Inhibitors of the nlrp3 inflammatomes and their uses

Description

1 / 168 “NLRP3 Inflammasome Inhibitors and Their Uses - Cross-Reference to Related Applications”

[001] This patent application claims the benefit of International Application No. PCT / CN2023 / 082488, filed on March 20, 2023, International Application No. PCT / CN2023 / 101049, filed on June 19, 2023, and International Application No. PCT / CN2024 / 079655, filed on March 1, 2024, each of which is incorporated herein by reference in its entirety. BACKGROUND

[002] The pyrin domain-containing protein 3 (NLRP3) of the NOD-like receptor (NLR) family is an intracellular sensor that detects a wide range of microbial motifs, endogenous danger signals, and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. NLRP3 inflammasome assembly leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18, as well as gasdermin D-mediated pyroptotic cell death. Studies have revealed novel regulators of the NLRP3 inflammasome, including new interactive or regulatory proteins, metabolic pathways, and a mitochondrial regulatory center. Aberrant activation of the NLRP3 inflammasome has been associated with several inflammatory disorders, including cryopyrin-associated periodic syndromes, Alzheimer's disease, diabetes, and atherosclerosis.

[003] Based on the above, there is a need to identify inhibitors of the NLRP3 inflammasome. SUMMARY

[004] In one aspect, the present description refers to compounds and compositions that are useful as inhibitors of the NLRP3 inflammasome pathway.

[005] In one aspect, the description provides a compound represented by Formula (I), or a pharmaceutically acceptable salt or Petition 870250084579, dated 09 / 19 / 2025, p. 8 / 201 2 / 168 a stereoisomer of it: Formula (I).

[006] In some embodiments, the description provides a compound represented by Formula (Ia), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (Ia).

[007] In some embodiments of a compound of Formula (Ia), it is a compound of Formula (II), or a pharmaceutically acceptable salt or a stereoisomer thereof: OH Formula (II).

[008] In another aspect, a compound represented by Formula (III) is provided here, or a pharmaceutically acceptable salt or a stereoisomer thereof: OH Formula (III).

[009] In another aspect, a compound represented by Formula (IV) is provided here, or a pharmaceutically acceptable salt or a stereoisomer thereof: Petition 870250084579, dated 09 / 19 / 2025, page 9 / 201 3 / 168 Formula (IV).

[010] Also described herein is a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt or a stereoisomer thereof, and a pharmaceutically acceptable excipient.

[011] Also described here is a method for modulating the NLRP3 inflammasome in an individual, the method comprising administering to the individual the compound described herein, or a pharmaceutically acceptable salt or a stereoisomer thereof.

[012] Also described here is a method for inhibiting NLRP3 in an individual, the method comprising administering to the individual the compound described herein, or a pharmaceutically acceptable salt or a stereoisomer thereof.

[013] Also described here is a method for treating an autoimmune or autoinflammatory disease or condition in an individual in need thereof, the method comprising administering to the individual a compound described herein, or a pharmaceutically acceptable salt or a stereoisomer thereof.

[014] In some modalities, the disease or disorder is selected from among inflammasome-related diseases / disorders, immunological diseases, inflammatory diseases, autoimmune diseases or autoinflammatory diseases, for example, autoinflammatory febrile syndromes (e.g., cryopyrin-associated periodic syndrome), liver-related diseases / disorders (e.g., chronic liver disease, viral hepatitis, non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis and alcoholic liver disease), inflammatory arthritis-related disorders (e.g., gout, pseudogout (chondrocalcinosis), osteoarthritis, rheumatoid arthritis, arthropathy, e.g., acute, Petition 870250084579, dated 09 / 19 / 2025, page 10 / 201 4 / 168 chronic), kidney diseases (e.g., hyperoxaluria, lupus nephritis, type I / type II diabetes and related complications (e.g., nephropathy, retinopathy), hypertensive nephropathy, hemodialysis-related inflammation), neuroinflammation-related diseases (e.g., multiple sclerosis, brain infection, acute injury, neurodegenerative diseases, Alzheimer's disease), cardiovascular / metabolic diseases / disorders (e.g., cardiovascular risk reduction (CvRR), hypertension, atherosclerosis, type I and type II diabetes and related complications, peripheral arterial disease (PAD), acute heart failure), inflammatory skin diseases (e.g., hidradenitis suppurativa, acne), wound healing and scar formation, asthma, sarcoidosis, age-related macular degeneration, and cancer-related diseases / disorders (e.g., colon cancer, lung cancer, myeloproliferative neoplasms, leukemias, syndromes myelodysplastic (MDS)myelofibrosis).

[015] Additional aspects and advantages of the present description will become readily apparent to those skilled in the art from the detailed description that follows, in which only illustrative embodiments of the present description are shown and described. As will be seen, the present description is susceptible to other and different embodiments, and its various details are subject to modifications in several obvious respects, all without departing from the description. Consequently, the drawings and description should be considered illustrative and not restrictive in nature. Incorporation by Reference

[016] All publications, patents and patent applications mentioned in this descriptive report are incorporated herein by reference, to the same extent as if each individual publication, patent or patent application were specifically and individually indicated for incorporation by reference. To the extent that publications, patents Petition 870250084579, dated 09 / 19 / 2025, p. 11 / 201 5 / 168 or patent applications incorporated by reference contradict the description contained in the descriptive report, this is intended to replace and / or take precedence over any contradictory material. DETAILED DESCRIPTION

[017] Although various embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided only as examples. Numerous variations, alterations, and substitutions may occur to those skilled in the art without deviation from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed. Definitions

[018] Unless otherwise defined, all technical and scientific terms used herein have the same meaning commonly understood by someone skilled in the art to which this invention pertains. All patents and publications mentioned herein are incorporated by reference.

[019] Unless the context requires otherwise, throughout the descriptive report and the claims that follow, the word “comprise” and its variations, such as “comprises” and “comprising,” should be interpreted in an open and inclusive sense, that is, as “including, but not limited to.” Furthermore, the headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.

[020] The reference, throughout this descriptive report, to “some modalities” or “a modality” means that a specific characteristic, structure or feature described in connection with the modality is included in at least one modality. Thus, the appearance of the expressions “in 1 modality” or “in a modality” at various points in this descriptive report does not necessarily refer to Petition 870250084579, dated 09 / 19 / 2025, p. 12 / 201 6 / 168 refers to the same modality. Furthermore, specific characteristics, structures, or features may be combined in any suitable manner in one or more modalities. Additionally, as used in this descriptive report and the accompanying claims, the singular forms “a / an,” “an,” and “the” include plural referents unless the content clearly indicates otherwise. It should also be noted that the term “or” is generally used in its inclusive sense of “and / or,” unless the content clearly indicates otherwise.

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

[022] “oxo” refers to =O.

[023] “Carboxyl” refers to -COOH.

[024] “Cyan” refers to -CN.

[025] “Alkyl” refers to a saturated monoradical hydrocarbon with a straight or branched chain having one to about ten carbon atoms, more preferably one to six carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl and hexyl, and longer alkyl groups such as heptyl, octyl and the like.Whenever a numerical range such as “C1-C6 alkyl” or “C1-6 alkyl” appears here, it means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some cases... Petition 870250084579, dated 09 / 19 / 2025, p. 13 / 201 7 / 168 embodiments, the alkyl is a C1-10 alkyl. In some embodiments, the alkyl is a C1-6 alkyl. In some embodiments, the alkyl is a C1-5 alkyl. In some embodiments, the alkyl is a C1-4 alkyl. In some embodiments, the alkyl is a C1-3 alkyl. Unless otherwise specified in the descriptive report, an alkyl group may be optionally substituted, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkyl is optionally substituted by oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2 or -NO2. In some embodiments, the alkyl group is optionally replaced by a halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl group is optionally replaced by a halogen.

[026] “Alkenyl” refers to a straight or branched chain hydrocarbon monoradical with one or more carbon-carbon double bonds and with from two to about ten carbon atoms, more preferably from two to about six carbon atoms. The group may be in the cis or trans conformation around the double bond(s) and should be understood as including both isomers. Examples include, but are not limited to, ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl and the like. Whenever a numerical range such as “C2-C6 alkenyl” or “C2-6 alkenyl” appears here, it means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no numerical range is designated.Unless otherwise indicated in the descriptive report, an alkenyl group may optionally be replaced, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate. Petition 870250084579, dated 09 / 19 / 2025, p. 14 / 201 8 / 168 aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkenyl group is optionally replaced by oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2 or -NO2. In some embodiments, the alkenyl group is optionally replaced by halogen, -CN, -OH or -OMe. In some embodiments, the alkenyl group is optionally replaced by halogen.

[027] “Alkynyl” refers to a straight- or branched-chain hydrocarbon monoradical with one or more carbon-carbon triple bonds and with from two to about ten carbon atoms, more preferably from two to about six carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl and the like. Wherever a numerical range such as “C2-C6 alkynyl” or “C2-6 alkynyl” appears herein, it means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated.Unless otherwise specified in the descriptive report, an alkynyl group may be optionally replaced, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the alkynyl is optionally replaced by oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl is optionally replaced by halogen, CN, -OH, or -OMe. In some embodiments, the alkynyl is optionally replaced by halogen.

[028] “Alkylene” refers to a straight or branched bivalent hydrocarbon chain. Unless otherwise specified in the descriptive report, an alkylene group may be optionally substituted, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, ha Petition 870250084579, dated 09 / 19 / 2025, p. 15 / 201 9 / 168 alkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkylene is optionally replaced by oxo, halogen, -CN, -COOH, COOMe, OH, -OMe, -NH2 or -NO2. In some embodiments, the alkylene is optionally replaced by halogen, -CN, -OH or -OMe. In some embodiments, the alkylene is optionally replaced by halogen.

[029] “Alkoxy” refers to a radical of the formula -ORa, where Ra is an alkyl radical, as defined. Unless otherwise specified in the descriptive report, an alkoxy group may be optionally substituted, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the alkoxy is optionally substituted by halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2 or -NO2. In some embodiments, the alkoxy is optionally substituted by halogen, -CN, -OH or -OMe. In some embodiments, the alkoxy is optionally substituted by halogen.

[030] “Aryl” refers to a radical derived from a monocyclic or multicyclic aromatic hydrocarbon ring system by removing a hydrogen atom from a carbon atom of the ring. The monocyclic or multicyclic aromatic hydrocarbon ring system may contain only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., contains a cyclic and delocalized π-electron system (4n+2) according to Hückel's theory. The ring system from which aryl groups are derived includes, but is not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include ring systems. Petition 870250084579, dated 09 / 19 / 2025, page 16 / 201 10 / 168 fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is linked through an aromatic ring atom) or bridged. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl (phenyl). Aryl radicals include, but are not limited to, aryl radicals derived from the hydrocarbon ring systems of anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. Unless otherwise indicated in the descriptive report, an aryl group may optionally be replaced, for example, by halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like.In some embodiments, the aryl group is optionally replaced by halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl group is optionally replaced by halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl group is optionally replaced by halogen.

[031] “Carbocycle” refers to saturated, unsaturated, or aromatic rings in which every ring atom is carbon. The carbocycle may include monocyclic rings of 3 to 10 members, bicyclic rings of 6 to 12 members, and bridging rings of 6 to 12 members. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, for example, phenyl, may be fused to a saturated or unsaturated ring, for example, cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings, as valence permits, is included in the definition of carbocycle. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Unless otherwise specified in the report, Petition 870250084579, dated 09 / 19 / 2025, p. 17 / 201 11 / 168 vo, a carbide cycle can be optionally replaced.

[032] “Cycloalkyl” refers to a carbocyclic, monocyclic or polycyclic ring, partially or fully saturated, which may include fused ring systems (when fused with an aryl or heteroaryl ring, the cycloalkyl is linked by a non-aromatic atom), spiro or bridging. In some embodiments, the cycloalkyl is fully saturated.Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (e.g., fully saturated C3-C15 cycloalkyl or C3-C15 cycloalkenyl), from three to ten carbon atoms (e.g., fully saturated C3-C10 cycloalkyl or C3-C10 cycloalkenyl), from three to eight carbon atoms (e.g., fully saturated C3-C8 cycloalkyl or C3-C8 cycloalkenyl), from three to six carbon atoms (e.g., fully saturated C3-C6 cycloalkyl or C3-C6 cycloalkenyl), from three to five carbon atoms (e.g., fully saturated C3-C5 cycloalkyl or C3C5 cycloalkenyl), or from three to four carbon atoms (e.g., fully saturated C3-C4 cycloalkyl or C3-C4 cycloalkenyl). In some embodiments, the cycloalkyl group is a fully saturated 3- to 10-membered cycloalkyl group or a 3- to 10-membered cycloalkenyl group.In some embodiments, the cycloalkyl is a fully saturated 3- to 6-membered cycloalkyl or a 3- to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a fully saturated 5- to 6-membered cycloalkyl or a 5- to 6-membered cycloalkenyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.2]decane and 7,7-dimethylbicyclo[2.2.1]heptanyl. Partially saturated cycloalkyls include. Petition 870250084579, dated 09 / 19 / 2025, p. 18 / 201 12 / 168 for example, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. Unless otherwise specified in the descriptive report, a cycloalkyl is optionally substituted, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, a cycloalkyl is optionally substituted by oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2 or -NO2. In some embodiments, a cycloalkyl is optionally substituted by oxo, halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the cycloalkyl is optionally substituted by halogen.

[033] “Cycloalkenyl” refers to a non-aromatic unsaturated monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, including fused or bridging ring systems, preferably with three to twelve carbon atoms and comprising at least one double bond. In certain embodiments, a cycloalkenyl comprises from three to ten carbon atoms. In other embodiments, a cycloalkenyl comprises from five to seven carbon atoms. The cycloalkenyl may be linked to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[034] “Halo” or “halogen” refers to bromine, chlorine, fluorine or iodine. In some forms, halogen is fluorine or chlorine. In some forms, halogen is fluorine.

[035] When used in this document, the term “haloalkyl” or “haloalkane” refers to an alkyl radical, as defined above, which is replaced by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl and the like. In some embodiments, the part Petition 870250084579, dated 09 / 19 / 2025, p. 19 / 201 The 13 / 168 alkyl group of the fluoroalkyl radical is optionally further substituted. Examples of halogen-substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di- and trihalomethane (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, I, etc.). When an alkyl group is replaced by more than one halogen radical, each halogen can be selected independently, for example, 1-chloro,2-fluoroethane.

[036] “Fluoroalkyl” refers to an alkyl radical, as defined above, which is substituted by one or more fluoro radicals, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl, 2-fluoroethyl and the like.

[037] “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyl groups. In some embodiments, the alkyl is substituted by a hydroxyl group. In some embodiments, the alkyl is substituted by one, two, or three hydroxyl groups. Hydroxyalkyl includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[038] “Aminoalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted by an amine. In some embodiments, the alkyl is substituted by one, two, or three amines. Aminoalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl. Petition 870250084579, dated 09 / 19 / 2025, p. 20 / 201 14 / 168

[039] “Heteroalkyl” refers to an alkyl group in which one or more skeletal alkyl atoms are selected from an atom other than carbon, for example, oxygen, nitrogen (e.g., NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof. A heteroalkyl is linked to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C1-C6 heteroalkyl in which the heteroalkyl is composed of 1 to 6 carbon atoms and one or more atoms other than carbon, for example, oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof, in which the heteroalkyl is linked to the rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl groups are, for example, -CH2OCH3, -CH2CH2OCH3, CH2CH2OCH2CH2OCH3, -CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, CH2CH2NHCH3 or -CH2CH2N(CH3)2.Unless otherwise specified in the descriptive report, a heteroalkyl group is optionally substituted, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, a heteroalkyl group is optionally substituted by oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a heteroalkyl group is optionally substituted by oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroalkyl group is optionally substituted by halogen.

[040] “Heterocycloalkyl” refers to a partially or fully saturated ring radical of 3 to 24 members, comprising 2 to 23 carbon atoms and one to eight heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur. In some embodiments, the heterocycloalkyl is fully saturated. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur. Petition 870250084579, dated 09 / 19 / 2025, page 21 / 201 15 / 168 hydrogen and sulfur. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl comprises one to three nitrogens. In some embodiments, the heterocycloalkyl comprises one or two nitrogens. In some embodiments, the heterocycloalkyl comprises one nitrogen. In some embodiments, the heterocycloalkyl comprises one nitrogen and one oxygen.Unless otherwise specifically indicated in the descriptive report, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused ring systems (when fused with an aryl or heteroaryl ring, the heterocycloalkyl is linked via a non-aromatic ring atom), spiro, or bridging systems; and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may optionally be oxidized; the nitrogen atom may optionally be quaternized.Representative heterocycloalkyls include, but are not limited to, heterocycloalkyls with two to fifteen carbon atoms (e.g., fully saturated C2-C15 heterocycloalkyl or C2-C15 heterocycloalkenyl), two to ten carbon atoms (e.g., fully saturated C2-C10 heterocycloalkyl or C2-C10 heterocycloalkenyl), two to eight carbon atoms (e.g., fully saturated C2-C8 heterocycloalkyl or C2-C8 heterocycloalkenyl), two to seven carbon atoms (e.g., fully saturated C2-C7 heterocycloalkyl or C2-C7 heterocycloalkenyl), two to six carbon atoms (e.g., fully saturated C2-C6 heterocycloalkyl or C2-C6 heterocycloalkenyl), two to five carbon atoms (e.g., fully saturated C2-C5 heterocycloalkyl or C2-C5 heterocycloalkenyl). or two to four carbon atoms (e.g., fully saturated C2-C4 heterocycloalkyl or C2-C4 heterocycloalkenyl).Examples of such radicals include... Petition 870250084579, dated 09 / 19 / 2025, p. 22 / 201 16 / 168 terocycloalkyl groups include, but are not limited to, aziridinyl, azetidinyl, oxetanil, dioxolanil, tienyl[1,3]ditianil, decahydroisoquinolyl, 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, 1,1 -dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of carbohydrates, including, but not limited to, monosaccharides, disaccharides and oligosaccharides. In some embodiments, heterocycloalkyl have from 2 to 10 carbons in the ring.It is understood that, when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including heteroatoms) that make up the heterocycloalkyl (i.e., skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a fully saturated 3- to 8-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a fully saturated 3- to 7-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a fully saturated 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a fully saturated 4- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a fully saturated 5- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkenyl.In some embodiments, the heterocycloalkyl group is a 3- to 7-membered heterocycloalkenyl group. In some embodiments, the heterocycloalkyl group is a 3- to 6-membered heterocycloalkenyl group. In some embodiments... Petition 870250084579, dated 09 / 19 / 2025, p. 23 / 201 17 / 168 des, a heterocycloalkyl is a 4- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkenyl. Unless otherwise indicated in the descriptive report, a heterocycloalkyl may be optionally substituted as described below, for example, by oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the heterocycloalkyl is optionally substituted by oxo, halogen, methyl, ethyl, -CN, COOH, COOMe, -CF3, -OH, -OMe, -NH2 or -NO2. In some embodiments, the heterocycloalkyl group is optionally replaced by a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl group is optionally replaced by a halogen.

[041] “Heteroaryl” refers to a radical with a 14-membered ring system comprising from one to thirteen carbon atoms, from one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus and sulfur, and at least one aromatic ring. In some embodiments, the heteroaryl comprises from one to three heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In some embodiments, the heteroaryl comprises from one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heteroaryl comprises from one to three nitrogens. In some embodiments, the heteroaryl comprises from one or two nitrogens. In some embodiments, the heteroaryl comprises from one nitrogen.The heteroaryl radical can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused ring systems (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is linked through an aromatic ring atom) or bridging systems; and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may optionally be... Petition 870250084579, dated 09 / 19 / 2025, p. 24 / 201 18 / 168 oxidized; the nitrogen atom may optionally be quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. In some embodiments, the heteroaryl is a 6-membered heteroaryl. In some embodiments, the heteroaryl is a 5-membered heteroaryl. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranyl, benzofuranyl, benzofuranyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2a]pyridinyl, carbazolyl, cinolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, isoindolyl,indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1Hpyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl and thiophenyl (i.e., thienyl). Unless otherwise specified in the descriptive report, a heteroaryl group may optionally be replaced, for example, by halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, the heteroaryl group is optionally replaced by halogen, methyl, ethyl, -CN,-COOH, COOMe, -CF3, -OH, -OMe, -NH2 or -NO2. In some embodiments, the heteroaryl group is optionally replaced by halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. In some embodiments, the heteroaryl group is optionally replaced by halogen, methyl, ethyl, -CN, -CF3, -OH or -OMe. Petition 870250084579, dated 09 / 19 / 2025, p. 25 / 201, 19 / 168 dalidades, the heteroaryl is optionally replaced by halogen.

[042] The term “substituted” refers to groups with substituents that replace a hydrogen atom on one or more carbons or replaceable heteroatoms, for example, NH, of the structure. It is understood that “substitution” or “substituted by” includes the implicit condition that such substitution conforms to the permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound that does not undergo spontaneous transformation, such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to groups that have substituents that replace two hydrogen atoms on the same carbon atom, such as the replacement of the two hydrogen atoms on a single carbon by an oxo, imino, or thioxo group. When used in this document, the term “substituted” is considered to include all permitted substituents of organic compounds.In a broad sense, permitted substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. Permitted substituents may be one or more, the same or different for appropriate organic compounds. For the purposes of this description, heteroatoms, such as nitrogen, may have hydrogen substituents and / or any permitted substituents of organic compounds described herein that satisfy the valences of heteroatoms.

[043] The term “one or more”, when referring to an optional substituent, means that the group in question is optionally replaced by one, two, three, or four substituents. In some embodiments, the group in question is optionally replaced by one, two, or three substituents. In some embodiments, the group in question is optionally replaced by one or two substituents. In some embodiments, the group in question is optionally replaced by one Petition 870250084579, dated 09 / 19 / 2025, p. 26 / 201 20 / 168 substitute. In some modalities, the group in question is optionally replaced by two substitutes.

[044] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, ptoluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with both inorganic and organic bases.Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines, including naturally occurring substituted amines, cyclic amines, basic ion-exchange resins, and the like, specifically isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salt is chosen from among ammonium, potassium, sodium, calcium, and magnesium salts.

[045] The terms “parenteral administration” and “administered parenterally”, when used in this document, mean modes of administration other than enteral and topical administration, in general. Petition 870250084579, dated 09 / 19 / 2025, page 27 / 201 21 / 168 mainly by injection, and include, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[046] The term “pharmaceutically acceptable” is used here to refer to compounds, materials, compositions and / or pharmaceutical forms that are, within the scope of good medical sense, suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic response or other problem or complication, consistent with a reasonable benefit / risk ratio.

[047] The expression “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier,” when used in this document, means a pharmaceutically acceptable material, composition, or carrier, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each vehicle must be “acceptable” in the sense of being compatible with the other ingredients in the formulation and not causing harm to the patient.Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents such as hydroxide. Petition 870250084579, dated 09 / 19 / 2025, page 28 / 201 22 / 168 magnesium and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline solution; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other compatible non-toxic substances used in pharmaceutical formulations.

[048] An “effective amount” or “therapeutically effective amount” refers to an amount of a compound administered to a mammalian individual, whether in a single dose or as part of a series of doses, that is effective in producing a desired therapeutic effect.

[049] The terms “treat”, “treating” or “treatment”, when used in this document, include relieving, attenuating or improving at least one symptom of a disease or condition, preventing additional symptoms, inhibiting the disease or condition, for example, stopping the development of the disease or condition, alleviating the disease or condition, causing the regression of the disease or condition, alleviating a condition caused by the disease or condition or stopping the symptoms of the disease or condition.

[050] When used in this document, an “NLRP3 inflammasome-associated disease or disorder” or, alternatively, “an NLRP3 inflammasome-mediated disease or disorder” means any disease or other deleterious condition in which the NLRP3 inflammasome is known or suspected to play a role. Description components

[051] Compounds, or a pharmaceutically acceptable salt thereof, useful in the treatment of a disease or disorder associated with the NLRP3 inflammasome are described herein.

[052] In one aspect, the description provides a compound represented by Formula (A) or Formula (B), or a pharmaceutically acceptable salt or a stereoisomer thereof: Petition 870250084579, dated 09 / 19 / 2025, p. 29 / 201 23 / 168 Formula (A), Formula (B), wherein; Y is C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl or 5- to 9-membered heteroaryl, wherein C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl or 5- to 9-membered heteroaryl is optionally replaced by one or more R6; X is NRX, -O-, -S-, -S(O)- or -S(O)2-; RX is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members; wherein each of the alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl groups is optionally substituted by 1 to 4 substituents independently selected from Re; Each R1Ae R1Bé is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -NRCRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl; R1A and R1B are used together to form an oxo; R1A and R1B are used together to form a 4- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl; each of which is optionally replaced by one or more R11; Each R11 is independently a halogen, -OH, -CN, NO2, -ORa, -NRCRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; R3 is phenyl, 5- to 12-membered heteroaryl, C3-C12 cycloalkyl, 4- to 12-membered heterocycloalkyl or C1-C6 alkyl; each of which is optionally replaced by one or more R8; Petition 870250084579, dated 09 / 19 / 2025, page 30 / 201 24 / 168 each R8 is independently halogen, -OH, -CN, -NO2, ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRCRd, -SH, -SRa, SF5, S(=O)Ra, -S(=O)2Ra, -S(=O)(=NRb)Ra, -S(=O)2NRCRd, -NRCRd, NRbC(=O)NRCRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, N=S(=O)RCRd, -P(=O)RCRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRCRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl, C6-C10 aryl or heterocycloalkyl of 4 to 6 members, wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl, aryl or heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re; RZN is hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; or RXe RZN, together with the atoms to which they are attached, form a 5- to 8-membered heterocycloalkyl group, which is optionally substituted by one or more R13; or R3e RZN, together with the atoms to which they are attached, form a 5- to 13-membered heterocycloalkyl group, which is optionally substituted by one or more R13; Each R13 is independently a halogen, -OH, -CN, NO2, -ORa, -NRCRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl;

[053] each R6 is independently halogen, -CN, -NO2, -OH, ORa, -SH, -SRa, -SF5, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRCRd, -NRCRd, NRbC(=O)NRCRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -C(=O)Ra,C(=O)ORb, -C(=O)NRCRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C8 cycloalkyl, wherein each of alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, alkenyl, alkynyl or cycloalkyl is optionally substituted with 1 to 4 substituents independently selected from Re; Petition 870250084579, dated 09 / 19 / 2025, p. 31 / 201 25 / 168 or two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, each of which is optionally replaced by one or more R12s; Each R12 is independently a halogen, -OH, -CN, NO2, -ORa, -NRCRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; each Ra is, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re; each Rbé, independently, hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, wherein each of alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re; Rce Rdsão each one independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with 1 to 4 substituents independently selected from Re; or Rce Rdsão employed in conjunction with the atom to Petition 870250084579, dated 09 / 19 / 2025, p. 32 / 201 26 / 168 which are linked to form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re; and each Re is independently halogen, oxo, -CN, -OH, S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or C3-C6 cycloalkyl.

[054] In some embodiments of Formula (A), Y is a 3- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl, wherein the 3- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl is optionally replaced by one or more R6. In some embodiments of Formula (A), Y is a 5- to 9-membered C6-C10 aryl or heteroaryl, wherein the 5- to 9-membered C6-C10 aryl or heteroaryl is optionally replaced by one or more R6. In some embodiments of Formula (A), Y is a 5- to 9-membered heteroaryl. In some embodiments of Formula (A), Y is a C6-C10 aryl. In some embodiments of Formula (A), Y is phenyl.

[055] In another aspect, the description provides a compound represented by Formula (I) or Formula (V), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (I), Formula (V), where; X is NRX, -O-, -S-, -S(O)- or -S(O)2-; RX is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members; wherein each alkyl, haloal Petition 870250084579, dated 09 / 19 / 2025, page 33 / 201 27 / 168 quila, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally replaced by 1 to 4 substituents independently selected from Re; Each R1Ae R1Bé is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl; R1A and R1B are used together to form an oxo; or R1A and R1B are used together to form a 4- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl, each of which is optionally replaced by one or more R11; each R11 is independently halogen, -OH, -CN, -NO2, -ORa, -NRCRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; R3 is phenyl, 5- to 12-membered heteroaryl, C3-C12 cycloalkyl, 4- to 12-membered heterocycloalkyl or C1-C6 alkyl; each of which is optionally replaced by one or more R8; each R8 is independently halogen, -OH, -CN, -NO2, ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRCRd, -SH, -SRa, SF5, S(=O)Ra, -S(=O)2Ra, -S(=O)(=NRb)Ra, -S(=O)2NRCRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, N=S(=O)RcRd, -P(=O)RcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members, wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re; RZN is hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; Petition 870250084579, dated 09 / 19 / 2025, p. 34 / 201 28 / 168 or RXe RZN, together with the atoms to which they are bonded, form a 4- to 8-membered ring that is optionally replaced by one or more R13; Each R13 is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl; R6A is -OH, -OCF2H, -CF2H or -CF3; each R6 is independently halogen, -CN, -NO2, -OH, ORa, -SH, -SRa, -SF5, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -C(=O)Ra, C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C8 cycloalkyl, wherein each of alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, alkenyl, alkynyl or cycloalkyl is optionally substituted with 1 4 independently selected substituents from Re; or two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, each of which is optionally replaced by one or more R12s; each R12é, independently, halogenium, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or heterocycloalkyl from 4 to 6 members; each Raé, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, in that each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents Petition 870250084579, dated 09 / 19 / 2025, page. 35 / 201 29 / 168 independently selected from Re; each Rbé independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, wherein each of alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re; Rce Rdsão, each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each of the alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally substituted by 1 to 4 substituents independently selected from Re; or Rce Rds are employed together with the atom to which they are attached to form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from among Re; each Re is independently halogen, oxo, -CN, -OH, S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or C3-C6 cycloalkyl; ep is 1, 2, 3 or 4.

[056] In some embodiments, a compound represented by Formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof is provided herein. In some embodiments, a compound represented by Formula (V) or a pharmaceutically acceptable salt is provided herein. Petition 870250084579, dated 19 / 09 / 2025, page 36 / 201 30 / 168 is mathematically acceptable or a stereoisomer thereof.

[057] In some Formula (I) configurations, the compound is not:

[058] In some Formula (I) or (V) modalities, R6A is -OH. In some disciplines, R6Aé -CF2H or -CF3. In some disciplines, R6Aé -CF2H. In some disciplines, R6Aé -CF3. In some disciplines, R6Aé -OCF2H.

[059] In another aspect, the description provides a compound represented by Formula (Ia) or Formula (Va), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (Ia), Formula (Va), where R1A, R1B, R3, RZN, R6, X and ep have the same meanings described here. In some embodiments, R1A, R1B, R3, RZN, R6, X and ep of Formula (Ia) have the meanings described in Formula (I). In some embodiments, R1A, R1B, R3, RZN, R6, X and ep of Formula (Va) have the meanings described in Formula (V).

[060] In some embodiments, a compound represented by Formula (Ia) or a pharmaceutically acceptable salt or a stereoisomer thereof is provided herein. In some embodiments, it is provided Petition 870250084579, dated 09 / 19 / 2025, p. 37 / 201 31 / 168 cido here a compound represented by Formula (Va) or a pharmaceutically acceptable salt or a stereoisomer thereof.

[061] In some forms of Formula (Ia), the compound is not: OH o or OH o

[062] In another aspect, the description provides a compound represented by Formula (Ia) or Formula (Va), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (Ia), Formula (Va), where; X is -S-, -S(O)- or -S(O)2-; R1A, R1B, R3, RZN, R6 and p have the same meanings described here. In some embodiments, R1A, R1B, R3, RZN, R6 and p of Formula (Ia) have the meanings described in Formula (I). In some embodiments, R1A, R1B, R3, RZN, R6 and p of Formula (Va) have the meanings described in Formula (V).

[063] In some Formula (Ia) configurations, the compound is not: °HPH\ o- OH fyó HOH( 2{ ^NH7! HO— / yNH^ \VNhsF , \= / V_sou S .

[064] In some Formula (I), (Ia), (V) or (Va) modalities, p is 2 or 3. In some modalities, p is 2. Petition 870250084579, dated 09 / 19 / 2025, p. 38 / 201 32 / 168

[065] In some Formula (Ia) configurations, the compound of Formula (Ia) has the structure of Formula (II), or a pharmaceutically acceptable salt, or a stereoisomer thereof: OH Formula (II).

[066] In another aspect, the description provides a compound represented by Formula (III*), or a pharmaceutically acceptable salt or a stereoisomer thereof: r6A Formula (III*), where p is 0, 1, 2 or 3; R1A, R1B, R3, RZN, R6, R6A and X have the same meanings described here. In some embodiments, R1A, R1B, R3, RZN, R6, R6A and X of Formula (III*) have the meanings described in Formula (I). In some embodiments, R1A, R1B, R3, RZN, R6 and X of Formula (III*) have the meanings described in Formula (III).

[067] In some Formula (III*) classes, R6A is -OH. In some classes, R6A is -CF2H or -CF3. In some classes, R6A is -CF2H. In some classes, R6A is -CF3. In some classes, R6A is -OCF2H.

[068] In another aspect, the description provides a compound represented by Formula (III), or a pharmaceutically acceptable salt or a stereoisomer thereof: OH Formula (III), Petition 870250084579, dated 09 / 19 / 2025, p. 39 / 201 33 / 168 in which; X is -NRX-, -O-, -S-, -S(O)- or -S(O)2-; RX is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members; wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re; Each R1Ae R1Bé is independently hydrogen, halogen, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl; R1A and R1B are used together to form an oxo; R1A and R1B are used together to form a 4- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl; each of which is optionally replaced by one or more R11; Each R11 is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; R3 is phenyl, 5- to 12-membered heteroaryl, C3-C12 cycloalkyl, 4- to 12-membered heterocycloalkyl or C1-C6 alkyl; each of which is optionally replaced by one or more R8; each R8 is independently a halogen, -OH, -CN, -NO2, ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, SF5, S(=O)Ra, -S(=O)2Ra, -S(=O)(=NRb)Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, N=S(=O)RcRd, -P(=O)RcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1C6aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 mem Petition 870250084579, dated 09 / 19 / 2025, p. 40 / 201 34 / 168 bros, wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally replaced by 1 to 4 substituents independently selected from Re; RZN is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; or RXe RZN, together with the atoms to which they are bonded, form a 4- to 8-membered ring that is optionally replaced by one or more R13; Each R13 is independently halogen, -OH, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl; each R6 is independently halogen, -CN, -NO2, -OH, ORa, -SH, -SRa, -SF5, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -C(=O)Ra, C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C8 cycloalkyl, wherein each of alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, alkenyl, alkynyl or cycloalkyl is optionally substituted with 1 4 independently selected substituents from Re; or two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, each of which is optionally replaced by one or more R12s; Each R12 is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; each Rae, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2 Petition 870250084579, dated 09 / 19 / 2025, page 41 / 201 35 / 168 C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, in that each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 independently selected substituents within Re; each Rbé, independently, hydrogen, C1-C6 alkyla, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, em that each one within alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl and optionally substituted by 1 to 4 substituents independently selected from Re; Rce Rdsão, each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re; or Rce Rds are employed together with the atom to which they are attached to form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from among Re; each Re is independently halogen, oxo, -CN, -OH, S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or C3-C6 cycloalkyl; ep is 0, 1, 2 or 3.

[069] In another aspect, the description provides a representative compound Petition 870250084579, dated 09 / 19 / 2025, p. 42 / 201 36 / 168 seated by Formula (IIIa), Formula (VIa), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (IIIa), Formula (VIa), wherein each R6B, R6C, R6D and R6E is independently either hydrogen or R6; R1A, R1B, R3, RZN, R6 and X have the same meanings described here. In some modalities, R1A, R1B, R3, RZN, R6 and X of Formula (IIIa) or (VIa) have the meanings described in Formula (III). In some modalities, R1A, R1B, R3, RZN, R6 and X of Formula (IIIa) or (VIa) have the meanings described in Formula (I). In some modalities, R6B is R6. In some modalities, R6B is H. In some modalities, R6C is R6. In some modalities, R6C is H. In some modalities, R6D is R6. In some modalities, R6D is H. In some modalities, R6E is R6. In some embodiments, R6E is H. In some embodiments, R6B, R6D, R6E are independently R6, and R6C is H. In some embodiments, R6D and R6E are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, each of which is optionally substituted by one or more R12 groups.In some embodiments, R6D and R6E are employed together with the atoms to which they are attached to form a 5- to 6-membered heterocycloalkyl group, each of which is optionally substituted by one or more R12 groups. In some embodiments, R6D and R6E are employed together with the atoms to which they are attached to form a 4- to 6-membered cycloalkyl group, each of which is optionally substituted by one or more R12 groups.

[070] In some embodiments, a compound is provided here Petition 870250084579, dated 09 / 19 / 2025, p. 43 / 201 37 / 168 represented by Formula (IIIa) or a pharmaceutically acceptable salt or a stereoisomer thereof. In some embodiments, a compound represented by Formula (VIa) or a pharmaceutically acceptable salt or a stereoisomer thereof is provided herein.

[071] In some embodiments of Formula (A), (I), (Ia), (II), (III*), (III) or (IIIa), RX and RZN, together with the atoms to which they are attached, form a 5- to 8-membered heteroalkyl, optionally substituted by one or more R13. In some embodiments, RX and RZN, together with the atoms to which they are attached, form a 6-membered heterocycloalkyl. In some embodiments, RX and RZN, together with the atoms to which they are attached, form a 7-membered heteroalkyl. In some embodiments, RX and RZN, together with the atoms to which they are attached, form an 8-membered heteroalkyl. In some embodiments, R3 and RZN, together with the atoms to which they are attached, form a 5- to 13-membered heterocycloalkyl, optionally substituted by one or more R13.

[072] In another aspect, the description provides a compound represented by Formula (IV), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (IV), in which ring B is a 5- to 8-membered cycloalkyl heterocycloalkyl; Each R13 is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl; q is 0, 1, 2, or 3; R1A, R1B, R3, R6 and p have the same meanings described here. In some embodiments, R1A, R1B, R3, R6 and p of Formula (IV) have the meanings described in Formula (I). In some embodiments Petition 870250084579, dated 09 / 19 / 2025, p. 44 / 201 38 / 168 des, R1A, R1B, R3, R6 and p of Formula (IV) have the meanings described in Formula (A).

[073] In some embodiments of Formula (IV), ring B is a 5-membered heterocycloalkyl. In some embodiments, ring B is a 6-membered heterocycloalkyl. In some embodiments, ring B is a 7-membered heterocycloalkyl. In some embodiments, ring B is an 8-membered heterocycloalkyl.

[074] In some embodiments, the compound of Formula (IV) has the structure of Formula (IVa), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (IVa).

[075] In some Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (V), (Va) or (VIa) modalities, X is -S-, -S(O)- or -S(O)2-. In some modalities, X is -S-. In some modalities, X is -S(O)-. In some modalities, X is -S(O)2-. In some modalities, X is -O-. In some modalities, X is NRX.

[076] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (V), (Va) or (VIa), RZN is hydrogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, RZN is hydrogen or C1C6 alkyl. In some embodiments, RZN is C1-C6 alkyl. In some embodiments, RZN is methyl. In some embodiments, RZN is hydrogen.

[077] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (V), (Va) or (VIa), RX is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members; wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1 to 4 Petition 870250084579, dated 09 / 19 / 2025, p. 45 / 201 39 / 168 substituents selected independently from Re. In some embodiments, RX is hydrogen or C1-C6 alkyl. In some embodiments, RX is C1-C6 alkyl. In some embodiments, RX is methyl or ethyl. In some embodiments, RX is methyl. In some embodiments, RX is ethyl. In some embodiments, RX is hydrogen.

[078] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R1A and R1B are each independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl. In some embodiments, R1A and R1B are each independently halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, R1A and R1B are each independently halogen or C1-C6 haloalkyl. In some embodiments, R1A and R1B are each independently fluorine, chlorine, bromine, CF3 or CHF2. In some embodiments, R1A and R1B are each CF3. In some embodiments, R1A and R1B are each independently C1-C6 alkyl. In some embodiments, R1A and R1B are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, or tert-butyl. In some embodiments, R1A and R1B are each independently methyl.In some forms, R1A and R1B are, each independently, hydrogen.

[079] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R1A is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl. In some embodiments, R1A is halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, R1A is halogen or C1-C6 haloalkyl. In some embodiments, R1A is fluorine, chlorine, bromine, CF3 or CHF2. In some embodiments, R1A is CF3. In some embodiments, R1A is C1-C6 alkyl. In some forms, R1A is methyl, ethyl, n-propyl, isopropyl, n-butyl, Petition 870250084579, dated 09 / 19 / 2025, p. 46 / 201 40 / 168 sec-butyl or tert-butyl. In some embodiments, R1A is methyl. In some embodiments, R1A is hydrogen.

[080] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R1B is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl. In some embodiments, R1B is halogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, R1B is halogen or C1-C6 haloalkyl. In some embodiments, R1B is fluorine, chlorine, bromine, CF3 or CHF2. In some embodiments, R1B is CF3. In some embodiments, R1B is C1-C6 alkyl. In some embodiments, R1B is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, or tert-butyl. In some embodiments, R1B is methyl. In some embodiments, R1B is hydrogen.

[081] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R1A and R1B are employed together to form a 4- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl; each of which is optionally replaced by one or more R11. In some embodiments, R1A and R1B are employed together to form a C3-C8 cycloalkyl. In some embodiments, R1A and R1B are employed together to form a 4- to 8-membered heterocycloalkyl. In some embodiments, R1 is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In some embodiments, R1 is cyclopropyl.

[082] In some forms of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R1A and R1B are used together to form an oxo.

[083] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R6 is independently a halogen, -CN, -OH, -ORa, -SH, -SRa, -SF5, -S(=O)Ra, S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, Petition 870250084579, dated 09 / 19 / 2025, p. 47 / 201 41 / 168 NRbC(=O)ORb, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C106 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein each of the alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, alkenyl or alkynyl groups is optionally substituted by 1 to 4 substituents independently selected from Re. In some embodiments, each R6 is independently halogen, -CN, -NO2, -OH, -ORa, -SH, SRa, -SF5, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl. In some embodiments, each R6 is independently a halogen, -OH, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, each R6 is independently a halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, each R6 is independently a halogen. In some embodiments, each R6 is independently a fluorine or chlorine.In some embodiments, each R6 is independently C1-C6 alkyl. In some embodiments, each R6 is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, or tert-butyl. In some embodiments, R6 is methyl or ethyl. In some embodiments, R6 is methyl. In some embodiments, R6 is -OH. In some embodiments, each R6 is independently halogen, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl, wherein the C1-C6 alkoxy is optionally replaced by 1 to 6 halogens. In some embodiments, each R6 is independently a halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 alkoxy, wherein the alkoxy is optionally replaced by one or three halogens. In some embodiments, one or more R6s are independently halogens, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl, wherein the C1-C6 alkoxy is optionally replaced by 1 to 6 halogens.In some embodiments, one or more R6s are independently halogen, -OH, C1-C6 alkyl, C1-C6 alkoxyl. Petition 870250084579, dated 09 / 19 / 2025, p. 48 / 201 42 / 168 C1-C6 haloalkyl or C1-C6 hydroxyalkyl, wherein C1-C6 alkoxy is optionally substituted by 1 to 6 halogens, and two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R12s.

[084] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R6 is independently C1-C6 haloalkyl. In some embodiments, each R6 is independently CF3, CF2H or CFH2. In some embodiments, R6 is CF3. In some embodiments, R6 is CF2H. In some embodiments, R6 is CFH2. In some embodiments, R6 is -OCF3. In some embodiments, R6 is -OCHF2. In some embodiments, R6 is -OCH3.

[085] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R12s. In some embodiments, two R6s are employed together with the atoms to which they are attached to form a heteroaryl. In some embodiments, two R6s are employed together with the atoms to which they are attached to form a cycloalkyl or heterocycloalkyl. In some embodiments, two R6s are employed together with the atoms to which they are attached to form a C4-C8 cycloalkyl. In some embodiments, two R6s are employed together with the atoms to which they are attached to form a C5-C6 cycloalkyl.In some embodiments, two R6s are employed together with the atoms to which they are attached to form a 4- to 8-membered heterocycloalkyl. In some embodiments, two R6s are employed together with the atoms to which they are attached to form a 5- to 6-membered heterocycloalkyl. In some embodiments, two... Petition 870250084579, dated 09 / 19 / 2025, p. 49 / 201 43 / 168 R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, each of which is optionally substituted by one or more R12s. In some embodiments, two R6s are employed together with the atoms to which they are attached to form a cycloalkyl or heterocycloalkyl group, each of which is optionally substituted by one or more R12s. In some embodiments, OH Ohou \ . In some modalities, OH | is \= / '. In some modalities,

[086] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is a 4- to 12-membered C3-C12 cycloalkyl or heterocycloalkyl; each of which is optionally substituted by one or more R8. In some embodiments, R3 is a C3-C6 cycloalkyl, which is optionally substituted by 1, 2 or 3 R8. In some embodiments, R3 is a 4- to 6-membered heterocycloalkyl, which is optionally substituted by 1, 2 or \ nh [ ) R8. In some embodiments, R3 is or '< , each of which is optionally replaced by 1, 2 or 3 R8. In some embodiments, R8 is each independently selected from -OH, ORa, -SH, -SRa, SF5, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl and C3-C6 cycloalkyl.

[087] In some embodiments, R3 is linked to a compound of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa) by means of a chiral carbon atom of the R3 group. In some Petition 870250084579, dated 09 / 19 / 2025, p. 50 / 201 44 / 168 but in some embodiments, the chiral carbon atom of the R3 group has an S configuration. In some embodiments, the chiral carbon atom of the R3 group has an R configuration.

[088] In some Formula (A), (B), (I), (Ia), (II), (III*), (III), (Illa), (IV), (IVa), (V), (Va) or (Via) categories, R3 is HO CN N— OH .o , ,, cf3OH In some modalities, R3é THE HO In some modalities, R3 is or HO or In some modalities, R3 is Petition 870250084579, dated 09 / 19 / 2025, p. 51 / 201 45 / 168 OH ϊ H2N ' P ' pP , ou'P . In some embodiments, R3é , or P. In some forms, R3 is 'P or p0H.

[089] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1C6 heteroalkyl, C3-C12 cycloalkyl or 4- to 12-membered heterocycloalkyl; each of which is optionally substituted. In some embodiments, R3 is optionally substituted by one or more R8. In some embodiments, R3 is hydrogen. In some embodiments, R3 is optionally substituted C1-C6 alkyl. In some embodiments, R3 is optionally substituted C1-C6 haloalkyl. In some embodiments, R3 is optionally substituted C1-C6 hydroxyalkyl. In some embodiments, R3 is <OH, ।OH, ou χ . Em algumas modalidades, R3é IOHou χ . Em algumas modalidades, R3éXPP X. In some modalities, R3 is I0H.

[090] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is an optionally substituted C1-C6 aminoalkyl. In some embodiments, R3 is an optionally substituted C1-C6 heteroalkyl. In some embodiments Petition 870250084579, dated 09 / 19 / 2025, p. 52 / 201 46 / 168 des, R3 is an optionally substituted C3-C12 cycloalkyl. In some embodiments, R3 is an optionally substituted 4- to 12-membered heterocycloalkyl.

[091] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is a C3-C12 cycloalkyl optionally substituted by one or more R8. In some embodiments, R3 is a C4-C6 cycloalkyl optionally substituted by one or more R8. In some embodiments, R3 is cyclobutyl, which is optionally substituted by one or more R8. In some embodiments, R3 is cyclopentyl, which is optionally substituted by one or more R8. In some embodiments, R3 is cyclohexyl, which is optionally substituted by one or more R8. In some embodiments, R3 is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In some embodiments, R3 is monocyclic. In some embodiments, R3 is bicyclic.

[092] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is a 4- to 12-membered heterocycloalkyl that is optionally substituted by one or more R8. In some embodiments, R3 is a 4- to 8-membered heterocycloalkyl. In some embodiments, R3 is a 5- to 6-membered heterocycloalkyl. In some embodiments, R3 is a 6-membered heterocycloalkyl. In some embodiments, R3 is a 5-membered heterocycloalkyl. In some embodiments, R3 is a 4-membered heterocycloalkyl. In some embodiments, R3 is monocyclic. In some embodiments, R3 is bicyclic.

[093] In some Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa) modalities, R3 is .

[094] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is cyclohexyl or piperidine. In some embodiments, R3 is piperidine. In some embodiments, R3 is morpholine. In some embodiments, R3 is cyclohexyl. In Petition 870250084579, dated 09 / 19 / 2025, p. 53 / 201 47 / 168 In some forms, R3 is cyclopentyl. In some forms, R3 is cyclobutyl.

[095] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), R3 is a phenyl or heteroaryl group of 5 to 12 members, each optionally replaced by one or more R8. In some embodiments, R3 is phenyl. In some embodiments, R3 is a heteroaryl group of 5 to 12 members. In some embodiments, R3 is a heteroaryl group of 5 to 10 members. In some embodiments, R3 is a heteroaryl group of 5 to 6 members. In some embodiments, R3 is a heteroaryl group of 5 members. In some embodiments, R3 is a heteroaryl group of 6 members.

[096] In some Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa) categories, R3 is optionally replaced by one to three R8.

[097] In some Formula (A), (B), (I), (Ia), (II) categories, (III*), (III), (IIIa), (IV), (IVa), (V), (Va), or (VIa), R3é OH CF3OH. In some forms, R3 is oh, or N — . In some fashions- I | λ XT — i ..... — lidades, R3é oh . In some modalities, R3é . In some modalities, R3é

[098] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va), or (VIa), each R8 is independently halogen, -OH, -CN, -NO2, -ORa, -OC(=O)Ra, -OC(=O)ORb, Petition 870250084579, dated 09 / 19 / 2025, p. 54 / 201 48 / 168 OC(=O)NRcRd, -SH, -SRa, SF5, -S(=O)Ra, -S(=O)2Ra, -S(=O)(=NRb)Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, NRbC(=O)ORb, -NRbS(=O)2Ra, -N=S(=O)RcRd, -P(=O)RcRd, -C(=O)Ra, C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6haloalkyl, C1C6hydroxyalkyl, C1-C6heteroalkyl, C1-C6 aminoalkyl, C3C6cycloalkyl, or heterocycloalkyl 4 to 6 members, in which each of the groups alkyls, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re. In some embodiments, each R8 is independently a halogen, -OH, C1-C6 alkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members, wherein each of the alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl groups is optionally substituted by 1 to 4 substituents independently selected from Re.

[099] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R8 is independently a halogen. In some embodiments, each R8 is independently fluoro, bromine or chlorine. In some embodiments, each R8 is independently -OH. In some embodiments, each R8 is independently C1-C6 alkyl. In some embodiments, each R8 is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl.

[0100] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R8 is independently a 4- to 6-membered C3-C6 cycloalkyl or heterocycloalkyl. In some embodiments, each R8 is independently a C3-C6 cycloalkyl. In some embodiments, each R8 is independently a cyclopropyl, cyclobutyl or cyclopentyl. In some embodiments, each R8 is independently a 4- to 6-membered heterocycloalkyl. In some Petition 870250084579, dated 09 / 19 / 2025, p. 55 / 201 In 49 / 168 embodiments, each R8 is independently a 4-membered cycloalkyl heterocycloalkyl. In some embodiments, each R8 is independently a 5-membered cycloalkyl heterocycloalkyl. In some embodiments, each R8 is independently selected from -OH, -ORa, -SH, -SRa, SF5, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, and C3-C6 cycloalkyl.

[0101] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R11 is independently a halogen, -OH, -NRcRd, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, each R11 is independently a halogen, or -OH, -NH2. In some embodiments, each R11 is independently C1-C6 alkyl. In some embodiments, each R11 is independently C1-C6 haloalkyl.

[0102] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R12 is independently halogen, -OH, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl. In some embodiments, each R12 is independently a halogen, -OH, -CN, -NO2, -ORa, -NRcRd, -S(=O)CH3, -S(=O)2CH3, S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl. In some embodiments, each R12 is independently halogen, -OH, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl or C1-C6 hydroxyalkyl, C1-C6 aminoalkyl.

[0103] In some embodiments of Formula (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa), each R13 is independently halogen, -OH, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1 Petition 870250084579, dated 09 / 19 / 2025, p. 56 / 201 50 / 168 C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl. In some embodiments, each R13 is independently C1-C6 alkyl. In some embodiments, each R13 is independently methyl, ethyl, n-propyl, isopropyl, sec-butyl, or tert-butyl.

[0104] In some Formula (IV) or (IVa) configurations, p is 5.

[0105] In some Formula (I), (Ia), (IV), (V) or (Va) modalities, p is 4.

[0106] In some Formula (A), (B), (I), (Ia), (II), (III*), (III), (IV), (IVa), (V) or (Va) modalities, p is 3. In some modalities, p is at least 3. In some modalities, p is 1, 2 or 3. In some modalities, p is 1 or 2. In some modalities, p is 2. In some modalities, p is 1.

[0107] In some embodiments of a compound described herein, each Ra is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene(cycloalkyl), C1-C6 alkylene(heterocycloalkyl), C1-C6 alkylene(aryl) or C1-C6 alkylene(heteroaryl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one or more R. In some embodiments of a compound described herein, each Ra is independently C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl, heterocycloalkyl; wherein each alkyl, cycloalkyl and heterocycloalkyl is independently optionally substituted by one or more R.In some embodiments of a compound described herein, each Ra is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene(cycloalkyl), C1-C6 alkylene(heterocycloalkyl), C1-C6 alkylene(aryl) or C1-C6 alkylene(heteroaryl). In some embodiments of a compound described herein, each Ra is independently C1-C6 alkyl, C1-C6 haloalkyl or... Petition 870250084579, dated 09 / 19 / 2025, page 57 / 201 51 / 168 cycloalkyl, heterocycloalkyl. In some embodiments of a compound described herein, each Rae independently is C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of a compound described herein, each Rae independently is C1-C6 alkyl.

[0108] In some embodiments of a compound described herein, each Rb is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene(cycloalkyl), C1-C6 alkylene(heterocycloalkyl), C1-C6 alkylene(aryl) or C1-C6 alkylene(heteroaryl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one or more R. In some embodiments of a compound described herein, each Rb is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl, heterocycloalkyl; where each alkyl, cycloalkyl and heterocycloalkyl group is independently and optionally replaced by one or more R groups.In some embodiments of a compound described herein, each Rbé independently is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene(cycloalkyl), C1-C6 alkylene(heterocycloalkyl), C1-C6 alkylene(aryl) or C1-C6 alkylene(heteroaryl). In some embodiments of a compound described herein, each Rbé independently is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl, heterocycloalkyl. In some embodiments of a compound described herein, each Rbé independently is hydrogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of a compound described herein, each Rbé independently is hydrogen or C1-C6 alkyl. In some embodiments of a compound described herein, each Rbé is hydrogen. In some embodiments of a compound described herein, each Rbé, independently, C1-C6 al. Petition 870250084579, dated 09 / 19 / 2025, page 58 / 201 52 / 168 quintals.

[0109] In some embodiments of a compound described herein, each Rce Rd is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene(cycloalkyl), C1-C6 alkylene(heterocycloalkyl), C1-C6 alkylene(aryl) or C1-C6 alkylene(heteroaryl); wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted by one or more R. In some embodiments of a compound described herein, each Rce Rd is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl, heterocycloalkyl; where each alkyl, cycloalkyl and heterocycloalkyl group is independently and optionally replaced by one or more R groups.In some embodiments of a compound described herein, each Rce Rd is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene(cycloalkyl), C1-C6 alkylene(heterocycloalkyl), C1-C6 alkylene(aryl) or C1-C6 alkylene(heteroaryl). In some embodiments of a compound described herein, each Rce Rd is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl or cycloalkyl, heterocycloalkyl. In some embodiments of a compound described herein, each Rce Rd is independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of a compound described herein, each Rce Rds is independently hydrogen or C1-C6 alkyl. In some embodiments of a compound described herein, each Rce Rds is hydrogen. In some embodiments of a compound described herein, each Rce Rds is independently C1-C6 alkyl.

[0110] In some embodiments of a compound described herein, Rce Rdsão are employed in conjunction with the atom to which they are bonded. Petition 870250084579, dated 09 / 19 / 2025, p. 59 / 201 53 / 168 of the to form a heterocycloalkyl optionally substituted by one or more Re.

[0111] In some embodiments of a compound described herein, each Re is independently halogen, oxo, -CN, -OH, -S(=O)CH3, S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or C3-C6 cycloalkyl. In some embodiments of a compound described herein, each Re is independently halogen, oxo, -CN, -OH, -S(=O)C1-6alkyl, -S(=O)2C1-6alkyl, -S(=O)2NH2, S(=O)2NHC1-6alkyl, -S(=O)2N(C1-6alkyl)2, -NH2, -NHC1-6alkyl, N(C1-6alkyl)2, -C(=O)C1-6alkyl, -C(=O)OH, -C(=O)OC1-6alkyl, NHC(=O)C1-6alkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, or C3C6 cycloalkyl. In some embodiments, Reé is -NHC(=O)C1-3 alkyl, such as -NHC(=O)CH3. In some embodiments of a compound described herein, each Reé independently is halogen, -CN, -OH, or C1-C6 alkyl.In some embodiments of a compound described herein, each Reé independently halogen, -OH, or C1-C6 alkyl. In some embodiments of a compound described herein, each Reé independently halogen or C1-C6 alkyl. In some embodiments of a compound described herein, each Reé independently halogen.

[0112] In some embodiments of a compound described herein, one or more of the groups R1A, R1B, R3, R6, R8, R11, R12, R13, RZN, RX, Ra, Rb, Rc, Rd, and Rc comprise deuterium in a percentage greater than the natural abundance of deuterium.

[0113] In some embodiments of a compound described herein, one or more 1H groups are replaced by one or more deuterium groups in one or more of the following groups: R1A, R1B, R3, R6, R8, R11, R12, R13, RZN, RX, Ra, Rb, Rce, Rd, and Re. Petition 870250084579, dated 09 / 19 / 2025, p. 60 / 201 54 / 168

[0114] In some embodiments of a compound described herein, the abundance of deuterium in each of the compounds R1A, R1B, R3, R6, R8, R11, R12, R13, RZN, RX, Ra, Rb, Rce, Rd, and Reé, independently, of at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% by molar mass.

[0115] Any combination of the groups described above for the various variables is considered here. Throughout the description, the groups and their substituents are chosen by someone skilled in the art to provide stable moieties and compounds.

[0116] In some embodiments, the compound described herein, or a pharmaceutically acceptable salt or a stereoisomer thereof, is one of the compounds in Table 1 or Table 2. TABLE 1. Comp. No. Structure Comp. No. Structure 1 OH / N— NN J-- / CF3^( \^NH 41 Loh / 0H D f3c—\^Hnh F 2 OH / NH NN >--ZCF3 \ / —C ^nh 42 5 cT F3C-f 2^NH 3 OH\- N^ H NNH 13 OH / / F3C—C 9--\ y-NH Petition 870250084579, of 09 / 19 / 2025, p. 61 / 201 55 / 168 4 r Q NN )--Ç CF3 \ ^NH OH x—s 44 LoH / 0H u NC— / Y—Y~ NH S 5 OH / N— NN >—ZCF3 NH Vs 45 J.OH / 0H U / Γ-( NN F3C^7 Y--OH NH < c3 CNN^ 6 ) / —C / ^NH 46 0H \ \ γΎ NN )—7S \ / --C Χ^νη 7 OH Ç YOH NN )--' Cl=3 -y Y--NH 47 / Ç ^OH 0H \ \ yY NN Ç Ç Ç V.—h \ / NN >—ZCF3 \ ^NH 48 J'OH f\ / oh d yy NN F3cy^ Y—x)—NH 9 F, OH / N— ^y( NN >—Z CF3^ Y—^NH 49 N— i Vy NN —70 \ / —C ^nh—Nh \=< 10 F-3^ Loh yV / OH O f yy NN y Ly \^NH \=< 11 OH NN Y-7CFs \ / --\ / NH 51 OH yo < / N 12 OH S] NN X CF3^ / —C ^NH 0H 52 OH / N— NN >— / F3— / NH — p— / Petition 870250084579, of 09 / 19 / 2025, p. 62 / 201 56 / 168 13 ,\OH OH 7 / N-N}--' CF3— / p--7 ')>—NH 7=7 53 Loh \ / 0H u yp N-N F3Cp 2—7 p~ NH 7=7 S 14 _ / CN OH < N—' n—t N-N J-- / CF3^ / -- / >—NH 54 0H 1 / r^. N-N ·— / 0 \ / —^NH \=< s 15 and 16 HO OH 7 N— yp N-N CF3 \ / —\ / NH 7=7 55 OH \ N— 1 VV N-N 1-- / o^Z \—( / \^N' s x HQ OH 7 N— ^P N-N >- / cf3P / —7 pNH 7=7 56 OH / N— / r-7 N-N ?-- / -=- / / -7 ^NH 7=7 x—S 17 OH / N^^O CF3 \ / --\ / NH 7= / 57 0H \ N— Í N-N >— / 0 \ / —C ^nh / \ F ' 18 and 19 OH HO—7 N— / rP N-N )—Z CF3p / -^NH 7=7 t_ s 58 Loh ^ / 0H u i N-N · 0 \ / —C / >—N H cf3 OH HO / N— CF3 \ / --\ / NH 7=7 ·—s 59 ],>OH / \^0H u p--7 NH \=7 ·—S 20 OH P^N yp N-N CF3 \ / --\ PNH 7=7 60 J,OH r\ / 0H u f N-N O \ / -^nh 7=( 7_ sz Cl 21 OH 7 N— zrp N-N >-- / O— / / P PnH FP 7=(^VS F ' 61 Ι.ΌΗ f yy N-N ° \ / --7 NH / \ S F 7 22 OH P^H ^P N-N pN CF3P / —( PNH 7=7 =S 62 Ι.ΌΗ .,-. oh rQ n-n P / \—7 ')—NH 7=7 S Petição 870250084579, de 19 / 09 / 2025, pág. 63 / 201 57 / 168 23 OH / N— yY NN )-- / 0—< 7—(zx)—NH 63 OH OH (f\ Γ νΎ nn V_y \^z 24 OH OH y\ / rY NN Y3 CF3y xy NH \=y 64 Jn°H f NH .0 Γόη cn NN our ')—7 'Vnh ^= / ^3 F x 65 OH^ r^0H d ' vy nn 0 \ / —(zx^nh 26 OH / / N“\ r\ CF3 y pe y NH OH Y \=< s 66 J-OH r7 —OH s · Y °y U > n / nH NN 4 CF3^i 2 / NH 0 \y S 67 JxOH oh ry Ay^ nn % <y d—d NH 28 OH < N — ' n-n ·— / 0 \ / —x^nh 68 h2n oh ry YyY n-n d—^nh 29 f3c OH çAOH r—L N-N F3C— / 2—{ NH ^y 69 JxNH2 oh ry AyY n-n y-3 d—d 'JyNH 30 LoH PH U Cl— / \NH ^y 70 HO rvY d? f yy n-n y-^ 0 \ / —^NH ^y s 31 Loh rx / 0H U f yy n-n 0 \ / — / ^nh \=< s 71 ΙλΟΗ yy / 0H O i yy n-n 0 \ / —C ^YNH cd3 32 OH HN— N-N F3C^ d—e y—NH 0 \=y 201 Loh ,0H o ^y n-n F3cy p—(z 'Jynh Petition 870250084579, of 09 / 19 / 2025, p. 64 / 201 58 / 168 33 and 34 ΟΠ OH 202 Loh OH O ^-040* OH OH βΛ / N-\ F3C \ / --C / ^N J 203 Ι.,ΟΗ / 0H U f n-n 0 \ ^nh 35 204 J.OH / OH u Cl— / p--(Z NH \=< 36 OH ( N— N-N )--Z F3C—ξ ^NH 7=< '·—N \ \ 205 OH \ N— í n-n >— / 0^7 —¢ / ^NH \=< 37 OH / N— / T^ N-N )—Z NC—7 2—NH x—S 206 Lnh2 / OH ΰ N-N Cl—\ ^nh \=< s—7 38 Loh ph o F \ / —C ^nh \=< Z S 207 h2n / oh 0' N-N Cl—7 \NH 39 72 Loh r^\ / °H U [ n-n ° \ / --^n'h 40 / -\ ^OH OH <f N z í N~N ·—Z ° \ / —C / ^nh \=< TABELA 2. Petição 870250084579, de 19 / 09 / 2025, pág. 65 / 201 59 / 168 OH / Ν — / rÁ. ν~ν / ^ΝΗ οΖ ' OH / N— NN ?-- / CF3—\^NN=<\ ^N^__) OH ( N— / r-^ NN )-- / CF3^ \' / >—N ) ο λ— / 0Η \ Ν-OH— \ > Ν λ— / 0Η \ Ν-OH— \ > Ν F—Ç N— NN ΟΡ3^ V—C 7—NH OH / N — NN )-- / Ci— / \NH OH ( Ν — r—L Ν-Ν '-- / - / \ΝΗ \=< Χ S OH / N— NN}-- / NNN '0 W— OH x—^nh \—(7 ^>— NH OH ( Ν — Ν-Ν --7 |>--\ ΝΗ OH < N— NN J-- / F5S~d p-^NH OH / N— n—L NN >-- / F / —^nh F FÁF Ο- Ν-η\ Zr-λCF3 Jr-λCF3 / —C ^NH OH / N^d NN <—f CF3 d--NH \=< S OH / NN / --ν-ΟΗ CF3y / —)^NH ' y0H Q NN 0 \ / --\ / NH OH F^ ^=( F \ / oh Q / N“\—0H 7 / —\ / NH 0H F^< WSFF x / °HQ / W ,N“\ O—(7 7--(7 7—NH OH 7 / oh Q nn y-ç C1—(7 p—7 y—NH OH \= / x—S y Q nn / 7—C p—NH OH—~T) ,oh N— NN °\ \= / \_ s / 0H Q / rA / N“ N\ FjSH' 7--7 y—NH OH \= / mOH Q i yy nn .—< 0 \ / —C / -nh °h \=< ·—s / °ho NN F \ / —\ ;^NH 0H OH / -^ y^ NN / —< J CP3^ 7—7 y—NH O- OH OH / H / N~N f\ cF3y / —\ / nh °h OH / OH / =-3 N^ X^N XW \= / OH OH \ NN )---(\ / ) cf3^ ynh ^7 ^0 y _ o CFs^^d ^NH OH HO \ OH Γ^\ n~L / N~N\ CF3 \ / --\ / NH N= / oh ( Ny° .y' nn ) —7 / -7 / \- \ \ \ \ \ \ C \ N \ . Petition 870250084579, of 19 / 09 / 2025, p. 66 / 201 60 / 168 C. Other Forms of Compounds Described Herein Isomers / Stereoisomers

[0117] In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein possess one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, entgegen (E) and zusammen (Z) isomers, as well as their corresponding mixtures. In some situations, the compounds described herein possess one or more chiral centers, and each center exists in the R configuration or S configuration. The compounds described herein include all diastereomeric, enantiomeric and epimeric forms, as well as their corresponding mixtures. In further embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereomers, resulting from a single preparative step, combination or interconversion, are useful for the applications described herein.In some embodiments, the compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereomeric compounds, separating the diastereomers and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are... Petition 870250084579, dated 09 / 19 / 2025, page 67 / 201 61 / 168 preferred. In some embodiments, diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by exploiting these dissimilarities. In some embodiments, diastereomers are separated by chiral chromatography. Labeled compounds

[0118] In some embodiments, the compounds described herein exist in their isotopically labeled forms. In some embodiments, the methods described herein include methods of treating diseases by administering such isotopically labeled compounds. In some embodiments, the methods described herein include methods of treating diseases by administering such isotopically labeled compounds as pharmaceutical compositions. Thus, in some embodiments, the compounds described herein include isotopically labeled compounds that are identical to those described herein, except that one or more atoms are replaced by an atom with an atomic mass or mass number different from the atomic mass or mass number normally found in nature.Examples of isotopes that can be incorporated into the compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chloride, such as 2H(D), 3H, 13C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, 18F, and 36Cl, respectively. The compounds described herein and their pharmaceutically acceptable salts, solvates, or stereoisomers containing the aforementioned isotopes and / or other isotopes of other atoms are within the scope of this invention. Certain isotopically labeled compounds, for example, those in which radioactive isotopes such as 3H and 14C are incorporated, are useful in assays of drug and / or substrate distribution in tissues. Tritiated isotopes, i.e., 3H, and carbon-14, i.e., 14C, are particularly preferred for their ease of preparation and... Petition 870250084579, dated 09 / 19 / 2025, page 68 / 201 62 / 168 detectability.

[0119] In some embodiments, the abundance of deuterium in each of the substituents described herein is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% molar. In some embodiments, one or more of the substituents described herein comprise deuterium in a percentage greater than the natural abundance of deuterium. In some embodiments, one or more 1H are substituted by one or more deuteriums in one or more of the substituents described herein.

[0120] In some embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent groups, bioluminescent markers or chemiluminescent markers. Pharmaceutically acceptable salts

[0121] In some embodiments, the compounds described herein exist as their pharmaceutically acceptable salts. In some embodiments, the methods described herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In some embodiments, the methods described herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions.

[0122] In some embodiments, the compounds described herein possess acidic or basic groups and therefore react with any of a series of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds described herein, or of a solvate, or stereoisomer thereof, or by the separate reaction of Petition 870250084579, dated 09 / 19 / 2025, page 69 / 201 63 / 168 a purified compound in its free form with a suitable acid or base, and isolation of the salt thus formed.

[0123] Examples of pharmaceutically acceptable salts include those salts prepared by reacting the compounds described herein with a mineral, organic acid or inorganic base, such salts including acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bromide, butyrate, butyn-1,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanopropionate, decanoate, digluconate, dihydrogen phosphate, dinitrobenzoate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glycoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hexyne-1,6-dioate, hydroxybenzoate, γ-hydroxybutyrate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate, methanesulfonate, methoxybenzoate, methylbenzoate, monohydrogen phosphate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, palmate, pectinate,persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate-undeconate and xylenesulfonate.

[0124] In addition, the compounds described herein may be prepared as pharmaceutically acceptable salts formed by the reaction of the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid, including, but not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, metaphosphoric acid and the like; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanopropionic acid, glycolic acid, pyruvic acid, Petition 870250084579, dated 09 / 19 / 2025, page 70 / 201 64 / 168 lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p-toluenesulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2ene-1-carboxylic acid, glycoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, laurylsulfuric acid, gluconic acid, acid glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and muconic acid.In some embodiments, other acids, such as oxalic acid, although not pharmaceutically acceptable on their own, are employed in the preparation of salts useful as intermediates in obtaining the compounds described herein, solvate or stereoisomer thereof and their pharmaceutically acceptable acid addition salts.

[0125] In some embodiments, the compounds described herein, comprising a free acid group, react with a suitable base, such as the hydroxide, carbonate, bicarbonate, sulfate of a pharmaceutically acceptable metal cation, with ammonia or with a pharmaceutically acceptable primary, secondary, tertiary or quaternary organic amine. Representative salts include alkaline or alkaline-earth salts, such as lithium, sodium, potassium, calcium and magnesium, and aluminum salts and the like. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, N+(C1-4 alkyl)4 and the like.

[0126] Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, and the like. It should be understood that the compounds described here also include the quaternization of Petition 870250084579, dated 09 / 19 / 2025, page 71 / 201 65 / 168 any nitrogen-containing basic groups that contain. In some embodiments, products soluble or dispersible in water or oil are obtained by this quaternization. Solvatos

[0127] In some embodiments, the compounds described herein exist as solvates. In some embodiments, the description provides methods of treating diseases by administering the compounds in the form of such solvates. In some embodiments, the description provides methods of treating diseases by administering a composition comprising the compounds in the form of such solvates. The solvates contain stoichiometric or non-stoichiometric amounts of a solvent and, in some embodiments, are formed during the crystallization process with pharmaceutically acceptable solvents. Tautomers

[0128] In some situations, compounds exist as tautomers. The compounds described here include all possible tautomers within the formulas described here. Tautomers are compounds that are interconvertible by the migration of a hydrogen atom, accompanied by the exchange of a single bond and an adjacent double bond, for example, In bonding arrangements where tautomerization is possible, a chemical equilibrium of the tautomers will exist. All tautomeric forms of the compounds described here are considered. The exact proportion of tautomers depends on several factors, including temperature, solvent, and pH. Treatment Method

[0129] A method for modulating the NLRP3 inflammasome in an individual is described here, the method comprising administering Petition 870250084579, dated 09 / 19 / 2025, page 72 / 201 66 / 168 to an individual of a compound, or a pharmaceutically acceptable salt thereof, described herein. A method for inhibiting the NLRP3 inflammasome in an individual is described herein, the method comprising administering to the individual a compound, or a pharmaceutically acceptable salt thereof, described herein.

[0130] Methods for treating a disease modulated, at least in part, by the NLRP3 inflammasome in an individual who needs it are described herein, comprising administering to the individual a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, described herein.

[0131] A method for treating an autoimmune or autoinflammatory disease or condition in an individual in need thereof is described herein, comprising administering to the individual a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, as described herein.

[0132] In some forms, the disease or condition is an autoimmune disease.

[0133] In some forms, the disease or condition is an autoinflammatory disease.

[0134] In some modalities, the disease or disorder is selected from among inflammasome-related diseases / disorders, immunological diseases, inflammatory diseases, autoimmune diseases or autoinflammatory diseases, for example, autoinflammatory febrile syndromes (e.g., cryopyrin-associated periodic syndrome), liver-related diseases / disorders (e.g., chronic liver disease, viral hepatitis, non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis and alcoholic liver disease), inflammatory arthritis-related disorders (e.g., gout, pseudogout (chondrocalcinosis), osteoarthritis, rheumatoid arthritis, arthropathy, e.g., acute, chronic), kidney diseases (e.g., hyperoxaluria, lupus nephritis, Petition 870250084579, dated 09 / 19 / 2025, page 73 / 201 67 / 168 Type I / Type II diabetes and related complications (e.g., nephropathy, retinopathy), hypertensive nephropathy, hemodialysis-related inflammation), neuroinflammation-related diseases (e.g., multiple sclerosis, brain infection, acute injury, neurodegenerative diseases, Alzheimer's disease), cardiovascular / metabolic diseases / disorders (e.g., cardiovascular risk reduction (CvRR), hypertension, atherosclerosis, Type I and Type II diabetes and related complications, peripheral arterial disease (PAD), acute heart failure), inflammatory skin diseases (e.g., hidradenitis suppurativa, acne), wound healing and scar formation, asthma, sarcoidosis, age-related macular degeneration, and cancer-related diseases / disorders (e.g., colon cancer, lung cancer, myeloproliferative neoplasms, leukemias, myelodysplastic syndromes (MDS), myelofibrosis).

[0135] In some modalities, the disease or condition is obesity. In some modalities, obesity is induced by a diet high in fat.

[0136] In one aspect, a method for reducing body weight in an individual who needs it is described herein, comprising administering to the individual a compound described herein or a pharmaceutically acceptable salt or a stereoisomer thereof, or a pharmaceutical composition described herein. In some embodiments, the patient is overweight or obese. In some embodiments, the patient has a metabolic disease. In some embodiments, the patient is diabetic or pre-diabetic. Dosage

[0137] In certain embodiments, compositions containing the compound(s) described herein are administered for therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient who already suffers from a disease or condition, Petition 870250084579, dated 09 / 19 / 2025, page 74 / 201 68 / 168 in sufficient quantity to cure, or at least partially alleviate, at least one of the symptoms of the disease or condition. The effective amounts for this use depend on the severity and course of the disease or condition, prior therapy, the patient's health status, weight and response to drugs, and the judgment of the physician responsible for treatment. Therapeutically effective amounts are optionally determined by methods that include, among others, dose escalation and / or dose-ranging clinical trials. Routes of Administration

[0138] Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ophthalmic, pulmonary, transmucosal, transdermal, vaginal, otic, nasal, and topical administration. In addition, by way of example only, parenteral administration includes intramuscular, subcutaneous, intravenous, and intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injections.

[0139] In certain embodiments, a compound, as described herein, is administered locally rather than systemically, for example, by injection of the compound directly into an organ, often in a depot preparation or extended-release formulation. In specific embodiments, extended-release formulations are administered by implantation (e.g., subcutaneous or intramuscular) or by intramuscular injection. Furthermore, in other embodiments, the drug is administered in a targeted delivery system, for example, in a liposome coated with an organ-specific antibody. In such embodiments, the liposomes are targeted and selectively absorbed by the organ. In still other embodiments, the compound, as described herein, is provided in the form of a rapid-release formulation, in the form of a formula... Petition 870250084579, dated 09 / 19 / 2025, page 75 / 201 69 / 168 extended-release formulation or in the form of an intermediate-release formulation. Pharmaceutical Compositions / Formulations

[0140] The compounds described herein are administered to an individual in need of them, alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a pharmaceutical composition, in accordance with standard pharmaceutical practice. In some embodiments, the compounds described herein are administered to animals.

[0141] In another aspect, pharmaceutical compositions are provided herein comprising a compound described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. The pharmaceutical compositions are formulated in a conventional manner, using one or more pharmaceutically acceptable excipients that facilitate the processing of the active compounds into preparations that can be used pharmaceutically. The appropriate formulation depends on the chosen route of administration. A summary of the pharmaceutical compositions described herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed. (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, (NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins 1999), incorporated herein by reference for such description.

[0142] In some embodiments, the pharmaceutically acceptable excipient is selected from among carriers, binders, bulking agents, suspending agents, flavoring agents, sweetening agents, disintegrating agents, dispersing agents, surfactants Petition 870250084579, dated 09 / 19 / 2025, page 76 / 201 70 / 168 tes, lubricants, colorants, diluents, solubilizers, wetting agents, plasticizers, stabilizers, penetration enhancers, wetting agents, antifoaming agents, antioxidants, preservatives and any combinations thereof. EXAMPLES

[0143] The following examples are offered to illustrate, but not to limit, the claimed invention. The following examples further illustrate the invention, but obviously should not be interpreted as limiting its scope.

[0144] The following synthetic schemes are provided for illustrative, not limiting, purposes. The following examples illustrate the various methods of producing the compounds described herein. It is understood that a person skilled in the art may be able to produce these compounds by similar methods or by combining other methods known to a person skilled in the art. It is further understood that a person skilled in the art would be able to produce them in a manner similar to that described below, using appropriate starting materials and modifying the synthetic route as necessary. In general, the starting materials and reagents may be obtained from commercial suppliers or synthesized according to sources known to those skilled in the art or prepared as described herein.

[0145] The compounds and salts of Formulas (A), (B), (I), (Ia), (II), (III*), (III), (IIIa), (IV), (IVa), (V), (Va) or (VIa) may be synthesized according to one or more illustrative schemes described herein and / or techniques known in the art. The materials used herein are commercially available or are prepared by synthetic methods generally known in the art. These schemes are not limited to the compounds listed in the examples or to any specific substituents, which are employed for illustrative purposes. Although several steps Petition 870250084579, dated 09 / 19 / 2025, p. 77 / 201 71 / 168 are described and represented in the summary schemes below, the steps, in some cases, may be performed in a different order than shown below. The numbering or R groups in each scheme do not necessarily correspond to those of the claims or other schemes or tables described herein. Abbreviations: ACN or MeCN Acetonitrile BAST Bis(2-methoxyethyl)aminosulfur trifluoride DBU 1,8-Diaza-7-bicyclo[5.4.0]undecene DCE 1,2-Dichloroethane DCM Dichloromethane DDQ 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone DIAD Diisopropyl diazodicarboxylate Dioxane 1,4-dioxane DIPEA or DIEA Diisopropylethylamine DMAP 4-Dimethylaminopyridine DMF N,N-Dimethylformamide DMSO Dimethyl sulfoxide EA or EtOAc Ethyl acetate ESI Electrovaporization ionization FA Formic acid HOAc or AcOH Acetic acid HPLC High Performance Liquid Chromatography KOAc Potassium acetate Lawesson's reagent 2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide LC-MS Liquid Chromatography - Mass Spectrometry NBS N-Bromosuccinimide NIS N-Iodosuccinimide PDC Bis(pyridinium) dichromate Petition 870250084579, dated 09 / 19 / 2025, page 78 / 201 72 / 168 PE Petroleum ether Prep-HPLC Preparative high-performance liquid chromatography Prep-SFC Preparative supercritical fluid chromatography TLC Preparative thin-layer chromatography Prep-TLC Preparative room temperature or TA S-Phos Dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine TBSCl or TBS-Cl tert-Butyldimethylsilyl chloride TEA Triethylamine TFA Trifluoroacetic acid THF Tetrahydrofuran Example 1 Sn(n-Bu)3 NBS 1-2 1-3 1-4 1-5 NH2NHBoc s, N — 1-6 BocHNHN H2N SCN N— BBr3 HCl / dioxane S -----------► h2n„ A. . 2n nHH Compound 1

[0146] To a solution of compound 1-1 (3 g, 9.49 mmol) and tri(n-butyl)(1-ethoxyvinyl)stanane (3.4 g, 9.41 mmol) in 1,4-dioxane (30 mL), CuI (0.2 g, 1.05 mmol) and TEA (1.9 g, 18.78 mmol) were added. The mixture was purged with N2 three times. Then, Pd(PPh3)2Cl2 (1.1 g, 1.57 mmol) was added. The mixture was purged. Petition 870250084579, dated 09 / 19 / 2025, p. 79 / 201 73 / 168 with N2 three times and stirred at 100°C for 2 hours. After cooling to room temperature, HCl (10 mL, 6 M) was added to the reaction mixture, and the resulting solution was stirred for 2 hours. Then, the reaction mixture was poured into H2O (50 mL) and extracted with ethyl acetate (50 mL x 2). The combined organic phase was washed with brine (40 mL), dried over anhydrous Na2SO2, filtered through celite, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with 0 to 20% ethyl acetate in petroleum ether to give intermediate 1-2 (1.2 g, 4.17 mmol, 80.6% purity, 43.9% yield) as a yellow oil. LC-MS (ESI+): m / z 233.1 (M+H)+.

[0147] To a solution of intermediate 1-2 (600 mg, 2.58 mmol) in DCM (5 mL) were added 4-methylbenzenesulfonic acid (667.4 mg, 3.88 mmol) and NBS (689.9 mg, 3.88 mmol). The resulting solution was stirred at 40°C for 30 minutes in a microwave. After cooling to room temperature, the mixture was concentrated under reduced pressure and purified by flash column chromatography on silica gel, eluted with 0 to 10% ethyl acetate in petroleum ether, to yield intermediate 1-3 (600 mg, 0.95 mmol, 49% purity, 36.8% yield) as a yellow oil. LC-MS (ESI+): m / z 311.0 (M+H)+.

[0148] A solution of compound 1-4 (1.2 g, 10.51 mmol) in DCM (10 mL) was added to di(1H-imidazol-1-yl)methanothione (2.1 g, 11.78 mmol) in portions at 0°C. The resulting solution was stirred at 25°C for 12 hours. The mixture was concentrated under reduced pressure to produce intermediate 1-5 (1.5 g, 9.60 mmol, 91.3% yield) as a white solid, which was used in the next step without further purification.

[0149] To a solution of intermediate 1-5 (1.5 g, 9.60 mmol) in acetonitrile (10 mL), tert-hydrazinecarboxylate Petition 870250084579, dated 09 / 19 / 2025, p. 80 / 201 74 / 168 butyl (1.9 g, 14.38 mmol) and TEA (2.66 mL, 19.21 mmol). The resulting solution was stirred at 25°C for 2 hours. The mixture was concentrated under reduced pressure and purified by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether to yield intermediate 1-6 (2.5 g, 8.67 mmol, 90.3% yield) as a white solid. LC-MS (ESI+): m / z 289.2 (M+H)+.

[0150] A solution of intermediate 1-6 (1 g, 3.47 mmol) in 1,4-dioxane (25 mL) was added to HCl / 1,4-dioxane (25 mL, 4 M, 0.1 mol). The resulting solution was stirred at 25°C for 4 hours. Then, the mixture was concentrated under reduced pressure to give intermediate 1-7 (1.1 g, crude) as a white solid, which was used in the next step without further purification.

[0151] To a solution of intermediate 1-7 (240 mg, 1.28 mmol) and intermediate 1-3 (396.5 mg, 1.27 mmol) in EtOH (12 mL), TEA (0.21 mL, 1.51 mmol) was added. The resulting solution was stirred at 25°C for 10 min, and at 80°C for a further 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure and purified by Prep-HPLC (Column: Phenomenex C18 75 x 30 mm x 3 pm, Mobile Phase A: water (NH3H2O ​​+ NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 30 mL / min, gradient from 50% B to 80%) and lyophilized to obtain intermediate 1-8 (140 mg, 0.35 mmol, yield of 27.4%) as a white solid. LC-MS (ESI+): m / z 401.2 (M+H)+.

[0152] To a solution of intermediate 1-8 (160 mg, 0.40 mmol) in DCM (2 mL) was added BBr3 (0.80 mL) at 0°C. The resulting solution was then heated to 25°C and stirred for 2 hours. After cooling to 0°C, the reaction was abruptly stopped with MeOH (1 mL) and stirred at 30°C for 1 hour. The mixture was concentrated under reduced pressure. The residue was diluted with H2O (3 mL) and then extracted with EA (3 mL x 2). The aqueous phase was adjusted to pH ~9 and then Petition 870250084579, dated 09 / 19 / 2025, page 81 / 201 75 / 168 extracted with EA (5 mL x 2). The combined organic layers were dried over anhydrous Na2SO4, filtered through celite, and concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Column: Phenomenex C18 75*30 mm*3um, Mobile Phase A: water (NH3H2O+NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 30 mL / min, gradient condition from 25% B to 55%) to provide compound 1. LC-MS (ESI+): m / z 387.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) 10.46 (br, 1 H), 7.09 (s, 1 H), 7.07 6.73 (m, 2 H), 4.06 - 3.91 (m, 1 H), 3.41 - 3.38 (m, 2 H), 3.02 - 2.92 (m, 1 H), 2.69 - 2.60 (m, 1 H), 2.29 (s, 3 H), 2.20 (s, 3 H), 1.94 - 1.77 (m, 3 H), 1.72 - 1.65 (m, 1 H), 1.57 - 1.47 (m, 1 H), 1.32 - 1.21 (m, 1 H). Example 2 2-4 Compound 2

[0153] To a solution of compound 2-1 (6 g, 29.96 mmol) in DCM (80 mL), di(1H-imidazol-1-yl)methethanethione (5871.8 mg, 32.95 mmol) was added in portions, and the resulting solution was stirred at 25 °C for 12 hours. The mixture was concentrated under reduced pressure and purified by flash column chromatography on silica gel eluted with 0 to 60% ethyl acetate in petroleum ether, to yield intermediate 2-2 (6.2 g, 25.58 mmol, 85.4% yield) as a yellow oil. 1H NMR (400 MHz, CDcys) δ = 3.77 - 3.24 (m, 5 H), 1.99 - 1.72 (m, 3 Petition 870250084579, dated 09 / 19 / 2025, page 82 / 201 76 / 168 H), 1.60 - 1.45 (m, 10H)

[0154] To a solution of intermediate 2-2 (2 g, 8.25 mmol) in acetonitrile (20 mL), hydrazine (0.49 mL, 12.38 mmol) was added at 0 °C. The reaction mixture was stirred at 25 °C for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain intermediate 2-3 (2.2 g, 8.02 mmol, 97.2% yield) as a white solid. LC-MS (ESI+): m / z 275.2 (M+H)+.

[0155] A solution of intermediate 2-3 (278 mg, 1.01 mmol), intermediate 1-3 (598.8 mg, 1.92 mmol) and TEA (0.17 mL, 1.22 mmol) in EtOH (3 mL) was stirred at 25°C for 10 min, and then the resulting solution was heated at 80°C for 2 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure and purified by Prep-HPLC (Welch Xtimate C18 150 x 25 mm x 5 µm, mobile phase A: water (FA), mobile phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 30% B to 60%) to produce intermediate 2-4 (25 mg, 0.026 mmol, 50% purity, 2.5% yield) as a white solid. LC-MS (ESI+): m / z 487.1 (M+H)+. To a solution of intermediate 2-4 (25 mg, 0.051 mmol) in DCM (2 mL), BBr3 (0.10 mL, 1 M in THF, 0.1 mmol) was added at 0°C. The resulting solution was stirred at 25°C for 2 hours. The reaction was abruptly stopped with MeOH (1 mL) and then concentrated under reduced pressure.The residue was purified by Prep-HPLC (Column: Boston Green ODS 150 x 30 mm x 5 pm, Mobile Phase A: water (AP), Mobile Phase B: acetonitrile, Flow rate: 40 mL / min, gradient from 10% B to 40%) and lyophilized to obtain compound 2. LC-MS (ESI+): m / z 373.2 (M+H)+. 1H NMR (400 MHz, CD3OD) δ = 8.53 (br, 1H HCOOH), 7.07 (s, 1 H), 6.98 (s, 1 H), 4.30 - 4.16 (m, 1 H), 3.67 - 3.58 (m, 1 H), 3.54 - 3.44 (m, 2 H), 3.30 3.25 (m, 1 H), 3.04 - 2.89 (m, 2 H), 2.37 (s, 3 H), 2.17 - 2.01 (m, 2 H), 1.89 - 1.77 (m, 1 H), 1.74 - 1.63 (m, 1H). Example 3 Petition 870250084579, dated 09 / 19 / 2025, p. 83 / 201 77 / 168 OH / / τΎ NN --- / CF3^( ))--NH X= / Compound 3

[0156] Similar to the procedure for the Compound 1. Compound 3 was synthesized by replacing intermediate 1-4 with (R)-1-ethylpiperidine-3-amine. The crude product was purified by PrepHPLC (column: Welch Xtimate C18 150 x 25 mm x 5 µm, water [NH3H2O ​​+ NH4HCO3)-ACN]; %B: 40% to 70%, 7 min) to obtain compound 3. LCMS (ESI+): m / z 401.2 (M+H)+. 1H NMR: (400 MHz, DMSO-d6) δ = 10.98 - 9.83 (m, 1 H), 7.07 (s, 1 H), 7.01 (s, 1 H), 4.05 - 3.87 (m, 1 H), 3.43 - 3.35 (m, 2 H), 3.11 - 2.96 (m, 1 H), 2.81 - 2.67 (m, 1 H), 2.41 - 2.27 (m, 5 H), 1.97 - 1.76 (m, 3 H), 1.73 - 1.62 (m, 1 H), 1.55 - 1.43 (m, 1 H), 1.34 - 1.21 (m, 1 H), 1.00 (t, J = 7.2 Hz, 3 H). Example 4 Compound 4

[0157] Similar to the procedure for the Compound 1. Compound 4 was synthesized by replacing intermediate 1-4 with (1R,2R)-2-(benzyloxy)cyclohexan-1-amine. The crude product was purified by Prep-HPLC (Column: Welch Xtimate C18 150*25mm*5um, Mobile Phase A: water (NH3H2O+NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 40% B to 70%) and lyophilized to obtain compound 4. LC-MS (ESI+): m / z 388.2 (M+H)+. 1H NMR (400 MHz, ACETONITRILE-ds) δ = 7.10 (s, 1 H), 7.05 (s, 1 H), 3.73 - 3.65 (m, 1 H), 3.59 - 3.44 (m, 2 H), 3.41 - 3.33 (m, 1 H), 2.40 Petition 870250084579, dated 09 / 19 / 2025, p. 84 / 201 78 / 168 (s, 3 H), 2.07 - 1.98 (m, 2 H), 1.73 - 1.65 (m, 2 H), 1.36 - 1.23 (m, 4 H). Example 5 5-1 MgBr 5-2 5-3

[0158] To a solution of compound 5-1 (1.2 g, 4.56 mmol) in THF (12 mL), ethylmagnesium bromide (1 M in THF, 4.56 mL, 4.56 mmol) was added dropwise at 0°C, and the mixture was stirred at 20°C for 12 hours. Volatiles were removed under vacuum. The residue was adjusted to pH = 5 with aqueous HCl solution (2 M) and extracted with ethyl acetate (200 mL x 2). The combined organic extracts were washed with brine (80 mL), dried over anhydrous Na2SO2, filtered through a celite pad, and concentrated under reduced pressure to obtain intermediate 5-2 (828.0 mg, 69.6% purity, 54.4% yield) as a yellow oil. LC-MS (ESI+): m / z 233.1 (M+H)+.

[0159] A solution of intermediate 5-2 (800.0 mg, 3.45 mmol) in DCE (4 mL) was added to a mixture of CuBr2 (1539.0 mg, 6.89 mmol) in ethyl acetate (12 mL) at 80°C, and the reaction mixture was stirred at 80°C for 3 hours. After cooling to room temperature, the volatiles were removed under vacuum. The residue was poured into water (100 mL) and extracted with ethyl acetate (80 mL x 3). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to provide the crude product. It was then purified by flash column chromatography on silica gel eluted with 0 to 15% ethyl acetate in petroleum ether to give intermediate 5-3 (829 mg, 89.1% purity, 68.8% yield) as orange oil. LC-MS (ESI+): m / z 311.0 (M+H)+. Example 6 Petition 870250084579, dated 09 / 19 / 2025, page 85 / 201 79 / 168 Compound 5

[0160] Similar to the procedure for the Compound 1. Compound 5 was synthesized by replacing intermediates 13 with intermediate 5-3. The crude product was purified by Prep-HPLC (Column: Phenomenex C18 75 x 30 mm x 3 pm, Mobile Phase A: water (NH3H2O ​​+ NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 55% B to 85%) and lyophilized to obtain compound 5. LC-MS (ESI+): m / z 387.2 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 14.99 - 14.88 (m, 1 H), 7.85 (d, J = 8.4 Hz, 1 H), 7.68 - 7.53 (m, 1 H), 7.25 - 7.19 (m, 2 H), 4.84 - 4.76 (m, 1 H), 4.17 - 3.97 (m, 1 H), 3.06 - 2.76 (m, 1 H), 2.65 - 2.55 (m, 1 H), 2.19 - 2.16 (m, 3 H), 1.96 - 1.75 (m, 3 H), 1.72 - 1.64 (m, 1 H), 1.58 1.46 (m, 1 H), 1.32 - 1.22 (m, 4 H). Example 7 (JnHBr^^OBn BocHN BocHN H2N ·ЗПЙ 6-1 6-2

[0161] To a solution of (R)-tert-butylpiperidin-3-ylcarbamate (2.00 g, 9.99 mmol) and ((2-bromoethoxy)methyl)benzene (2.14 g, 9.99 mmol) in MeCN (20 mL), K2CO3 (2.76 g, 20.0 mmol) was added. The resulting mixture was stirred at 60°C for 1 hour. After cooling to room temperature, the mixture was filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether, to produce intermediate 6-1 (2.16 g, 64.7% yield) as a white solid. LC-MS (ESI+): m / z 335.3 (M+H)+.

[0162] To a solution of intermediate 6-1 (500.0 mg, 1.49 mmol) Petition 870250084579, dated 09 / 19 / 2025, p. 86 / 201 80 / 168 in MeOH (2.0 mL), HCl / MeOH (2.0 mL, 4 M) was added, and the resulting mixture was stirred at 20°C for 12 hours. The reaction mixture was concentrated under reduced pressure to yield intermediate 6-2 (570.0 mg, crude) as a white solid. LC-MS (ESI+): m / z 235.2 (M+H)+.

[0163] Similar to the procedure for the Compound 1. Compound 6 was synthesized by replacing intermediates 14 with intermediate 6-2. The crude product was purified by HPLC column: Welch Xtimate C18 150 x 25 mm x 5 µm, water (NH3H2O ​​+ NH4HCO3) -ACN]; B %: 30% to 60%, 7 min, to obtain compound 6. LC-MS (ESI+): m / z 417.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 7.05 (s, 1 H), 6.99 (s, 1 H), 4.54 4.26 (m, 1 H), 4.09 - 3.90 (m, 1 H), 3.49 - 3.46 (m, 4 H), 3.01 - 2.92 (m, H), 2.71 - 2.62 (m, 1 H), 2.39 (t, J = 6.0 Hz, 2 H), 2.29 (s, 3 H), 2.06 1.92 (m, 2 H), 1.86 - 1.75 (m, 1 H), 1.72 - 1.60 (m, 1 H), 1.56 - 1.42 (m, H), 1.37 - 1.25 (m, 1 H). Example 9 s 7-1 7-2

[0164] To a solution of di(1H-imidazol-1-yl)methanothione (1.00 g, 5.61 mmol) in dioxane (10 mL), tert-butyl hydrazine carboxylate (700.0 mg, 5.50 mmol) was slowly added, and the reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (20 mL x 3). The organic extracts Petition 870250084579, dated 09 / 19 / 2025, page 87 / 201 81 / 168 combined samples were washed with brine (10 mL), dried over anhydrous Na2SO2, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to obtain a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether, yielding intermediate 7-1 (1.00 g, 73.3% yield) as a yellow solid. LC-MS (ESI+): m / z 243.0 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 8.82 (s, 1 H), 8.52 (s, 1 H), 7.80 (s, 1 H), 7.43 (s, 1 H), 7.22 (s, 1 H), 1.44 (s, 9 H).

[0165] To a solution of intermediate 7-1 (552.1 mg, 2.28 mmol) and (1S,3R)-3-aminocyclohexan-1-ol hydrochloride (380.0 mg, 2.51 mmol) in dioxane (5.0 mL), TEA (0.95 mL, 6.84 mmol) was added. The resulting mixture was stirred at 80°C for 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether to produce intermediate 7-2 (300.0 mg, 97.7% purity, 44.4% yield) as a white solid. LC-MS (ESI+): m / z 290.1 ​​(M+H)+. Example 10 Compound 7

[0166] Similar to the procedure for the Compound 1. Compound 7 was synthesized by replacing intermediate 1-6 with intermediate 7-2. The crude product was purified by Prep-HPLC (column: Welch Xtimate C18 150 x 25 mm x 5 µm, mobile phase A: water (NH4HCO3), mobile phase B: acetonitrile, flow rate: 25 mL / min, gradient from 35% B to 65%) and lyophilized to obtain compound 7. LC-MS (ESI+): m / z 388.2 (M+H)+. Petition 870250084579, dated 09 / 19 / 2025, p. 88 / 201 82 / 168 1H NMR (400 MHz, DMSO-d6) δ = 10.47 (br.s., 1 H), 7.08 (s, 1 H), 7.01 (s, 1 H), 4.69 - 4.60 (m, 1 H), 3.91 - 3.73 (m, 1 H), 3.50 - 3.37 (m, 3 H), 2.29 (s, 3H),2.19 - 2.10 (m, 1H), 1.92 - 1.84 (m, 1H), 1.83 - 1.75 (m, 1H), 1.72 - 1.65 (m, 1H), 1.31 - 1.01 (m, 4H). Example 11 8-1 8-2

[0167] To a solution of (3R,5R)-tert-butyl (5-fluoropiperidin-3yl)carbamate (2.0 g, 9.16 mmol) and (CH2O)n (1.0 g) in MeOH (20 mL), HOAc (0.52 mL, 9.16 mmol) was added. The mixture was then stirred at 25°C for 0.5 hours. NaBHaCN (2.65 g, 42.14 mmol) was added, and the resulting mixture was stirred at 25°C for 5 hours. The mixture was filtered through a celite pad, and the filtrate was concentrated under reduced pressure to provide the crude product, which was purified by Prep-HPLC (column: Welch Xtimate C18 150 x 25 mm x 5 µm, water [NH3H2O ​​+ NH4HCO3) - ACN]); B%: 25% to 55%, 7 min) to produce intermediate 8-1 (1.88 g, 88.3% yield) as a white solid. LC-MS (ESI+): m / z 233.2 (M+H)+.

[0168] To a solution of intermediate 8-1 (900.0 mg, 3.87 mmol) in MeOH (3.0 mL), 4 M HCl in MeOH (2.0 mL) was added, and the resulting solution was stirred at 20°C for 12 hours. The volatiles were removed under vacuum, resulting in intermediate 8-2 (688 mg, crude) as a white solid.

[0169] A mixture of intermediate 8-2 (588.0 mg, 3.49 mmol), intermediate 7-1 (929.0 mg, 3.83 mmol) and TEA (0.48 mL, 3.49 mmol) in dioxane (6.0 mL) was stirred at 80°C for 1 hour. The reaction mixture was filtered through a celite pad, and the filtrate was concentrated under reduced pressure, resulting in a residue. It was then purified Petition 870250084579, dated 09 / 19 / 2025, page 89 / 201 83 / 168 was obtained by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether, to produce intermediate 8-3 (210.0 mg, 19.7% yield) as a yellow solid. LC-MS (ESI+): m / z 307.1 (M+H)+. Example 12

[0170] Similar to the procedure for the Compound 1. Compound 8 was synthesized by replacing intermediate 1-6 with intermediate 8-3. The crude product was purified by Prep-HPLC (column: Welch Xtimate C18 150 x 25 mm x 5 pm, water [NH3H2O ​​+ NH4HCO3) -ACN]; B %: 42% to 72%, 7 min) and lyophilized to obtain compound 8. LC-MS (ESI+): m / z 405.2 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.36 (br.s., 1 H), 7.07 (s, 1 H), 7.01 (s, 1 H), 5.11 - 4.74 (m, 1 H), 4.40 - 4.12 (m, 1 H), 3.44 - 3.37 (m, 2 H), 2.98 - 2.88 (m, 1 H), 2.87 - 2.75 (m, 1 H), 2.29 (s, 3 H), 2.20 (s, 3 H), 2.17 - 2.00 (m, 2 H), 1.95 - 1.85 (m, 1 H), 1.71 - 1.46 (m, 1 H). Example 13

[0171] Similar to the procedure for the Compound 8, Compound 9 was synthesized by replacing tert-butyl ((3R,5R)-5-fluoropiperidin-3-yl)carbamate with tert-butyl ((3R,5S)-5-fluoropiperidin-3-yl)carbamate. The crude product was purified by PrepHPLC (column: Welch Xtimate C18 150*30 mm*5um, water (FA)-ACN]; B %: 10% to 40%, 7 min) and lyophilized to obtain compound 9. Petition 870250084579, dated 09 / 19 / 2025, pp. 90 / 201 84 / 168 LC-MS (ESI+): m / z 405.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 11.27 - 9.92 (m, 1 H), 8.18 (s, 0.46H HCOOH), 7.08 (s, 1 H), 7.01 (s, 1 H), 4.78 - 4.56 (m, 1 H), 4.11 - 3.95 (m, 1 H), 3.41 - 3.37 (m, 2 H), 3.08 - 2.91 (m, 2 H), 2.36 2.26 (m, 4 H), 2.25 (s, 3 H), 1.98 - 1.88 (m, 1 H), 1.84 - 1.69 (m, 1 H), 1.53 - 1.37 (m, 1 H). Example 14 BocHN ''0HBzCI '°'Bz TFA %z BocHN H2N 10-1 10-2BzHCl / dioxane NH2NHBoc St. Street s, SCN BocHNHN 10-4 h2nhn °'Bz Br

[0172] To a mixture of tert-butyl ((1s,3s)-3-hydroxy-3-methylcyclobutyl)carbamate (1.00 g, 4.97 mmol), benzoyl chloride (0.58 mL, 4.97 mmol), and TEA (0.69 mL, 4.97 mmol) in DCM (15.0 mL), DMAP (607.2 mg, 4.97 mmol) was added, and the mixture was stirred at 25°C for 12 hours. The reaction mixture was then concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 25% ethyl acetate in petroleum ether to yield intermediate 10⁻¹ (408.3 mg, 61.4% purity, 16.5% yield) as a single product. Petition 870250084579, dated 09 / 19 / 2025, page 91 / 201 85 / 168 read white. LC-MS (ESI+): m / z: 328.1 (M+Na)+.

[0173] To a solution of intermediate 10-1 (440.0 mg, 1.44 mmol) in DCM (5.0 mL), TFA (1.0 mL, 13.06 mmol) was added, and the mixture was stirred at 20°C for 1 hour. The reaction mixture was concentrated under reduced pressure to produce a residue. The residue was adjusted to pH = 8.9 with TEA and diluted with ethyl acetate (20 mL). The mixture was filtered, and the filtrate was concentrated under reduced pressure to produce intermediate 10-2 (300.0 mg, crude) as a brown oil. LC-MS (ESI+): m / z: 206.2 (M+H)+. To a solution of intermediate 102 (300.0 mg, crude) in DCM (10.0 mL), di(1H-imidazol-1yl)methethanethione (286.4 mg, 1.61 mmol) was added in portions at 0°C, and the mixture was stirred at 25°C for 12 hours. The reaction mixture was concentrated under reduced pressure to yield intermediate 10-3 (350.0 mg, crude) as a brown oil, which was used in the next step without further purification.

[0174] A solution of intermediate 10-3 (350.0 mg, crude) in MeCN (5.0 mL) was added to tert-butyl hydrazine carboxylate (374.2 mg, 2.83 mmol) and TEA (0.20 mL, 1.42 mmol), and the reaction mixture was stirred at 25°C for 2 hours. The reaction mixture was concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 25% ethyl acetate in petroleum ether to produce intermediate 10⁻⁴ (552.6 mg, 97.7% purity, 98.8% yield in 3 steps) as a white solid. LC-MS (ESI+): m / z: 380.2 (M+H)⁺.

[0175] To a solution of intermediate 10-4 (150.0 mg, 0.40 mmol) in dioxane (5.0 mL) was added HCl / dioxane (3.0 mL, 4 M). The mixture was stirred at 20°C for 1.5 hours. The volatiles were removed under vacuum, resulting in intermediate 10-5 (110.0 mg, crude) as a white solid, which was used in the next step without further purification.

[0176] A solution of the intermediate 10-5 (110.0 mg, crude), inter Petition 870250084579, dated 09 / 19 / 2025, page 92 / 201 86 / 168 intermediate 1-3 (122.5 mg, 0.39 mmol) and TEA (50 μL, 0.36 mmol) in EtOH (3.0 mL) was stirred at 25°C for 10 minutes, and at 80°C for a further 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure to produce a residue. The residue was poured into water (100 mL) and extracted with ethyl acetate (80 mL x 3). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce intermediate 10-6 (150.0 mg, crude) as a yellow oil. LC-MS (ESI+): m / z: 492.2 (M+H)+.

[0177] To a solution of intermediate 10-6 (110.0 mg, 0.22 mmol) in DCM (2.0 mL), BBr3 (0.22 mL, 1 M in DCM, 0.22 mmol) was added dropwise at 0°C, and the mixture was stirred at 20°C for 1 hour. The reaction mixture was tempered by the slow addition of MeOH (5.0 mL), and the volatiles were removed under vacuum to obtain the residue. The residue was poured into water (20 mL) and extracted with ethyl acetate (30 mL x 3). The combined organic extracts were washed with brine (15 mL), dried over anhydrous Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by Prep-HPLC (column: Phenomenex C18 80*45mm*3um, mobile phase: water (NH3H2O+NH4HCO3)-ACN; B %: 48% to 78%, 9 min) and lyophilized to produce intermediate 10-7 (30.0 mg, 88.2% purity, 27.6% yield) as a yellow solid. LC-MS (ESI+): m / z: 436.1 (M+H)+.

[0178] A mixture of intermediate 10-7 (15.0 mg, 0.034 mmol) and silver acetate (14.3 mg, 0.086 mmol) in acetic acid (2.0 mL) was stirred at 20°C for 12 hours. The mixture was filtered through a celite pad, and the filtrate was lyophilized to give intermediate 10-8 (15.0 mg, crude) as a brown solid. LC-MS (ESI+): m / z: 416.1 Petition 870250084579, dated 09 / 19 / 2025, p. 93 / 201 87 / 168 (M+H)+.

[0179] To a solution of intermediate 10-8 (20.0 mg, 0.048 mmol) in MeOH (2.0 mL) was added K2CO3 (6.7 mg, 0.048 mmol). The mixture was stirred at 20°C for 0.5 hours. Then, the mixture was filtered through a celite pad, and the filtrate was concentrated under reduced pressure to provide a residue. The residue was purified by Prep-HPLC (Column: Phenomenex C18 75*30 mm*3um, Mobile Phase A: water (NH3H2O+NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient condition from 23% B to 53%) to provide compound 10. LC-MS (ESI+): m / z: 374.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 10.93 - 10.08 (m, 1 H), 7.08 (s, 1 H), 7.02 (s, 1 H), 5.01 (s, 1 H), 4.01 - 3.90 (m, 1 H), 3.47 - 3.40 (m, 2 H), 2.35 - 2.30 (m, 2 H), 2.28 (s, 3 H), 2.06 - 1.99 (m, 2 H), 1.25 (s, 3 H). Example 15 Compound 11

[0180] Similar to the procedure for the Compound 1. Compound 11 was synthesized by replacing intermediate 1-4 with (R)-1-methylpyrrolidine-3-amine. The crude product was purified by Prep-HPLC (column: Phenomenex C18 75 x 30 mm x 3 pm, mobile phase A: water (NH3H2O ​​+ NH4HCO3), mobile phase B: acetonitrile, flow rate: 25 mL / min, gradient from 35% B to 65%) to obtain compound 11. LC-MS (ESI+): m / z: 373.2 (M+H)+, RMN de1H (400 MHz, DMSO-d6) δ = 11,05 - 9,91 (m, 1 H), 7,07 (s, 1 H), 7,00 (s, 1 H), 4,45 - 4,31 (m, 1 H), 3,42 - 3,38 (m, 2 H), 2,76 - 2,68 (m, 1 H), 2,62 - 2,54 (m, 1 H), 2,48 - 2,43 (m, 1 H), 2,42 - 2,35 (m, 1 H), Petição 870250084579, de 19 / 09 / 2025, pág. 94 / 201 88 / 168 2,28 (s, 3 H), 2,25 (s, 3 H), 2,21 - 2,11 (m, 1 H), 1,75 - 1,65 (m, 1 H). Exemplo 16 • HCI OH Η H OH 12-1

[0181] A solution of (1R,2R)-2aminocyclopentan-1-ol hydrochloride (400.0 mg, 2.91 mmol) and TEA (1.21 mL, 8.72 mmol) in dioxane (10.0 mL), tert-butyl 2-(1H-imidazol-1-carbonothioyl)hydrazine-1-carboxylate (1000.0 mg, 4.13 mmol) was mixed at 20°C, and the mixture was stirred at 110°C for 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 24% THF in DCM to produce intermediate 12-1 (450.0 mg, 94.8% purity, 53.3% yield) as a white solid. LC-MS (ESI+): m / z: 297.9 (M+Na)+. Example 17 OH ¢ / N-NCF3^f / ANH 0H Compound 12

[0182] Similar to the procedure for the Compound 1. Compound 12 was synthesized by replacing intermediate 1-6 with intermediate 12-1. The residue was purified by Prep-HPLC (column: Phenomenex C18 80 x 40 mm x 3 pm, mobile phase A: water (NH3H2O ​​+ NH4HCO3), mobile phase B: acetonitrile, flow rate: 30 mL / min, gradient from 32% B to 62%) to obtain compound 12. LC-MS (ESI+): m / z: 374.1 (M+H)+, 1H NMR (400 MHz, DMSO-de) δ = 10.46 (br, s, 1 H), 7.08 (s, 1 H), 7.01 (s, 1 H), 5.38 - 5.05 (m, 1 H), 3.98 - 3.89 (m, 2 H), 3.43 - 3.38 (m, Petition 870250084579, dated 09 / 19 / 2025, p. 95 / 201 89 / 168 H), 2.29 (s, 3 H), 2.09 - 1.98 (m, 1 H), 1.90 - 1.81 (m, 1 H), 1.70 1.59 (m, 2 H), 1.55 - 1.42 (m, 2 H). Example 18 Compound 13

[0183] Similar to the procedure for the Compound 12, Compound 13 was synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with (1S,3R)-3-aminocyclopentan-1-ol. The crude product was purified by Prep-HPLC (column: Welch Xtimate C18 150*30 mm*5um, mobile phase: water (FA)-ACN) and lyophilized to obtain compound 13. LC-MS (ESI+): m / z 374.2 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ = 8.13 (s, 1H from HCOOH), 7.08 (s, 1 H), 7.01 (s, 1 H), 5.01 - 4.45 (m, 1 H), 4.27 - 4.14 (m, 1 H), 4.13 4.01 (m, 1 H), 3.43 - 3.40 (m, 2 H), 2.29 (s, 3 H), 2.25 - 2.15 (m, 1 H), 1.99 - 1.84 (m, 1 H), 1.78 - 1.54 (m, 3 H), 1.52 - 1.43 (m, 1 H). Example 19 Compound 2 Compound 14

[0184] To a solution of compound 2 (150.0 mg, 0.23 mmol, 70% purity) and DIPEA (90 μL, 0.56 mmol) in THF (5.0 mL), 2-chloroacetonitrile (21.3 mg, 0.28 mmol) was added, and the reaction mixture was stirred at 67°C for 2 hours. After cooling to room temperature, the volatiles were removed under vacuum to produce a residue. The residue was purified by Prep-HPLC (Column: Phenomenex Gemini-NX 80*40 mm*3um, Mobile Phase A: water (0.05% NH3H2O+NH4HCO3 10 mM), Mobile Phase B: acetonitrile, Flow rate: Petition 870250084579, dated 09 / 19 / 2025, pp. 96 / 201 90 / 168 mL / min, gradient condition from 30% B to 60%), then by PrepSFC (Column: DAICEL CHIRALCEL OJ (250 mm*30 mm, 10 µm), Condition: CO2-EtOH (0.1% NH3H2O), Initial B: 30%, Flow rate: 70 mL / min) and lyophilized to produce compound 14. LC-MS (ESI+): m / z 412.2 (M+H)+, de1H NMR (400 MHz, DMSO-de) δ =10.50 (br, s, 1 H), 7.07 (s, 1 H), 7.00 (s, 1 H), 4.10 - 3.93 (m, 1 H), 3.77 (s, 2 H), 3.42 - 3.27 (m, 26 H 2.96 (m, 1 H), 2.71 - 2.64 (m, 1 H), 2.28 (s, 3 H), 2.18 - 2.02 (m, 2 H), 1.89 - 1.82 (m, 1 H), 1.31 - 1.22 (m, 1 H). Example 20 15-Cis 15-trans racemic racemic OH OH HCl / dioxane 15-Cis racemic 15-1 racemic

[0185] To a solution of tert-butyl(5-hydroxypiperidin-3-yl)carbamate (900.0 mg, 4.16 mmol) and (CH2O)2 (900.0 mg, 29.97 mmol) in MeOH (3.0 mL), HOAc (0.24 mL, 4.16 mmol) was added, and the mixture was stirred at 25°C for 30 min. Then, NaB^CN (653.3 mg, 10.40 mmol) was added, and the reaction mixture was stirred at 25°C for 12 hours. The volatiles were removed under vacuum to produce a residue. The residue was purified by Prep-HPLC (column: Phenomenex C18 75 x 30 mm x 3 pm, mobile phase A: water (NH3H2O ​​+ NH4HCO3), mobile phase B: acetonitrile, flow rate: 25 mL / min, gradient from 17% B to 47%) and lyophilized to produce the 15-Cis intermediate (310.0 mg, yield of 32.3%) as a white solid, and the Petition 870250084579, dated 09 / 19 / 2025, pp. 97 / 201 91 / 168 intermediate 15-trans (320.0 mg, yield of 33.4%) as a white solid. LC-MS (ESI+): m / z 231.2 (M+H)+.

[0186] To a solution of intermediate 15-Cis (310.0 mg, 1.35 mmol) in MeOH (5.0 mL), HCl / dioxane (5.0 mL, 4 M) was added, and the reaction mixture was stirred at 20°C for 1 hour. The volatiles were removed under vacuum to yield intermediate 15-1 (324.0 mg, crude) as a white solid, which was used in the next step without further purification. Example 21 Compounds 15 and 16

[0187] Similar to the procedure for the Compound 12, Compounds 15 and 16 were synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with Intermediate 15-1. The crude product was purified by Prep-SFC (Column: DAICEL CHIRALPAK IG (250 mm x 30 mm, 10 pm), Mobile Phase: CO2-EtOH (0.1% NH2H2O), Flow Rate: 80 mL / min, gradient from 35% B to 35%) to yield compounds 15 and 16. Composto 15 (o primeiro pico): LC-MS (ESI+): m / z 403,2 (M+H)+, RMN de1H (400 MHz, DMSO-de) δ = 10,47 (br, s, 1 H), 7,37 - 7,06 (m, 2 H), 7,00 (s, 1 H), 4,87 - 4,80 (m, 1 H), 4,08 - 3,85 (m, 1 H), 3,61 3,50 (m, 1 H), 3,43 - 3,37 (m, 2 H), 3,03 - 2,91 (m, 1 H), 2,85 - 2,75 (m, 1 H), 2,28 (s, 3 H), 2,19 (s, 3 H), 2,11 - 2,03 (m, 1 H), 1,68 - 1,56 (m, 2 H), 1,19 - 1,08 (m, 1 H).

[0188] Composto 16 (o segundo pico): LC-MS (ESI+): m / z 403,2 (M+H)+, RMN de1H (400 MHz, DMSO-de) δ = 10,47 (br, s, 1 H), 7,08 (s, 1 H), 7,05 - 6,74 (m, 2 H), 4,87 - 4,80 (m, 1 H), 4,08 - 3,85 (m, 1 H), 3,61 - 3,50 (m, 1 H), 3,44 - 3,37 (m, 2 H), 3,04 - 2,92 (m, 1 H), 2,85 Petição 870250084579, de 19 / 09 / 2025, pág. 98 / 201 92 / 168 2,75 (m, 1 H), 2,28 (s, 3 H), 2,19 (s, 3 H), 2,12 - 2,03 (m, 1 H), 1,69 1,54 (m, 2 H), 1,20 - 1,08 (m, 1 H). Exemplo 22 Composto 2 Composto 17

[0189] To a solution of compound 2 (150.0 mg, 0.25 mmol, 75% purity, HBr salt) in MeOH (1.5 mL), TEA (84 μL, 0.60 mmol) was added, and the reaction mixture was stirred at 25°C for 15 min. Then, oxetan-3-one (54.4 mg, 0.76 mmol) and HOAc (112.7 mg, 1.88 mmol) were added sequentially, and the mixture was stirred at 25°C for 30 min. Then, NaBH3CN (19.0 mg, 0.30 mmol) was added, and the mixture was stirred at 25°C for 2 hours. The mixture was purified by Prep-TLC (DCM: MeOH = 10:1), Prep-SFC (Column: DAICEL CHIRALCEL OD (250 mm*30 mm, 10 µm), Condition: CO2-EtOH (0.1% NH3H2O), Initial B: 20%, Flow rate: 150 mL / min) and then by Prep-HPLC (Column: Phenomenex C18 80*40 mm*3 µm, Mobile phase A: water (NH3H2O+NH4HCO3), Mobile phase B: acetonitrile, Flow rate: 30 mL / min, gradient condition from 29% B to 59%) to produce compound 17. LC-MS (ESI+): m / z 429.1 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ = 10.47 (br, s, 1 H), 7.08 (s, 1 H), 7.04 - 6.82 (m, 2 H), 4.56 - 4.49 (m, 2 H), 4.47 - 4.40 (m, 2 H), 4.08 3.91 (m, 1 H), 3.44 - 3.41 (m, 2 H), 2.89 - 2.79 (m, 1 H), 2.60 - 2.52 (m, 2 H), 2.30 (s, 3 H), 1.93 - 1.67 (m, 4 H), 1.59 - 1.46 (m, 1 H), 1.37 1.28 (m, 1 H). Example 23 Petition 870250084579, dated 09 / 19 / 2025, pp. 99 / 201 93 / 168 Compounds 18 and 19

[0190] Similar to the procedure for the Compound Compounds 18 and 19 were synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with (trans)-3-amino-1-methylpiperidin-4-ol hydrochloride. The crude product was separated by Prep-SFC (Column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 µm), Mobile Phase: CO2-EtOH (0.1% NH2H2O), Flow Rate: 70 mL / min, 25% gradient) and then purified by Preparative HPLC (Welch Xtimate C18 150 x 25 mm x 5 µm, Mobile Phase: water (NH2H2O + NH2HCO2)-ACN, Taxa de vazão: 25 mL / min, gradiente de 12 % a 42 % para obter os compostos título 18 e 19. Composto 18 (o primeiro pico): LC-MS (ESI+): m / z 403,2 (M+H)+, RMN de1H (400 MHz, DMSO-d6) δ = 10,49 (br, s,, 1 H), 7,08 (s, 1 H), 7,05 - 6,62 (m, 2 H), 5,11 - 4,66 (m, 1 H), 3,96 - 3,64 (m, 1 H), 3,44 3,40 (m, 2 H), 3,04 - 2,89 (m, 1 H), 2,72 - 2,58 (m, 1 H), 2,29 (s, 3 H), 2,16 (s, 3 H), 2,14 - 2,02 (m, 1 H), 1,98 - 1,88 (m, 1 H), 1,87 - 1,73 (m, 2 H), 1,56 - 1,41 (m, 1 H). Composto 19 (o segundo pico): LC-MS (ESI+): m / z 403,2 (M+H)+, RMN de1H (400 MHz, DMSO-d6) δ = 10,49 (br, s,, 1 H), 7,08 (s, 1 H), 7,05 - 6,62 (m, 2 H), 5,11 - 4,66 (m, 1 H), 3,96 - 3,64 (m, 1 H), 3,44 3,40 (m, 2 H), 3,04 - 2,89 (m, 1 H), 2,72 - 2,58 (m, 1 H), 2,29 (s, 3 H), 2,16 (s, 3 H), 2,14 - 2,06 (m, 1 H), 1,98 - 1,88 (m, 1 H), 1,87 - 1,73 (m, 2 H), 1,56 - 1,41 (m, 1 H). Exemplo 24 Composto 20 Petition 870250084579, dated 09 / 19 / 2025, p. 100 / 201 94 / 168

[0191] Similar to the procedure for the Compound 1. Compound 20 was synthesized by replacing intermediate 1-4 with (R)-quinuclidin-3-amine. The crude product was purified by PrepHPLC (Column: Phenomenex C18 75 x 30 mm x 3 pm, Mobile Phase A: water (NH3H2O ​​+ NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 30% B to 60%) to obtain compound 20. LC-MS (ESI+): m / z: 399.1 (M+H)+, 1H NMR (400 MHz, DMSO-de) δ = 7.07 (s, 1 H), 7.01 (s, 1 H), 4.02 3.91 (m, 1 H), 3.41 - 3.37 (m, 2 H), 3.19 - 3.10 (m, 1 H), 2.90 - 2.79 (m, H), 2.74 - 2.65 (m, 3 H), 2.62 - 2.54 (m, 1 H), 2.29 (s, 3 H), 2.03 1.97 (m, 1 H), 1.87 - 1.77 (m, 1 H), 1.65 - 1.54 (m, 2 H), 1.39 - 1.29 (m, H). Example 25

[0192] To a solution of 1-(2,4-dihydroxy-6-methylphenyl)ethan-1-one (2.40 g, 14.44 mmol) and K2CO3 (3.00 g, 21.71 mmol) in DMF (12.0 mL) and H2O (5.0 mL) at 90°C was added a solution of sodium 2-chloro-2,2-difluoroacetate (2.20 g, 14.44 mmol) in DMF (8.0 mL) at 90°C under N2. The resulting mixture was stirred at 90°C for 4 hours. After cooling to room temperature, the mixture was tempered with H2O (60 mL) and diluted with ethyl acetate (60 mL). Then, the mixture was acidified with aqueous citric acid solution (20 mL), and the aqueous phase was extracted with ethyl acetate (50 mL x 3). Organic extracts Petition 870250084579, dated 09 / 19 / 2025, p. 101 / 201 95 / 168 combined samples were dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to provide the crude product. The crude product was purified by flash column chromatography on silica gel eluted with 0 to 20% ethyl acetate in petroleum ether, to produce intermediate 21-1 (370.0 mg, 11.9% yield) as a colorless oil.

[0193] To a solution of intermediate 21-1 (370.0 mg, 1.71 mmol) in DCM (6.0 mL), TBSCl (567.4 mg, 3.76 mmol), DMAP (33.5 mg, 0.27 mmol) and TEA (0.71 mL, 5.13 mmol) were added at 20°C, and the mixture was stirred at 20°C for 1.5 hours. H2O (30 mL) was added, and the mixture was extracted with DCM (30 mL x 3). The combined organic extracts were dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to provide a crude product. The crude product was purified by flash column chromatography on silica gel eluted with 0 to 20% ethyl acetate in petroleum ether to give intermediate 21-2 (520.0 mg, 98.68% purity, 90.7% yield) as a colorless oil. LC-MS (ESI+): m / z 331.2 (M+H)+.

[0194] A solution of intermediate 21-2 (520.0 mg, 1.57 mmol) in DCE (3.0 mL) was added to a mixture of CuBr2 (632.7 mg, 2.83 mmol) in ethyl acetate (6.0 mL) at 80°C, and the mixture was stirred at 80°C for 1 hour. After cooling to room temperature, the mixture was concentrated under reduced pressure to provide a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 10% ethyl acetate in petroleum ether to yield intermediate 21-3 (270.0 mg, 90.7% purity, 38.1% yield) as a colorless oil. LC-MS (ESI+): m / z 409.1 (M+H)+.

[0195] To a solution of intermediate 21-3 (170.0 mg, 0.42 mmol) and intermediate 1-7 (93.4 mg, 0.42 mmol) in EtOH (2.0 mL), concentrated HCl (51.9 μL, 0.62 mmol) at 30°C was added, and the mixture Petition 870250084579, dated 09 / 19 / 2025, page 102 / 201 96 / 168 was stirred at 80°C for 1 hour. After cooling to room temperature, the mixture was adjusted to pH = 13 with NHa^O (0.3 mL), and the volatiles were removed under vacuum to produce a residue. The residue was purified by Prep-HPLC (column: Welch Xtimate C18 150 x 25 mm x 5 µm, mobile phase A: water (NH4HCO3 10 mM), mobile phase B: acetonitrile, flow rate: 25 mL / min, gradient from 30% B to 60%) and lyophilized to produce compound 21. LC-MS (ESI+): m / z: 385.2 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ = 10.28 (br, s, 1 H), 7.19 (t, J = 74.4 Hz, 1 H), 6.94 - 6.72 (m, 1 H), 6.55 - 6.50 (m, 2 H), 4.03 - 3.84 (m, 1 H), 3.39 - 3.37 (m, 2 H), 2.96 - 2.86 (m, 1 H), 2.64 - 2.56 (m, 1 H), 2.22 (s, 3 H), 2.16 (s, 3 H), 1.90 - 1.71 (m, 3 H), 1.69 - 1.61 (m, 1 H), 1.53 1.45 (m, 1 H), 1.25 - 1.22 (m, 1 H). Example 26 Compound 22

[0196] Similar to the procedure for Compound 12, the Compound 22 was synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-3-amine. The crude product was purified by Prep-HPLC (column: Welch Xtimate C18 150*30 mm*5 µm, mobile phase: water(FA)-ACN, flow rate: 25 mL / min, gradient condition from 23% B to 53%) and preparative SFC (column: DAICEL CHIRALPAK AD (250 mm*30 mm, 10 µm), mobile phase: CO2-EtOH (0.1% NH3H2O), flow rate: 80 mL / min, gradient condition from 45% B to 45%) to yield compound 22. LC-MS (ESI+): m / z 356.0 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ = 12.32 (br, s, 1 H), 11.21 (br, s, 1 H), 7.62 - 7.53 (m, 1 H), 7.03 (s, 1 H), 6.99 (s, 1 H), 6.12 - 5.71 (m, 1 Petition 870250084579, dated 09 / 19 / 2025, p. 103 / 201 97 / 168 H), 3.55 - 3.47 (m, 2 H), 2.30 (s, 3 H). Example 27 OBz OBz 23-1 23-2 23-3 Compound 23

[0197] To a solution of 1-(2-hydroxy-4-methoxy-6-methylphenyl)ethanone (1.00 g, 5.55 mmol) and DMAP (135.6 mg, 1.11 mmol) in DCM (30.0 mL), TEA (0.77 mL, 5.55 mmol) was added at 25°C. Then, benzoyl chloride (0.97 mL, 8.32 mmol) was added to the mixture dropwise at 0°C. The resulting mixture was stirred at 25°C for 1 hour. The mixture was diluted with water (20 mL), and the aqueous phase was extracted with dichloromethane (20 mL x 3). The combined organic layers were dried over anhydrous Na2SO2, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether, to produce intermediate 23-1 (1.50 g, 95.1% yield) as a colorless oil.

[0198] To a solution of intermediate 23-1 (500.0 mg, 1.76 mmol) in DCE (5.0 mL) and EA (5.0 mL), CuBr2 (706.9 mg, 3.16 mmol) was added at 20°C, and the resulting mixture was stirred at 80°C for 3 hours. After cooling to room temperature, the volatiles were removed under vacuum, resulting in a residue. The residue was purified by flash column chromatography on silica gel eluted with 0 to 50% dichloromethane in petroleum ether, to yield intermediate 23-2 (500.0 mg, 78.2% yield) as a colorless oil.

[0199] To a solution of intermediate 1-7 (154.7 mg, 0.69 mmol) Petition 870250084579, dated 09 / 19 / 2025, page 104 / 201 98 / 168 and acetic acid (0.08 mL, 1.40 mmol) in EtOH (4.0 mL), intermediate 23-2 (250.0 mg, 0.69 mmol) was added at 20°C. The resulting mixture was then heated to 60°C and stirred for 2 hours. After cooling to room temperature, the mixture was adjusted to pH = 13 with NH3^H2O (0.3 mL) and concentrated under reduced pressure to produce a residue. The residue was purified by Prep-HPLC (column: Welch Xtimate C18 150 x 25 mm x 5 µm, mobile phase A: water (NH3H2O ​​+ NH4HCO3), mobile phase B: acetonitrile, flow rate: 25 mL / min, gradient from 30% to 60% B) and lyophilized to produce intermediate 23-3 (50.0 mg, 94.9% purity, 15.2% yield) as a yellow solid. LC-MS (ESI+): m / z: 453.4 (M+H)+.

[0200] To a solution of intermediate 23-3 (45.0 mg, 0.10 mmol) in MeOH (2.0 mL), K2CO3 (41.2 mg, 0.30 mmol) was added at 20°C, and the mixture was heated to 50°C and stirred for 1 hour. After cooling to room temperature, the volatiles were removed under vacuum to produce a residue. The residue was purified by PrepHPLC (column: Welch Xtimate C18 150 x 25 mm x 5 µm, mobile phase A: water (NH3H2O ​​+ NH4HCO3), mobile phase B: acetonitrile, flow rate: 25 mL / min, gradient from 18% to 48% B) to produce compound 23. LC-MS (ESI+): m / z: 349.1 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ = 10.13 (br, s, 1 H), 6.31 - 6.27 (m, 2 H), 3.98 - 3.87 (m, 1 H), 3.70 (s, 3 H), 3.40 - 3.36 (m, 2 H), 2.96 2.87 (m, 1 H), 2.64 - 2.57 (m, 1 H), 2.21 (s, 3 H), 2.17 (s, 3 H), 1.92 1.73 (m, 3 H), 1.70 - 1.62 (m, 1 H), 1.55 - 1.43 (m, 1 H), 1.28 - 1.15 (m, 1 H). Example 28 Compound 24

[0201] Similar to the procedure for the Compound Petition 870250084579, dated 09 / 19 / 2025, p. 105 / 201 99 / 168 12, Compound 24 was synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with (1s,3s)-3-aminocyclobutan-1-ol. The crude product was purified by Prep-HPLC (Column: Phenomenex C18 75*30 mm*3um, Mobile Phase: water (NH3H2O+NH4HCO3)-ACN, Flow rate: 25 mL / min, gradient from 27% B to 57%) to obtain compound 24. LC-MS (ESI+): m / z 360.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 10.38 (br, s, 1 H), 7.07 (s, 1 H), 7.00 (s, 1 H), 5.14 - 5.04 (m, 1 H), 3.94 - 3.76 (m, 2 H), 3.40 - 3.35 (m, 2 H), 2.63 - 2.53 (m, 2 H), 2.28 (s, 3 H), 1.89 - 1.76 (m, 2 H). Example 29 Compound 25

[0202] To a solution of intermediates 21-3 (160.0 mg, 0.39 mmol) and 10-5 (218.4 mg, 0.78 mmol) in EtOH (4.0 mL), HOAc (0.14 mL, 2.42 mmol) was added at 30°C, and the mixture was heated to 60°C and stirred for 4 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to produce a residue. The residue was adjusted to pH = 8 with saturated aqueous NaHCO3 solution and then extracted with ethyl acetate (20 mL x 3). The combined organic extracts were dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a crude product. The crude product was purified by flash column chromatography on silica gel eluted with 0 to 100% ethyl acetate in petroleum ether, to produce intermediate 25-1 (50.0 mg, 94.07% purity, 25.3% yield) as a yellow oil. LC-MS (ESI+): m / z 476.3 (M+H)+.

[0203] To a solution of intermediate 25-1 (35.0 mg, 0.074 mmol) in MeOH (2.0 mL) was added K2CO3 (30.5 mg, 0.22 mmol) at 20°C, Petition 870250084579, dated 09 / 19 / 2025, page 106 / 201 100 / 168 and the mixture was stirred at 35°C for 7 hours. Volatiles were removed under vacuum, resulting in a residue. The residue was purified by Prep-HPLC (Column: Phenomenex C18 75*30 mm*3um, Mobile Phase A: water (0.05% NH3H2O+NH4HCO3 10 mM), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient condition from 25% B to 55%) and lyophilized to produce compound 25. LC-MS (ESI+): m / z 372.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.33 (br.s., 1 H), 7.19 (t, J = 74.0 Hz, 1 H), 6.55 - 6.53 (m, 1 H), 6.53 - 6.50 (m, 1 H), 4.97 (s, 1 H), 3.99 - 3.86 (m, 1 H), 3.39 - 3.35 (m, 2 H), 2.35 - 2.27 (m, 2 H), 2.22 (s, 3 H), 2.05 - 1.96 (m, 2 H), 1.25 (s, 3 H). Example 30 Compound 26

[0204] Similar to the procedure for the Compound 12. Compound 26 was synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with (R)-2-((tert-butyldiphenylsilyl)oxy)propan-1-amine. In the last step, the reaction mixture was stirred at -78°C for 8 hours. The crude product was purified by Prep-HPLC (Column: Welch Xtimate C18 150*25mm*5um, Mobile Phase A: water (NH3^H2O+NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 37% B to 67%) and lyophilized to obtain compound 26. LC-MS (ESI+): m / z: 347.9 (M+H)+.

[0205] 1H NMR (400 MHz, DMSO-de) δ = 10.46 (br.s., 1 H), 7.1 0 - 7.04 (m, 1 H), 7.04 - 6.98 (m, 1 H), 4.92 - 4.81 (m, 1 H), 3.90 3.78 (m, 1 H), 3.39 - 3.36 (m, 2 H), 3.28 - 3.25 (m, 2 H), 2.29 (s, 3 H), 1.08 (d, J = 5.6 Hz, 3 H). Example 31 Petition 870250084579, dated 09 / 19 / 2025, p. 107 / 201 101 / 168 Compound 27

[0206] Similar to the procedure for the Compound 12, Compound 27 was synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with 3-aminopyrrolidin-2-one. The crude product was purified by Prep-HPLC (Column: Welch Xtimate C18) 150*25mm*5um, Mobile Phase A: water (NH3H2O+NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 38% B to 68%) to obtain compound 27. LC-MS (ESI+): m / z: 373.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 10.83 - 10.13 (m, 1 H), 7.86 (s, 1 H), 7.08 (s, 1 H), 7.02 (s, 1 H), 4.74 - 4.21 (m, 1 H), 3.48 - 3.42 (m, 2 H), 3.25 - 3.19 (m, 2 H), 2.47 - 2.38 (m, 1 H), 2.30 (s, 3 H), 2.01 - 1.88 (m, 1 H). Example 32

[0207] To a solution of 2-(2,6-dimethoxy-4-methylphenyl)ethan-1-ol (5.00 g, 25.48 mmol, prepared according to reference: JACS, 2004, 126, 11966-11983) in DCM (100 mL), BBr3 (5.40 mL, 56.07 mmol) was added dropwise at 0°C, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was tempered by the addition of MeOH (15 mL) at 0°C, and the volatiles were removed under vacuum, resulting in a residue. H2O (20 mL) was added, and the aqueous phase was extracted with DCM (20 mL x 3). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce intermediate 28-1 (5.0 g, crude). Petition 870250084579, dated 09 / 19 / 2025, page 108 / 201 102 / 168 like a brown oil.

[0208] To a solution of intermediate 28-1 (5.0 g, crude) in acetone (400 mL), K2CO3 (15.00 g, 108.54 mmol) was added, and the mixture was stirred at 70°C for 1 hour. The reaction mixture was concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 20% ethyl acetate in petroleum ether to produce intermediate 28-2 (2.74 g, 84% purity, 60.2% yield in 2 steps) as a white solid. LC-MS (ESI+): m / z: 151.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 9.25 (br.s, 1 H) 6.10 (s, 1 H) 6.05 (s, 1 H) 4.44 (t, J = 8.80 Hz, 2 H) 2.96 (t, J = 8.80 Hz, 2 H) 2.13 (s, 3 H).

[0209] To a solution of intermediate 28-2 (2.74 g, 18.24 mmol) in DCM (50.0 mL), acetic anhydride (5.64 mL, 60.20 mmol) and a solution of TiCl4 (13.00 mL, 118.58 mmol) in DCM (25.0 mL) at 0°C were added sequentially. The mixture was stirred at 0°C for 1 hour, and at 25°C for a further 5 hours. The mixture was tempered with H2O (20 mL) at 0°C, diluted with DCM (90 mL) and washed with H2O (30 mL x 2) and brine (30 mL), dried over anhydrous Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue. The residue was purified by flash column chromatography on silica gel eluted with 20% ethyl acetate in petroleum ether to produce intermediate 28-3 (2.22 g, yield of 63.3%) as a white solid. LC-MS (ESI+): m / z: 193.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.77 (br, s, 1 H) 6.21 (s, 1 H) 4.54 (t, J = 8.80 Hz, 2 H) 3.06 (t, J = 8.80 Hz, 2 H) 2.47 (s, 3 H) 2.22 (s, 3 H). Example 33 Petition 870250084579, dated 09 / 19 / 2025, p. 109 / 201 103 / 168 Compound 28

[0210] Similar to the procedure for the Compound 23, Compound 28 was synthesized by replacing 1-(2-hydroxy-4-methoxy-6-methylphenyl)ethan-1-one with intermediate 28-3. The crude product was purified by Prep-HPLC (column: Phenomenex C18 75 x 30 mm x 3 pm, mobile phase A: water (NH3H2O ​​+ NH4HCO3), mobile phase B: acetonitrile, flow rate: 20 mL / min, gradient from 40% B to 70%) and lyophilized to obtain compound 28. LC-MS (ESI+): m / z 361.2 (M+H)+. 1H NMR (400 MHz, CD3CN) δ = 6.26 (s, 1 H), 4.58 (t, J = 8.80 Hz, 2 H), 4.14 - 4.03 (m, 1 H), 3.55 (s, 2 H), 3.10 (t, J = 8.80 Hz, 2 H), 2.85 2.71 (m, 1 H), 2.52 - 2.41 (m, 1 H), 2.34 (s, 3 H), 2.22 (s, 3 H), 2.12 2.08 (m, 2 H), 1.83 -1.70 (m, 2 H), 1.62 - 1.53 (m, 1 H), 1.51 - 1.43 (m, 1 H). Example 34 Compound 29

[0211] Similar to the procedure for the Compound 12, Compound 29 was synthesized by replacing (1R,2R)-2-aminocyclopentan-1-ol with (1s,3s)-3-amino-1-(trifluoromethyl)cyclobutan-1-ol. The crude product was purified by Prep-HPLC (Column: C18 150x30 mm, Mobile Phase A: water (NH3H2O+NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 42% B to 72%) and lyophilized to obtain compound 29. LC-MS (ESI+): m / z 428.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 10.45 (br, s,, 1 H), 7.52 (br, s,, 1 Petition 870250084579, dated 09 / 19 / 2025, p. 110 / 201 104 / 168 H), 7.08 (s, 1 H), 7.00 (s, 1 H), 6.63 (s, 1 H), 4.21 - 4.00 (m, 1 H), 3.50 3.40 (m, 2 H), 2.85 - 2.73 (m, 2 H), 2.28 (s, 3 H), 2.27 - 2.21 (m, 2H). Example 35

[0212] Similar to the procedure for the Compound 25, Compound 30 was synthesized by replacing intermediate 21-1 with 1-(4-chloro-2-hydroxy-6-methylphenyl)ethan-1-one. The crude product was purified by Prep-HPLC (Column: Xtimate C18 150 x 40 mm x 10 µm, Mobile Phase A: water (FP), Mobile Phase B: acetonitrile, Flow rate: 30 mL / min, gradient from 12% B to 42%) and lyophilized to obtain compound 30. LC-MS (ESI+): m / z 340.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.67 (br, s, 1 H), 8.14 (s, 1H HCOOH), 6.79 (d, J = 1.6 Hz, 1 H), 6.76 (d, J = 1.6 Hz, 1 H), 4.96 (s, 1 H), 4.01 - 3.86 (m, 1 H), 3.39 - 3.35 (m, 2 H), 2.34 - 2.26 (m, 2 H), 2.20 (s, 3 H), 2.04 - 1.96 (m, 2 H), 1.24 (s, 3 H).

[0213] Example 36. Intermediate 37-4 was used to synthesize compound 37. Similarly, other intermediates (from example 37 to example 54) were used to synthesize the corresponding compounds. 37-1 37-2 37-3 37.4

[0214] A mixture of compound 37-1 (5.00 g, 19.16 mmol) in DMF (50.0 mL) was added to NaOMe (40 mL, 30% in MeOH) at 25°C, and the mixture was stirred at 50°C for 1 hour. 60 mL of cold H2O was added, and the mixture was extracted with ethyl acetate (50 mL x 3). The combined organic extracts were dried over Na2SO4, filtered Petition 870250084579, dated 09 / 19 / 2025, page 111 / 201 105 / 168 of the samples were placed on a celite pad, and the filtrate was concentrated under reduced pressure to provide the crude product. The crude product was purified by flash column chromatography on silica gel eluted with 0 to 10% ethyl acetate in petroleum ether, to produce intermediate 37-2 (1.30 g, 90.0% purity, 22.4% yield) as a white solid. LC-MS (ESI+): m / z: 274.0 (M+H)+. 1H NMR (400 MHz, CDCh) δ 7.16 (d, J = 1.2 Hz, 1 H), 6.83 (d, J = 1.2 Hz, 1 H), 3.93 (s, 3 H), 2.51 (s, 3 H).

[0215] To a mixture of intermediate 37-2 (200.0 mg, 0.73 mmol), CuI (14.0 mg, 0.074 mmol) and TEA (0.20 mL, 1.47 mmol) in dioxane (4.0 mL), tributyl(1-ethoxyvinyl)stanane (100.0 mg, 0.28 mmol) was added. Then, Pd(PPh3)2Cl2 (84.6 mg, 0.12 mmol) was added under N2, and the mixture was stirred at 100°C for 12 hours under N2. After cooling to room temperature, HCl (10 mL, 1 M) was added, and the mixture was stirred for 1 h. The reaction mixture was quenched with saturated aqueous KF solution (40 mL) and extracted with ethyl acetate (50 mL x 2). The combined organic extracts were washed with brine (50 mL), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to obtain the crude product.The crude product was purified by flash column chromatography on silica gel eluted with 0 to 10% ethyl acetate in petroleum ether, to produce intermediate 37-3 (90.0 mg, 86.5% purity, 56.2% yield) as a yellow oil. LC-MS (ESI+): m / z: 190.1 (M+H)+.

[0216] A solution of CuBr2 (191.2 mg, 0.86 mmol) in EtOAc (1.0 mL) was added dropwise to a mixture of intermediate 373 (90.0 mg, 0.48 mmol) in DCE (1.0 mL) at 80°C. After addition, the mixture was stirred at 80°C for 3 hours. The reaction mixture was concentrated under reduced pressure and purified by column chromatography. Petition 870250084579, dated 09 / 19 / 2025, page 112 / 201 106 / 168 flash in silica gel eluted with 0 to 10% ethyl acetate in petroleum ether, to produce intermediate 37-4 (80.0 mg, 75.0% purity, 46.6% yield) as a white solid. LC-MS (ESI+): m / z: 268.0 (M+H)+. Example 37 Hydrotribromide Pirrolidone F 41-4

[0217] A solution of compound 41-1 (5.00 g, 25.76 mmol) in THF (30 mL) was added to n-BuLi (10.3 mL, 25.76 mmol, 2.5 M in hexane) at -78°C under N2. After stirring at -78°C for 1 h, a solution of I2 (7.19 g, 28.34 mmol) in THF (25 mL) was added, and the mixture was stirred at -78°C for a further 2 h. Water (100 mL) was added to the reaction mixture and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with petroleum ether to yield intermediate 41-2 (4.00 g, 48.5% yield) as a yellow oil. 1H NMR (400 MHz, CDCh) δ = 7.03 - 6.97 (m, 1 H), 6.82 (s, 1 H), 3.97 (s, 3 H).

[0218] To a solution of intermediate 41-2 (3.50 g, 10.94 mmol) in toluene (25 mL), tributyl(1-ethoxyvinyl)estanane (5.53 g, 15.31 mmol) and Pd(PPh3)4 (253.0 mg, 0.22 mmol) were added. The reaction was stirred at 110°C for 16 h under N2. To the cooled reaction mixture, 6 N HCl (15 mL) was added and stirred at room temperature for 2 h. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (40 mL x 2). The combined organic layers were washed with brine (40 mL x 3), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under pressure. Petition 870250084579, dated 09 / 19 / 2025, p. 113 / 201 107 / 168 reduced to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 8%) in petroleum ether, to produce intermediate 41-3 (2.50 g, 96.8% yield) as a yellow oil. 1H NMR (400 MHz, CDCh) δ = 7.05 - 6.96 (m, 1 H), 6.96 (s, 1 H), 3.91 (s, 3 H), 2.55 (s, 3 H).

[0219] To a solution of intermediate 41-3 (2.50 g, 10.59 mmol) in THF (15 mL), pyrrolidone hydrotribromide (4.13 g, 12.70 mmol) was added. The reaction was stirred at 40°C for 3 h. The reaction mixture was added with water (10 mL) and extracted with EtOAc (15 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by silica gel column chromatography eluted with 0-7% ethyl acetate in petroleum ether to produce intermediate 41-4 (2.40 g, 72.0% yield) as yellow oil. 1H NMR (400 MHz, CDCh) δ = 7.12 - 7.02 (m, 2 H), 4.34 (s, 2 H), 3.95 (s, 3 H). Example 38

[0220] A solution of compound 42-1 (1.60 g, 5.30 mmol) in DMF (10 mL), sodium chlorodifluoroacetate (2.00 g, 13.11 mmol) and Cs2CO3 (3.50 g, 10.74 mmol) were added. The reaction was stirred at 100°C for 2 h. Water (20 mL) was added to the cooled reaction mixture, and the mixture was extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified. Petition 870250084579, dated 09 / 19 / 2025, p. 114 / 201 108 / 168 fixed by column chromatography on silica gel eluted with petroleum ether to produce intermediate 42-2 (0.80 g, 42.9% yield) as a colorless oil. 1H NMR (400 MHz, CDCh) δ = 7.37 (s, 1 H), 7.19 (s, 1 H), 6.57 (t, J = 72.8 Hz, 1 H), 2.57 (s, 3 H). Example 39 tert-butyl nitrite BBr3 BzCI 44-3 BΒζχb 44-4

[0221] To a solution of 4-amino-3-methoxy-5-methylbenzene-1-carbonitrile (3.50 g, 21.58 mmol) in ACN (50 mL), CuI (6.16 g, 32.37 mmol) and tert-butyl nitrite (4.45 g, 43.16 mmol) were added. The reaction was stirred at room temperature for 16 h. The mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 8% ethyl acetate in petroleum ether, to produce intermediate 44-1 (4.10 g, 69.6% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 7.15 (d, J = 1.2 Hz, 1 H), 6.82 (d, J = 1.2 Hz, 1 H), 3.91 (s, 3 H), 2.50 (s, 3 H).

[0222] To a solution of intermediate 44-1 (2.50 g, 9.15 mmol) in DCM (80 mL), tribromoborane (45.8 mL, 45.80 mmol, 1 M in DCM) was added at 0°C. The mixture was stirred at 50°C for 32 h. The mixture was quenched with MeOH at 0°C, dropwise, and then concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 8% ethyl acetate in petroleum ether, to produce intermediate 44-2 (1.10 g, 46.4% yield) as a white solid. Petition 870250084579, dated 09 / 19 / 2025, p. 115 / 201 109 / 168 1H NMR (400 MHz, CDCh) δ = 7.08 - 7.06 (m, 2 H), 5.83 (s, 1 H), 2.49 (s, 3 H).

[0223] To a solution of intermediate 44-2 (1.10 g, 4.25 mmol) and TEA (0.43 g, 4.25 mmol) in DCM (10 mL) were added, along with 4(dimethylamino)pyridine (0.095 g, 0.85 mmol) and benzoyl chloride (0.90 g, 6.37 mmol). The reaction was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 8% ethyl acetate in petroleum ether to yield intermediate 44-3 (1.50 g, 97.2% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 8.28 - 8.26 (m, 2 H), 7.72 - 7.68 (m, 1 H), 7.66 - 7.56 (m, 2 H), 7.42 (d, J = 1.2 Hz, 1 H), 7.33 (d, J = 1.2 Hz, 1 H), 2.57 (s, 3 H).

[0224] To a solution of intermediate 44-3 (1.50 g, 4.13 mmol) in toluene (15 mL), tributyl(1-ethoxyvinyl)stanane (2.09 g, 5.78 mmol) and Pd(PPh3)4 (0.1 g, 0.087 mmol) were added. The reaction was stirred at 120°C for 16 h under an Ar atmosphere. To the cooled reaction mixture, 1 M HCl (10 mL) was added, and the reaction was stirred at room temperature for a further 4 h. Water (40 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (40 mL x 2). The combined organic layers were washed with brine (80 mL), dried over Na2SO2, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 8% ethyl acetate in petroleum ether, to produce intermediate 44-4 (897.0 mg, 77.7% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ = 8.06 - 8.04 (m, 2 H), 7.65 - 7.57 (m, 1 H), 7.48 - 7.37 (m, 4 H), 2.40 (s, 3 H), 2.29 (s, 3 H). Example 40 Petition 870250084579, dated 09 / 19 / 2025, page 116 / 201 110 / 168 LDA DMF Sn(n-Bu)3 Pyrrolidone Hydrotribromide C1J2O 46-4 46-5

[0225] To a solution of 5-fluoro-2-iodo-1-methoxy-3-methylbenzene (3.90 g, 14.66 mmol) in THF (30 mL), lithium diisopropylamide (8.8 mL, 17.59 mmol, 2 M in THF) was added dropwise at -78°C under a N2 atmosphere. After stirring at -78°C for 1 h, dry DMF (1.6 mL, 20.52 mmol) was added dropwise to the mixture, and the reaction mixture was stirred at -78°C for 45 minutes. The reaction was abruptly stopped with HCl (30 mL, 1 M) at 20°C. The mixture was extracted with EtOAc (40 mL x 2). The combined organic layers were washed with brine (40 mL x 2), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-9% ethyl acetate in petroleum ether to produce intermediate 46-1 (3.10 g, 71.9% yield) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 10.27 (s, 1 H), 6.95 (d, J = 10.8 Hz, 1 H), 3.91 (s, 3 H), 2.53 (s, 3 H).

[0226] To a solution of intermediate 46-1 (3.36 g, 11.43 mmol) in DMF (20 mL), methyl 2-mercaptoacetate (1.82 g, 17.14 mmol) and K2CO3 (4.74 g, 34.27 mmol) were added. The mixture was stirred at 80°C for 1 h. To the cooled reaction mixture, water (20 mL) was added, and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL x 2), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 9% of Petition 870250084579, dated 09 / 19 / 2025, p. 117 / 201 111 / 168 ethyl acetate in petroleum ether, to produce intermediate 46-2 (2.20 g, 53.1% yield) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 8.11 (s, 1 H), 7.53 (s, 1 H), 4.00 (s, 3 H), 3.95 (s, 3 H), 2.60 (s, 3 H).

[0227] Lithium hydroxide (0.73 g, 30.37 mmol) was added to a solution of intermediate 46-2 (2.20 g, 6.07 mmol) in THF / H2O (15 mL / 5 mL). The reaction was stirred at room temperature for 16 h. Water (10 mL) was added to the reaction mixture, and the pH was adjusted to 4 by adding 4N HCl (10 mL). The mixture was extracted with EtOAc (40 mL x 2). The combined organic layers were washed with brine (40 mL x 2), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce intermediate 46-3 (2.00 g, 94.6% yield) as a yellow solid, which was used directly in the next step. LC-MS(ESI-): m / z 346.9 (MH)-.

[0228] A solution of intermediate 46-3 (1.00 g, 2.87 mmol) in DMF (10 mL) was added to CU2O (1.64 g, 11.49 mmol). The reaction was stirred at 140°C for 16 h under N2. After cooling to room temperature, the mixture was filtered through a celite pad, the filtrate was added to water (15 mL), and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-5% ethyl acetate in petroleum ether, to produce intermediate 46-4 (0.60 g, 68.7% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ = 7.77 (s, 1 H), 7.72 (d, J = 5.2 Hz, 1 H), 7.48 - 7.46 (m, 1 H), 3.89 (s, 3 H), 2.52 (s, 3 H).

[0229] To a solution of intermediate 46-4 (400.0 mg, 1.32 mmol) Petition 870250084579, dated 09 / 19 / 2025, page 118 / 201 To 112 / 168 toluene (10 mL), tributyl(1-ethoxyvinyl)estanane (665.0 mg, 1.84 mmol) and Pd(PPh3)4 (30.0 mg, 0.026 mmol) were added. The reaction was stirred at 120°C for 16 h under a N2 atmosphere. After cooling to room temperature, 6 N HCl (10 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 h. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (20 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 10% ethyl acetate in petroleum ether, to produce intermediate 46-5 (280.0 mg, 96.2% yield) as a yellow oil. 1H NMR (400 MHz, CDCh) δ = 7.46 (s, 1 H), 7.42 - 7.37 (m, 2 H), 3.95 (s, 3 H), 2.58 (s, 3 H), 2.36 (s, 3 H).

[0230] To a solution of intermediate 46-5 (380.0 mg, 1.73 mmol) in THF (10 mL), pyrrolidone hydrotribromide (1121.0 mg, 3.45 mmol) was added. The reaction was stirred at 40°C for 4 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 5% ethyl acetate in petroleum ether, to produce intermediate 46-6 (210.0 mg, 40.5% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-de) δ = 7.78 (d, J = 5.6 Hz, 1 H), 7.69 (s, 1 H), 7.59 - 7.58 (m, 1 H), 4.71 (s, 2 H), 3.97 (s, 3 H), 2.29 (s, 3 H). Example 41 Petition 870250084579, dated 09 / 19 / 2025, p. 119 / 201 113 / 168 Tert-butyl nitrite, Cul ------------------------ F3c 48-4 48-5 48-6

[0231] A solution of compound 48-1 (3.80 g, 19.68 mmol) in A solution of NBS (3.87 g, 21.76 mmol) in ACN (30 mL) at 0°C was added to ACN (40 mL). The mixture was stirred at room temperature for 2 h. Water (80 mL) was added to the mixture, and the mixture was extracted with EtOAc (80 mL x 2). The combined organic layers were washed with brine (80 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 5% ethyl acetate in petroleum ether, to produce intermediate 48-2 (4.30 g, 80.3% yield) as a yellow oil. 1H NMR (400 MHz, CDCh) δ = 7.19 (d, J = 7.6 Hz, 1 H), 4.51 (br.s, 2 H), 2.20 (s, 3 H).

[0232] To a solution of intermediate 48-2 (4.30 g, 15.81 mmol) in dioxane (80 mL), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolan (8.03 g, 31.62 mmol), Pd(dppf)CLCH2Cl2 (1.28 g, 1.58 mmol) and KOAc (3.88 g, 39.52 mmol) were added. The mixture was stirred at 100°C for 16 h under a N2 atmosphere. Water (80 mL) was added to the cooled mixture, and the mixture was extracted with EtOAc (80 mL x 2). The combined organic layers were washed with brine (80 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with Petition 870250084579, dated 09 / 19 / 2025, pp. 120 / 201 114 / 168 at 5% ethyl acetate in petroleum ether, to produce intermediate 48-3 (4.20 g, crude) as a yellow oil. 1H NMR (400 MHz, CDCh) δ = 7.26 - 7.15 (m, 1 H), 4.60 - 4.47 (m, 2 H), 2.09 (s, 3 H), 1.37 (s, 12 H).

[0233] To a solution of intermediate 48-3 (4.20 g, crude) in THF (50 mL), NaOH (1.58 g, 39.49 mmol, 2N) and H2O2 (8.95 g, 78.97 mmol, 30% in H2O) were slowly added at 0 °C. The mixture was stirred at room temperature for 2 h. Water (50 mL) was added to the mixture, and the mixture was extracted with EtOAc (60 mL x 2). The combined organic layers were washed with brine (60 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 5% ethyl acetate in petroleum ether, to produce intermediate 48-4 (0.85 g, 25.7% yield in two steps) as a yellow oil. LC-MS (ESI+): m / z 210.1 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 6.85 (d, J = 7.6 Hz, 1 H), 5.18 (sb, 1 H), 4.07 (sb, 2 H), 2.15 (s, 3 H).

[0234] A mixture of intermediate 48-4 (0.85 g, 4.06 mmol) and K2CO3 (843.0 mg, 6.10 mmol) in DMF (12 mL) was stirred at 0 °C for 0.5 h. CH3I (634.0 mg, 4.47 mmol) was slowly added to the mixture, and the mixture was stirred at 0 °C for 1.5 h. Water (50 mL) was added to the mixture and extracted with EtOAc (60 mL x 2). The combined organic layers were washed with brine (50 mL x 2), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-5% ethyl acetate in petroleum ether, to produce intermediate 48-5 (0.50 g, 55.2% yield) as a yellow oil. LC-MS (ESI+): m / z 224.1 (M+H)+. Petition 870250084579, dated 09 / 19 / 2025, p. 121 / 201 115 / 168 1H NMR (400 MHz, CDCl3) δ = 6.96 (d, J = 7.2 Hz, 1 H), 4.16 (br.s, 2 H), 3.94 (d, J = 1.6 Hz, 3 H), 2.13 (s, 3 H).

[0235] To a solution of intermediate 48-5 (400.0 mg, 1.79 mmol) in ACN (12 mL), tert-butyl nitrite (369.2 mg, 3.58 mmol) and CuI (512.0 mg, 2.69 mmol) were added. The reaction was stirred at 60 °C for 4 h. After cooling to room temperature, the mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with petroleum ether, resulting in intermediate 48-6 (400.0 mg, 67.0% yield) as a colorless oil. 1H NMR (400 MHz, CDCh) δ = 7.27 - 7.16 (m, 1 H), 3.97 (d, J = 1.6 Hz, 3 H), 2.48 (s, 3 H). Example 42 THE I Λ λ ' Λ—λ P pyrrolidone hydrotribromide [ \—λO O--# y—Br O--# __A ,;ΆA \ ^Br 49-149-2

[0236] To a solution of 5-bromo-6-methyl-2,3-dihydrobenzofuran (130.0 mg, 0.61 mmol) in toluene (4 mL), tributyl(1-ethoxyvinyl)-stanane (308.0 mg, 0.85 mmol) and Pd(PPh3)4 (13.0 mg, 0.011 mmol) were added. The reaction was stirred at 120°C for 16 h under a N2 atmosphere. After cooling to room temperature, 6 N HCl (3 mL, 18.00 mmol) was added to the reaction mixture. The mixture was stirred at room temperature for 2 h. Water (10 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-5% ethyl acetate in petroleum ether, to produce intermediate 49-1 (80.0 mg, 74.4% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 7.64 (s, 1 H), 6.64 (s, 1 H), 4.63 (t, J Petition 870250084579, dated 09 / 19 / 2025, p. 122 / 201 116 / 168 = 8.4 Hz, 2 H), 3.22 (t, J = 8.4 Hz, 2 H), 2.54 (s, 3 H), 2.53 (s, 3 H).

[0237] To a solution of intermediate 49-1 (80.0 mg, 0.45 mmol) in THF (4 mL), pyrrolidone hydrotribromide (146.7 mg, 0.45 mmol) was added. The reaction was stirred at 40°C for 4 h. To the cooled reaction mixture, water (10 mL) was added, and the mixture was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na2SO2, filtered, and the filtrate was concentrated under reduced pressure to yield intermediate 49-2 (110.0 mg, 95.6%) as a yellow oil, which was used in the next step without further processing. 1H NMR (400 MHz, CDCh) δ = 7.63 (s, 1 H), 6.69 (s, 1 H), 4.66 (t, J = 8.8 Hz, 2 H), 4.37 (s, 2 H), 3.24 (t, J = 8.4 Hz, 2 H), 2.53 (s, 3 H). Example 43

[0238] To a solution of 6-methyl-2,3-dihydro-1H-inden-4-ol (2.40 g, 16.19 mmol) in DCM (50 mL), acetic anhydride (5.46 g, 53.44 mmol) and TiCk (19.66 g, 103.64 mmol) in DCM (30 mL) at 0°C were added. The reaction was stirred at 0°C for 1 h, then stirred at room temperature for 2 h. The mixture was tempered with water (15 mL) at 0°C, and the mixture was extracted with DCM (60 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 3% ethyl acetate in petroleum ether to produce intermediate 50-1 (2.3 g, crude) as a yellow oil, which was used directly in the next step. LC-MS (ESI+): m / z 191.2 (M+H)+.

[0239] A mixture of intermediate 50-1 (2.30 g, raw) and K2CO3 Petition 870250084579, dated 09 / 19 / 2025, page 123 / 201 117 / 168 (2.51 g, 18.14 mmol) in DMF (30 mL), CH3I (2.23 g, 15.72 mmol) was added. The mixture was stirred at room temperature for 1.5 h. Water (30 mL) was added to the mixture, and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (40 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by silica gel column chromatography eluted with 0-3% ethyl acetate in petroleum ether to produce intermediate 50-2 (1.00 g, 30.2% yield in 2 steps) as a yellow solid. LC-MS (ESI+): m / z 205.2 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 6.82 (s, 1 H), 3.79 (s, 3 H), 2.95 (t, J = 7.2 Hz, 2 H), 2.86 (t, J = 7.2 Hz, 2 H), 2.49 (s, 3 H), 2.22 (s, 3 H), 2.13 - 2.06 (m, 2 H). Example 44 Br I Methylboronic acid

[0240] To a solution of 5-bromo-2-iodo-4-(trifluoromethyl)aniline (22.20 g, 60.67 mmol) in DMF (200 mL), methylboronic acid (3.83 g, 63.95 mmol), Pd(OAc)2 (0.34 g, 1.52 mmol), RuPhos2 (1.41 g, 3.03 mmol) and K2CO2 (50.3 g, 364.03 mmol) were added. The mixture was degassed with nitrogen for 2 min, heated to 110°C and stirred for 16 h. To the cooled reaction mixture, water (200 mL) was added, and the mixture was extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-20% ethyl acetate in petroleum ether to produce intermediate 53-1 (6.00 g, 52.3% yield) as a light yellow oil. LC-MS (ESI+): m / z 190.1 (M+H)+. Petition 870250084579, dated 09 / 19 / 2025, page 124 / 201 118 / 168 Example 45 55-1

[0241] To a solution of tert-butyl-(R)-3-(methylamino)piperidine-1-carboxylate (2.00 g, 9.33 mmol) in EtOH (20 mL), methyl hydrazinecarbodithioate (0.57 g, 4.67 mmol) was added. The reaction was stirred at 90°C for 16 h. After cooling to room temperature, the mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 5% MeOH in DCM, to produce intermediate 55-1 (650.0 mg, 24.1% yield) as a yellow oil. LC-MS (ESI+): m / z 289.2 (M+H)+.

[0242] To a solution of 5-bromo-2-iodo-1-methoxy-3-methylbenzene (2.90 g, 8.87 mmol) in toluene (50 mL), tributyl(1-ethoxyvinyl)stanane (3.52 g, 9.76 mmol) and Pd(PPh3)4 (0.21 g, 0.18 mmol) were added under N2. The reaction was stirred at 120°C for 16 h under N2. To the cooled reaction mixture, HCl (68.0 mL, 6 mol / L) was added, and the mixture was stirred at room temperature for 2 h. Water (30 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by chromatography. Petition 870250084579, dated 09 / 19 / 2025, p. 125 / 201 119 / 168 of a silica gel column eluted with 0-3% ethyl acetate in petroleum ether, to produce intermediate 56-1 (1.18 g, yield of 54.7%) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 6.98 (s, 1 H), 6.90 (s, 1 H), 3.82 (s, 3 H), 2.46 (s, 3 H), 2.21 (s, 3 H).

[0243] A solution of intermediate 56-1 (1.20 g, 4.94 mmol) and but-2-inoic acid (623.0 mg, 7.41 mmol) in DMSO (15 mL), DBU (1.50 g, 9.87 mmol), 1,4-bis(diphenylphosphine)butane (42.2 mg, 0.099 mmol) and PdCl2(PPh3)2 (35.8 mg, 0.049 mmol) under N2. The mixture was stirred at 100°C for 4 h. Water (60 mL) was added to the cooled mixture, and the mixture was extracted with EtOAc (60 mL x 2). The combined organic layers were washed with brine (60 mL x 2), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-3% ethyl acetate in petroleum ether, to produce intermediate 56-2 (850.0 mg, 85.1% yield) as a yellow solid. LC-MS (ESI+): m / z 203.2 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 6.85 (s, 1 H), 6.77 (s, 1 H), 3.80 (s, 3 H), 2.46 (s, 3 H), 2.19 (s, 3 H), 2.05 (s, 3 H).

[0244] To a solution of intermediate 56-2 (850.0 mg, 4.20 mmol) in EA / DCE (5 mL / 5 mL), CuBr2 (1314.0 mg, 5.88 mmol) was added. The reaction was stirred at 80°C for 16 h. The reaction was filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0 to 3% ethyl acetate in petroleum ether, to produce intermediate 56-3 (550.0 mg, 46.7% yield) as a yellow solid. LC-MS (ESI+): m / z 281.0 (M+H)+. Example 47 Petition 870250084579, dated 09 / 19 / 2025, page 126 / 201 120 / 168 / o Selectfluor / q— 57-1

[0245] To a solution of 1,3-dimethoxy-2-(2-methoxyethyl)-5-methylbenzene (2.60 g, 12.36 mmol) in MeCN (60 mL), Selectfluor (3.94 g, 11.13 mmol) was added at 0°C. The mixture was stirred at 0°C for 2 h. Water (50 mL) was added to the mixture, which was extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na2SO2, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with petroleum ether, resulting in intermediate 57-1 (1.70 g, 60% yield) as a light yellow oil. LC-MS (ESI+): m / z 229.1 (M+1)+. Example 48 57-2

[0246] Similar to the procedure for intermediate 28-3, intermediate 57-2 was synthesized by replacing 2-(2,6-dimethoxy-4-methylphenyl)ethan-1-ol with intermediate 57-1.

[0247] To a solution of intermediate 57-2 (500.0 mg, 2.38 mmol) in DMF (10 mL), K2CO3 (657.8 mg, 4.76 mmol) and iodomethane (675.0 mg, 4.76 mmol) were added. The mixture was stirred at room temperature for 16 h. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (40 mL x 2). The combined organic layers were washed with brine (80 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by colorimetric chromatography. Petition 870250084579, dated 09 / 19 / 2025, page 127 / 201 121 / 168 in silica gel eluted with 0-6% ethyl acetate in petroleum ether to produce intermediate 57-3 (510.0 mg, 95.4%) as a white solid. LC-MS (ESI+): m / z 225.1 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 4.69 (t, J = 8.8 Hz, 2 H), 3.80 (s, 3 H), 3.34 (t, J = 8.8 Hz, 2 H), 2.47 (s, 3 H), 2.13 (d, J = 2.4 Hz, 3 H).

[0248] To a solution of intermediate 57-3 (450.0 mg, 2.00 mmol) in DCE / EA (10 mL / 10 mL), CuBr2 (583.0 mg, 2.61 mmol) was added. The reaction was stirred at 80°C for 16 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by preparative TLC (PE / EtOAc = 5 / 1) to produce intermediate 57-4 (430.0 mg, 71.0% yield) as a white solid. LC-MS (ESI+): m / z 303.0 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 4.72 (t, J = 8.8 Hz, 2 H), 4.32 (s, 2 H), 3.84(s, 3 H), 3.38 (t, J = 8.4 Hz, 2 H), 2.17 (t, J = 2.4 Hz, 3 H). Example 49 58-1 NIS 58-2 Honey

[0249] Similar to the procedure for the intermediary 28-3, intermediate 58-1 was synthesized by replacing 1,3-dimethoxy-5-methylbenzene with 1,3-dimethoxy-5-(trifluoromethyl)benzene.

[0250] To a solution of intermediate 58-1 (2.80 g, 13.72 mmol) in toluene (30 mL), NIS (2.46 g, 10.97 mmol) was added at 0°C. The reaction was stirred at room temperature for 16 h. Water (40 mL) was added to the reaction mixture and extracted with EtOAc (40 mL x 3). The combined organic layers were washed with saturated aqueous Na2S2O3 solution (40 mL x 2), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce the intermediate. Petition 870250084579, dated 09 / 19 / 2025, p. 128 / 201 122 / 168 medium 58-2 (4.20 g, raw) as a yellow oil, which was used directly in the next step. LC-MS (ESI-): m / z 328.9 (MH)-

[0251] To a solution of intermediate 58-2 (4.20 g, crude) in DMF (30 mL), iodomethane (2.17 g, 15.27 mmol) and potassium carbonate (2.64 g, 19.09 mmol) were added. The reaction was stirred at room temperature for 2 h. Water (40 mL) was added to the reaction mixture and extracted with EtOAc (40 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 10%) in petroleum ether to produce intermediate 58-3 (1.90 g, 40.2% yield in 2 steps) as a white solid. 1H NMR (400 MHz, CDCh) δ= 6.92 (s, 1 H), 4.66 (t, J = 8.4 Hz, 2 H), 3.89 (s, 3 H), 3.38 (t, J = 8.8 Hz, 2 H). Example 50 59-1 59-2 59-3

[0252] Tributyl(1-ethoxyvinyl)stanane (3356.0 mg, 9.29 mmol) and Pd(PPh3)4 (107.0 mg, 0.093 mmol) were added to a solution of compound 59-1 (990.0 mg, 4.65 mmol) in toluene (10 mL). The reaction was stirred at 120°C for 16 h under an Ar atmosphere. HCl (10 mL) was added to the cooled reaction, and the mixture was stirred at room temperature for 2 h. Water (30 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography. Petition 870250084579, dated 09 / 19 / 2025, page 129 / 201 123 / 168 in silica gel eluted with ethyl acetate (0% to 7%) in petroleum ether to produce intermediate 59-2 (500.0 mg, 61.0% yield) as a yellow oil. 1H NMR (400 MHz, CDCh) δ = 12.20 (s, 1 H), 6.53 (s, 1 H), 3.26 3.13 (m, 2 H), 3.12 - 3.02 (m, 2 H), 2.63 (s, 3 H), 2.57 (s, 3 H).

[0253] To a solution of intermediate 59-2 (528.0 mg, 3.00 mmol) in DMF (8 mL), iodomethane (851 mg, 5.99 mmol) and K2CO3 (1.24 g, 8.99 mmol) were added. The mixture was stirred at room temperature for 1 h. Water (20 mL) was added to the reaction mixture, and the mixture was extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (40 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 7%) in petroleum ether to produce intermediate 59-3 (340.0 mg, 59.7% yield) as a yellow solid. 1H NMR (400 MHz, CDCh) δ= 6.52 (s, 1 H), 3.90 (s, 3 H), 3.39 (t, J = 4.0 Hz, 2 H), 3.14 (t, J = 4.4 Hz, 2 H), 2.45 (s, 3 H), 2.19 (s, 3 H). Example 51

[0254] To a solution of compound 60-1 (10.50 g, 38.82 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (11.35 g, 58.20 mmol) and potassium fluoride (4.50 g, 77.45 mmol) in 1,4-dioxane / water (100 mL / 20 mL), Pd(dppf)Cl2 (2.84 g, 3.88 mmol) was added. The mixture was stirred at 110°C for 16 h under an Ar atmosphere. Petition 870250084579, dated 09 / 19 / 2025, page 130 / 201 124 / 168 cooled reaction mixture, water (300 mL) was added and extracted with EtOAc (300 mL x 2). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 65%) in petroleum ether to produce intermediate 60-2 (1.10 g, 13.4% yield) as a yellow solid. LC-MS (ESI+): m / z 212.0 (M+H)+

[0255] To a solution of intermediate 60-2 (1.10 g, 5.20 mmol) in EtOH / Water (5 mL / 5 mL) was added KOH (1.50 g, 26.74 mmol). The mixture was stirred at 110°C for 16 h under an Ar atmosphere. To the cooled reaction mixture, water (20 mL) was added. The pH of the mixture was adjusted to 2 with 1N HCl. Then, the mixture was extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by reversed-phase chromatography and eluted with ACN (0% to 20%) in H2O to produce intermediate 60-3 (400.0 mg, 38.0% yield) as a yellow solid. LC-MS (ESI): m / z 201.0 (MH)-

[0256] To a solution of intermediate 60-3 (400.0 mg, 1.97 mmol) in THF (5 mL), BH3 (5.92 mL, 5.92 mmol, 1 M in THF) was added at 0°C under an Ar atmosphere. The reaction was stirred at room temperature for 2 h. Water (50 mL) was added to the reaction mixture. The mixture was adjusted to pH = 3 with 1N HCl. Then, the mixture was extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on eluted silica gel. Petition 870250084579, dated 09 / 19 / 2025, page 131 / 201 125 / 168 with ethyl acetate (0% to 60%) in petroleum ether to produce intermediate 60-4 (370.0 mg, 99.6% yield) as a colorless oil. 1H NMR (400 MHz, CDCh) δ = 6.86 (s, 2 H), 6.47 (s, 2 H), 3.95 (t, J = 4.8 Hz, 2 H), 2.93 (t, J = 4.8 Hz, 2 H), 2.58 (s, 1 H).

[0257] To a solution of intermediate 60-4 (370.0 mg, 1.96 mmol) in THF (5 mL), triphenylphosphine (772.0 mg, 2.94 mmol) and DIAD (0.57 mL, 2.94 mmol) were added at 0°C under an Ar atmosphere. The reaction was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 15%) in petroleum ether, to produce intermediate 60-5 (200.0 mg, 59.8% yield) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 6.42 (s, 1 H), 6.34 (s, 1 H), 4.99 (s, 1 H), 4.64 - 4.59 (m, 2 H), 3.13 - 3.09 (m, 2 H).

[0258] To a solution of intermediate 60-5 (200.0 mg, 1.17 mmol) in DCM (5 mL), AC2O (395.09 mg, 3.87 mmol) and a solution of TiCl4 (0.84 mL, 7.66 mmol) in DCM (5 mL) at 0°C were added. The reaction was stirred at 0°C for 1 h. Then, the reaction was heated to room temperature and stirred for 3 h. Water (20 mL) was added to the reaction mixture and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 5%) in petroleum ether to produce intermediate 60-6 (200.0 mg, 80.4% yield) as a white solid. LC-MS (ESI+): m / z 213.1 (M+H)+ 1H NMR (400 MHz, CDCh) δ = 13.38 (s, 1 H), 6.50 (s, 1 H), 4.70 (t, Petition 870250084579, dated 09 / 19 / 2025, page 132 / 201 126 / 168 J = 8.8 Hz, 2 H), 3.17 (t, J = 8.8 Hz, 2 H), 2.80 (s, 3 H).

[0259] To a solution of intermediate 60-6 (100.0 mg, 0.47 mmol) in DMF (5 mL), iodomethane (79.5 mg, 0.56 mmol) and K2CO3 (97.0 mg, 0.70 mmol) were added. The reaction was stirred at room temperature for 2 h. Water (10 mL) was added to the reaction mixture and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (10 mL x 3), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 10%) in petroleum ether to produce intermediate 60-7 (100.0 mg, 93.6% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 6.55 (s, 1 H), 4.61 (t, J = 8.8 Hz, 2 H), 3.86 (s, 3 H), 3.32 (t, J = 8.8 Hz, 2 H), 2.49 (s, 3 H). Example 52 62-1 62-2 62-3 62-4 Sodium formate Brx62-5 62-6 62-7

[0260] A solution of compound 62-1 (6.10 g, 45.45 mmol) in To THF (80 mL), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolan) (12.70 g, 50.00 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (0.24 g, 0.91 mmol) and [Ir(COD)OMe]2 (0.30 g, 0.46 mmol) were added. The reaction was stirred at 70°C for 2 h under N2. The reaction mixture was concentrated under reduced pressure to yield intermediate 62-2 (11.00 g, crude) as brown oil, which was used in the next step without further purification. LC-MS (ESI+): m / z 261.1 (M+H)+. Petition 870250084579, dated 09 / 19 / 2025, page 133 / 201 127 / 168

[0261] To a solution of intermediate 62-2 (11.00 g, crude) in THF (90 mL), NaOH (42.5 mL, 85.00 mmol, 2 mol / L in H2O) and H2O2 (28.80 g, 254.12 mmol, 30% by weight in H2O) were slowly added at 0°C. The mixture was stirred at room temperature for 2 h. Water (90 mL) was added to the mixture and extracted with EtOAc (90 mL x 3). The combined organic layers were washed with saturated aqueous sodium sulfite solution (60 mL x 2), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 20%) in petroleum ether to produce intermediate 62-3 (1.40 g, 20.5% yield in 2 steps) as a whitish solid. LC-MS (ESI+): m / z 151.2 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 6.62 (s, 1 H), 6.47 (s, 1 H), 5.33 (s, 1 H), 5.11 (s, 2 H), 5.08 (s, 2 H), 2.31 (s, 3 H).

[0262] To a solution of intermediate 62-3 (700.0 mg, 4.66 mmol) in HOAc (15 mL), NBS (830.0 mg, 4.66 mmol) was added at 0 °C. The reaction was stirred at room temperature for 1 h. Water (30 mL) was added to the reaction mixture and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 15%) in petroleum ether to produce intermediate 62-4 (550.0 mg, 51.5% yield) as a yellow solid. LC-MS (ESI): m / z 226.9 (MH)-. 1H NMR (400 MHz, CDCh) δ = 6.58 (s, 1 H), 5.19 (s, 2 H), 5.11 5.06 (m, 2 H), 2.33 (s, 3 H).

[0263] To a solution of intermediate 62-4 (550.0 mg, 2.40 mmol) in acetonitrile (12 mL), NIS (1.08 g, 4.80 mmol) was added. Petition 870250084579, dated 19 / 09 / 2025, page 134 / 201 128 / 168 The mixture was stirred at room temperature for 1 h. Saturated aqueous sodium sulfite solution (20 mL) was added to the reaction mixture and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 12%) in petroleum ether, to produce intermediate 62-5 (720.0 mg, 84.5% yield) as a yellow solid. LC-MS (ESI): m / z 352.7 (MH)-. 1H NMR (400 MHz, CDCh) δ = 5.26 - 5.19 (m, 2 H), 5.08 - 5.02 (m, 2 H), 2.65 (s, 3 H).

[0264] To a solution of intermediate 62-5 (700.0 mg, 1.97 mmol) in toluene (20 mL), tributyl(1-ethoxyvinyl)estanane (783.0 mg, 2.17 mmol) and Pd(PPh3)4 (46.0 mg, 0.039 mmol) were added. The reaction was stirred at 120°C for 16 h under a N2 atmosphere. To the cooled reaction mixture, HCl (15.1 mL, 90.6 mmol, 6 mol / L in H2O) was added, and the mixture was stirred at room temperature for a further 2 h. Water (30 mL) was added to the reaction mixture and extracted with EtOAc (30 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 12%) in petroleum ether, to produce intermediate 62-6 (300.0 mg, 56.2% yield) as a yellow solid. LC-MS (ESI+): m / z 271.0 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 11.34 (s, 1 H), 5.23 (s, 2 H), 5.10 5.02 (m, 2 H), 2.65 (s, 3 H), 2.62 (s, 3 H).

[0265] To a solution of intermediate 62-6 (2.60 g, 9.59 mmol) in DMF (30 mL), sodium formate (978.0 mg, Petition 870250084579, dated 09 / 19 / 2025, page 135 / 201 129 / 168 14.38 mmol) and Pd(PPh3)4 (665.0 mg, 0.58 mmol). The mixture was stirred at 95°C for 16 h under a H2 atmosphere. Water (30 mL) was added to the cooled reaction mixture and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by silica gel column chromatography eluted with ethyl acetate (0% to 12%) in petroleum ether to produce intermediate 62-7 (1.00 g, 54.2% yield) as a yellow solid. LC-MS (ESI+): m / z 193.1 (M+H)+. 1H NMR (400 MHz, CDCh) δ = 12.66 (s, 1 H), 6.63 (s, 1 H), 5.11 (s, 2 H), 5.08 - 5.00 (m, 2 H), 2.67 (s, 3 H), 2.62 (s, 3 H). Example 53

[0266] A solution of compound 64-1 (4.54 g, 21.11 mmol) in 1,4-dioxane (50 mL), K3PO4 (8.96 g, 42.20 mmol), methylboronic acid (7.60 g, 127.00 mmol), Pd(OAc)2 (143.0 mg, 0.64 mmol), and S-Phos (521.4 mg, 1.27 mmol) were added. The mixture was stirred at 110 °C for 16 h under an Ar atmosphere. The mixture was concentrated to provide the residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 75%) in petroleum ether to give intermediate 64-2 (2.50 g, 78.9% yield) as a white solid. LC-MS (ESI+): m / z 151.1 (M+H)+. 1H NMR: (400 MHz, CDCh) δ = 6.59 (s, 1 H), 6.55 (s, 1 H), 4.58 (t, J = 8.8 Hz, 2 H), 3.19 (t, J = 8.8 Hz, 2 H), 2.24 (s, 3 H). Petition 870250084579, dated 09 / 19 / 2025, page 136 / 201 130 / 168

[0267] To a solution of intermediate 64-2 (1.10 g, 7.32 mmol) in DMF (10 mL), benzyl bromide (1.50 g, 8.79 mmol) and K2CO3 (3.0 g, 21.97 mmol) were added at room temperature. The reaction was stirred at room temperature for 16 h. Water (20 mL) was added to the reaction mixture and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 15%) in petroleum ether to produce intermediate 64-3 (1.70 g, 96.6% yield) as a white solid. 1H NMR: (400 MHz, CDCh) δ = 7.45 - 7.29 (m, 5 H), 6.65 (s, 1 H), 6.59 (s, 1 H), 5.12 (s, 2 H), 4.60 (t, J = 8.8 Hz, 2 H), 3.18 (t, J = 8.8 Hz, 2 H), 2.24 (s, 3 H).

[0268] To a solution of intermediate 64-3 (1.70 g, 7.07 mmol) in DCM (20 mL), NBS (1.66 g, 9.34 mmol) was added at 0°C. The reaction was stirred at room temperature for 16 h. The mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 7%) in petroleum ether to produce intermediate 64-4 (2.20 g, 97.5% yield) as a white solid. 1H NMR: (400 MHz, CDCh) δ = 7.50 - 7.30 (m, 5 H), 6.67 (s, 1 H), 5.11 (s, 2 H), 4.65 (t, J = 8.8 Hz, 2 H), 3.22 (t, J = 8.8 Hz, 2 H), 2.27 (s, 3 H).

[0269] To a solution of intermediate 64-4 (2.20 g, 6.89 mmol) in DCM (25 mL) was added NIS (1.55 g, 6.89 mmol) at 0°C. The mixture was stirred at room temperature for 10 min. Silver trifluoromethanesulfonate (0.91 g, 3.54 mmol) was added to the mixture, and the reaction was stirred at room temperature for 3 h. Water (50 mL) was added to the reaction mixture and extracted with EtOAc (50 mL x 2). The Petition 870250084579, dated 09 / 19 / 2025, page 137 / 201 131 / 168 combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 6%) in petroleum ether to produce intermediate 64-5 (2.40 g, 78.3% yield) as a white solid. RMN de1H: (400 MHz, CDCh) δ = 7,56 - 7,32 (m, 5 H), 5,13 (s, 2 H), 4,65 (t, J = 8,8 Hz, 2 H), 3,22 (t, J = 8,8 Hz, 2 H), 2,62 (s, 3 H).

[0270] To a solution of intermediate 64-5 (2.35 g, 5.28 mmol) in toluene (25 mL), tributyl(1-ethoxyvinyl)stanane (2.29 g, 6.34 mmol) and Pd(PPh3)4 (122.0 mg, 0.11 mmol) were added. The reaction was stirred at 120°C for 16 h under an Ar atmosphere. To the cooled reaction mixture, HCl (50 mL, 200 mmol) (4 M) was added, and the mixture was stirred at room temperature for a further 2 h. Water (50 mL) was added to the reaction mixture and extracted with EtOAc (50 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 6%) in petroleum ether to produce intermediate 64-6 (390.0 mg, 20.4% yield) as a colorless oil. 1H NMR: (400 MHz, CDCh) δ = 7.35 - 7.25 (m, 5 H), 5.05 (s, 2 H), 4.59 (t, J = 8.8 Hz, 2 H), 3.17 (t, J = 8.8 Hz, 2 H), 2.31 (s, 3 H), 2.10 (s, 3 H).

[0271] To a solution of intermediate 64-6 (160.0 mg, 0.44 mmol) in EtOH / dioxane (1 mL / 1 mL), TEA (0.06 mL, 0.44 mmol), 10% Pd / C (24 mg, 50% in water), and ammonium formate (17.0 mg, 0.27 mmol) were added. The reaction was stirred at 60°C for 16 h under a water-filled flask. The mixture was filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by chromatography. Petition 870250084579, dated 09 / 19 / 2025, page 138 / 201 132 / 168 column in silica gel eluted with ethyl acetate (0% to 10%) in petroleum ether, to produce intermediate 64-7 (85.0 mg, 100% yield) as a yellow solid. LC-MS (ESI+): m / z 193.1 (M+H)+. 1H NMR: (400 MHz, CDCh) δ = 11.77 (s, 1 H), 6.62 (s, 1 H), 4.64 (t, J = 9.2 Hz, 2 H), 3.21 (t, J = 9.2 Hz, 2 H), 2.64 (s, 3 H), 2.52 (s, 3 H). Example 54 68-1 68-2 68-4

[0272] A solution of compound 68-1 (0.70 g, 1.65 mmol) in MeOH (10 mL) was added to Pd(OH)2 (579 mg, 0.82 mmol). The reaction was heated to 30°C and stirred at that temperature for 16 h under a flask of H2. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain intermediate 68-2 (0.40 g, 99.2% yield) as a colorless oil. LC-MS (ESI+): m / z 245.1 (M+H)+.

[0273] To a mixture of CaCO3 (184.0 mg, 1.84 mmol) in DCM (6 mL) and water (3 mL), intermediate 68-2 (150 mg, 0.61 mmol) and thiophosgene (105.8 mg, 0.92 mmol) were slowly added at 0°C under N2. After the addition, the reaction was stirred at room temperature for 1 h. The mixture was filtered, and the filtrate was extracted with DCM (30 mL x 3) and water (30 mL). The combined organic layers were dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce intermediate 68-3 (150.0 mg, 85.8% yield) as a yellow oil, which was used in the next step without further processing.

[0274] To a solution of intermediate 68-3 (150.0 mg, 0.52 mmol) in MeOH (5 mL), a solution of hydrazinium hydroxide (46 mg, 0.78 mmol, 85% by weight) under N2 was added. The reaction was stirred at room temperature for 1 h. The mixture was concentrated under pressure. Petition 870250084579, dated 09 / 19 / 2025, page 139 / 201 133 / 168 was reduced to produce the residue, which was lyophilized to produce intermediate 68-4 (140.0 mg, 84.5% yield) as a white solid. LC-MS (ESI+): m / z 319.1 (M+H)+.

[0275] The compounds below were prepared using a synthesis method similar to that described in Compound 1 or Compound 2, substituting the appropriate starting materials, reagents, and reaction conditions. The reaction temperatures ranged from -78°C to 0°C for the last step, under BBr3 conditions. Compound No. Analytical data 32 LC-MS (ESI+): m / z: 361.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.50 (br,s, 1 H), 7.92 7.75 (m, 1 H), 7.51 - 7.16 (m, 1 H), 7.08 (s, 1 H), 7.01 (s, 1 H), 3.89 (s, 2 H), 3.45 - 3.36 (m, 2 H), 2.62 (d, J = 4.8 Hz, 3 H), 2.28 (s, 3 H). 33 and 34 Preparative HPLC: (Column: C18 150*30 mm, Moving Phase A: water (FA), Moving Phase B: acetonitrile, Vase rate: 30 mL / min, gradient from 15 % of B to 45 %) Primeiro pico, LC-MS (ESI+): m / z 388.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.52 (br,s, 1 H), 7.08 (s, 1 H), 7.01 (s, 1 H), 3.98 - 3.85 (m, 2 H), 3.70 - 3.60 (m, 2 H), 3.45 - 3.40 (m,1 H), 3.29 - 3.18 (m, 1 H), 2.31 (s, 3 H), 1.94 1.85 (m, 4 H), 1.02 (d, J = 6.4 Hz, 3 H). Secondly, LC-MS (ESI+): m / z 388.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 10.90 (br,s, 1 H), 7.16 (s, 1 H), 7.07 (s, 1 H), 4.18 - 4.03 (m, 2 H), 3.98 - 3.81 (m, 2 H), 3.79 - 3.66 (m, 2 H), 2.34 (s, 3 H), 2.21 - 2.07 (m, 2 H), 2.03 1.88 (m, 2 H), 1.09 (d, J = 6.4 Hz, 3 H).35 LC-MS (ESI+): m / z 413.1 (M+H)+. 1H NMR (400 MHz, DMSO-de) δ = 8.19 (s, 1H, HCOOH), 7.07 (s, 1 H), 7.01 (s, 1 H), 4.13 - 4.04 (m, 1 H), 3.67 - . Petition 870250084579, dated 09 / 19 / 2025, page 140 / 201 134 / 168 3,62 (m, 1 H), 3,57 - 3,51 (m, 1 H), 3,47 - 3,26 (m, 2 H), 3,13 2,88 (m, 1 H), 2,64 - 2,54 (m, 1 H), 2,42 - 2,32 (m, 1 H), 2,29 (s, 3 H), 2,23 (s, 3 H), 2,16 - 2,07 (m, 1 H), 2,07 - 1,99 (m, 1 H), 1,99 - 1,87 (m, 2 H), 1,86 - 1,77 (m, 1 H), 1,71 - 1,62 (m, 1 H). 37 LC-MS (ESI+): m / z: 344,2 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 7,20 (s, 1 H), 7,06 (s, 1 H), 4,03 - 3,87 (m, 1 H), 3,48 - 3,34 (m, 2 H), 2,97 - 2,84 (m, 1 H), 2,65 - 2,55 (m, 1 H), 2,25 (s, 3 H), 2,16 (s, 3 H), 1,90 - 1,76 (m, 3 H), 1,72 - 1,61 (m, 1 H), 1,55 - 1,45 (m, 1 H), 1,29 - 1,17 (m, 1 H). 41 LC-MS (ESI+): m / z 378,0 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 7,21 - 7,12 (m, 1 H), 7,08 (s, 1 H), 5,00 (s, 1 H), 4,03 - 3,98 (m, 1 H), 3,78 (s, 2 H), 2,35 - 2,30 (m, 2 H), 2,05 - 2,00 (m, 2 H), 1,25 (s, 3 H). 42 LC-MS (ESI+): m / z 424,1 (M+H)+.RMN de 1H (400 MHz, DMSO-de) δ = 7,61 (s, 1 H), 7,53 - 7,16 (m, 3 H), 4,97 (s, 1 H), 4,04 - 3,90 (m, 1 H), 3,39 (s, 2 H), 2,35 (s, 3 H), 2,34 - 2,29 (m, 2 H), 2,04 - 1,99 (m, 2 H), 1,25 (s, 3 H). 43 LC-MS (ESI+): m / z 361,0 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 10,46 (br,s, 1 H), 7,56 6,68 (m, 5 H), 3,60 - 3,48 (m, 2 H), 3,37 (s, 2 H), 2,41 (t, J = 7,2 Hz, 2 H), 2,29 (s, 3 H). 45 LC-MS (ESI+): m / z 394,0 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ= 7,34 (s, 1 H), 7,15 (s, 1 H), 4,97 (s, 1 H), 4,02 - 3,90 (m, 1 H), 3,43 (s, 2 H), 2,34 - 2,29 (m, 2 H), 2,04 - 1,99 (m, 2 H), 1,25 (s, 3 H). 46 LC-MS (ESI+): m / z 389,1 (M+H)+. RMN de 1H (400 MHz, CDCh) δ = 7,54 (d, J = 5,2 Hz, 1 H), 7,25 - 7,20 (m, 2 H), 4,81 - 4,70 (m, 1 H), 3,70 - 3,60 (m, 1 H), 3,56 (s, 2 H), 3,48 - 3,39 (m, 1 H), 2,99 - 2,91 (m, 2 H), 2,91 -. Petição 870250084579, de 19 / 09 / 2025, pág. 141 / 201 135 / 168 2,78 (m, 1 H), 2,66 - 2,62 (m, 1 H), 2,51 (s, 3 H), 2,41 - 2,35 (m, 1 H), 2,21 - 2,17 (m, 1 H), 1,89 - 1,85 (m, 1 H), 1,78 - 1,71 (m, 1 H), 1,45 - 1,30 (m, 3 H). 47 LC-MS (ESI+): m / z 405,1 (M+H)+. RMN de 1H (400 MHz, CDCh) δ = 8,12 (s, 1H, de HCOOH), 7,56 (d, J = 5,6 Hz, 1 H), 7,30 - 7,26 (m, 2 H), 4,80 - 4,72 (m, 1 H), 4,05 - 3,98 (m, 2 H), 3,70 - 3,62 (m, 1 H), 3,60 (s, 2 H), 3,58 - 3,50 (m, 1 H), 3,21 - 3,07 (m, 2 H), 2,90 - 2,82 (m, 1 H), 2,50 (s, 3 H), 2,48 - 2,42 (m, 1 H), 2,41 - 2,35 (m, 1 H), 2,21 2,07 (m, 2 H), 1,98 - 1,90 (m, 1 H), 1,87 - 1,80 (m, 1 H). 48 LC-MS (ESI+): m / z 392,0 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 7,12 - 7,05 (m, 1 H), 4,96 (br,s, 1 H), 4,07 - 3,90 (m, 1 H), 3,41 (s, 2 H), 2,33 - 2,29 (m, 2 H), 2,25 (s, 3 H), 2,04 - 1,99 (m, 2 H), 1,25 (s, 3 H). 49 LC-MS (ESI+): m / z 345,3 (M+H)+.RMN de 1H (400 MHz, DMSO-de) δ= 8,22 (s, 1H, de HCOOH), 7,22 (s, 1 H), 6,67 (s, 1 H), 4,53 (t, J = 8,4 Hz, 2 H), 3,95 - 3,92 (m, 1 H), 3,61 - 3,50 (m, 2 H), 3,17 - 3,10 (m, 2 H), 2,89 - 2,81 (m, 1 H), 2,68 - 2,64 (m, 1 H), 2,29 (s, 3 H), 2,18 (s, 3 H), 1,88 - 1,81 (m, 3 H), 1,69 - 1,65 (m, 1 H), 1,52 - 1,48 (m, 1 H), 1,29 -1,19 (m, 1 H). 50 LC-MS (ESI+): m / z 346,1 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 9,59 (br,s, 1 H), 6,65 (s, 1 H), 5,06 (br,s, 1 H), 4,02 - 3,92 (m, 1 H), 3,68 - 3,59 (m, 2 H), 2,82 - 2,75 (m, 4 H), 2,36 - 2,33 (m, 2 H), 2,20 (s, 3 H), 2,11 1,95 (m, 4 H), 1,26 (s, 3 H). 53 LC-MS (ESI+): m / z 388,0 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 7,10 (s, 1 H), 4,03 - 3,90 (m, 1 H), 3,53 (s, 2 H), 2,35 - 2,27 (m, 5 H), 2,25 (s, 3 H), 2,08 - 1,95 (m, 2 H), 1,26 (s, 3 H). 56 LC-MS (ESI+): m / z 357,1 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 10,01 (br.s, 1 H), 6,74 (s,. Petição 870250084579, de 19 / 09 / 2025, pág. 142 / 201 136 / 168 1 H), 6,71 (s, 1 H), 3,95 - 3,94 (m, 1 H), 3,39 - 3,32 (m, 2 H), 3,00 - 2,92 (m, 1 H), 2,66 - 2,60 (m, 1 H), 2,21 (s, 3 H), 2,18 (s, 3 H), 2,02 (s, 3 H), 1,95 - 1,81 (m, 3 H), 1,71 - 1,67 (m, 1 H), 1,57 - 1,46 (m, 1 H), 1,30 - 1,19 (m, 1 H). 57 LC-MS (ESI+): m / z 379,0 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 8,18 (s, 1H, de HCOOH), 4,63 (t, J = 8,4 Hz, 2 H), 4,02 - 3,92 (m, 1 H), 3,47 - 3,38 (m, 2 H), 3,15 (t, J = 8,8 Hz, 2 H), 3,08 - 2,97 (m, 1 H), 2,76 2,71 (m, 1 H), 2,27 (s, 3 H), 2,12 (s, 3 H), 2,06 - 1,90 (m, 2 H), 1,88 - 1,82 (m, 1 H), 1,73 - 1,65 (m, 1 H), 1,55 - 1,48 (m, 1 H), 1,29 - 1,22 (m, 1 H). 58 LC-MS (ESI+): m / z 402,1 (M+H)+ RMN de 1H (400 MHz, CD3CN) δ= 6,74 (s, 1 H), 4,67 (t, J = 8,8 Hz, 2 H), 4,05 - 3,98 (m, 1 H), 3,48 (s, 2 H), 3,22 (t, J = 8,4 Hz, 2 H), 2,47 - 2,42 (m, 2 H), 2,09 - 2,01 (m, 2 H), 1,30 (s, 3 H).59 LC-MS (ESI+): m / z 332,1 (M+H)+ RMN de 1H (400 MHz, CD3CN) δ = 6,56 (s, 1 H), 4,05 - 3,97 (m, 1 H), 3,49 (s, 2 H), 3,16 - 3,01 (m, 4 H), 2,50 - 2,43 (m, 2 H), 2,30 (s, 3 H), 2,14 - 2,05 (m, 2 H), 1,31 (s, 3 H). 60 LC-MS (ESI+): m / z 368,1 (M+H)+ RMN de 1H (400 MHz, CD3CN) δ = 6,51 (s, 1 H), 4,64 (t, J = 8,4 Hz, 2 H), 4,11 - 4,00 (m, 1 H), 3,75 (s, 2 H), 3,13 (t, J = 8,8 Hz, 2 H), 2,52 - 2,41 (m, 2 H), 2,07 - 2,00 (m, 2 H), 1,31 (s, 3 H). 61 LC-MS (ESI+): m / z 366,1 (M+H)+ RMN de 1H (400 MHz, CD3CN) δ = 4,69 (t, J = 8,8 Hz, 2 H), 4,08 - 3,96 (m, 1 H), 3,53 (s, 2 H), 3,17 (t, J = 8,8 Hz, 2 H), 2,52 - 2,42 (m, 2 H), 2,26 - 2,22 (m, 3 H), 2,07 - 2,00 (m, 2 H), 1,31 (s, 3 H). 67 LC-MS (ESI+): m / z 332,1 (M+H)+ RMN de 1H (400 MHz, CD3CN) δ = 6,55 (s, 1 H), 4,52 - 4,44. Petição 870250084579, de 19 / 09 / 2025, pág. 143 / 201 137 / 168 (m, 1 H), 3.46 (s, 2 H), 3.10 - 3.00 (m, 4 H), 2.48 - 2.40 (m, 2 H), 2.31 (s, 3 H), 2.06 - 2.01 (m, 2 H), 1.93 (s, 3 H). 68 LC-MS (ESI+): m / z 331.2 (M+H)+ 1H NMR (400 MHz, CD3CN) δ = 8.18 (s, 1H from HCOOH), 6.55 (s, 1 H), 4.24 - 4.15 (m, 1 H), 3.46 (s, 2 H), 3.12 - 3.02 (m, 4 H), 2.50 - 2.41 (m, 2 H), 2.30 (s, 3 H), 2.12 - 2.01 (m, 2 H), 1.29 (s, 3 H). 69 LC-MS (ESI+): m / z 331.1 (M+H)+

[0276] The compounds below were prepared using a synthesis method similar to that described in Compound 25, substituting the appropriate starting materials, reagents, and reaction conditions. Composto No. Analytical data 38 LC-MS (ESI+): m / z 324,1 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 10,42 (br, s, 1 H), 6,60 6,47 (m, 2 H), 4,96 (s, 1 H), 3,99 - 3,88 (m, 1 H), 3,36 - 3,35 (m, 2 H), 2,36 - 2,26 (m, 2 H), 2,21 (s, 3 H), 2,04 - 1,96 (m, 2 H), 1,24 (s, 3 H). 39 LC-MS (ESI+): m / z: 370,1 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 7,21 (s, 1 H), 7,06 (s, 1 H), 4,14 - 3,98 (m, 1 H), 3,68 - 3,62 (m, 1 H), 3,58 - 3,50 (m, 2 H), 3,32 - 3,23 (m, 1 H), 2,97 - 2,87 (m, 1 H), 2,40 - 2,31 (m, 1 H), 2,26 (s, 3 H), 2,17 (s, 3 H), 2,07 - 1,78 (m, 6 H), 1,69 - 1,61 (m, 1 H). Exemplo 55 Petição 870250084579, de 19 / 09 / 2025, pág. 144 / 201 138 / 168 CSCI2, CaCO- OH 8“ΗΞΝHC| 66-15 Composto 66

[0277] To a mixture of CaCO3 (37.10 g, 370.68 mmol) in DCM (150 mL) and H2O (75 mL), compound 66-15 (17.00 g, 123.54 mmol) and thiophosgene (28.4 g, 247.02 mmol) were added at 0°C under N2. The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was filtered, and the filtrate was extracted with DCM (200 mL x 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to yield intermediate 66-16 (15.00 g, 104.75 mmol, 85% yield) as a yellow oil, which was used in the next step without further purification. 1H NMR: (400 MHz, DMSO-de) δ = 3.99 - 3.80 (m, 1 H), 2.46 - 2.32 (m, 2 H), 2.24 - 2.09 (m, 2 H), 1.00 (s, 3 H).

[0278] To a solution of intermediate 66-16 (15.00 g, 104.75 mmol) in MeOH (100 mL), hydrazine hydrate (7.40 g, 125.65 mmol, 85% by weight) was added under N2. The mixture was stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure. Petition 870250084579, dated 09 / 19 / 2025, p. 145 / 201 139 / 168 is used to produce intermediate 66-14 (17.70 g, 96.4% yield) as a yellow solid. 1H NMR: (400 MHz, DMSO-d6) δ = 8.64 (s, 1 H), 7.73 - 7.62 (m, 1 H), 4.94 (s, 1 H), 4.48 (s, 2 H), 4.29 - 4.18 (m, 1 H), 2.37 - 2.24 (m, 2 H), 2.01 - 1.94 (m, 2 H), 1.21 (s, 3 H).

[0279] A solution of compound 66-1 (10.00 g, 36.35 mmol) in dioxane / water (150 mL / 30 mL), potassium trifluoro(vinyl)borate (6.30 g, 47.03 mmol), Pd(dppf)Cl2 (2.70 g, 3.69 mmol) and K2CO3 (12.6 g, 91.17 mmol) was added. The mixture was stirred at 100°C for 16 h. To the cooled reaction mixture, water (100 mL) was added and extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 12%) in petroleum ether, to produce intermediate 66-2 (7.70 g, 95.3% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 7.25 (s, 2 H), 7.01 - 6.93 (m, 1 H), 6.18 (dd, J = 18.0, 2.8 Hz, 1 H), 5.55 (dd, J = 12.4, 2.8 Hz, 1 H), 3.92 (s, 3 H), 3.90 (s, 6 H).

[0280] To a solution of intermediate 66-2 (8.10 g, 36.45 mmol) in THF (100 mL), 9-BBN (146 mL, 0.5 M in THF, 73.00 mmol) was added. The mixture was stirred at room temperature for 16 h, and the reaction was diluted with THF / water (50 mL / 50 mL). Sodium perborate tetrahydrate (33.60 g, 218.38 mmol) was added to the mixture, and the mixture was stirred vigorously for 1 h. The suspension was diluted with saturated aqueous NaHCO3 solution (50 mL) and filtered. The aqueous phase was extracted with EtOAc (100 mL x 3). The combined organic phases were washed with brine (100 mL) and dried over Na2SO4. The solvent was evaporated, and the residue was purified by chromatography. Petition 870250084579, dated 09 / 19 / 2025, p. 146 / 201 140 / 168 column in silica gel eluted with ethyl acetate (0% to 20%) in petroleum ether, to produce intermediate 66-3 (8.60 g, 98.2% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 7.25 (s, 2 H), 3.92 (s, 3 H), 3.88 (s, 6 H), 3.78 - 3.72 (m, 2 H), 3.01 (t, J = 6.8 Hz, 2 H).

[0281] A solution of intermediate 66-3 (6.60 g, 27.47 mmol) in HOAc (35 mL) and HBr (48 wt% in water, 35 mL) was stirred at 120°C for 16 h. Water (50 mL) was added to the cooled reaction mixture, and the mixture was extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with MeOH (0% to 5%) in DCM to produce intermediate 66-4 (3.20 g, 64.7% yield) as a yellow solid. LC-MS (ESI+): m / z 181.1 (M+H)+

[0282] To a solution of intermediate 66-4 (1.00 g, 5.55 mmol) in MeOH (10 mL), sulfur dichloride (2 mL) was added at 0°C. The reaction was stirred at 65°C for 6 h. The solvent was evaporated to produce the residue. The residue was dissolved in saturated aqueous NaHCO3 solution (30 mL) and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 50%) in petroleum ether to produce intermediate 66-5 (0.37 g, 34.3% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ = 9.92 (s, 1 H), 6.98 (s, 1 H), 6.76 (s, 1 H), 4.56 (t, J = 8.8 Hz, 2 H), 3.79 (s, 3 H), 3.09 (t, J = 8.8 Hz, 2 H).

[0283] To a solution of intermediate 66-5 (680.0 mg, 3.50 mmol) Petition 870250084579, dated 09 / 19 / 2025, page 147 / 201 141 / 168 in THF (10 mL), L1AIH4 (292.0 mg, 7.69 mmol) was added at 0°C under N2. The reaction was stirred at room temperature for 1 h. The mixture was diluted with DCM (10 mL), water (0.5 mL), 15% NaOH (0.5 mL) and water (1 mL) were added sequentially at 0°C. Na2SO2 was added to the mixture and the mixture was stirred at room temperature for 10 min. The suspension was filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 50%) in petroleum ether to produce intermediate 66-6 (494.0 mg, 84.9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ = 9.33 (s, 1 H), 6.28 (s, 1 H), 6.18 (s, 1 H), 5.03 (t, J = 5.6 Hz, 1 H), 4.47 (t, J = 8.8 Hz, 2 H), 4.32 (d, J = 5.6 Hz, 2 H), 2.99 (t, J = 8.8 Hz, 2 H).

[0284] To a solution of intermediate 66-6 (0.60 g, 3.61 mmol) in DCM (10 mL), PDC (2.70 g, 7.18 mmol) was added in portions, while maintaining the internal temperature at 0°C. After the addition, the reaction was stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 30%) in petroleum ether, to produce intermediate 66-7 (0.21 g, 35.4% yield) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 9.83 (s, 1 H), 6.90 - 6.87 (m, 2 H), 5.12 (s, 1 H), 4.68 (t, J = 8.8 Hz, 2 H), 3.23 (t, J = 8.8 Hz, 2 H).

[0285] To a solution of intermediate 66-7 (0.26 g, 1.58 mmol) in DCM (5 mL), BAST (0.80 mL, 4.34 mmol) was added under N2 at 0°C. The reaction was stirred at room temperature for 16 h. Water (20 mL) and a saturated aqueous solution of NaHCO3 (5 mL) were added to the reaction mixture, and the mixture was extracted with DCM (20 mL x 2). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under pressure. Petition 870250084579, dated 09 / 19 / 2025, page 148 / 201 142 / 168 was reduced to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 22%) in petroleum ether, to produce intermediate 66-8 (0.23 g, yield 78.2%) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 6.64 - 6.36 (m, 3 H), 4.94 (br.s, 1 H), 4.65 (t, J = 8.4 Hz, 2 H), 3.18 (t, J = 8.8 Hz, 2 H). 19F NMR (376 MHz, CDCl3) δ = -110.16.

[0286] To a solution of intermediate 66-8 (230 mg, 1.23 mmol) in DCM (5 mL), NBS (0.22 g, 1.24 mmol) was added at -40°C. The reaction was stirred at room temperature for 2 h. Water (20 mL) was added to the reaction mixture, and the pH of the mixture was adjusted to 4 with HCl (2N) and then extracted with DCM (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with DCM (0% to 50%) in petroleum ether, to produce intermediate 66-9 (0.28 g, 85.2% yield) as a white solid. LC-MS (ESI): m / z 263.0 (MH)-.

[0287] To a solution of intermediate 66-9 (0.28 g, 1.06 mmol) in toluene (5 mL), tributyl(1-ethoxyvinyl)stanane (459.0 mg, 1.27 mmol) and Pd(PPh3)4 (23.0 mg, 0.020 mmol) were added under an Ar atmosphere. After the addition, the reaction was stirred at 120°C for 16 h. To the cooled reaction, 4 M HCl (5 mL) was added, and the mixture was stirred at room temperature for a further 2 h. Water (20 mL) was added to the reaction mixture and extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 15%) in ether. Petition 870250084579, dated 09 / 19 / 2025, page 149 / 201 143 / 168 of petroleum to produce intermediate 66-10 (0.16 g, yield of 66.1%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ = 12.87 (s, 1 H), 7.06 (t, J = 54.8 Hz, 1 H), 6.76 (s, 1 H), 4.74 (t, J = 8.8 Hz, 2 H), 3.22 (t, J = 8.8 Hz, 2 H), 2.66 (s, 3H).

[0288] To a solution of intermediate 66-10 (155.0 mg, 0.68 mmol) and TEA (69.0 mg, 0.68 mmol) in DCM (5 mL), DMAP (17.0 mg, 0.14 mmol) and benzoyl chloride (124.0 mg, 0.88 mmol) were added. The reaction was stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 12%) in petroleum ether, to produce intermediate 66-11 (220.0 mg, 97.4% yield) as a yellow solid. 1H NMR (400 MHz, CDCh) δ = 8.25 - 8.12 (m, 2 H), 7.71 - 7.65 (m, 1 H), 7.57 - 7.50 (m, 2 H), 7.05 - 6.75 (m, 2 H), 4.70 (t, J = 8.6 Hz, 2 H), 3.16 (t, J = 8.6 Hz, 2 H), 2.46 (s, 3 H).

[0289] Copper(II) bromide (36.0 mg, 0.16 mmol) was added to a solution of intermediate 66-11 (40.0 mg, 0.12 mmol) in EtOAc / DCE (1 mL / 1 mL). The reaction was stirred at 80°C for 16 h. After cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by pre-TLC (PE / EA = 5 / 1) to produce crude intermediate 66-12 (49.0 mg) as a white solid, which was used directly in the next step without further purification.

[0290] To a solution of intermediate 66-12 (156.0 mg, 0.38 mmol) and intermediate 66-14 (67.0 mg, 0.38 mmol) in EtOH (5 mL) was added HBr (48% by weight in water, 96 mg). After stirring at room temperature for 1 h, the reaction was stirred at 60°C for 16 h. The solvent was removed under vacuum and the residue was diluted with EA. At the mis Petition 870250084579, dated 09 / 19 / 2025, pp. 150 / 201 144 / 168 tura NH4OH was added until pH = 10 at 0°C. H2O (10 mL) was added to the mixture and the mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with MeOH (0% to 4.9%) in DCM to produce intermediate 6613 (105.0 mg, 56.7% yield) as a yellow solid. LC-MS (ESI+): m / z 488.1 (M+H)+.

[0291] To a solution of intermediate 66-13 (95.0 mg, 0.19 mmol) in MeOH (3 mL) was added K2CO3 (131.0 mg, 0.95 mmol) at room temperature. The mixture was stirred at 50 °C for 1 h. The reaction mixture was filtered and washed with MeOH. The filtrate was concentrated under reduced pressure to produce a residue, which was purified by preparative HPLC (Waters 3767 / QDA) Column: SunFire C18,19*250mm,10 μm; Mobile phase A: 0.1% FA / H2O, B: ACN; Flow rate: 20 mL / min; gradient: 15-25%; Retention time: 6.7-7.8 of 17 min) to produce compound 66. LC-MS (ESI+): m / z 384.0 (M+H)+. 1H NMR (400 MHz, CD3CN) δ = 6.83 (t, J = 55.2 Hz, 1 H), 6.67 (s, 1 H), 4.65 (t, J = 8.8 Hz, 2 H), 4.07 - 3.98 (m, 1 H), 3.47 (s, 2 H), 3.25 3.18 (m, 2 H), 2.49 - 2.42 (m, 2 H), 2.08 - 1.95 (m, 2 H), 1.31 (s, 3 H). Example 56 31'3Compound 31

[0292] To a solution of intermediate 28-3 (1200 mg, 6.24 mmol) Petition 870250084579, dated 09 / 19 / 2025, p. 151 / 201 145 / 168 and TEA (632 mg, 6.24 mmol) in DCM (5 mL), 4-(dimethylamino)pyridine (153 mg, 1.25 mmol) and benzoyl chloride (1141 mg, 8.12 mmol) were added. The reaction was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-4% ethyl acetate in petroleum ether, resulting in intermediate 31-1 (1561 mg, 84.4% yield) as a white solid. 1H NMR: (400 MHz, CDCh) δ = 8.21 - 8.12 (m, 2 H), 7.72 - 7.64 (m, 1 H), 7.58 - 7.48 (m, 2 H), 6.59 (s, 1 H), 4.62 (t, J = 8.8 Hz, 2 H), 3.08 (t, J = 8.8 Hz, 2 H), 2.41 (s, 3 H), 2.31 (s, 3 H).

[0293] To a solution of intermediate 31-1 (500 mg, 1.69 mmol) in EtOAc (3 mL) and DCE (3 mL), CuBr2 (490 mg, 2.19 mmol) was added. The reaction was stirred at 80°C for 16 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-6% ethyl acetate in petroleum ether, resulting in intermediate 31-2 (500 mg, 79.0% yield) as a yellow solid. 1H NMR: (400 MHz, CDCh) δ = 8.20 - 8.08 (m, 2 H), 7.71 - 7.61 (m, 1 H), 7.61 - 7.47 (m, 2 H), 6.63 (s, 1 H), 4.64 (t, J = 8.4 Hz, 2 H), 4.23 (s, 2 H), 3.09 (t, J = 8.8 Hz, 2 H), 2.33 (s, 3 H).

[0294] To a solution of intermediate 66-14 (300 mg, 1.71 mmol) in EtOH (10 mL), intermediate 31-2 (705 mg, 1.88 mmol) and concentrated HCl (85 mg, 0.86 mmol, 37 wt%) at room temperature were added. After 10 min of stirring at room temperature, the mixture was stirred at 80°C for 1 h. NH4OH was added to the mixture until pH = 10 at 0°C. The mixture was then extracted with EtOAc (30 mL x 3) and water (30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a Petition 870250084579, dated 09 / 19 / 2025, page 152 / 201 146 / 168 residue, which was purified by column chromatography on silica gel eluted with 0-10% MeOH in DCM to produce intermediate 31-3 (230 mg, 29.8% yield) as red oil. LC-MS (ESI+): m / z 452.2 (M+H)+.

[0295] To a solution of intermediate 31-3 (200 mg, 0.44 mmol) in MeOH (10 mL), K2CO3 (304 mg, 2.20 mmol) was added at room temperature. The mixture was stirred at 50°C for 1 h. The mixture was then filtered and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by HPLC (Waters Sun Fire Prep C18 OBD 10 μm 19*250 mm column; mobile phase [0.1% FA in water - ACN]; B% 5% - 95% ACN, 6.97 min) to produce compound 31. LC-MS (ESI+): m / z 348.0 (M+H)+. 1H NMR (400 MHz, CD3CN) δ = 8.11 (s, 0.7H, HCOOH), 6.26 (s, 1H), 4.57 (t, J = 8.8 Hz, 2H), 4.07 - 3.98 (m, 1H), 3.55 (s, 2H), 3.10 (t, J = 8.8 Hz, 2H), 2.49 - 2.43 (m, 2H), 2.32 (s, 3H), 2.11 - 2.00 (m, 2H), 1.31 (s, 3H).

[0296] The compounds below were prepared using a synthesis method similar to that described in Compound 66, substituting the appropriate starting materials, reagents, and reaction conditions. No. do Composto Dados analíticos 40 LC-MS (ESI+): m / z: 391,2 (M+H)+. RMN de 1H (400 MHz, DMSO-de) δ = 10,49 (br, s, 1H), 7,29 6,56 (m, 1H), 6,21 (s, 1H), 4,58 - 4,42 (m, 3H), 4,09 - 3,88 (m, 1H), 3,53 - 3,47 (m, 2H), 3,46 - 3,42 (m, 2H), 3,11 - 2,95 (m, 3H), 2,82 - 2,65 (m, 1H), 2,49 - 2,36 (m, 2H), 2,20 (s, 3H), 2,15 - 1,94 (m, 2H), 1,87 - 1,76 (m, 1H), 1,74 - 1,62 (m, 1H), 1,58 - 1,44 (m, 1H), 1,40 - 1,22 (m, 1H). 44 LC-MS (ESI+): m / z 331,2 (M+H) +. RMN de 1H (400 MHz, DMSO-de) δ = 10,46 (br,s, 1 H), 7,23 Petição 870250084579, de 19 / 09 / 2025, pág. 153 / 201 147 / 168 (s, 1 H), 7,09 (s, 1 H), 6,58 - 6,42 (m, 1H), 5,18 - 5,06 (m, 1 H), 5,03 - 4,92 (m, 1 H), 3,50 - 3,85 (m, 2 H), 2,45 - 2,40 (m, 2 H), 2,18 (s, 3 H), 2,15 - 2,08 (m, 2 H), 1,29 (s, 3 H). 51 LC-MS (ESI+): m / z 387,1 (M+H)+. RMN de 1H: (400 MHz, DMSO-d6) δ = 10,42 (br,s, 1 H), 6,21 (s, 1 H), 4,51 (t, J = 8,4 Hz, 2 H), 4,06 - 3,96 (m, 1 H), 3,68 3,58 (m, 1 H), 3,56 - 3,50 (m, 2 H), 3,37 (s, 2 H), 3,06 (t, J = 8,4 Hz, 2 H), 2,94 - 2,85 (m, 1 H), 2,38 - 2,32 (m, 1 H), 2,20 (s, 3 H), 2,16 (s, 3 H), 2,04 - 1,95 (m, 2 H), 1,93 - 1,88 (m, 1 H), 1,87 - 1,81 (m, 2 H), 1,78 - 1,23 (m, 1 H). 54 LC-MS (ESI+): m / z 375,1 (M+H)+.RMN de 1H: (400 MHz, DMSO-d6) δ = 10,47 (br,s, 1 H), 6,94 6,82 (m, 1 H), 6,21 (s, 1 H), 4,51 (t, J = 8,8 Hz, 2 H), 4,02 - 3,91 (m, 1 H), 3,49 - 3,38 (m, 2 H) 3,14 - 3,06 (m, 2 H), 3,03 - 2,98 (m, 1 H), 2,73 - 2,66 (m, 1 H), 2,36 - 2,32 (m, 2 H), 2,21 (s, 3 H), 2,02 - 1,94 (m, 1 H), 1,86 - 1,80 (m, 2 H), 1,68 - 1,62 (m, 1 H), 1,52 - 1,44 (m, 1 H), 1,42 - 1,29 (m, 1 H), 0,99 (t, J = 6,4 Hz, 3 H). 55 LC-MS (ESI+): m / z 375,1 (M+H) +. RMN de 1H (400 MHz, DMSO-d6) δ = 10,40 (br,s, 1 H), 6,22 (s, 1 H), 4,52 (t, J = 8,8 Hz, 2 H), 4,32 - 4,21 (m, 1 H), 3,50 3,40 (m, 2 H), 3,06 (t, J = 8,8 Hz, 2 H), 3,03 (s, 3 H), 2,76 2,66 (m, 2 H), 2,21 (s, 3 H), 2,19 (s, 3 H), 2,05 - 1,99 (m, 2 H), 1,75 - 1,66 (m, 2 H), 1,60 - 1,52 (m, 2 H). 62 LC-MS (ESI+): m / z 348,0 (M+H)+. RMN de 1H (400 MHz, CD3CN) δ = 6,71 (s, 1 H), 5,03 - 4,96 (m, 4 H), 4,08 - 4,04 (m, 1 H), 3,57 (s, 2 H), 2,52 - 2,45 (m, 2 H), 2,39 (s, 3 H), 2,15 - 2,08 (m, 2 H), 1,31 (s, 3 H). 63 LC-MS (ESI+): m / z 374,0 (M+H)+.1H NMR (400 MHz, CD3CN) δ = 6.26 (s, 1 H), 4.58 (t, J = 8.4 Hz, 2 H), 3.53 (s, 2 H), 3.10 (t, J = 8.4 Hz, 2 H), 2.33 (s, 3 H), 1.80 - 1.58 (m, 10 H). Petition 870250084579, dated 09 / 19 / 2025, p. 154 / 201 148 / 168 64 LC-MS (ESI+): m / z 348,1 (M+H)+. RMN de 1H: (400 MHz, CD3CN) δ = 6,68 (s, 1 H), 4,56 (t, J = 8,4 Hz, 2 H), 4,02 - 3,95 (m, 1 H), 3,55 (s, 2 H), 3,19 (t, J = 8,8 Hz, 2 H), 2,53 - 2,45 (m, 2 H), 2,27 (s, 3 H), 2,11 - 2,02 (m, 2 H), 1,31 (s, 3 H). 65 LC-MS (ESI+): m / z 348,1 (M+H)+. RMN de 1H (400 MHz, CD3CN) δ = 6,26 (s, 1 H), 4,58 (t, J = 8,4 Hz, 2 H), 4,55 - 4,48 (m, 1 H), 3,54 (s, 2 H), 3,10 (t, J = 8,8 Hz, 2 H), 2,44 - 2,38 (m, 2 H), 2,33 (s, 3 H), 2,06 - 2,01 (m, 2 H), 1,33 (s, 3 H). 70 LC-MS (ESI+): m / z 360,4 (M+H)+. RMN de 1H (400 MHz, CD3CN) δ = 6,26 (s, 1H), 4,58 (t, J = 8,8 Hz, 2H), 3,54 (s, 2H), 3,10 (t, J = 8,8 Hz, 2H), 2,33 (s, 3H), 2,02 - 1,96 (m, 2H), 1,90 - 1,82 (m, 4H), 1,74 - 1,63 (m, 2H). 71 LC-MS (ESI+): m / z 351,3 (M+H)+. RMN de 1H (400 MHz, CD3CN) δ = 6,25 (s, 1H), 4,57 (t, J = 8,8 Hz, 2H), 4,11 - 3,98 (m, 1H), 3,54 (s, 2H), 3,09 (t, J = 8,8 Hz, 2H), 2,52 - 2,40 (m, 2H), 2,05 - 1,98 (m, 2H), 1,31 (s, 3H). Exemplo 57 Composto 36

[0297] To the MeNH2 solution (6.9 mL, 13.80 mmol, 2 M in THF), a solution of intermediate 1-3 (1.0 g, 3.21 mmol) in THF (6.0 mL) at 0°C was added and the mixture was stirred at 0°C for 20 minutes to Petition 870250084579, dated 09 / 19 / 2025, p. 155 / 201 149 / 168 to obtain intermediate 36-1. To the mixture, TEA (0.45 mL, 3.22 mmol) and intermediate 2-2 (1.45 g, 5.99 mmol) were added at 0°C and the mixture was stirred at 0°C for 0.5 hours. The volatiles were removed under vacuum to produce a residue. The residue was purified by preparative HPLC (Column: Xtimate C18 150*40mm*10μm, Mobile Phase A: water (0.05% NH3H2O ​​+ 10 mM NH4HCO3), Mobile Phase B: acetonitrile, Flow rate: 55 mL / min, gradient from 60% B to 90%) to produce intermediate 36-2 (660.0 mg, 97.86% purity, 39.9% yield) as a yellow solid. LC-MS (ESI+): m / z 504.3 (M+H)+.

[0298] To a mixture of intermediate 36-2 (300.0 mg, 0.60 mmol) and K2CO3 (247.0 mg, 1.79 mmol) in acetone (4.0 mL), CH3I (0.11 mL, 1.79 mmol) was added at 25°C and the mixture was stirred at 25°C for 1 hour. H2O (30 mL) was added to the mixture and the mixture was extracted with ethyl acetate (20 mL x 3). The combined organic extracts were dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to obtain intermediate 36-3 (310.0 mg, crude). To a solution of intermediate 36-3 (310.0 mg, crude) in EtOH (3.0 mL), hydrazine hydrate (0.47 mL, 85% purity, 8.14 mmol) was added at 25°C and the mixture was stirred at 50°C for 6 hours. The mixture was concentrated under reduced pressure to produce a residue.The residue was purified by preparative HPLC (Column: Welch Xtimate C18 150*30 mm*5 µm, Mobile Phase A: water (0.225% FA), Mobile Phase B: acetonitrile, Flow rate: 30 mL / min, gradient from 23% B to 53%) to obtain intermediate 36-4 (130.0 mg, 86.26% purity, 38.9% yield in 2 steps) as a white solid. LC-MS (ESI+): m / z 484.0 (M+H)+.

[0299] To a solution of intermediate 36-4 (90.0 mg, 0.19 mmol) in DCM (2.0 mL), BBr3 (89.7 µL, 0.93 mmol) was added at 0°C and the mixture was stirred at 0°C for 1 hour and at 30°C for 2 hours. BBr3 added Petition 870250084579, dated 09 / 19 / 2025, p. 156 / 201 150 / 168 liquid (89.7 pL, 0.91 mmol) was added at 30°C and the mixture was stirred at 30°C for 1 hour. The mixture was tempered with MeOH (20.0 mL) at 0°C and the volatiles were removed under vacuum to obtain the crude product. The crude product was purified by HPLC. (Column: Welch Xtimate C18 150*30 mm*5 pm, Mobile Phase A: water (0.225% FA), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient condition from 1% B to 31%), SFC (Column: DAICEL CHIRALPAK IG (250 mm*30 mm, 10 pm), Mobile Phase: CO2-EtOH (0.1% NH3H2O), Flow rate: 80 mL / min, gradient condition from 40% to 40%) and by HPLC Prep. (Column: Welch Xtimate C18 150*30 mm*5 µm, Mobile Phase A: water (0.225% FA), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient condition from 2% B to 32%) sequentially to produce intermediate 36-5 (3.0 mg, 4.3% yield) as a brown oil. LC-MS (ESI+): m / z 370.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 7.06 (s, 1H), 7.02 (s, 1H), 4.00 (s, 2H), 3.83 - 3.80 (m, 1H), 3.17 - 3.10 (m, 1H), 2.96 (s, 3H), 2.95 2.91 (m, 1H), 2.65 - 2.56 (m, 2H), 2.30 (s, 3H), 1.94 - 1.85 (m, 1H), 1.79 - 1.70 (m, 1H), 1.58 - 1.46 (m, 2H).

[0300] To a solution of intermediate 36-5 (60.0 mg, 0.13 mmol) in MeOH (1.0 mL) TEA (36.9 pL, 0.27 mmol) was added at 20°C. Then, HOAc (24.0 mg, 0.40 mmol) and (CH2O)n (12.0 mg, 0.40 mmol) were added to the mixture at 30°C. NaBH(OAc)3 (112.4 mg, 0.53 mmol) was added at 30°C and the mixture was stirred at 40°C for 8 hours. Additional NaBH(OAc)3 (112.4 mg, 0.53 mmol) was added at 40°C and the mixture was stirred for a further 3 hours. H2O (20 mL) was added and the mixture was extracted with ethyl acetate (20 mL x 3). The combined organic extracts were dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce the crude product. The crude product was purified by SFC. Petition 870250084579, dated 09 / 19 / 2025, p. 157 / 201 151 / 168 (Column: DAICEL CHIRALCEL OD (250 mm*30 mm, 10 pm), Mobile Phase: CO2-EtOH (0.1% NH3H2O), Flow rate: 150 mL / min, gradient from 20% to 20%) and Preparatory HPLC (Column: Welch Xtimate C18 150*30 mm*5 pm, Mobile Phase A: water (0.225% FA), Mobile Phase B: acetonitrile, Flow rate: 25 mL / min, gradient from 2% B to 32%) sequentially to produce compound 36. LC-MS (ESI+): m / z 384.2 (M+H)+. 1H NMR (400MHz, DMSO-d6) δ = 7.11 (s, 1H), 7.01 (s, 1H), 4.13 (s, 2H), 3.87 - 3.78 (m, 1H), 3.07 (s, 3H), 2.89 - 2.79 (m, 1H), 2.70 - 2.61 (m, 1H), 2.30 (s, 3H), 2.21 (s, 3H), 2.09 - 1.99 (m, 1H), 1.96 - 1.81 (m, 2H), 1.73 - 1.50 (m, 2H), 1.41 - 1.28 (m, 1H). Example 58 HCI

[0301] A solution of intermediate 1-3 (2.00 g, 6.43 mmol) in EtOH (12 mL) was added to a solution of NaOAc (580.0 mg, 7.07 mmol) in H2O / HOAc (6 mL / 0.6 mL). The reaction was stirred at 100 °C for 16 h. To the cooled reaction mixture, water (20 mL) was added and the mixture was extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-3.3% ethyl acetate in petroleum ether, resulting in intermediate 52-1 (1.10 g, 58.9% yield) as a white solid. 1H NMR: (400 MHz, CDCh) δ = 7.11 (s, 1 H), 6.98 (s, 1 H), 4.99 (s, 2 H), 3.88 (s, 3 H), 2.33 (s, 3 H), 2.16 (s, 3 H).

[0302] To a solution of intermediate 52-1 (1.10 g, 3.79 mmol) in EtOH (10 mL), HCl (5 mL, 1 N) was added. The reaction was stirred at 85°C for 2 h. To the cooled reaction mixture, water (20 Petition 870250084579, dated 09 / 19 / 2025, page 158 / 201 152 / 168 mL) and the mixture was extracted with EtOAc (20 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with 0-20% ethyl acetate in petroleum ether to produce intermediate 52-2 (700.0 mg, 2.82 mmol, 74.4% yield) as a white solid. 1H NMR: (400 MHz, CDCh) δ = 7.12 (s, 1 H), 6.99 (s, 1 H), 4.63 4.52 (m, 2 H), 3.87 (s, 3 H), 3.23 - 3.12 (m, 1 H), 2.29 (s, 3 H). Example 59 Compound 52

[0303] Similar to the procedure for the Compound 36, Compound 52 was synthesized by replacing intermediate 36-1 with intermediate 52-2. In the final step, NaBH3CN was used, and the crude product was purified by pre-HPLC (column: Waters Xbridge C18 10μm OBD 19*250mm; mobile phase: 0.1% NH4HCO3 in water, 9.088 min) to yield compound 52. LC-MS (ESI+): m / z 371.2 (M+H)+. 1H NMR: (400 MHz, DMSO-d6) δ = 9.76 (br.s, 1 H), 7.25 - 7.16 (m, 2 H), 6.70 - 6.62 (m, 1 H), 5.16 (s, 2 H), 3.85 - 3.72 (m, 1 H), 2.58 (s, 3 H), 2.44 - 2.40 (m, 1 H), 2.33 - 2.27 (m, 1 H), 2.25 - 2.19 (m, 2 H), 2.17 (s, 3 H), 1.65 - 1.61 (m, 1 H), 1.58 - 1.51 (m, 2 H), 1.49 - 1.47 (m, 1 H). Example 60 Petition 870250084579, dated 09 / 19 / 2025, page 159 / 201 153 / 168

[0304] To a solution of intermediate 28-3 (164 mg, 0.85 mmol) in toluene (4 mL), DDQ (386 mg, 1.70 mmol) was added at room temperature. The reaction was stirred at 110°C for 16 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 22%) in petroleum ether, resulting in intermediate 72-1 (64 mg, 40% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-de) δ = 10.51 (s, 1 H), 7.81 (d, J = 2.0 Hz, 1 H), 7.09 (s, 1 H), 6.96 (s, 1 H), 2.26 (s, 3 H), 1.24 (s, 3 H).

[0305] To a solution of intermediate 72-1 (85 mg, 0.45 mmol) and TEA (46 mg, 0.45 mmol) in DCM (2 mL) were added to DMAP (11 mg, 0.09 mmol) and benzoyl chloride (83 mg, 0.59 mmol). The reaction was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 10%) in petroleum ether, resulting in intermediate 72-2 (75 mg, 56% yield) as a white solid. LC-MS (ESI+): m / z 295.2 (M+H)+. 1H NMR (400 MHz, CDCI3) δ = 8.26 - 8.21 (m, 2 H), 7.73 - 7.65 (m, 1 H), 7.58 - 7.50 (m, 3 H), 7.31 (s, 1 H), 6.60 (d, J = 2.0 Hz, 1 H), 2.50 (s, 3H), 2.44 (s, 3H).

[0306] To a solution of intermediate 72-2 (75 mg, 0.25 mmol) in DCM (3 mL), DIEA (39 mg, 0.30 mmol) and trifluo were added. Petition 870250084579, dated 09 / 19 / 2025, pp. 160 / 201 154 / 168 trimethylsilyl romethanesulfonate (67 mg, 0.30 mmol) at 0°C. After stirring at room temperature for 0.5 h, NBS (53 mg, 0.30 mmol) was added to the mixture. The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure to produce a residue, which was purified by silica gel column chromatography eluted with ethyl acetate (0% to 7%) in petroleum ether, resulting in crude intermediate 72-3 (65 mg) as a yellow oil, which was used directly in the next step. To a solution of crude intermediate 72-3 (65 mg) and intermediate 66-14 (39 mg, 0.22 mmol) in EtOH (3 mL), HBr (38 mg, 0.23 mmol, 48% by weight in water) was added. After stirring at room temperature for 1 h, the mixture was heated to 60°C and stirred for a further 16 h. The solvent was removed under vacuum and the mixture was diluted with EtOAc. NH4OH was added to the mixture until pH = 10 at 0°C.Next, H2O (10 mL) was added and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by pre-TLC (DCM / MeOH = 10 / 1) to produce intermediate 72-4 (18 mg, 16% yield in two steps) as a yellow solid. LC-MS (ESI+): m / z 450.1 (M+H)+.

[0307] To a solution of intermediate 72-4 (18 mg, 0.04 mmol) in MeOH (1 mL) was added K2CO3 (28 mg, 0.20 mmol). The reaction was stirred at 50°C for 1 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by preparative HPLC (Waters 3767 / QDA). Column: SunFire C18, 19*250 mm; 10 μm; Mobile phase A: 0.1% FA / H2O, B: ACN; Flow rate: 20 mL / min; gradient: 12-22% Retention time: 8.4-9.2 min (17 min) to produce compound 72. LC-MS (ESI+): m / z 345.9 (M+H)+. Petition 870250084579, dated 09 / 19 / 2025, p. 161 / 201 155 / 168 1H NMR (400 MHz, CD3CN) δ = 7.64 - 7.58 (m, 1 H), 6.99 (s, 1 H), 6.92 - 6.86 (m, 1 H), 4.11 - 4.04 (m, 1 H), 3.60 (s, 2 H), 2.55 - 2.45 (m, 5 H), 2.08 - 2.03 (m, 2 H), 1.32 (s, 3 H). Example 61 h2n-NHBOC co \ 201-2 Reagent of Lawesson Lawesson's reagent 201-5 201-6 201-7 201-8 Compound 201

[0308] A solution of compound 201-1 (1.00 g, 3.16 mmol), Pd(OAc)2 (142.0 mg, 0.63 mmol), tert-Butyl carbazate (627.0 mg, 4.74 mmol) and K2CO3 (874.0 mg, 6.32 mmol) in dry DMF (10 mL) was stirred at 90°C for 16 h under a CO2 atmosphere. Water (30 mL) was added to the cooled reaction mixture and the mixture was extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (50 mL x 3), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 8%) in petroleum ether to produce intermediate 201-2 (0.88 g, 79.9% yield) as a white solid. 1H NMR (400 MHz, CDCh) δ = 7.62 (s, 1 H), 7.11 (s, 1 H), 6.97 (s, 1 H), 6.70 (s, 1 H), 3.87 (s, 3 H), 2.46 (s, 3 H), 1.46 (s, 9 H).

[0309] A solution of intermediate 201-2 (0.83 g, 2.38 mmol) and Lawesson's reagent (964.0 mg, 2.38 mmol) in dioxane (5 mL) was stirred at 85°C for 16 h. The reaction mixture was concentrated under reduced pressure to produce a residue, which was purified by cro Petition 870250084579, dated 09 / 19 / 2025, p. 162 / 201 156 / 168 column photography on silica gel eluted with ethyl acetate (0% to 20%) in petroleum ether to produce intermediate 201-3 (0.50 g, 57.7% yield) as a yellow oil. LC-MS (ESI+): m / z 309.0 (M+H-56)+.

[0310] To a solution of intermediate 201-3 (0.50 g, 1.37 mmol) in DMF (5 mL), methyl bromoacetate (0.14 mL, 1.51 mmol) and TEA (0.23 mL, 1.64 mmol) were added. The mixture was stirred at 65°C for 3 h. To the cooled reaction mixture, water (20 mL) was added and the mixture was extracted with EtOAc (20 mL x 3). The combined organic layers were washed with brine (30 mL x 3), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by column chromatography on silica gel eluted with ethyl acetate (0% to 25%) in petroleum ether, to produce intermediate 201-4 (200.8 mg, 33.6% yield) in the form of a yellow oil. LC-MS (ESI+): m / z 381.0 (M+H-56)+.

[0311] To a solution of intermediate 201-4 (0.20 g, 0.46 mmol) in DCM (5 mL), TFA (1 mL) was added. The reaction was stirred at room temperature for 30 min. The mixture was evaporated to give the crude product, which was diluted with water (10 mL) and the mixture was adjusted to pH = 7-8 with saturated aqueous sodium bicarbonate solution. The mixture was extracted with DCM (20 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered on a celite pad, and the filtrate was concentrated under reduced pressure to produce intermediate 201-5 (139.0 mg, 99.3% yield) as a yellow solid, which was used in the next step without further processing. LC-MS (ESI+): m / z 305.0 (M+H)+ 1H NMR (400 MHz, CDCh) δ = 8.80 (s, 1 H), 7.13 (s, 1 H), 6.99 (s, 1 H), 3.89 (s, 3 H), 3.58 (s, 2 H), 2.37 (s, 3 H). Petition 870250084579, dated 09 / 19 / 2025, page 163 / 201 157 / 168

[0312] To a solution of intermediate 201-5 (149.1 mg, 0.49 mmol) in dioxane (2 mL), Lawesson's reagent (206.3 mg, 0.51 mmol) was added. The reaction was stirred at 65°C for 16 h. The mixture was concentrated under reduced pressure to produce a residue, which was purified by preparative TLC (PE / EtOAc = 5 / 1) to produce intermediate 201-6 (85.0 mg, 54.2% yield) as a yellow solid. LC-MS (ESI+): m / z 321.0 (M+H)+.

[0313] To a solution of intermediate 201-6 (85.0 mg, 0.27 mmol) in THF (5 mL) / water (2.5 mL), K2CO3 (92.0 mg, 0.67 mmol) and iodomethane (98.0 mg, 0.69 mmol) were added at 0°C. The mixture was stirred at room temperature for 2 h. Water (10 mL) was added to the reaction mixture and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was purified by preparative TLC (PE / EtOAc = 5 / 1) to produce intermediate 201-7 (72.0 mg, 0.22 mmol, 79.8% yield) as a yellow solid. LC-MS (ESI+): m / z 335.0 (M+H)+.

[0314] To a solution of intermediate 201-7 (69.0 mg, 0.21 mmol) in EtOH (1 mL), (1s,3s)-3-amino-1-methylcyclobutan-1-ol hydrochloride (85.0 mg, 0.63 mmol) and TEA (0.09 mL, 0.63 mmol) were added. The mixture was stirred at room temperature for 30 min and then at 60°C for 16 h. To the cooled reaction mixture, water (15 mL) was added and the mixture was extracted with EtOAc (15 mL x 3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered through a celite pad, and the filtrate was concentrated under reduced pressure to produce a residue, which was recrystallized in diethyl ether (10 mL) to produce the intermediate. Petition 870250084579, dated 09 / 19 / 2025, page 164 / 201 158 / 168 201-8 (50.0 mg, 61.5% yield) as a white solid. LC-MS (ESI+): m / z 388.1 (M+H)+.

[0315] To a solution of intermediate 201-8 (45.0 mg, 0.12 mmol) in DCM (2 mL), tribromoborane (0.36 mL, 0.36 mmol, 1 M in DCM) was added at -78°C. The reaction was stirred at -78°C for 3 h. The reaction was abruptly stopped with MeOH at -78°C and then the mixture was concentrated under reduced pressure at room temperature to yield the crude product, which was purified by preparative HPLC (Column: C18 OBD 10μm 19*250 mm; Mobile Phase: [0.1% FA in water - ACN]; B %: 5% - 10% ACN, 8.7 min) to yield compound 201. LC-MS (ESI+): m / z 374.1 (M+H)+ 1H NMR (400 MHz, DMSO-d6) δ= 7.32 - 7.10 (m, 1 H), 7.06 (s, 1 H), 6.99 (s, 1 H), 4.99 (br.s, 1 H), 4.02 - 3.90 (m, 1 H), 3.15 (s, 2 H), 2.39 - 2.30 (m, 2 H), 2.27 (s, 3 H), 2.04 - 1.92 (m, 2 H), 1.26 (s, 3 H).

[0316] The compounds below were prepared using a synthesis method similar to that described in Compound 201, substituting the appropriate starting materials, reagents, and reaction conditions. Compound No. Analytical data 202 LC-MS (ESI+): m / z 402.0 (M+H)+. 1H NMR: (400 MHz, DMSO-d6) δ = 10.50 (br,s, 1 H), 7.05 (s, 1 H), 6.98 (s, 1 H), 6.81 - 6.59 (m, 1 H), 5.01 - 4.88 (m, 1 H), 3.96 - 3.90 (m, 1 H), 2.36 - 2.31 (m, 2 H), 2.29 (s, 3 H), 2.06 - 1.98 (m, 2 H), 1.39 (s, 6 H), 1.26 (s, 3 H). 203 LC-MS (ESI+): m / z 348.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ = 10.69 (br,s, 1 H), 7.41 7.11 (m, 1 H), 6.19 (s, 1 H), 5.02 (br,s, 1 H), 4.51 (t, J = 8.4 Hz, 2 H), 3.98 - 3.90 (m, 1 H), 3.22 (s, 2 H), 3.05 (t, J = 8.4 Hz, 2 H), 2.45 - 2.32 (m, 2 H), 2.18 (s, 3 H), 2.01 - 1.95 (m, 2 H), 1.26 (s, 3 H). Petition 870250084579, dated 09 / 19 / 2025, page 165 / 201 159 / 168 204 LC-MS (ESI+): m / z 340.0 (M+H)+. RMN de 1H: (400 MHz, DMSO-d6) δ = 10,33 (br,s, 1 H), 7,18 7,02 (m, 1 H), 6,78 - 6,70 (m, 2 H), 5,00 (br,s, 1 H), 3,95 - 3,88 (m, 1 H), 3,12 (s, 2 H), 2,39 - 2,34 (m, 2 H), 2,18 (s, 3 H), 1,99 - 1,88 (m, 2 H), 1,26 (s, 3 H). 205 LC-MS (ESI+): m / z 361,2 (M+H)+. RMN de 1H (400 MHz, CD3CN) δ = 8,29 (s, 1 H, from HCOOH), 6,22 (s, 1 H), 4,57 (t, J = 8,8 Hz, 2 H), 4,38 - 4,29 (m, 1 H), 3,20 (s, 2 H), 3,09 (t, J = 8,8 Hz, 2 H), 3,01 - 2,99 (m, 1 H), 2,86 - 2,78 (m, 2 H), 2,73 - 2,68 (m, 1 H), 2,48 (s, 3 H), 2,41 (s, 3 H), 2,00 - 1,98 (m, 1 H), 1,76 - 1,71 (m, 3 H). 206 LC-MS (ESI+): m / z 339,1 (M+H)+. RMN de 1H (400 MHz, CD3OD) δ = 6,78 (s, 1H), 6,74 (s, 1H), 4,31 - 4,12 (m, 1H), 3,28 (s, 2H), 2,71 - 2,58 (m, 2H), 2,53 2,42 (m, 2H), 2,24 (s, 3H), 1,52 (s, 3H). 207 LC-MS (ESI+): m / z 339,0 (M+H)+. RMN de 1H (400 MHz, CD3OD) δ = 6,77 (s, 1H), 6,73 (s, 1H), 4,54 - 4,40 (m, 1H), 3,34 (s, 2H), 2,85 - 2,73 (m, 2H), 2,35 2,25 (m, 2H), 2,24 (s, 3H), 1,56 (s, 3H). Example B-1: NLRP3 inflammosome assay Reagent and Material Reagent Name Article Number Assay Buffer 1X 250 mol / L HEPES (pH 7.4), Sigma-H3375 10 mmol / L KCl, Sigma-P9333 5 mmol / L MgCl2, Sigma-449172 Wash Buffer Same as assay buffer, store at 4°C NLRP3 Cell Lysate Prepared by WuXi AppTec [3H]-MCC950 Pharmaron-TRQ42137 MCC950 TOCRIS-5479 Assay Plate / Source 96-well plate (Corning-3631) GF / B plate PerkinElmer-600517 DMSO Sigma-472301 Petition 870250084579, dated 09 / 19 / 2025, page 166 / 201 160 / 168 Microscint-20 PerkinElmer-6013621 Test Procedure

[0317] 1) Dilutions of the compound for the IC50 test: Starting from 100 μM, triple dilutions were performed. Then, 11 doses were distributed at a concentration of 1% DMSO. 9 pL of the compound (10 mM stock from the compound management team) were added to the 384LDV plate. Echo was used for dilution and the compounds were transferred to the assay plate at 100 μM (maximum concentration of 1% DMSO, 1.25 μL).

[0318] 2) Dilution of the radioligand: the working concentration was 25 nM of [3H]-MCC950. 1 μL of [3H]-MCC950 (stock of 23 μM) was added to 919 μL of assay buffer.

[0319] 3) Prepare and transfer 100 μL of insect cell lysate to a 96-well assay plate. Final concentration: 15 μg / well for IC50 test.

[0320] 4) Transfer 25 μL of the diluted binder to the test plate.

[0321] 5) Cover the test plates with adhesive tape and incubate for 1.5 hours at room temperature with gentle stirring.

[0322] 6) Using the Packard Harvester, filter the test plate wells through the GF / B filter plate wells. Wash 8 times with cold wash buffer (4°C, 0.4 mL per well per wash).

[0323] 7) Place the filter plates in an oven for 0.5 hours at °C.

[0324] 8) Seal the bottom of the dry filter plates with adhesive tape. Distribute 50 μL of Microscint-20 into each well of the filter plate and cover the GF / B plate with TopSeal-A.

[0325] 9) Microbeta was used to count the signal.

[0326] 10) Microbeta configuration: The counting time was 30 seconds per well. Petition 870250084579, dated 09 / 19 / 2025, page 167 / 201 161 / 168 Example B-2: NLRP3 Inflammasome Activation Assay in Human Monocytes Day 1: Isolate human monocytes from PBMCs.

[0327] Isolate monocytes from PBMCs using the human panmonocyte isolation kit and an LS column. Resuspend the monocytes in RPMI 1640 medium and count the cells. Then, seed the monocytes into 96-well plates and incubate at 37°C, 5% CO2 overnight. Day 2: Stimulate the cells with LPS and ATP.

[0328] Remove the culture medium and pretreat the monocytes by adding different concentrations of compounds or DMSO as a control to the corresponding wells and incubate at 37°C, 5% CO2. The compounds and DMSO are diluted using serum-free RPMI 1640 medium.

[0329] Add serum-free RPMI 1640 medium containing LPS to all wells and incubate the cells for some time at 37°C, 5% CO2.

[0330] At the end of the incubation, the cells were stimulated with ATP is retained for some time, except for the cells in the negative control wells. Transfer the supernatants to new plates and store at 80°C. Day 3: Run ELISA

[0331] Execute Elisa according to the BD procedures Biosciences. Example B-3: THP-1 assay for IL-Iβ release

[0332] Culture of THP-1 cells in RPMI1640 medium, 10% FBS, 1% PS, 55 μΜ β-Mer at 37°C and 5% CO2 in incubator. Detection of IL-Iβ release

[0333] 1) Seed THP-1 in complete RPMI 1640 medium containing Petition 870250084579, dated 09 / 19 / 2025, pp. 168 / 201 162 / 168 PMA in 96-well plates coated with poly-L-lysine and incubate for 24 hours.

[0334] 2) Remove the medium, wash the differentiated THP-1 cells with PBS and add FBS-free RPMI 1640 medium.

[0335] 3) Add LPS and incubate for 3 hours at 37°C and 5% CO2 in an incubator.

[0336] 4) Add the compounds and incubate for 30 minutes at 37°C and 5% CO2 in an incubator.

[0337] 5) Add Nigericin and incubate for 1 hour at 37°C and 5% CO2 in an incubator.

[0338] 6) Collect the supernatant to test IL-Iβ by Elisa. Data Analysis

[0339] a) Verification of the robustness of the DMSO test and low control data: H = Mean (DMSO) L = Average (Low control) SD (H) = Standard Deviation (DMSO) SD (L) = STANDARD DEVIATION (Low control) % CV (H) = 100 * (SD_H / Ave_H) % CV (L) = 100 * SD_L / Ave_L Z'=1-3*(SD_H+ SD_L) / (Ave_H - Ave_L) % variation = Sample / Average_L*100

[0340] b) Adjust the IC50 of the compound from the non-linear regression equation: Y = Base + (Top-Base) / (1+10A((LogIC50-X)*Hill Slope)) X: concentration of the compound Y: % variation Top and Base: Plateaus in the same units as Y logIC50: same units as the logarithm of X Hill Slope: Slope Factor or Hill Slope Petition 870250084579, dated 09 / 19 / 2025, page 169 / 201 163 / 168

[0341] The IC50 data for THP-1 IL-Iβ for selected compounds are shown in Table 3. Example B-4: ADP-Glo ​​Assay of NLRP3 Enzyme Activity

[0342] The NLRP3 activity test experiment, measuring the hydrolysis of NLRP3 on the substrate ATP using the ADP-Glo ​​assay. First, after adding an inhibitor containing 0.5% DMSO with Echo, add 5 μL of the NLRP3 enzyme solution (ICE, YM2306T-H06MHS) to each well, centrifuge at 1000 rpm for 1 min at room temperature and allow to react for 10 min. Then, add 5 μL of the ATP substrate solution (Promega, V915A) to each well for 90 min at room temperature; NLRP3 and ATP were prepared in HEPES 50 mM, MgCb 10 mM, Brij-35 0.01%, EGTA 1 mM and DTT 2 mM buffers at final concentrations of 15 nM and 1 μM, respectively. Subsequently, 10 pL of ADP-Glo ​​reagent solution (Promega, V9102) were added to each test well, centrifuged at 1000 rpm for 1 min, and then incubated at room temperature for 45 min.Finally, 20 µL of ADP-Glo ​​detection solution (Promega, V9102) were added to each well, centrifuged at 1000 rpm for 1 min, and reacted for 45 min at room temperature. Luminescence signal values ​​were read using a BMG instrument, and IC50 values ​​were determined by fitting the data to an S-shaped dose-response curve using nonlinear regression. Data from the ADP-Glo ​​Enzyme Assay for selected compounds are shown in Table 3. Example B-5: hERG screening assay using electrophysiological hand patch clamp

[0343] Cell lines: hERG-CHO cells

[0344] Method: CHO cells that stably express the hERG transcript were investigated using the em clamp technique. Petition 870250084579, dated 09 / 19 / 2025, pp. 170 / 201 164 / 168 whole-cell manual plastid. hERG-CHO cells were cultured in 35 mm plates to a maximum confluence of 70-80% at 37°C and 5% CO2 in the incubator. The culture medium (F12 medium (Invitrogen 11765062, ThermoFisher, USA) supplemented with 10% fetal bovine serum (Invitrogen 10099141, ThermoFisher, USA), 100 ug / mL G418 (Invitrogen 11811023, ThermoFisher, USA) and 100 ug / mL Hygromycin B (Invitrogen 10687010, ThermoFisher, USA)) was removed and the hERG-CHO cells were washed with extracellular solution (in mM): 140 NaCl, 5 KCl, 1 CaCl2, 1.25 MgCb, 10 HEPES and 10 Glucose, pH 7.4 with NaOH. Next, the cells were dissociated with 0.25% trypsin-EDTA for 3 to 5 min. After this, the digestion solution was removed and the cells were resuspended in the extracellular solution using a pipette, pipetting up and down several times. The resuspended cells were transferred to plates for registration and the cells were perfused with extracellular solution.Electrodes (a 3-5 MegOhm tip resistance) were taken from a borosilicate gram pipette (Sutter BF150-86-10 instrument) and filled with intracellular solution (in mM): 140 KCl, 1 MgCl2, 1 CaCl2, 10 EGTA, and 10 HEPES, pH 7.2 with KOH. Data were obtained using a patch clamp amplifier; signals were filtered at 2 kHz and sampled at 10 kHz frequencies using pClamp 10 software. Cells were maintained at -100 mV, and hERG potassium currents were activated by a depolarization potential of +20 mV for 2 s, followed by a repolarization potential of -50 mV for 1 s, then returning to the holding potential. Experiments were performed at room temperature.

[0345] Data analysis: The data were retrieved and analyzed using pClamp 10, GraphPad Prism 8, and Excel software. The peak amplitude of hERG currents was measured using clampfit and exported to Excel and GraphPad Prism 8 for subsequent analysis. Petition 870250084579, dated 09 / 19 / 2025, page 171 / 201 165 / 168 te. The concentrations of the compounds to produce 50% blockade of the currents (IC50) were obtained by fitting the normalized concentration-inhibition relationships to the equation in the Prism 8 software, as shown below: Y = Base + (Top-Base) / (1 + 10A((LogIC50 X)*Hill Slope)) where Y is the % inhibition corresponding to X, [X] is the logarithmic value of the compound concentration in the external solution, and Hill Slope is the Hill coefficient. The inhibition ratio was calculated using the equation: Inhibition = (1-I / Io)*100%, where Io and I are the current amplitude measured in the control and in the presence of the compounds, respectively. n is not less than 2 cells for each concentration.

[0346] Results: IC50 of compounds in hERG and concentration-response curves

[0347] hERG inhibition data for selected compounds are shown in Table 4. TABLE 3. IC50 of the ADP-Glo ​​Enzyme Activity Assay (nM): 0 <A<10; 10<B<100; 100<C<1000; 1000<D. IC50 of THP-1 IL-Iβ (nM): 0 <A<10; 10<B<100; 100<C<1000; 1000<D. No. of the Compound NLRP3_ADP-Glo_IC50 (nM), Example B-4 Power, THP-1 IL-Iβ, IC50 (nM), Example B-3 1 BA 2 A 3 A 5 C 6 A 7 B 8 BB 9 B 10 BB Petition 870250084579, dated 09 / 19 / 2025, p. 172 / 201 166 / 168 11 B 16 B 17 B 20 B 21 B 22 C 23 BA 24 C 25 BB 26 C 28 BA 29 B 30 BB 31 BB 32 D 33 D 34 D 35 BB 36 CC 37 BB 39 C 40 BB 41 C 42 D 43 D 45 BB 46 AA 47 AA 48 BC Petition 870250084579, dated 09 / 19 / 2025, p. 173 / 201 167 / 168 49 D 50 BB 51 BA 52 D 54 A 55 C 56 C 57 BB 58 BB 59 AA 60 BB 61 B 62 C 63 C 64 B 65 C 66 BB 67 BB 68 BB 69 C 70 C 71 B 72 A 201 BB 202 BB 203 BB 204 BA 205 AA 206 BB Petition 870250084579, dated 09 / 19 / 2025, p. 174 / 201 168 / 168 207 C TABLE 4. hERG inhibition Compound No. Inhibition of hERG_IC50 (μM), Example B-5 8 19.1 10 >30 28 29.4 31 >30 59 >30

[0348] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or alterations thereof are suggested to persons skilled in the art and should be included within the spirit and scope of this application and the scope of the appended claims. All publications, patents and patent applications cited herein are incorporated by reference in their entirety for all purposes. Petition 870250084579, dated 09 / 19 / 2025, p. 175 / 201

Claims

1 / 12 CLAIMS 1. Compound having the structure of Formula (A) or Formula (B), or a pharmaceutically acceptable salt or a stereoisomer thereof: , , Formula (A), Formula (B), characterized in that; Y is C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl or 5- to 9-membered heteroaryl, wherein the C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C6-C10 aryl or 5- to 9-membered heteroaryl is optionally replaced by one or more R6; X is NRX, -O-, -S-, -S(O)- or -S(O)2-; RX is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members; wherein each of the alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl groups is optionally substituted by 1 to 4 substituents independently selected from Re;Each R1A and R1B is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl; or R1A and R1B are employed together to form an oxo; or R1A and R1B are employed together to form a 4- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl; each of which is optionally substituted by one or more R11; each R11 is independently halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1 Petition 870250084579, dated 09 / 19 / 2025, page. 176 / 201 2 / 12 C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; R3 is phenyl, 5- to 12-membered heteroaryl, C3-C12 cycloalkyl, 4- to 12-membered heterocycloalkyl or C1-C6 alkyl; each of which is optionally replaced by one or more R8;Each R8 is independently a halogen, -OH, -CN, -NO2, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, SF5, S(=O)Ra, -S(=O)2Ra, -S(=O)(=NRb)Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, N=S(=O)RcRd, -P(=O)RcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl, C6-C10 aryl or 4- to 6-membered heterocycloalkyl, wherein each of the alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl, aryl or heterocycloalkyl groups is optionally substituted by 1 to 4 substituents independently selected from Re; RZN is hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; or RX and RZN, together with the atoms to which they are attached, form a 5- to 8-membered heterocycloalkyl, which is optionally substituted by one or more R13;or R3 and RZN, together with the atoms to which they are attached, form a 5- to 13-membered heterocycloalkyl group, which is optionally substituted by one or more R13 groups; each R13 group is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1C6 hydroxyalkyl, or C1-C6 aminoalkyl group; each R6 is independently halogen, -CN, -NO2, -OH, ORa, -SH, -SRa, -SF5, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -C(=O)Ra, C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydro Petition 870250084579, dated 19 / 09 / 2025, p. 177 / 201 3 / 12 xyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2C6 alkynyl or C3-C8 cycloalkyl, wherein each of alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, alkenyl, alkynyl or cycloalkyl is optionally substituted with 1 to 4 substituents independently selected from Re;or two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R12s; each R12 is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; each Ra is, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re;each Rb is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, wherein each of alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re;Rc and Rd are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re; or Rc and Rd are employed together with the atom to which they are attached to form a heterocycloalkyl group, wherein the heterocycloalkyl group is optionally substituted by 1 to 4 substituents independently selected from among Re;and each Re is, independently, halogen, oxo, -CN, -OH, S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, NH2, = -CH3,) -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or C3-C6 cycloalkyl.; 2. A compound having the structure of Formula (I) or Formula (V), or a pharmaceutically acceptable salt or a stereoisomer thereof: Formula (I), Formula (V), characterized in that; X is NRX, -O-, -S-, -S(O)- or -S(O)2-; RX is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 heteroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or heterocycloalkyl of 4 to 6 members; wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re; Each R1A and R1B is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl or C1-C6 aminoalkyl; Petition 870250084579, dated 09 / 19 / 2025, page 179 / 201 5 / 12or R1A and R1B are employed together to form a 4- to 8-membered C3-C8 cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R11; each R11 is independently halogen, -OH, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; or R1A and R1B are employed together to form an oxo; R3 is phenyl, 5- to 12-membered heteroaryl, C3-C12 cycloalkyl, 4- to 12-membered heterocycloalkyl or C1-C6 alkyl; each of which is optionally substituted by one or more R8;each R8 is independently halogen, -OH, -CN, -NO2, ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SH, -SRa, SF5, S(=O)Ra, -S(=O)2Ra, -S(=O)(=NRb)Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, N=S(=O)RcRd, -P(=O)RcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl, wherein each alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re; RZN is hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; or RX and RZN, together with the atoms to which they are attached, form a 4- to 8-membered ring that is optionally substituted by one or more R13;each R13 is independently halogen, -OH, -CN, -NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroalkyl or C1-C6 aminoalkyl; R6A is -OH, -OCF2H, -CF2H or -CF3; each R6 is independently halogen, -CN, -NO2, -OH, ORa, -SH, -SRa, -SF5, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, NRbC(=O)NRcRd, -NRbC(=O)Ra, -NRbC(=O)ORb, -C(=O)Ra, C(=O)ORb, -C(=O)NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C8 cycloalkyl, wherein each of alkyl, haloalkyl, hydroxyalkyl, heteroalkyl, aminoalkyl, alkenyl, alkynyl or cycloalkyl is optionally substituted with 1 4 independently selected substituents from Re;or two R6s are employed together with the atoms to which they are attached to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R12s; each R12 is independently a halogen, -OH, -CN, NO2, -ORa, -NRcRd, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl or 4- to 6-membered heterocycloalkyl; each Ra is, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re;each Rb is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, wherein each of alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re;Rc and Rd are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein each alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by 1 to 4 substituents independently selected from Re; or Rc and Rd are employed together with the atom to which they are attached to form a heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted by 1 to 4 substituents independently selected from Re;each Re is independently halogen, oxo, -CN, -OH, S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or C3-C6 cycloalkyl; ep is 1, 2, 3 or 4; / °H NN X- / HOy %— / vnh\ provided that the compound is not « F Petition 870250084579, of 19 / 09 / 2025, p. 182 / 201 8 / 12; 3. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R6A is -OH.

4. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R6A is -CF2H or -CF3.

5. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R6A is -OCF2H.

6. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R3 is a 4- to 12-membered heterocycloalkyl group; which is optionally substituted by one or more R8 groups.

7. Compound according to claim 6, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that F 8. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R3 is C3C12cycloalkyl, which is optionally substituted by one or more R8.

9. Compound according to claim 8, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized by the fact that R3 OH OH 10. A compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that each R6 is independently halogen, -CN, -NO2, -OH, -C(=O)Ra, -ORa, -SH, -SRa, SF5, -NRcRd, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1C6 aminoalkyl or C3-C8 cycloalkyl.

11. Compound according to claim 10, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that each R6 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 hydroxyalkyl.

12. Compound according to claim 10 or 11, or a pharmaceutically acceptable salt or stereoisomer thereof, characterized in that each R6 is independently methyl or CF3.

13. A compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that two R6s are employed together to form an aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R12s.

14. Compound according to claim 13, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that two R6s are employed together to form a cycloalkyl or heterocycloalkyl, each of which is optionally substituted by one or more R12s.

15. Compound according to claim 14, either a pharmaceutically acceptable salt or a stereoisomer thereof, characterized by the fact that ' * is \= / 1 or \.

16. Compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R1A is hydrogen, halogen or C1-C6 alkyl (e.g., methyl).

17. A compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R1B is hydrogen or methyl.

18. Compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R1A and R1B are employed together to form a C3-C8 cycloalkyl.

19. Compound, according to any one of claims 1 to 18, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that R1A and R1B are employed together to form an oxo.

20. A compound, according to any one of claims 1 to 19, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that RX and RZN, together with the atoms to which they are attached, form a 5- to 8-membered ring that is optionally replaced by one or more R13.

21. A compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that RZN is hydrogen. Petition 870250084579, dated 19 / 09 / 2025, p. 185 / 201 11 / 12 22. A compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that X is -S-, -S(O)- or S(O)2-.

23. Compound according to claim 22, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that X is -S-.

24. A compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt or a stereoisomer thereof, characterized in that it is a compound of Table 1 or Table 2 or a pharmaceutically acceptable salt or a stereoisomer thereof.

25. Compound, characterized in that it has the structure of Formula (III), (IIIa) or (VIa), or a pharmaceutically acceptable salt or a stereoisomer thereof, as described in this document.

26. Pharmaceutical composition, characterized in that it comprises a compound as defined in any one of claims 1 to 25, or a pharmaceutically acceptable salt or a stereoisomer thereof, and at least one pharmaceutically acceptable excipient.

27. A method for modulating or inhibiting the activity of the NOD-like receptor (NLR) family pyrin domain-containing protein 3 (NLRP3) in an individual, characterized in that it comprises administering to the individual a compound as defined in any one of claims 1 to 25, or a pharmaceutically acceptable salt or a stereoisomer thereof, or a pharmaceutical composition as defined in claim 26.

28. Method for treating a disease or disorder in which NLRP3 signaling contributes to the pathology and / or symptoms and / or progression of the disease or disorder, characterized in that it comprises administering a therapeutically effective amount of a compound according to any one of claims 1 to 25, or a pharmaceutically acceptable salt or a stereoisomer thereof, or a pharmaceutical composition as defined in claim 26.

29. A method according to claim 28, characterized in that the disease or disorder is an autoimmune or autoinflammatory disease, or in that the disease or disorder is obesity.

30. A method for reducing body weight in an individual in need thereof, characterized in that it comprises administering to the individual a compound, as defined in any one of claims 1 to 25, or a pharmaceutically acceptable salt or a stereoisomer thereof, or a pharmaceutical composition, as defined in claim 26. Petition 870250084579, dated 19 / 09 / 2025, pp. 187 / 201