condition / disease and continues throughout the patient's life. EXAMPLES

[0656] The present invention is further illustrated by reference to the following Examples. However, it should be noted that these Examples, as well as the embodiments described above, are illustrative and should not be interpreted as restricting the scope of the invention in any way.

[0657] In some embodiments, the compounds of the present invention can be synthesized using the following methods. General reaction conditions are provided, and the reaction products can be purified by generally known methods, including silica gel chromatography using various organic solvents such as hexane, dichloromethane, ethyl acetate, methanol and Petition 870250103180, dated 11 / 11 / 2025, page 154 / 393 147 / 383 similar or preparative reversed-phase high-performance liquid chromatography.

[0658] In the following examples, the term “presumed”, when present, refers to the particular stereochemistry of the respective product. Further characterization will confirm the absolute stereochemistry of the products. GENERAL EXPERIMENTAL 1H NMR ANALYSIS:

[0659] 1H NMR spectra are recorded on a Bruker Ultrashield (400 MHz). The multiplicity of a signal is designated by the following abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of triplets; m, multiplet.

[0660] All observed coupling constants, J, are reported in Hertz (Hz).

[0661] Exchangeable protons are not always observed.

[0662] LC / MS Analysis:

[0663] LC / MS Method AN01_001_012:

[0664] The LC-MS data were generated using a system Waters Acquity: TUV detector, SQD2 MS detector, Sedere SEDEX 80 (light scattering detector).

[0665] LC-MS method: reversed-phase HPLC analysis

[0666] Agilent Column: Cortecs C18

[0667] Solvent A: Water with Formic Acid (0.1% V / V)

[0668] Solvent B: Acetonitrile

[0669] Gradient table: Time (min) Flow (ml / min) %A %B Curve 0 0.7 98 2 Initial 2 0.7 0 100 Linear 2.5 0.7 0 100 Linear 2.6 0.7 98 2 Linear 5 0.7 98 2 Linear Petition 870250103180, dated 11 / 11 / 2025, page 155 / 393 148 / 383

[0670] LC / MS Method AN01_001_026:

[0671] LC-MS data were generated using a Waters Acquity system: TUV detector, SQD2 MS detector, Sedere SEDEX 80 (light scattering detector).

[0672] LC-MS method: reversed-phase HPLC analysis

[0673] Agilent Column: Poroshell

[0674] Solvent A: Water with Formic Acid (0.1% V / V)

[0675] Solvent B: Acetonitrile

[0676] Gradient table: Time (min) Flow (ml / min) %A %B Curve 0 1 98 2 initial 2 1 98 2 6 12 1 0 100 6 15.4 1 0 100 6 16.7 1 98 2 6 18.4 1 98 2 6

[0677] UV Detection: 220 nm GENERAL SYNTHETIC PROCEDURES PROCEDURE A

[0678] For an argon-purged solution of protected alcohol (1 eq.) in EtOH (4.78 ml / mmol of protected alcohol), 10% Pd / C (0.1 eq.) is added at room temperature. The resulting mixture is purged with argon (x3) and then with H2 (3x). The reaction mixture is stirred under atmospheric pressure of H2 at room temperature for 18 hours. The reaction mixture is purged with argon, filtered through a celite pad, and rinsed with EtOH (3x5 ml). The filtrate is concentrated under reduced pressure to provide the expected compound. PROCEDURE B

[0679] For a solution of alcohol derivative (1 eq.) in acetone (16.7 ml / mmol of alcohol) and sodium bromide (0.3 eq.) a Petition 870250103180, dated 11 / 11 / 2025, p. 156 / 393 149 / 383 Saturated aqueous solution of NaHCO3 (2.59 mL / mmol alcohol) at room temperature. Trichlorocyanuric acid (2.2 eq.) and 2,2,6,6-tetramethylpiperidine-1-oxyl (0.03 eq.) at 0 °C are added to the resulting mixture. The reaction mixture is allowed to warm to room temperature and stirred for 18 hours. Isopropanol (10 mL) at room temperature is added and the reaction mixture is stirred for 30 min. The reaction mixture is diluted with EtOAc (50 mL) and a saturated aqueous solution of NaHCO3 (50 mL) is added. The two layers are separated and the aqueous layer is washed with EtOAc (50 mL). The aqueous layer is then acidified with 3M aqueous HCl solution to pH ~1 and extracted with DCM (2 x 50 mL). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure to yield the desired compound. PROCEDURE C

[0680] To a solution of amine derivative (1 eq.) in anhydrous DMF (7.14 mL / mmol amine) and carboxylic acid derivative (1.05 eq.), DIPEA (2.5 eq.) and TBTU (1.5 eq.) are added at room temperature under an argon atmosphere. The reaction mixture is stirred at room temperature for 18 hours. The reaction mixture is diluted with EtOAc (10 mL) and water (10 mL). The aqueous layer is extracted with EtOAc (2 x 10 mL) and the combined organic layers are washed with brine (3 x 10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude oil is purified by flash chromatography over SiO2 (see conditions for each compound) to provide the expected compound. PROCEDURE D

[0681] To a pre-heated flask (50 °C) containing a Boc-protected amine derivative (1 eq.), formic acid (7.6 mL / mmol), also pre-heated to 50 °C, is added. The reaction mixture is stirred at 50 °C for 15 min. The reaction mixture is cooled to room temperature and added dropwise to a cooled mixture (0 °C) of stirred aqueous solution of saturated NaHCO3 (40 mL) and DCM (40 mL). The layers are separated and the aqueous layer is extracted with DCM (2 x 40 mL). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified. Petition 870250103180, dated 11 / 11 / 2025, page 157 / 393 150 / 383 by flash chromatography on S1O2 and / or preparative HPLC (see conditions for each compound) to provide the expected compound. PROCEDURE AND

[0682] To a solution of alcohol derivative (1 eq.) in anhydrous DMF (5.49 mL / mmol of alcohol derivative) and iodomethane (2 eq.), 60% NaH in oil (1.1 eq.) is added at 0 °C under an argon atmosphere. The resulting mixture is allowed to warm to room temperature and stirred for 22 hours. The reaction mixture is tempered with a saturated aqueous solution of NH4Cl (10 mL) at room temperature. EtOAc (50 mL) and water (50 mL) are then added and the two layers are separated. The aqueous layer is extracted with EtOAc (2 x 50 mL) and the combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue is purified by flash chromatography on silica gel (see conditions for each compound) to give the expected compound. EXAMPLE 1: PREPARATION OF B1-46-1-(S)* AND B1-46-1-IR) OH HoN. X. / OH BOC2O, EtjN MeOH / DCM, RT, 18 h 100%, quantity OH BocHFI A. OH Bu2SnO, TBAB DIPEA, BnBr °C, 24 h 75% B1-2-2 OH BocHN. / OBn NaH (60% in oil) DMF, 0 °C, 3 h 44% 2,6-lutidine, NalO4, RUCI33H2O DCM:ACN:H2O, RT, 1.5 h 89% B1-2-3 MeMgBr (3M in EhO THF, 0 C at RT, 4 h 75% B1-46-1-(S)* B1 -46-1 -( / ?)*

[0683] tert-butyl N -[(2S)-2,3-di-hydroxypropyl]carbamate Petition 870250103180, of 11 / 11 / 2025, p. 158 / 393 151 / 383 (B1-2-2) OH BocHNL Α,ΟΗ B1-2-2

[0684] To a solution of 2S)-3-aminopropane-1,2-diol (1 eq., 14.4 g, 158.1 mmol) and Et3N (1.01 eq., 22.2 mL, 159.6 mmol) in anhydrous MeOH (245 mL) a solution of Boc2O (1.2 eq., 41.4 g, 189.7 mmol) in anhydrous DCM (41 mL) was added at room temperature under an argon atmosphere. The reaction mixture was stirred at room temperature for 18 hours and then concentrated under reduced pressure to give B1-2-2 as a light yellow oil (30.2 g, quant.). The crude oil was considered quantitative and used as such.

[0685] LC / MS (AN01_001_012): Rt = 1.69 min, not UV active, [M+Na]+ = 214.1.

[0686] tert-butyl N -[(2S )-3-(benzyloxy)-2hydroxypropyl]carbamate (B1-2-3) OH BocHN^^z^^OBn B1-2-3

[0687] To a solution of B1-2-2 (1 eq., 1.72 g, 8.99 mmol), di(n-butyl)tin oxide (0.1 eq., 0.224 g, 0.899 mmol) and TBAB (0.3 eq., 0.870 g, 2.70 mmol) were added DIPEA (2 eq., 3.13 mL, 18.0 mmol) and BnBr (2 eq., 2.15 mL, 18.0 mmol) at room temperature under an argon atmosphere. The reaction mixture was stirred at 70 °C for 6 hours. The reaction mixture was concentrated under reduced pressure and then added to EtOAc (50 mL) and filtered over a silica gel pad. The latter was rinsed with EtOAc (3 x 150 mL) and the filtrate was concentrated under reduced pressure. The resulting orange oil (4.46 g) was purified by flash chromatography on silica gel (120 g, gradient: cyclohexane / EtOAc 100:0 to 50:50) to give B1-2-3 as a light yellow oil (2.31 g, 75%) which was contaminated by the other regioisomer - the protected Bn at position 2 (17 wt% by 1H NMR analysis). Petition 870250103180, dated 11 / 11 / 2025, page 159 / 393 152 / 383

[0688] LC / MS (AN01_001_012): Rt = 2.28 min, 100%, [M+Na] + = 304.1.

[0689] tert-butyl (2S)-2-[(benzyloxy)methyl]-6-methylidene-1,4-oxazepane-4-carboxylato B1-2-13 B1-2-13

[0690] To a 60% NaH suspension in oil (2.1 eq., 3.40 g, 85.1 mmol) in anhydrous DMF (72 mL), 3-chloro-2-chloromethyl-1-propene (1 eq., 4.69 mL, 40.5 mmol) was added at 0 °C. The reaction mixture was stirred at 0 °C for 10 min, then a solution of B1-2-3 (1 eq., 11.4 g, 40.5 mmol) in anhydrous THF (50 mL) was added dropwise at 0 °C. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with water (200 mL) and the aqueous layer was extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (330 g, gradient: Cyclohexane / EtOAc 100:0 to 90:10) to give B1-2-13 as a colorless oil (5.93 g, 44%).

[0691] LC / MS (AN01_001_012): Rt = 2.73 min, 100%, [MC4H8+H]+= 278.1.

[0692] tert-butyl (2S )-2-[(benzyloxy)methyl]-6-oxo-1,4oxazepane-4-carboxylate B1-2-14 OBn fsA·, / Ή-'' Boc B1-2-14

[0693] To a solution of B1-2-13 (1 eq., 2.10 g, 6.30 mmol) in a mixture of DCM (38 mL) and acetonitrile (38 mL), 2,6-lutidine (2 eq., 1.47 mL, 12.6 mmol), water (57 mL), and sodium periodate (4 eq., 5.39 g, 25.2 mmol) were added at room temperature. A solution of RuCl3.3H2O (0.035 eq., 57.6 Petition 870250103180, dated 11 / 11 / 2025, p. 160 / 393 A concentration of 153 / 383 mg, 0.220 mmol) in water (6.3 mL) was added dropwise to form a brown suspension. The reaction mixture was vigorously stirred at room temperature for 2 hours. The reaction mixture was diluted with water (150 mL) and extracted with DCM (3 x 150 mL). The combined organic layers were washed with brine (150 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (120 g, gradient: Cyclohexane / EtOAc 100:0 to 85:15) to give B1-2-14 as a colorless oil (1.88 g, 89%).

[0694] LC / MS (AN01_001_012): Rt = 2.56 min, 100%, [M+H]+= 336.1.

[0695] tert-butyl (2S, 6S*)-2-[(benzyloxy)methyl]-6-hydroxy-6methyl-1,4-oxazepane-4-carboxylate B1-46-1-( S )* & tert-butyl (2S, 6R* )-2[(benzyloxy)methyl]-6-hydroxy-6-methyl-1,4-oxazepane-4-carboxylate B1-46-1-(R)* Boc Boc B1-46-1-(S)* B1-46-1-( / ?)*

[0696] For a solution of B1-2-14 (1 eq., 1.28 g, 3.82 mmol) in anhydrous THF (35 mL), a 3M solution of MeMgBr in Et2O (2.5 eq., 3.18 mL, 9.54 mmol) was added at 0 °C under an argon atmosphere. The reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was diluted with a saturated aqueous solution of NH4Cl (100 mL) and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (80 g, gradient: Cyclohexane / EtOAc from 100:0 to 70:30) to yield B1-46-1-(S)* (0.650 g, 48%) and B1-46-1-(R)* (0.363 g, 27%) as colorless oils. The stereochemistry (S)* was assigned to the first product eluted by flash chromatography, and then (R)* was assigned to the second product eluted.

[0697] B1-46-1-( S )*: LC / MS (AN01_001_012): Rt = 2.47 Petition 870250103180, dated 11 / 11 / 2025, p. 161 / 393 154 / 383 min, 100%, [M-C4H8+H]+= 296.2.

[0698] B1-46-1-( / ?)*: LC / MS (AN01_001_012): Rt = 2.41 min, 100%, [M-C4H8+H]+= 296.2. EXAMPLE 2. SYNTHESIS OF B1-46-3-(IR)* AND B1-46-5-(S)*

[0699] Synthetic scheme for preparation of Compound 2-A: Approach (A) without protection group 10%Pd / C, H2, (1 atm.) EtOH, RT, 18 h B1-46-1-(R)' 100% TIME, NaBr, NaHCOa sat. aq tricolorisocyanuric acid, acetone, 0 °C at RT, 18 h 37% B1 -46-2-( R)' Boc B1 -46-3-( R)'

[0700] tert-butyl (2S,6 / ?*)-6-hydroxy-2-(hydroxymethyl)-6-methyl1,4-oxazepane-4-carboxylate B1-46-2-( / ?)* B1-46-2-(R)*

[0701] Starting from B1-46-1-( / ?)* (1 eq., 0.160 g, 0.455 mmol) and using general procedure A, B1-46-2-( / ?)* was obtained as a colorless oil (0.119 g, 100%).

[0702] LC / MS (AN01_001_012): Rt = 1.83 min, not UV active, [M+Na]+ = 284.1.

[0703] (2S, 6R*)-4-[(tert-butoxy)carbonyl]-6-hydroxy-6methyl-1,4-oxazepane-2-carboxylic acid B1-46-3-( / ?)* B1-46-3-(R)*

[0704] To a solution of B1-46-2-( / ?)* (1 eq., 0.110 g, 0.421 mmol) and sodium bromide (0.3 eq., 13.2 mg, 0.126 mmol) in acetone (7 mL), a saturated aqueous solution of NaHCO3 (2 mL) was added at temperature Petition 870250103180, dated 11 / 11 / 2025, p. 162 / 393 155 / 383 ambient environment. Trichlorocyanuric acid (2.2 eq., 0.215 mg, 0.926 mmol) and 2,2,6,6-tetramethylpiperidine-1-oxyl (0.03 eq., 1.97 mg, 0.0126 mmol) were added to the resulting mixture at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred for 18 hours. Isopropanol (10 mL) was added at room temperature and the reaction mixture was stirred for 30 min. The reaction mixture was diluted with EtOAc (50 mL) and a saturated aqueous solution of NaHCO3 (50 mL) was added. The two layers were separated and the aqueous layer was washed with EtOAc (50 mL). The aqueous layer was then acidified with 3M aqueous HCl solution to pH ~1 and extracted with DCM (2 x 50 mL). The aqueous layer was further extracted with a mixture of CHCb / isopropanol (8:2, 2 x 50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to give B1-46-3( / ?)* as a yellowish oil (42.6 mg, 37%).

[0705] LC / MS (AN01_001_012): Rt = 1.83 min, not UV active, [M+Na]+ = 298.1.

[0706] Synthetic scheme for preparation of Compound 2-B: Approach (B) with protecting group TBDMSOTf, 2,6-lutidine DCM, 0 °C at RT, 2 h B1-46-1-(S)' 93% B1-46-2-(S)* BOC2O, EtjN DCM / MeOH, RT, 6 PM 100% quantity 99% 10% Pd / C, Hz, (1 atm.) EtOH, RT, 72 h TIME, NaBr, NaHCOs sat. aq tricolorisocyanuric acid, acetone, 0 °C at RT, 18 h 73% B1-46-4-(S)* B1-46-3-{S)· B1-46-5-( S)*

[0707] (2S, 6S*)-2-[(benzyloxy)methyl]-6-[(tertbutyldimethylsilyl)oxy]-6-methyl-1,4-oxazepane B1 -46-2-(S)* OBn B1-46-2-(S)* Petition 870250103180, dated 11 / 11 / 2025, p. 163 / 393 156 / 383

[0708] To a solution of B1-46-1-(S)* (1 eq., 0.320 g, 0.911 mmol) and 2,6-lutidine (2.5 eq., 0.265 mL, 2.28 mmol) in anhydrous DCM solution (3 mL), TBDMSOTf (1.5 eq., 0.310 mL, 1.37 mmol) and DMAP (0.05 eq., 5.56 mg, 0.0455 mmol) were added under an argon atmosphere. The reaction mixture was stirred at room temperature for 6 h. The resulting mixture was diluted with DCM (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with DCM (2 x 50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (40 g, gradient: cyclohexane / EtOAc 100 / 0 to 50:50) to give B1-46-2-(S)* as a light yellow oil (0.308 g, 93%).

[0709] LC / MS (AN01_001_012): Rt = 2.30 min, 100%, [M+H]+= 366.3.

[0710] tert-butyl (2S,6S*)-2-[(benzyloxy)methyl]-6-[(tert-butyldimethylsilyl)oxy]-6-methyl-1,4-oxazepane-4-carboxylate B1 -46-3-( S )* TBDMSO Boc B1-46-3-(S)*

[0711] To a solution of B1-46-2-(S)* (1 eq., 0.305 g, 0.834 mmol) and Et3N (1.01 eq., 0.117 mL, 0.843 mmol) in anhydrous MeOH (1.3 mL) a solution of Boc2O (1.2 eq., 0.218 g, 1.00 mmol) in anhydrous DCM (0.25 mL) was added under an argon atmosphere. The reaction mixture was stirred at room temperature for 18 hours and then concentrated under reduced pressure to give B1-46-3-(S)* as a colorless oil (0.389 g, quant.). The crude mixture was considered quantitative and used as such.

[0712] LC / MS (AN01_001_012): Rt = 3.38 min, 100%, [M+Na]+= 488.3.

[0713] tert-butyl (2S,6S*)-6-[(tert-butyldimethylsilyl)oxy]-2(hydroxymethyl)-6-methyl-1,4-oxazepane-4-carboxylate B1 -46-4-( S )* Petition 870250103180, dated 11 / 11 / 2025, p. 164 / 393 157 / 383 TBDMSO <V7~O OH I® isA-.. / O7Boc B1-46-4-( S)'

[0714] From B1-46-3-(S)* (1 eq., 0.385 g, 0.827 mmol), using general procedure A, B1-46-4-(S)* was obtained as a colorless oil (0.306 g, 99%).

[0715] LC / MS (AN01_001_012): Rt = 2.95 min, not UV active, [M-C4H8+H]+= 320.2.

[0716] (2S,6S* )-4-[(tert-butoxy)carbonyl]-6-[(tertbutyldimethylsilyl)oxy]-6-methyl-1,4-oxazepane-2-carboxylic acid B1 -46-5-(S)* TBDMSO χί / ΤΌ O f 4·.^ OH Boc B1-46-5-(S)*

[0717] From B1-46-4-( S )* (1 eq., 0.290 g, 0.772 mmol), using general procedure B, B1-46-5-( S )* was obtained as a yellowish oil (0.219 g, 73%).

[0718] LC / MS (AN01_001_012): Rt = 2.84 min, not UV active, [M+Na]+ = 412.2. EXAMPLE 3: SYNTHESIS OF B1-47-3-(S)* AND B1-47-3-(R)* Petition 870250103180, dated 11 / 11 / 2025, p. 165 / 393 158 / 383 OBn NaH, Mel OBn 10% Pd / C, H2, (1 atm.) DMF, 0 to RT, 22 h / EtOH, RT, 18 h 81% N'791% Boc Boc B1-47-2-(S)* B1-46-1-(S)* B1-47-1-(S)* TIME, NaBr, sat. aq. NaHCO3Tricolorisocyanuric acid, acetone, 0 °C at RT, 18 h 80% B1-47-3-(S)*

[0719] tert-butyl (2S,6S*)-2-[(benzyloxy)methyl]-6-methoxy-6methyl-1,4-oxazepane-4-carboxylate B1 -47-1 -(S)* Boc B1-47-1-(S)*

[0720] Starting from B1-46-1-(S)* (1 eq., 0.320 g, 0.910 mmol), using general procedure E, B1-47-1-(S)* was obtained as a colorless oil (0.268 g, 81%) after purification by flash chromatography on silica gel (25 g, gradient: cyclohexane / EtOAc from 100:0 to 80:20).

[0721] LC / MS (AN01_001_012): Rt = 2.65 min, 100%, [M+Na]+= 388.2.

[0722] tert-butyl (2S,6S*)-2-(hydroxymethyl)-6-methoxy-6-methyl1,4-oxazepane-4-carboxylate B1 -47-2-(S)* Boc B1 -47-2-( S)*

[0723] From B1-47-1-(S)* (1 eq., 0.265 g, 0.725 mmol), Petition 870250103180, dated 11 / 11 / 2025, p. 166 / 393 159 / 383 using general procedure A, B1-47-2-(S)* was obtained as a colorless oil (0.181 g, 91%).

[0724] LC / MS (AN01_001_012): Rt = 2.00 min, not UV active, [M+Na]+ = 298.2.

[0725] (2S,6S*)-4-[(tert-butoxy)carbonyl]-6-methoxy-6-methyl1,4-oxazepane-2-carboxylic B1 -47-3-(S)* MeO 'Α / Γ'θ p OH Boc B1-47-3-(S)*

[0726] From B1-47-2-(S)* (1 eq., 0.175 g, 0.636 mmol), using general procedure B, B1-47-3-(S)* was obtained as a white solid (0.147 g, 80%).

[0727] LC / MS (AN01_001_012): Rt = 1.98 min, not UV active, [M+Na]+ = 312.1. NaH, Mel DMF, 0 to RT, 22 h 83% B1-46-1-( / ?)* OBn 10% Pd / C, H2, (1 atm.) .„ / EtQH.RT, 18 h 89% B1-47-1-( / ?)* B1-47-2-( / ?)* TIME, NaBr, sat. aq. NaHCO3Tricolorisocyanuric acid, acetone, 0 °C at RT, 18 h 58% MeO Boc B1-47-34R)*

[0728] tert-butyl (2S,6 / ?*)-2-[(benzyloxy)methyl]-6-methoxy-6methyl-1,4-oxazepane-4-carboxylate B1 -47-1 -( / ?)* Petition 870250103180, dated 11 / 11 / 2025, p. 167 / 393 160 / 383 Boc B1-47-1-( / ?)*

[0729] Starting from B1-46-1-(R)* (1 eq., 0.360 g, 1.02 mmol), using general procedure E, B1-47-1-(R)* was obtained as a colorless oil (0.311 g, 83%) after purification by flash chromatography on silica gel (25 g, gradient: cyclohexane / EtOAc from 100:0 to 75:25).

[0730] LC / MS (AN01_001_012): Rt = 2.65 min, 100%, [M+Na]+= 388.2.

[0731] tert-butyl (2S,6R*)-2-(hydroxymethyl)-6-methoxy-6-methyl1,4-oxazepane-4-carboxylate B1 -47-2-( R )* Boc B1-47-2-(R)*

[0732] From B1-47-1-(R)* (1 eq., 0.310 g, 0.848 mmol), using general procedure A, B1-47-2-(R)* was obtained as a colorless oil (0.208 g, 89%).

[0733] ​​​​LC / MS (AN01_001_012): Rt = 2.00 min, not UV active, [M+Na]+= 298.1.

[0734] (2S,6R* )-4-[(tert-butoxy)carbonyl]-6-methoxy-6-methyl1,4-oxazepane-2-carboxylic B1 -47-3-( R )* MeO Boc B1-47-3-(R)*

[0735] From B1-47-2-(R)* (1 eq., 0.205 g, 0.744 mmol), using general procedure B, B1-47-3-(R)* was obtained as a white solid (0.124 g, 58%). Petition 870250103180, dated 11 / 11 / 2025, p. 168 / 393 161 / 383

[0736] LC / MS (AN01_001_012): Rt = 2.00 min, not UV active, [M+Na]+ = 312.1. EXAMPLE 4: SYNTHESIS OF H1-2-7 .HCI h2n^^ Ethyl acrylate, EtsN EtOH.RT, 16 h EtO (Boc)2O DCM. RT, 19 h EtO Boc 100% (quantity) THE H1-2-2 (gross) H1-2-3 3-iodopropene LiHMDS, THF -78 CarT, 7 PM 71% EtO Boc hL 56% Grubbs Catalyst 1 DCM, reflux, 7 h 40% (more than 2 steps) THE OEt H2, (1 atm), 10% Pd / C EtOH, RT, 19 h N Boc H1-2-5 92% THE H1-2-4 THE OEt H1-2-6 N Boc 100% (quantity) 1M aq. LiOH THE RT, 19 h THE OH N Boc H1-2-7

[0737] Ethyl 3-[(but-3-en-1 -i I )[(tertbutoxy)carbonyl]amino]propanoate H1-2-3 EtO. Boc THE H1-2-3

[0738] An argon-purged solution of but-3-en-1-amine H1-2-1 hydrochloride (1 eq., 1.99 g, 18.5 mmol) and triethylamine (1.05 eq., 2.70 mL, 19.4 mmol) in EtOH (28 mL) was stirred at room temperature for 30 minutes. Ethyl acrylate (1 eq., 2.01 mL, 18.5 mmol) was then added and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was concentrated under reduced pressure to provide a crude mixture containing H1-2-2 (4.88 g, estimated purity: 50%) as a colorless oil.

[0739] For a solution purged with argon from the mixture Petition 870250103180, dated 11 / 11 / 2025, p. 169 / 393 Crude 162 / 383 containing H1-2-2 (4.88 g, estimated purity: 50%, 14.2 mmol, 1 eq.) in DCM (30 mL) was added to diisopropylamine (1.2 eq., 2.42 mL, 17.1 mmol), BOC2O (1.2 eq., 3.73 g, 17.1 mmol) and DMAP (0.1 eq., 0.170 g, 1.42 mmol) at room temperature. The resulting mixture was stirred at room temperature for 19 hours. The reaction mixture was diluted with water (50 mL) and extracted with DCM (2 x 50 mL). The combined organic layers were washed with brine (25 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting yellow oil was purified twice by flash chromatography on silica gel (1st flash chromatography: 120 g, gradient: cyclohexane / EtOAc from 100:0 to 80:20; 2nd flash chromatography: 40 g, gradient: cyclohexane / DCM from 80:20 to 0:100, then DCM / EtOAc from 100:0 to 80:20) to provide H1-2-3 as a colorless oil (1.99 g, 40% in 2 steps).

[0740] LC / MS (AN01_001_012): Rt = 2.65 min, 100%, [MC4H8+H]+= 216.2.

[0741] 2-{[(but-3-en-1-yl)[(tert-butoxy)carbonyl]amino]methyl}ethyl pent-4-enoate H1-2-4 either H1-2-4

[0742] For an argon-purged solution of H1-2-3 (1 eq., 1.99 g, 7.33 mmol) in THF (20 mL), a 1M LiHMDS solution in THF (1.1 eq., 8.07 mL, 8.07 mmol) was added dropwise at -78 °C. The resulting mixture was stirred at -78 °C for 1 hour before the dropwise addition of allyl iodide (1.1 eq., 0.740 mL, 8.07 mmol). The resulting mixture was allowed to warm to room temperature and stirred for 15 hours. The reaction mixture was cooled to -78 °C and a 1M LiHMDS solution in THF (0.2 eq., 1.47 mL, 1.47 mmol) was added dropwise at -78 °C. The reaction was stirred at this temperature for 30 minutes before the dropwise addition of allyl iodide (0.2 eq., 0.135 mL, 1.47 mmol). The resulting mixture was allowed to warm to room temperature and stirred for 3 hours. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc. Petition 870250103180, dated 11 / 11 / 2025, p. 170 / 393 163 / 383 (3x100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting orange oil was purified by flash chromatography on silica gel (80 g, gradient: cyclohexane / EtOAc from 100:0 to 80:20) to give H1-2-4 as a yellow oil (1.62 g, 71%).

[0743] LC / MS (AN01_001_012): Rt = 2.85 min, 100%, [MC5H8O2+H]+= 212.2.

[0744] 1-tert-butyl 3-ethyl 1,2,3,4,7,8-hexahydroazocine-1,3dicarboxylate H1-2-5 ,ΥΥ o \ J OEt N Boc H1-2-5

[0745] To an argon-purged solution of H1-2-4 (1 eq., 1.20 g, 3.85 mmol) in DCM (200 mL), benzylidene-bis(tricyclohexylphosphine)dichlorouthenium (0.1 eq., 0.318 g, 0.385 mmol) was added at room temperature. The resulting mixture was stirred and refluxed for 7 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting black oil was purified by flash chromatography on silica gel (80 g, gradient: cyclohexane / EtOAc 100:0 to 80:20) to give H1-2-5 as a black oil (0.613 g, 56%).

[0746] LC / MS (AN01_001_012): Rt = 2.67 min, 81%, [MC4H8+H]+= 228.1.

[0747] 1-tert-butyl 3-ethyl azocane-1,3-dicarboxylate H1-2-6 to OEt IN Boc H1-2-6

[0748] To an argon-purged solution of H1-2-5 (1 eq., 0.350 g, 1.24 mmol) in EtOH (6 mL), 10% Pd / C (0.2 eq., 0.263 g, 0.247 mmol) was added at room temperature. The resulting mixture was purged with Petition 870250103180, dated 11 / 11 / 2025, p. 171 / 393 164 / 383 argon (x3) and then with H2 (3x). The reaction mixture was stirred under atmospheric pressure of H2 at room temperature for 19 hours. The reaction mixture was purged with argon, filtered through a celite pad, and rinsed with EtOH (2 x 15 mL). The filtrate was concentrated under reduced pressure to give H1-2-6 as a yellow oil (0.323 g, 92%).

[0749] LC / MS (AN01_001_012): Rt = 2.73 min, not UV active, [MC4H8 +H]+= 230.1.

[0750] 1-[(tert-butoxy)carbonyl]azocano-3-carboxylic acid H1-2-7 Boc H1-2-7

[0751] To a solution of H1-2-6 (1 eq., 0.323 g, 1.13 mmol) in THF (11 mL) a solution of LiOH (5 eq., 0.237 g, 5.66 mmol) in water (5.5 mL) at room temperature was added. The reaction mixture was stirred at room temperature for 19 hours. The reaction mixture was poured dropwise into a stirred mixture of 1M aqueous HCl solution (50 mL) and DCM (100 mL) at 0 °C. The resulting mixture was stirred for 1 hour (pH ~1) and the layers were separated. The aqueous layer was extracted with DCM (2 x 50 mL) and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to give H1-2-7 as a yellow oil (0.291 g, 100%).

[0752] LC / MS (AN01_001_012): Rt = 2.29 min, not UV active, [M+Na]+ = 280.2. EXAMPLE 5. GENERAL SCHEME FOR THE SYNTHESIS OF (S)-N((S)-1-CYANO-2-(4-(3-METHYL-2-OXO-2,3-DIHYDROBENZORDIOXAZOL-5YL)BICYCLOR2,2,2-OCTAN-1-YL)ETHYL)-1,4-OXAZEPANO-2-CARBOXAMIDE

[0753] (S)-N-((S)-1-cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[2.2.2]octan-1-yl)ethyl)-1,4-oxazepane-2-carboxamide can be prepared according to the diagram below. Petition 870250103180, dated 11 / 11 / 2025, p. 172 / 393 165 / 383 DIC 1.5 equiv. DMAP 5% by mole EtOAc rl. 16 h NaHCO3 4.0 equiv DMA. rt. 16 h Kessil lamp 4CzlPN 2% mol K2HPO4 2.5 equiv DMF, RT. 16 h blue LEDs CO2Meíí^NBoc21.0 equiv. aq 6N HCl MeOH 'C ti EXAMPLE 6. GENERAL SCHEME FOR THE SYNTHESIS OF (2S)-N(1-CYANQ-2-(6-(3-METHYL-2-QXQ-2,3-DI-HYDRQBENZQ[D1QXAZQL-5IL)BENZORB1THIOPHEN-2-IL)ETHYL)-1,4-OXAZEPANO-2-CARBOXAMIDE

[0754] (2S)-N-(1 -cyano-2-(6-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)benzo[b]thiophen-2-yl)ethyl)-1,4-oxazepane-2-carboxamide can be prepared according to Scheme 0 below. Petition 870250103180, of 11 / 11 / 2025, p. 173 / 393 166 / 383 Br NaBH,, MeOH THF, 0°C, 16 h Br NBS, PPtij DCM, rt:2 h BnMe3NCI, NaOH DCM / HjO, 40°C, 36 h EXAMPLE 7. GENERAL SCHEME FOR THE SYNTHESIS OF (2S)-N(1-CIANO-2-(2-(3-METHYL-2-OXO-2,3-DI-HYDROBENZO[D1OXAZOL-5) lL)BENZO[B1THIOPHEN-6-YL)ETHYL)-1,4-OXAZEPANO-2-CARBOXAMIDE

[0755] (2S)-N-(1 -cyano-2-(2-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)benzo[b]thiophen-6-yl)ethyl)-1,4-oxazepane-2-carboxamide can be prepared according to the scheme below. Ph n BnMe3NCI, NaOHr DCM / H2O, * 40°CT24 h Petition 870250103180, dated 11 / 11 / 2025, page 174 / 393 167 / 383 EXAMPLE 8: IC50 TESTS DPP1 enzyme IC50 assay in mice

[0756] Test articles are applied to mouse active DPP1 enzyme (R&D Systems; Minneapolis, MN) in assay buffer (50 mM MES pH 5.5, 50 mM NaCl, 5 mM DTT) in a total reaction volume of 125 μL. 25 μL of the compound in assay buffer plus 5% DMSO are first added to 50 μL of mouse active DPP1 enzyme at a concentration of 62.5 pg^L and left to pre-incubate for 10 minutes at 37 °C, after which 50 μL of 1000 μM HGly-Arg-AMC substrate (Bachem; St. Torrance, CA) is added, resulting in a final substrate concentration of 400 μM and a final DMSO concentration of 1%. Substrate cleavage is measured for 90 minutes at 37 °C, with excitation / emission fluorescence measured every 5 minutes. DPP1 concentration is interpolated based on its activity relative to a standard curve of recombinant active mouse DPP1 enzyme. IC50 values ​​for each compound are calculated using XLFit (IDBS Version 5.3.1).3) Add-On for Microsoft Excel using the four-parameter fitting equation y = (A+((BA) / (1+((C / x)AD)))), which appears as equation number 205 (4-parameter logistic model or sigmoidal dose-response model) in XLFit. Standard constraints are used for each parameter. IC50 is defined as the concentration of the compound at which 50% of the enzymatic activity is inhibited when compared to the control without compound. HUMAN DPP1 ENZYME IC50 ASSAY

[0757] Recombinant human DPP1 enzyme (R&D Systems; Minneapolis, MN) is first proteolytically processed into its mature form using recombinant human cathepsin L (R&D Systems) in a buffer consisting of 20 mM citric acid pH 4.5, 150 mM NaCl, 1 mM EDTA, and 10 mM DTT. Test articles are applied to activated human DPP1 enzyme in assay buffer (25 mM MES pH 6.0, 50 mM NaCl, 5 mM DTT) in a total reaction volume of 125 μL. 25 μL of the compound in assay buffer plus 5% DMSO are first added to 50 μL of activated human DPP1 enzyme in a Petition 870250103180, dated 11 / 11 / 2025, page 175 / 393 168 / 383 concentration of 1 ng^jL and left to pre-incubate for 10 minutes at 37 °C, after which 50 μL of 1000 μM H-Gly-Arg-AMC substrate (Bachem; St. Torrance, CA) is added, resulting in a final substrate concentration of 400 μM and a final DMSO concentration of 1%. Substrate cleavage is measured for 90 minutes at 37 °C, with fluorescence in Excitation / Emission 350 / 450 nm measured every 5 minutes. The DPP1 concentration is interpolated based on its activity relative to a standard curve of activated recombinant human DPP1 enzyme. The IC50 values ​​for each compound are calculated using the XLFit (IDBS Version 5.3.1.3) Add-On for Microsoft Excel using the four-parameter fitting equation y = {A+[(BA)] / [1+((C / x)AD)]}, which appears as equation number 205 (4-parameter logistic model or sigmoidal dose-response model) in XLFit. Standard constraints are used for each parameter.The IC50 is defined as the concentration of the compound at which 50% of the enzymatic activity is inhibited when compared to the control without the compound. The IC50 table is included below. TABLE 2. IC50 VALUES OF DPP1[1] DPP1 IC50 Compound No., nM; Human[2] DPP1 IC50, nM; Mouse[2] Cellular Assay, nM[2] 112b * NA NA 131b * NA * 113b * (n=3) * (n=3) * (n=3) 114b * (n=3) * (n=3) * (n=3) 134a * NA * 130b * (n=2) NA * (n=2) 115b * (n=3) * (n=3) * (n=3) 113b * (n=3) NA * (n=2) 133b * NA * 118b * (n=3) * (n=3) * (n=3) 128b * (n=3) NA * (n=3) 101d * NA NA Petition 870250103180, dated 11 / 11 / 2025, page 176 / 393 169 / 383 138b * (n=3) NA * 138c * NA * 139b * (n=3) NA * 139c * NA * 142b ** (n=3) NA * (n=2) [1] NA means that the data for this composite are not available. [2]The symbols correspond to the IC50 ranges as per the table below. symbol DPP1 IC50, nM; Human DPP1 IC50, nM; Camundongo Cellular Assay, nM *** <5 <5 <1 ** 5-15 5-20 1-1.5 * >15 >20 >1.5 EXAMPLE 9. SYNTHESIS OF COMPOUND 112A: (2S)-N-{1CYANO-2-[2-(3-METHYL-2-OXO-1,3-BENZOXAZOL-5-YL)-1-BENZOTHIOPHEN-6-YL1ETHYL}1.4-OXAZEPANO-CARBON-2-AMIDAMIDA Ph -o rvJl lda EtBr; - -° Λ—\ f THF. -78-0¾. 3 h —C 7 O ^=7 O ^=7 M° N -Λ,ό 9 / S^Br Ά ph—fí Y-AyJ K2CO51 Pd(dppf)CI2 ph \= / dioxane / HíO 80°C, 2 h Mc ΪΟ P ,,N íl Ί Ί SA J / ^ ^ ^ ^\

[0758] carboxylate ~°\ NC^trYh e Br c Br Y DIBAL-H __ / Y PBrj __BnMe2NCI NaOH. THF ' Ά W Et2O, rt,3h ' A >> DCM / H2O, η o K ^=7 40°C 24 h -78 C*rt, 2 h OOAAN ipY .N í| Ύ N-7 O / 7 HCI, THHH2O_ 77 Boc___________~ N—< 4—ζ II rt 3h Mj—( / / \ jl HATU, DIEA.DCM 0°C, 2 h Ph > v O Μ tsoh acn . Α°)··<0 / sUU rt. methyl 2-bromo-1-benzothiopheno-6- ,s^ S^Br H LDA, EtBr2 — q ZJ THF, -78~0°C, 3 h \ / Petition 870250103180, of 11 / 11 / 2025, p. 177 / 393 170 / 383

[0759] To a stirred solution of methyl 1-benzothiophene-6-carboxylate (2 g, 10.404 mmol, 1 equiv) and THF (30 mL) was added LDA (in 2M THF) (6.24 mL, 12.49 mmol, 1.2 equiv) by drop at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred for 1 hour at -78 °C under a nitrogen atmosphere. To the above mixture was added dibromoethane (2.15 g, 11.44 mmol, 1.1 equiv) by drop at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred for a further 1 hour at room temperature under a nitrogen atmosphere. The reaction was stopped by the addition of water (50 mL) at room temperature. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure.The residue was purified by silica gel column chromatography, eluted with PE / EA (12:1) to give methyl 2-bromo-1-benzothiophene-6-carboxylate (1.7 g, 60.26%) as a light yellow oil. (No MS signal on LCMS).

[0760] 1H NMR (300 MHz, DMSO-d6) δ 8.63 (dt, J = 1.6, 0.8 Hz, 1H), 7.95 (dd, J = 8.4, 1.4 Hz, 1H), 7.91 (dd, J = 8.3, 0.8 Hz, 1H), 7.77 (d, J = 0.7Hz, 1H), 3.89 (s, 3H).

[0761] Synthesis of (2-bromo-1-benzothiophen-6-yl)methanol

[0762] A solution of methyl 2-bromo-1-benzothiophene-6-carboxylate (0.9 g, 3.32 mmol, 1 equiv) and DIBAL-H (9.96 mL, 9.96 mmol, 3 equiv) in tetrahydrofuran (40 mL, 14.38 mmol) was stirred for 2 hours at -78 °C at room temperature under a nitrogen atmosphere. The reaction was stopped with HCl (1 M) at 0 °C. The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (3 x 50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to Petition 870250103180, dated 11 / 11 / 2025, page 178 / 393 171 / 383 provide (2-bromo-1-benzothiophen-6-yl)methanol (0.65 g, 80.54%) as a white solid. LCMS (ES, m / z): [M-18+H]+: 225

[0763] 1H NMR (300 MHz, DMSO-d6) δ 7.86 (s, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.61 (s, 1H), 7.34 (dd, J = 8.2, 1.5 Hz, 1H), 5.30 (t, J = 5.7 Hz, 1H), 4.59 (d, J = 5.7 Hz, 2H).

[0764] Synthesis of 2-bromo-6-(bromomethyl)-1-benzothiophene

[0765] A solution of (2-bromo-1-benzothiophen-6-yl)methanol (0.65 g, 2.674 mmol, 1 equiv.) in Et2O (10 mL) was added to PBr3 (0.36 g, 1.337 mmol, 0.5 equiv.) at 0 °C. The resulting mixture was stirred for 2 hours at room temperature. The reaction was stopped by the addition of water at 0 °C. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (1 x 50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 2-bromo-6(bromomethyl)-1-benzothiophene (700 mg, 85.56%) as a white solid. (NO MS signal in LCMS)

[0766] 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, J = 1.6 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.66 (s, 1H), 7.46 (dd, J = 1.2 Hz, 138 Hz), (s, 2H).

[0767] Synthesis of 3-(2-bromo-1-benzothiophene-6-yl)-2[(diphenylmethylidene)amino] propanonitrile Ph NC^N^PhN / / / qo,__ / Yf BnMe3NCI, NaOH. 7 / YY Br fi—λ -----4--!-----* μ— / \__( / y-1dcm / h2o, / / \ ( / yJ \=7 40°C, 24 hPh\„u\— / Ph

[0768] A solution of 2-bromo-6-(bromomethyl)-1Petition 870250103180, dated 11 / 11 / 2025, p. 179 / 393 172 / 383 benzothiophene (600 mg, 1.96 mmol, 1.0 equiv) in DCM (5 mL) was added 2[(diphenylmethylidene)amino]acetonitrile (432 mg, 1.96 mmol, 1.0 equiv), benzyltrimethylazanium chloride (36.41 mg, 0.196 mmol, 0.1 equiv), NaOH (156 mg, 3.92 mmol, 2.0 equiv) in H2O (1 mL) and stirred for 36 hours at 40 °C. The resulting mixture was extracted with CH2Cl2 (3 x 100 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2Cl4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 3-(2-bromo-1-benzothiophen-6-yl)-2-[(diphenylmethylidene)amino]propanenitrile (800 mg crude) as a yellow solid. LCMS (ES, m / z): [M+H]+: 445.

[0769] Synthesis of 2-[(diphenylmethylidene)amino]-3-[2-(3-methyl2-OXO-1,3-benzoxazol-6-yl)-1-benzothiophen-5-yl]propanenitrile [(diphenylmethylidene)amino]propanenitrile (800 mg, 1.80 mmol, 1.0 equiv), 3-methyl-5(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-one (468 mg, 1.80 mmol, 1.0 equiv), K2CO3 (496 mg, 3.59 mmol, 2.0 equiv) and Pd(dppf)Cb (131 mg, 0.18 mmol, 0.1 equiv) in 1,4-dioxane (10 mL), H2O (1 mL) was stirred for 2 hours at 80 °C under a nitrogen atmosphere. The residue was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 2-[(diphenylmethylidene)amino]-3-[2-(3-methyl-2-oxo-1,3-benzoxazol-6-yl)-1-benzothiophen-5-yl]propanenitrile (600 mg, 65.04%) as a white solid. LCMS (ES, m / z): [M+H]+: 514. Petition 870250103180, dated 11 / 11 / 2025, page 180 / 393 173 / 383

[0771] Synthesis of benzoxazol-5-yl)-1-benzothiophen-6-yl]propanenitrile 2-amino-3-[2-(3-methyl-2-oxo-1,3- hci, thf / h2Q rt, 3h

[0772] In a 100 mL round-bottom flask, 2-[(diphenylmethylidene)amino]-3-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]propanenitrile (600 mg, 1.17 mmol, 1 equiv) and THF (50 mL), H2O (5 mL) were added at room temperature. The resulting mixture was stirred for 3 hours at room temperature. The mixture was basified to pH 12 with NaOH. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:2) to give 2amino-3-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]propanenitrile (300 mg, 73.50%) as a white solid. LCMS (ES, m / z): [M+H]+: 350.

[0773] Synthesis of tert-butyl (2S)-2-({1-cyano-2-[2-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]ethyl}carbamoyl)-1,4-oxazepane-4carboxylate

[0774] To a stirred mixture of 2-amino-3-[2-(3-methyl-2-[2-(3-methyl-2-[2-(3-methyl-2-[2-(3-methyl-2-[2-(3-methyl-2-[2-Petition 870250103180, 11 / 11 / 2025, page 181 / 393 174 / 383 oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]propanenitrile (110 mg, 0.32 mmol, 1.2 equiv), (2S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (64 mg, 0.26 mmol, 1.0 equiv) and DIEA (102 mg, 0.79 mmol, 3.0 equiv) in DCM (5 mL) were added to HATU (120 mg, 0.32 mmol, 1.2 equiv) at 0 °C. The resulting mixture was stirred for a further 2 hours at 0 °C. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give tert-butyl(2S)-2-({1-cyano-2-[2(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]ethyl}carbamoyl)-1,4-oxazepane4-carboxylate (120 mg, 79.32%) as a light yellow oil. LCMS (ES, m / z): [M+H]+: 577.

[0775] Synthesis of (2S)-N-{1-cyano-2-[2-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-6-yl]ethyl}-1,4-oxazepane-2-carboxamide

[0776] In a 50 mL round-bottom flask, tert-butyl (2S)-2-({1-cyano-2-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (120 mg, 0.21 mmol, 1 equiv), TsOH (108 mg, 0.62 mmol, 3.0 equiv) and ACN (3 mL) were added at room temperature. The resulting mixture was stirred for 3 hours at room temperature. The residue was purified by reversed-phase flash chromatography under the following conditions: column, silica gel C18; mobile phase, MeCN in water (0.1% NH3.H2O), gradient from 10% to 50% in 10 min; detector, UV 254 nm. This resulted in (2S)-N-{1-cyano-2-[2(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-6-yl]ethyl}-1,4-oxazepane-2-carboxamide (18.5 mg, 18.66%) as a white solid. ANALYTICAL DATA

[0777] LCMS (ES, m / z): [M+H]+: 477.

[0778] NMR de1H (400 MHz, DMSO- d6) δ 8.62 (dd, J = Petition 870250103180, of 11 / 11 / 2025, p. 182 / 393 175 / 383 11.8, 8.5 Hz, 1 Η), 7.91 - 7.84 (m, 2H), 7.79 (dd, J = 8.2, 2.9 Hz, 1H), 7.73 (d, J = 1.9 Hz, 1H), 7.51 (dt, J = 8.3 Hz, 1.2H), (d, J = 8.3 Hz, 1H), 7.33 (dt, J = 8.1, 1.7 Hz, 1H), 5.13 - 4.93 (m, 1H), 4.01 - 3.80 (m, 2H), 3.78 - 3.65 (m, 1H, 2H), 3.78 - 3.65 (m, 1H, 33H), 3.27 (m, 2H), 3.05 (ddd, J = 52.3, 14.2, 3.7 Hz, 1H), 2.84 - 2.63 (m, 2H), 2.60 -2.53 (m, 1H), 2.49-2.41 (m, 1H, 19, 16H). EXAMPLE 10. SYNTHESIS OF COMPOUND 113A: (2C)-N-(1CYANO-2-(6-(3-METHYL-2-OXO-2,3-DI-HYDROBENZO[D1OXAZOL-5YL)BENZORB1THIOPHEN-2-YL)ETHYL)-1,4-OXAZEPANO-2-CARBOXAMIDE Synthesis of (6-bromo-1-benzothiophene-2-yl)methanol NaBH4, MeOH THF, 0°C, 16 h To a solution of methyl 6-bromo-1-benzothiophene-2-carboxylate (4.0 g, 14.75 mmol, 1.0 equiv) in MeOH (30.0 mL) and THF (60.0 mL), NaBH4 (1.1 g, 29.50 mmol, 2.0 equiv) was added at 0°C. The mixture was stirred for 16 hours at 0°C. The reaction was quenched with water (100 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layer was washed with brine (3 x 30 mL) and dried. Petition 870250103180, dated 11 / 11 / 2025, pp. 183 / 393 176 / 383 on anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give (6-bromo-1-benzothiophen-2-yl)methanol (3.3 g, 92%) as a greenish-yellow solid. LCMS (ES, m / z): [M+H]+: 243.

[0781] Synthesis of 6-bromo-2-(bromomethyl)-1-benzothiopheneHO\__AXX nbs, pph3Br\ / flX sAABr DCMi rt>2 h S ΑΑβγ

[0782] To a solution of (6-bromo-1-benzothiophen-2-yl)methanol (2.0 g, 8.22 mmol, 1.0 equiv) in DCM (40 mL), NBS (1.8 g, 9.87 mmol, 1.2 equiv) and PPh3 (2.6 g, 9.87 mmol, 1.2 equiv) were added sequentially. The mixture was stirred for 2 h at room temperature. Concentrated to remove solvent, the residue was purified by silica gel column chromatography, eluted with PE / EA (20:1) to give 6-bromo-2-(bromomethyl)-1-benzothiophene (2.3 g, 91%) as a greenish-yellow solid. LCMS (ES, m / z): [M+H]+: 305.

[0783] Synthesis of 3-(6-bromo-1-benzothiophen-2-yl)-2[(diphenylmethylidene)amino] propanenitrile

[0784] To a solution of 6-bromo-2-(bromomethyl)-1-benzothiophene (2.3 g, 7.51 mmol, 1.0 equiv) in DCM (20 mL) was added 2[(diphenylmethylidene)amino]acetonitrile (1.7 g, 7.53 mmol, 1.0 equiv), benzyltrimethylazanium chloride (0.1 g, 0.75 mmol, 0.1 equiv), NaOH (0.6 g, 15.03 mmol, 2.0 equiv) in H2O (2 mL) and stirred for 2 hours at 40°C. The reaction was diluted with water (30 mL), extracted with CH2O2 (3 x 100 mL). The combined organic layer was washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography in Petition 870250103180, dated 11 / 11 / 2025, pp. 184 / 393 177 / 383 silica gel column, eluted with PE / THF (5:1) to give 3-(6-bromo-1-benzothiophen-2-yl)-2-[(diphenylmethylidene)amino]propanenitrile (1.3 g, 39%) as a white solid. LCMS (ES, m / z): [M+H]+: 445.

[0785] Synthesis of 2-[(diphenylmethylidene)amino]-3-[6-(3-methyl2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile

[0786] To a solution of 3-(6-bromo-1-benzothiophen-2-yl)-2[(diphenylmethylidene)amino]propanenitrile (700 mg, 1.57 mmol, 1.0 equiv) and 3-methyl-5(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-one (518 mg, 1.88 mmol, 1.2 equiv) in 1,4-dioxane (10 mL) and H2O (1 mL), K2CO3 (434 mg, 3.14 mmol, 2.0 equiv) and Pd(dppf)Cb (115 mg, 0.15 mmol, 0.1 equiv) were added sequentially. The mixture was stirred for 2 hours at 90 °C under a nitrogen atmosphere. The reaction was cooled to room temperature, concentrated to remove solvent, the residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give 2-[(diphenylmethylidene)amino]-3-[6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (800 mg, 99%) as a yellow oil. LCMS (ES, m / z): [M+H]+: 514.

[0787] Synthesis of benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile 2-amino-3-[6-(3-methyl-2-oxo-1,3- hci, thf / h2o rt, 3h

[0788] In a 100 mL round-bottom flask, the following were Petition 870250103180, dated 11 / 11 / 2025, pp. 185 / 393 178 / 383 added 2-[(diphenylmethylidene)amino]-3-[6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (400 mg, 0.77 mmol, 1.0 equiv), THF (25 mL), H2O (2.5 mL) and HCl (1M) (1 mL) were added sequentially at room temperature. The resulting mixture was stirred for 3 h at room temperature. The reaction was diluted with water (50 mL), extracted with Et2O (50 mL). The aqueous phase was basified to pH = 8 with solid Na2CO3, extracted with CH2O2 (3 x 50 mL). The combined organic layer was washed with brine (3 x 50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 2-amino-3[6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (140 mg, 51%) as a white solid. LCMS (ES, m / z): [M+H]+: 350.

[0789] Synthesis of tert-butyl (2S)-2-({1-cyano-2-[6-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4carboxylate DIEA, HATU DCM, 0°C, 3 h A solution of 2-amino-3-[6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (140 mg, 0.40 mmol, 1.2 equiv) in DCM (5 mL) was treated with (2S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (82 mg, 0.33 mmol, 1.0 equiv), DIEA (129 mg, 1.00 mmol, 3.0 equiv) followed by the addition of HATU (152 mg, 0.40 mmol, 1.2 equiv) in portions at 0°C. The resulting mixture was stirred for a further 3 hours at 0°C. Concentrated to remove solvent, the residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give tert-butyl(2S)-2-({1-cyano-2-[6-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (190 mg, 98%) as a white solid. LCMS (ES, m / z): [M+H]+: 577.

[0791] Synthesis of (2S)-N-(1-cyano-2-(6-(3-methyl-2-oxo-2,3dihydrobenzo[d]oxazol-5-yl)benzo[b]thiophen-2-yl)ethyl)-1,4-oxazepane-2-carboxamide Petition 870250103180, dated 11 / 11 / 2025, pp. 186 / 393 179 / 383

[0792] In a 50 mL round-bottom flask, tert-butyl(2S)-2-({1-cyano-2-[6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (100 mg, 0.17 mmol, 1.0 equiv), TsOH (90 mg, 0.51 mmol, 3.0 equiv) and ACN (3 mL) were added at room temperature. The resulting mixture was stirred for 3 h at room temperature. The reaction solution was purified by reversed-phase flash chromatography under the following conditions: column, C18-120 g; mobile phase, MeCN in water (0.1% NH3.H2O); gradient from 10% to 80% in 10 min; detector, UV 254 nm. The fraction was lyophilized, resulting in (2S)-N-(1-cyano-2-(6-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)benzo[b]thiophen-2-yl)ethyl)-1,4-oxazepane-2-carboxamide (16.3 mg, 20%) as a white solid. ANALYTICAL DATA

[0793] LCMS (ES, m / z): [M+H]+: 477.

[0794] 1H NMR (400 MHz, DMSO- de) δ 8.74 (d, J = 8.2 Hz, 1H), 8.28 (s, 1H), 7.88 (dd, J = 8.3, 2.5 Hz, 1H), 7.72 (d, J = 8.3 Hz, 1H), 7.69 (d, J = 1.8 Hz, 1H), 7.51 (dd, J = 8.7, 1.7 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.35 (s, 1H), 5.14 - 5.04 (m, 1H), 4.07 - 3.95 (m, 1H), 3.95 - 3.83 (m, 1H), 3.77 - 3.72 (m, 1H), 3.59 - 3.51 (m, 2H), 3.43 (s, 3H), 3.20 - 3.03 (m, 1H), 2.88 - 2.59 (m, 3H), 1.81 - 1.72 (m, 2H). EXAMPLE 11. SYNTHESIS OF COMPOUND 114A: (2S)-N-{1CYAN-2-r5-(3-METHYL-2-OXO-1,3-BENZOXAZOL-5-YL)-1-BENZOTHIOPHEN-2-ILLETHYL}1,4-OXAZEPAN-2-CARBOXAMIDE Petition 870250103180, dated 11 / 11 / 2025, pp. 187 / 393 180 / 383

[0795] Synthesis of (5-bromo-1-benzothiophen-2-yl)methanol / Br NaBH4 Br THF / MeOHHO 0°C, 16 h

[0796] A solution of methyl 5-bromo-1-benzothiophene-2-carboxylate (3.0 g, 11.06 mmol, 1.0 equiv) and NaBhl (0.84 g, 22.130 mmol, 2.0 equiv) in MeOH (20 mL) and THF (40 mL) was stirred for 16 hours at 0 °C. The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give (5-bromo-1-benzothiophen-2-yl)methanol (2.7 g, crude) as a greenish-yellow solid.

[0797] 1H NMR (300 MHz, DMSO-d6) δ 8.01 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.44 (dd, J = 8.5, 2.0 Hz, 1H), 7.25 (q, J = 1.0 Hz, 1H), 5.72 (t, J = 5.8 Hz, 1H), 4.76 (dd, J = 5.8, 1.2 Hz, 2H).

[0798] Synthesis of 5-bromo-2-(bromomethyl)-1-benzothiophene NBS, PPh3 DCM, rt, 2 h A solution of (5-bromo-1-benzothiophen-2 Petition 870250103180, dated 11 / 11 / 2025, pp. 188 / 393 181 / 383 yl)methanol (2.0 g, 8.22 mmol, 1.0 equiv), NBS (1.8 g, 9.87 mmol, 1.2 equiv) and PPhs (2.6 g, 9.87 mmol, 1.2 equiv) in DCM (40 mL) was stirred for 2 hours at room temperature. The residue was purified by silica gel column chromatography, eluted with PE / EA (20:1) to give 5-bromo-2-(bromomethyl)-1-benzothiophene (2.2 g, 87.3%) as a greenish-yellow solid.

[0800] Synthesis of 3-(5-bromo-1-benzothiophen-2-yl)-2[(diphenylmethylidene)amino] propanenitrile pH A solution Rr / x. NC N Ph BnMe3NCI, NaOH DCM / H2O 40°C, 36 h Benzothiophene Br (2.2 g, 7.18 mmol, 1.0 equiv) in DCM 5-bromo-2-(bromomethyl)-1 (20 mL) was added to 2[(diphenylmethylidene)amino]acetonitrile (1.6 g, 7.18 mmol, 1.0 equiv), benzyltrimethylazanium chloride (0.1 g, 0.71 mmol, 0.1 equiv), NaOH (0.6 g, 14.37 mmol, 2.0 equiv) in H2O (2 mL) and stirred for 2 hours at 40 °C. The resulting mixture was extracted with CH2Cl2 (3 x 100 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 3-(5-bromo-1-benzothiophen-2-yl)-2[(diphenylmethylidene)amino]propanenitrile (2.3 g, 71.8%) as a white solid. LCMS (ES, m / z): [M+H]+:445

[0802] Synthesis of 2-[(diphenylmethylidene)amino]-3-[5-(3-methyl2-OXO-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile Petition 870250103180, dated 11 / 11 / 2025, pp. 189 / 393 182 / 383

[0803] A solution of 3-(5-bromo-1-benzothiophen-2-yl)-2 [(diphenylmethylidene)amino]propanenitrile (1.0 g, 2.24 mmol, 1.0 equiv) and 3-methyl-5(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-one (0.7 g, 2.694 mmol, 1.2 equiv), K2CO3 (0.6 g, 4.49 mmol, 2.0 equiv), Pd(dppf)Cb (0.2 g, 0.22 mmol, 0.1 equiv) in 1,4-dioxane (10 mL) and H2O (1 mL) was stirred for 2 hours at 90 °C under a nitrogen atmosphere. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give 2-[(diphenylmethylidene)amino]-3-[5(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (1.1 g, 95.3%) as a yellow solid. LCMS (ES, m / z): [M+H]+:514

[0804] Synthesis of 2-amino-3-[5-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile

[0805] In a 100 mL round-bottom flask, 2-[(diphenylmethylidene)amino]-3-[5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (500 mg, 0.97 mmol, 1.0 equiv) and HCl (1 M) (1 mL), THF (30 mL), and H2O (3 mL) were added at room temperature. The resulting mixture was stirred for 3 hours at room temperature. The resulting mixture was extracted with Et2O (1 x 50 mL). The organic layers were extracted with CH2O2 (3 x 100 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 2-amino-3-[5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (220 mg, 64.6%) as a white solid. LCMS (ES, m / z): [M+H]+:350

[0806] Synthesis of (2S)-N-{1-cyano-2-[5-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4-oxazepane-2-carboxamide Petition 870250103180, dated 11 / 11 / 2025, pp. 190 / 393 183 / 383 HATU, DIEA DCM, 0°C, 3 h

[0807] A solution of 2-amino-3-[5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (156 mg, 0.44 mmol, 1.1 equiv) in DCM (5 mL) was treated with (2S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (100 mg, 0.40 mmol, 1.0 equiv), DIEA (158 mg, 1.22 mmol, 3.0 equiv) followed by the addition of HATU (186 mg, 0.49 mmol, 1.2 equiv) in portions at 0 °C. The resulting mixture was stirred for a further 2 hours at 0 °C. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give (2S)N-{1-cyano-2-[5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4oxazepane-2-carboxamide (220 mg, crude) as a white solid. LCMS (ES, m / z): [M+H]+:577

[0808] Synthesis of (2S)-N-{1-cyano-2-[5-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4-oxazepane-2-carboxamide TsOH, ACN, rt In an 8 mL flask, tert-butyl(2S)-2-({1-cyano-2-[5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (100 mg, 0.17 mmol, 1.0 equiv), TsOH (89 mg, 0.51 mmol, 3.0 equiv) and ACN (3 mL) were added at room temperature. The resulting mixture was stirred for 3 hours at room temperature. The residue was purified by reversed-phase flash chromatography under the following conditions: column, silica gel C18; mobile phase, MeCN in water (0.1% NH3.H2O), gradient from 10% to 50% in 10 min; detector, UV 254 nm. This resulted in (2S)-N-{1-cyano-2-[5(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4-oxazepane-2 Petition 870250103180, dated 11 / 11 / 2025, pp. 191 / 393 184 / 383 carboxamide (21.9 mg, 26.50%) as a white solid. ANALYTICAL DATA

[0810] LCMS (ES, m / z): [M+H]+:477.2.

[0811] RMN de1H (400 MHz, DMSO-d6) δ 8,73 (d, J = 8,3 Hz, 1H), 8,11 (t, J = 2,3 Hz, 1H), 8,06-7,98 (m, 1H), 7,71 -7,63 (m, 2H), 7,49 (d, J = 8,4 Hz, 1H), 7,43 (d, J = 8,3 Hz, 1H), 7,38 (s, 1H), 5,10 (dq, J = 15,4, 8,2 Hz, 1H), 4,00 (ddd, J = 25,9, 7,9, 3,6 Hz, 1H), 3,94 - 3,84 (m, 1H), 3,81 - 3,67 (m, 1H), 3,62 - 3,46 (m, 2H), 3,43 (s, 3H), 3,15 (dd, J = 14,2, 3,7 Hz, 1H), 3,06 (dd, J = 14,2, 3,6 Hz, 1H), 2,85-2,67 (m, 2H), 2,60 (dd, J = 14,4, 8,1 Hz, 1H), 1,81 -1,67 (m, 2H). EXEMPLO 12. SÍNTESE DO COMPOSTO 115A: (2S)-N-{1CIANO-2-[3-FLUORO-5-(3-METIL-2-OXO-1,3-BENZOXAZOL-5-IL)-1BENZOTIOFEN-2-IL1ETIL}-1,4-OXAZEPANO-2-CARBOXAMIDA

[0812] Síntese de ácido 5-bromo-3-fluoro-1-benzotiofeno2-carboxílico LDA, NFSI THF, -78°C F

[0813] To a stirred solution of 5-bromo-1-benzothiophene-2-carboxylic acid (10 g, 38.90 mmol, 1 equiv) in THF (300 mL) LDA (in 2M THF) (97 mL, 194 mmol, 5 equiv) was added by drop at -78 °C Petition 870250103180, dated 11 / 11 / 2025, pp. 192 / 393 185 / 383 under a nitrogen atmosphere. The resulting mixture was stirred for 1 hour at -78 °C under a nitrogen atmosphere. To the above mixture, NFSI (61.32 g, 194 mmol, 5 equiv.) in THF (300 mL) was added dropwise over 30 min at -78 °C. The resulting mixture was stirred for a further 16 hours at room temperature. The reaction was stopped with water at room temperature. The mixture was acidified to pH 7-8 with saturated NaHCO3 (aq.). The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined water layers were acidified to pH 4 with conc. HCl. The precipitated solids were collected by filtration and washed with H2O (3 x 60 mL). This resulted in 5-bromo-3-fluoro-1-benzothiophene-2-carboxylic acid (7 g, 65.42%) as a whitish solid. LCMS (ES, m / z): [MH]-: 273.

[0814] Synthesis of (5-bromo-3-fluoro-1-benzothiophen-2-yl)methanol HO HO \—ά 1 1 BH3-Me2S, THF —d Jfi 1 0-60°C, 16 h FF

[0815] To a stirred solution of 5-bromo-3-fluoro-1-benzothiophene-2-carboxylic acid (1.5 g, 5.45 mmol, 1 equiv.) and THF (30 mL), BH3-Me2S (1.24 g, 16.36 mmol, 3 equiv.) was added dropwise at 0 °C. The resulting mixture was stirred for 16 hours at 60 °C. The reaction was stopped with MeOH at room temperature. The resulting mixture was extracted with EtOAc (3 x 50 mL). The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to give (5-bromo-3-fluoro-1-benzothiophene-2-yl)methanol (1 g, 70.24%) as a whitish solid.

[0816] 1H NMR (400 MHz, DMSO-d6) δ 7.96 (dd, J = 8.6, 1.9 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.58 (dd, J = 8.6, 2.0 Hz, 1H), 5.77 (t, J = 5.8 Hz, 1H), 4.74 (dd, J = 5.8, 1.8 Hz, 2H).

[0817] Synthesis of 5-bromo-2-(bromomethyl)-3-fluoro-1-benzothiophene Petition 870250103180, dated 11 / 11 / 2025, pp. 193 / 393 186 / 383

[0818] To a stirred solution of (5-bromo-3-fluoro-1-benzothiophen-2-yl)methanol (950 mg, 3.64 mmol, 1 equiv) and NBS (777 mg, 4.37 mmol, 1.2 equiv) in DCM (20 mL) was added PPh3 (1145 mg, 4.37 mmol, 1.2 equiv) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred for 3 hours at room temperature under a nitrogen atmosphere. The resulting mixture was extracted with CH2O2 (3 x 50 mL). The combined organic layers were washed with brine (3 x 50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 5-bromo-2(bromomethyl)-3-fluoro-1-benzothiophene (1.1 g, 93.31%) as a light yellow oil.

[0819] Synthesis of 3-(5-bromo-3-fluoro-1-benzothiophen-2-yl)2-[(diphenylmethylidene) amino] propanenitrile

[0820] A solution of 5-bromo-2-(bromomethyl)-3-fluoro-1-benzothiophene (1.1 g, 3.40 mmol, 1 equiv) in THF (10 mL) was added to 2[(diphenylmethylidene)amino]acetonitrile (0.75 g, 3.40 mmol, 1 equiv), benzyltrimethylazanium chloride (0.06 g, 0.34 mmol, 0.1 equiv), NaOH (0.27 g, 6.79 mmol, 2 equiv) in H2O (2 mL) and stirred for 4 hours at 60 °C. The resulting mixture was extracted with CH2Cl2 (3 x 100 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to give 3-(5-bromo-3-fluoro-1-benzothiophen-2-yl)-2[(diphenylmethylidene)amino]propanenitrile (1.5 g, 95.35%) as a whitish solid. LCMS (ES, m / z): [M+H]+: 463. Petition 870250103180, dated 11 / 11 / 2025, pp. 194 / 393 187 / 383

[0821] Synthesis of 2-[(diphenylmethylidene)amino]-3-[3-fluoro5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile

[0822] A solution of 3-(5-bromo-3-fluoro-1-benzothiophen2-yl)-2-[(diphenylmethylidene)amino]propanenitrile (800 mg, 1.73 mmol, 1 equiv), K2CO3 (477 mg, 3.45 mmol, 2 equiv), 3-methyl-5-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)-1,3benzoxazol-2-one (496 mg, 1.90 mmol, 1.1 equiv) and Pd(dppf)Cl2 (131 mg, 0.18 mmol, 0.1 equiv) in 1,4-dioxane (10 mL), H2O (1.5 mL) was stirred for 2 hours at 80 °C under a nitrogen atmosphere. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 2-[(diphenylmethylidene)amino]-3-[3fluoro-5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (700 mg, 76.27%) as a light yellow oil. LCMS (ES, m / z): [M+H]+: 532.

[0823] Synthesis of 2-amino-3-[3-fluoro-5-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile

[0824] In a 100 mL round-bottom flask, 2-[(diphenylmethylidene)amino]-3-[3-fluoro-5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (700 mg, 1.32 mmol, 1 equiv) and THF (30 mL), H2O (3 mL), HCl (2 mL, 10.00 mmol, 7.59 equiv) were added at room temperature. The resulting mixture was stirred for 3 hours at room temperature. The mixture was Petition 870250103180, dated 11 / 11 / 2025, pp. 195 / 393 188 / 383 basified to pH 12 with NaOH. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:2) to give 2-amino-3-[3-fluoro-5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (350 mg, 72.35%) as a white solid. LCMS (ES, m / z): [M+H]+: 368.

[0825] Synthesis of tert-butyl (2S)-2-({1-cyano-2-[3-fluoro-5(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane4-carboxylate To a stirred mixture of 2-amino-3-[3-fluoro-5-(3methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (99 mg, 0.270 mmol, 1.1 equiv), (2S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (60 mg, 0.25 mmol, 1.00 equiv) and DIEA (95 mg, 0.74 mmol, 3 equiv) in DCM (5 mL) were added to HATU (112 mg, 0.29 mmol, 1.2 equiv) in portions at 0 °C. The resulting mixture was stirred for a further 3 hours at 0 °C. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give tert-butyl(2S)-2-({1cyano-2-[3-fluoro-5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (120 mg, 82.49%) as a light yellow oil. LCMS (ES, m / z): [M+H]+: 595.

[0827] Synthesis of (2S)-N-{1-cyano-2-[3-fluoro-5-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4-oxazepane-2-carboxamide Petition 870250103180, dated 11 / 11 / 2025, pp. 196 / 393 189 / 383 TsOH, ACN rt, 2 h

[0828] In a 50 mL round-bottom flask, tert-butyl(2S)-2-({1-cyano-2-[3-fluoro-5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (120 mg, 0.20 mmol equiv), TsOH (108 mg, 0.62 mmol equiv), and ACN (3 mL) were added at room temperature. The resulting mixture was stirred for 3 hours at room temperature. The residue was purified by reversed-phase flash chromatography under the following conditions: column, C18 silica gel; mobile phase, MeCN in water (0.1% NH3.H2O), gradient from 10% to 50% in 10 min; detector, UV 254 nm. This resulted in (2S)-N-{1-cyano-2-[3-fluoro-5-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4-oxazepane-2-carboxamide (20 mg, 20.04%) as a white solid. ANALYTICAL DATA

[0829] LCMS (ES, m / z): [M+H]+: 495.

[0830] 1H NMR (400 MHz, DMSO-d6) 1.8 Hz, 1H), 7.59 - 7.49 (m, 1H), 7.44 (d, J = 8.3 Hz, 1H), 5.14 - 5.03 (m, 1H), 4.07 - 3.82 (m, 2H), 3.74 (td, J = 7.8, 3.5 Hz, 1H), 3.58 (dd, J = 14.5, 7.0 Hz, 1H), 3.51- 3.43 (m, 1H), 3.44 (s, 3H), 3.22 - 3.02 (m, 1H), 2.88 - 2.58 (m, 4H), 1.78 - 1.67 (m, 2H). EXAMPLE 13. SYNTHESIS OF COMPOUND 130A: (2S)-N-{1CYANO-2-[3-FLUORO-6-(3-METHYL-2-OXO-1,3-BENZOXAZOL-5-YL)-1BENZOTIOPHEN-2-YL]ETHYL}-1,4-OXAZEPAN-2-CARBOXAMIDE Petition 870250103180, dated 11 / 11 / 2025, pp. 197 / 393 190 / 383 pH

[0831] Synthesis of 6-bromo-3-fluoro-1-benzothiophene-2-carboxylic acid LTDA, NFSI THF, -78°C~rt 16 h

[0832] To a solution of 6-bromo-1-benzothiophene-2-carboxylic acid (5.5 g, 21.39 mmol, 1.0 equiv) in THF (100 mL) was added LDA (2 M in THF) (53.5 mL, 106.96 mmol, 5.0 equiv) by drop at -78°C under a nitrogen atmosphere. After the addition, the mixture was stirred for 1 hour, followed by the addition of NFSI (33.7 g, 106.96 mmol, 5.0 equiv) in THF (50 mL) by drop. The reaction was heated slowly to room temperature and stirred for 12 hours. The reaction was quenched with HCl (aq) (200 mL), extracted with ethyl acetate (200 mL x 2). The combined organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated, resulting in 6-bromo-3-fluoro-1-benzothiophene-2-carboxylic acid (1.9 g, 32%) as a yellow solid, which was used in the next step without further purification.

[0833] Synthesis of (6-bromo-3-fluoro-1-benzothiophen-2-yl)methanol F b2h6-thf rt~60°C, 2 h F Petition 870250103180, dated 11 / 11 / 2025, pp. 198 / 393 191 / 383

[0834] To a solution of 6-bromo-3-fluoro-1-benzothiophene-2-carboxylic acid (1.9 g, 6.90 mmol, 1.0 equiv) in THF (30 mL) was added B2H6 (1 M in THF) at room temperature under a nitrogen atmosphere. The reaction was heated to 60°C and stirred for 3 hours. The reaction was cooled to room temperature, quenched with HCl(1 N) (20 mL), diluted with water (30 mL), and extracted with ethyl acetate (50 mL x 2). The combined organic phase was dried over anhydrous sodium sulfate. The filtrate was filtered and concentrated and purified by silica gel column with ethyl acetate / petroleum ether 5-10%, resulting in (6-bromo-3fluoro-1-benzothiophene-2-yl)methanol (1 g, 55.4%) as a white solid. LCMS (ES, m / z): [M-H2O+H]+: 243.

[0835] Synthesis of 6-bromo-2-(bromomethyl)-3-fluoro-1-benzothiophene Br Br NBS, PPh3DCM, rt, 3 h

[0836] A solution of (6-bromo-3-fluoro-1-benzothiophen-2-yl)methanol (1.0 g, 3.83 mmol, 1.0 equiv) and NBS (0.8 g, 4.59 mmol, 1.2 equiv) in DCM (10 mL) was stirred for 3 hours at room temperature under a nitrogen atmosphere. Concentrated to remove solvent, the residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to give 6-bromo-2-(bromomethyl)3-fluoro-1-benzothiophene (1.0 g, 80.5%) as a white solid (no LCMS signal).

[0837] Synthesis of 3-(6-bromo-3-fluoro-1-benzothiophen-2-yl)2-[(diphenylmethylidene) amino]propanenitrile

[0838] A solution of 6-bromo-2-(bromomethyl)-3-fluoro-1-benzothiophene (1.0 g, 3.08 mmol, 1.0 equiv) in THF (10 mL) was added to 2[(diphenylmethylidene)amino]acetonitrile (0.7 g, 3.08 mmol, 1.0 equiv), chloride Petition 870250103180, dated 11 / 11 / 2025, pp. 199 / 393 192 / 383 benzyltrimethylazanium (0.1 g, 0.30 mmol, 0.1 equiv), NaOH (0.3 g, 6.17 mmol, 2.0 equiv) in H2O (2 mL) was stirred for 2 hours at 60 °C. The resulting mixture was diluted with water (20 mL) and extracted with EtOAc (3 x 50 mL). The combined organic layer was washed with brine (3 x 30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 3-(6-bromo-3-fluoro-1-benzothiophen-2-yl)-2-[(diphenylmethylidene)amino]propanenitrile (1.3 g, 90.9%) as a yellow solid. LCMS (ES, m / z): [M+H]+: 463.

[0839] Synthesis of 2-[(diphenylmethylidene)amino]-3-[3-fluoro6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile benzothiophen-2-yl)-2-[(diphenylmethylidene)amino]propanenitrile (1.3 g, 2.80 mmol, 1.1 equiv), 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-one (0.7 g, 2.55 mmol, 1.0 equiv), in 1,4-dioxane (10 mL) and H2O (1 mL), K2CO3 (0.7 g, 5.10 mmol, 2.0 equiv) and Pd(dppf)Cb (0.2 g, 0.25 mmol, 0.1 equiv) were added sequentially. The reaction was stirred for 3 hours at 80 °C under a nitrogen atmosphere. The reaction was cooled to room temperature, concentrated to remove solvent, the residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give 2-[(diphenylmethylidene)amino]-3-[3-fluoro-6-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (1.3 g, 95.8%) as yellow oil. LCMS (ES, m / z): [M+H]+: 532.

[0841] Synthesis of 2-amino-3-[3-fluoro-6-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile Petition 870250103180, dated 11 / 11 / 2025, pp. 200 / 393 193 / 383

[0842] In a 100 mL round-bottom flask, 2-[(diphenylmethylidene)amino]-3-[3-fluoro-6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (1.3 g, 2.44 mmol, 1.0 equiv) and 1 M HCl (3 mL) and 6 mL of H2O were added at room temperature. The resulting mixture was stirred for 3 h at room temperature. The resulting mixture was extracted with Et2O (1 x 50 mL). The mixture was basified to pH ~12 with 2 M NaOH in water. The aqueous layer was extracted with 3 x 50 mL CH2O2. The combined organic layer was washed with brine (3 x 50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 2-amino-3-[3-fluoro-6-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (560 mg, 62.3%) as a white solid. LCMS (ES, m / z): [M+H]+: 367.

[0843] Synthesis of tert-butyl (2S)-2-({1-cyano-2-[3-fluoro-6(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane4-carboxylate

[0844] A solution of 2-amino-3-[3-fluoro-6-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]propanenitrile (89 mg, 0.24 mmol, 1.2 equiv) in DMF (2 mL) was treated with (2S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (50 mg, 0.20 mmol, 1.0 equiv), DIEA (79 mg, 0.61 mmol, 3.0 equiv) followed by the addition of HATU (93 mg, 0.24 mmol, 1.2 equiv) in portions at 0°C. The resulting mixture was stirred for a further 2 hours at 0°C. The residue was purified. Petition 870250103180, dated 11 / 11 / 2025, pp. 201 / 393 194 / 383 by silica gel column chromatography, eluted with PE / THF (1:1) to give tert-butyl(2S)-2-({1-cyano-2-[3-fluoro-6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (100 mg, 82.4%) as colorless oil. LCMS (ES, m / z): [M+H]+: 595.

[0845] Synthesis of (2S)-N-{1-cyano-2-[3-fluoro-6-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}-1,4-oxazepane-2-carboxamide

[0846] In a 25 mL round-bottom flask, tert-butyl(2S)-2-({1-cyano-2-[3-fluoro-6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (100 mg, 0.16 mmol, 1.0 equiv) in ACN (3 mL) and TsOH.H2O (96 mg, 0.50 mmol, 3.0 equiv) were added at room temperature. The resulting mixture was stirred for 3 h at room temperature. The reaction solution was purified by reversed-phase flash chromatography under the following conditions: column, C18-120 g silica gel; Mobile phase, MeCN in water (0.1% NH3.H2O), gradient from 10% to 50% in 10 min; detector, UV 254 nm. This resulted in (2S)-N-{1-cyano-2-[3-fluoro-6-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-2yl]ethyl}-1,4-oxazepane-2-carboxamide (20.5 mg, 24.6%) as a white solid. ANALYTICAL DATA

[0847] LCMS (ES, m / z): [M+H]+: 495.4

[0848] de1H NMR (400 MHz, DMSO- d6) δ 8.80 (dd, J = 8.5, 1.3 Hz, 1H), 8.34 (s, 1H), 7.83 (t, J = 1.6 Hz, 2H), 7.72 (d, J = 1.59 Hz), 7.5 Hz (dd, J = 8.4, 1.9 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 5.08 (dtd, J = 11.4, 8.4, 6.9 Hz, 1H), 4.06 - 3.84 (m, 2H), 4.3 Hz, 1H), 3.56 (ddd, J = 14.6, 6.9, 2.3 Hz, 1H), 3.51 - 3.42 (m, 4H), 3.11 (ddd, J = 35.1, 14.2, 3.6 Hz, 1H, 14.2, 3.5 Hz), 1.88 -1.62 (m, 2H). Petition 870250103180, of 11 / 11 / 2025, p. 202 / 393 195 / 383 EXAMPLE 14. SYNTHESIS OF COMPOUND 131A: (2S)-N-{1CYANO-2-[2-(3-METHYL-2-OXO-1,3-BENZOXAZOL-5-YL)-1-BENZOTHIOPHENE-5-YL1ETHYL}1,4-OXAZEPANO-2

[0849] Synthesis of methyl 2-bromobenzo[b]thiophene-5carboxylate —ο S LDA, EtBr2—O / / )— S $ thf, -78°C qZ

[0850] To a stirred solution of methylbenzo[b]thiophene-5-carboxylate (2 g, 10.40 mmol, 1.0 equiv) and THF (30 mL) was added LDA (2 M in THF) (6.24 mL, 12.48 mmol, 1.2 equiv) by drop at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred for 1 hour at -78 °C under a nitrogen atmosphere. To the above mixture was added dibromoethane (2.15 g, 11.44 mmol, 1.1 equiv) by drop at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred for a further 1 hour at room temperature under a nitrogen atmosphere. The reaction was stopped by the addition of water (50 mL) at room temperature and extracted with EtOAc (3 x 50 mL). The combined organic layer was dried over Petition 870250103180, dated 11 / 11 / 2025, pp. 203 / 393 196 / 383 Anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12:1) to give methyl 2-bromobenzo[b]thiophene-5-carboxylate (1.7 g, 60%) as a light yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 8.44 (s, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.91 (dd, J = 8.5, 1.6 Hz, 1H), 7.81 (s, 1H), 3.90 (s, 3H).

[0851] Synthesis of (2-bromo-1-benzothiophen-5-yl)methanol —n DIBAL-H, THF , / ==\ °k / S ΗΟχ__ / λ—S O -78°C~rt, 1 h ^\Αβγ

[0852] To a solution of methyl 2-bromobenzo[b]thiophene-5-carboxylate (1.3 g, 4.79 mmol, 1.0 equiv) and tetrahydrofuran (25 mL), DIBAL-H (14.4 mL, 14.38 mmol, 3.0 equiv) (1 M in toluene) was added dropwise under a nitrogen atmosphere at -78°C. After addition, the mixture was slowly heated to room temperature and stirred for 1 hour. The reaction was quenched with HCl (1 N) (10 mL) at 0°C, diluted with water (20 mL), and extracted with EtOAc (2 x 50 mL). The combined organic layer was washed with brine (50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to give (2-bromo-1-benzothiophen-5-yl)methanol (1.0 g, 85.7%) as a white solid. LCMS (ES, m / z): [M-H2O+H]+: 225.

[0853] Synthesis of 2-bromo-5-(bromomethyl)-1-benzothiophene HO SPBr3> Et2OBrs \ '-^X^Br rt, 2 h —\XBr

[0854] A solution of (2-bromo-1-benzothiophen-5-yl)methanol (1 g, 4.11 mmol, 1.0 equiv) in Et2O (10 mL) was treated with PBr3 (0.6 g, 2.05 mmol, 0.5 equiv) at 0°C. The resulting mixture was stirred for 2 hours at room temperature. The reaction was quenched with water (20 mL) at 0°C, extracted with EtOAc (30 mL), washed with brine (30 mL), and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Petition 870250103180, dated 11 / 11 / 2025, pp. 204 / 393 197 / 383 silica gel column chromatography, eluted with PE / EA (3:1) to give 2-bromo-5-(bromomethyl)-1-benzothiophene (700 mg, 55.6%) as a white solid (no LCMS signal).

[0855] Synthesis of 3-(2-bromo-1-benzothiophen-5-yl)-2[(diphenylmethylidene) amino]propanenitrile 40°C, 36 h

[0856] To a solution of 2-bromo-5-(bromomethyl)-1-benzothiophene (600 mg, 1.96 mmol, 1.0 equiv) in DCM (5 mL) was added 2[(diphenylmethylidene)amino]acetonitrile (432 mg, 1.96 mmol, 1.0 equiv), benzyltrimethylazanium chloride (36 mg, 0.19 mmol, 0.1 equiv), NaOH (159 mg, 3.92 mmol, 2.0 equiv), and H2O (1 mL) in sequence. The mixture was stirred for 36 hours at 40°C. The reaction solution was diluted with water (20 mL), extracted with CH2Cl2 (2 x 30 mL). The combined organic layer was washed with brine (30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 3-(2-bromo-1-benzothiophen-5-yl)-2-[(diphenylmethylidene)amino]propanenitrile (800 mg, crude) as a yellow solid. LCMS (ES, m / z): [M+H]+: 445.

[0857] Synthesis of 2-[(diphenylmethylidene)amino]-3-[2-(3-methyl2-OXO-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]propanenitrile Pb dioxane / HLO, 80 °C, 2 h

[0858] To a solution of 3-(2-bromo-1-benzothiophen-5-yl)-2[(diphenylmethylidene)amino]propanenitrile (350 mg, 0.78 mmol, 1.0 equiv), 3-methyl-5 Petition 870250103180, dated 11 / 11 / 2025, pp. 205 / 393 198 / 383 (4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol-2-one (205 mg, 0.78 mmol, 1.0 equiv) in 1,4-dioxane (10 mL) and H2O (1 mL), K2CO3 (217 mg, 1.57 mmol, 2.0 equiv) and Pd(dppf)Cb (58 mg, 0.07 mmol, 0.1 equiv) were added under a nitrogen atmosphere. The mixture was stirred for 2 hours at 80°C. The reaction was cooled to room temperature, concentrated to remove solvent, the residue was purified by silica gel column chromatography, eluted with PE / THF (5:1) to give 2[(diphenylmethylidene)amino]-3-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]propanenitrile (120 mg, 30%) as a white solid. LCMS (ES, m / z): [M+H]+: 514.

[0859] Synthesis of 2-amino-3-[2-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-5-yl]propanenitrile HCI, THF / H2O rt, 3h In a 100 mL round-bottom flask, 2-[(diphenylmethylidene)amino]-3-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]propanenitrile (350 mg, 0.68 mmol, 1.0 equiv) and THF (30 mL), H2O (3 mL) were added at room temperature. The resulting mixture was stirred for 3 h at room temperature. The mixture was basified to pH 12 with NaOH (2 N). The resulting mixture was extracted with EtOAc (2 x 50 mL). The combined organic layer was washed with brine (50 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / THF (1:2) to give 2-amino-3-[2-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]propanenitrile (120 mg, 50.4%) as a white solid. LCMS (ES, m / z): [M+H]+: 349.

[0861] Synthesis of tert-butyl (2S)-2-({1-cyano-2-[2-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]ethyl}carbamoyl)-1,4-oxazepane-4carboxylate Petition 870250103180, dated 11 / 11 / 2025, pp. 206 / 393 199 / 383

[0862] To a stirred mixture of 2-amino-3-[2-(3-methyl-2oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]propanenitrile (110 mg, 0.31 mmol, 1.2 equiv), (2S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (64 mg, 0.26 mmol, 1.0 equiv) and DIEA (102 mg, 0.78 mmol, 3.0 equiv) in DCM (5 mL) was added HATU (119 mg, 0.31 mmol, 1.2 equiv) in portions at 0°C. The resulting mixture was stirred for a further 3 hours at 0°C. Concentrated under reduced pressure, the residue was purified by silica gel column chromatography, eluted with PE / THF (1:1) to give tert-butyl(2S)-2-({1-cyano-2-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]ethyl}carbamoyl)-1,4-oxazepane-4-carboxylate (120 mg, 79%) as a white solid. LCMS (ES, m / z): [M+H]+: 577.

[0863] Synthesis of (2S)-N-{1-cyano-2-[2-(3-methyl-2-oxo-1,3benzoxazol-5-yl)-1-benzothiophen-5-yl]ethyl}-1,4-oxazepane-2-carboxamide tert-butyl (2S)-2-{[(1S)-1-cyano-2-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]ethyl]carbamoyl}-1,4-oxazepane-4-carboxylate (120 mg, 0.20 mmol, 1.0 equiv), TsOH (108 mg, 0.62 mmol, 3.0 equiv) and ACN (3 mL) were added at room temperature. The resulting mixture was stirred for 3 h at room temperature. The reaction solution was purified by reversed-phase flash chromatography under the following conditions: column, C18 silica gel 120 g; mobile phase, MeCN in water (0.1% NH3.H2O), gradient from 10% to 50% in 10 min; detector, UV 254 nm. This resulted in (2S)-N{1-cyano-2-[2-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)-1-benzothiophen-5-yl]ethyl}-1,4-oxazepane-2-carboxamide (16.3 mg, 16.44%) as a white solid. Petition 870250103180, dated 11 / 11 / 2025, p. 207 / 393 200 / 383 ANALYTICAL DATA

[0865] LCMS (ES, m / z): [M+H]+: 477.2

[0866] NMR de1H (400 MHz, DMSO- de) δ 8.61 (dd, J = 8.4, 6.0 Hz, 1H), 7.93 (dd, J = 8.2, 3.0 Hz, 1H), 7.86 (d, J = 2.2 Hz, 1H), 7.75 - 7.73 (m, 2H), 7.51 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.3 Hz, 1H), 7.30 (d, J = 8.3 Hz, 1H), 5.10 - 4.97 (m, 1H), 4.00 - 3.80 (m, 2H), 3.75 - 3.67 (m, 1H), 3.43 (s, 3H), 3.29 - 3.26 (m, 2H), 3.14 - 2.97 (m, 1H), 2.83 - 2.63 (m, 2H), 2.56 - 2.41 (m, 2H), 1.78 - 1.68 (m, 2H). EXAMPLE 15. SYSTEM OF (2 S)-A / -(1-CYANO-2-(3-(3-METHYL2-OXO-2,3-DI-HYDROBENZO[D]OXAZOL-5-IL)BICICLO[1.1.1]PENTAN-1-IL)ETHYL)1,4-OXAZEPAN-2-CARBOXAMIDA (COMPOUND 101E) Methyl 3-phenylbicyclo[1.1.1]pentane-1-carboxylate, MeOOC Pb(OAc)4(1.25 eq) MeOOC COOH 2.0 g benzene C=0.55m, 80 °C, 6 h, Watered by 400 W halogen lamp 1.68 g. 71%

[0867] 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (2.00 g, 1 Eq, 11.8 mmol) and lead tetraacetate (6.86 g, 95% by weight, 1.25 Eq, 14.7 mmol) were dissolved in benzene (214 mL), the flask was fitted with a condenser sealed with a septum and a small N2 balloon (CO2 release). The mixture was irradiated by a 400 W tungsten lamp for 6 h, and a large amount of white inorganic precipitate was formed.

[0868] After cooling the reaction flask, the white suspension was filtered through a shallow bed (30 g) of celite and a celite bed was washed with a mixture of ethyl acetate:cyclohexane 1:4 (3 x 100 mL). The clear, colorless filtrate was then concentrated under reduced pressure to give 2.82 g of crude oil.

[0869] Purification by flash column chromatography - 80g [cHex / EA] - 0% of 1CV, then 0->15% of 2CV and 15% of 4CV. To produce methyl 3-phenylbicyclo[1,1,1]pentane-1-carboxylate as colorless oil (1.68 g, 8.31 mmol) Petition 870250103180, dated 11 / 11 / 2025, pp. 208 / 393 201 / 383 (71% return).

[0870] TLC: cHex / DCM / EA 90:5:5,

[0871] The product can be visualized by staining with KMnO4.

[0872] 1H NMR (400 MHz, DMSO) δ 7.35 - 7.29 (m, 2H), 7.28 - 7.21 (m, 3H), 3.64 (s, 3H), 2.26 (s, 6H).

[0873] 3-phenylbicyclo[1.1.1]pentane-1-carboxylic acid LiOH (2.0 eq) THF / water 1:1, C=0.025M, RT

[0874] To a biphasic solution of methyl 3-phenylbicyclo[1.1.1]pentane-1-carboxylate (1600 mg, 1 Eq, 7.911 mmol) in a mixture of THF (79.0 mL) and H2O (79.0 mL), lithium hydroxide monohydrate (663.9 mg, 2 Eq, 15.82 mmol) was added in a portion. The reaction mixture was stirred at 25 °C for 16 hours. The conversion was determined by LCMS - total conversion. The basic mixture was diluted with 200 mL of water and washed with DCM 2 x 50 mL. LCMS of the organic phase - confirms that there is no product, only impurities. The aqueous phase was acidified with 1M KHSO4 (20 mL) and extracted with EtOAc (3 x 100 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated to dryness to give 3-phenylbicyclo[1,1,1]pentane-1-carboxylic acid as a white solid (1.31 g, 6.96 mmol - 88% yield).

[0875] Alternatively:

[0876] To a biphasic solution of crude methyl 3-phenylbicyclo[1.1.1]pentane-1-carboxylate (assuming 4750 mg, 1 Eq, 23.50 mmol) in a mixture of THF (235 mL) and H2O (235 mL), excess sodium hydroxide (2.82 g, 3 Eq, 70.50 mmol) was added in a portion. The reaction mixture was stirred at 25 °C for 16 hours. The conversion was determined by LCMS total conversion. Purification as described above, this method leads to 3-phenylbicyclo[1.1.1]pentane-1-carboxylic acid with a slightly better total yield (2.96 Petition 870250103180, dated 11 / 11 / 2025, pp. 209 / 393 202 / 383 g, 15.70 mmol - 67% yield in two steps).

[0877] The product can be visualized by staining with KMnO4.

[0878] 1H NMR (400 MHz, DMSO) δ 12.40 (s, 1H), 7.35 - 7.29 (m, 2H), 7.27 - 7.20 (m, 3H), 2.21 (s, 6H).

[0879] 3-Phenylbicyclo[1,1,1]pentane-1-carboxamide hoocl oxalyl chloride (1.5 eq), _________DMF(0.1eq). Cl EtaO. C-0.02M, 25 *C. 2h

[0880] To a solution of 3(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (1430 mg, 1 Eq, 7.597 mmol) and oxalyl chloride (1253 mg, 1.3 Eq, 9.876 mmol, 864.5 μL) in Et20 (38 mL), DMF (55 mg, 0.1 Eq, 0.76 mmol, 60 pL) as a catalyst was added dropwise. The mixture was stirred for about 2 h, until no further gas evolution was observed.

[0881] TLC - [EA] — >[A 20 pL sample was collected and tempered with MeOH], visualization by KMnCu staining shows total SM consumption - formation of a less polar point.

[0882] The reaction mixture was concentrated to dryness in a rotary evaporator to obtain an orange liquid, used as crude in the next step.

[0883] Crude 3-phenylbicyclo[1,1,1]pentane-1-carbonyl chloride (assumed to be 1.570 g, 1 Eq, 7.597 mmol) was dissolved in DCM (44 mL) and added dropwise to the cold (-20 °C) ammonia solution in MeOH (5.175 g, 43.5 mL, 7 molar, 40 Eq, 304 mmol) over 15 minutes. The mixture was stirred at -20 °C for a further 2 h and allowed to reach 25 °C overnight (16 h).

[0884] LCMS shows the complete conversion of the initial material.

[0885] The reaction mixture was concentrated under vacuum and coevaporated with CH2Cl2 twice. The solid was dissolved in DCM (150 mL) and washed with NaHCO3 / brine [2:8] (150 mL) and brine (150 mL), dried and Petition 870250103180, dated 11 / 11 / 2025, pp. 210 / 393 203 / 383 evaporated to obtain 3-phenylbicyclo[1.1.1]pentane-1-carboxamide (1.35 g, 7.21 mmol - 95% yield) as a white solid.

[0886] 1H NMR (400 MHz, DMSO) δ 7.36 - 7.27 (m, 3H), 7.27 - 7.18 (m, 3H), 6.96 (s, 1H), 2.14 (s, 6H).

[0887] Alternatively:

[0888] Crude 3-phenylbicyclo[1,1,1]pentane-1-carbonyl chloride (assumed to be 1.437 g, 1 Eq, 6.954 mmol) was dissolved in DCM (70 mL) and cooled to 0 °C, ammonium chloride (1.488 g, 4 Eq, 27.82 mmol) was added in a portion followed by the dropwise addition of triethylamine (7.037 g, 9.69 mL, 10 Eq, 69.54 mmol). The mixture was stirred for 2 hours at 0 °C and allowed to reach 25 °C overnight; stirring continued over the weekend. LCMS shows a mixture of acid and amide. The compounds were separated by 2M HCl / 1M NaOH extractions...

[0889]

[0890] 3-Phenylbicyclo[1.1,1]pentane-1-carbonitrile TFAA (2.0 eq), Et3N (5.0 eq) DCM. C=0.1M, 0->25 °C. 18h A solution 3-phenylbicyclo[1.1.1]pentane-1-carboxamide (1.311 g, 1 Eq, 7.000 mmol) in dry DCM (70.00 mL), triethylamine (3.542 g, 4.88 mL, 5 Eq, 35.00 mmol) was added followed by the dropwise addition of trifluoroacetic anhydride (2.940 g, 1.955 mL, 2 Eq, 14.00 mmol). The resulting reaction mixture was allowed to reach 25 °C and stirring continued for 18 hours. After LCMS showed complete conversion of the starting material, the flask was cooled in an ice bath and the reaction was stopped with NaHCO3 (30 mL), extracted with DCM (2 x 50 mL), then the organic layer was washed with 1N KHSO4 to pH 2, water and brine, and the organic extract was dried over anhydrous Na2SO4.

[0891] Purification by flash column chromatography - 20g Petition 870250103180, dated 11 / 11 / 2025, page 211 / 393 204 / 383 [pentane / Et2O] - 0%-1CV, then 0->15%-1CV and 15%-4CV. To produce 3-phenylbicyclo[1.1.1]pentane-1-carbonitrile as colorless oil (1.185 g, 7.00 mmol - >99% yield).

[0892] 1H NMR (400 MHz, CDCI3) δ 7.35 - 7.27 (m, 3H), 7.19-7.15 (m, 2H), 2.51 (s, 6H).

[0893] 5-(4-(3cyanobicyclo[1.1,1]pentan-1-yl)phenyl)-5H-tianthren-5-ium tetrafluoroborate, TFAA (3.0 eq), HBF4-Et2O (2.0 eq) MeCN, C=0.2M, -35->22 °C. 3h

[0894] Under ambient atmosphere, a 50 mL RBF was sequentially charged with 3-phenylbicyclo[1.1.1]pentane-1-carbonitrile (694 mg, 4.10 mmol), thianthrene-S oxide (1.0 g, 1.05 Eq, 4.30 mmol), and dry MeCN (20.5 mL, c = 0.20 M). After most of the solids had dissolved (approximately 5 min), the solution was cooled to -35 °C, then TFAA (2.58 g, 1.74 mL, 3.0 Eq, 12.30 mmol) was added in a portion, followed by the dropwise addition of tetrafluoroboric acid (1.32 g, 1.11 mL, 2.0 Eq, 8.20 mmol). The mixture was heated to 23 °C for 1.5 hours and stirred at room temperature for the next 1.5 hours. LCMS shows complete conversion of SM. The solution was then diluted with 150 mL of DCM and poured into a separatory funnel. The organic layer was washed with 50 mL of NaHCO3 / 100 mL of brine, and the aqueous phase was extracted three times with 50 mL of DCM.The combined organic extracts were washed with 150 ml of 10% aqueous NaBF4 solution and dried with Na2SO4, filtered and concentrated under reduced pressure.

[0895] The crude oil was purified by column: FCC-12g, silica, [DCM / MeOH — 2CV-100% - DCM, then 4CV 0->10% and 4CV-10% (Pure product with 8 to 10% methanol). To obtain the product (1.35 g, 2.86 mmol, 70%).

[0896] TLC (DCM:MeOH 9:1), Product rf 0.42. Petition 870250103180, dated 11 / 11 / 2025, p. 212 / 393 205 / 383

[0897] 1H NMR (400 MHz, DMSO) δ 8.56 (d, J = 6.8 Hz, 2H), 8.05 (dd, J = 7.8, 1.2 Hz, 2H), 7.92 (td, J = 7.7, 1.5 Hz, 2H), 7.85 (td, J = 7.7, 1.4 Hz, 2H), 7.38 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.6 Hz, 2H), 2.50 (s, 6H).

[0898] 5-(4-(3(methoxycarbonyl)bicyclo[1.1,1]pentan-1-yl)phenyl)-5H-tianthren-5-ium tetrafluoroborate

[0899] Under ambient atmosphere, a 50 mL RBF was sequentially charged with 3-phenylbicyclo[1.1.1]pentane-1-carbonitrile (1.75 g, 8.65 mmol), thianthrene-S oxide (2.21 g, 1.10 Eq, 9.52 mmol), and dry MeCN (43.2 mL, c = 0.20 M). After most of the solids had dissolved (approximately 5 min), the solution was cooled to -35 °C, then TFAA (5.45 g, 3.66 mL, 3.0 Eq, 25.96 mmol) was added in a portion, followed by the dropwise addition of tetrafluoroboric acid (2.78 g, 2.35 mL, 2.0 Eq, 17.31 mmol). The mixture was heated to 23 °C for 1.5 hours and stirred at room temperature for the next 1.5 hours. LCMS shows complete conversion of SM. The solution was then diluted with 150 mL of DCM and poured into a separatory funnel. The organic layer was washed with 50 mL of NaHCO3 / 100 mL of brine, and the aqueous phase was extracted three times with 50 mL of DCM.The combined organic extracts were washed with 150 ml of 10% aqueous NaBF4 solution and dried with Na2SO4, filtered and concentrated under reduced pressure.

[0900] The crude oil was purified by column: FCC-12g, silica, [DCM / MeOH — 2CV-100% - DCM, then 4CV 0->10% and 4CV-10% (Pure product with 8 to 10% methanol). To obtain the product (3.06 g, 6.08 mmol, 70%).

[0901] TLC (DCM:MeOH 9:1), Product rf 0.42.

[0902] 1H NMR (400 MHz, DMSO) δ 8.56 (dd, J = 7.9, Petition 870250103180, dated 11 / 11 / 2025, pp. 213 / 393 206 / 383 1.3 Hz, 2H), 8.06 (dd, J = 7.9, 1.2 Hz, 2H), 7.92 (td, J = 7.8, 1.5 Hz, 2H), 7.85 (td, J = 7.7, 1.4 Hz, 2H), 7.41 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.6 Hz, 2H), 3.61 (s, 3H), 2.24 (s, 6H).

[0903] methyl 3-(4-hydroxyphenyl)bicyclo[1.1.1]pentane-1-carboxylate MeO,C CuTc 1.5 equiv. lr[dF(CF3)ppy]2(dtbpy)PFe] 1 mol% MeO,C Θ BF. MeCN / H2O Blue LEDs, 16 hours

[0904] A loaded bottle 5-(4-(3(methoxycarbonyl)bicyclo[1.1.1]pentan-1-yl)phenyl)-5 / - / -tiantren-5-io tetrafluoroborate (252 mg, 1 Eq, 0.500 mmol), copper(1)thiophene-2-carboxylate (143 mg, 1.5 Eq, 750 pmol) and (4,4'-di-t-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-(5-trifluoromethyl-2-pyridinyl-kN)phenylkC]iridium(1 11) hexafluorophosphate (5.61 mg, 0.01 Eq, 5.00 pmol). The flask was evacuated and filled with nitrogen three times. MeCN (2.50 mL) and H2O (180 mg, 180 pL, 20 Eq, 10.0 mmol) were added. A blue LED lamp (450 nm) was installed. The reaction mixture was stirred overnight under irradiation. The lamp was switched off, EtOAc was added, the mixture was filtered over S1O2, and the flask was concentrated to dryness. The crude product was purified by MPLC Biotage Cyclohexane to EtOAc to provide methyl 3-(4-hydroxyphenyl)bicyclo[1,1,1]pentane-1-carboxylate (76.0 mg, 70%).

[0905] 1H NMR (400 MHz, CDCb) δ 7.12 - 7.06 (m, 2H), 6.80 - 6.75 (m, 2H), 3.71 (s, 3H), 2.28 (s, 6H).

[0906] ethyl / methyl 3-(4-hydroxy-3-nitrophenyl)bicyclo[1.1.1]pentane-1-carboxylate Fe(NO3)39H2O 1.1 equiv EtOH NO2 MeO2C °C 3h Et / MeO2C

[0907] To a solution of methyl 3-(4-hydroxyphenyl)bicyclo[1.1.1]pentane-1-carboxylate (305.6 mg, 1 Eq, 1.400 mmol) in EtOH Petition 870250103180, dated 11 / 11 / 2025, pp. 214 / 393 207 / 383 (14.00 mL) was added to a portion of iron(III) nitrate nonahydrate (622.2 mg, 1.1 Eq, 1.540 mmol). The mixture was stirred at 60 °C for 3 h. Aqueous 6N HCl was added to the brown solution and the mixture was extracted with DCM. The organic phases were combined, washed with brine, dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using hexane / EtOAc as eluent to give methyl 3-(4-hydroxy-3-nitrophenyl)bicyclo[1,1,1]pentane-1-carboxylate (158 mg, 600 pmol, 42.9%). Mixture of Me and Et esters.

[0908] 1H NMR (400 MHz, CDCb) δ 10.52 (s, 1H), 7.89 (d, J=2.2 Hz, 1H), 7.44 (dd, J = 8.6, 2.2 Hz, 1H), 7.11 (d, J=8.6Hz, 1H), 4.17 (q, J = 7.1 Hz, 1H), 3.72 (s, 1H), 2.33 (2 s, 6H), 1.29 (t, J= 7.1 Hz, 2H).

[0909] ethyl / methyl 3-(3-amino-4-hydroxyphenyl)bicyclo[1,1,1]pentane-1-carboxylate

[0910] A flask was loaded with methyl 3-(4-hydroxy-3-nitrophenyl)bicyclo[1,1,1]pentane-1-carboxylate (158 mg, 1 Eq, 600 pmol), palladium on carbon (36.8 mg, 0.576 Eq, 346 pmol), and MeOH (3.00 mL). It was evacuated and filled with N2 three times and then with H2 three times. The reaction mixture was filtered after three hours. The solvent was removed under vacuum. Crude NMR: pure. Quant, assumed.

[0911] 1H NMR (60 MHz, CDCb) δ 6.59 (s, 3H), 4.17 (m, 2H), 3.71 (s, 1H), 2.23 (s, 6H), 1.28 (t, J= 7.2 Hz, 2H).

[0912] ethyl / methyl 3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5yl)bicyclo[1,1,1]pentane-1-carboxylate GDI (1.3 equiv) THF °C 16h Et / MeO2C THE ÍUo Petition 870250103180, dated 11 / 11 / 2025, pp. 215 / 393 208 / 383

[0913] A sealed 4 mL tube was loaded with ethyl / methyl 3-(3-amino-4-hydroxyphenyl)bicyclo[1.1.1]pentane-1-carboxylate (140.0 mg, 1 Eq, 600.2 pmol) + di(1H-imidazol-1-yl)methanone (126.5 mg, 1.3 Eq, 780.2 pmol) and THF (1200 mL). The reaction mixture was stirred at 65 °C for 16 hours. Then, it was allowed to cool to room temperature, water was added, and it was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. Quant, presumed

[0914] 3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5yl)bicyclo[1,1,1]pentane-1-carboxylate ethyl / methyl

[0915] In a 50 mL RBF, a solution of ethyl / methyl 3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1,1,1]pentane-1-carboxylate (155.61 mg, 1 Eq, 600.200 pmol) in DMF (2.00067 mL) was added at room temperature to potassium carbonate (207.37 mg, 2.5 Eq, 1.50050 mmol) and methyl iodide (170.38 mg, 75.06 pL, 2 Eq, 1.20040 mmol). The reaction mixture was stirred at room temperature for 16 hours. The water and precipitate were filtered. The cake was dissolved in EtOAc and dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified by FC (S1O2, cyclohexane to cyclohexane:EtOAc) to give ethyl / methyl 3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentane-1-carboxylate (145.7 mg, 533.1 pmol, 88.83%) as a solid. Mixture of Me and Et esters.

[0916] 1H NMR (60 MHz, CDCb) δ 7.22 - 6.75 (m, 3H), 4.12 (m, 2H), 3.72 (s, 1H), 3.40 (s, 3H), 1.23 (m, 3H).

[0917] 3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1,1,1]pentane-1-carboxylic acid Petition 870250103180, dated 11 / 11 / 2025, pp. 216 / 393 209 / 383 HCl 6N 1,4-dioxane 110 °C 1 h to a solution of 3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentane-1-carboxylate methyl (146 mg, 1 Eq, 534 pmol) in 1,4-dioxane (3.56 mL) was added at room temperature to 6N HCl (1.78 mL). The rxn was stirred at 110 °C for 2 hours. Water was added and the precipitate was filtered. The cake was dissolved in EtOAc and dried over anhydrous Na2SO4 and concentrated to dryness. Quant, presumed

[0919] 1H NMR (60 MHz, CDCb) δ 8.77 (s, 1H), 7.21 6.75 (m, 3H), 3.40 (s, 3H), 2.37 (s, 6H).

[0920] Methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(3-(3-methyl-2oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanoate co2Me Y^NBoCj 1,2 equiv DMF, RT, 16 h blue LEDs 4CzlPN 2% mol K2HPO42.5 equiv

[0921] Flask charged with 3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1,1,1]pentane-1-carboxylic acid (50.000 mg, 1 Eq, 192.86 pmol), 4CzlPN (2.8576 mg, 0.02 Eq, 3.8571 pmol), methyl 2-(bis(tert-butoxycarbonyl)amino)acrylate (69.738 mg, 1.2 Eq, 231.43 pmol), dibasic potassium phosphate (83.975 mg, 2.5 Eq, 482.14 pmol) and DMF (1.9286 mL). Degassed for 15 min. A 450 blue LED lamp was installed and the reaction mixture was irradiated for 16 hours. Addition of water and extraction with EtOAc, dried over Na2SO4, concentrated to dryness. Purification by MPLC (cyclohexane / EtOAc) to give methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanoate (47.2 mg, 91.4 pmol, 47.4%).

[0922] 1H NMR (400 MHz, CDCh) <5 7.13-7.03 (m, 2H), Petition 870250103180, dated 11 / 11 / 2025, p. 217 / 393 210 / 383 6.88 (d, J = 1.9 Hz, 1 Η), 4.98 (dd, J = 7.6, 3.5 Hz, 1H), 3.71 (s, 3H), 3.39 (s, 3H), 2.25 -2.19 (m, 1H), 1.82 (t, J= 7.8 Hz, 6H), 1.51 (s, 18H).

[0923] 2-Amino-3-(3-(3-methyl-2-oxo-2,3dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanoic acid hydrochloride HCl 6N 1,4-dioxane 110 °C 2 h

[0924] to a solution of methyl 2-(bis(tert-butoxycarbonyl)amino)3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1,1,1]pentan-1-yl)propanoate (47.2000 mg, 1 Eq, 91.368 pmol) in 1,4-dioxane (609.12 pl) was added at room temperature 6N HCl (304.56 μL). The reaction mixture was stirred at 110 °C for 2 hours. The solvent was removed under vacuum. Quant, assumed

[0925] NMR de1H (400 MHz, D2O) δ 6.89 (d, J = 8.2 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 6.78 (s, 1H), 4.12 (t, J = 5.8 Hz, 1H), J = 6.3, J Hz, 1H), 3.12 (s, 3H), 2.34-2.21 (m, 2H), 2.02 (s, 6H).

[0926] 2-((terc -butoxycarbonyl)amino)-3-(3-(3-methyl2-oxo-2,3-di-hydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanoic acid In Boc2O 2.0 equiv. I CO2H Na2CO310.0 equiv. CO2H Ν^,Ο H2N—( / / =< f --------------► BocHN—( . / =< Γ \—O—C .xothf / h2o \—Zx—g V_7 rt. 4 p.m.

[0927] A flask was charged with 2-amino-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1,1,1]pentan-1yl)propanoic acid hydrochloride (30.955 mg, 1 Eq, 91.368 pmol), sodium carbonate (96.841 mg, 10 Eq, 913.68 pmol) and di-tert-butyl dicarbonate (39.882 mg, 40.8 pL, 2.0 Eq, 182.74 pmol) in a mixture of THF (913.68 pL) and H2O (913.68 pL). The reaction mixture was stirred at room temperature. Addition of saturated NaHCO3, extraction with EtOAc, drying over Na2SO4 and concentration to dryness to give 2-((tert-butoxycarbonyl)amino)-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanoic acid (36.8 mg, 91.4 pmol, 100%), assuming Petition 870250103180, dated 11 / 11 / 2025, pp. 218 / 393 211 / 383 quantitative yield.

[0928] de1H NMR (400 MHz, CDCb) δ 7.07 (d, J = 8.2 Hz, 1H), 6.90 (dd, J = 8.2, 1.7 Hz, 1H), 6.75 (d, J = 1.6 Hz, 1.7 Hz, 1H), 5.08 (d, J = 1.6 Hz, 1H), d 4.41 - 4.32 (m, 1H), 3.37 (s, 3H), 2.04 - 1.88 (m, 8H), 1.45 (s, 9H).

[0929] (1 -amino-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1] pentan-1-yl)-1-oxopropan-2-yl)tert -butyl carbamate 1)EtOC(O)CI 1.5 equiv

[0930] To a solution of 2-((tert-butoxycarbonyl)amino)-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanoic acid (36.771 mg, 1 Eq, 91.368 pmol) in dry THF (1.8274 mL), triethylamine (27.737 mg, 38.2 pL, 3.000 Eq, 274.10 pmol) and ethyl chloroformate (14.873 mg, 13.08 pL, 1.5 Eq, 137.05 pmol) were added at 0 °C. The reaction mixture was stirred at room temperature for 2 hours. The reaction is considered quantitative. Ammonium chloride (7.331 mg, 137.05 pL, 1 molar, 1.5 eq, 137.05 pmol) was added. The reaction mixture was stirred at room temperature for 3 hours. 1N KHSO4 was added, followed by extraction with EtOAc three times, drying over Na2SC>4, filtration, and concentration to dryness. [Quantity, presumed] [0931 ] tert-butyl (1-cyano-2-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1] pentan-1-yl)ethyl)carbamate TFAA 1.5 equiv Pyridine 3.0 equiv. THF 0 °C at rt, 3 h Trifluoroaceticanidride (28.785 mg, 19.14 pL, 1.5 Eq, 137.05 pmol) and pyridine (21.68 mg, 22.2 pL, 3 Eq, 274.10 pmol) were added to a chilled solution of tert-butyl (1-amino-3-(3-(3-methyl-2-oxo-2,3-di Petition 870250103180, dated 11 / 11 / 2025, p. 219 / 393 212 / 383 hydrobenzo[c / ]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)-1-oxopropan-2-yl)carbamate (36.681 mg, 1 Eq, 91.368 pmol) in dry THF (913.68 μL) at 0 °C. The resulting reaction mixture was stirred for 2 h. The solvent was removed under vacuum and the residue was dissolved in ethyl acetate. The organic layer was washed with 1N KHSO4, water and brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness. Quant, presumed

[0933] 1H NMR (400 MHz, CDCb) δ 7.12 (d, J = 8.2 Hz, 1H), 6.96 - 6.92 (m, 1H), 6.79 (d, J = 1.6 Hz, 1H), 5.00 (s, 1H), 4.62 (s, 1H), 3.40 (s, 3H), 2.14-2.03 (m, 8H).

[0934] 2-amino-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1,1]pentan-1-yl)propanenitrile

[0935] In a 10 mL flask, tert-butyl (1-cyano-2-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1,1,1]pentan-1-yl)ethyl)carbamate (35.035 mg, 1 Eq, 91.368 pmol), MeCN (1 mL), and PTSOH (52.137 mg, 3 Eq, 274.10 pmol) were added at room temperature. The resulting mixture was stirred for 3 h at room temperature. The reaction mixture was cooled in an ice bath and basified to 8°C with saturated NaHCO3 (aq.), extracted with ethyl acetate (15 mL x 3). The combined organic layer was washed with brine (100 mL) and dried over anhydrous MgSO4. After filtration, the filtrate was concentrated under reduced pressure. RMN: ok - assumed quantity.

[0936] NMR de1H (400 MHz, CDCb) δ 7.10 (d, J = 8.2 Hz, 1H), 6.93 (dd, J= 8.2, 1.6 Hz, 1H), 6.77 (d, J= 1.7 Hz, 1.6 Hz, 1H), 3, 73, J= 1.8 Hz, 6.8 Hz 1H), 3.39 (s, 3H), 2.09 (s, 6H), 2.05 (dd, J= 8.8, 7.0 Hz, 2H).

[0937] (2S)-2-((1 -cyano-2-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1,1]pentan-1-yl)ethyl)carbamoyl)-1,4-oxazepano-4-carboxylate -tercbutyl Petition 870250103180, of 11 / 11 / 2025, p. 220 / 393 213 / 383 I THREE 1.2 equiv DIPEA 1.5 equiv DMF rt. 4 p.m. I Boc

[0938] To a solution of 2-amino-3-(3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)bicyclo[1.1.1]pentan-1-yl)propanenitrile (25.887 mg, 1 Eq, 91.368 pmol) and (S)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid (24.651 mg, 1.1 Eq, 100.50 pmol) in dry DMF (1 mL) was added HATU (41.690 mg, 1.2 Eq, 109.64 pmol) and diisopropylethylamine (17.714 mg, 23.7 pL, 1.5 Eq, 137.05 pmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated to give a residue to which a saturated aqueous solution of NaHCO3 (30 mL) at 0 °C was added and extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with brine (...

Claims

1. Compound of Formula I, (I) or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that: R0 is a 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the monocyclic heterocycle is optionally substituted by 1 to 3 R8, or • a 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the polycyclic heterocycle is optionally substituted by 1 to 3 R8, each R8 being independently selected from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)2, COOH, C1-6 alkyl, C1-ealkylOH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy, C1-6 halogenated alkoxy, C1-6 alkylenecarbocyclyl or C1-6 alkylene-heteroaryl; L is a polycyclic cycloalkylene, polycyclic arylene or polycyclic heteroarylene.wherein a first atom of a first ring of polycyclic arylene or heteroarylene is connected to and a second atom of a second ring of polycyclic arylene or heteroarylene is connected to R1; wherein L is independently substituted by 0-4 R10; Petition 870250082273, dated 12 / 09 / 2025, p. 846 / 908 2 / 61 each R10 is independently =0, halogen, C1-salkyl, C1-alkoxy, S-C1-ealkyl, C2-6-alkenyl, C2-alkynyl, C1-ecycloalkyl, cyano, hydroxyl, NH2, -NH-C1-6 alkyl, N(C1-salkyl)2, COOH, COC1-ealkyl, COOC1-ealkyl, CON1-ealkyl, CON(C1-6alkyl)2, NHCOC1-ealkyl or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle is optionally and independently substituted by 1 to 3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH; R1 is a carbocyclyl group of 5 to 12 members, optionally replaced by 1 to 3 Rg groups, and an aryl group of 6 to 18 members, optionally replaced by 1 to 3 R9 groups.• Monocyclic heterocycline of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, or O, wherein the monocyclic heterocycline is optionally replaced by 1 to 3 Rg, • Monocyclic heteroaryl of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S, or O, wherein the monocyclic heteroaryl is optionally replaced by 1 to 3 Rg, • Bicyclic heteroaryl of 7 to 14 members containing 1 to 3 heteroatoms selected from N, S, or O, wherein the bicyclic heteroaryl is optionally replaced by 1 to 4 Rg, or • Tricyclic heteroaryl of 7 to 20 members containing 1 to 3 heteroatoms selected from N, S, or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg, each Rs is independently selected from hydrogen, SF5, =0, halogen, cyano, hydroxyl, nitro, NH2, -COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C 2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, -NHC1-6 alkyl,-N(Ci-6 alkyl)2, -COCi-ealkyl, -COOC1-6 alkyl, -CONH2, CONHC1-6 alkyl, -CONHC3-6 cycloalkyl, -C0N(Ci-6 alkyl)2, -NHCOCi-ealkyl, Petition 870250082273, of 12 / 09 / 2025, p. 847 / 908 3 / 61 NHCOCs-cycloalkyl, -P(O)(C1-6 alkyl), -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3scycloalkyl, -SO2-3 to 7 membered heterocycle, -S(O)NH2, -S(O)NHC1-6 alkyl, S(O)N(C1-6 alkyl)2, -S(O)2NH2, -OSO2-C1-6 alkyl, C1-6 alkylene-O-C1-6 alkyl, C3-8 cycloalkenyloxy, aryl, heteroaryl, 3 to 7 membered heterocycle containing 1 to 3 heteroatoms selected from N, S and O, and the Rg is optionally further substituted by 1 to 3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, -CONH2, NH2, C1-6-alkoxy, hydroxyl, -COOH, halogen, or a 5- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S, or O, wherein the 5- to 7-membered heterocycle is optionally substituted by 1 to 2 groups selected from =O, halogen, cyano,C1-6 alkyl, and C1-6 haloalkyl.

2. A compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R° is a 5- to 12-membered monocyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, or O, wherein the monocyclic heterocycle is optionally replaced by 1 to 3 R8 3. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R° is Xi and X2 are independently O, S, NH, N(Ci-e-alkyl) or Cr12r13 wherein at least one of Xi and X2 is not CR12R13; X3 is O, S, NH or N(Ci-e-alkyl); R8 is H, halogen, oxo, cyano, hydroxyl, NH2, NH(Ci-e-alkyl), N(Ci-e-alkyl)2, COOH, C1-6 alkyl, C1-6-alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1e-alkoxy or halogenated Ci-e-alkoxy; Petition 870250082273, dated 12 / 09 / 2025, p.848 / 908 4 / 61 R12 is H, halogen, cyano, hydroxyl, NH2, NH(C1-e-alkyl), N(C1-e-alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C16 alkoxy or C1-6 alkoxy halogenated; R13 is independently H, halogen or C1-C6 alkyl; RA is H, C1-6 alkyl, C1-6 alkylene-carbocyclyl, or C1-6 alkylene-heteroaryl; and RB is C1-6 alkyl, C2-6 alkenyl, C1-6 alkylene-carbocyclyl, or C16 alkylene-heteroaryl, or RA and RB are combined to form a heterocyclyl; in is 0, 1, 2 or 3.

4. Compound according to claim 3, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that r8 X2>X where R0 is , in is 2 or 3.

5. Compound according to claim 3 or 4, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is X2, X2'', X2o or X2'', X1 and X2 are independently O, S, NH, N(C1-6-alkyl) or CR12R13, wherein at least one of X1 and X2 is not CR12R13; Each R8 is independently selected from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)2, COOH, C1-6 alkyl, C1-6alkylOH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy or C1-6 halogenated alkoxy; and R12 is H, halogen, C1-6 alkyl; and each R13 is independently H, halogen or C1-C6 alkyl. Petition 870250082273, dated 12 / 09 / 2025, p. 849 / 908 5 / 61 6. Compound according to claim 3, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is X2-I; Xi and X2 are independently O, S, NH, N(C1-6-alkyl) or CR12R13, wherein at least one of Xi and X2 is not CR12R13; X3 is O, S, NH or N(C1-6-alkyl); RA is H, C1-6-alkyl, C1-6-alkylene-carbocyclyl, or C1-6-alkylene-heteroaryl; and RB is C1-6-alkyl, C2-6-alkenyl, C1-6-alkylene-carbocyclyl, or C16-alkylene-heteroaryl; or RA and RB are combined to form a heterocyclyl; R12 is H, halogen, C1-6-alkyl; Each R13 is independently H, halogen, or C1-C6 alkyl.

7. Compound according to claim 5, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R8 is x2, X1 is O, X2 is NH and R8 is C1-6 alkoxy.

8. Compound according to claim 1 or 2, (CH2)n2 (CH2)n1X2\ '' ....... AH2)A characterized in that R0 is , , each n1, n2 and n3 is independently an integer from 0 to 3, and the total sum of n1, n2 and n3 is < 4; X1 and X2 are independently O, S, NR6 or CR12R13, and at least one of X1 and X2 is not CR12R13; each R6, R12 and R13 is independently H, halo or C1-C6 alkyl. Petition 870250082273, dated 12 / 09 / 2025, p. 850 / 908 6 / 61 9. A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is OH or in that R8 is H, F, OH, CH3, OCH3, OCHF2, OCF3, OCH2CH3, or -CH2OCH3.

10. Compound, according to any one of claims 1-4, characterized in that R0 is either 11. A compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is a 5- to 12-membered polycyclic heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the polycyclic heterocycle is optionally replaced by 1 to 3 R8.

12. Compound according to claim 1 or 11, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is Petition 870250082273, dated 12 / 09 / 2025, page 851 / 908 7 / 61 • spiro-heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S or O, wherein the spiro-heterocycle is optionally replaced by 1 to 3 R8, • fused heterocycle of 5 to 12 members containing 1 to 3 heteroatoms selected from N, S or O, wherein the spiral heterocycle is optionally replaced by 1 to 3 R8, or • bridging heterocycle of 7 to 12 members, containing 1 to 3 heteroatoms selected from N, S or O, wherein the bridging heterocycle is optionally replaced by 1 to 3 R8.

13. A compound according to any one of claims 1, 11 or 12, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is a 5 to 12 membered spiroheterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the spiroheterocycle is optionally replaced by 1 to 3 R8.

14. Compound, according to claim 12 or 13, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is 1 / p, wherein m1 and m2 are independently 0, 1 or 2, provided that m1 and m2 are not 0, or m1 and m2 are not 2, and p is 1 or 2.

15. A compound, according to any one of claims 12 to 14, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, p. 852 / 908 8 / 61, characterized in that R0 is the or 16. A compound according to claim 1, 11 or 12, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is a 5- to 12-membered fused heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the fused heterocycle is optionally replaced by 1 to 3 R8.

17. Compound according to claim 16, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is m4 is 0 or 1, m5 is 1 or 2, X2 is O, S, NH, N(C1-e-alkyl), or CR12R13, R12 is selected from H, halogen, cyano, hydroxyl, NH2, NH(C1-6-alkyl), N(C1-6-alkyl)2, COOH, C1-6 alkyl, -CONH2, -S(=O)NH2, -S(O)2NH2, C16 alkoxy or C1-6 alkoxy halogenated; R13 is independently H, F, Cl, Br, I or C1-C6 alkyl.

18. Compound according to claim 16, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is Petition 870250082273, dated 12 / 09 / 2025, p. 853 / 908 9 / 61 X2 is O, S, NH, N(C1-6 alkyl) or CR12R13 R12 is H, halogen, cyano, hydroxyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, COOH, C1-6 alkyl, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy or C1-6 alkoxy halogenated; R13 is H, halogen or C1-C6 alkyl; Each mem' is independently an integer from 0 to 3, and the total sum of mem' is < 3.

19. Compound according to claim 17, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 20. Compound according to claim 12 or 16, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is X2 is O, S, NH, N(C1-6 alkyl) or CR12R13, R12 is H, halogen, C1-6 alkyl, R13 is H, halogen or C1-C6 alkyl and each mem' is independently an integer from 0 to 3, and the total sum of mc and mc' is 3. Petition 870250082273, dated 12 / 09 / 2025, page 854 / 908 10 / 61 21. Compound according to claim 20, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is 's / i~, X2 is NH, O or S.

22. Compound according to claim 21, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is v or v.

23. Compound according to claim 20, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is / or / .

24. Compound according to claim 18, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that JCH2)m x2 V \ )—NH m'(H2C)— / 5 z wherein R0 is / , X2 is O, S, NH, N(C1-ealkyl) or CR12R13, R12 is H, halogen, C1-6 alkyl; and R13 is H, halogen or C1-C6 alkyl.

25. Compound according to claim 24, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that \ / —NH I____ / < 1 < \__ that R0 is '—' ! .

26. Compound according to claim 11 or 12, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is a 7- to 12-membered bridging heterocycle containing 1 to 3 heteroatoms selected from N, S, O, wherein the bridging heterocycle is optionally replaced by 1 to 3 R8.

27. Compound according to claim 26, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is or each of which is optionally replaced by 1 to 4 R8, wherein A is a linkage, -O-, -O-CH2-, -CH2-O-CH2-, -CH2OCH2CH2-, CH2-, -CH2CH2- or -CH2NH-, B is N or CH, m4 is 0 or 1, p1 is 0, 1 or 2, q1 is 1, 2 or 3.

28. A compound according to claim 26 or 27, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is 29. Compound, according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is 30. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a 5 to 12 membered carbocyclyl optionally substituted by 1 to 3 Rg groups.

31. Compound according to claim 30, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is each of which is optionally replaced by 1 to 3 Rg.

32. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is an aryl of 6 to 18 members optionally replaced by 1 to 3 Rg.

33. A compound according to claim 32, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is or is linked to R1 by the substitution of any hydrogen atom of R1, and in which each R1 is optionally replaced by 1-3 Rg.

34. Compound according to claim 32, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that y F>(R9)0.3 where R1 is . Petition 870250082273, dated 12 / 09 / 2025, pp. 857 / 908 13 / 61 35. Compound according to claim 34, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is R9 or Rg.

36. Compound according to claim 34 or 35, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is sf5 sf5 o HNP' II O =N or O,—< II / \ S—NN— II \ / O'—' 37. Compound according to claim 34, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R9 R9 is 38. Compound according to claim 37, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is cf3 CN 39. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a 5- to 12-membered monocyclic heterocycline containing heteroatoms selected from N, S or O, wherein the monocyclic heterocycline is optionally substituted by 1 to 3 Rg groups.

40. Compound, according to claim 39, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that Petition 870250082273, dated 12 / 09 / 2025, page 858 / 908 14 / 61, in which R1 is Õ AH or I wherein each of R1 is optionally replaced by 1 to 3 Rg.

41. A compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a 5- to 12-membered monocyclic heteroaryl containing heteroatoms selected from N, S, or O, wherein each of the monocyclic heteroaryls is optionally substituted by 1 to 3 Rg groups.

42. Compound according to claim 41, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is NA, nY H - A ' A / , or , each of which is optionally replaced by 1 to 3 Rg groups.

43. Compound according to claim 41 or 42, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that each Rg is independently H, halogen, C1-C6 alkyl, OSO2C1s alkyl or CN.

44. Compound according to claim 42 or 43, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is z / An __ / An >. 7—=N jfY 1 λ— \ A^ , CN \ or \ 45. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a 7- to 14-membered bicyclic heteroaryl containing heteroatoms selected from N, S, or O, wherein the bicyclic heteroaryl is optionally substituted by 1 to 4 Rg groups. Petition 870250082273, dated 12 / 09 / 2025, pp. 859 / 908 15 / 61 46. ​​Compound according to claim 1 or 45, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that Rg is R6 or R7, wherein each R6 is independently selected from H, C16 alkyl, C16-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; Each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NH1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O;wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted with 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH.

47. A compound according to claim 45, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that each of R1 is optionally replaced by 1 to 3 Rg groups.

48. A compound according to claim 45 or 46, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is or R6, wherein Y is independently O, S, CHR6 or NR6; and R6 is C1-6 alkyl optionally substituted by 1, 2 or 3 F, or by OH, O-C1-6 alkyl, N(C1-6 alkyl)2, cycloalkyl or heterocyclyl. Petition 870250082273, dated 12 / 09 / 2025, p. 860 / 908 16 / 61 49. Compound according to claim 48, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is either 50. Compound according to claim 45 or 46, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X4 is NR6, O, CR7, CR14R15, S, S(O) or S(O)2, Q is CH or N, each R6 is independently selected from H, C16 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; Each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, cyano, hydroxyl, NH2, NH1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O;wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted with 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2 3-7 membered heterocycle, and a 4- to 7 membered heterocycle containing 1 to 3 heteroatoms selected from Petition 870250082273, dated 12 / 09 / 2025, page. 861 / 908 17 / 61 N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle groups are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH; alternatively, R14 and R15 form =O.; 51. Compound according to any one of claims 45-46, or a pharmaceutically acceptable salt or deuterated form thereof, R7R7 á-V. . 1 y-Cx· LY2 / SiYN\ ' (Y characterized in that R1 is R6 , , r® or , ?7 ,r6 ' / ÍA-n 'TΎ h° \^x4 , each X4 is independently NR6, O, CR14R15, S, S(O) or S(O)2, each R6 is independently selected from H, C16 alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C3-6 cycloalkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; each R7 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, alkynyl C2-6, C3-6cycloalkyl, cyano, hydroxyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CONHC1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl and a 4- to 7-membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O;wherein the alkyl, alkenyl, alkynyl, cycloalkyl and heterocycle groups within R7 are optionally substituted with 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C1 Petition 870250082273, dated 12 / 09 / 2025, page. 862 / 908 18 / 61 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 Cycloalkyl, -SO2- 3-7 membered heterocyclyl, and a 4- to 7 membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH; alternatively, R14 and R15 form =O.; 52. Compound according to claim 50, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that each X4 is independently O, S, NR6 or CR14R15; R6 is C1-salkyl optionally substituted by 1,2 or 3 F, or by OH, O-C1-salkyl, N(C1-salkyl)2, cycloalkyl or heterocyclyl; R7 is H, halo or C1-6 alkyl, R14 and R15 are independently H, halo or C1-6 alkyl.

53. A compound according to claim 52 or 53, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that each X4 is independently NH, O, S, CHF or CHF2.

54. Compound, according to any one of claims 52-53, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is .

55. Compound, according to any one of claims 52-53, or a pharmaceutically acceptable salt or deuterated form thereof, 'XzX characterized in that R1 is \ .

56. Compound according to any one of claims 45-46 or 51, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, p. 863 / 908 19 / 61 57. A compound according to any one of claims 45-46, 51 or 56, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is 58. Compound according to claim 45 or 46, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is optionally replaced by 1-4 R6 or R7 groups, in Petition 870250082273, dated 12 / 09 / 2025, page 864 / 908 20 / 61, wherein ring C is a 7- to 8-membered heterocycle comprising 1- to 3 heteroatoms selected from O, S and N.

59. A compound according to claim 58, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is either R6 or R7, each of which is optionally replaced by 1 to 4 R6 or R7.

60. Compound according to claim 58 or 59, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by 61. A compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a 7-20 membered tricyclic heteroaryl containing heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg, wherein Rg is R6, R7, R11, R14 or R15.

62. Compound according to claim 1 or 61, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a 7- to 20-membered tricyclic spiro heteroaryl containing heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg.

63. A compound according to any one of claims 61-62, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, p. 865 / 908 21 / 61, is characterized in that R1 → R6, wherein either R6 is independently selected from among H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or alkylene-O-alkyl; wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH;and, R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C16 alkyl, -S(O)2C16 alkyl, -S(O)2C3-6 cycloalkyl, -SO2- 3-7 membered heterocycle and a 4- to 7 membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH; Alternatively, R14e R15 form =O. Petition 870250082273, dated 12 / 09 / 2025, p. 866 / 908 22 / 61; 64. Compound according to claim 62-63, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is D~EJ, wherein W, X4 and Y2 are each independently CH or N, provided that at most one of W, X4 and Y2 may be N; DE is N(H)-C(=O), N(C1-6alkyl)-C(=O), CH2CH2, C(=O)-O or CH2-O; R11 is H, C1-6alkyl, alkylene-O-alkyl or heterocyclyl; eiej are each independently 1, 2 or 3; provided that the sum of i+j is 2, 3 or 4.

65. Compound according to any one of claims 61-64, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, p. 867 / 908 23 / 61 66. A compound according to any one of claims 61 to 65, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is .

67. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is a fused tricyclic heteroaryl of 7 to 20 members containing heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally replaced by 1 to 5 Rg.

68. Compound according to claim 1 or 67, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is optionally substituted by 1 to 5 Rg, wherein X5 and X6 are independently selected from single bonding, -C(R14R15)-O-, -C(R14R15)-C(R14R15)-, -OC(R14R15)-, -C(R14R15)-, -O- and -NR6J. R14 and R15 are independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C3-6 cycloalkoxy, cyano, hydroxyl, NH2, COOH, -S(O)C1-6 alkyl, -S(O)2C1-6 alkyl, -S(O)2C3-6 cycloalkyl, -SO2- 3-7 membered heterocyclyl and a 4- to 7 membered heterocycle containing 1 to 3 heteroatoms selected from N, S or O, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and heterocycle are optionally substituted by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and -COOH;Each R6 is independently selected from H, C16 alkyl, -COC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or alkylene-O-alkyl; Petition 870250082273, dated 12 / 09 / 2025, p. 868 / 908 24 / 61 wherein the alkyl, alkenyl, alkynyl and cycloalkyl are optionally replaced by 1 to 3 groups selected from halogen, cyano, hydroxyl, NH2 and COOH; The D ring is selected from 5- to 8-membered aryl and heteroaryl rings containing 1 to 3 heteroatoms, wherein the aryl and said heteroaryl rings are 5- to 8-membered rings containing 1 to 3 heteroatoms, each independently and optionally substituted by 1 to 3 Rg, provided that when the D ring is aryl, X5 and X6 are not both C(R14R15)-C(R14R15)- or -C(R14R15)-.

69. Compound according to claim 68, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that which is optionally replaced by 1 to 5 Rg.

70. Compound according to claim 68 or 69, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that Ring D or each of which is optionally replaced by 1 to 3 Rg groups.

71. Compound, according to any one of claims 68 to 70, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, p. 869 / 908 25 / 61 characterized in that R1 Petition 870250082273, dated 12 / 09 / 2025, p. 870 / 908 26 / 61 72. A compound according to any one of claims 1 to 71, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is a polycyclic cycloalkylene.

73. A compound according to any one of claims 1 to 72, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic cycloalkylene comprises 4 to 10 carbon atoms.

74. Compound, according to any one of claims 1-73, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic cycloalkylene is linked to R1 on a first quaternary carbon of the polycyclic cycloalkylene and independently connected to via a second quaternary carbon of the polycyclic cycloalkylene.

75. Compound, according to any one of claims 1 to 74, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic cycloalkylene is I ii 76. A compound according to any one of claims 1 to 75, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic cycloalkylene is or 77. A compound according to any one of claims 1 to 76, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is a polycyclic heteroarylene substituted by 0 to 4 R10 78. Compound according to claim 77, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene comprises 8 to 12 atoms in the ring and is substituted by 0 to 4 R10.

79. Compound, according to any one of claims 77 to 78, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, page 872 / 908 28 / 61 characterized in that the polycyclic heteroarylene comprises 8 to 10 atoms in the ring and is substituted by 0 to 4 R10.

80. A compound according to any one of claims 77 to 79, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene comprises 8-9 atoms in the ring and is substituted by 0 to 4 R10 81. Compound according to claim 77, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that the polycyclic heteroarylene is substituted by 0 to 4 R10, wherein ring B is a heteroaryl ring.

82. A compound according to any one of claims 77 to 81, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene comprises 9 ring atoms and 1 or 2 heteroatoms selected from O, N or S, and the polycyclic heteroarylene is substituted by 0 to 4 R10 83. Compound according to any one of claims 77 to 82, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is substituted by 0 to 4 R10, wherein X' is O, S, NH or N(C1-6 alkyl).

84. Compound according to any one of claims 77 to 83, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is benzothienylene, indolylene or benzofuranylene substituted by 0 to 4 R10 85. Compound, according to any of claims 77 to 84, or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, pp. 873 / 908 29 / 61 characterized in that the polycyclic heteroarylene is each of which is substituted by 0 to 4 R10.

86. Compound according to claim 85, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that OH x nJ R1 or is attached to the ring of H x NA, wherein is attached to the phenyl ring of or is substituted by O to 4 R10.

87. Compound according to claim 85, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that it is linked to the 5-member ring of Petition 870250082273, dated 12 / 09 / 2025, page 874 / 908 30 / 61 or 88. A compound according to any one of claims 77 to 87, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is Hv or 89. A compound according to any one of claims 77 to 88, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is HNHN or 90. A compound according to any one of claims 77 to 87, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is 1 to 4 R10. or replaced by 1 91. Compound, according to any of the claims in 90, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is 1 R10. or replaced by a Petition 870250082273, dated 12 / 09 / 2025, p. 875 / 908 31 / 61 92. Compound according to claim 90 or 91, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R10 is halo.

93. Compound according to any one of claims 90 to 92, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that LF or f 94. A compound according to any one of claims 90 to 93, or a pharmaceutically acceptable salt or deuterated form thereof, F characterized in that L is 95. A compound according to any one of claims 77 to 80, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene comprises 8 ring atoms and 1 or 2 heteroatoms selected from O, N, or S, and the polycyclic heteroarylene is substituted by 0 to 4 R10 96. A compound according to any one of claims 77-80 or 95, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is 1 ' 1 , wherein each of the E and F rings is a 5-membered heteroaryl or a 5-membered heterocycline comprising 1 to 3 heteroatoms selected from O, N or S.

97. Compound, according to any one of claims 77-80 or 95-96, or a pharmaceutically acceptable salt or deuterated form of Petition 870250082273, dated 12 / 09 / 2025, page 876 / 908 32 / 61 -ι-ΓεΥε)-; even, characterized in that the polycyclic heteroarylene is 1 '—« , wherein each of the E and F rings is a 5-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N or S.

98. Compound according to any one of claims 77 to 80 or 95 to 96, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is ss, rS, z~~^xS, or Se 99. A compound according to any one of claims 77 to 80, 95 to 96 or 98, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the polycyclic heteroarylene is S 100. A compound according to any one of claims 1 to 71, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is polycyclic arylene.

101. A compound according to claim 100, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is 102. Compound, according to claim 100 or 101, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that L is Petition 870250082273, dated 12 / 09 / 2025, page 877 / 908 33 / 61 103. Compound, according to any one of claims 1 to 71, characterized in that the compound is of Formula (II), (II) or a pharmaceutically acceptable salt or deuterated form thereof.

104. Compound according to any one of claims 1 to 71, characterized in that the compound is of Formula (III), or a pharmaceutically acceptable salt or deuterated form thereof.

105. Compound according to any one of claims 1 to 71, characterized in that the compound is of Formula (IV), or a pharmaceutically acceptable salt or deuterated form thereof.

106. Compound according to claim 1, wherein the compound is characterized in that it is Formula (V), Petition 870250082273, 12 / 09 / 2025, p. 878 / 908 34 / 61 (V) or a pharmaceutically acceptable salt or deuterated form thereof, wherein n is 0 or 1, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

107. Compound according to claim 1, wherein the compound is characterized in that it is of Formula (VI), (VI) or a pharmaceutically acceptable salt or deuterated form thereof, wherein n is 0 or 1, and R10 is substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

108. Compound according to claim 1, wherein the compound is characterized in that it is of Formula (VII), (VII) or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, 12 / 09 / 2025, p. 879 / 908 35 / 61 where n is 0 or 1, and R10 can be substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

109. A compound according to any one of claims 103 to 108, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that n is 0.

110. A compound according to any one of claims 103 to 108, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that n is 1 and R10 is halo.

111. A compound according to any one of claims 103 to 108 or 110, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that n is 1 and R10 is F.

112. A compound according to any one of claims 1 to 111, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6, , or ; X is O, S, or CF2; Y is O or S; Q is CH or N; R6 is C1-3 alkyl, wherein said C1-3 alkyl is optionally substituted by 1, 2, or 3 F, OH, OC1-3 alkyl, N(C1-3 alkyl)2, cyclopropyl, or tetrahydropyran; and R7 is H, F, Cl, or CH3. Petition 870250082273, dated 12 / 09 / 2025, p. 880 / 908 36 / 61 113. A compound according to any one of claims 1 to 112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X is O, SY is O or CF2; St; R6 is C1-3 alkyl, wherein said C1-3 alkyl is optionally substituted by 1, 2 or 3 F, OH, OC1-3 alkyl, N(C1-3 alkyl)2, cyclopropyl or tetrahydropyran; and R7 is H, F, Cl or CH3.

114. A compound according to any one of claims 1 to 112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is 115. Compound according to claim 114, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X is O; R6 is C1-3 alkyl; and R7 is H.

116. A compound according to any one of claims 1 to 112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R7 R1 is R6; JX is O; Petition 870250082273, dated 12 / 09 / 2025, p. 881 / 908 37 / 61 R6 is C1-3 alkyl, wherein said C1-3 alkyl is optionally substituted by 1, 2 or 3 F; and R7 is H.

117. Compound according to any one of claims 1-112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X is O; R6 is C1-3 alkyl; and R7 is H.

118. Compound according to any one of claims 1-112, or a pharmaceutically acceptable salt thereof, R7 characterized in that R1 is R6 119. A compound according to any one of claims 1-112, or a pharmaceutically acceptable salt or deuterated form of R7 itself, characterized in that R1 is R6.

120. Compound, according to any one of claims 1-112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is Petition 870250082273, dated 12 / 09 / 2025, page 882 / 908 38 / 61 121. A compound according to any one of claims 105 to 120, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6 is methyl.

122. Compound according to any one of claims 105 to 120, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6 is ethyl.

123. A compound according to any one of claims 105 to 120, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6 is propyl.

124. A compound according to any one of claims 1 to 112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is 125. Compound according to any one of claims 1 to 112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is \ .

126. Compound, according to any one of claims 1 to 112, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R1 is ''' .

127. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that the compound is of Formula (VIII): Petition 870250082273, dated 12 / 09 / 2025, page 883 / 908 39 / 61 (VIII) or a pharmaceutically acceptable salt or deuterated form thereof.

128. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (IX), or a pharmaceutically acceptable salt or deuterated form thereof.

129. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (X), Petition 870250082273, dated 12 / 09 / 2025, pp. 884 / 908 40 / 61 (X) or a pharmaceutically acceptable salt or deuterated form thereof.

130. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (XI), (XI) or a pharmaceutically acceptable salt or deuterated form thereof, wherein n is 0 or 1, and R10 can be substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

131. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (XII), (XII) or a pharmaceutically acceptable salt or deuterated form thereof, Petition 870250082273, dated 12 / 09 / 2025, pp. 885 / 908 41 / 61 where n is 0 or 1, and R10 can be substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

132. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (XIII), or a pharmaceutically acceptable salt or deuterated form thereof, wherein n is 0 or 1, and R10 can be substituted on the phenyl ring or on the thiophenyl ring of the benzothienylene ring.

133. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (XVI), (XVI) Petition 870250082273, dated 12 / 09 / 2025, p. 886 / 908 42 / 61 or a pharmaceutically acceptable salt or deuterated form thereof, wherein each of rings E and F is a 5-membered heteroarylene or 5-membered heterocycline, n is 0 or 1, and R10 is substituted in ring E or ring F.

134. Compound according to claim 133, characterized in that 135. Compound, according to claim 133 or 134, characterized in that 'xZ—' 1 is 136. Compound according to any one of claims 133 to 135, characterized in that R10 is halo.

137. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (XVII), (XVII) Petition 870250082273, dated 12 / 09 / 2025, p. 887 / 908 43 / 61 the same, or a pharmaceutically acceptable salt or deuterated form thereof wherein X' is O, S, NH or N(C1-6 alkyl), n is 0 or 1, and R10 is substituted on the phenyl ring or on the 5-membered ring of 138. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is of Formula (XVIII), (XVIII) or a pharmaceutically acceptable salt or deuterated form thereof, wherein X' is O, S, NH or N(C1-6 alkyl), n is 0 or 1, and R10 is substituted on the phenyl ring or on the 5-membered ring of 139. A compound according to any one of claims 120-138, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that n is 0. Petition 870250082273, dated 12 / 09 / 2025, p. 888 / 908 44 / 61 140. A compound according to any one of claims 120 to 138, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that n is 1 and R10 is halo.

141. Compound according to any one of claims 120 to 138 or 140, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that n is 1 and R10 is F.

142. A compound according to any one of claims 127 to 141, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X is O.

143. Compound according to any one of claims 127 to 142, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6 is C1-3 alkyl.

144. Compound according to any one of claims 127 to 143, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R7 is H.

145. Compound according to any one of claims 127 to 144, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X is O, R6 is C1-3 alkyl and R7 is H.

146. A compound according to any one of claims 1 to 145, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is 147. Compound, according to any one of claims 1 to 146, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is Petition 870250082273, dated 12 / 09 / 2025, p. 889 / 908 45 / 61 148. Compound according to any one of claims 146 to 147, characterized in that R8 is H.

149. Compound, according to any one of claims 1 to 145, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is X2X1 08 Ã! r8—kT / ' x2 R® __ X1 O» ( / x2 / R® xi R® X2 Rb rA-X3 x X1 or x2 claims 1 150. Compound, according to either of 145 or 149, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is x2 R® R8—çX2 Z: RA o or x2 R® ___ 'X1 r® ___ 'X1 R® X1 R® X2 151. Compound according to claim 150, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R® R8—çde where R0 is x2 X1 152. Compound according to any one of claims 150 to 151, or a pharmaceutically acceptable salt or deuterated form thereof, r8—V / characterized in that R0 is A-nh, wherein each R8 is independently selected from H, halogen, oxo, cyano, hydroxyl, NH2, Petition 870250082273, dated 12 / 09 / 2025, page 890 / 908 46 / 61 NH(C1-e-alkyl), N(C1-e-alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, -CONH2, -S(=O)NH2, -S(O)2NH2, C1-6 alkoxy or halogenated C1-6 alkoxy.

153. Compound according to any one of claims 150 to 152, or a pharmaceutically acceptable salt or deuterated form thereof, R<°f' characterized in that R0 is —nh , wherein each R8 is independently selected from H, halogen, C1-6 alkyl, C1-6 alkoxy or C1-6 alkoxy halogenated.

154. Compound according to claim 150, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that r® ReJfj9, where R0 is x2 ! .

155. Compound according to claim 150, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R®__ Αγ,· such that R0 is x2 ! .

156. Compound according to claim 150, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R® *·-ίθ< where R0 is x? : .

157. Compound according to any one of claims 1 or 149 to 156, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that at least one R8 is H.

158. A compound according to any one of claims 1 or 149 to 156, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that at least one R8 is methoxy. Petition 870250082273, dated 12 / 09 / 2025, p. 891 / 908 47 / 61 159. Compound according to any one of claims 1 or 149 to 156, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that at least one R8 is ethoxy.

160. A compound according to any one of claims 1 or 149 to 156, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that at least one R8 is OH.

161. A compound according to any one of claims 1 to 148, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is h or 162. A compound according to any one of claims 1 to 148 or 161, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is H.

163. A compound according to any one of claims 1 to 148 or 161, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is H 164. Compound, according to any one of claims 149 to 150, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is: HN or Petition 870250082273, dated 12 / 09 / 2025, p. 892 / 908 48 / 61 165. A compound according to any one of claims 149 to 153 or 164, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is: HN or 166. A compound according to any one of claims 149 to 153 or 164 to 165, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is hn 167. A compound according to any one of claims 149 to 153 or 164 to 165, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is: hn 168. Compound, according to any one of claims 149 to 153 or 164 to 165, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is / ' .

169. Compound according to claim 164, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is .

170. Compound according to claim 164, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is hn^ / z'. Petition 870250082273, dated 12 / 09 / 2025, p. 893 / 908 49 / 61 171. Compound according to claim 164, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is hn^A' .

172. A compound according to any one of claims 1 to 145 or 149, or a pharmaceutically acceptable salt or deuterated form of the same rb Ra-x3, characterized in that R0 is x2~ / / .

173. Compound according to claim 172, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is HN—'z'.

174. Compound according to any one of claims 149 or 172-173, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RA is H or C1-6 alkyl.

175. Compound according to claim 174, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RA is H.

176. Compound according to claim 174, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RA is methyl.

177. Compound according to any one of claims 149 or 172-176, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RB is C1-6 alkyl, C2-6 alkenyl, C1-6 alkylenecarbocyclyl or C1-6 alkyleneheteroaryl.

178. Compound according to claim 177, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RB is 5 to 6 membered C1-6 alkyl, C1-6 alkylene-aryl or C1-6 alkylene-heteroaryl.

179. Compound according to claim 172 or 173, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is .

180. Compound according to claim 172 or 173, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is .

181. Compound according to claim 172 or 173, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is X2 Ά 182. Compound according to any one of claims 177 to 181, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RB is methyl.

183. A compound according to any one of claims 177 to 181, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RB is ethyl.

184. Compound, according to any one of claims 177 to 181, characterized in that RB is H. Petition 870250082273, dated 12 / 09 / 2025, pp. 895 / 908 51 / 61 185. Compound according to claim 180, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is 186. A compound according to claim 181, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R0 is 187. Compound according to claim 182, or a pharmaceutically acceptable salt or deuterated form thereof, characterized by the fact that R0 is HN— 188. Compound according to any one of claims 185 to 187, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RB is methyl.

189. A compound according to any one of claims 185 to 187, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that RB is ethyl.

190. Compound according to any one of claims 172 to 178, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that X3 is O.

191. A compound according to any one of claims 1 to 145, or a pharmaceutically acceptable salt or deuterated form thereof, / A Υγ N' / ' characterized in that R0 is H2N '' or H . Petition 870250082273, dated 12 / 09 / 2025, p. 896 / 908 52 / 61 192. Compound according to any one of claims 127 to 191, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6 is C1-3 alkyl.

193. Compound according to claim 192, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R6 is CH3.

194. Compound according to any one of claims 127 to 193, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R7 is H.

195. A compound according to any one of claims 127 to 194, or a pharmaceutically acceptable salt or deuterated form thereof, characterized in that R10 is -H or -F.

196. Compound according to claim 1, or a pharmaceutically acceptable salt or deuterated form thereof, wherein the compound is characterized in that it is selected from Table 1.

197. Pharmaceutical composition characterized in that it comprises an effective amount of a compound, as defined in any one of claims 1 to 196, or a pharmaceutically acceptable salt or deuterated form thereof and a pharmaceutically acceptable adjuvant, diluent or vehicle.

198. A method for treating an obstructive airway disease in a patient requiring such treatment, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

199. Method, according to claim 198, characterized in that the obstructive airway disease is asthma, chronic obstructive pulmonary disease (COPD), bronchitis, emphysema, cystic fibrosis (CF), bronchiectasis, sarcoidosis, alpha-1 antitrypsin (A1AT) deficiency, farmer's lung and related diseases, hypersensitivity pneumonitis, pulmonary fibrosis, complications of Petition 870250082273, dated 12 / 09 / 2025, p.897 / 908 53 / 61 lung transplantation, vasculitic and thrombotic disorders of the pulmonary vasculature, pulmonary hypertension, antitussive activity including treatment of chronic cough associated with inflammatory and secretory conditions of the airways, iatrogenic cough, acute and chronic rhinitis including rhinitis medicamentosa and vasomotor rhinitis; perennial and seasonal allergic rhinitis including nervous rhinitis (hay fever), nasal polyposis; acute viral infection including common cold and infection due to a respiratory virus, acute lung injury or acute respiratory distress syndrome (ARDS).

200. Method, according to claim 199, characterized in that the obstructive airway disease is asthma.

201. Method, according to claim 199, characterized in that the obstructive airway disease is acute respiratory distress syndrome (ARDS).

202. Method, according to claim 199, characterized in that the obstructive airway disease is bronchitis.

203. Method, according to claim 199, characterized in that the obstructive airway disease is pulmonary fibrosis.

204. Method, according to claim 199, characterized in that the obstructive airway disease is emphysema.

205. Method, according to claim 199, characterized in that the obstructive airway disease is cystic fibrosis (CF).

206. Method, according to claim 199, characterized in that the obstructive airway disease is bronchiectasis.

207. Method, according to claim 199, characterized in that the obstructive airway disease is sarcoidosis.

208. Method according to claim 199, characterized in that the obstructive airway disease is alpha-1 antitrypsin (A1AT) deficiency.

209. Method, according to claim 199, characterized in that the obstructive airway disease is the farmer's lung. Petition 870250082273, dated 12 / 09 / 2025, pp. 898 / 908 54 / 61 210. Method according to claim 199, characterized in that the obstructive airway disease is hypersensitivity pneumonitis.

211. Method according to claim 199, characterized in that obstructive airway disease is a complication of lung transplantation.

212. Method, according to claim 199, characterized in that the obstructive airway disease is a vasculitic or thrombotic disorder of the pulmonary vasculature.

213. Method, according to claim 199, characterized in that the obstructive airway disease is pulmonary hypertension.

214. Method, according to claim 199, characterized in that the obstructive airway disease is iatrogenic cough.

215. Method, according to claim 199, characterized in that the obstructive airway disease is acute rhinitis.

216. Method, according to claim 199, characterized in that the obstructive airway disease is chronic rhinitis.

217. Method according to claim 199, characterized in that the obstructive airway disease is either rhinitis medicamentosa or vasomotor rhinitis.

218. Method, according to claim 199, characterized in that the obstructive airway disease is nasal polyposis.

219. Method, according to claim 199, characterized in that the obstructive airway disease is COPD.

220. Method according to claim 200, characterized in that the asthma is bronchial, allergic, intrinsic, extrinsic, exercise-induced or drug-induced.

221. Method according to claim 200, characterized in that the bronchitis is infectious bronchitis or eosinophilic bronchitis. Petition 870250082273, dated 12 / 09 / 2025, pp. 899 / 908 55 / 61 222. Method according to claim 203, characterized in that the pulmonary fibrosis is idiopathic pulmonary fibrosis, cryptogenic fibrosing alveolitis, idiopathic interstitial pneumonia, or fibrosis that complicates antineoplastic therapy or chronic infection.

223. Method according to claim 206, characterized in that the bronchiectasis is non-cystic fibrosis bronchiectasis (NCFBE).

224. Method according to claim 206, characterized in that bronchiectasis is associated with cystic fibrosis25.

225. Method according to claim 213, characterized in that pulmonary hypertension is pulmonary arterial hypertension.

226. Method according to claim 213, characterized in that pulmonary hypertension is pulmonary hypertension due to left heart disease.

227. Method according to claim 213, characterized in that pulmonary hypertension is pulmonary hypertension associated with chronic lung disease.

228. Method for treating cystic fibrosis in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

229. Method according to claim 228, characterized in that the treatment comprises improving the patient's lung function, compared with the patient's lung function before treatment.

230. Method according to claim 229, characterized in that the improvement in the patient's lung function comprises increasing the patient's forced expiratory volume in 1 second (FEV1), increasing the patient's forced vital capacity (FVC), increasing the patient's peak expiratory flow rate (PEF) or increasing the patient's forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)), compared to the patient's respective value before treatment. Petition 870250082273, dated 12 / 09 / 2025, pp. 900 / 908 56 / 61 231. Method according to claim 229 or 230, characterized in that lung function is measured by spirometry.

232. Method for treating bronchiectasis in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

233. Method according to claim 232, characterized in that the bronchiectasis is non-cystic fibrosis bronchiectasis (NCFBE).

234. Method according to claim 232, characterized in that bronchiectasis is associated with cystic fibrosis.

235. A method according to any one of claims 232 to 234, characterized in that the treatment comprises improving the patient's lung function, compared with the patient's lung function before treatment.

236. Method according to claim 235, characterized in that the improvement in the patient's lung function comprises increasing the patient's forced expiratory volume in 1 second (FEV1), increasing the patient's forced vital capacity (FVC), increasing the patient's peak expiratory flow rate (PEF) or increasing the patient's forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)), compared to the respective value for the patient before treatment.

237. Method according to claims 235 to 236, characterized in that lung function is measured by spirometry.

238. A method according to any one of claims 232 to 234, characterized in that the treatment comprises decreasing the rate of pulmonary exacerbation, compared with the patient's rate of pulmonary exacerbation before treatment.

239. Method according to any one of claims 232 to 238, characterized in that the treatment comprises increasing the time to the first pulmonary exacerbation, compared to an untreated patient. Petition 870250082273, dated 12 / 09 / 2025, pp. 901 / 908 57 / 61 240. Method according to claim 238 or 239, characterized in that the pulmonary exacerbation is characterized by three or more of the following symptoms exhibited for at least 48 hours by the patient: (1) increased cough; (2) increased sputum volume or change in sputum consistency; (3) increased sputum purulence; (4) increased shortness of breath and / or decreased exercise tolerance; (5) fatigue and / or malaise; (6) hemoptysis.

241. A method for treating chronic rhinosinusitis (CRS) in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

242. Method according to claim 241, characterized in that the chronic rhinosinusitis is chronic rhinosinusitis without nasal polyps (CRSsNP).

243. Method according to claim 241, characterized in that chronic rhinosinusitis is chronic rhinosinusitis with nasal polyps (CRSwNP).

244. Method according to any one of claims 241 to 242, characterized in that the chronic rhinosinusitis is a refractory chronic rhinosinusitis.

245. A method according to any one of claims 241 to 244, characterized in that the treatment comprises reducing, lessening the severity, delaying the onset, or eliminating one or more symptoms of CRS.

246. Method, according to claim 245, characterized in that one or more CRS symptoms are nasal congestion; nasal obstruction; nasal discharge; post-nasal drip; facial pressure; facial pain; facial fullness; reduced sense of smell; depression; mucosal edema; mucopurulent discharge; middle meatus obstruction; mucosal changes within the ostiomeatal complex and sinuses; or rhinorrhea. Petition 870250082273, dated 12 / 09 / 2025, pp. 902 / 908 58 / 61 247. Method for treating hidradenitis suppurativa (HS) in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

248. Method according to claim 247, characterized in that hidradenitis suppurativa (HS) is Hurley stage I.

249. Method according to claim 247, characterized in that the hidradenitis suppurativa (HS) is Hurley stage II.

250. Method according to claim 247, characterized in that the hidradenitis suppurativa (HS) is Hurley stage III.

251. A method for treating cancer in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

252. Method according to claim 251, characterized in that the cancer is metastatic cancer.

253. Method according to claim 252, characterized in that the metastatic cancer is a metastatic cancer from the breast to the lung.

254. Method according to claim 252, characterized in that the metastatic cancer comprises metastasis from breast cancer to the brain, bone, pancreas, lymph nodes or liver.

255. Method according to claim 252, characterized in that the metastatic cancer comprises metastasis from bone cancer to the lung.

256. Method according to claim 252, characterized in that the metastatic cancer comprises metastasis from colorectal cancer to the peritoneum, pancreas, stomach, lung, liver, kidney, or spleen. Petition 870250082273, dated 12 / 09 / 2025, pp. 903 / 908 59 / 61 257. Method according to claim 252, characterized in that the metastatic cancer comprises metastasis from stomach cancer to the mesentery, spleen, pancreas, lung, liver, adrenal gland or ovary.

258. Method according to claim 252, characterized in that the metastatic cancer comprises metastasis from liver cancer to the intestine, spleen, pancreas, stomach, lung or kidney.

259. Method according to claim 252, characterized in that the metastatic cancer comprises lymphoma metastasis to the kidney, ovary, liver, bladder, or spleen.

260. Method for treating lupus nephritis in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

261. A method for treating rheumatoid arthritis in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

262. A method for treating inflammatory bowel disease (IBD) in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

263. Method according to claim 262, characterized in that the inflammatory bowel disease (IBD) is Crohn's disease.

264. Method according to claim 262, characterized in that the inflammatory bowel disease (IBD) is ulcerative colitis.

265. Method for treating vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

266. Method according to claim 265, characterized in that the disease associated with ANCA is granulomatosis with polyangiitis (GPA).

267. Method according to claim 265, characterized in that the disease associated with ANCA is microscopic polyangiitis (MPA).

268. A method for treating a disease in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197, wherein the disease is giant cell arteritis, polyarteritis nodosa, anti-GBM (Goodpasture's) disease, systemic scleroderma, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic ulcers, Duchenne muscular dystrophy, bronchiolitis obliterans, atopic dermatitis, pyoderma gangrenosum, Sweet's syndrome, dermatomyositis / polymyositis, neutrophilic dermatoses, thrombosis, bronchopulmonary dysplasia, amyotrophic lateral sclerosis, sickle cell anemia, psoriasis, or ventilator-induced lung injury.

269. A method for treating heart failure in a patient in need thereof, characterized in that it comprises administering to the patient an effective amount of a compound, as defined in any one of claims 1 to 196, or the composition, as defined in claim 197.

270. Method according to claim 269, characterized in that the heart failure is heart failure with reduced ejection fraction.

271. Method, according to claim 269, characterized in that the heart failure is heart failure with preserved ejection fraction. Petition 870250082273, dated 12 / 09 / 2025, pp. 905 / 908 61 / 61 272. Compound characterized in that it is selected from Table 1, either a pharmaceutically acceptable salt or a deuterated form thereof.