COMPOSTO, COMPOSIÇÃO FARMACÊUTICA, USO DE UM COMPOSTO, E, MÉTODO PARA TRATAR OU PREVENIR UM DISTÚRBIO

Abstract

There is provided a compound having the Formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug thereof. A pharmaceutical composition comprising the compound or Formula (I) or the pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier, diluent or excipient is also provided. The compound or pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition comprising the same, can be used for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated. In some embodiments, the compound or pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition comprising the same, can be used for the treatment or prevention of pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough, or acute lung injury.

Description

[001] The present application claims priority over provisional application no. US 63 / 491,473, filed on March 21, 2023, which is incorporated herein by reference. TECHNICAL FIELD

[002] The technical field refers generally to compounds, compositions and their uses in the treatment of disorders and conditions in which the inhibition of Acid Sensitive Ion Channels, also called ASICs, is indicated. For example, the application refers to thiophene-substituted fused cyclohexanone derivatives, pharmaceutical compositions comprising them and their use as ASIC inhibitors. BACKGROUND

[003] Since the discovery of acid-sensitive ion channels (ASICs) in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant importance. ASICs play important roles in mediating the sensation of pain, and their activity contributes to diseases such as stroke, inflammation, arthritis, cancer, and migraine.

[004] ASICs are permeable to Na+ ions (and other cations), are activated by low extracellular pH, and are widely expressed in the central nervous system (CNS) and peripheral nervous system (PNS). ASICs are formed by homo- and heterotrimeric sets of subunits including ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3. ASIC1a are expressed in the PNS and CNS, ASIC1b in the PNS.

[005] Tissue injuries and inflammation cause acidosis, and acidification is considered a significant contributing factor to pain. Petition 870250103125, dated 11 / 11 / 2025, p. 7 / 470 / 431 associated. The literature indicates that ASIC inhibitors can relieve pain in a variety of clinical conditions. Furthermore, because their mechanism of action is distinct, ASIC antagonists may provide new treatment options for patients who do not benefit from or cannot tolerate the adverse side effects of current analgesics.

[006] Therefore, it is important to develop new small molecule inhibitors that are specific for ASICs to provide more useful therapeutic agents in the treatment of ASIC-related disorders or conditions, such as pain. SUMMARY

[007] In one aspect, the present application relates to a compound of Formula (I), or a pharmaceutically acceptable salt, solvate or prodrug thereof, where: Raé -NH2, -NH-OH, -OH, -NHRbou -NRcRd; Rbé C1-C6 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocycloalkyl, wherein the C1-C6 alkyl is optionally substituted by 1 to 3 halogens, 1 to 3 -OH, -OC1-C3 alkyl, -COOH, or cyclopropyl optionally substituted by -OH, and wherein the C3-C6 cycloalkyl is optionally substituted by -CN; Rce Rdformam with the nitrogen to which they are attached a 4-membered heterocycloalkyl, wherein the 4-membered heterocycloalkyl is optionally substituted by at least one of -OH and C1C3alkyl; Petition 870250103125, dated 11 / 11 / 2025, p. 8 / 470 / 431 represents one of the following residues Ao a A12 a® ,A® ,A™,AouAl2; given that: R is H, C1-C6 alkyl or phenyl; R1 and R2 are independently -CN, C6-C10 aryl, C1-C6 alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, and each C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents, each C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents, with the condition that when Ra is OH, CZZ represents Ao, and R1 is , then R2 in the Ao residue is different / OH from O each R5 is independently C1-C6alkyl, and each C1C6alkyl is optionally substituted by 1 to 3 R9 substituents; each R6 is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl or C6-C10aryl; Each R7 is independently -OH, -C(O)Rn, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), -N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC1 Petition 870250103125, dated 11 / 11 / 2025, p. 9 / 470 / 431 C3C-alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, and each C3C-cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl or oxo; each R8 is independently a halogen, C1-C-alkyl, -OC1-C-alkyl, C3-C6-cycloalkyl, or 5- to 10-membered heteroaryl, wherein each -OC1-C-alkyl is optionally substituted by -OC1-C4-alkyl, and each 5- to 10-membered heteroaryl is optionally substituted by C1-C4-alkyl; each R22 is independently C1-C6 alkyl optionally substituted with phenyl; each R9 is independently -OH, -C(O)R15, C3C-cycloalkyl, -CN, C-C1-Aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OC1-C-alkyl, -SC1-C-alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, wherein each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl, and each -OC1C6alkyl is optionally substituted by -OC1-C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or a 4- to 6-membered heterocycloalkyl; each R20 is independently a 5- to 10-membered C1-C6 alkyl or heteroaryl group, wherein each C1-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents and each 5- to 10-membered heteroaryl group is optionally substituted by -OH or -NH (cyclopropyl); each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, or -SPh, with each C1-C4 alkyl being optionally replaced by -OH; each R13 is independently halogen, C1-C4 alkyl, C3C6 cycloalkyl, -OH, -OC1-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1-C6 alkyl, NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, wherein each -OC1 Petition 870250103125, dated 11 / 11 / 2025, page 10 / 470 / 431 C-alkyl, -SCi-C-alkyl, -S(O)2Ci-C6-alkyl, -NH(C1-C4-alkyl), and -N(C1C4-alkyl)2 is optionally replaced by 1 to 3 R9 substituents; Each R14 is independently halogen, -OC1-C4 alkyl, or C3-C6 cycloalkyl; each R15 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or a 4- to 6-membered heterocycloalkyl; R4 is a C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, partially unsaturated heterocyclic group of 7 to 10 members or heteroaryl of 5 to 10 members, wherein C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl and heteroaryl of 5 to 10 members are optionally substituted by 1 to 3 R10 substituents, with the condition that: (i) when Ra is -OH, -NH2, or , and — represents (i) If Ra represents A2, then R4 in residue A2 is different from -CH3; and (ii) if Ra represents -NH2 and xA·' represents A3, then R4 in residue A3 is different from -C(CH3)3; each R10 is independently C1-C4 alkyl, halogen, -OC1C6 alkyl, -NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, with each C1C4 alkyl being optionally substituted by 1 to 3 halogens; R2a is C1-C6 alkyl, C3-C8 cycloalkyl, or C6-C10 aryl, wherein C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl is optionally substituted by 1 to 3 R10 substituents; R1 and R2 are independently -CN, C6-C10aryl, C1C6alkyl, C3-C8cycloalkyl, -C(O)NH2, -C(O)NHR5, or -C(O)OC1-C6alkyl, wherein each C1-C6alkyl is optionally substituted by 1 to 3 R16 substituents and each C6-C10aryl is optionally substituted by 1 to 3 R17 substituents; each R16 is independently -OH, -C(O)NH2, -C(O)NH(C1C4alkyl), C3-C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), heterocycloalkyl Petition 870250103125, dated 11 / 11 / 2025, p. 11 / 470 / 431 of 4 to 6 members, -NH(C(O)C1-C6alkyl) or -OCi-C4alkyl(OCiC4alkyl), wherein each C3-C6cycloalkyl is optionally substituted by 1 to 3 R18 substituents, each 5 to 10 member heteroaryl is optionally substituted by 1 to 3 R21 substituents and each 4 to 6 member heterocycloalkyl is optionally substituted by C1-C4alkyl; each R17 is independently a halogen, C1-C6 alkyl, -OC1C6 alkyl or 5- to 10-membered heteroaryl, wherein each 5- to 10-membered heteroaryl is optionally substituted by C1-C4 alkyl; Each R18 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, or -OC1-C4 alkyl; Each R21 is independently halogen or C1-C4 alkyl; R4a is C1-C6 alkyl or C3-C8 cycloalkyl, and each C1-C6 alkyl and C3-C8 cycloalkyl are optionally replaced by 1 to 3 R19 substituents; each R19 is independently halogen, -OH, -OC1C4alkyl, -SC1-C4alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl); R1be and R2c, together with the carbon atom to which they are attached, form a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and wherein the 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group is optionally substituted by oxo (=O), oxime (=NOH), C1-C3 alkoxyoxime (= N-OC 1-C3 alkyl), or 1 to 3 substituents independently selected from -OH and -CF3; R2d and R4b, together with the carbon atoms to which they are attached, form a 4- to 14-membered C3-C8 cycloalkyl or heterocycloalkyl, and the C3-C8 cycloalkyl is optionally substituted by 1 to 3 Petition 870250103125, dated 11 / 11 / 2025, p. 12 / 470 / 431 substitutes R19; and R1 and R3, together with the carbon atoms to which they are attached, form a 4- to 14-membered C3-C8 cycloalkyl or heterocycloalkyl, and the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents.

[008] In some embodiments, the compound of Formula (I) may be a compound of Formula (Ia), of Formula (Ia'), of Formula (Ib), of Formula (Ib'), of Formula (Ic), of Formula (Ic'), of Formula (Id), of Formula (Id'), of Formula (Ie), of Formula (Ie'), of Formula (If), of Formula (If') or of Formula (Ig), as described herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[009] In some embodiments, the compound of Formula (I) may be a compound from Table 1 of the present description, or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[0010] Another aspect relates to pharmaceutical compositions comprising: a compound, as defined herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof; and a pharmaceutically acceptable carrier, diluent or excipient.

[0011] An additional aspect relates to the use of a compound, as defined herein, or a salt, solvate or pharmaceutically acceptable prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASIC inhibitor is indicated. This aspect also relates to a compound, as defined herein, or a salt, solvate or pharmaceutically acceptable prodrug thereof, for use in the treatment or prevention of a disorder for which an ASIC inhibitor is indicated. Similarly, this aspect relates to a method for treating or preventing a disorder for which an ASIC inhibitor is indicated comprising administering to a patient in need thereof a compound, Petition 870250103125, dated 11 / 11 / 2025, page 13 / 470 / 431 as defined herein, or a salt, solvate or pharmaceutically acceptable prodrug thereof. In one embodiment, the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

[0012] An additional aspect relates to the use of a compound, as defined herein, or a salt, solvate or pharmaceutically acceptable prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough and acute lung injury.This aspect also refers to a compound, as defined herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for use in the treatment or prevention of a selected disorder among pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough and acute lung injury.Similarly, this aspect refers to a method for treating or preventing a selected disorder among pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, comprising administering to a patient in need thereof a compound, as defined herein, or a pharmaceutically acceptable salt, solvate, or prodrug thereof. In one embodiment, the disorder is pain, such as inflammatory pain or neuropathic pain. In another embodiment, the disorder is neuropathic pain. BRIEF DESCRIPTION OF THE FIGURES Petition 870250103125, dated 11 / 11 / 2025, page 14 / 470 / 431

[0013] Figure 1 shows a dose-dependent antinociceptive effect of Compound 61 (A, B) and Compound 63 with naproxen as a positive control (C, D) in the carrageenan model in rats (upper and lower left graphs: thermal hyperalgesia response; upper and lower right graphs: mechanical allodynia response). Compound 61 responses are from two independent studies combined. Data are expressed as mean ± standard deviation of the mean. * p<0.05, ** p<0.01, *** p<0.001.

[0014] Figure 2 shows a dose-dependent antinociceptive effect of Compound 61 in the Chronic Constriction Injury (CCI) model in rats (thermal hyperalgesia response (A); and mechanical allodynia response (B)). Data are expressed as mean ± standard deviation of the mean. * p<0.05, ** p<0.01, *** p<0.001.

[0015] Figure 3 shows a dose-dependent antinociceptive effect of Compound 63 in the rat CCI model evaluating thermal hyperalgesia responses. Data are expressed as mean ± standard deviation of the mean. * p<0.05, ** p<0.01, *** p<0.001. DETAILED DESCRIPTION General definitions

[0016] All technical and scientific terms used in the present invention have the same meaning commonly understood by one skilled in the art to which the present technology relates. For convenience, the meanings of certain terms and phrases used in the present invention are provided below.

[0017] To the extent that the definitions of terms in the publications, patents and patent applications incorporated herein by reference are contrary to the definitions presented in this descriptive report, the definitions in this descriptive report shall prevail. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter disclosed. Petition 870250103125, dated 11 / 11 / 2025, page 15 / 470 / 431

[0018] The terminology used herein is intended to describe specific embodiments only and is not intended to be limiting. It should be noted that the singular forms a, an, or also include plural forms unless the content clearly indicates otherwise. Thus, for example, reference to a composition containing a compound also includes a mixture of two or more compounds. It should also be noted that the term or is generally employed in its inclusive and / or sense unless the content clearly indicates otherwise. Furthermore, insofar as the terms including, includes, having, has, with, or variants thereof are used in the detailed description and / or claims, such terms are intended to be inclusive in a manner similar to the term comprising.

[0019] The term approximately means within an acceptable range of error for the specific value, as determined by one skilled in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, approximately may mean within 1 or more than 1 standard deviation, according to practice in the art. Alternatively, approximately may mean a range up to 20%, preferably up to 10%, more preferably up to 5%, and even more preferably up to 1% of a given value. Alternatively, particularly with regard to biological systems or processes, the term may mean within an order of magnitude, preferably within 5 times, and more preferably within 2 times of a value.When specific values ​​are described in the application and claims, unless otherwise indicated, the term "approximately" should be assumed to mean within an acceptable error range for the specific value. Compounds

[0020] This application relates to innovative compounds of general formula (I) Petition 870250103125, dated 11 / 11 / 2025, p. 16 / 470 / 431 (a jf ^NH2 S (I) or pharmaceutically acceptable salts, solvates or prodrugs thereof, with Rae v—will be defined in more detail below.

[0021] The compounds described in this application therefore encompass those represented by the chemical structure of Formula I, with reference to any of the applicable embodiments described below, and exemplary compounds such as Compounds 4, 8, 9, 14 to 39, 47 to 54, 59, 60a, 60b, 61 to 72, 75, 81 to 84, 89, 91, 97, 101, 108, 109, 119 to 136, 138 to 150, 154, 155, 163, 168 to 170, 173 to 175, 178 to 181, 183, 189 to 195, 197 to 202, 211 to 216, 219, 221, 227 to 232, 237, 238, 239, 245 to 251, 253, 254, 255, 257, 258, 263, 264, 271, 272, 273, 278 to 281, 287, 288, 290, 291, 297, 298, 305, 306, 313, 314, 321, 322, 330, 331, 337 to 349, 352 to 358, 360, 362, 371, 378, 391 to 393, 394a, 394b, 395a, 395b, 396, 397, 401 to 403, 406 to 408, 412 to 414, 416, 418, 422, 427 to 431, 433, 434, 445 to 454, 462 to 466, 468 to 476, 478 to 483, 486, 488, 489, 492, 495 to 498, 511-515, 520, 523, 524 or 534 from Table 1, as well as their pharmaceutically acceptable salts, solvates and prodrugs, when applicable.Compounds can be identified by their chemical structure or by their chemical name. In a case where the chemical structure and the chemical name conflict, the chemical structure will prevail.

[0022] Unless otherwise indicated, the structures represented in the present invention shall also include all isomeric forms (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers, as well as enantiomeric, diastereomeric, and geometric mixtures (or Petition 870250103125, dated 11 / 11 / 2025, page 17 / 470 / 431. The conformational forms of the present compounds are within the scope of the present description. Unless otherwise indicated, all tautomeric forms of the compounds are within the scope of the present description. Furthermore, unless otherwise indicated, the structures represented in the present invention should also include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures, including the substitution of hydrogen by deuterium or tritium, or the substitution of a carbon by an enriched 13C or 14C carbon, are within the scope of the present description. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents according to the present description.

[0023] Definitions of specific functional groups and chemical terms are provided below.

[0024] The chemical structures in the present invention are drawn according to conventional patterns known in the art. Thus, when an atom, such as a carbon atom, as drawn appears to have an unsatisfied valence, then this valence is presumed to be satisfied by a hydrogen atom, although this hydrogen atom is not necessarily explicitly drawn. Hydrogen atoms are to be inferred as part of the compound.

[0025] The number of carbon atoms in a hydrocarbyl substituent can be indicated by the prefix Cx-Cy, where x is the minimum, and y is the maximum number of carbon atoms in the substituent. When reference is made to the heterocyclic group of xay members (e.g., heterocycloalkyl, partially unsaturated heterocyclic group, or heteroaryl), then xey define, respectively, the minimum and maximum numbers of atoms in the cyclic group, including carbons, as well as heteroatom(s).

[0026] The term halogen, as used here, refers to an atom Petition 870250103125, dated 11 / 11 / 2025, page 18 / 470 / 431 selected from among fluorine (fluorine, -F), chlorine (chlorine, -Cl), bromine (bromine, -Br) and iodine (iodine, -I).

[0027] The term heteroatom means one or more of the following: oxygen, sulfur, nitrogen, phosphorus or silicon, more particularly, oxygen, sulfur or nitrogen.

[0028] The term alkyl, as used herein, refers to a saturated hydrocarbon radical, straight (linear) or branched chain. In some embodiments, the alkyl group may contain from 1 to 6 carbon atoms, although alkyl groups with more than 6 carbon atoms may be contemplated. For example, C1-C6 alkyl contains from one to six carbon atoms. Examples of alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, neopentyl, n-hexyl, heptyl, octyl and the like.

[0029] The term alkenyl, as used herein, denotes a linear or branched chain hydrocarbon radical containing one or more double bonds. In some embodiments, alkenyl groups may contain from 2 to 6 carbon atoms, although alkenyl groups with more than 6 carbon atoms may be contemplated. For example, Cz-C-alkenyl contains from two to six carbon atoms. Alkenyl groups include, but are not limited to, for example, ethenyl, propenyl, butenyl, pentenyl, 1-methyl-2-buten-1-yl, hexenyl and the like.

[0030] The term alkynyl, as used herein, denotes a linear or branched chain hydrocarbon radical containing one or more triple bonds. In some embodiments, alkynyl groups may contain from 2 to 6 carbon atoms, although alkynyl groups with more than 6 carbon atoms may be contemplated. For example, Cz-Coalkynyl contains from two to six carbon atoms. Alkynyl groups include, but are not limited to, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Petition 870250103125, dated 11 / 11 / 2025, p. 19 / 470 / 431

[0031] The term cycloalkyl, used alone or as part of a larger moiety, refers to a group comprising a saturated carbocyclic ring in a monocyclic or polycyclic ring system, including spiro (sharing one atom), fused (sharing at least one bond) or bridging (sharing two or more bonds) carbocyclic ring systems, having from three to fifteen ring members. In some embodiments, cycloalkyl groups may contain from 3 to 8 carbon atoms. For example, C3-C5cycloalkyl contains from three to eight carbon atoms in the cyclic ring. Examples of cycloalkyl groups may include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[4.2.0]octyl, norbornyl and the like.

[0032] The term aryl used in the present invention refers to a monocyclic moiety or a bicyclic or tricyclic fused ring system, wherein the ring system is carbocyclic and completely aromatic. In some embodiments, the aryl groups may contain from 6 to 14 carbon atoms, such as 6 to 10 carbon atoms, for example. For example, a C6-C10 aryl group contains from six to ten carbon atoms in the aromatic system. In certain embodiments, aryl refers to an aromatic ring system that includes, but is not limited to, phenyl, naphthyl, azulenyl, anthracil and the like.

[0033] As used herein, the term heterocyclic group refers to a chemically stable, saturated, partially unsaturated, or fully aromatic monocyclic or polycyclic ring system, including spiro (sharing one atom), fused (sharing at least one bond), or bridging (sharing two or more bonds), including at least one heteroatom, as defined above. A heterocyclic group may be a heterocycloalkyl group, a heteroaryl group, or a partially unsaturated heterocyclic group, as defined herein.

[0034] The term heterocycloalkyl used alone or as part of Petition 870250103125, dated 11 / 11 / 2025, p. 20 / 470 / 431, a larger portion refers to a saturated cyclic group containing at least one heteroatom, as defined herein, which may include a single ring, or two or more rings. In some embodiments, heterocycloalkyl groups may include from 3 to 14 atoms in the ring, although heterocycloalkyl groups with more than 14 atoms in the ring may be contemplated. In some embodiments, heterocycloalkyl groups may contain from 4 to 14 atoms in the ring, or from 4 to 6 atoms in the ring, or from 3 to 6 atoms in the ring, for example. For example, a 3- to 14-membered heterocycloalkyl group contains from three to fourteen atoms, counting the total number of carbon atoms and heteroatoms, in the saturated heterocyclic portion. In some embodiments, the heterocycloalkyl group may contain from one to four heteroatoms.Heterocycloalkyl groups may include, without limitation, oxiranyl, aziridinyl, oxetanyl, tetrahydropyranyl (oxanyl), tetrahydrofuranyl (oxolanyl), pyrrolidinyl (azolidinyl), piperidinyl, dioxanyl, morpholinyl, thietanyl, azetidinyl, diazetidinyl, oxathiolanyl, oxepanyl, azocanyl (octahydroazocinyl), thiocanyl, azonanyl (octahydroazoninyl), 1,3-dioxolanyl, pyrazolidinyl, imidazolidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrodithienyl, thiomorpholinyl, thioxanyl, homopiperidinyl, thiepanil, ditianil, dithiolanil, 3-azabicyclo[3,1,0]hexanil, 3azabicyclo[4,1,0]heptanil, quinuclidinil, decahydroquinolinyl, octahydroindolyl and the like. A heterocycloalkyl group can be attached to its pendant group at any heteroatom or carbon atom that results in a chemically stable structure.

[0035] The term heteroaryl, used alone or as part of a larger portion, refers to a completely aromatic cyclic group containing at least one heteroatom, as defined herein, which may include a single ring, or two or more fused rings. In some embodiments, heteroaryl groups may include 5 to 10 atoms in the ring, although groups Petition 870250103125, dated 11 / 11 / 2025, p. 21 / 470 / 431 heteroaryl with more than 10 nonanel atoms possam be contemplated. In some embodiments, the heteroaryl group may contain from one to four heteroatoms. The heteroaryl groups may include, without limitation, thienyl, furanyl (furyl), pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, benzofuranyl, dibenzofuranyl, benzimidazolyl, benzothiazolyl, benzothienyl (benzothiophenyl), benzoxazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furopyrinyl, indolyl, indazolyl, isoindolyl, indolizinyl, purinyl, quinolyl (quinolinyl), isoquinolyl (isoquinolinyl), acridinyl, cinolinyl, quinazolinyl, naphtridinyl, carbazolyl, phenanthridinyl, phenazinyl, phenothiazinyl, phenoxazinyl and pteridinyl.A heteroaryl group can be attached to its pendant group on any heteroatom or carbon atom, resulting in a chemically stable structure.

[0036] As used herein, the term partially unsaturated heterocyclic group refers to a carbocyclic ring system including at least one double bond between ring atoms, but not being completely aromatic and comprising at least one heteroatom. The partially unsaturated heterocyclic group aims to encompass ring systems, which may be mono-, bi-, or tricyclic and having one or more unsaturation sites. In some embodiments, the partially unsaturated heterocyclic group may include a multicyclic ring system in which at least one ring is aromatic while at least one other ring is not aromatic. For example, the partially unsaturated heterocyclic group may include an aryl fused to a heterocycloalkyl, a heteroaryl fused to a cycloalkyl, or a heteroaryl fused to a heterocycloalkyl, wherein each of the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl may be monocyclic or bicyclic.In some embodiments, the partially unsaturated heterocyclic groups may contain from 7 to 14 carbon atoms, such as 7 to 10 carbon atoms or 8 to 14 carbon atoms, for example. For example, one. Petition 870250103125, dated 11 / 11 / 2025, page 22 / 470 / 431: A partially unsaturated heterocyclic group of 7 to 10 members contains seven to ten atoms, counting the total number of carbon atoms and heteroatoms in the heterocyclic portion. The partially unsaturated heterocyclic group may contain, in some embodiments, one to four heteroatoms. The partially unsaturated heterocyclic group may be attached to its pendant group at any heteroatom or carbon atom that results in a chemically stable structure.Non-limiting examples of partially unsaturated heterocyclic groups include pyrazolinyl, imidazolinyl, 1,2,3,6-tetrahydropyridinyl, 2-pyrrolinyl, 3-pyrrolinyl, 2H-pyranyl, 4H-pyranyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, quinolizinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, 1,3-benzodioxolyl, cromanyl, chromenyl, indolinyl, quinolonyl, isoquinolonyl, oxazepinyl, diazepinyl, thiazepinyl, phthalazinyl, quinoxalinyl, pyrido[2,3-b]N₂N₂ and α. When used in reference to a ring atom of a heterocyclic group, the term nitrogen includes a substituted nitrogen. For example, in a saturated or partially unsaturated ring with 1 to 3 heteroatoms selected from oxygen, sulfur, and nitrogen, the nitrogen can be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or NR0 (as in N-substituted pyrrolidinyl).

[0037] As used herein, the term partially unsaturated carbocyclic group refers to a carbocyclic ring system including at least one double bond between ring atoms, but is not completely aromatic. The partially unsaturated carbocyclic group aims to encompass ring systems comprising only carbon atoms within the ring, wherein said ring is mono-, bi-, or tricyclic and has one or multiple unsaturation sites. In some embodiments, the group Petition 870250103125, dated 11 / 11 / 2025, page 23 / 470 / 431. A partially unsaturated carbocyclic group may include a multicyclic ring system in which at least one ring is aromatic while at least one other ring is not aromatic. For example, the partially unsaturated heterocyclic group may include an aryl group fused to a cycloalkyl group, wherein each of the aryl and cycloalkyl groups may be monocyclic or bicyclic. In some embodiments, the partially unsaturated carbocyclic groups may contain from 7 to 14 carbon atoms, such as 7 to 10 carbon atoms or 8 to 14 carbon atoms, for example. For example, an 8- to 14-membered partially unsaturated carbocyclic group contains eight to fourteen carbon atoms in the cyclic portion. A partially unsaturated carbocyclic group can be attached to its pendant group on any carbon atom that results in a chemically stable structure. A non-limiting example of a partially unsaturated carbocyclic group includes

[0038] As described herein, various chemical groups present in the compounds of the present description, such as any of the groups defined above, may be optionally substituted. In general, the term substituted means that one or more hydrogen atoms of the designated portion are replaced by a suitable substituent. Unless otherwise indicated, a substituted chemical group may have a suitable substituent at each substituteable position of the group, and, when more than one position in any given structure may be substituted by more than one substituent selected from a specified group, the substituent may be the same or different at each position. The combinations of substituents provided for in the present description are preferably those that result in the formation of chemically stable or chemically viable compounds.The term chemically stable, as used here, refers to compounds that are not substantially altered when subjected to conditions that allow it. Petition 870250103125, dated 11 / 11 / 2025, p. 24 / 470 / 431 its production, detection and, in certain modalities, its recovery, purification and use for one or more of the purposes disclosed herein.

[0039] In some specific embodiments, when any chemical group is substituted, it may be substituted by independent substitution of one, two, three or more of the hydrogen atoms by substituents including, but not limited to, halogen (i.e., -F, -CI, -Br, -I), -OH, CO2H, alkoxy, such as methoxy, ethoxy or propyloxy, -OCHF2, -OCH2CHF2, OCH2CF3, -OCH2CH2OCH3, protected alkoxy, alkyl groups, as defined above, such as methyl, ethyl, propyl or -C(CH3)3, aryl groups, as defined above, such as phenyl, cycloalkyl groups, as defined above, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, oxo (=O), thioxo (=S), (=O), oxime (=N-OH), C1-C3 alkoxyoxime (= N-OC 1C3 alkyl), -NO 2, -CN, -NH2, -NHMe, -NHEt, -N(Me)2, -NHCOMe, NH(COOtBu), -N(Et)(COOtBu), protected amino, -CH2OH, -COOH, COOMe, -COOEt, -CONH2, -CONHMe, -CONHEt, -CF- 3, -CHF2, -CH2F, Si(Me), -OSi (Me)2(tBu), -SMe, -SO2NH(CH2)3OH, -SO2Me, -SO2Ph, -SPh, pyrazolyl, pyrrolyl, pyridyl,piperidinyl, triazolyl, tetrazolyl, morpholinyl, isoxazolyl, oxazolyl, thiazolyl, imidazolyl, benzothiazolyl, benzimidazolyl, and

[0040] The expression "pharmaceutically acceptable salt" refers to salts of the compounds of the present description that are suitable for use in Petition 870250103125, dated 11 / 11 / 2025, page 25 / 470 / 431. Contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are proportionate to a reasonable risk / benefit ratio. The pharmaceutically acceptable salts are well known in the art. The salts can be prepared in situ during the final isolation and purification of the compounds of the present description or separately by the reaction of a free base function of the compound with a suitable organic or inorganic acid (acidic addition salts) or by the reaction of an acidic function of the compound with a suitable organic or inorganic base (basic addition salts).Examples of pharmaceutically acceptable salts include, but are not limited to, non-toxic acid addition salts or salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids, such as acetic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or using other methods employed in the art, such as ion exchange.Other pharmaceutically acceptable salts include, but are not limited to, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, iodide, 2-hydroxyethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate and the like. Representative alkali or alkaline earth metal salts of base addition include sodium, lithium, potassium, calcium or magnesium salts and the like.Other pharmaceutically acceptable salts include, when appropriate, non-toxic ammonium, quaternary ammonium, and amine cations. Petition 870250103125, dated 11 / 11 / 2025, page 26 / 470 / 431 formed using counterions, such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, sulfonate and aryl sulfonate.

[0041] The term solvate refers to a physical association of one of the present compounds with one or more solvent molecules. This physical association includes hydrogen bonding. In certain cases, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. Solvate encompasses isolable and solution-phase solvates. Exemplary solvates include, without limitation, hydrates, hemihydrates, ethanolates, hemiethanolates, n-propanolates, isopropanolates, 1-butanolates, 2-butanolates, and solvates of other physiologically acceptable solvents. The compounds as described herein also include each of their solvates and mixtures thereof.

[0042] The term prodrug, as used herein, refers to prodrugs of the compounds of the present description that are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, proportionate to a reasonable risk / benefit ratio and effective for their intended use. Prodrug, as used herein, means a compound that is convertible in vivo by metabolic means (e.g., by hydrolysis) to produce any compound outlined by the formulas of the present description. Several forms of prodrugs are known in the art.

[0043] The compounds of the present application can be prepared by conventional chemical synthesis, as exemplified in the general schemes provided below and in Examples 1 to 260, for example. As can be recognized by those skilled in the art, other methods of synthesizing the compounds of the formulas in the present invention will be apparent to those skilled in the art. Furthermore, the various synthetic steps can be carried out in an alternative sequence or order to yield the compounds. Petition 870250103125, dated 11 / 11 / 2025, page 27 / 470 / 431 desired. Furthermore, the solvents, temperatures, reaction duration, etc., outlined in the present invention are for illustrative purposes only, and one skilled in the art will recognize that varying the reaction conditions can produce the desired products of the present description. The synthetic chemical transformations and / or protecting group methodologies (protection and deprotection) useful in the synthesis of the compounds described herein are known in the art. The synthesized compounds can be separated from a reaction mixture and further purified by standard methods such as column chromatography, high-performance liquid chromatography, or recrystallization.

[0044] The compounds of the present description can be modified by attaching various functionalities through any synthetic means outlined in the present invention to improve selective biological properties. Such modifications are known in the art and include those that increase biological penetration into a given biological system (e.g., blood, lymphatic system, central nervous system), increase oral bioavailability, increase solubility to allow administration by injection, alter metabolism, and alter the rate of excretion.

[0045] In some embodiments, the present disclosure therefore provides a compound with Formula (I), or a pharmaceutically acceptable salt, solvate or prodrug thereof, where: Raé -NH2, -NH-OH, -OH, -NHRb or -NRcRd; Rb is a 6-membered C1-C6 alkyl, C3-C6 cycloalkyl, or heterocycloalkyl, wherein the C1-C6 alkyl is optionally substituted with 1 to 3 halogens, 1 to 3 -OH, -OC1-C3 alkyl, -COOH, or cyclopropyl Petition 870250103125, dated 11 / 11 / 2025, p. 28 / 470 / 431 optionally replaced by -OH, and C3-C6cycloalkyl is optionally replaced by -CN; Rce Rdformam with the nitrogen to which they are attached a 4-membered heterocycloalkyl, wherein the 4-membered heterocycloalkyl is optionally substituted by at least one of -OH and C1C3alkyl; represents one of the following residues Ao a A12 Al0, Al1 or Al2; Ag Aθ and given that: R is H, C1-C6 alkyl or phenyl; R1 and R2 are independently -CN, C6-C10 aryl, C1-C6 alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, and each C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents, each C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents, with the condition that when Ra is OH, CZZ represents Ao, and R1 is , then R2 in the Ao residue is different from o; each R5 is independently C1-C6 alkyl, with each C1 Petition 870250103125, dated 11 / 11 / 2025, p. 29 / 470 / 431 Cóalquila is optionally replaced by 1 to 3 R9 substituents; each R6 is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl or C6-C10aryl; Each R7 is independently -OH, -C(O)Rn, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), -N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC1C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, wherein each C3C6cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl. or oxo; each R8 is independently halogen, C1-C6 alkyl, -OC1-C6 alkyl, C3-C6 cycloalkyl, or 5- to 10-membered heteroaryl, wherein each -OC1-C6 alkyl is optionally substituted by -OC1-C4 alkyl, and each 5- to 10-membered heteroaryl is optionally substituted by C1-C4 alkyl; each R22 is independently C1-C6 alkyl optionally substituted with phenyl; each R9 is independently -OH, -C(O)R15, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NB(C(O)C1-C6alkyl), -OC1-C6alkyl, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, wherein each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl, and each -OC1C6alkyl is optionally substituted by -OC1-C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or a 4- to 6-membered heterocycloalkyl; Each R20 is independently a 5- to 10-membered C1-C6 alkyl or heteroaryl group, and each C1-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents, and each 5- to 10-membered heteroaryl group is optionally Petition 870250103125, dated 11 / 11 / 2025, p. 30 / 470 / 431 replaced by -OH or -NH(cyclopropyl); each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, or -SPh, with each C1-C4 alkyl being optionally replaced by -OH; each R13 is independently halogen, C1-C4 alkyl, C3C6 cycloalkyl, -OH, -OC1-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1-C6 alkyl, NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, wherein each -OC1C6 alkyl, -SC1-C6 alkyl, -S(O)2C1-C6 alkyl, -NH(C1-C4 alkyl), and -N(C1C4 alkyl)2 is optionally substituted by 1 to 3 R9 substituents; Each R14 is independently halogen, -OC1-C4 alkyl, or C3-C6 cycloalkyl; each R15 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or a 4- to 6-membered heterocycloalkyl; R4 is a C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, partially unsaturated heterocyclic group of 7 to 10 members or heteroaryl of 5 to 10 members, wherein C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl and heteroaryl of 5 to 10 members are optionally substituted by 1 to 3 R10 substituents, with ah The condition that: (i) when Ra is -OH, -NH2, or ?, and < . represents (i) If Ra represents A2, then R4 in residue A2 is different from -CH3; and (ii) if Ra represents -NH2 and CZZ represents A3, then R4 in residue A3 is different from -C(CH3)3; each R10 is independently C1-C4 alkyl, halogen, -OC1C6 alkyl, -NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, with each C1C4 alkyl being optionally substituted by 1 to 3 halogens; R2a is C1-C6 alkyl, C3-C8 cycloalkyl, or C6-C10 aryl, wherein C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl is optionally substituted by 1 to 3 R10 substituents; R1 and R2 are independently -CN, C6-C10arila, C1 Petition 870250103125, dated 11 / 11 / 2025, p. 31 / 470 / 431 C3-C8cycloalkyl, -C(O)NH2,-C(O)NHR5, or -C(O)OC1-C6alkyl, wherein each C1-C6alkyl is optionally substituted by 1 to 3 R16 substituents and each C6-Cwaryl is optionally substituted by 1 to 3 R17 substituents; each R16 is independently -OH, -C(O)NH2, -C(O)NH(C1C4alkyl), C3-C6cycloalkyl, -CN, C6-Cwaryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl) or -OC1-C4alkyl(OC1C4alkyl), wherein each C3-C6cycloalkyl is optionally substituted by 1 to 3 R18 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R21 substituents and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl; each R17 is independently a halogen, C1-C6 alkyl, -OC1C6 alkyl or 5- to 10-membered heteroaryl, wherein each 5- to 10-membered heteroaryl is optionally substituted by C1-C4 alkyl; Each R18 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, or -OC1-C4 alkyl; Each R21 is independently halogen or C1-C4 alkyl; R4a is C1-C6 alkyl or C3-C8 cycloalkyl, wherein each C1-C6 alkyl and C3-C8 cycloalkyl are optionally replaced by 1 to 3 R19 substituents; each R19 is independently halogen, -OH, -OC1C4alkyl, -SC1-C4alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2; R1b and R2c, together with the carbon atom to which they are attached, form a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and wherein the 4- to 14-membered heterocycloalkyl, a partially unsaturated heterocyclic group Petition 870250103125, dated 11 / 11 / 2025, p. 32 / 470 / 431 unsaturated group of 8 to 14 members or partially unsaturated carbocyclic group of 8 to 14 members is optionally replaced by oxo (=O), oxime (=NOH), C1-C3 alkoxyoxime (= N-OC 1-C3 alkyl) or 1 to 3 substituents selected independently of -OH and -CF3; R2d and R4b, together with the carbon atoms to which they are attached, form a 4- to 14-membered C3-C8 cycloalkyl or heterocycloalkyl, and the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents; and R1 and R3, together with the carbon atoms to which they are attached, form a 4- to 14-membered C3-C8 cycloalkyl or heterocycloalkyl, and the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents.

[0046] In some embodiments, the compound of Formula (I) is such that: (i) when Rae is -OH, CZZ represents Ao, and R1 is , then R2 in the residue Ao is different from O; (ii) when Rae is -OH, and < represents A2, then, R4 in residue A2 is different from -CH3 and -CH2CH3; (iii) when Ra is NH2, and CZ2 represents A2, then, R4 in residue A2 is different from -CH3; and (iv) when Ra is -NH2 and ^A·' represents A3, then R4 in residue A3 is different from -C(CH3)3.

[0047] In some embodiments, the compound of Formula (I) is such that: (i) when Rae is -OH, represents Ao, and R1 is , then R2 in the residue Ao is different from O ; (ii) when Rae is -OH, ev , represents A2, then, R4 in residue A2 is different from -CH3 and -CH2CH3; (iii) when Ra is NH2, and CAZ represents A2, then, R4 in residue A2 is different from -CH3; there is ___. x , .. 4nrr (iv) when Raé , ev , represents A2, then R4no residue A2 is different from -CH3; and (v) when Raé -NH2 and ^A·' represents A3, then R4no residue A3 is different from -C(CH3)3.

[0048] In other forms, the compound of Formula (I) is such that: Petition 870250103125, dated 11 / 11 / 2025, page 33 / 470 / 431 (i) when Raé -OH, represents Ao, and R1é V , then, R2no OH residue Ao is different from O ; (ii) when Raé -OH, and represents A2, then, R4 in residue A2 is different from alkyl; (iii) when Ra is -NH2, and CAZ represents A2, then, R4 in residue A2 is different from -CH3; and (iv) when Ra is -NH2 and ^A·' represents A3, then R4 in residue A3 is different from C(CH3)3.

[0049] In other embodiments, the compound of Formula (I) is such that: (i) when Rae is -OH, CEZ represents Ao, and R1 is ^^^7, then R2 in the ηOHcT residue Ao is different from O; (ii) when Rae is -OH, ev— represents A2, then R4 in the residue A2 is different from alkyl; (iii) when Rae is -NH2, and CAZ represents A2, then R4 in the residue A2 is different from -CH3; (iv) when h A ___. .. Rae, ev, represents A2, so R4 in residue A2 is different from CH3; and (v) when Rae is -NH2 and ^A·' represents A3, then R4 in residue A3 is different from -C(CH3)3.

[0050] In some embodiments, the compound of Formula (I), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that R is H.

[0051] In some embodiments, the compound of Formula (I), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raé -NHRb, and Rb represents C1-C6 alkyl, C3-C6 cycloalkyl or 3- to 6-membered heterocycloalkyl, wherein the C1-C6 alkyl is optionally substituted by 1 to 3 halogens, 1 to 3 -OH, -OC1-C3 alkyls, COOH or cyclopropyls optionally substituted by -OH, and wherein the C3-C6 cycloalkyl is optionally substituted by -CN.

[0052] In some embodiments, the compound of Formula (I) or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raé -NHRb, and Rb represents: Petition 870250103125, dated 11 / 11 / 2025, p. 34 / 470 / 431 -CH3, =N

[0053] In some embodiments, the compound of Formula (I) or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raé -NHRb, and Rb represents: -Cm, '''y, , AOH

[0054] In some disciplines, Raé -NHRb, and Rb represents

[0055] In other embodiments, Rae -NRcRd, and Rce Rd form with the nitrogen to which they are attached a 4-membered heterocycloalkyl, wherein the 4-membered heterocycloalkyl is optionally substituted by at least one of -OH and C1-C3 alkyl; _ / OH

[0056] In other embodiments, Ra is ^ , ^ or • ,^ / OH 5 / N^OH

[0057] In other embodiments, Ra is ou7' .

[0058] In other embodiments, Ra is -OH

[0059] In other embodiments Ra is NH2.

[0060] In other embodiments, Ra is -NH-OH.

[0061] In some embodiments, the compound of Formula (I), or the The salt, the solvate, or a pharmaceutically acceptable prodrug thereof, may be in the form of a racemate or any enantiomer thereof. Petition 870250103125, dated 11 / 11 / 2025, p. 35 / 470 / 431

[0062] In some forms, the compound of Formula (I) may have the following structures (Ia), (Ia'), (Ib), (Ib'), (Ic), (Ic'), (Id), (Id'), (Ie), (Ie'), (If), (If') or (Ig): (Ig) , where R1, R2, R3, R4, R1a, R1b, R1c, R2a, R2b, R2c, R2d, R4a, R4b, R and Ratio as defined herein. Compounds of Formulas (Ia) and (Ia')

[0063] In some embodiments, the compound is of Formula (Ia) or (Ia'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. Petition 870250103125, dated 11 / 11 / 2025, p. 36 / 470 / 431

[0064] The groups R, Ra, R1 and R2 can be defined as follows: General formula (I) above.

[0065] In some embodiments, the compound is of Formula (Ia), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[0066] The Ra, R1 and R2 groups can be as defined for the general Formula (I) above.

[0067] In some embodiments, R1 and R2 may independently represent -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkynyl, C3C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, C(O)R6 or -C(O)OR5, and each C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents, each C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R22 substituents, and R5, R6, R7, R8 and R22 are as defined herein.

[0068] In some embodiments, R1 and R2 are independently CN, C6-C10aryl, C1-C6alkyl, C2-C6alkynyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl or -C(O)NH2, wherein each C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents, each C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents, and R7, R8 and Petition 870250103125, dated 11 / 11 / 2025, p. 37 / 470 / 431 R22 are as defined here.

[0069] In additional embodiments, R1 and R2 may independently represent -CN, phenyl, C1-C4 alkyl, C2-C4 alkynyl, C3C6 cycloalkyl, 5-membered heteroaryl or -C(O)NH2, wherein each C1C4 alkyl is optionally substituted by 1 or 2 R7 substituents, each phenyl is optionally substituted by 1 or 2 halogens, and each 5-membered heteroaryl is optionally substituted by 1 or 2 -CH3.

[0070] According to some embodiments, R1 and R2 independently represent -CN, C6-C10aryl, C1-C6alkyl, C3-C8cycloalkyl or C(O)NH2, and each C1-C6alkyl is optionally replaced by 1 to 2 R7 substituents, as defined herein.

[0071] In some embodiments, when R1 and / or R2 represent C(O)NHR5 or -C(O)OR5, each R5 may be a C1-C6 alkyl. In other embodiments, when R1 and / or R2 represent -C(O)R6, each R6 may be a 4- to 6-membered heterocycloalkyl.

[0072] In some embodiments, when R1 and / or R2 represent C1C6 alkyl substituted by 1 to 3 R7 substituents, then each R7 may independently represent -OH, -C(O)R11, C3-C6 cycloalkyl, -CN, C6C10 aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1C6 alkyl), -N(C1-C4 alkyl)(C(O)OC1-C6 alkyl), -NH(C(O)C1-C6 alkyl), 4- to 6-membered heterocycloalkyl, -OR20, -SC1-C6 alkyl, -NH2 or -N(C1C4 alkyl)2, wherein each C3-C6 cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 substituents R13, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4 alkyl or oxo.

[0073] In some embodiments, R7 may independently represent -OH, -C(O)Rn, -OR20, C3-C6cycloalkyl, -CN, C6C10aryl, halogen, -C(O)OH or 5- to 10-membered heteroaryl, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 3 R12 substituents, Petition 870250103125, dated 11 / 11 / 2025, p. 38 / 470 / 431 and each heteroaryl group of 5 to 10 members is optionally replaced by 1 to 3 R13 substitutes.

[0074] In additional embodiments, R7 may independently represent -OH, -C(O)NH2, -OR20, C3-C6cycloalkyl, -CN, phenyl, halogen, -C(O)OH or 5-membered heteroaryl, wherein each C3C6cycloalkyl is optionally replaced by -CH-3.

[0075] In another embodiment, R7 may independently represent -OH, -C(O)NH2, C3-C6cycloalkyl, -CN, C6-C10aryl, halogen or 5- to 8-membered heteroaryl, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 2 C1-C4alkyl, and each 5- to 8-membered heteroaryl is optionally substituted by 1 to 2 R13 substituents.

[0076] In some embodiments, the substituents R11 mentioned above may independently represent -NH2, -NH(C1-C4 alkyl) or 4- to 6-membered heterocycloalkyl. In some specific embodiments, R11 may represent -NH2.

[0077] In some embodiments, the R12 substituents mentioned above may independently represent C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl or -SPh, and each C1-C4 alkyl is optionally substituted by -OH. In some specific embodiments, R12 is C1-C4 alkyl.

[0078] In some embodiments, the R13 substituents mentioned above may independently represent halogen, C1-C4 alkyl or C3C6 cycloalkyl. In some specific embodiments, R13 is independently halogen or C1-C4 alkyl.

[0079] In some embodiments, the R14 substituents mentioned above may independently represent halogen, -OC1-C4 alkyl or C3-C6 cycloalkyl. In some specific embodiments, R14 is halogen.

[0080] In some embodiments, the R20 substituents mentioned above may independently represent C1-C6 alkyl or heteroaryl of Petition 870250103125, dated 11 / 11 / 2025, p. 39 / 470 / 431 to 10 members, wherein each C1-C-alkyl is optionally substituted by 1 to 3 R14 substituents, as defined herein, and each 5 to 10 member heteroaryl is optionally substituted by -OH or -NH(cyclopropyl). In some specific embodiments, R20 is C1-C-alkyl, and each C1-C-alkyl is optionally substituted by 1 to 3 R14 substituents, as defined herein. In additional embodiments, R20 is C1-C-alkyl, and each C1-C-alkyl is optionally substituted by 1 to 3 halogens. In some embodiments, R20 is a 5 to 10 member heteroaryl substituted by -OH or NH(cyclopropyl). In certain embodiments, R20 is a 5- to 10-membered heteroaryl group substituted by -OH. In other embodiments, R20 is a 5- or 6-membered heteroaryl group substituted by -OH.

[0081] In some embodiments, the R22 substituents mentioned above may independently represent C1-C4 alkyl.

[0082] In some embodiments, when R1 and / or R2 represent C10 aryl substituted by 1 to 3 R8 substituents, then each R8 can independently represent halogen, C1-C6 alkyl or -OC1-C6 alkyl, wherein each -OC1-C6 alkyl is optionally substituted by -OC1-C4 alkyl. In some specific embodiments, R8 is a halogen. In some embodiments, when R1 and / or R2 represent 5 to 10 membered heteroaryl substituted by 1 to 3 R22 substituents, then each R22 can independently represent C1-C6 alkyl optionally substituted by phenyl. In some embodiments, R22 is C1-C2 alkyl substituted by phenyl.

[0083] In some embodiments, R1 and R2 are independently CN, C-C10aryl, C1-C-alkyl, C2-C-alkyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6 or -C(O)OR5, and each C1-C-alkyl is optionally substituted by 1 to 3 R7 substituents, each C-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents. Petition 870250103125, dated 11 / 11 / 2025, p. 40 / 470 / 431 each R5 is independently Ci-Co-alkyl; each R6 is independently a 4- to 6-membered heterocycloalkyl group; each R7 is independently -OH, -C(O)Rn, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), -N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC1C6alkyl, -NH2, or -N(C1-C4alkyl)2, and each C3-C6cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1C4alkyl or oxo; Each R8 is independently halogen, C1-C6 alkyl, or OC1-C6 alkyl, and each -OC1-C6 alkyl is optionally replaced by -OC1-C4 alkyl; each R22 is independently C1-C6 alkyl optionally substituted with phenyl; each R11 is independently -NH2, -NH(C1-C4alkyl) or a 4- to 6-membered heterocycloalkyl; each R20 is independently a 5- to 10-membered C1-C6 alkyl or heteroaryl group, wherein each C1-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents and each 5- to 10-membered heteroaryl group is optionally substituted by -OH or -NH (cyclopropyl); each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, or -SPh, and each C1-C4 alkyl is optionally replaced by -OH; Each R13 is independently halogen, C1-C4 alkyl, or C3-C6 cycloalkyl; and each R14 is independently halogen, C1-C4 alkyl, or Petition 870250103125, dated 11 / 11 / 2025, p. 41 / 470 / 431 Cs-C-cycloalkyl.

[0084] In some embodiments, R1 and R2 are independently CN, C-Cyoaryl, C1-Cyoalkyl, C2-Cykyl, C5-C8cycloalkyl, 5- to 10-membered heteroaryl or -C(O)NH2, wherein each C1-Cyoalkyl is optionally substituted by 1 to 3 R7 substituents, each C-Cyoaryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents, and each R7 is independently -OH, -C(O)Rn, C3Cycoalkyl, -CN, C-Cwaryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-Cykyl), -N(C1-C4alkyl)(C(O)OC1-C-alkyl), NH(C(O)C1-C-alkyl), 4- to 6-membered heterocycloalkyl, -OR20, -SC1C-alkyl, -NH2, or -N(C1-C4alkyl)2, and each C3-C-cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1C4alkyl or oxo; each R8 is independently halogen, C1-C6 alkyl or OC1-C-alkyl, with each -OC1-C-alkyl optionally replaced by -OC1-C4 alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl) or a 4- to 6-membered heterocycloalkyl; each R20 is independently a 5- to 10-membered C1-C6 alkyl or heteroaryl group, wherein each C1-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents and each 5- to 10-membered heteroaryl group is optionally substituted by -OH or -NH (cyclopropyl); each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, or -SPh, with each C1-C4 alkyl being optionally replaced by -OH; Each R13 is independently halogen, C1-C4 alkyl, or C3 Petition 870250103125, dated 11 / 11 / 2025, page 42 / 470 / 431 Cocycloalkyl; Each R14 is independently halogen, -OCi-C4 alkyl, or C3-C6 cycloalkyl; and each R22 is independently C1i-C4 alkyl.

[0085] In some embodiments, R1 and R2 are independently CN, C-C-Cyoaryl, C1-Cyoalkyl, C2-Cyoalkyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl or -C(O)NH2, with each C1-Cyoalkyl optionally substituted by 1 to 3 R7 substituents, each C-C1yoaryl optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl optionally substituted by 1 to 3 R2 substituents, and each R7 is independently -OH, -C(O)Rn, -OR20, C3Ccycloalkyl, -CN, C-Cwaryl, halogen, -C(O)OH or 5- to 10-membered heteroaryl, with each C3-C6cycloalkyl optionally substituted by 1 to 3 R1 substituents. The 5- to 10-membered heteroaryl group is optionally replaced by 1 to 3 R13 substituents; Each R8 is a halogen; each R11 is -NH2; each R20 is a 5- or 6-membered C1-coalkyl or heteroaryl group, wherein each C1-coalkyl group is optionally substituted by 1 to 3 R14 substituents and each 5- or 6-membered heteroaryl group is optionally substituted by -OH or -NH (cyclopropyl); each R12 is C1-C4 alkyl; Each R13 is independently halogen or C1-C4 alkyl; Each R14 is a halogen; and each R22 is independently C1-C4 alkyl.

[0086] In some embodiments, R1 and R2 independently represent -CN, phenyl, C1-C4 alkyl, C2-C4 alkynyl, C3-C6 cycloalkyl, 5-membered heteroaryl or -C(O)NH2, with each C1-C4 alkyl optionally substituted by 1 or 2 substituents. R7, each phenyl Petition 870250103125, dated 11 / 11 / 2025, p. 43 / 470 / 431 is optionally substituted by 1 or 2 halogens, and each 5-membered heteroaryl is optionally substituted by 1 or 2 -CH3, and each R7 is independently -OH, -C(O)NH2, -OR20, C3C6cycloalkyl, -CN, phenyl, halogen, -C(O)OH or 5-membered heteroaryl, wherein each C3-C6cycloalkyl is optionally substituted by -CH3; and each R20 is C1-C6alkyl or 5- or 6-membered heteroaryl, wherein each C1-C6alkyl is optionally substituted by 1 to 3 halogens and each 5- or 6-membered heteroaryl is optionally substituted by -OH.

[0087] In some embodiments, R1 and R2 independently represent -CN, C6-C10 aryl, C1-C6 alkyl, C3-C8 cycloalkyl, 5-membered heteroaryl or -C(O)NH2, and each C1-C6 alkyl is optionally substituted by 1 to 2 R7 substituents; Each R7 is independently -OH, -C(O)NH2, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, or 5- to 8-membered heteroaryl, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 2 C1C4alkyl, and each 5- to 8-membered heteroaryl is optionally substituted by 1 to 2 R13 substituents; and each R13 is independently halogen or C1-C4alkyl. In some modes, R1 and R2, which may be identical or

[0088] different, may represent: -CN, -CH3, Petition 870250103125, dated 11 / 11 / 2025, p. 44 / 470 / 431 EM HN~n' Cl or

[0089] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3, X oh, X , V^-^oh.V^o , Petition 870250103125, dated 11 / 11 / 2025, p. 45 / 470 / 431 ON EM hn-n'

[0090] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3, V^oh, -OH, V^-^oh, Petition 870250103125, dated 11 / 11 / 2025, p. 46 / 470 / 431 0-N EM HN~n' Cl or

[0091] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3,1V CN V , , , Petition 870250103125, dated 11 / 11 / 2025, p. 47 / 470 / 431 EM hn-n' or Cl.

[0092] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3, V^oh.X , ν^-^ΟΗ,ν^ο , V O V CN \ , , , Petition 870250103125, dated 11 / 11 / 2025, p. 48 / 470 / 431 or Cl.

[0093] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3, ' V CN V , , , i N HN~n' Petition 870250103125, dated 11 / 11 / 2025, p. 49 / 470 / 431 or Cl.

[0094] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3, V^oh, X , V^-^oh.V^o , Petition 870250103125, dated 11 / 11 / 2025, p. 50 / 470 / 431 F F or

[0095] In some modalities, R1 and R2, which may be identical or different, may represent: . / / / OH -CN, -CH3, V^oh, X CN CN F F or

[0096] In some modalities, R1 and R2, which may be identical or different, may represent: -CN, -CH3, Petition 870250103125, dated 11 / 11 / 2025, p. 51 / 470 / 431 EM HN^n' n'N or In some modes, R1 and R2, which may be identical or different, can represent: ,OH -CN, -CH3A OH CN N HN^n' F or Petition 870250103125, dated 11 / 11 / 2025, p. 52 / 470 / 431

[0098] In some modes, R1 and R2, which may be identical or different, can represent: -CN, CN NH2 THE OH -CH3,

[0099] No or In some specific modalities, R1 and R2 are different. In another specific embodiment, one of R1 and R2 is -CN. Other embodiments include compounds of Formula (Ia) or (Ia'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, wherein one of R1 and R2 is Compounds of Formulas (Ib) and (Ib')

[00100] In some embodiments, the compound is of Formula (Ib) or (Ib'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. Frog

[00101] The R and R4 groups can be defined as follows: General formula (I) above.

[00102] In some embodiments, the compound is of Formula (Ib), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. Petition 870250103125, dated 11 / 11 / 2025, p. 53 / 470 / 431 (Ib)

[00103] The Rae R4 groups can be as defined for the general Formula (I) above.

[00104] In some embodiments, R4 may represent C1-C6 alkyl, C6-C10 aryl, a 7- to 10-membered partially unsaturated heterocyclic group or a 5- to 10-membered heteroaryl group, wherein C1-C6 alkyl is optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl and 5- to 10-membered heteroaryl groups are optionally substituted by 1 to 3 R10 substituents, wherein R9 and R10 are as defined herein.

[00105] In some embodiments, R4 may represent C1-C6 alkyl, C6-C10 aryl, a 7- to 10-membered partially unsaturated heterocyclic group or a 5- to 10-membered heteroaryl group, wherein the C6-C10 aryl and 5- to 10-membered heteroaryl groups are optionally substituted by 1 to 3 R10 substituents, and wherein the R10 substituents are as defined herein.

[00106] In some embodiments, R4 may represent C1-C4 alkyl, phenyl, a 9-membered partially unsaturated heterocyclic group or a 5- to 6-membered heteroaryl group, wherein the phenyl and 5- to 6-membered heteroaryl groups are optionally substituted by 1 or 2 R10 substituents, and wherein the R10 substituents are as defined herein.

[00107] In some embodiments, the R10 substituents may independently represent C1-C4 alkyl, halogen, -OC1-C6 alkyl, NH2, -NH(C1-C4 alkyl) or -N(C1-C4 alkyl)2, wherein each C1-C4 alkyl is optionally substituted by 1 to 3 halogens.

[00108] In other embodiments, the R10 substituents may independently represent C1-C4 alkyl, halogen, -OC1-C6 alkyl or N(C1-C4 alkyl)2, wherein each C1-C4 alkyl is optionally substituted by 1 to 3 halogens.

[00109] In other embodiments, the R10 substituents may independently represent -CF3, halogen, -OCH3 or -N(CH3)2. Petition 870250103125, dated 11 / 11 / 2025, page 54 / 470 / 431

[00110] In some embodiments, R4 is C1-C10 alkyl, C1-C10 aryl, a partially unsaturated heterocyclic group of 7 to 10 members or a heteroaryl group of 5 to 10 members, wherein the C1-C10 aryl and the 5 to 10 member heteroaryl are optionally substituted by 1 to 3 R10 substituents, and each R10 is independently C1-C4 alkyl, halogen, -C1-C1 alkyl, -NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, wherein each C1-C4 alkyl is optionally substituted by 1 to 3 halogens.

[00111] In some embodiments, R4 is C1-C-alkyl, C-C10aryl, a 7- to 10-membered partially unsaturated heterocyclic group or a 5- to 10-membered heteroaryl, wherein the C-C10aryl and the 5- to 10-membered heteroaryl are optionally substituted by 1 to 3 R10 substituents, and each R10 is independently C1-C4alkyl, halogen, -C1-C-alkyl, or -N(C1-C4alkyl)2, wherein each C1-C4alkyl is optionally substituted by 1 to 3 halogens.

[00112] In some embodiments, R4 is a C1-C4 alkyl, phenyl, 9-membered partially unsaturated heterocyclic group or a 5- to 6-membered heteroaryl group, wherein the phenyl and 5- to 6-membered heteroaryl groups are optionally substituted by 1 or 2 R10 substituents, and each R10 is independently -CF3, halogen, -OCH3 or N(CH3)2.

[00113] Examples of specific R4 groups may include: Petition 870250103125, dated 11 / 11 / 2025, p. 55 / 470 / 431 Compounds of Formulas (Ic) and (Ic')

[00114] In some embodiments, the compound is of Formula (Ic) or (Ic'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[00115] Frog The R and R2a groups can be defined as follows: General formula (I) above.

[00116] a salt, a In some embodiments, the compound is of Formula (Ic), or a solvate or a pharmaceutically acceptable prodrug thereof.

[00117] The Rae R2a groups can be as defined for the General formula (I) above.

[00118] In some embodiments, R2a may represent C1-C6 alkyl or C6-C10 aryl, wherein C1-C6 alkyl is optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl is optionally substituted by 1 to 3 R10 substituents, and R9 and R10 are as defined herein.

[00119] In some embodiments, R2a may represent C1-C6 alkyl or C6-C10 aryl, and C1-C6 alkyl is optionally replaced by 1 to 3 halogens. Petition 870250103125, dated 11 / 11 / 2025, p. 56 / 470 / 431

[00120] In some embodiments, R2a is C1-C6 alkyl, such as C1-C4 alkyl or, preferably, ethyl. Compounds of Formulas (Id) and (Id')

[00121] In some embodiments, the compound is of Formula (Id) or (Id'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. (Id) (Id')

[00122] The groups R, Ra, R1a, R2b and R4a can be as defined for the general Formula (I) above.

[00123] In some embodiments, the compound is of Formula (Id), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[00124] The Ra, R1a, R2b and R4a groups can be as defined for the general Formula (I) above.

[00125] In some embodiments, R1 and R2b may independently represent -CN, C-C10aryl, C1-C-alkyl, C3-Cscycloalkyl or C(O)NH2, and each C1-C-alkyl is optionally replaced by 1 to 2 R16 substituents, as defined herein.

[00126] In some embodiments, R1ae R2b can independently represent -CN or C6-C10arila.

[00127] In some embodiments, R4a may represent C1-C6 alkyl.

[00128] In some forms, the R16 substitutes may Petition 870250103125, dated 11 / 11 / 2025, p. 57 / 470 / 431 independently represent -OH, -C(O)NH2, C3-C6cycloalkyl, -CN, C3-C6cycloaryl, halogen or heteroaryl of 5 to 8 members, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 2 C3-C4alkyls, and each heteroaryl of 5 to 10 members is optionally substituted by 1 to 2 R21 substituents, as defined herein.

[00129] In some embodiments, each R21 may independently represent halogen or C1-C4 alkyl.

[00130] In some embodiments, R1 and R2 are independently CN, C6-C10aryl, C1-C6alkyl, C3-C8cycloalkyl or -C(O)NH2, each C1-C6alkyl being optionally replaced by 1 to 2 R16 substituents; Each R16 is independently -OH, -C(O)NH2, C3C-cycloalkyl, -CN, C-C10aryl, halogen, or heteroaryl of 5 to 8 members, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 2 C1C4alkyl, and each heteroaryl of 5 to 10 members is optionally substituted by 1 to 2 R21 substituents; and each R21 is independently halogen or C1-C4alkyl. Compounds of Formulas (Ie) and (Ie')

[00131] In some embodiments, the compound is of Formula (Ie) or (Ie'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[00132] The groups R, Ra, R1b and R2c can be as defined for the general Formula (I) above.

[00133] In some embodiments, the compound is of Formula (Ie), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. Petition 870250103125, dated 11 / 11 / 2025, p. 58 / 470 / 431

[00134] The Ra, R1b and R2c groups can be as defined for the general Formula (I) above.

[00135] In some embodiments, R1b and R2c can form, together with the carbon atom to which they are attached, a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group, wherein each 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group is optionally substituted by oxo (=O), oxime (=N-OH), C1-C3 alkoxyoxime (=N-OC1C3alkyl) or 1 to 3 substituents independently selected from -OH and CF3.

[00136] In some embodiments, R1be R2c can form, together with the carbon atom to which they are attached, a C3-C8cycloalkyl or an 8- to 10-membered partially unsaturated carbocyclic group, wherein the 8- to 10-membered partially unsaturated carbocyclic group is optionally substituted by oxo (=O), oxime (=N-OH), methoxyoxime (=NOCH3) or 1 to 2 substituents independently selected from among -OH and CF3.

[00137] In some embodiments, R1b and R2c can form, together with the carbon atom to which they are attached, a C4-C6 cycloalkyl group or a group selected from Petition 870250103125, dated 11 / 11 / 2025, p. 59 / 470 / 431 N '0 / with the dashed lines representing the cyclohexanone fraction of the compound with formula (Ie) or (Ie') containing R1b and R2c.

[00138] In some embodiments, R1b and R2c can form, together with the carbon atom to which they are attached, a cyclopentyl group or a group selected from Nso or , with the dashed lines representing the cyclohexanone fraction of the compound with formula (Ie) or (Ie') containing R1b and R2c.

[00139] In some embodiments, R1b and R2c can form, together with the carbon atom to which they are attached, a group selected from , with the dashed lines representing the cyclohexanone fraction of the compound with formula (Ie) or (Ie') containing R1b and R2c.

[00140] In some embodiments, R1be and R2c can form, together with the carbon atom to which they are attached, a cyclopentyl group. Compound Formulas (If) and (If)

[00141] In some embodiments, the compound is of Formula (If) or (If'), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. Petition 870250103125, dated 11 / 11 / 2025, p. 60 / 470 / 431 (If) (If)

[00142] The groups R, Ra, R2 and R4b can be as defined for the general Formula (I) above.

[00143] In some embodiments, the compound is of Formula (If), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[00144] The Ra, R2 and R4b groups can be as defined for the general Formula (I) above.

[00145] In some embodiments, R2 and R4b can form, together with the carbon atom to which they are attached, a C3-C8 cycloalkyl, and each C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents, as defined herein.

[00146] In some embodiments, R2 and R4b can form, together with the carbon atom to which they are attached, a C3-C8 cycloalkyl group.

[00147] In some embodiments, R2d and R4b can form, together with the carbon atom to which they are attached, a cyclohexyl group. Formula Compound (Ig)

[00148] In some embodiments, the compound is of Formula (Ig), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. Petition 870250103125, dated 11 / 11 / 2025, p. 61 / 470 / 431 (Ig)

[00149] The Ra, R1 and R3 groups can be as defined for the general Formula (I) above.

[00150] In some embodiments, R1 and R3 can form, together with the carbon atom to which they are attached, a C3-C8 cycloalkyl, and each C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents, as defined herein.

[00151] In some embodiments, R1 and R3 can form, together with the carbon atom to which they are attached, a C3-C8 cycloalkyl group.

[00152] In some embodiments, R1 and R3 can form, together with the carbon atom to which they are attached, a cyclohexyl group.

[00153] In some embodiments, the compound of Formula (I) as described herein may be selected from Compounds 4, 8, 9, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60a, 60b, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 108, 109, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 154, 155, 163, 168, 169, 170, 173, 174, 175, 178, 179, 180, 181, 183, 189, 190, 191, 192, 193, 194, 195, 197, 198, 199, 200, 201, 202, 211, 212, 213, 214, 215, 216, 219, 221, 227, 228, 229, 230, 231, 232, 237, 238, 239, 245, 246, 247, 248, 249, 250, 251, 253, 254, 255, 257, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 290, 291, 297, 298, 305, 306, 313, 314, 321, 322, 330, 331, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 352, 353, 354, 355, 356, 357, 358, 360, 362, 371, 378, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 401, 402, 403, 406, 407, 408, 412, Petition 870250103125, dated 11 / 11 / 2025, page 62 / 470 / 431 413, 414, 416, 418, 422, 427, 428, 429, 430, 431, 433, 434, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 462, 463, 464, 465, 466, 468, 469, 470, 471, 472, 473, 474, 475, 476, 478, 479, 480, 481, 482, 483, 486, 488, 489, 492, 495, 496, 497, 498, 511, 512, 513, 514, 515, 520, 523, 524 and 534 of Table 1 below, or a salt, a solvate, or a pharmaceutically acceptable prodrug thereof. Table 1 O n|_]2 ( ]] / ^nh2 ii'8 0 Compound 4 O VOH Γ Y / -nh2 0 Compound 8 1 Yy—nh2 χ / χ / 'α o Compound 9 °^OH Cl T \ TVnh2 NC Í1 O Compound 14 Y^NH2 Λ \ ΥΓ [l / NH2 NC II 0 Compound 15 oCl o u-yNH2 l YYnh2 [τ'8 0 Compound 16 O / °nA Vnh2 1 ]] )^nh2 0 Compound 17 °yNH2 1 [l / NH2 []S 0 Compound 18 / 0YT °vnh2 1 JJ rí s 0 Compound 19 °TNH2 | Y y-nh2 ri s 0 Compound 20 hp,°r 0 Compound 21 íti,,V \ΙλΝΗ2 0 Compound 22 O.,' \XsVnh2 0 Compound 23 °N^NH2 f Y Ynh2 0 Compound 24 °A^NH2 1 1 Jl / -nh2 ri'8 0 Compound 25 Petition 870250103125, dated 11 / 11 / 2025, p. 63 / 470 / 431 pO °^nh2 1 [l / -nh2 [Is 0 Compound 26 OMe °yNH2 [ / ^NH2 0 Compound 27 °γ^ΝΗ2 1 [l )^nh2 11 s 0 Compound 28 r^ji °yNH2 Vnh2 °γ^ΝΗ2 CM XZ} CM X z CM X z 0 Compound 29 0 Compound 30 0 Compound 31 Cl ΓΊ C\ P>| °yNH2 °-^nh2 F'Vr|l °yNH2 | / ^NH2 11 s 0 Compound 32 TT ^NH2 0 Compound 33 TT ^NH2 11 s 0 Compound 34 °^0H ,-xOf3 0 oh CM XZA ~ TT >νη2 1 T IJ X^nh2 Compound 3 0 Compound 3 0 Compound 3<YCF3 °VNH / \ °^OH z X K> z X ro Vj / NH2 iV s NC II 0 Compound 38 0 Compound 39 u Compound 47 ° <x^NH2 Q °^OH p. °<pNH2 \T jj ^nh2 θ NC II 0 Composto 48 Vj ^NH2 θ NC II 0 Composto 49 Vj X^nh2 s NC II 0 Composto 50 Petition 870250103125, dated 11 / 11 / 2025, p. 64 / 470 / 431 KZ °υοη ZJ )Anh2 Z\ys NC II 0 Compound 51 ZK ° <ynh2 ZJ )ANH2 Z\ys NC II 0 Composto 52 °Y0H ZJ ]J ;Anh2 Λγ^δ NC II 0 Composto 53 °<ynh2 Vj ]]γΝΗ2 Zv^s NC II 0 Composto 54 °Y0H \ ZJ 1 / NH2 Ζ / ΖγΥ nc II 0 Composto 59 °yoH __[(R) iT^ / —NH2 ^Tv^s / / / o N Composto 60a °V0H \ %.f jT^NH2 NC II 0 Composto 60b ovnh2 \ ZJ 1J / NH2 ZZJKs nc II 0 Composto 61 O. ^YNH2 Jj ;Anh2 η2νΛοΠ Composto 62 °YYH2 \ Z 1 JyNH2 NC II 0 Composto 63 ovnh2 \ 1J / NH2 nc II 0 Composto 64 ,-Z \ KJ [l / ^nh2 NC II o Composto 65 \ ZJ / -nh2 Z / r / S nc II 0 Composto 66 °^NH \ ZJ IJ / -nh2 WZyy nc II 0 Composto 67 9 °yNH \ ZJ TKNH2 ^ / Zaz^s NC II 0 Composto 68 0 Z^NH \ ZJ T / nh2 Z / ZyZ NC II 0 Composto 69 xf3 <vZ \ ZJ JJ )^NH2 ^^Z / Y / Y NC O Composto 70 ^CHF; °^ΝΗ \ Zj JKKnh2 ^ / / Y^S NC II 0 Composto 71 Petition 870250103125, dated 11 / 11 / 2025, p. 65 / 470 / 431 ]] yNH2 Ay'S NC II 0 Compound 72 °<γΝΗ2 Vj b / NH2 Ay'S NC II o Compound 75 °^OH \ kJ}>—nh2s NCA Compound 81 ......α \ kJ ||yNH2 / Ϊ s NCJ 82 ° \ g Compound ^ / yyyy NC^ Compound 83 ° <ynh2 \=" / / y'''S" kj jj nh2 h2v s 0 composto 84 ox yoh y hc>Compound 89 °yNH2 | * <yNH2 \ kJ JJ / NH2 ^ / y^y^s hoa Composto 109 °V0H \ yJ / nh2 0 Composto 119 °^OH VJ [l ^nh2 / Va S NC II 0 Composto 120 °^OH Vj b / NH2 / yy^s NC II 0 Composto 121 °VOH F ^^A F \ | ]] ^hnh2 / γ S X / ° Composto 122 °^OH Lj nh2 NC II 0 Composto 123 °y-OH \ | Wnh2 yAy^s HO ° Composto 124 Petition 870250103125, dated 11 / 11 / 2025, p. 66 / 470 / 431 °^OH \ | || j^NH2 s HO^ Π 0 Compound 125 °^OH \ | || j^NH2 s nc— / ΓΙ 0 Compound 126 \ VJ ]J ^NH2 0 Compound 127 o ,-,r jj ^nh2 θ NC H 0 Compound 128 VJ [1 )^nh2 Ίγ / γ NC II2 o Compound <YNH FF \ [ ]T)^NH2 / 0 Composto 130 \j [I nh2 / Y / S NC II o Composto 131 ^γΝΗ \ | nh2 / Sf'S HO 0 Composto 132 Y^NH \ | nh2 HO—' Π O Composto 133 o F ΤγΝΗ \ | ]] nh2 nc—' ΙΊ o Composto 134 o? VNH / T~\ [ jT^—NH2 \_ / γγγ^3 / ° HOZ Composto 135 \ KJ ÍJ ^NH2 HO^ Composto 136 Ox \ ]T / —NH2 \= / / Yf's / 0 NC Composto 138 °^OH / ΓΛ1 TVnh2 \_ / 7\Z's \ 0 °^\ nh2 Composto 139 OK iYNH2 | J| )^NH2 \= / / Y^s \ 0 NC Composto 140 Petition 870250103125, dated 11 / 11 / 2025, p. 67 / 470 / 431 three Xnh2 X\ \ Ί| ^νη2 \_ / 7\As / 0 oj nh2 Compound 141 Ox XNH2 X\ \ ]] J—n h2 \_ / XX □ ° nh2 Compound 142 0v y^NH2 Ο·£χN2 \ / 0 °03 °χ 1^4 nh2 ]| xnh2 \_ / ΧΧ \ O NC Compound 144 «X \ zJ h Xnh2 XXX / 0 H2N^o Compound 145 ° <yNH2 \ kJ JJ / NH2 0 Composto 146 °vnh2 \T |X^nh2 / χΧ NC II 0 Composto 147 OK Xnh2 \ | Xx / X s HO 0 Composto 148 Ox X^NH2 \ | x^nh2 / X^s HO^ Π 0 Composto 149 Ox Xnh2 \ | || Xnh2 / χΧ nc— / ΓΙ 0 Composto 150 °X0H Y / NH2 \ Jns 0 Composto 154 °<yNH2 Z-J IJ / NH2 \ rn^s 0 Composto 155 οα^νη2 \ KJ jT)^NH2 XXx J 0 HO^7 Composto 163 %-OH \ YY YJ^NH2 J 0 HO^ Composto 168 / Jr™ \ Jl / -nh2s j 0 HO^7 Composto 169 \ kJ / ^nh2 XXx NC II 0 Composto 170 0 a / 0H VT ]] )^nh2 / X^s NC II 0 Composto 173 °<yNH2 Vj TVnh2 NC II 0 Composto 174 Petition 870250103125, dated 11 / 11 / 2025, p. 68 / 470 / 431 \ kJ jT / ^nh2 h2n4 π or Compound 175 O VoH \ ]T)^NH2S ! ° Compound 178 ° <yNH2 \ / nh2 ! ° Composto 179 °<γΟΗ \ KJ nh2 Α / ΊγΑδ 1 0 1 NH n'n Composto 180 °<yNH2 \ kJ ]] / ^nh2 1 0 \ NH N-n Composto 181 Ox ^nh2 \ KJ ]T)^NH2 / 0N<Z Br Composto 183 °N^OH \ | ]] y-nh2 NC 0 Composto 189 Cr y°H ij / -nh2 h2n^( 0 0 Composto 190 Ox y^NH2 \ | ]P^nh2 h2n^< 0 0 Composto 191 \ | ]] )^nh2 / γγ^3 NC ° Composto 192 OY N^NH \ | )^nh2 NC ° Composto 193 3γΝΗ / YY^s NC ° Composto 194 Ox N^nh2 \ | J)^nh2 NC 0 Composto 195 °y-OH r / Vj jf^NH2 \\ / ]fs h2n 0 Composto 197 ΎΝΗ nVJ T^nh2 Y / γγ'-'Β H2N 0 Composto 198 Petition 870250103125, dated 11 / 11 / 2025, p. 69 / 470 / 431 ox y^NH2 Aj jVNH2 h2n 0 Compound 199 °y^OH Vj ]j / ^NH2 h2nA Π V Compound 200 °γ^ΝΗ2 Vj ]j / ^NH2 h2nA Π V Compound 201 Vj jj h2nH\ / va °<γΟΗ \ \ Jj γΝΗ2 / v^s HO^ 0 Compound 211 Ox ^NH2 \ | J)^nh2 / ^Y^S HO^ 0 Compound 212 o? ^NH \ | J] )^nh2 Vv^s HO ° Compound 213 \ kJ TV NH2 W / X / S NC II 0 Compound 214 °ΎΝΗ2 \ kJ 1j / nh2 / o HO Compound 215 Λ OH °^NH \ KJ Compound s O Ίυ II / nh2 °yNH2 f )l / NH2 Compound 219 Ο 0<γΝΗ2 ZJ ΤΥΝΗ2 Compound 221 0 Γ VNH H2N<J T> NH2 / yy s / 0 Compound 228 °Ύ^νη2 \ TVNH2 Γ' or HO Compound 229 °ΎΝΗ2 \ \ | [1 γΝΗ2 ^==:= / / I HAVE Composed 230 Petition 870250103125, dated 11 / 11 / 2025, p. 70 / 470 / 431 οα^νη2 \ XX X / NH2 ^Zjy / ^S yo IJM / N'N Compound 231 °7yNH2 \ XX X / nh2 ^Zjyy^s ° \ ,N / N~n' Compound 232 °yyOH \ XXA s NX2 HX2Nh2 <yNH2 \ KJ XXNH2 y 0 nAu i N hn'N Composto 238 \ XX TX NH2 ZZyyy^s y 0N Kl 1 N hn~n Composto 239 °-^OH \ XX X^^nh2 / 0 1 / N / N^n' Composto 245 °7yNH2 \ XX JJ )^nh2 z^ZyyZ^s y 0 r ,n / N^n' Composto 246 \ XX XXNH2 NC H 0 Composto 247 \ \ | XX^nh2 NC II 0 Composto 248 °7yNH2 \ XX X / ^NH2 Z^ / ^Zy^s ' 0 Composto 249 °^yNH2 \ X 1 JJ / NH2 '‘Zy^S 0 Composto 250 V / \ 7^NH XX XX^NH2 / SjZ^s nc II 0 Composto 251 0 'JZoh \ XX ]T)^NH2 ZZ j / yy-s y 0 °~N Composto 253 V y^NH jZi s 1 0 O~N^ Composto 254 O y^NH2 \ XX XX^nh2V^==Z yyZ^-s / ° °'N Composto 255 Petition 870250103125, dated 11 / 11 / 2025, p. 71 / 470 / 431 0 ^nh2 \ KJ ΊΓ / ^νη2 7y^s / 0 i P Compound 258 Ox ^yOH \ VjT ]T)^nh2 / 0 h NçJ Br Compound 263 'yNH \ 1T)^NH2 / 0 Ny / Br Compound 263 'yNH \ 1T)^NH2 / 0 Ny / Br Compound 263 'yNH \ 1T)^NH2 / 0 Ny / Br Compound 263 ° ^ ^ TOH / Pf S \ 0 nn / > N Compound 271 ^NH \ j] / -NH2 / 0 NN / > N Compound 272 Ox Υ^νη2 \ J| nh2 \_ / 7Λγ>-'5 / ° NN / > N Compound 273 °%-OH \ j| )^nh2 \_ / 7yy^s N^x S 0 < / N\ OH Composto 278 y^NH 1 J| )^nh2 W / Y^s N^x ) 0 < y° N\ OH Composto 279 oj ^nh | Y^)^nh2 \= / 7ΐΓ^δ N O O po N=( hn^o Composto 280 Ox ^νη2 y-nh2 \= / 7ti^sN^\ / 0 < yo N\ OH Composto 281 0^0H \ kj im^nh2 / 11 sΒγ~^Γύ 0 N-0 Composto 287 Ox ^NH2 \ kj im^nh2 / 11 sΒγ~^Γύ 0 N-0 Composto 288 Ox ^yNH2 \ kJ nh2 yyy^s N-0 Composto 291 Ox VOH nc^£ JT / ^nh2 7ri^s 4 o Composto 297 Ox ^ΝΗ2 NC^L TV nh2 <\ o Composto 298 Petition 870250103125, of 11 / 11 / 2025, p. 72 / 470 / 431 Ο y-oH Ox yNH2 O yoH NC-X jT / ^NH2 NC-X JSSnH2 NCUT JySNH2 7fi~s 7fi~s 7yy^s O ry ° / \ ° Composto 305 Composto 306 Composto 313 O NcHX O yNH-X2 yo XSSnH2 nc4 TVnh2 s / yy^s / Y^sn ° / \ o / \ o Compound 314 Compound 321 Compound 322 Ox OO yNH2 yoH yNH2 |Γ / ^νη2 °r / -\í Xj X> V / n jj / N^ϊ V \ / s Compound 331 Compound 337 Compound 338 ox «A yNH2 Ox n^nh2 1 oxkl,N VNH2 o / \ 1 H )^nh2 / yy^s \ X XuX N >—2 Xyy^s yo 0 / 0 Compound 339 F Compound 340 Compound 341 Οχ ^yNH2 0. kll, o. NH2 iyNH2 \ I ]] X^N H2 UJs jTsnh2 \ | T>nh2 Xri^s / Sr s / 0 OO'í 0 Compound 342 Compound 343 HN-N Compound 344 Petition 870250103125, dated 11 / 11 / 2025, p. 73 / 470 / 431 Cl· A^nh2 [ j| )^nh2 L / TY^s \ o Ãzo N Compound 345 ox γΝΗ2 \Ví ]J^nh2 s Is No ^N'N U· Compound 346 °-^OH \_[ ]T)^NH2 / TI s / 0 0 y—FF Compound 347 VOH f 'Lj}^nh2 fjM0 <-·Ν'Ν à Compound 348 y oh \ | V^S^nh2 / V s / 0 0 Compound 349 y^NH V^NH2 s J|^l° <-N'N ó Compound 352 V NH2 [(ίΤ'ΊΓ / ^ΝΙ / Sr sN- i Compound 353 ° <yNH2 <S(R) ]T)^NH2 ^Sr s Composto 354 Ox y-NH2 \ Jj S^NH2 NoHN'N Composto 355 0J \VJ ]l ;>nh2 N 0 HN'N Compound 356 / í\ / CF3 ox Vnh2 's^stVnh2 s 0 Compound 357 / í\ / CF3 ox Vnh2s 0 Compound 358 Petition 870250103125, dated 11 / 11 / 2025, p. 74 / 470 / 431 Petition 870250103125, dated 11 / 11 / 2025, p. 75 / 470 / 431 ox A-nh2 T^^NH2 V ° οΠ N \ Compound 407 0 F y-NH ||^NH2 V ° N^X Compound 408 4yOH Vj b / NH2 94Π s ΝγΝ 0 Compound 412 Ox Ν yN4-ΠN Vj2 [ Compound 413 or F y-NH \ΓΊΡχνη2 X 0 Compound 414 °^NH2 \l Η XNH2 / X^s NC II 0 Compound 416 < ° <yNH2 / 0 Xy4 \l H Xnh2 / AL'S NC II O Composto 418 Ox y-NH2 ncXÃvNH2 / 1"! Composto 422 4yOH V / Kj ΤχΝΗ2 7 0 0 Composto 427 Ox lyNH2 0 F χΝΗ Ox ^NH2 ( T^nh2 j> fs / o N OH Compound 430 J yNH2 Ox Η nh2 / / o 0 Compound 428 / 7 OO Compound 429 N OH With ~yNH jf / -nh2 [l~s 0 post 431 With ox iyNH2 |j 0 KJn X1 43 No. ii V----- nn \ Compound 445 Petition 870250103125, dated 11 / 11 / 2025, p. 76 / 470 / 431 Compound 446 O Anh2 \ AÍ Α^Ανη2 γγγ^5 / o Compound 447 o, 7 V^NH \ ]J)^nh2 / o Cn Compound \48 !' O Aoh J;^nh2 yxx^s / O ..N n Compound 449 V \ AA ]T)^nh2 jaa-s / o £ / > Compound 450 O 'YOH \ kJ ]Γ)^νη2v^= / jSf'8 / o £ / > Compound 451 Oj>y 1 ^γ2 / > Άν° hn-n Compound 452 Ox A^nh2Xo-A AaA \__ H nh2 AAs NC II 0 Compound 453 / Οχ;γΝΗ2 \__ l| ;^nh28 NC II 0 Compound 454 °^OH no N JÁ 1 ANH2 0 Compound 462 Ox ^γΝΗ2 / ^o N Aj 1 xXnh2 7-711 so Compound 463 y^NH / τθ N A4 46 s 7L o nh2 Anh2N\AA ΊΓ ^nh2 γ / γ S 0 Compound 465 Z=NO Vnh2 Μ 1Γ / nh2 ^711 S <c / > 0 Compound 466 F^F °^γΝΗ2 Zví \ll| )^nh2 / >r^8 NC II 0 Compound 468 Petition 870250103125, dated 11 / 11 / 2025, p. 77 / 470 / 431 ox / ^o 'VN\ / / T~\ [ jT )ANH2 \ / Av^sx= / nc ΙΊ o Compound 469 J ox / VNH AA\ .1 ΊΓ )Anh2 \ / AaA^s V= / NC Π 0 Compound aa 270 y^T yΟN OH / \ / AaA^s V= / NC Π 0 Compound 471 Ox ANH | ]] )ANH2 \ / / Ar s \=Aic Π 0 Compound 472 Οχ / A^ Alt / \ j OH / AA\ [ ΊΓ ;anh2 \ / 'Y^S v= / nc ΙΊ 0 Compound 473 Oh ox í\^ y [ / =yANCH aa\ Π O Compound 474 Οχ V^NH AA\ \ ]T ;Anh2 \ / AAr^s X= / NC Π O Compound 475 O / ANH AA\ [ y >nh2 Α / ΤγΑ N7 O Compound 476 AAH=AH=Tan °2^A\NΟ Π O Compound 478 OH ox 'ANH \ ΊΓ / ^nh2 \ \ .À^V^s ^NC Π o Compound 479 Ox / A^NH / AA\ fy >nh2 \ / / AA^s O Compound 480 Ox a-nh2 c ν^ yy 481 , 57F~-ZV^NH °A ΑΑΛ AJ T )Anh2 / Ar s NC II 0 Compound 482 f^F o <aoh °A AA^ Aj T ^νη2 / AA^S NC II 0 Composto 483 F °γ^ΝΗ2 r^o ΑΆΑ F Al ll anh2 yAf'8 oQa N Composto 486 Petition 870250103125, dated 11 / 11 / 2025, p. 78 / 470 / 431 N b / Coi Ox A^OH T / -NH2 \zz 0 nposto 488 ox ^NH2 í zkj ΓΗη2 AAS / 0 N b / Composto 489 0 Anh2 NcJ J Ah' / Ar^s F^( / —' Π Vo / 0 Composto 492 F3N H2 °A H2 AH\ AAs 0 Compound 495 F3C ΑνΗ^ A / ^A || Anh2 / 0 Compound 511 ox 'VnWhere? NcA AAnh2 7Ai^s / 0 Compound 512 ox VOH NcJ / -NH2 AA-s 0 0 Compound 513 Ox Vnh2 NcA AANH2 / y S po FF Compound 514 0 Vnh2 ncA T xAnh2 / A / Yf s 0 Compound yj 515 Ox Z-NH2NC\AAaANH2 F^ OF Compound 520 ox Vnh2 1Γ )^NH2 C / Ar s C) 0 F^F Compound 524 A^OH h2nA 1 |AAnh2 AAAS / A> o Compound 227 Petition 870250103125, of 11 / 11 / 2025, p. 79 / 470 / 431

[00154] In some embodiments, the compound of Formula (I) as described here is Compound 4, 9, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60a, 60b, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 109, 119, 120, 121, 122, 123, 124, 125, 126, 127 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 189, 191, 192, 193, 194, 195, 197, 198, 199, 200, 201, Petition 870250103125, dated 11 / 11 / 2025, p. 80 / 470 / 431 202, 211, 212, 213, 214, 215, 216, 219, 221, 228, 229, 230, 231, 232, 237, 238, 239, 246, 247, 248, 249, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 291, 297, 298, 305, 306, 313, 314, 321, 322, 331, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 352, 353, 354, 355, 356, 357 or 358 of Table 1 above or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00155] In some embodiments, the compound of Formula (I) as described here is Compound 4, 9, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60b, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 109, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 189, 191, 192, 193, 194, 195, 198, 199, 200, 201, 202, 211, 212, 213, 214, 215, 216, 219, 228, 230, 231, 232, 237, 238, 239, 246, 247, 248, 249, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 291, 297, 298, 305, 306, 313, 314, 321, 322, 331, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 352, 353, 354, 355, 356, 357 or 358 of Table 1 above or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00156] In some embodiments, the compound of Formula (I) as described here is Compound 4, 9, 15, 16, 17, 18, 19, 20, 21, 22, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60b, 61, 62, 63, 64, 65, 66, 67, 68, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 109, 119, 120, 121, 122, 123, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 189, 191, 192, 194, 195, 198, 199, 201, 202, 212, 213, 214, 215, 216, 228, 230, 231, 232, 237, 238, 239, 246, 248, 249, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, Petition 870250103125, dated 11 / 11 / 2025, p. 81 / 470 / 431 273, 278, 279, 280, 281, 287, 288, 291, 297, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 352, 353, 354, 355, 356, 357 or 358 from Table 1 above or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00157] In some forms, the compound of Formula (I) as described here is Compound 4, 9, 15, 16, 17, 18, 19, 20, 21, 22, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60b, 61, 62, 63, 64, 65, 66, 67, 68, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 109, 119, 120, 121, 122, 123, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 189, 191, 192, 194, 195, 198, 199, 201, 202, 212, 213, 214, 215, 216, 228, 230, 231, 232, 237, 238, 239, 245, 246, 248, 249, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 291, 297, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 352, 353, 354, 355, 356, 357, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 401, 402, 403, 406, 407, 408, 413, 414, 416, 418, 422, 427, 428,429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451, 453, 454, 462, 463, 464, 465, 466, 468, 470, 472, 474, 475, 476, 478, 479, 480, 481, 482, 486, 489, 492, 495, 496, 498, 511, 512, 513, 514, 515, 520 or 524 from Table 1 above, or any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00158] In some embodiments, the compound of Formula (I) as described here is Compound 4, 15, 16, 17, 20, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60b, 61, 62, 63, 64, 65, 66, 67, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 109, 119, 120, 121, 122, 123, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 191, 192, 194, 195, 198, 199, 201, 202, 212, 213, Petition 870250103125, dated 11 / 11 / 2025, p. 82 / 470 / 431 214, 215, 216, 228, 230, 231, 232, 237, 238, 239, 246, 248, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 291, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 352, 353, 354, 355, 356, 357, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 401, 402, 403, 406, 407, 408, 413, 414, 416, 418, 422, 428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451, 453, 454,462, 463, 464, 465, 466, 468, 470, 472, 474, 475, 476, 479, 480, 481, 482, 486, 489, 495, 496, 498, 511, 512, 513, 514, 515, 520 or 524 from Table 1 above, or any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00159] In some embodiments, the compound of Formula (I) as described here is Compound 4, 15, 16, 20, 25, 26, 29, 30, 31, 32, 33, 34, 37, 47, 48, 49, 50, 51, 52, 54, 59, 60b, 61, 62, 63, 64, 65, 72, 75, 82, 83, 84, 89, 91, 97, 101, 109, 119, 121, 123, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 191, 192, 194, 195, 201, 212, 213, 214, 215, 216, 230, 231, 232, 238, 239, 246, 248, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 288, 291, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 346, 352, 353, 354, 355, 356, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 401, 402, 403, 406, 407, 408, 413, 414, 416, 418, 422,428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451, 453, 454, 462, 463, 464, 465, 466, 468, 470, 472, 474, 475, 476, 479, 480, 481, 482, 486, 489, 495, 496, 498, 511, 512, 513, 514, 515, 520 or 524 from Table 1 above, or any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00160] In some embodiments, the compound of Formula (I) as described here is Compound 4, 15, 16, 20, 25, 26, 29, 30, 31, 32, 33, 34, 37, 47, 48, 49, 50, 51, 52, 54, 59, 60b, 61, 62, 63, 64, 65, 72, 75, 82, 83, 84, 89, 91, 97, 101, 109, 119, 121, 123, 127, 128, 129, 130, 131, 132, 133, Petition 870250103125, dated 11 / 11 / 2025, page 83 / 470 / 431 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 191, 192, 194, 195, 201, 212, 213, 214, 215, 216, 230, 231, 232, 238, 239, 245, 246, 248, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 288, 291, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 346, 352, 353, 354, 355, 356, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 402, 403, 407, 408, 413, 414, 416, 418, 422, 428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451, 453, 454, 462, 463, 464, 465, 466, 468, 472, 475, 476, 479, 480, 481, 482, 486, 489, 495, 496, 498, 511, 512, 514, 515, 520 or 524 from Table 1 above or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00161] In some embodiments, the Formula (I) compound as described herein is Compound 4, 15, 25, 32, 33, 47, 48, 49, 50, 52, 54, 59, 60b, 61, 62, 63, 72, 75, 82, 83, 89, 97, 101, 109, 119, 121, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 163, 169, 170, 174, 179, 181, 183, 191, 192, 194, 195, 212, 213, 214, 215, 230, 231, 232, 238, 239, 246, 248, 250, 251, 253, 254, 255, 258, 263, 264, 272, 273, 278, 279, 280, 281, 288, 291, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 353, 355, 356, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 402, 403, 407, 408, 413, 418, 422, 428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451, 454, 463, 464, 465, 466, 472, 475, 476, 479, 481, 486, 489, 495, 498, 512, 514, 515, 520 or 524 from Table 1 above, or any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00162] In some forms, the Formula (I) compound as described here is Compound 15, 25, 32, 48, 49, 50, 52, 54, 59, 60b, 61, 62, 63, 72, 75, 82, 83, 97, 101, 109, 119, 127, 128, 129, 130, 135, 136 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 163, 169, 170, 174, 179, 181, 183, 191, 192, 194, 195, 212, 213, 215, 230, 231, 232, 238, 239, 246, Petition 870250103125, dated 11 / 11 / 2025, p. 84 / 470 / 431 248, 250, 251, 254, 255, 258, 263, 272, 273, 279, 281, 288, 291, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 353, 355, 356, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 402, 403, 407, 408, 413, 418, 422, 428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450,451, 454, 463, 464, 465, 466, 472, 475, 476, 479, 481, 486, 489, 495, 498, 512, 514, 515, 520 or 524 from Table 1 above, or any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00163] In some forms, the Formula (I) compound as described here is Compound 15, 25, 32, 48, 49, 50, 52, 54, 59, 60b, 61, 62, 63, 72, 75, 82, 83, 97, 101, 109, 119, 127, 128, 129, 130, 135, 136 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 163, 169, 170, 174, 179, 181, 183, 191, 192, 194, 195, 212, 213, 215, 230, 231, 232, 238, 239, 246, 248, 250, 251, 254, 255, 258, 263, 272, 273, 279, 281, 288, 291, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 353, 355, 356, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 402, 403, 407,418, 428, 430, 431, 434, 445, 446, 447, 448, 449, 450, 454, 463, 464, 465, 466, 476, 489, 512, 514, 515 or 524 from Table 1 above, or any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00164] In some forms, the Formula (I) compound as described herein is Compound 48, 50, 54, 60b, 61, 63, 72, 75, 83, 97, 101, 109, 127, 135, 140, 141, 143, 144, 145, 146, 147, 149, 163, 169, 170, 174, 179, 181, 191, 194, 195, 212, 215, 230, 231, 232, 238, 246, 248, 250, 251, 255, 258, 272, 273, 279, 281, 291, 306, 314, 321, 322, 331, 338, 339, 340, 341, 342, 345, 353, 355, 356, 391, 393, 395a, 395b, 397, 402, 428,430, 431, 434, 446, 447, 448, 450, 463, 464, 465, 466, 489, 512, 514, 515 or 524 from Table 1 above or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00165] In some forms, the Formula (I) compound as described here is Compound 48, 50, 54, 60b, 61, 63, 75, 83, 97, 101, Petition 870250103125, dated 11 / 11 / 2025, page 85 / 470 / 431 127, 135, 140, 141, 143, 144, 146, 147, 149, 163, 170, 174, 181, 191, 195, 215, 230, 231, 232, 238, 246, 248, 250, 251, 255, 258, 272, 273, 279, 281, 306, 314, 322, 338, 339, 340, 345, 353, 355, 356, 391, 393, 397, 402, 428, 430, 431, 434, 446, 447, 450, 463, 465, 466, 489, 512, 514, 515 or 524 of Table 1 above or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00166] In some embodiments, the compound of Formula (I) as described herein is Compound 54, 61, 63, 75, 140, 143, 146, 174, 215, 230, 250, 251, 273, 306, 322, 430, 446, 463, or 512 of Table 1 above or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 61, 63, 75, 143, 146, 174, 230, 250, 273, 306, 446, or 512 of Table 1 above or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.

[00167] In some embodiments, the compound of Formula (I) as described herein is Compound 4 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 33 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 47 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 89 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 121 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some forms, the compound of Formula (I) as described here is Compound 131 from the Table. Petition 870250103125, dated 11 / 11 / 2025, p. 86 / 470 / 431 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 132 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 133 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 134 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 138 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 139 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 214 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 253 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 264 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 278 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 280 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is the... Petition 870250103125, dated 11 / 11 / 2025, p. 87 / 470 / 431 Compound 298 of Table 1 above, or any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 305 of Table 1 above, or any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 408 of Table 1 above, or any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 413 of Table 1 above, or any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 422 of Table 1 above, or any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 429 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 451 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 472 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 475 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 479 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 481 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I). Petition 870250103125, dated 11 / 11 / 2025, page 88 / 470 / 431 as described herein is Compound 486 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 495 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 498 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 520 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00168] In some embodiments, the compound of Formula (I) as described herein is Compound 15 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 25 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 32 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 49 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 52 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 59 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 62 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some. Petition 870250103125, dated 11 / 11 / 2025, p. 89 / 470 / 431 embodiments, the compound of Formula (I) as described herein is Compound 72 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 82 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 109 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 119 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 128 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 129 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 130 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 136 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 145 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 148 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 150 of Table 1 above, or is any pharmaceutically available salt, solvate, or prodrug. Petition 870250103125, dated 11 / 11 / 2025, p. 90 / 470 / 431 acceptable thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 169 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 179 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 183 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 192 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 194 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 212 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 213 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 239 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 254 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 263 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 288 of Table 1 above, or is any salt, solvate, or prodrug. Petition 870250103125, dated 11 / 11 / 2025, p. 91 / 470 / 431 pharmaceutically acceptable thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 291 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 313 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 321 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 331 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 341 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 342 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 343 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 344 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 358 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 392 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 394a of Table 1 above, or is any. Petition 870250103125, dated 11 / 11 / 2025, p. 92 / 470 / 431 salt, solvate or pharmaceutically acceptable prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 394b of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 395a of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 395b of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 396 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 403 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 407 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 418 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 445 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 448 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 449 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 454 of the Table. Petition 870250103125, dated 11 / 11 / 2025, p. 93 / 470 / 431 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 464 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 476 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.

[00169] In some embodiments, the compound of Formula (I) as described herein is Compound 48 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 50 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 54 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 60b of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 61 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 63 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 75 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 83 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the... Petition 870250103125, dated 11 / 11 / 2025, p. 94 / 470 / 431. Compound of Formula (I) as described herein is Compound 97 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, Compound of Formula (I) as described herein is Compound 101 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, Compound of Formula (I) as described herein is Compound 127 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, Compound of Formula (I) as described herein is Compound 135 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 140 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 141 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 143 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 144 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 146 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 147 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 149 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In. Petition 870250103125, dated 11 / 11 / 2025, p. 95 / 470 / 431 In some embodiments, the compound of Formula (I) as described herein is Compound 163 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 170 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 174 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 181 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 191 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 195 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 215 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 230 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 231 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 232 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 238 of Table 1 above, or is any pharmaceutically available salt, solvate, or prodrug. Petition 870250103125, dated 11 / 11 / 2025, p. 96 / 470 / 431 acceptable thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 246 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 248 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 250 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 251 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 255 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 258 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 272 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 273 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 279 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 281 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 306 of Table 1 above, or is any salt, solvate, or prodrug. Petition 870250103125, dated 11 / 11 / 2025, p. 97 / 470 / 431 pharmaceutically acceptable thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 314 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 322 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 338 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 339 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 340 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 345 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 353 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 355 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 356 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 391 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 393 of Table 1 above, or is any. Petition 870250103125, dated 11 / 11 / 2025, p. 98 / 470 / 431 salt, solvate or pharmaceutically acceptable prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 397 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 402 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 428 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 430 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 431 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 434 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 446 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 447 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 450 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 463 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 465 of the Table. Petition 870250103125, dated 11 / 11 / 2025, p. 99 / 470 / 431 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 466 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 489 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 512 of Table 1 above, or is any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 514 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof.In some embodiments, the compound of Formula (I) as described herein is Compound 515 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound of Formula (I) as described herein is Compound 524 of Table 1 above, or is any pharmaceutically acceptable salt, solvate or prodrug thereof. Methods, uses, formulations and administration

[00170] The thiophene-substituted fused cyclohexanone compounds disclosed herein, or their pharmaceutically acceptable salts, solvates, or prodrugs, may be useful for the treatment or prevention of a disorder for which an ASIC inhibitor is indicated. Thus, in some embodiments, the compounds of Formula (I) may be formulated into a pharmaceutical composition comprising an effective amount of one or more of the compounds of Formula (I), or their pharmaceutically acceptable salts, solvates, or prodrugs, and a pharmaceutically acceptable carrier, diluent, or excipient.

[00171] In certain forms, the present description thus provides, Petition 870250103125, dated 11 / 11 / 2025, page 100 / 470 / 431 a method for treating or preventing a disorder for which an ASIC inhibitor is indicated comprising administering to a patient or individual identified as needing the same at least one compound of Formula (I), as defined herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[00172] Identifying those patients who need treatment for the disorders described above is well within the capacity and knowledge of one skilled in the art. Some of the methods for identifying patients who are at risk of developing the above disorders and who can be treated by the method in question are recognized in medical techniques, such as family history and the presence of risk factors associated with the development of this disorder in the patient in question. A clinician skilled in the art can readily identify such candidate patients by using, for example, clinical tests, physical examination, and medical / family history.

[00173] As used herein, the term effective amount means the quantity of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal, or human being that is being sought, for example, by a researcher or clinician. Furthermore, the term therapeutically effective amount means any amount that, compared with a corresponding individual who has not received such an amount, results in treatment, cure, prevention, or improvement of a disorder or a side effect, or a decrease in the rate of progression of a disorder. The term also includes within its scope quantities that are effective in improving normal physiological function.

[00174] As used herein, the terms treatment, treat, and treating refer to reversing, alleviating, delaying the onset of, or inhibiting the progression of a disorder or one or more symptoms thereof, as described herein. In some modalities, treatment may be administered after the Petition 870250103125, dated 11 / 11 / 2025, page 101 / 470 / 431 development of one or more symptoms. In other modalities, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual before the onset of symptoms (e.g., in view of a history of symptoms and / or in view of genetic or other susceptibility factors). Treatment may also be continued after resolution of symptoms, for example, to prevent or delay their recurrence.

[00175] The terms patient or individual, as used herein, generally refer to a mammal. An individual, therefore, refers to, for example, dogs, cats, horses, cows, pigs, guinea pigs, and the like. Preferably, the individual is a human being. When the individual is a human being, the individual may be a patient or a healthy human being.

[00176] The term pharmaceutically acceptable carrier, diluent or excipient and equivalent terms refer to a non-toxic carrier, diluent or excipient that does not destroy the pharmacological activity of the compound with which it is formulated.Pharmaceutically acceptable carriers, diluents, or excipients that may be used in the compositions of this disclosure include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial mixtures of glycerides of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene block polymers, polyethylene glycol, and wool fat.

[00177] As used herein, the term ASIC inhibitor denotes a Petition 870250103125, dated 11 / 11 / 2025, page 102 / 470 / 431 compound that inhibits acid-sensitive ion channels, such as acid-sensitive ion channel 1a (ASIC1a) or acid-sensitive ion channel 1b (ASIC1b).

[00178] In some embodiments, the disorders or conditions that may be treated using the compounds of Formula (I) described herein or their pharmaceutically acceptable salts, solvates or prodrugs may include pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough and acute lung injury.

[00179] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of a disorder, wherein the disorder is pain. In some embodiments, pain may include acute pain or chronic pain. In some embodiments, pain may include nociceptive pain, inflammatory pain, neuropathic pain, idiopathic pain, musculoskeletal pain, visceral pain or abdominal pain. In some embodiments, pain may include inflammatory pain or neuropathic pain. In some embodiments, pain may include inflammatory pain. In other embodiments, pain may include neuropathic pain.

[00180] In some modalities, pain may include pain related to rheumatic disorders. In other modalities, pain may include arthritis pain. In some modalities, pain may include osteoarthritis pain, rheumatoid arthritis pain, ankylosing spondylitis pain, gouty arthritis pain, psoriatic arthritis pain, juvenile arthritis pain, juvenile rheumatoid arthritis pain, bursitis pain, tendinitis pain, tenosynovitis pain, periarthritis pain, or polymyalgia rheumatica pain.

[00181] In certain modalities, pain may include inflammatory osteoarthritis pain or neuropathic osteoarthritis pain. In some modalities, pain may include osteoarthritis pain of the hip, osteoarthritis pain of the knee, Petition 870250103125, dated 11 / 11 / 2025, p. 103 / 470 / 431 pain from osteoarthritis of the spine, pain from osteoarthritis of the shoulder, pain from osteoarthritis of the hand, pain from osteoarthritis of the finger, pain from osteoarthritis of the thumb, pain from osteoarthritis of the foot, or pain from osteoarthritis of the toe. In certain modalities, the pain may include inflammatory pain from rheumatoid arthritis or neuropathic pain from rheumatoid arthritis. In certain modalities, the pain may include shoulder bursitis pain or hip bursitis pain. In some modalities, the pain may include shoulder tendinitis pain, elbow tendinitis pain, hip tendinitis pain, wrist tendinitis pain, knee tendinitis pain, or heel tendinitis pain. In certain modalities, the pain may include shoulder periarthritis pain or hip periarthritis pain.

[00182] In some modalities, pain may include pain associated with musculoskeletal trauma and / or soft tissue trauma, including pain associated with sprains, strains, swelling, or stiffness. In certain modalities, pain may include pain associated with musculoskeletal trauma and / or soft tissue trauma of the back, shoulder, or ankle. In certain modalities, pain may include myofascial pain syndrome. In other modalities, pain may include exercise-induced pain, repetitive motion injury pain, or pain due to a bone fracture. In other modalities, pain may include temporomandibular joint disorder pain.

[00183] In certain modalities, pain may include eye pain. In certain modalities, pain may include postoperative pain after cataract surgery, postoperative pain after refractive surgery, eye pain from a non-penetrating wound, foreign body sensation eye pain, burning or stinging in the eye, uveitis pain, iritis pain, retinopathy pain, or optic neuritis pain.

[00184] In some modalities, pain may include dental pain. In certain modalities, pain may include toothache or postoperative pain following dental surgery, including pain after tooth extraction.

[00185] In certain modalities, pain may include postoperative pain. Petition 870250103125, dated 11 / 11 / 2025, page 104 / 470 / 431 In some modalities, pain may include postoperative pain after minor surgery, postoperative pain after general surgery, postoperative pain after orthopedic surgery, postoperative pain after bunionectomy, postoperative pain after hernioplasty, postoperative pain after herniorrhaphy, postoperative pain after arthroplasty, including pain after knee arthroplasty or pain after hip arthroplasty, postoperative pain after gynecological surgery, postoperative pain after cesarean section, postoperative pain after abdominoplasty, postoperative pain after laminectomy, postoperative pain after hemorrhoid removal, or postoperative pain after thoracotomy.

[00186] In certain modalities, pain may include dysmenorrhea pain, episiotomy pain, endometriosis pain, or postpartum pain, including postpartum cramping pain.

[00187] In certain modalities, pain may include pain due to the common cold, pain due to the flu, sore throat, sinus pain including sinusitis pain, pain due to immunization, earache, fever pain, body aches, muscle pain, bone pain, joint pain, back pain, or neck pain.

[00188] In certain modalities, pain may include neuralgia. In some modalities, this pain may include trigeminal neuralgia, postherpetic neuralgia, occipital neuralgia, postsurgical neuralgia, pudendal neuralgia, diabetic neuralgia, glossopharyngeal neuralgia, intercostal neuralgia, or drug-induced neuralgia, including cancer chemotherapy-induced neuralgia or antiretroviral therapy-induced neuralgia.

[00189] In certain modalities, pain may include nerve injury pain, peripheral nerve injury pain, nerve compression pain, nerve avulsion injury pain, nerve entrapment injury pain, radiculopathy pain, brachial plexus injury pain, burning mouth syndrome pain, complex regional pain syndrome type 1, complex regional pain syndrome type 2, neuroma pain, Morton's neuroma pain, injury pain of Petition 870250103125, dated 11 / 11 / 2025, page 105 / 470 100 / 431 spinal cord, spinal cord compression pain, radicular pain, sciatica, spinal stenosis pain, cervical spine injury pain, brain injury pain, or post-stroke pain.

[00190] In some modalities, pain may include neuropathy pain. In certain modalities, pain may include peripheral neuropathy pain, polyneuropathy pain, mononeuropathy pain, multiple mononeuropathy pain, proximal neuropathy pain, sensory neuropathy pain, small fiber sensory neuropathy pain, idiopathic neuropathy pain, or distal sensory polyneuropathy pain. In certain modalities, pain may include diabetic neuropathy pain. In some modalities, pain may include diabetic peripheral neuropathy pain, diabetic polyneuropathy pain, diabetic proximal neuropathy pain, or diabetic mononeuropathy pain. In certain modalities, pain may include autoimmune disease neuropathy pain. In some modalities, pain may include Sjögren's syndrome neuropathy pain, Guillain-Barré syndrome neuropathy pain, chronic inflammatory demyelinating polyneuropathy pain, or vasculitis neuropathy pain.In some modalities, pain may include neuropathic pain from multiple sclerosis. In certain modalities, pain may include pain from carpal tunnel syndrome. In certain modalities, pain may include neuropathy pain associated with a bacterial infection or neuropathy pain associated with a viral infection. In some modalities, pain may include neuropathy pain from Lyme disease, neuropathy pain from Epstein-Barr virus, neuropathy pain from hepatitis B virus, neuropathy pain from hepatitis C virus, neuropathy pain from leprosy, neuropathy pain from diphtheria, or neuropathy pain from human immunodeficiency virus (HIV), including distal symmetrical polyneuropathy pain from HIV. In certain modalities, pain may include hereditary neuropathy pain. In some modalities, pain may include neuropathy pain from Charcot-Marie-Tooth disease or hereditary neuropathy pain with susceptibility to... Petition 870250103125, dated 11 / 11 / 2025, p. 106 / 470 101 / 431 pressure palsy (HNPP - hereditary neuropathy with pressure palsies). In certain modalities, pain may include neuropathy pain caused by a malignant tumor, neuropathy pain caused by a benign tumor, or paraneoplastic neuropathy pain. In some modalities, pain may include myeloma neuropathy pain, lymphoma neuropathy pain, or amyloid neuropathy pain. In certain modalities, pain may include liver disease neuropathy pain, uremic neuropathy pain, connective tissue disorder neuropathy pain, hypothyroidism neuropathy pain, alcohol use neuropathy pain, or vitamin deficiency neuropathy pain. In some modalities, pain may include vitamin B deficiency neuropathy pain, including vitamin B1, niacin, vitamin B6, or vitamin B12 deficiency neuropathy pain, or vitamin E deficiency neuropathy pain.In certain modalities, pain may include neuropathic pain from exposure to toxic substances, including neuropathic pain after lead exposure or neuropathic pain after mercury exposure. In certain modalities, pain may include neuropathic pain induced by antiretroviral therapy or neurotoxic drug-induced neuropathic pain. In certain modalities, pain may include chemotherapy-induced neuropathic pain, including platinum-based antineoplastic drug-induced neuropathic pain or chemotherapy-induced peripheral neuropathy (CIPN), radiation therapy-induced pain, including radiation therapy-induced neuropathic pain, cancer-targeted therapy-induced neuropathic pain, or immunotherapy-induced neuropathic pain. In some modalities, this pain may include central neuropathic pain.In certain conditions, the pain may include central post-stroke pain, central neuropathic pain related to spinal cord injury, central neuropathic pain related to brain injury, or central neuropathic pain related to multiple sclerosis.

[00191] In certain modalities, pain may include cancer pain. In Petition 870250103125, dated 11 / 11 / 2025, page 107 / 470 102 / 431 In some modalities, pain may include bone cancer pain, episodic pain, cancer neuropathy pain including neuropathy caused by a tumor pressing on a nerve. In some modalities, pain may include mucositis pain, stomatitis pain, or post-mastectomy pain syndrome (PMPS).

[00192] In certain modalities, pain may include post-amputation pain. In some modalities, pain may include phantom pain, phantom limb pain, or residual limb pain.

[00193] In some forms, the pain may include headache pain, migraine pain including migraine pain with aura, migraine pain without aura, tension headache pain or cluster headache pain.

[00194] In certain modalities, pain may include Paget's disease pain. In other modalities, pain may include fibromyalgia-associated pain. In certain modalities, pain may include lupus-associated pain, including lupus-related inflammatory pain and lupus-related neuropathy pain. In some modalities, pain may include gastrointestinal motility disorder pain, irritable bowel syndrome pain, Crohn's disease pain, ulcer-related pain, or ulcerative colitis pain. In other modalities, pain may include incontinence pain or interstitial cystitis pain. In certain modalities, pain may include herpes zoster pain. In certain modalities, pain may include angina-induced pain. In certain modalities, pain may include animal bite or sting pain or burn pain, including first-degree, second-degree, or third-degree burn pain.

[00195] In some embodiments, compounds of Formula (I) or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of arthritis, including rheumatoid arthritis (Xu, Petition 870250103125, dated 11 / 11 / 2025, p. 108 / 470 103 / 431 Y. et al., 2021).

[00196] In some embodiments, compounds of Formula (I) or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of stroke (Chassagnon, IR et al., 2017; Qi, X. et al., 2022).

[00197] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of an epileptic disorder (Cheng, Y. et al., 2021).

[00198] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of anxiety (Cittaro, D. et al., 2016; Battaglia, M. et al., 2019; Yellepeddi, V. et al., 2020).

[00199] In some embodiments, compounds of Formula (I) or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of post-traumatic stress disorder (PTSD) (Wemmie, JA et al., 2004).

[00200] In some embodiments, compounds of Formula (I) or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of depression (Coryell, MW et al., 2009; Mango, D. et al., 2019).

[00201] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising them, may be used. Petition 870250103125, dated 11 / 11 / 2025, p. 109 / 470 104 / 431 for the treatment or prevention of multiple sclerosis (Vergo S. et al., 2011; Wei W. et al., 2021).

[00202] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of Alzheimer's disease (Mango, D. et al., 2023).

[00203] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of gastroesophageal reflux disease (Han, X. et al., 2022).

[00204] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of cancer. In certain modalities, cancer may include glioma, such as glioblastoma multiforme (Sheng, Y. et al., 2021), hepatocellular carcinoma (HCC) (Zhang, Y. et al., 2022), gastric cancer (Zhang, Q. et al., 2017; Chen, X. et al., 2018), pancreatic cancer (Zhu, L. et al., 2021), lung cancer (Wu, Y. et al., 2017), breast cancer (Gupta, SC et al., 2016; Yang, C. et al., 2020), skin cancer including melanoma (Bychkov, ML et al., 2021), prostate cancer (Chen, B. et al., 2016) or chronic myeloid leukemia (Bychkov, ML et al., 2020).

[00205] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of a migraine (Holland, PR et al., 2012; Karsan, N. et al., 2018).

[00206] In some forms, compounds of Formula (I) or Petition 870250103125, dated 11 / 11 / 2025, p. 110 / 470 105 / 431 their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of cough (Reznikov, LR et al., 2016).

[00207] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of acute lung injury (Liu, Y. et al., 2023).

[00208] In some embodiments, compounds of Formula (I) or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of itching (Papalampropoulou-Tsiridou, M. et al., 2022; Jung, M. et al., 2023).

[00209] In some embodiments, the therapeutically effective amount of a compound, as defined herein, may be administered to a patient or individual, alone or mixed with a pharmaceutically acceptable carrier, diluent, or excipient.

[00210] The compositions described herein may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implanted reservoir. The term parenteral, as used herein, includes subcutaneous, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrathecal, intrahepatic, intralesional, and intracranial injection or infusion techniques. Other modes of administration also include intradermal or transdermal administration.

[00211] Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compounds, liquid dosage forms may contain diluents. Petition 870250103125, dated 11 / 11 / 2025, p. 111 / 470 106 / 431 inert substances commonly used in the art, such as, for example, water or other solvents, solubilizing and emulsifying agents, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, peanut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan fatty acid esters and mixtures thereof. In addition to inert diluents, oral compositions may also include excipients, such as humectants, emulsifying and suspending agents, sweetening agents, flavorings and fragrances.

[00212] Injectable preparations, for example, sterile aqueous or oily injectable suspensions, may be formulated according to known techniques using dispersing agents or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension, or emulsion in a parenterally acceptable non-toxic diluent or solvent, for example, a solution in 1,3-butanediol. Among the acceptable carriers and solvents that may be employed are water, Ringer's solution, USP, and isotonic sodium chloride solution. In addition, sterile fixed oils are conventionally employed as a solvent or a suspension medium. For this purpose, any mild, mild fixed oil may be employed, including synthetic mono- or diglycerides. Furthermore, fatty acids, such as oleic acid, are used in the preparation of injectables.

[00213] Injectable formulations can be sterilized, for example, by filtration through a filter that retains bacteria or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium before use.

[00214] In order to prolong the effect of a supplied compound, it is Petition 870250103125, dated 11 / 11 / 2025, page 112 / 470 107 / 431 It is often desirable to delay the absorption of the compound from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of crystalline or amorphous material with low water solubility. The rate of absorption of the compound then depends on its rate of dissolution, which in turn may depend on the size of the crystals and the crystalline form. Alternatively, delayed absorption of a parenterally administered compound form is achieved by dissolving or suspending the compound in an oil carrier. Injectable depot forms are made by forming matrices of the microencapsulated compound in biodegradable polymers such as polylactidepolyglycolide. Depending on the compound-to-polymer ratio and the nature of the specific polymer employed, the rate of compound release can be controlled.

[00215] Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by trapping the compound in liposomes or microemulsions that are compatible with body tissues.

[00216] Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of the present description with non-irritating excipients or carriers, such as cocoa butter, polyethylene glycol or a suppository wax, which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.

[00217] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one pharmaceutically acceptable inert excipient or carrier, such as sodium citrate or dicalcium phosphate, and / or a) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol. Petition 870250103125, dated 11 / 11 / 2025, page 113 / 470 108 / 431 and silicic acid, b) binders, such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone (PVP), sucrose and acacia, c) humectants, such as glycerol, d) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate, e) solution retarders, such as paraffin, f) absorption accelerators, such as quaternary ammonium compounds, g) wetting agents, such as cetyl alcohol and glycerol monostearate, h) absorbents, such as kaolin and bentonite clay, and i) lubricants, such as calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also include buffering agents.

[00218] Solid compositions of a similar type may also be employed as fillers in soft or hard gelatin capsules using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like. Solid dosage forms of tablets, dragees, capsules, pills and granules may be prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical formulation art. They may optionally contain opacifying agents and may also be of a composition in which they release the active ingredient(s) only or, preferably, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of incorporation compositions that may be used include polymeric substances and waxes.Solid compositions of a similar type can also be used as fillers in soft or hard gelatin capsules using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like.

[00219] The supplied compounds may also be in the form Petition 870250103125, dated 11 / 11 / 2025, page 114 / 470 109 / 431 microencapsulated with one or more excipients, as mentioned above. Solid dosage forms of tablets, dragees, capsules, pills and granules may be prepared with coatings and shells, such as enteric coatings, release control coatings and other coatings well known in the pharmaceutical formulation art. In such solid dosage forms, the active compound may be mixed with at least one inert diluent, such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances that are not inert diluents, for example, tablet-forming lubricants and other tablet-forming aids, such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents.They may optionally contain opacifying agents and may also be of a composition in which they release the active ingredient(s) only or, preferably, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of incorporation compositions that may be used include polymeric substances and waxes.

[00220] Dosage forms for topical or transdermal administration of a compound of the present description include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The active component is mixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservatives or buffers that may be required. Ophthalmic formulations, ear drops, and eye drops are also contemplated as being within the scope of the present description. In addition, the description contemplates the use of transdermal patches, which have the added advantage of providing controlled application of a compound to the body. Such dosage forms may be made by dissolving or dispensing the compound in the appropriate medium. The Petition 870250103125, dated 11 / 11 / 2025, page 115 / 470 110 / 431 absorption enhancers can also be used to increase the flow of the compound through the skin. The rate can be controlled by providing a rate control membrane or by dispersing the compound in a gel or polymeric matrix.

[00221] The pharmaceutically acceptable compositions provided herein may also be administered by nasal spray or inhalation. Such compositions are prepared in accordance with well-known techniques in the art of pharmaceutical formulation and may be prepared as solutions in saline solution, employing benzyl alcohol or other suitable preservatives, absorption enhancers to increase bioavailability, fluorocarbons and / or other conventional solubilizing or dispersing agents.

[00222] The pharmaceutically acceptable compositions provided herein may be formulated for oral administration. These formulations may be administered with or without food. In some embodiments, pharmaceutically acceptable compositions of this disclosure are administered without food. In other embodiments, pharmaceutically acceptable compositions of this disclosure are administered with food.

[00223] The amount of supplied compounds that can be combined with carrier materials to produce a composition in a single dosage form will vary depending on the patient being treated and the specific mode of administration. The supplied compositions can be formulated so that a dosage between 0.01 and 100 mg / kg body weight / day of the inhibitor can be administered to a patient receiving these compositions.

[00224] It should also be understood that a specific dosage and treatment regimen for any particular patient will depend on a variety of factors, including age, body weight, general health, sex, diet, administration schedule, excretion rate, and a combination of Petition 870250103125, dated 11 / 11 / 2025, page 116 / 470 111 / 431 medications, the discernment of the attending physician, and the severity of the specific disorder being treated. The amount of a compound provided in the composition will also depend on the specific compound in the composition.

[00225] The compounds or compositions described herein may be administered using any amount and any route of administration effective to treat or lessen the severity of the disorders contemplated in the present invention. The exact amount required will vary from individual to individual, depending on the species, age and general condition of the individual, the severity of the infection, the specific agent, its mode of administration, and the like. The compounds provided are preferably formulated in unit dosage form to facilitate administration and uniformity of dosage. The expression "unit dosage form," as used herein, refers to a physically distinct unit of the agent suitable for the patient to be treated. It will be understood, however, that the total daily use of the compounds and compositions of the present disclosure will be decided by the attending physician within the scope of medical judgment.The specific effective dose level for any given patient or organism will depend on a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the patient's age, body weight, general health, sex, and diet; the time of administration, the route of administration, and the rate of excretion of the specific compound employed; the duration of treatment; drugs used in combination with or concurrently with the specific compound employed; and similar factors well known in medical techniques.

[00226] The pharmaceutically acceptable compositions of this disclosure may be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (such as by means of Petition 870250103125, dated 11 / 11 / 2025, page 117 / 470 112 / 431 of powders, ointments or drops), buccal, as an oral or nasal spray, or similar, depending on the severity of the infection to be treated. In certain modalities, the supplied compounds may be administered orally or parenterally at dosage levels of about 0.01 mg / kg to about 50 mg / kg and, preferably, about 1 mg / kg to about 25 mg / kg of the individual's body weight per day, once or more times a day, to obtain the desired therapeutic effect.

[00227] After an individual's condition improves, a maintenance dose of a compound or composition described herein may be administered, if necessary. Subsequently, the dosage or frequency of administration, or both, may be reduced, depending on the symptoms, to a level at which the improved condition is maintained. When symptoms are relieved to the desired level, treatment should cease. The individual may, however, require long-term intermittent treatment in case of recurrence of the disorder's symptoms.

[00228] It is understood, however, that the total daily use of the compounds and compositions of this description will be decided by the attending physician within the scope of medical judgment. The specific inhibitory dose for each patient will depend on a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex, and diet of the patient; the time of administration, the route of administration, and the excretion rate of the specific compound employed; the duration of treatment; drugs used in combination with or concurrently with the specific compound employed; and similar factors well known in medical techniques.

[00229] The total daily inhibitory dose of the compounds described herein administered to an individual in single or divided doses may be in amounts, for example, from 0.01 to 50 mg / kg of body weight or Petition 870250103125, dated 11 / 11 / 2025, p. 118 / 470 113 / 431 most commonly from 0.1 to 25 mg / kg of body weight. Single-dose compositions may contain such amounts or submultiples thereof to compose the daily dose. In one embodiment, treatment regimens according to the present description comprise administering to a patient requiring such treatment about 10 mg to about 1000 mg of the compound(s) of the present description per day in single or multiple doses. Examples General methods Preparation of compounds

[00230] Reagent-grade chemicals and anhydrous solvents were purchased from commercial sources and, unless otherwise stated, were used without further purification. Product names were determined using the nomenclature software included in ChemDraw (PerkinElmer). Where it is stated that compounds were prepared analogously to previous or intermediate examples, the reaction time, number of reagent equivalents, temperature, finishing and purification techniques may differ slightly from the example described. Purifications

[00231] Chromatographic separations were performed on: - Teledyne ISCO CombiFlash flash chromatography systems, using pre-packed SiO2 or C18 columns.

[00232] - High-performance preparatory liquid chromatography system Teledyne ISCO ACCQPrep; Column: Gemini 5 um C18 110 A, 150 x 30 mm.

[00233] - Biotage Isolera flash chromatography systems, using pre-packed SiO2 or C18 columns.

[00234] HPLC Semi-Prep Waters Mass Trigger; Column: Gemini 5 um NX-C18 110 A, 100 x 30 mm.

[00235] Chiral separations were performed in: - Mettler Toledo Berger supercritical fluid chromatography Petition 870250103125, dated 11 / 11 / 2025, page 119 / 470 114 / 431 Minigram; Column: ChiralPak IG, 20 x 250 mm or ChiralPak IG, 10 x 250 mm.

[00236] - Waters ACQUITY Supercritical Fluid Chromatography UPC2; Column: ChiralPak IG, 10 x 250 mm. Analytical methods

[00237] LC-MS were executed on: - Waters UPLC-MS; Column: UPLC Acquity, CSH C18, 1.7 µm, 2.1 x 30 mm; Methods: 5% to 95% CH3CN in H2O with 0.1% (v / v) formic acid for 2 min or 5% to 95% CH3CN in 10 mM ammonium bicarbonate for 2 min.

[00238] - Agilent HPLC-MS; Column: Kinetex EVO C18 100 A 2.6 µm, 50 x 3 mm; Method: 10% to 95% CH3CN with 0.1% (v / v) formic acid in H2O with 0.1% (v / v) formic acid for 4.5 min.

[00239] - Agilent UPLC-MS; Column: Kinetex EVO C18 100 A 1.7 µm, 50 x 3 mm; Method: 5% to 95% CH3CN with 0.1% (v / v) formic acid in H2O with 0.1% (v / v) formic acid for 3 min.

[00240] Analytical CFS tests were performed at Waters ACQUITY UPC2; Column: ChiralPak IG 4.6 x 250 mm or ChiralPak IC 4.6 x 150 mm.

[00241] NMR spectroscopy was performed using a 400 MHz Varian NMR spectrometer (AS 400) with an Inova interface. In all cases, the NMR data were consistent with the proposed structures. Characteristic chemical shifts (δ) are given in parts per million using conventional abbreviations for peak designation: e.g., s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of triplets; etc. Abbreviations 9-BBN 9-Borabicyclo[3.3.1]nonane δ Chemical shift An Angstrom Acetyl Petition 870250103125, dated 11 / 11 / 2025, page 120 / 470 115 / 431 Bn Benzyl Boc tert-Butoxycarbonyl bs Broad singlet Bu Butyl Calcified d Doublet DAST Diethylaminosulfur trifluoride dd Doublet of doublets dt Doublet of triplets DCM Dichloromethane DDQ DIBALH 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone Diisobutylaluminum hydride DIPEA N,N-Diisopropylethylamine DMAP 4-Dimethylaminopyridine DMF N,N-Dimethylformamide DMP Dess-Martin periodinane DMPU N,N'-Dimethylpropylene urea DMSO Dimethyl sulfoxide Dppf EA 1,1'-Bis(diphenylphosphino)ferrocene Ethyl acetate ee Enantiomeric excess Et Ethyl EtOH Ethanol eq Equivalents g HATU Grams Hexafluorophosphate Azabenzotriazole Tetramethyluronium Hz Hertz HPLC High-performance liquid chromatography i-Pr Isopropyl J Coupling constant L Liter LC-MS Liquid chromatography-mass spectrography LDA Lithium diisopropylamide LHMDS Lithium bis(trimethylsilyl)amide M Molar m Multiplet Petition 870250103125, dated 11 / 11 / 2025, page 121 / 470 116 / 431 mCPBA meta-chloroperoxybenzoic acid; Me Methyl MeOH Methanol mg MHz Milligram Megahertz min Minutes ml Milliliter mm Millimeter mmol Millimol mol Mol MS Mass spectrometry N Normal NBS N-bromosuccinimide PCC Pyridinium chlorochromate pH PH Hydrogen potential Phenyl PPh3 Triphenylphosphine ppm PyBOP Parts per million Benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate q RT Quadruplet Room temperature rt Retention time NMR Nuclear magnetic resonance s Singlet sat Saturated SFC Supercritical fluid chromatography sxt sextuplet t ter t Triplet tt Triplet of triplet t-But ter-Butyl TMS Trimethylsilyl TFA Trifluoroacetic acid THF Tetrahydrofuran Ts Tosyl uL Microliter Petition 870250103125, dated 11 / 11 / 2025, page 122 / 470 117 / 431 µmol Micromol v / v Volume / volume ° Degree % Percentage Example 1 2-Amino-7-oxo-5-(2-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (4) Scheme 1 Step 1. 2-(3-Oxo-5-(2-(trifluoromethyl)phenyl)cyclohexylidene)malononitrile (2)

[00242] A solution of malononitrile (100 mg, 1.51 mmol, recrystallized from EtOH), triethylamine (253 µl, 1.82 mmol) and 5-(2-(trifluoromethyl)phenyl)cyclohexane-1,3-dione (1.396 mg, 1.51 mmol) in EtOH (1.30 ml) was stirred at 80 °C for 2 hours. Then, a further 62 mg of malononitrile (0.94 mmol) and 250 µl of triethylamine (1.82 mmol) were added, and the mixture was stirred at 80 °C for 16 hours. The mixture was then allowed to cool to room temperature, concentrated to dryness, and the crude product 2 was used in Step 2 without purification. LC-MS: rt = 1.94 min, MS: 304.1 (calculated), 305.1 (M+H+, found). Step 2.2-Amino-7-oxo-5-(2-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carbonitrile (3)

[00243] A mixture of sulfur (50.9 mg, 198 µmol), diethylamine (157 µl, 1.52 mmol) and 2 (461 mg, 1.52 mmol, assuming the quantitative yield in Step 1) in EtOH (2.00 ml) was stirred at 80 °C for 16 hours. The mixture was then allowed to cool to room temperature and concentrated by rotary evaporation, and the residue was purified by Petition 870250103125, dated 11 / 11 / 2025, page 123 / 470 118 / 431 Flash column chromatography (40% to 100% EA eluent gradient in hexane) to produce the title compound 3 as a light brown solid (220 mg, 43% yield in two steps). LC-MS: rt = 1.73 min, MS: 336.1 (calculated), 337.0 (M+H+, found). Step 3.2-Amino-7-oxo-5-(2-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (4)

[00244] A 30% aqueous hydrogen peroxide solution (0.33 ml) was added to a suspension of 3 (41.1 mg, 122 µmol) and potassium carbonate (33.8 mg, 244 µmol) in DMSO (1.64 ml). The mixture was stirred at RT for 2 hours, then partitioned between EA and water (20 ml each). The layers were separated, and the aqueous phase was extracted with a further 20 ml of EA. The combined organic compounds were washed with brine (20 ml), dried with Na2SO4, filtered, concentrated, and vacuum dried to yield the title compound 4 as a light yellow solid (36.7 mg, 85% yield).

[00245] 1H NMR: 400 MHz, DMSO-dô, δ (ppm): 8.06 (s, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.76-7.68 (m, 2H), 7.49 (t, J = 7.7 Hz, 1H), 6.96 (bs, 2H), 3.73-3.58 (m, 1H), 3.40-3.29 (m, 1H), 3.07-2.90 (m, 2H), 2.36 (dd, J = 16.3, 3.8 Hz, 1H). 19F NMR: 376 MHz, DMSO-do, δ (ppm): -57.5 (s). LC-MS: rt = 1.40 min, MS: 354.1 (calculated), 355.1 (M+H+, found). Example 2 2-Amino-N-cyclopropyl-6-ethyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (9) Scheme 2 Petition 870250103125, dated 11 / 11 / 2025, page 124 / 470 119 / 431 Step 1. Ethyl 2-Cyano-2-(4-ethyl-3-oxocyclohexylidene)acetate (6)

[00246] A mixture of 4-ethylcyclohexane-1,3-dione (5,150 mg, 910 µmol) (Synlett. 2012, 1199 to 1204), triethylamine (380 µl, 2.73 mmol) and ethyl 2-cyanoacetate (145 µl, 1.36 mmol) in EtOH (784 µl) was stirred at 80 °C for 16 hours. Then, a further 100 µl of ethyl 2-cyanoacetate (0.94 mmol) and 130 µl of triethylamine (0.93 mmol) were added, and the resulting mixture was stirred at 80 °C for a further 24 hours. The mixture was then allowed to cool to room temperature, concentrated to dryness, and the crude product 6 was used in Step 2 without purification. LC-MS: rt = 1.73 min, MS: 235.1 (calculated), 236.1 (M+H+, found). Step 2. Ethyl 2-Amino-6-ethyl-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxylate (7)

[00247] A mixture of crude 6 (214 mg, 910 µmol; assuming quantitative yield in Step 1), sulfur (30.6 mg, 119 µmol) and diethylamine (94.1 µl, 910 µmol) in EtOH (910 µl) was stirred at 80 °C for 2 hours. The mixture was then allowed to cool to RT, concentrated to dry, and the residue was purified by flash column chromatography (5% to 50% EA eluent gradient in hexane) to yield title compound 7 as a yellow solid (135.2 mg, 52% yield over two steps). LC-MS: rt = 1.77 min, MS: 267.1 (calculated), 268.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 125 / 470 120 / 431 Step 3. 2-amino-6-ethyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (8)

[00248] Lithium hydroxide monohydrate (68.0 mg, 1.62 mmol) was added to 7 (86.6 mg, 324 µmol) suspended in a mixture of MeOH (4.86 ml) and H2O (1.62 ml). The resulting mixture was stirred under reflux for 2 hours, then allowed to cool to RT, diluted with water (20 ml) and washed with EA (20 ml). The organic phase was discarded, and the aqueous phase was then acidified to pH 2 to 3 using 3 N HCl and extracted using EA (3 x 20 ml). The combined organic compounds were washed with brine (20 ml), dried with Na2SO4, filtered, and concentrated to produce compound 8 as a dirty white solid (60.5 mg, 78% yield). The crude product was used in Step 4 without further purification. (see Table 6 for characterization) Step 4 2-Amino-N-cyclopropyl-6-ethyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (9)

[00249] To a solution of 8 (60.5 mg, 253 µmol) in DMF (3.16 ml), N,N-diisopropylethylamine (132 µl, 758 µmol), cyclopropylamine (19.3 µl, 278 µmol) and HATU (115 mg, 303 µmol) were added. The resulting mixture was stirred at RT for 16 hours. The mixture was then diluted with aqueous saturated NH4Cl (30 ml) and extracted with EA (3 x 20 ml). The combined organic compounds were washed with ice-cold brine (40 ml), dried with Na2SO4, filtered and concentrated to dryness. The residue was first purified by flash column chromatography (1% to 10% MeOH eluent gradient in DCM) and then recrystallized from hot EA to produce the title compound 9 as a white solid (16.4 mg, 23% yield).

[00250] 1H NMR: 400 MHz, DMSO-dô, δ (ppm): 7.68 (d, J = 5.7 Hz, 2H), 7.34 (d, J = 3.8 Hz, 1H), 2.86 (dt, J = 17.3, 5.2 Hz, 1H), 2.76 (ddt, J = 19.0, 7.1, 4.2 Hz, 2H), 2.20 (ddt, J = 9.4, 7.8, 4.7 Hz, 1H), 2.06 (dq, J = Petition 870250103125, dated 11 / 11 / 2025, p. 126 / 470 121 / 431 13.2, 5.0 Hz, 1H), 1.82-1.67 (m, 2H), 1.50-1.33 (m, 1H), 0.90 (t, J = 7.4 Hz, 3H), 0.66 (td, J = 7.0, 4.6 Hz, 2H), 0.57-0.47 (m, 2H). LC-MS: rt = 1.26 min, MS: 278.1 (calculated), 279.1 (M+H+, found). Example 3 2-Amino-6-(2-chlorophenyl)-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (15) Scheme 3 Step 1 2-((Di-ter-butoxycarbonyl)amino)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (11)

[00251] A suspension of ethyl 2-amino-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (10, 2.26 g, 9.25 mmol) in DCM (58.2 ml), triethylamine (2.85 ml, 20.4 mmol), 4-dimethylaminopyridine (228 mg, 1.85 mmol), and di-tert-butyldicarbonate (4.44 g, 20.4 mmol) was prepared. The resulting solution was stirred under reflux for 4 hours. The mixture was then allowed to cool to RT, diluted with DCM (50 ml), and washed successively with 1 N HCl, water, and brine (70 ml each). The organic phase was dried with Na2SÜ4, filtered and concentrated, and the residue was purified by Petition 870250103125, dated 11 / 11 / 2025, p. 127 / 470 122 / 431 Flash column chromatography (10% to 60% eluent gradient in hexane) to yield the title compound 11 as a light orange solid (3.42 g, 84% yield). LC-MS: rt = 1.78 min, MS: 439.2 (calculated), 462.2 (M+Na+, found). Step 2. 2-((Di-ter-butoxycarbonyl)amino)-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (12)

[00252] To a solution of LDA (10.4 ml, 1 M in THF / hexane, 10.4 mmol) cooled to -78 °C under Ar, a solution of 11 (2.29 g, 5.22 mmol) in anhydrous THF (16 ml) was added. The resulting mixture was stirred at -78 °C for 15 min, then a solution of TsCN (975 mg, 5.22 mmol) in anhydrous THF (16 ml) was added dropwise. The mixture was stirred at -78 °C for 20 min, then from -78 °C to RT for 4 hours. Subsequently, the mixture was rapidly cooled with aqueous saturated NH4Q (200 ml) and extracted with DCM (2 x 200 ml). The combined organic compounds were dried with Na2SO4, filtered and concentrated, and the residue was purified by flash column chromatography (5% to 50% EA eluent gradient in hexane) to yield compound 12 as a light yellow solid (1.13 g, 46% yield). LC-MS: rt = 1.73 min, MS: 464.2 (calculated), 487.2 (M+Na+, found). Step 3. 2-(( ter-Butoxycarbonyl)amino)-6-(2-chlorophenyl)-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylate ethyl (13)

[00253] To a flame-dried microwave flask loaded with t-BuOK (57.5 mg, 512 µmol) and anhydrous DMF (860 µl) under Ar, 12 (200 mg, 431 µmol) in anhydrous DMF (1.3 ml) was added. The resulting mixture was stirred at 0 °C for 35 min, then bis(2-chlorophenyl)iodonium tetrafluoroborate (188 mg, 431 µmol) (J. Am. Chem. Soc. 2016, 13183 to 13186.) in anhydrous DMF (430 µl) was added dropwise, and the mixture was stirred at RT for 2.5 hours. Then, more bis(2-chlorophenyl)iodonium tetrafluoroborate (40 mg, 92 µmol dissolved in 500 µl of anhydrous DMF) was added. Petition 870250103125, dated 11 / 11 / 2025, page 128 / 470 123 / 431 added and the mixture was stirred at RT for 16 hours. The mixture was then diluted with water (2 ml) and acidified with 1 N HCl to pH 6 to 7. A further 10 ml of water were added, and the product was extracted with EA (3 x 20 ml). The combined organic compounds were washed with brine (20 ml), dried with Na2SO4, filtered, and concentrated. The residue was absorbed in heptanes and concentrated by rotary evaporation several times to remove residual DMF. The resulting solid was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 13 as a light yellow solid (40 mg, 20% yield). LC-MS: rt = 2.06 min, MS: 474.1 (calculated), 475.1 (M+H+, found). Step 4. 2-amino-6-(2-chlorophenyl)-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (14)

[00254] TFA (2.26 ml, 29.6 mmol) was added dropwise to a solution of 13 (40.0 mg, 84.2 µmol) in DCM (4.6 ml) at 0 °C. The resulting mixture was stirred at 0 °C for 1 hour, then concentrated to dry to produce a crude intermediate as a brown solid (33 mg), which was dissolved in MeOH (10 ml). A solution of lithium hydroxide monohydrate (17.4 mg, 414 µmol) in water (10 ml) was added to the solution, which was stirred under reflux for 1 hour. The mixture was then allowed to cool to RT and concentrated to dry. The residue was washed with EA (10 ml), then acidified to pH 1 to 2 using 1 N HCl and extracted with EA (3 x 10 ml). The combined organic compounds were dried with Na2SO4, filtered, and concentrated to yield compound 14 as a brown solid (26.9 mg, 94% yield). The crude product was used in Step 5 without further purification. (see Table 6 for characterization) Step 5.2-Amino-6-(2-chlorophenyl)-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (15)

[00255] To a suspension of 14 (19.9 mg, 57.4 µmol) in Cl ICl· (398 Petition 870250103125, dated 11 / 11 / 2025, p. 129 / 470 To 124 / 431 µl, N,N-diisopropylethylamine (30.0 µl, 172 µmol), saturated NH3 solution in CHCl3 (0.3 ml) (prepared internally), and HATU (24.0 mg, 63.1 µmol) were added. The mixture was stirred at room temperature. After stirring for 5 hours, a further 24 mg of HATU (63.1 µmol) and 0.5 ml of saturated NH3 solution in CHCl3 were added. The mixture was stirred for 16 hours, then a further 25 mg of HATU (65.7 µmol) and 0.6 ml of saturated NH3 solution in CHCl3 were added, and stirring continued for another 4.5 hours. The mixture was then diluted with 5 ml of water and 5 ml of CHCl3. The layers were separated, and the aqueous phase was extracted with CHCl3 (2 x 5 ml). The combined organic compounds were dried with Na2SO4, filtered and concentrated, and the residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 15 as a white solid (6.2 mg, 31% yield).

[00256] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.73-7.68 (m, 1H), 7.50-7.45 (m, 1H), 7.45-7.40 (m, 2H), 3.29-3.11 (m, 3H), 2.48-2.41 (m, 1H). LC-MS: rt = 1.15 min, MS: 345.0 (calculated), 346.0 (M+H+, found). Examples 4 to 27

[00257] Compounds 16 to 34 (examples 4 to 22) were synthesized starting from suitably substituted diketones following the procedures described above during the synthesis of compound 4 (example 1, diagram 1). Compounds 35 and 36 (examples 23 and 24) were synthesized in a similar manner following the procedures described above during the synthesis of compound 8 (scheme 2). Compounds 37 to 39 (examples 25 to 27) were synthesized in a similar manner following the procedures described above during the synthesis of compound 9 (scheme 2). The characterization of compounds 16 to 39 (examples 4 to 27) is given in Table 2. Petition 870250103125, dated 11 / 11 / 2025, p. 130 / 470 125 / 431 Table 2. Characterization of compounds 16 to 39 (examples 4 to 27). Example No. Compound No. Structure Characterization 4 16 Oχ y ll yNH2 T XXnh2 ri s 0 2-Amino-5-(benzo[u][1,3]dioxol5-yl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-dō, δ (ppm): 8.01 (s, 2H), 7.01 (d, J = 1.6 Hz, 1H), 6.96 (bs, 1H), 6.86 (d, J = 7.9 Hz, 1H), 6.82 (dd, J = 8.0, 1.6 Hz, 1H), 5.98 (s, 2H), 3.40-3.35 (m, 1H), 3.10-3.04 (m, 2H), 2.74 (dd, J = 16.2, 12.9 Hz, 1H), 2.42 (dd, J = 16.2, 3.9 Hz, 1H). LC-MS: rt = 1.14 min, MS: 330.1 (calculated), 331.0 (M+H+, found). 5 17 'o / O. ox ΥΊ Vnh2 T T'Xnh2 ii'3 o 2-Amino-5-(3,4-dimethoxyphenyl)-7oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-dô, δ (ppm): 8.00 (s, 2H), 7.06-6.82 (m, 5H), 3.76 (s, 3H), 3.73 (s, 3H), 3.403.30 (m, 1H), 3.14-3.06 (m, 2H), 2.77 (dd, J = 16.2, 12.9 Hz, 1H), 2.45 (dd, J = 16.6, 4.5Hz, 1H). LC-MS: rt = 1.03 min, MS: 346.1 (calculated), 347.0 (M+H+, found). 6 18 F3C.ox |1 y-NHí TX' 8.2 Hz, 2H), 7.63 (d, J = 8.1 Hz, 2H), 6.98 (bs, 2H), 3.62-3.51 (m, 1H), 3.20-3.13 (m, 2H), 2.82 (dd, J = 16.1, 12.8 Hz, 1H), 2.53 (d, J = 4.4Hz, 1H). 19F NMR: 376 MHz, DMSO-de, δ (ppm): -60.8 (s). LC-MS: rt = 1.48 min, MS: 354.1 (calculated), 355.0 (M+H+, found). 7 19 Y | 8.3 Hz, 2H), 6.97 (bs, 2H), 6.89 (d, J = 8.3 Hz, 2H), 3.73 (s, 3H), 3.40-3.33 (m, 1H), 3.12-3.05 (m, 2H), 2.72 (dd, J = 16.2, 12.8 Hz, 1H), 2.44 (dd, J = 16.3, 4.0 Hz, 1H). LC-MS: rt = 1.15 min, MS: 316.1 (calculated), 317.0 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 131 / 470 126 / 431 8 20 y |A yNH2 T ]T y nh2 [í~so 2-Amino-5-(2-methoxyphenyl)-7oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 8.01 (s, 2H), 1-4. 7.33 (d, J = 7.3 Hz, 1H), 7.24 (t, J = 7.7 Hz, 1H), 7.04–6.91 (m, 4H), 3.80 (s, 3H), 3.74–3.63 (m, 1H), 3.21–2.97 (m, 2H), 2.76 (dd, J = 16.1, 12.9 Hz, 1H), 2.43 (dd, J = 16.0, 3.8 Hz, 1H). LC-MS: rt = 1.23 min, MS: 316.1 (calc.), 317.1 (M+H+, found). 9 21 ox A |j yNH2N ri so 2-Amino-7-oxo-5-(pyridin-2-yl)- 4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-dô, δ (ppm): 8.54 (dd, J = 5.0, 1.7 Hz, 1H), 7.98 (s, 2H), 7.77 (td, J = 7.7, 1.9 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.27 (ddd, J = 7.6, 4.8, 1.1 Hz, 1H), 7.00 (bs, 2H), 3.66–3.52 (m, 1H), 3.28–3.14 (m, 2H), 2.85 (dd, J = 16.4, 12.1 Hz, 1H), 2.60–2.53 (m, 1H). LC-MS: rt = 0.31 min, MS: 287.1 (calc.), 288.1 (M+H+, found).10 22 ox Ç |j yNH2N <yyyy T nh2 íl^S 0 2-Amino-7-oxo-5-(piridin-3-il)4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-de, δ (ppm): 8,62 (d, J = 2,3 Hz, 1H), 8,47 (dd, J = 4,8, 1,6 Hz, 1H), 8,07 (s, 2H), 7,82 (dt, J = 8,0, 2,0 Hz, 1H), 7,38 (dd, J = 7,9, 4,7 Hz, 1H), 7,02 (bs, 2H), 3,55-3,44 (m, 1H), 3,233,10 (m, 2H), 2,83 (dd, J = 16,2, 12,9 Hz, 1H), 2,55-2,45 (m, 1H, sobrepondo-se parcialmente ao sinal de solvente). LC-MS: rt = 0,80 min, MS: 287,1 (calculado), 288,0 (M+H+, encontrado). 11 23 |Ί y-NH2 T ]Γ y nh2 Sy's o 2-Amino-7-oxo-5-(piridin-4-il)4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-de, δ (ppm): 8,53 (d, J = 5,3 Hz, 2H), 8,06 (s, 2H), 7,42 (d, J = 5,8 Hz, 2H), 7,02 (bs, 2H), 3,48 (dtd, J = 11,9, 7,5, 3,8 Hz, 1H), 3,14 (d, J = 7,7 Hz, 2H), 2,79 (dd, J = 16,2, 12,7 Hz, 1H), 2,53 (d, J = 4,2 Hz, 1H, sobrepondo-se parcialmente ao sinal do solvente). LC-MS: rt = 0,71 min, MS: 287,1 (calculado), 288,1 (M+H+, encontrado). Petition 870250103125, dated 11 / 11 / 2025, p. 132 / 470 127 / 431 12 24 Ox γΝΗ2 í T / NH2 s 0 2-Amino-6-ethyl-7-oxo-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-de: δ (ppm): 7.97 (s, 2H), 6.94 (bs, 2H), 2.98 (dt, J = 17.3, 5.1 Hz, 1H), 2.86 (ddd, J = 17.2, 9.0, 4.7 Hz, 1H), 2.23 (ddt, J = 12.2, 9.2, 4.7 Hz, 1H), 2.10 (dq, J = 14.1, 4.6Hz, 1H), 1.84-1.71 (m, 2H), 1.48-1.35 (m, 1H), 0.90 (t, J = 7.4 Hz, 3H). LC-MS: rt = 0.92 min, MS: 238.1 (calculated), 239.1 (M+H+, found). 13 25 0 V—nh2 T [ J] >^NH2 ri s 0 2-Amino-5-isobutyl-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.08 (dd, J = 16.86, 4.03 Hz, 1H), 2-62-2.49 (m, 2H), 2.26-2.19 (m, 2H), 1.78-1.71 (m, 1H), 1,391.31 (m, 2H), 0.92 (d, J = 6.56 Hz, 6H). LC-MS: rt = 1.30 min, MS: 266.1 (calculated), 267.1 (M+H+, found).14 26 0 V- nh2 T ]J / -nh2 s 0 2-Amino-5-(furan-2-yl)-7-oxo4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41 (s, 1H), 6.33 (s, 1H), 6.16 (s, 1H), 3.65-3.55 (m, 1H), 3.37 (dd, J = 16.83, 4.48 Hz, 1H), 3.15 (dd, J = 16.83, 9.56 Hz, 1H), 2.83-270 (m, 2H). LC-MS: rt = 0.99 min, MS: 276.1 (calculated), 277.1 (M+H+, found). 15 27 o Á. o [ l] γΝΗ2 T ]Γ / -nh2 it'3 o 2-Amino-5-(3-methoxyphenyl)-7oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-dó, δ (ppm): 7.99 (s, 2H), 7.24 (t, J = 7.85 Hz, 1H), 6.94-6.92 (m, 4H), 6.80 (d, J = 8.15 Hz, 1H), 3.73 (s, 3H), 3,173.04 (m, 3H), 2.75 (t, J = 14.49 Hz, 1H), 2.45-2.40 (m, 1H). LC-MS: rt = 1.22 min, MS: 316.1 (calculated), 317.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 133 / 470 128 / 431 16 28 0 Vnh2 T jl ^nh2 γ-s 0 2-Amino-5-ethyl-7-oxo-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.95 (s, 2H), 6.95 (sbs, 2H), 2.95 (d, J = 16.99 Hz, 1H), 2.60 (dd, J = 16.97, 10.34 Hz, 1H), 2.36 (d, J = 16.35 Hz, 1H), 2.14 (t, J = 14.16 Hz, 1H), 2.10-1.94 (m, 1H), 1,481.33 (m, 2H), 0.90 (t, J = 7.36 Hz, 3H). LC-MS: rt = 0.94 min, MS: 238.1 (calculated), 239.1 (M+H+, found). 17 29 [ 1 2^nh2 [ J] / ^NH2 ii'8 o 2-Amino-7-oxo-5-phenyl-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-dó, δ (ppm): 8.01 (s, 2H), 7.40-7.32 (m, 4H), 7.26-7.23 (m, 1H), 6.97 (bs, 2H), 3.47-3.39 (m, 1H), 3.18-3.09 (m, 2H), 2.78 (dd, J = 8.0, 2.1 Hz, 1H), 2.54-2.45 (m, 1H). LC-MS: rt = 1.05 min, MS: 286.1 (calculated), 287.1 (M+H+, found).18 30 1 T lj yNH2 [ ΊΓ / ^nh2 ri^so 2-Amino-5-(4(dimethylamino)phenyl)-7-oxo4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.98 (s, 2H), 7.17 (d, J = 8.3 Hz, 2H), 6.95 (bs, 2H), 6.70 (d, J = 8.3 Hz, 2H), 3.31-3.25 (m, 1H), 3.06 (d, J = 7.6 Hz, 2H), 2.86 (s, 6H), 2.70 (dd, J = 16.2, 12.4 Hz, 1H), 2.43 (dd, J = 16.2, 3.9 Hz, 1H). LC-MS: rt = 2.48 min, MS: 329.1 (calculated), 330.1 (M+H+, found). 19 31 OI \^nh2 [ j| Ynh2 0 2-Amino-5-isopropyl-7-oxo4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.98 (s, 2H), 7.00 (bs, 2H), 2.87 (dd, J = 16.9, 4.2 Hz, 1H), 2.70 (dd, J = 16.9, 11.0 Hz, 1H), 2.31 (dd, J = 16.0, 4.0 Hz, 1H), 2.20 (dd, J = 16.0, 12.6 Hz, 1H), 1.97-1.88 (m, 1H), 1.69-1.61 (m, 1H), 0.94-0.91 (m, 6H). LC-MS: rt = 3.15 min, MS: 252.1 (calculated), 253.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 134 / 470 129 / 431 20 32 Cl 0 L X ύ NH2 [ YYnh2 ri^s 0 2-Amino-5-(3-clorofenil)-7-oxo4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-de, δ (ppm): 8,04 (s, 2H), 7,50 (s, 1H), 7,40-7,35 (m, 2H), 7,34-7,30 (m, 1H), 6,99 (bs, 2H), 3,50-3,42 (m, 1H), 3,18-3,08 (m, 2H), 2,79 (dd, J = 16,1, 13,0 Hz, 1H), 2,50-2,45 (m, 1H). LC-MS: rt = 2,74 min, MS: 320,0 (calculado), 321,1 (M+H+, encontrado). 21 33 ^x.CI °\ I 1] W [ T>NH2 Í1 s 0 2-Amino-5-(2-clorofenil)-7-oxo4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-de, δ (ppm): 8,04 (s, 2H), 7,58 (d, J = 7,7, 1H), 7,47 (d, J = 7,9, 1H), 7,38 (t, J = 7,4, 1H), 7,30 (t, J = 7,6, 1H), 7,00 (bs, 2H), 3,80-3,73 (m, 1H), 3,203,09 (m, 2H), 2,82-2,75 (m, 1H), 2,50-2,44 (m, 1H). LC-MS: rt = 2,65 min, MS: 320,0 (calculado), 321,0 (M+H+, encontrado).22 34 °\ T |1 ^nh2 [ YYnh2 0 2-Amino-5-(4-fluorophenyl)-7-oxo4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-dó, δ (ppm): 8.03 (s, 2H), 7.45-7.41 (m, 2H) 3.6Hz, 1H). 19F NMR: 376 MHz, DMSO-de, δ (ppm): -116.5 (m). LC-MS: rt = 1.08 min, MS: 304.1 (calculated), 305.0 (M+H+, found). 23 35 co2h TTJ ;> nh2 0 2-Amino-5-isobutyl-7-oxo4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxylic acid 1H NMR: 400 MHz, DMSO-de, δ (ppm): 12.49 (bs, 1H), 8.22 (bs, 2H), 3.26 (dd, J = 17.5, 3.4 Hz, 1H), 2,452.30 (m, 2H), 2.22-2.10 (m, 2H), 1.65 (hept, J = 6.7 Hz, 1H), 1,311.21 (m, 2H), 0.86 (d, J = 6.5 Hz, 6H). LC-MS: rt = 1.27 min, MS: 267.1 (calculated), 268.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 135 / 470 130 / 431 36 2-amino-7-oxo-5-(2-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.82 (d, J = 7.9 Hz, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 3.88-3.75 (m, 1H), 3.58 (ddd, J = 18.0, 4.1, 1.1 Hz, 1H), 3.05 (dd, J = 17.9, 11.7 Hz, 1H), 2.96 (dd, J = 16.4, 13.2 Hz, 1H), 2.53 (ddd, J = 16.3, 4.0, 1.3Hz, 1H). 19F NMR: 376 MHz, CD3OD, δ (ppm): -60.1 (s). LC-MS: rt = 1.34 min, MS: 355.1 (calculated), 356.1 (M+H+, found). 2-Amino-N-cyclopropyl-5isobutyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide 2-Amino-N-cyclopropyl-7-oxo-5-(2-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide RMN de 1H: 400 MHz, CDCh, δ (ppm): 6,88 (bs, 2H), 5,68 (bs, 1H), 2,98-2,87 (m, 1H), 2,86-2,78 (m, 1H), 2,60 (dd, J = 15,8, 2,8 Hz, 1H), 2,43-2,31 (m, 2H), 2,27-2,14 (m, 1H), 1,76-1,63 (m, 1H), 1,45-1,22 (m, 3H), 0,95-0,83 (m, 7H), 0,620,56 (m, 2H). LC-MS: rt = 1,31 min, MS: 306,1 (calculado), 307,2 (M+H+, encontrado). RMN de 1H: 400 MHz, CDCh, δ (ppm): 7,71 (d, J = 7,9 Hz, 1H), 7,64-7,56 (m, 2H), 7,42 (t, J = 7,4 Hz, 1H), 6,97 (bs, 2H), 5,59 (bs, 1H), 4,01-3,89 (m, 1H), 3,10 (dd, J = 15,8, 4,5 Hz, 1H), 2,93-2,78 (m, 2H), 2,79-2,66 (m, 2H), 0,84-0,77 (m, 2H), 0,55-0,47 (m, 2H). RMN de19F: 376 MHz, CDCl3, δ (ppm): -58,7 (s). LC-MS: rt = 1,36 min, MS: 394,1 (calculado), 395,1 (M+H+, encontrado). 2-Amino-N-ciclopropil-7-oxo-5fenil-4,5,6,7-tetrahidrobenzo[b]tiofeno-3carboxamida 1H NMR: 400 MHz, DMSO-do, δ (ppm): 7.72 (s, 2H), 7.49-7.48 (m, 1H), 7.37-7.32 (m, 4H), 7.27-7.23 (m, 1H), 3.45-3.37 (m, 1H), 3,112.95 (m, 2H), 2.78-2.67 (m, 2H), 2.50-2.46 (m, 1H), 0.66-0.59 (m, 2H), 0.50-0.42 (m, 2H). LC-MS: rt = 2.81 min, MS: 326.1 (calculated), 327.1 (M+H+, found). Example 28 Petition 870250103125, dated 11 / 11 / 2025, p. 136 / 470 131 / 431 2-amino-6-cyano-6-(cyclobutylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzoj b ]thiophene-3-carboxylic acid (47) and Example 29 2-Amino-6-cyano-6-(cyclobutylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzoj b ]thiophene-3-carboxamide (48) Scheme 4 Step 1. 8-(Cyclobutylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (41)

[00258] A flame-dried round-bottom flask was charged with a solution of LDA (2.69 ml, 1 M in THF / hexane, 2.69 mmol) in anhydrous THF (3.60 ml) under Ar. The solution was cooled to -78 °C, and 1,4-dioxaspiro[4.5]decane-8-carbonitrile (40, 265 µl, 1.79 mmol) was added. The mixture was stirred at -78 °C for 30 min, then (bromomethyl)cyclobutane (202 µl, 1.79 mmol) was added. The reaction vessel was removed from the acetone / dry ice bath, and the solution was stirred at RT for 64 hours. The mixture was then partitioned between EA and water (15 ml each), the layers were separated, and the aqueous phase was extracted with EA (2 x 15 ml). The combined organic compounds were dried with Na2SO4, filtered, and concentrated to produce the crude compound 41 as an orange oil, which was used in Step 2 without purification and without Petition 870250103125, dated 11 / 11 / 2025, p. 137 / 470 132 / 431 characterization. Step 2. 1-(Cyclobutylmethyl)-4-oxocyclohexane-1-carbonitrile (42)

[00259] A solution of 41 (422 mg, 1.79 mmol, assuming quantitative yield in Step 1) in acetone (25.3 ml) was treated with 2 N HCl (4.59 ml, 9.19 mmol), and the resulting mixture was stirred at 40 °C for 64 hours. The mixture was then allowed to cool to RT, concentrated by rotary evaporation to remove the acetone, and the aqueous residue was extracted with EA (3 x 30 ml). The combined organic compounds were dried with Na2SO4, filtered, and concentrated to yield the crude title compound 42 as a brown solid, which was used in Step 3 without purification and without characterization. Step 3.2-Amino-6-cyano-6-(cyclobutylmethyl)-4,5,6,7-tetrahydrobenzo[b]ethylthiophene-3-carboxylate (43)

[00260] A suspension of ethyl 2-cyanoacetate (210 µl, 1.97 mmol), morpholine (172 µl, 1.97 mmol), sulfur (63 mg, 247 µmol) and 42 (342 mg, 1.79 mmol, assuming quantitative yield in Step 2) in EtOH (1.8 ml) was stirred at 60 °C for 16 hours. The mixture was allowed to cool to RT, then concentrated by rotary evaporation, and the residue was partitioned between EA and water (20 ml each). The organic phase was dried with Na2SO4, filtered and concentrated, and the residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 43 as a light yellow solid (353 mg, 62% yield over three steps). LC-MS: rt = 1.74 min, MS: 318.1 (calculated), 319.1 (M+H+, found). Step 4 Ethyl 2-Acetamido-6-cyano-6-(cyclobutylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylate (44)

[00261] A suspension of 43 (227 mg, 713 µmol) in acetic acid (4.09 ml) was treated with acetic anhydride (80.9 µl, 856 µmol), and the resulting mixture was stirred at 70 °C for 3 hours. The mixture was then left Petition 870250103125, dated 11 / 11 / 2025, p. 138 / 470 133 / 431 cool to RT and concentrate to dry. The residue was diluted with DCM (10 ml) and washed successively with aqueous saturated NaHCO3, water and brine (10 ml each), then dried with Na2SO4, filtered and concentrated to produce the compound of title 44 as a yellow solid (227 mg, 88% yield). LC-MS: rt = 1.79 min, MS: 360.2 (calculated), 361.1 (M+H+, found). Step 5. 2-Acetamido-6-cyano-6-(cyclobutylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[ethyl bthiophene-3-carboxylate (45)

[00262] To a suspension of 44 (227 mg, 630 µmol) in acetic acid (2.1 ml) and water (6.3 ml), ceric sulfate (1.81 g, 5.44 mmol) was added. The mixture was sonicated for 1 min, then stirred at RT for 88 hours. Subsequently, the mixture was diluted with water and EA (30 ml each), sonicated for 3 minutes, and transferred to a separatory funnel. The layers were separated, and the organic phase was successively washed with NaOH and 1 N brine (30 ml each), then dried with Na2SO4, filtered, and concentrated to yield the title compound 45 as a yellow gum (175.1 mg, 74% yield), which was used in Step 6 without purification. LC-MS: rt = 1.71 min, MS: 374.1 (calculated), 375.2 (M+H+, found). Step 6 2-Amino-6-cyano-6-(cyclobutylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[ethyl b lthiophene-3-carboxylate (46)

[00263] A solution of 45 (170 mg, 454 µmol) in toluene (744 µl) was treated with pyrrolidine (559 µl, 6.81 mmol) and stirred at RT for 1 hour. The mixture was then concentrated by rotary evaporation, and the residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 46 as a dirty white solid (118.1 mg, 78% yield). LC-MS: rt = 1.63 min, MS: 332.1 (calculated), 333.1 (M+H+, found). Step 7. 2-amino-6-cyano-6-(cyclobutylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b-thiophene-3-carboxylic acid (47) Petition 870250103125, dated 11 / 11 / 2025, p. 139 / 470 134 / 431

[00264] A solution of lithium hydroxide monohydrate (66.9 mg, 1.59 mmol) in water (38.4 ml) was added to a solution of 46 (100 mg, 261 µmol) in MeOH (38.4 ml). The mixture was stirred under reflux for 16 hours, then allowed to cool to RT and concentrated by rotary evaporation to remove most of the MeOH. The aqueous residue was washed with EA (2 x 25 ml), then acidified to pH 1 to 2 using 3 N HCl and extracted with EA (3 x 25 ml). The organic compounds were dried with Na2SO4, filtered, and concentrated to yield the title compound 47 as a dirty white solid (78.2 mg, 81% yield).

[00265] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 12.75 (bs, 1H), 8.48 (bs, 2H), 3.08-3.02 (m, 2H), 2.55-2.42 (m, 1H), 2.43-2.29 (m, 1H), 2,272.16 (m, 1H), 2.13-1.96 (m, 3H), 1.93-1.61 (m, 5H). LC-MS: rt = 1.32 min, MS: 304.1 (calculated), 305.1 (M+H+, found). Step 8.2-Amino-6-cyano-6-(cyclobutylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (48)

[00266] To a suspension of 47 (38.3 mg, 126 µmol), saturated NH3 solution in chloroform (780 µl) (prepared internally), ammonium chloride (135 mg, 2.52 mmol) and N,N-diisopropylethylamine (43.8 µl, 252 µmol) in DMF (1.39 ml), HATU (73.2 mg, 189 µmol) was added. The resulting mixture was stirred at RT for 16 hours, then diluted with aqueous saturated NH4Cl (20 ml) and extracted with EA (3 x 10 ml). The combined organic compounds were washed with ice-cold brine (2 x 15 ml), dried with Na2SO4, filtered and concentrated. The residue was first purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) and then by semi-preparatory HPLC-MS (eluent gradient from 25% to 100% CH3CN in 10 mM ammonium bicarbonate) to yield the title compound 48 as a white solid (14.5 mg, 38%).

[00267] 'H NMR (400 MHz, CD 3 OD): δ 3.16-3.08 (m, 2H), 2.65 Petition 870250103125, dated 11 / 11 / 2025, p. 140 / 470 135 / 431 2.57 (m, 1H), 2.47 (ddd, J = 13.3, 7.7, 5.4 Hz, 1H), 2.30 (ddd, J = 13.7, 6.0, 5.0 Hz, 1H), 2.20-2.10 (m, 3H), 2.00-1.90 (m, 2H), 1.87-1.74 (m, 3H). LCMS: rt = 1.15 min, MS: 303.1 (calculated), 304.1 (M+H+, found). Example 30 2-amino-6-cyano-6-(cyclopentylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (49) and Example 31 2-Amino-6-cyano-6-(cyclopentylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (50) Scheme 5 2-amino-6-cyano-6-(cyclopentylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (49)

[00268] Compound 49 (example 30) was synthesized similarly to compound 47 (example 28, scheme 4) starting from 1,4dioxaspiro[4.5]decane-8-carbonitrile (40) and using (bromomethyl)cyclopentane instead of (bromomethyl)cyclobutane in the first step.

[00269] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 12.75 (bs, 1H), 8.48 (bs, 2H), 3.13-3.00 (m, 2H), 2.48-2.38 (m, 1H), 2.29 (dt, J = 13.5, 5.2 Hz, 1H), 2.04-1.76 (m, 5H), 1.63-1.37 (m, 4H), 1.25-1.05 (m, 2H). LC-MS: rt = 1.41 min, MS: 318.1 (calculated), 319.1 (M+H+, found). 2-Amino-6-cyano-6-(cyclopentylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (50)

[00270] A suspension of 49 (40.0 mg, 126 µmol), saturated solution of NH3 in chloroform (741 µl) (prepared internally), ammonium chloride (134 mg, 2.51 mmol) and N,N-diisopropylethylamine (43.8 µl, 252 µmol) in Petition 870250103125, dated 11 / 11 / 2025, page 141 / 470 136 / 431 DMF (1.39 ml) was added to HATU (73.1 mg, 188 µmol). The resulting mixture was stirred at room temperature for 16 hours, then a further 40 µl of N,N-diisopropylethylamine (230 µmol), 550 µl of saturated NH3 solution in chloroform, and 65 mg of HATU (167 µmol) were added, and the mixture was stirred at 40 °C for 24 hours. Subsequently, the mixture was partitioned between aqueous saturated NH4Cl and EA (20 ml each), the layers were separated, and the organic phase was washed with ice-cold brine (2 x 15 ml), dried with Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 50 as a dirty white solid (14.5 mg, 36%).

[00271] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.25-3.05 (m, 2H), 2.54 (ddd, J = 13.4, 7.9, 5.4 Hz, 1H), 2.38 (ddd, J = 13.7, 5.9, 5.0 Hz, 1H), 2.12 (dd, J = 13.5, 6.7 Hz, 1H), 2.07-1.85 (m, 4H), 1.73-1.51 (m, 4H), 1,261.18 (m, 2H). LC-MS: rt = 1.25 min, MS: 317.1 (calculated), 318.0 (M+H+, found). Example 32 2-amino-6-cyano-6-(cyclohexylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (51) and Example 33 2-Amino-6-cyano-6-(cyclohexylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (52) Scheme 6 2-amino-6-cyano-6-(cyclohexylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (51) Petition 870250103125, dated 11 / 11 / 2025, p. 142 / 470 137 / 431

[00272] Compound 51 (example 32) was synthesized similarly to compound 47 (example 28, scheme 4) starting from 1,4dioxaspiro[4.5]decane-8-carbonitrile (40) and using (bromomethyl)cyclohexane instead of (bromomethyl)cyclobutane in the first step.

[00273] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 12.69 (bs, 1H), 8.48 (bs, 2H), 3.12-2.97 (m, 2H), 2.47-2.36 (m, 1H), 2.27 (dt, J = 13.7, 5.5 Hz, 1H), 1.84-1.54 (m, 6H), 1.53-1.46 (m, 1H), 1.28-1.07 (m, 4H), 1.03-0.90 (m, 2H). LC-MS: rt = 1.49 min, MS: 332.1 (calculated), 333.0 (M+H+, found). 2-Amino-6-cyano-6-(cyclohexylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (52)

[00274] To a solution of 51 (24.0 mg, 72.2 µmol) in DMF (798 µl), PyBOP (56.5 mg, 108 µmol), N,N-diisopropylethylamine (40.0 µl, 230 µmol) and ammonium chloride (38.6 mg, 722 µmol) were added. The resulting mixture was stirred at RT for 80 minutes, then diluted with aqueous saturated NH4Cl (5 ml) and extracted with EA (3 x 5 ml). The combined organic compounds were washed with ice-cold brine (2 x 10 ml), dried with Na2SO4, filtered and concentrated, and the residue was purified by flash column chromatography (10% to 100% EA eluent gradient in hexane) to yield the title compound 52 as an orange solid (13.6 mg, 57% yield).

[00275] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.18-3.09 (m, 2H), 2.51 (ddd, J = 13.3, 7.5, 5.6 Hz, 1H), 2.36 (dt, J = 13.6, 5.5 Hz, 1H), 1,981.80 (m, 3H), 1.79-1.59 (m, 5H), 1.38-1.16 (m, 4H), 1.13-0.97 (m, 2H). LCMS: rt = 1.34 min, MS: 331.1 (calculated), 332.2 (M+H+, found). Example 34 2-amino-6-cyano-6-(cyclopropylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (53) and Example 35 Petition 870250103125, dated 11 / 11 / 2025, page 143 / 470 138 / 431 2-Amino-6-cyano-6-(cyclopropylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (54) Scheme 7 2-amino-6-cyano-6-(cyclopropylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzof b ]thiophene-3-carboxylic acid (53).

[00276] Compound 53 (example 34) was synthesized similarly to compound 47 (example 28, scheme 4) starting from 1,4dioxaspiro[4.5]decane-8-carbonitrile (40) and using (bromomethyl)cyclopropane instead of (bromomethyl)cyclobutane in the first step.

[00277] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.23-3.19 (m, 2H), 2.54-2.50 (m, 1H), 2.42-2.39 (m, 1H), 1.89 (dd, J = 14.27, 7.15 Hz, 1H), 1.78 (dd, J = 14.26, 6.72 Hz, 1H), 0.91-0.87 (m, 1H), 0.57-0.53 (m, 2H), 0.22-0.19 (m, 2H). LC-MS: rt = 1.18 min, MS: 290.1 ​​(calculated), 291.0 (M+H+, found). 2-Amino-6-cyano-6-(cyclopropylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzof b ]thiophene-3-carboxamide (54).

[00278] To a suspension of 53 (36.4 mg, 0.125 mmol) in CHCb (871 µl), HATU (52.4 mg, 0.138 mmol) and N,N-diisopropylethylamine (65.5 µl, 0.376 mmol) were added. The mixture was stirred for 20 min at RT, and saturated NH3 solution in CHCE (0.8 ml) (prepared internally) and NH4Cl (6.71 mg, 0.125 mmol) were added. The reaction mixture was stirred for 16 hours and partitioned between EA and a saturated aqueous solution of NaHCO3. The layers were separated, and the organic phase was washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (20 eluent gradient). Petition 870250103125, dated 11 / 11 / 2025, p. 144 / 470 139 / 431% to 100% EA in hexane) to produce the title compound 54 as a white solid (20.0 mg, 55% yield).

[00279] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.13 (t, J = 6.03 Hz, 2H), 2.60-2.53 (m, 1H), 2.48-2.42 (m, 1H), 1.93 (dd, J = 14.28, 7.11 Hz, 1H), 1.80 (dd, J = 14.28, 6.79 Hz, 1H), 0.94-0.84 (m, 1H), 0.58-0.55 (m, 2H), 0.24-0.20 (m, 2H). LC-MS: rt = 1.02 min, MS: 289.1 (calculated), 290.1 ​​(M+H+, found). Example 36 2-amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (59) Scheme 8 Step 1. 2-Amino-6-cyano-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (56).

[00280] To a solution of 4-oxo-1-phenylcyclohexane-1-carbonitrile (55) (6.00 g, 30.1 mmol) and ethyl 2-cyanoacetate (2.91 ml, 27.4 mmol) in EtOH (48.0 ml), morpholine (2.60 ml, 30.1 mmol) and sulfur (969 mg, 3.78 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours. The mixture was allowed to cool to RT, and a white precipitate appeared. This solid was collected by filtration, washed with EtOH, and dried under vacuum to yield the title compound 56 as a white solid (8.15 g, 91% yield). LC-MS: rt = 1.55 min, MS: 326.1 (calculated), 327.0 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 145 / 470 140 / 431 Step 2. 2-Acetamido-6-cyano-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (57).

[00281] To a solution of 56 (8.15 g, 25.0 mmol) in acetic acid (143 ml), acetic anhydride (2.83 ml, 30.0 mmol) was added. The mixture was stirred at 60 °C for 1 day, then allowed to cool to RT and concentrated to dry. The residue was partitioned between DCM and water. The layers were separated, and the organic phase was washed with saturated aqueous solution of NaHCO3, water, and brine. The organic layer was dried with Na2SO4, filtered, and concentrated to yield the title compound 57 as a white solid (9.0 g, 98% yield). LC-MS: rt = 1.61 min, MS: 368.1 (calculated), 369.1 (M+H+, found). Step 3.2-Acetamido-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (58).

[00282] To a solution of 57 (9.00 g, 24.4 mmol) in acetic acid (66 ml) and water (66 ml), ceric sulfate (70.1 g, 211 mmol) was added. The mixture was sonicated until homogeneous and stirred at RT for 24 hours. The suspension was partitioned between EA and water. The layers were separated, and the organic phase was washed with 1 N NaOH, water, and brine. The organic layer was then dried with Na2SO4, filtered, and concentrated to yield the title compound 58 as a dirty white solid (9.10 g, 97% yield). LC-MS: rt = 1.56 min, MS: 382.1 (calculated), 383.1 (M+H+, found). Step 4 2-amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (59).

[00283] To a suspension of 58 (4.00 g, 10.44 mmol) in MeOH (1.26 l), a solution of lithium hydroxide monohydrate (2.20 g, 52.4 mmol) in water (1.26 l) was added. The reaction mixture was stirred under reflux for 2 hours, then allowed to cool to RT. The mixture was diluted with water and concentrated to remove most of the organic solvent, then, Petition 870250103125, dated 11 / 11 / 2025, pp. 146 / 470 141 / 431 washed with EA. The aqueous layer was acidified by the slow addition of 3 N HCl and extracted with EA. This organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by grinding with a DCM / pentane mixture to produce the compound of title 59 as a grayish solid (2.54 g, 78% yield).

[00284] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.43-7.31 (m, 5H), 3.27-3.23 (m, 1H), 2.88-2.73 (m, 2H), 2.71-2.61 (m, 1H). LC-MS: rt = 1.23 min, MS: 312.1 (calculated), 313.1 (M+H+, found). Example 37 (R)-2-Amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxylic acid (60a) (S)-2-Amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxylic acid (60b) Scheme 9

[00285] Racemic compound 59 (86.0 mg) was subjected to chiral separation by CFS (isocratic 35% MeOH in CO2) to yield the enantioenriched compound 60a as a light pink solid (33.1 mg, 38% separation yield) and 60b as a white solid (35.4 mg, 41% separation yield) (absolute configurations were assigned based on the resolved crystal structure of enantiomer 60a).

[00286] 60a: 1H NMR: equal to the racemic mixture (59). LC-MS: rt = 1.23 min, MS: 312.1 (calculated), 313.1 (M+H+, found). Analytical CFS (IG column with a gradient of 5 to 60% MeOH in water (95 to 40% CO2)): rt = 3.84 min, ee. = 99.9%.

[00287] 60b: 1H NMR: same as racemic mixture (59). LC-MS: rt = Petition 870250103125, dated 11 / 11 / 2025, p. 147 / 470 142 / 431 1.23 min, MS: 312.1 (calculated), 313.1 (M+H+, found). Analytical CFS (IG column with a gradient of 5 to 60% MeOH in water (95 to 40% CO2)): rt = 4.76 min, ee. = 97.6%. Example 38 2-Amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (61) and Example 39 2-Amino-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3,6-dicarboxamide (62) Scheme 10 Step 1. 2-Amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (61).

[00288] To a solution of 59 (2.54 g, 8.13 mmol) in DMF (90.0 ml), HATU (4.73 g, 12.2 mmol) and N,N-diisopropylethylamine (2.83 ml, 16.4 mmol) were added, and the mixture was stirred at RT for 20 min. Then, ammonium chloride (8.74 g, 163 mmol), NH3 solution in THF (45.0 ml, 18.0 mmol, 0.4 M) and saturated NH3 solution in chloroform (45.0 ml) (prepared internally) were added to the mixture. The reaction mixture was stirred at RT for 16 hours and partitioned between EA and the saturated aqueous NaHCO3 solution. The layers were separated, and the organic phase was washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (20% to 100% EA eluent gradient in hexane) and then by reversed-phase flash column chromatography (0% to 100% CH3CN eluent gradient in H2O with 0.1% (v / v) formic acid) to yield the title compound 61 as a solid. Petition 870250103125, dated 11 / 11 / 2025, pp. 148 / 470 143 / 431 white (1.20 g, 47% yield).

[00289] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41-7.36 (m, 5H), 3.17-3.11 (m, 1H), 2.87-2.77 (m, 2H), 2.74-2.66 (m, 1H). LC-MS: rt = 1.04 min, MS: 311.1 (calculated), 312.0 (M+H+, found). Step 2. 2-Amino-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3,6dicarboxamide (62)

[00290] A 30% aqueous hydrogen peroxide solution (170 µl) was added to a suspension of 61 (13.2 mg, 42.4 µmol) and potassium carbonate (11.7 mg, 84.8 µmol) in DMSO (569 µl). The mixture was stirred at room temperature for 3 hours, then partitioned between EA and water (5 ml each). The layers were separated, the organic phase was washed with 5 ml of water, and the combined aqueous phase was extracted with EA (2 x 3 ml). The combined organic compounds were washed with brine (5 ml), dried with Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 70% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 62 as a white solid (3.6 mg, 28% yield).

[00291] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41-7.25 (m, 5H), 3.05 (dt, J = 16.8, 4.2 Hz, 1H), 2.78-2.59 (m, 3H). LC-MS: rt = 0.86 min, MS: 329.1 (calculated), 329.9 (M+H+, found). Example 40 (S)-2-Amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (63) and Example 41 (R)-2-Amino-6-cyano-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (64) Scheme 11 Petition 870250103125, dated 11 / 11 / 2025, p. 149 / 470 144 / 431

[00292] Racemic compound 61 (96.5 mg) was subjected to chiral separation by CFS (isocratic: 45% CH3CN / EtOH 1:1 in CO2) to produce enantioenriched compound 63 as a white solid (29.0 mg, 30% separation yield) and enantioenriched compound 64 as a white solid (29.0 mg, 30% separation yield) (absolute configurations were assigned based on the resolved crystal structure of enantiomer 64).

[00293] 63: 1H NMR: same as racemic mixture (61). LC-MS: rt = 1.04 min, MS: 311.1 (calculated), 312.0 (M+H+, found). Analytical CFS (IG column with a gradient of 5 to 60% ACN / EtOH (95 to 40% CO2)): rt = 4.71 min, ee. = >99.9%.

[00294] 64: 1H NMR: same as racemic mixture (61). LC-MS: rt = 1.04 min, MS: 311.1 (calculated), 312.0 (M+H+, found). Analytical SCF (IG column with a gradient of 5 to 60% ACN / EtOH (95 to 40% CO2)): rt = 4.09 min, ee. = >99.9%. Examples 42-49

[00295] Compounds 65 to 71 (examples 42 to 48) were synthesized following a procedure similar to that described above for the synthesis of compound 9 (example 2, scheme 2), starting from compound 59 (example 36, scheme 8) instead of compound 8 and using cyclobutylamine, cyclopentylamine, 3-aminoxethane, 3-aminotetrahydrofuran, 4-aminotetrahydropyran, 2,2,2-trifluoroethylamine and 2,2-difluoroethan-1-amine, respectively, instead of cyclopropylamine. Compound 72 (example 49) was obtained in the same way starting from compound 53 (example 34, scheme 7). The characterization of compounds 65 to 72 (examples 42 to 49) is provided in Table 3. Petition 870250103125, dated 11 / 11 / 2025, page 150 / 470 145 / 431 Table 3. Characterization of compounds 65 to 72 (examples 42 to 49). Ex. Compound Structure Characterization 2-Amino-6-cyano-N-cyclobutyl-7oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.42-7.40 (m, 4H), 7.39-7.35 (m, 1H), 4.37 (t, J = 8.33 Hz, 1H), 3.12-3.06 (m, 1H), 2.85-2.74 (m, 2H), 2.71-2.66 (m, 1H), 2.31-2.25 (m, 2H), 2.04-1.97 (m, 2H), 1.75-1.69 (m, 2H). LC-MS: rt = 1.39 min, MS: 365.1 (calculated), 366.1 (M+H+, found). 2-Amino-6-cyano-N-cyclopentyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz CD3OD, δ (ppm): 7.40-7.35 (m, 5H), 4.20 (t, J = 6.96 Hz, 1H), 3.10-3.03 (m, 1H), 2.82-2.74 (m, 2H), 2.70-2.65 (m, 1H), 1.98-1.92 (m, 2H), 1.73-1.67 (m, 2H), 1.60-1.55 (m, 2H), 1.52-1.45 (m, 2H). LC-MS: rt = 1.46 min, MS: 379.1 (calculated), 380.1 (M+H+, found). 2-Amino-6-cyano-N-(oxetan-3yl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41-7.36 (m, 5H), 5.00-4.95 (m, 1H), 4.87-4.85 (m, 2H), 4.61 (t, J = 6.76 Hz, 2H), 3.15 (ddd, J = 17.50, 6.18, 4.45 Hz, 1H), 2.90-2.76 (m, 2H), 2.71-2.67 (m, 1H). LC-MS: rt = 1.13 min, MS: 367.1 (calculated), 368.2 (M+H+, found). 2-Amino-6-cyano-7-oxo-6-phenylN-(tetrahydrofuran-3-yl)-4,5,6,7tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41-7.36 (m, 5H), 4.47-4.44 (m, 1H), 3.92-3.85 (m, 2H), 3.80-3.74 (m, 1H), 3.69-3.62 (m, 1H), 3.13-3.05 (m, 1H), 2.84-2.75 (m, 2H), 2.71-2.66 (m, 1H), 2.26-2.20 (m, 1H), 1.93-1.87 (m, 1H). LC-MS: rt = 1.15 min, MS: 381.1 (calculated), 382.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 151 / 470 146 / 431 46 69 \ V-dT jTVnh2 W / / V^S NC II O 2-Amino-6-cyano-7-oxo-6-phenylN-(tetrahydro-2H-pyran-4-yl)4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41-7.36 (m, 5H), 4.02-3.96 (m, 1H), 3.93-3.89 (m, 2H), 3.50-3.43 (m, 2H), 3.12-3.05 (m, 1H), 2.87-2.74 (m, 2H), 2.72-2.64 (m, 1H), 1.90-1.81 (m, 2H), 1.65-1.51 (m, 2H). LC-MS: rt = 1.21 min, MS: 395.1 (calculated), 396.1 (M+H+, found). 47 70 o / —CF3 ZNH \ vJ ]T)^nh2 W / ν' S NC II 0 2-Amino-6-cyano-7-oxo-6-phenylN-(2,2,2-trifluoroethyl)-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.41-7.36 (m, 5H), 4.10-3.86 (m, 2H), 3.14-3.05 (m, 1H), 2.87-2.77 (m, 2H), 2.75-2.66 (m, 1H). 19F NMR: 376 MHz, CD3OD, δ (ppm): -73.7 (t, J = 9.2 Hz). LC-MS: rt = 1.37 min, MS: 393.1 (calculated), 394.1 (M+H+, found).48 71 o ^chf2 vnh \ P__[ ¥Vnh2 WAV's NC II 0 2-Amino-6-cyano- N-(2,2difluoroethyl)-7-oxo-6-phenyl4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.42-7.37 (m, 5H), 5.95 (tt, J = 56.4, 4.07 Hz, 1H), 3.69-3.57 (m, 2H), 3.13-3.07 (m, 1H), 2.85-2.76 (m, 2H), 2.73-2.63 (m, 1H). 19F NMR: 376 MHz, CD3OD, δ (ppm): -124.4 (dt). LC-MS: rt = 1.27 min, MS: 375.1 (calculated), 376.1 (M+H+, found). 49 72 V <7 / H ]J )VNH2 ZVS NC II o 2-Amino-6-cyano-N-cyclopropyl6-(cyclopropylmethyl)-7-oxo4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.01 (t, J = 6.04 Hz, 2H), 2,782.72 (m, 1H), 2.57-2.48 (m, 1H), 2.45-2.36 (m, 1H), 1.91 (dd, J = 14.26, 7.18 Hz, 1H), 1.80 (dd, J = 14.24, 6.72 Hz, 1H), 0.90-0.86 (m, 1H), 0.79-0.74 (m, 2H), 0.60-0.53 (m, 4H), 0.23-0.19 (m, 2H). LC-MS: rt = 1.23 min, MS: 329.1 (calculated), 330.1 (M+H+, found). Example 50 2-Amino-6-cyano-6-isobutyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (75) Scheme 12 Petition 870250103125, dated 11 / 11 / 2025, p. 152 / 470 147 / 431 Step 1. 1-Isobutyl-4-oxocyclohexane-1-carbonitrile (73).

[00296] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (40, 221 µl, 1.50 mmol, Scheme 4) in THF (3.0 ml) at -78 °C, LDA (2.39 ml, 1 M in THF / hexane, 2.39 mmol) was added dropwise. After 30 min, 1-bromo-2-methylpropane (164 µl, 1.50 mmol) was added dropwise, and the reaction mixture was stirred at RT for 72 hours. The reaction mixture was then partitioned between hexane and water. The layers were separated, and the aqueous phase was extracted with EA. The combined organic layers were combined, dried with Na2SO4, filtered, and concentrated. The dry residue was dissolved in acetone (19.7 ml), and 3 N HCl (4.98 ml, 15.0 mmol) was added slowly. The mixture was stirred for 16 hours, then neutralized by slowly adding saturated and concentrated NaHCO3 solution to remove the organic solvent.The remaining aqueous solution was extracted with EA, and the organic layer was dried with Na2SO4, filtered, and concentrated to dryness to produce compound 73 (141 mg, 52% yield over two steps). LC-MS: rt = 1.45 min, MS: 179.1 (calculated), 180.0 (M+H+, found). Step 2. 2-Amino-6-cyano-6-isobutyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide (74).

[00297] To a solution of 73 (141 mg, 0.784 mmol) and cyanoacetamide (59.9 mg, 0.713 mmol) in EtOH (713 µl), morpholine (67.6 Petition 870250103125, dated 11 / 11 / 2025, p. 153 / 470 148 / 431 µl, 0.784 mmol) and sulfur (25.2 mg, 98.3 µmol). The reaction mixture was stirred at 60 °C for 19 hours, allowed to cool to RT, and concentrated to dryness. The residue was partitioned between EA and water. The layers were separated, and the organic phase was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane) to yield the title compound 74 as a beige solid (115 mg, 58% yield). LC-MS: rt = 1.49 min, MS: 277.1 (calculated), 277.9 (M+H+, found). Step 3.2-Amino-6-cyano-6-isobutyl-7-oxo-4,5,6,7-tetrahydrobenzo[ b lthiophene-3-carboxamide (75).

[00298] To a solution of 74 (30 mg, 0.108 mmol) in DMSO (643 µl), selenium dioxide (12.0 mg, 0.108 mmol) was added. The reaction mixture was stirred at RT for 12 hours, then partitioned between brine and EA. The layers were separated, and the organic phase was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 10% MeOH in DCM), then by semi-preparative HPLC-MS (35% to 100% MeOH in 10 mM ammonium formate pH = 3.8) to yield the title compound 75 as a white solid (3.20 mg, 10% yield).

[00299] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.19-3.09 (m, 2H), 2.51 (ddd, J = 13.71, 7.59, 5.42 Hz, 1H), 2.36 (dt, J = 13.65, 5.45 Hz, 1H), 1.97-1.85 (m, 2H), 1.80-1.75 (m, 1H), 1.03 (d, J = 6.05 Hz, 6 H). LC-MS: rt = 1.11 min, MS: 291.1 (calculated), 292.1 (M+H+, found). Example 51 2-amino-6-(cyanomethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (81) and Example 52 2-Amino-6-(cyanomethyl)-N-cyclopropyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (82) Petition 870250103125, dated 11 / 11 / 2025, page 154 / 470 149 / 431 Scheme 13 Step 1. 2-Amino-6-(cyanomethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (77).

[00300] To a solution of 2-(4-oxo-1-phenylcyclohexyl)acetonitrile (76) (Bioorg. Med. Chem. Lett., 21, p. 405, 2011) (705 mg, 3.31 mmol) and ethyl 2-cyanoacetate (351 µl, 3.01 mmol) in EtOH (3.01 mL), morpholine (285 µl, 3.31 mmol) and sulfur (106 mg, 0.415 mmol) were added. The mixture was stirred at 60 °C for 16 hours, then allowed to cool to RT and a white precipitate was formed. This solid was collected by filtration, washed with EtOH and dried under vacuum to yield the title compound 77 as a white solid (682 mg, 67% yield). LC-MS: rt = 1.55 min, MS: 340.1 (calculated), 341.1 (M+H+, found). Step 2 2-Acetamido-6-(cyanomethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (78).

[00301] To a solution of 77 (682 mg, 2.00 mmol) in acetic acid (11.5 ml), acetic anhydride (227 µl, 2.40 mmol) was added. The mixture was stirred at 60 °C for 24 hours, then allowed to cool to RT and concentrated to dryness. The residue was partitioned between DCM and water. The layers were separated, and the organic phase was washed with a saturated aqueous solution of Petition 870250103125, dated 11 / 11 / 2025, p. 155 / 470 150 / 431 NaHCO3, water, and brine. The organic layer was dried with Na2SÜ4, filtered, and concentrated to produce compound 78 as a white solid (766 mg, >99% yield). LC-MS: rt = 1.61 min, MS: 382.1 (calculated), 383.1 (M+H+, found). Step 3.2-Ethyl Acetamido-6-(cyanomethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzoj b lthiophene-3-carboxylate (79).

[00302] To a solution of 78 (766 mg, 2.00 mmol) in acetic acid (6.73 ml) and water (6.73 ml), ceric sulfate (5.75 g, 17.3 mmol) was added. The suspension was sonicated until homogeneous and stirred at RT for 1 day, then partitioned between EA and water. The layers were separated, and the organic phase was washed with 1 N NaOH, water, and brine. The organic layer was dried with Na2SO4, filtered, and concentrated to yield the title compound 79 as a dirty white solid (794 mg, >99% yield). LCMS: rt = 1.47 min, MS: 396.1 (calculated), 397.1 (M+H+, found). Step 4 2-Amino-6-(cyanomethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (80).

[00303] To a suspension of 79 (793 mg, 2.00 mmol) in toluene (3.28 ml), pyrrolidine (2.46 ml, 30.0 mmol) was added. The suspension became a solution after a few minutes of stirring, and the reaction mixture was stirred at 80 °C for 1 hour, then allowed to cool to RT and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane) to yield the title compound 80 as a white solid (408 mg, 57% yield). LC-MS: rt = 1.43 min, MS: 354.1 (calculated), 355.0 (M+H+, found). Step 5. 2-amino-6-(cyanomethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (81).

[00304] To a suspension of 80 (408 mg, 1.15 mmol) in MeOH (139 ml), a solution of lithium hydroxide monohydrate (242 mg, 5.76 mmol) in water (139 ml) was added. The reaction mixture was stirred under Petition 870250103125, dated 11 / 11 / 2025, page 156 / 470 151 / 431 reflux for 16 hours, then allowed to cool to RT. The mixture was diluted with water and concentrated to remove most of the organic solvent, then washed with EA. The aqueous layer was collected, acidified by the slow addition of 2N HCl, and extracted with EA. This organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 10% MeOH in DCM) to yield the title compound 81 as a white solid (376 mg, >99% yield).

[00305] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.34-7.27 (m, 5H), 3.35-3.30 (m, 1H), 3.01 (d, J = 16.71 Hz, 1H), 2.89 (d, J = 16.71 Hz, 1H), 2.77-2.74 (m, 1H), 2.49-2.45 (m, 2H). LC-MS: rt = 1.16 min, MS: 326.1 (calculated), 327.0 (M+H+, found). Step 6. 2-Amino-6-(cyanomethyl)-N-cyclopropyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (82).

[00306] To a suspension of 81 (154 mg, 0.472 mmol) in THF (5.90 ml), HATU (359 mg, 0.944 mmol) and N,N-diisopropylethylamine (164 µl, 0.944 mmol) were added. The mixture was stirred at RT for 20 min, and then cyclopropylamine (327 µl, 4.72 mmol) was added. The reaction mixture was stirred for a further 16 hours, then partitioned between EA and a saturated aqueous solution of NH4Cl. The layers were separated, and the organic phase was collected, washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (20% to 100% EA eluent gradient in hexane) and then by reversed-phase flash column chromatography (0% to 100% CH3CN eluent gradient in H2O with 0.1% (v / v) formic acid) to yield the title compound 82 as a white solid (46.5 mg, 27% yield).

[00307] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.35-7.27 (m, 5H), 3.00 (d, J = 16.70 Hz, 1H), 2.89 (d, J = 16.71 Hz, 1H), 2.82-2.78 (m, 1H), Petition 870250103125, dated 11 / 11 / 2025, p. 157 / 470 152 / 431 2.77-2.74 (m, 1H), 2.69-2.64 (m, 2H), 2.49-2.42 (m, 1H), 0.72-0.67 (m, 2H), 0.54-0.48 (m, 2H). LC-MS: rt = 1.20 min, MS: 365.1 (calculated), 366.1 (M+H+, found). Example 53 2-Amino-6-(cyanomethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (83) and Example 54 2-Amino-6-(2-amino-2-oxoethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (84) Scheme 14 L-Step 2-Amino-6-(cyanomethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (83).

[00308] A suspension of 81 (50.0 mg, 0.153 mmol) in anhydrous DMF (1.69 ml) was saturated with gaseous NH3. Then, PyBOP (120 mg, 0.230 mmol) and N,N-diisopropylethylamine (53.4 µl, 0.306 mmol) were added, and the reaction mixture was stirred at RT for 16 hours. Subsequently, the mixture was partitioned between EA and a saturated aqueous solution of NH4Cl. The layers were separated, and the aqueous phase was extracted with EA. The combined organic compounds were dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (20% to 100% EA eluent gradient in hexane), then by reversed-phase flash column chromatography (0% to 100% CH3CN eluent gradient in H2O with 0.1% (v / v) formic acid) to yield the title compound 83 as a white solid (47.0 mg, 94% yield). Petition 870250103125, dated 11 / 11 / 2025, page 158 / 470 153 / 431

[00309] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.39-7.29 (m, 5H), 3.02-2.95 (m, 2H), 2.90 (d, J = 16.72 Hz, 1H), 2.80 (ddd, J = 13.55, 4.09, 2.50 Hz, 1H), 2.67 (ddd, J = 17.32, 11.78, 4.10 Hz, 1H), 2.49 (ddd, J = 13.53, 11.79, 4.45 Hz, 1H). LC-MS: rt = 1.01 min, MS: 325.1 (calculated), 326.0 (M+H+, found). Step 2. 2-Amino-6-(2-amino-2-oxoethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (84).

[00310] A suspension of 83 (47.0 mg, 0.144 mmol) in concentrated sulfuric acid (470 µl) was stirred at RT for 72 hours, then poured over crushed ice, and the resulting mixture was basified using a 4 N NaOH solution. The solution was extracted with DCM. The organic extract was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 10% MeOH in DCM, then 100% isopropanol) to yield the title compound 84 as a white solid (17.5 mg, 35% yield).

[00311] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.32-7.27 (m, 4H), 7.23-7.19 (m, 1H), 2.99 (d, J = 14.78 Hz, 1H), 2.92-2.87 (m, 1H), 2.78-2.71 (m, 1H), 2.65 (d, J = 14.76 Hz, 2H), 2.60-5.50 (m, 1H). LC-MS: rt = 0.84 min, MS: 343.1 (calculated), 344.1 (M+H+, found). Example 55 2-amino-6-(2-hydroxyethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (89). Scheme 15 Petition 870250103125, dated 11 / 11 / 2025, page 159 / 470 154 / 431 Step 1. 2-Amino-6-(2-hydroxyethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxylate ethyl (86).

[00312] To a solution of 4-(2-hydroxyethyl)-4-phenylcyclohexan-1-one (85) (Bioorg. Med. Chem. Lett., 21, p. 405, 2011) (7.95 g, 36.4 mmol) and ethyl 2-cyanoacetate (4.26 ml, 40.1 mmol) in EtOH (36.4 ml), morpholine (3.50 ml, 40.1 mmol) and sulfur (1.29 g, 5.03 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, then allowed to cool to RT and a white precipitate was formed. This solid was collected by filtration, washed with EtOH and dried under vacuum to yield the title compound 86 as a white solid (9.40 g, 72% yield). LC-MS: rt = 1.41 min, MS: 345.1 (calculated), 346.1 (M+H+, found). Step 2 2-Acetamido-6-(2-hydroxyethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (87).

[00313] To a solution of 86 (8.30 g, 24.0 mmol) in acetic acid (138 ml), acetic anhydride (2.73 ml, 28.8 mmol) was added. The mixture was stirred at 60 °C for 2 hours, then allowed to cool to RT and concentrated to dry to produce the title compound 87 as a brown oil which was used directly for the next step. LC-MS: rt = 1.78 min, MS: 387.2 (calculated), 388.2 (M+H+, found). Step 3.2-Acetamido-6-(2-hydroxyethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (88).

[00314] For a solution of 87 (24.0 mmol) in acetic acid (160 ml), Petition 870250103125, dated 11 / 11 / 2025, pp. 160 / 470 155 / 431 water (160 ml) and dioxane (160 ml), ceric sulfate (69.0 g, 208 mmol) was added. The mixture was sonicated until homogeneous, stirred at RT for 24 hours, and partitioned between EA and water. The layers were separated, and the organic phase was washed with 1 N NaOH, water, and brine. The organic layer was then dried with Na2SO4, filtered, and concentrated to yield compound 88 as an orange solid (9.60 g, 91% yield). LC-MS: rt = 1.56 min, MS: 401.1 (calculated), 402.1 (M+H+, found). Step 4. 2-amino-6-(2-hydroxyethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (89).

[00315] To a suspension of 88 (9.60 g, 24.1 mmol) in MeOH (1.11 l), a solution of lithium hydroxide monohydrate (6.86 g, 163.4 mmol) in water (1.11 l) was added. The reaction mixture was stirred at 55 °C for 24 hours, then allowed to cool to RT. The cooled mixture was diluted with water and concentrated to remove most of the organic solvent, then washed with EA. The aqueous layer was collected, acidified by the slow addition of 2 N HCl, and extracted with EA. This organic extract was dried with Na2SO4, filtered, and concentrated to yield the title compound 89 as an orange solid (7.0 g, 88% yield).

[00316] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.29-7.16 (m, 5H), 3.53-3.38 (m, 2H), 3.20-3.12 (m, 1H), 2.61-2.53 (dt, J = 13.63, 3.48 Hz, 1H), 2.44 (ddd, J = 18.55, 11.61, 4.01 Hz, 1H), 2.34-2.23 (m, 1H), 2.15-2.03 (m, 2H). LC-MS: rt = 1.04 min, MS: 331.1 (calculated), 332.0 (M+H+, found). Example 56 2-Amino-7-oxo-5-propyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (91) Scheme 16 Petition 870250103125, dated 11 / 11 / 2025, p. 161 / 470 156 / 431 9091: Example 56

[00317] Compound 90 (277 mg, 1.18 mmol, synthesized similarly to compound 3 in Scheme 1 starting from 5-propyl-1,3-cyclohexanedione instead of 5-(2-(trifluoromethyl)phenyl)cyclohexane-1,3-dione) was dissolved in 98% H2SO4 (2.5 ml), and the mixture was stirred at RT for 24 hours. Then, the reaction mixture was slowly poured into ice-cold aqueous K2CO3, diluted with water, and extracted with EA (Part of the product precipitated. It was collected by filtration and combined with the rest of the crude product). The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (50% to 100% EA eluent gradient in hexane) to yield the title compound 91 as a dirty white solid (144 mg, 48% yield).

[00318] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 7.97 (s, 2H), 6.96 (bs, 2H), 2.99-2.95 (m, 1H), 2.67-2.57 (m, 1H), 2.38-2.32 (m, 1H), 2.19-2.07 (2H, m), 1.36 (bs, 4H), 0.88 (bs, 3H). LC-MS: rt = 2.30 min, MS: 252.1 (calculated), 253.1 (M+H+, found). Example 57 2-Amino-6-(2,2-difluoroethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (97) Scheme 17 Petition 870250103125, dated 11 / 11 / 2025, p. 162 / 470 157 / 431 Step 1. 2-(8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)acetaldehyde (93)

[00319] To a solution of 2-(8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)acetonitrile (92) (1.0 g, 3.89 mmol) (Bioorg Med. Chem Lett. 21, p. 405, 2011) in anhydrous toluene (24.5 ml) at -78 °C, DIBALH (3.92 ml, 25% in toluene, 5.83 mmol) was added dropwise. The reaction mixture was stirred at -78 °C for 2 hours before being carefully cooled with MeOH and saturated NH4Cl solution. Subsequently, the mixture was left in the open air until RT was reached and diluted with Et2O, then filtered through a Celite filter. The layers were separated and the organic phase was concentrated. The residue was dissolved in THF (15.0 ml), and 1 N HCl (3.89 ml 3.89 mmol) was added. The mixture was stirred at room temperature for 15 min before being rapidly cooled with a saturated NaHCO3 solution and extracted with Et2O. The organic layer was dried with Na2SO4, filtered, and concentrated.The residue was purified by flash column chromatography (5% to 100% eluent gradient of EA in hexane) to yield the title compound 93 (605 mg, 60% yield) as a colorless oil, which was not characterized and used directly for the next step. Petition 870250103125, dated 11 / 11 / 2025, page 163 / 470 158 / 431 Step 2. 8-(2,2-Difluoroethyl)-8-phenyl-1,4-dioxaspiro[4.5]decane (94)

[00320] To a solution of 93 (200 mg, 0.77 mmol) in anhydrous DCM (9.5 ml) at 0 °C, DAST (0.19 ml, 1.54 mmol) was added. The reaction mixture was stirred at RT for 1 hour, then rapidly cooled with saturated NaHCO3 solution and extracted with DCM. The organic layer was dried with Na2SO4, filtered, and concentrated to yield the title compound 94 (213 mg, 98% yield) as a colorless oil, which was not characterized and used directly for the next step. Step 3. 4-(2,2-Difluoroethyl)-4-phenylcyclohexan-1-one (95)

[00321] To a solution of 94 (213 mg, 0.75 mmol) in acetone (10.5 ml) was added 2 N HCl (1.89 ml, 3.77 mmol), and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized by slowly adding saturated NaHCO3 solution and concentrated to remove the organic solvent. The residue was extracted with EA, and the organic layer was washed with brine, dried with Na2SO4, filtered, and concentrated to dryness to yield the title compound 95 (169 mg, 94% yield) as a colorless oil, which was not characterized and used directly for the next step. Step 4 2-Amino-6-(2,2-difluoroethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (96)

[00322] To a solution of 95 (169 mg, 0.709 mmol) and cyanoacetamide (66 mg, 0.78 mmol) in EtOH (0.7 mL), morpholine (0.068 mL, 0.78 mmol) and sulfur (25 mg, 0.098 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, then allowed to cool to RT and concentrated to dryness. The residue was partitioned between water and EA. The layers were separated, and the organic phase was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (50% to 100% EA eluent gradient in hexane) to yield the title compound 96 (93 mg, 39% yield). LC-MS: rt = 1.39 min, MS: 336.1 (calculated) Petition 870250103125, dated 11 / 11 / 2025, page 164 / 470 159 / 431 337.1 (M+H+, found). Step 5 2-Amino-6-(2,2-difluoroethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b-thiophene-3-carboxamide (97)

[00323] To a mixture of 96 (40 mg, 0.119 mmol) in THF (0.4 ml) and water (0.08 ml) at 0 °C, a solution of DDQ (82 mg, 0.36 mmol) in THF (0.4 ml) was added dropwise. The reaction mixture was stirred at 0 °C for 30 min, then the mixture was rapidly cooled with saturated NaHCO3 solution and extracted with EA. The organic layer was dried with Na2SU4, filtered, and concentrated. The residue was purified by flash column chromatography (50% to 100% EA eluent gradient in hexane) to yield the title compound 97 as a pale yellow solid (3 mg, 7% yield).

[00324] 1H NMR: 400 MHz, CDCb, δ (ppm): 7.37-7.27 (m, 5H), 7.04 (s, 2H), 5.80 (tt, J = 56.4, 4.6, 1H), 5.32 (s, 2H), 2.97-2.92 (m, 1H), 2,832.78 (m, 1H), 2.65-2.57 (m, 1H), 2.53-2.42 (m, 3H). 19F NMR: 376 MHz, CDCl3, δ (ppm): -110.4 (ddt, J = 287.8, 56.1, 18.0 Hz, 1F), -111.5 (ddt, J = 287.8, 56.5, 16.3 Hz, 1F). LC-MS: rt = 1.25 min, MS: 350.1 (calculated), 351.0 (M+H+, found). Example 58 2-Amino-6-cyano-6-isopropyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (101) Scheme 18 Petition 870250103125, dated 11 / 11 / 2025, pp. 165 / 470 160 / 431 Step 1. 8-Isopropyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (98)

[00325] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (40, Scheme 4) (1.0 g, 5.98 mmol) in anhydrous THF (12.0 ml) at 0 °C, LHMDS (6.88 ml, 1 M in THF, 6.88 mmol) was added dropwise. The reaction mixture was stirred at 0 °C for 1 hour before the dropwise addition of 2-iodopropane (0.597 ml, 5.98 mmol). Then, the reaction mixture was allowed to slowly reach RT and stirred for 16 hours. Subsequently, the reaction mixture was rapidly cooled with water and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated to dryness to yield the compound of title 98 as a brown solid, which was used directly for the next step. LC-MS: rt = 3.05 min, MS: 209.1 (calculated), 210.1 (M+H+, found). Step 2. 1-Isopropyl-4-oxocyclohexane-1-carbonitrile (99)

[00326] To a solution of 98 (5.98 mmol) in acetone (80 ml), 2 N HCl (23.9 ml, 47.8 mmol) was added, and the reaction mixture was stirred at RT for 2 days. Then, the mixture was neutralized by slowly adding saturated NaHCl solution and concentrated to remove the organic solvent. The residue was extracted with EA, and the organic layer was dried with Na2SU, filtered, and concentrated to dryness to yield the title compound 99 (445 mg, 45% yield over two steps). LC-MS: rt = 2.35 min, MS: 165.2 (calculated), 166.1 (M+H+, found). Step 3. 2-Amino-6-cyano-6-isopropyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (100)

[00327] To a solution of 99 (445 mg, 2.69 mmol) and cyanoacetamide (206 mg, 2.45 mmol) in EtÜH (4.9 ml), morpholine (0.24 ml, 2.69 mmol) and sulfur (87 mg, 0.338 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, and an abundant precipitate appeared. This solid was collected by filtration to yield the compound of title 100 (477 mg, 74% yield) as a white solid. LC-MS: rt = 2.60 min, Petition 870250103125, dated 11 / 11 / 2025, pp. 166 / 470 161 / 431 MS: 263.1 (calculated), 264.1 (M+H+, found). Step 4.2-Amino-6-cyano-6-isopropyl-7-oxo-4,5,6,7-tetrahydrobenzo[b-thiophene-3-carboxamide (101)]

[00328] To a solution of 100 (100 mg, 0.38 mmol) in DMSO (2.25 ml), selenium dioxide (42 mg, 0.38 mmol) was added. The reaction mixture was stirred at RT for 16 hours, then partitioned between brine and EA, and the organic layer was concentrated. The residue was purified by flash column chromatography (eluent gradient from 0.5% to 10% MeOH in DCM), then purified again by semi-preparative HPLC-MS (eluent gradient from 30% to 100% MeOH in 10 mM ammonium bicarbonate) to yield the title compound 101 as a white solid (5.0 mg, 5% yield).

[00329] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.18 (ddd, J = 17.9, 8.2, 5.1 Hz, 1H), 3.06 (dt, J = 17.9, 5.4 Hz, 1H), 2.50-2.39 (m, 3H), 1.12-1.08 (m, 6H). LC-MS: rt = 0.97 min, MS: 277.1 (calculated), 278.1 (M+H+, found). Example 59 2-Amino-6-(hydroxymethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (109) Scheme 19 Petition 870250103125, dated 11 / 11 / 2025, page 167 / 470 162 / 431 Step 1. 4-((( tert-butyldimethylsilyl)oxy)methyl)-4-phenylcyclohexan-1-one (103)

[00330] To a solution of 4-(hydroxymethyl)-4-phenylcyclohexan-1-one (102) (Bioorg. Med. Chem. Lett., 21, p. 405, 2011) (890 mg, 4.36 mmol) in anhydrous DMF (40 ml), tert-butyldimethylsilyl chloride (737 mg, 4.79 mmol) and imidazole (653 mg, 9.59 mmol) were added. The resulting mixture was stirred at RT for 16 hours, then diluted with water (30 ml) and extracted with EA (70 ml). The organic phase was dried with Na2SO4, filtered and concentrated, and the residue was purified by flash column chromatography (eluent gradient from 0% to 20% EA in hexane) to produce the title compound 103 as a white solid (1.20 g, 86% yield), which was not characterized and used directly for the next step. Step 2. 2-Amino-6-((( ter -butyldimethylsilyl)oxy)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylate ethyl (104)

[00331] A suspension of 103 (1.20 g, 3.77 mmol), morpholine (330 µl, 3.77 mmol), sulfur (121 mg, 473 µmol), and ethyl 2-cyanoacetate (364 µl, 3.42 mmol) in EtOH (6.01 ml) was stirred at 60 °C for 16 hours. The mixture was then allowed to cool to RT and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane) to yield the title compound 104 as a Petition 870250103125, dated 11 / 11 / 2025, pp. 168 / 470 163 / 431 off-white solid (1.49 g, 97% yield). LC-MS: rt = 2.34 min, MS: 445.2 (calculated), 446.2 (M+H+, found). Step 3. 2-((ter-Butoxycarbonyl)amino)-6-(((ter-butyldimethylsilyl)oxy)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[ethyl thiophene-3-carboxylate (105)

[00332] To a solution of 104 (1.49 g, 3.34 mmol), DMAP (41.7 mg, 334 µmol) and triethylamine (699 µl, 5.01 mmol) in DCM (66.8 ml) at 0 °C, a solution of di-tert-butyldicarbonate (802 mg, 3.68 mmol) was added dropwise into DCM. The resulting mixture was stirred at RT for 16 hours, then rapidly cooled with a saturated aqueous solution of NH4Cl. The layers were separated, and the aqueous phase was extracted with DCM. The combined organic compounds were dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane) to yield the title compound 105 as a dirty white solid (1.66 g, 91% yield). LC-MS: rt = 2.63 min, MS: 545.3 (calculated), 546.0 (M+H+, found). Step 4. 2-((ter-Butoxycarbonyl)amino)-6-(((ter-butyldimethylsilyl)oxy)methyl)-7oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (106)

[00333] A suspension of pyridinium chlorochromate (4.50 g, 20.9 mmol), Celite (1.50 g) and 105 (1.50 g, 2.75 mmol) in anhydrous benzene (40.7 ml) was stirred at 80 °C for 4 hours. The mixture was then allowed to cool to RT, filtered through a Celite filter, and the solid residue was washed with CHCl3. The filtrate was concentrated, and the residue was purified by flash column chromatography (eluent gradient from 0% to 30% EA in hexane) to yield the title compound 106 as a white solid (395 mg, 26% yield). LC-MS: rt = 2.52 min, MS: 559.2 (calculated), 560.2 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, pp. 169 / 470 164 / 431 Step 5 2-(( tert-butoxycarbonyl)amino)-6-((( tert-butyldimethylsilyl)oxy)methyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylic acid (107)

[00334] To a solution of 106 (380 mg, 679 µmol) in EtOH (20.0 ml), a solution of NaOH (136 mg, 3.39 mmol) in water (20.0 ml) was added. The resulting mixture was sonicated for 1 min and then vigorously stirred at RT for 68 hours. Subsequently, the mixture was diluted with water (15 ml) and extracted with EA (3 x 30 ml). The combined organic compounds were dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane, then from 0% to 30% MeOH in DCM) to yield the title compound 107 as a white solid (264 mg, 73% yield). LC-MS: rt = 1.60 min, MS: 531.2 (calculated), 532.1 (M+H+, found). Step 6. 2-amino-6-(hydroxymethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (108)

[00335] Trifluoroacetic acid (5.99 ml, 78.2 mmol) was added dropwise to a solution of 107 (260 mg, 489 µmol) in DCM (30.0 ml) at 0 °C. The mixture was stirred at 0 °C for 2 hours, then the reaction vessel was removed from the ice bath, and stirring continued at RT for a further 2 hours. The mixture was then concentrated, the residue was absorbed in DCM and concentrated 3 times, then purified by flash column chromatography (eluent gradient from 0% to 13% MeOH in DCM) to yield the title compound 108 as a light yellow solid (80 mg, 52% yield). (see Table 6 for characterization) Step 7.2-Amino-6-(hydroxymethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (109)

[00336] A suspension of 108 (54.0 mg, 170 µmol), ammonium chloride (182 mg, 3.40 mmol) and HATU (97.0 mg, 255 µmol) in DMF (4.00 Petition 870250103125, dated 11 / 11 / 2025, page 170 / 470 165 / 431 ml), N,N-diisopropylethylamine (59.3 µl, 340 µmol) was added dropwise. The mixture was stirred at room temperature for 16 hours, then a further 97 mg of HATU (255 µmol) was added, and stirring continued for 1 hour. The mixture was diluted with saturated aqueous NH4Q solution and extracted with EA (3 x 20 ml). The combined organic compounds were successively washed with brine (3 x 20 ml) and 0.05 N aqueous HCl, then concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 15% MeOH in DCM), then purified again by reversed-phase flash column chromatography (eluent gradient from 10% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 109 as a dirty white solid (17.2 mg, 32% yield).

[00337] 1H NMR: 400 MHz, DMSO-dô, δ (ppm): 8.06 (s, 2H) 7.32-7.27 (m, 4H), 7.23-7.20 (m 1H), 6.88 (bs, 2H), 4.77 (t, J = 5.5 Hz, 1H), 3.92 (dd, J = 10.4, 5.6 Hz, 1H), 3.35-3.32 (m, 1H), 2.89-2.84 (m, 1H), 2.73-2.67 (m, 1H), 2.50-2.48 (m, 1H, partially superimposed on the solvent signal). LCMS: rt = 0.88 min, MS: 316.1 (calculated), 317.0 (M+H+, found). Examples 60 to 67 Intermediate compound 111 1-Benzyl-4-oxocyclohexane-1-carbonitrile (111) Scheme 20 Step 1. 8-Benzyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (110).

[00338] To a solution of 40 (scheme 4) (1.0 g, 5.98 mmol) in anhydrous THF (24.0 ml) at -78 °C, LDA (6.58 ml, 1 M) was added dropwise. Petition 870250103125, dated 11 / 11 / 2025, p. 171 / 470 166 / 431 in THF / hexane, 6.58 mmol). The reaction mixture was stirred at -78 °C for 45 min, then benzyl bromide (0.870 ml, 7.18 mmol) was added dropwise. The reaction mixture was left in the open air until RT was reached and stirred for 2.5 hours. Subsequently, the reaction mixture was rapidly cooled with water and extracted with EA. The organic layer was washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 30% EA in hexane) to yield the title compound 110 (1.22 g, 79% yield) as a white solid, which was not characterized and used directly for the next step. Step 2. 1-Benzyl-4-oxocyclohexane-1-carbonitrile (111).

[00339] To a solution of 110 (1.21 g, 4.70 mmol) in acetone (63 ml), 2 N HCl (11.8 ml, 23.5 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized by slowly adding saturated NaHCl solution and concentrated to remove the organic solvent. The residue was extracted with EA, and the organic layer was dried with Na2SU, filtered, and concentrated to dryness to yield the title compound 111 (1.00 g, >99% yield). LC-MS: rt = 2.93 min, MS: 213.1 (calculated), 214.1 (M+H+, found). Intermediate compound 115 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)ethan-1-ol (115) Scheme 21 Petition 870250103125, dated 11 / 11 / 2025, p. 172 / 470 167 / 431 Step 1. 8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbaldehyde (113)

[00340] Diisobutylaluminum hydride (25% solution in toluene; 121 ml, 180.0 mmol) was added dropwise to a solution of 8(cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (112) (24.3 g, 110 mmol) (ACS Med. Chem. Lett. 2010, 350-354) in anhydrous toluene (600 ml) at 78 °C, and the resulting mixture was stirred at -78 °C for 2 hours. The reaction mixture was then rapidly cooled with methanol (15 ml) to -78 °C and partitioned between saturated aqueous NH4Cl solution (200 ml) and diethyl ether (300 ml). The mixture was allowed to slowly reach RT, and a saturated aqueous Rochelle salt solution (1 l) was added. The layers were separated, and the organic phase was washed with brine (2 x 200 ml), dried with Na2SO4, filtered, and concentrated. The residue was dissolved in THF (400 ml) and treated with 2 N aqueous HCl (27.5 ml, 54.9 mmol).The mixture was stirred at RT for 1 hour, then rapidly cooled with aqueous saturated NaHCO3 and concentrated to remove the organic solvent. The aqueous residue was extracted with diethyl ether, and the organic compounds were dried with Na2SO4, filtered, and concentrated to yield compound 113 as a colorless oil (24.6 g, >99% yield), which was not characterized and used directly for the next step. Step 2. 8-(Cyclopropylmethyl)-8-vinyl-1,4-dioxaspiro[4.5]decane (114)

[00341] To a 1 M solution of LHMDS in THF (10 ml, 10.0 mmol) diluted with anhydrous THF (55.0 ml) at 60 °C, methyltriphenylphosphonium bromide (2.23 g, 6.24 mmol) was added in 4 portions over 30 minutes. The reaction mixture was stirred at 60 °C for 1 hour after the last addition. Then, 113 (700 mg, 3.12 mmol) in anhydrous THF (10.0 ml) was added dropwise, and the reaction mixture was stirred at 60 °C for a further 30 minutes. The mixture was then allowed to cool to RT, rapidly cooled with a saturated NH4Cl solution (40 ml), and extracted twice with EA (2 x 50 ml). The combined organic compounds were dried with Petition 870250103125, dated 11 / 11 / 2025, page 173 / 470 168 / 431 Na2SÜ4, filtered and concentrated, and the residue was purified by flash column chromatography (eluent gradient from 0% to 30% Et2Ü in hexane) to yield the title compound 114 as a colorless oil (527 mg, 76% yield), which was not characterized and used directly for the next step. Step 3. 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiror4.5]decan-8-yl)ethan-1-ol (115)

[00342] To a solution of 114 (520 mg, 2.34 mmol) in anhydrous THF (12 ml) at 0 °C, 9-BBN (9.35 ml, 0.5 M in THF, 4.68 mmol) was added dropwise. The reaction mixture was stirred at RT for 2.5 hours, then cooled to 0 °C again, and water (42 µl, 2.34 mmol), 1 N NaOH (7.0 ml, 7.0 mmol) and 30% H2O2 (12 ml) were added. The reaction mixture was stirred at 0 °C for 10 min, then stirred at RT for 16 hours. Subsequently, the mixture was diluted with EA and water. The layers were separated, and the organic phase was washed with brine, dried with Na2SÜ4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 30% to 100% EA in hexane) to yield the title compound 115 as a colorless oil (479 mg, 85% yield), which was not characterized and used directly for the synthesis of the relevant examples. Intermediate compound 118 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acetonitrile (118) Scheme 22 Step 1. (8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)methanol (116)

[00343] Sodium borohydride (816 mg, 21.1 mmol) was added to Petition 870250103125, dated 11 / 11 / 2025, page 174 / 470 169 / 431 a solution of 113 (scheme 21) (3.16 g, 14.1 mmol) in MeOH (86.8 ml) at 0 °C. The resulting solution was stirred at RT for 1 hour, then the reaction mixture was rapidly cooled with saturated aqueous NH4Cl solution (30 ml). The mixture was diluted with EA (30 ml), the layers were separated, and the aqueous layer was extracted with EA (30 ml). The combined organic compounds were washed with 0.2 N HCl (50 ml) and brine, then dried with Na2SO4, filtered, and concentrated to yield the title compound 116 (2.95 g, 93% yield) as a colorless oil, which was not characterized and used directly for the next step. Step 2. (8-(cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)methyl 4-Methylbenzenesulfonate (117)

[00344] To a solution of 116 (2.70 g, 11.9 mmol) in pyridine (51.9 ml), p-toluenesulfonyl chloride (7.96 g, 41.8 mmol) was added, and the resulting mixture was stirred at RT for 16 hours. The mixture was then diluted with EA and water (30 ml each), and the layers were separated. The aqueous phase was extracted with EA (30 ml), and the combined organic compounds were washed with water (30 ml) and brine (2 x 30 ml), then dried with Na2SO4, filtered, and concentrated. The residue was diluted with heptanes and concentrated to dryness, then purified by flash column chromatography (eluent gradient from 0% to 40% EA in hexane) to yield the title compound 117 (3.65 g, 80% yield) as a colorless oil. LC-MS: rt = 1.78 min. MS: 380.2 (calculated), 381.3 (M+H+, found). Step 3. 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acetonitrile (118)

[00345] To a solution of 117 (3.65 g, 9.59 mmol) in DMSO (57.1 ml), sodium cyanide (1.41 g, 28.8 mmol) was added, and the resulting mixture was stirred at 60 °C for 96 hours. The mixture was allowed to cool to RT and diluted with saturated aqueous solution of NaHCO3 (50 ml). The mixture was then diluted with EA (50 ml) and water (40 ml), the layers were Petition 870250103125, dated 11 / 11 / 2025, p. 175 / 470 170 / 431 separated, and the aqueous phase was extracted with EA (2 x 50 ml). The combined organic compounds were washed with water (2 x 30 ml) and brine (30 ml), dried with Na2SO4, filtered, and concentrated to produce compound 118 (2.5 g, 72% yield) as a yellow oil, which was not characterized and used directly for the synthesis of the relevant examples. Compounds 119 to 126

[00346] Compounds 119 to 123 (examples 60 to 64) were synthesized similarly to compound 81 (example 51, scheme 13) starting from 4-methyl-4-phenylcyclohexan-1-one, compound 111 (scheme 20), compound 73 (scheme 12), compound 95 (scheme 17) and compound 99 (scheme 18), respectively, instead of 2-(4-oxo-1-phenylcyclohexyl)acetonitrile (76). Compounds 124 to 126 (examples 65 to 67) were synthesized similarly to compound 47 (example 28, Scheme 4), starting from compound 115 (Scheme 21), compound 116 (Scheme 22), and compound 118 (Scheme 22), respectively, instead of compound 41. The characterization of compounds 119 to 126 (examples 60 to 67) is provided in Table 4. Table 4. Characterization of compounds 119 to 126 (examples 60 to 67). Ex. No. Compound No. Structure Characterization 60 119 O XoH \ KÁ 1XXnh2 0 2-amino-6-methyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 12.47 (s, 1H), 8.24 (s, 2H), 7.32-7.19 (m, 5H), 3.05 (dt, J = 18.5, 3.9 Hz, 1H), 2.56-2.51 (m, 1H), 2.43-2.33 (m, 1H), 2.15-2.08 (m, 1H), 1.35 (s, 3H). LC-MS: rt = 1.30 min, MS: 301.1 (calculated), 302.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 176 / 470 171 / 431 61 120 / y 0 VL z / / OH VJ V'ynh2 a / a NC II 0 2-amino-6-benzyl-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid 1H NMR: 400 MHz, DMSO-de, δ (ppm): 8.71 (bs, 2H), 7.37-7.28 (m, 5H), 3.26-3.22 (m, 2H), 3.09-2.97 (m, 2H), 2.20-2.14 (m, 1H), 2.11-2.04 (m, 1H). LC-MS: rt = 1.30 min, MS: 326.1 (calculated), 327.1 (M+H+, found). 62 121 0 / 0H \T ]] YNH2 A / ^S NC II o 2-amino-6-cyano-6-isobutyl-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylic acid 1H NMR: 400 MHz, DMSO-de, δ (ppm): 12.76 (s, 1H), 8.48 (s, 2H), 3.13-2.99 (m, 2H), 2.47-2.40 (m, 1H), 2.31-2.25 (m, 1H), 1.87-1.74 (m, 2H), 1.71-1.65 (m, 1H), 0.98-0.94 (m, 6H). LC-MS: rt = 1.28 min, MS: 292.1 (calculated), 293.1 (M+H+, found).63 122 O γΟΗ \ Vj Ύ>ΝΗ2 ; Y^S Fx| 0 F 2-Amino-6-(2,2difluoroethyl)-7-oxo-6-phenyl4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxylic acid 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.34-7.28 (m, 4H), 7.26-7.21 (m, 1H), 5.86 (tt, J = 56.6, 4.5 Hz, 1H), 3.27-3.21 (m, 1H), 2.73-2.69 (m, 1H), 2.51-2.34 (m, 4H). LC-MS: rt = 1.40 min, MS: 351.1 (calculated), 352.1 (M+H+, found). 64 123 O VOH \r jinh2 NC II 0 2-amino-6-cyano-6-isopropyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid 1H NMR: 400 MHz, DMSO-de, δ (ppm): 12.74 (s, 1H), 8.47 (s, 2H), 3.10-2.97 (m, 2H), 2.37-2.27 (m, 3H), 1.01 (d, J = 6.7 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H). LC-MS: rt = 1.15 min, MS: 278.1 (calculated), 279.1 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 177 / 470 172 / 431 65 124 O ho 2-amino-6-(cyclopropylmethyl)-6-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.66-3.55 (m, 2H), 3.19-3.04 (m, 2H), 2.25-2.19 (m, 1H), 2.11-2.00 (m, 2H), 1.86-1.79 (m, 1H), 1.71 (dd, J = 14.1, 6.1 Hz, 1H), 1.38 (dd, J = 14.2, 7.2 Hz, 1H), 0.71-0.65 (m, 1H), 0.49-0.41 (m, 2H), 0.11-0.00 (m, 2H). LC-MS: rt = 1.05 min, MS: 309.1 (calculated), 310.2 (M+H+, found). 66 125 O <7 Υ0H \r jj xnh2 s ho 2-amino-6-(cyclopropylmethyl)-6(hydroxymethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid 1H NMR: 400 MHz, DMSO-δ, δ (ppm): 12.38 (bs, 1H), 8.19 (s, 2H), 4.57 (bs, 1H), 3.68 (d, J = 10.5 Hz, 1H), 3.36-3.33 (m, 1H), 3.07-2.99 (m, 1H), 2.95-2.88 (m, 1H), 2.16-2.09 (m, 1H), 2.07-2.00 (m, 1H), 1.57 (dd, J = 14.1, 6.2 Hz, 1H), 1.27 (dd, J = 14.1, 7.3 Hz, 1H), 0.61-0.53 (m, 1H), 0.390.30 (m, 2H), 0.01 - -0.10 (m, 2H). LC-MS: rt = 1.01 min, MS: 295.1 (calculated), 296.1 (M+H+, found).67 126 oyoH \ [ TJnh2 / Nt'S NCX Π 0 2-amino-6-(cyanomethyl)6-(cyclopropylmethyl)-7-oxo4,5,6,7-tetrahidrobenzo[ b ]thiophene-3carboxylic acid 1H NMR: 400 MHz, DMSO-de, δ (ppm): 12.58 (s, 1H), 8.30 (s, 2H), 3.18-3.11 (m, 1H), 2.92-2.78 (m, 3H), 2.12-2.05 (m, 2H), 1.50 (d, J = 6.74 Hz, 2H), 0.62-0.57 (m, 1H), 0.43-0.35 (m, 2H), 0.07-0.02 (m, 1H), -0.05 -0.09 (m, 1H). LC-MS: rt = 1.10 min. MS: 304.1 (calculated), 305.0 (M+H+, encontrado). Examples 68 to 77

[00347] Compounds 127 to 133 (examples 68 to 74) were synthesized similarly to compound 82 (example 52, scheme 13) starting from compounds 119 to 125 (examples 60 to 66, Table 4), respectively, instead of compound 81. Compounds 134 to 135 (examples 75 to 76) were synthesized similarly to compound 9 (example 2, scheme 2) starting from compound 126 (example 67, Table 4) and compound 89 (example 55, scheme 15), respectively, instead of compound 8. Compound 136 (example 77) was synthesized similarly to Petition 870250103125, dated 11 / 11 / 2025, page 178 / 470 173 / 431 compound 82 (example 52, scheme 13) starting from compound 108 (scheme 19) instead of compound 81. The characterization of compounds 127 to 136 (examples 68 to 77) is provided in Table 5. Table 5. Characterization of compounds 127 to 136 (examples 68 to 77). Ex. Compound No. Structure Characterization 127 2-Amino-N-cyclopropyl-6-methyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.32-7.27 (m, 4H), 7.24-7.18 (m, 1H), 2.81-2.74 (m, 1H), 2,722.66 (m, 1H), 2.63-2.55 (m, 2H), 2.24-2.17 (m, 1H), 1.47 (s, 3H), 0.770.69 (m, 2H), 0.56-0.49 (m, 2H). LC-MS: rt = 1.35 min, MS: 340.1 (calculated), 341.2 (M+H+, found). 128 2-Amino-6-benzyl-6-cyano-Ncyclopropyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide 129 2-Amino-6-cyano-N-cyclopropyl-6-isobutyl-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 8.08 (bs, 2H), 7.61 (bs, 1H), 7.38-7.29 (m, 5H), 3.24 (d, J = 13.6 Hz, 1H), 3.10-3.02 (m, 2H), 2,972.89 (m, 1H), 2.77-2.72 (m, 1H), 2.19-2.13 (m, 1H), 2.09-2.02 (m, 1H), 0.70-0.65 (m, 2H), 0.55-0.51 (m, 2H). LC-MS: rt = 1.33 min, MS: 365.1 (calculated), 366.2 (M+H+, found). 1H NMR: 400 MHz, DMSO-de, δ (ppm): 8.02 (s, 2H), 7.55 (s, 1H), 3.04-2.87 (m, 2H), 2.78-2.72 (m, 1H), 2.38 (ddd, J = 13.6, 7.9, 4.9 Hz, 1H), 2.24 (dt, J = 13.7, 5.4 Hz, 1H), 1.86-1.78 (m, 2H), 1.73-1.66 (m, 1H), 0.97 (d, J = 4.2 Hz, 3H), 0.95 (d, J = 3.9 Hz, 3H), 0.70-0.66 (m, 2H), 0.55-0.51 (m, 2H). LC-MS: rt = 1.30 min, MS: 331.1 (calculated), 332.2 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 179 / 470 174 / 431 71 130 ^NH \ KJ J / ^nh2 TV'S FY 0 F 2-Amino-N-cyclopropyl-6-(2,2difluoroethyl)-7-oxo-6-phenyl4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CDCh, δ (ppm): 7.37-7.28 (m, 5H), 6.98 (s, 2H), 5.80 (tt, J = 56.4, 4.6 Hz, 1H), 5.50 (s, 1H), 2.83-2.70 (m, 3H), 2.542.40 (m, 4H), 0.88-0.76 (m, 2H), 0.57-0.49 (m, 2H). LC-MS: rt = 1.43 min, MS: 390.1 (calculated), 391.2 (M+H+, found). 72 131 V γΝΗ T / —nh2 NC II o 2-Amino-6-cyano-N-cyclopropyl6-isopropyl-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-dó, δ (ppm): 8.00 (s, 2H), 7.52 (d, J = 3.8 Hz, 1H), 3.04 (ddd, J = 18.0, 7.8, 5.4 Hz, 1H), 2.84 (dt, J = 18.0, 5.2 Hz, 1H), 2.78-2.72 (m, 1H), 2.37-2.28 (m, 3H), 1.00 (d, J = 6.7, 3H), 0.97 (d, J = 6.8 Hz, 3H), 0.70-0.65 (m, 2H), 0.54-0.51 (m, 2H). LC-MS: rt = 1.18 min, MS: 317.1 (calculated), 318.1 (M+H+, found).73 132 V <7 γΝΗ ]] y—nh2 jYs / o HO 2-Amino-N-cyclopropyl-6(cyclopropylmethyl)-6-(2hydroxyethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.66-3.55 (m, 2H), 2.99-2.85 (m, 2H), 2.79-2.73 (m, 1H), 2.23 (dt, J = 13.8, 5.9 Hz, 1H), 2.12-2.01 (m, 2H), 1.84 (ddd, J = 13.7, 8.9, 6.2Hz, 1H), 1.74 (dd, J = 14.1, 6.1 Hz, 1H), 1.40 (dd, J = 14.1, 7.3 Hz, 1H), 0.820.77 (m, 2H), 0.72-0.65 (m, 1H), 0.63-0.59 (m, 2H), 0.50-0.41 (m, 2H), 0.10-0.00 (m, 2H). LC-MS: rt = 1.10 min, MS: 348.2 (calculated), 349.2 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, pp. 180 / 470 175 / 431 74 133 V vT Jj >^nh2 HCP 2-Amino-N-ciclopropil-6(ciclopropilmetil)-6(hidroximetil)-7-oxo-4,5,6,7tetra-hidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-de, δ (ppm): 7,70 (s, 2H), 7,33 (d, J = 3,8 Hz, 1H), 4,53 (t, J = 5,4 Hz, 1H), 3,70 (dd, J = 10,5, 5,5 Hz, 1H), 3,37 (dd, J = 10,5, 5,2 Hz, 1H), 2,93-2,79 (m, 2H), 2,78-2,71 (m, 1H), 2,132,06 (m, 1H), 2,03-1,97 (m, 1H), 1,56 (dd, J = 14,0, 6,3 Hz, 1H), 1,31 (dd, J = 14,0, 7,2 Hz, 1H), 0,69-0,64 (m, 2H), 0,62-0,56 (m, 1H), 0,54-0,50 (m, 2H), 0,40-0,32 (m, 2H), 0,040,00 (m, 1H), -0,05 - -0,10 (m, 1H). LC-MS: rt = 1,07 min, MS: 334,1 (calculado), 335,1 (M+H+, encontrado).75 134 od 'pNH \ | jT / > nh2 NC^ íl 0 2-Amino-6-(cyanomethyl)-Ncyclopropyl-6-(cyclopropylmethyl)7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.82 (s, 2H), 7.38 (d, J = 3.83 Hz, 1H), 3.08-2.98 (m, 1H), 2.90 (d, J = 16.76 Hz, 1H), 2.78-2.71 (m, 3H), 2.12-2.04 (m, 2H), 1.57-1.46 (m, 2H), 0.68-0.56 (m, 3H), 0.540.50 (m, 2H), 0.47-0.35 (m, 2H), 0.10-0.06 (m, 1H), 0.00 - -0.09 (m, 1H). LC-MS: rt = 1.13 min. MS: 343.1 (calculated), 344.1 (M+H+, found). 76,135 V 4H), 7.25-7.21 (m, 1H), 3.54-3.41 (m, 2H), 2.822.74 (m, 1H), 2.71-2.55 (m, 3H), 2.37-2.30 (m, 1H), 2.17-2.04 (m, 2H), 0.76-0.65 (m, 2H), 0.56-0.48 (m, 2H). LC-MS: rt = 1.11 min, MS: 370.1 (calculated), 371.2 (M+H+, found). Petition 870250103125, dated 11 / 11 / 2025, p. 181 / 470 176 / 431 136 2-Amino-N-cyclopropyl-6(hydroxymethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.35-7.29 (m, 4H), 7.26-7.22 (m, 1H), 4.09 (d, J = 11.0 Hz, 1H), 3.56 (d, J = 11.0 Hz, 1H), 2.84-2.78 (m, 1H), 2.70-2.65 (m, 2H), 2,602.53 (m, 2H), 0.74-0.70 (m, 2H), 0.54-0.52 (m, 2H). LC-MS: rt = 1.09 min, MS: 356.1 (calculated), 357.2 (M+H+, found). Example 78 2-amino-6-(2-cyanoethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (138) and Example 79 2-amino-6-(3-amino-3-oxopropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (139) Scheme 23

[00348] To a solution of 137 (1.0 g, 2.71 mmol, synthesized similarly to compound 80 in Scheme 13 starting from 3-(4-oxo-1-phenylcyclohexyl)propanenitrile (Bioorg Med. Chem Lett. 21, p. 405, 2011) instead of 2-(4-oxo-1-phenylcyclohexyl)acetonitrile (76)) in MeOH (330 ml), a solution of lithium hydroxide monohydrate (569 mg, 13.6 mmol) was added in water (330 ml). The reaction mixture was stirred at 80 °C for 16 hours, then allowed to cool to RT. The mixture was concentrated to remove most of the organic solvent. The aqueous layer was acidified by adding 1 N HCl slowly and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 30% MeOH). Petition 870250103125, dated 11 / 11 / 2025, p. 182 / 470 177 / 431 in DCM) to produce the title compound 138 as a yellow solid (648 mg, 70% yield) and the title compound 139. The latter was purified again by semi-preparatory HPLC-MS (15% to 100% MeOH eluent gradient in 10 mM ammonium bicarbonate) to produce a white solid (142 mg, 15% yield).

[00349] 138: 1H NMR: 400 MHz, DMSO-do, δ (ppm): 12.51 (bs, 1H), 8.28 (s, 2H), 7.36-7.32 (m, 2H), 7.27-7.24 (m, 3H), 3.15-3.09 (m, 1H), 2.60-2.55 (m, 1H), 2.48-2.42 (m, 1H), 2.38-2.30 (m, 1H), 2.26-2.18 (m, 2H), 2.12-2.07 (m, 2H). LC-MS: rt = 1.23 min, MS: 340.1 (calculated), 341.1 (M+H+, found).

[00350] 139: 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.30 (bs, 2H) 2.00-1.91 (m, 4H). LCMS: rt = 0.98 min, MS: 358.1 (calculated), 359.1 (M+H+, found). Example 80 2-Amino-6-(2-cyanoethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (140) Scheme 24 oo / 0HNHa, NH4CI / dmf / thf / chci3~-zJT]'8 / 0 / O NCNC 138 140: Example 80

[00351] To a suspension of 138 (500 mg, 1.47 mmol) and ammonium chloride (1.57 g, 29.4 mmol) in anhydrous DMF (16.2 ml), HATU (855 mg, 2.20 mmol) and N,N-diisopropylethylamine (0.512 ml, 2.94 mmol) were added. Then, a saturated solution of NH3 in CHCl3 (8.7 ml) (prepared internally) and a solution of 0.4 M NH3 in THF (9.2 ml) were added dropwise, and the reaction mixture was stirred at RT for 16 hours. Subsequently, the reaction mixture was rapidly cooled with Petition 870250103125, dated 11 / 11 / 2025, page 183 / 470 178 / 431 a saturated solution of NH4Cl and extracted with EA. The organic layer was dried with Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 140 as a white solid (419 mg, 84% yield).

[00352] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 8.13 (s, 2H), 7.377.24 (m, 5H), 6.88 (bs, 2H), 2.91-2.84 (m, 1H), 2.68-2.56 (m, 2H), 2.46-2.42 (m, 1H), 2.25-2.17 (m, 2H), 2.13-2.07 (m, 2H). LC-MS: rt = 1.10 min, MS: 339.1 (calculated), 340.1 (M+H+, found). Example 81 2-Amino-6-(2-cyanoethyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (141) 141: Example 81

[00353] Compound 141 (example 81) was synthesized in a similar manner to compound 62 (example 39, scheme 10) starting from compound 140 (example 80, scheme 24) instead of compound 61.

[00354] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 8.08 (s, 2H), 7.357.21 (m, 5H), 7.17 (s, 1H), 6.87 (bs, 2H), 6.63 (s, 1H), 2.91-2.84 (m, 1H), 2.73-2.65 (m, 1H), 2.55-2.53 (m, 1H), 2.20-2.12 (m, 1H), 2.02-1.90 (m, 4H). LC-MS: rt = 0.88 min, MS: 357.1 (calculated), 358.2 (M+H+, found). Example 82 (S)-2-Amino-6-(3-amino-3-oxopropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (142) and Example 83 Petition 870250103125, dated 11 / 11 / 2025, p. 184 / 470 179 / 431 (R )-2-Amino-6-(3-amino-3-oxopropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzof b ]thiophene-3-carboxamide (143) Scheme 25

[00355] 100.3 mg of racemic compound 141 were subjected to chiral separation by CFS to produce enantioenriched title compound 142 as a white solid (29.9 mg, 30% separation yield) and enantioenriched title compound 143 as a white solid (26.2 mg, 26% separation yield). The absolute configurations of compounds 142 and 143 were assigned based on analogy with the assignment of the absolute configuration of a compound crystallized within an equal or similar series.

[00356] 142: 1H NMR: same as racemic mixture (141). LC-MS: rt = 0.88 min, MS: 357.1 (calculated), 358.2 (M+H+, found). Analytical CFS (IC column with a gradient of 5 to 60% MeOH + 10 mM AmFor (95 to 40% CO2)): rt = 5.80 min, ee. = 99.76%.

[00357] 143: 1H NMR: same as racemic mixture (141). LC-MS: rt = 0.88 min, MS: 357.1 (calculated), 358.2 (M+H+, found). Analytical CFS (IC column with a gradient of 5 to 60% MeOH + 10 mM AmFor (95 to 40% CO2)): rt = 6.45 min, ee. = 97.82%. Example 84 2-Amino-6-(2-cyanoethyl)-N-cyclopropyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzof b ]thiophene-3-carboxamide (144) e Example 85 2-Amino-6-(3-amino-3-oxopropyl)-N-cyclopropyl-7-oxo-6-phenyl-4,5,6,7-tetra Petition 870250103125, dated 11 / 11 / 2025, p. 185 / 470 180 / 431 hydrobenzo[ b ]thiophene-3-carboxamide (145) Scheme 26

[00358] Compound 144 (example 84) was synthesized in a similar manner to compound 82 (example 52, scheme 13) starting from compound 138 (example 78, scheme 23) instead of compound 81.

[00359] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.87 (s, 2H), 7.377.25 (m, 6H), 2.74-2.52 (m, 4H), 2.48-2.41 (m, 1H), 2.24-2.07 (m, 4H), 0.640.57 (m, 2H), 0.50-0.43 (m, 2H). LC-MS: rt = 1.27 min, MS: 379.1 (calculated), 380.2 (M+H+, found).

[00360] To a suspension of 144 (35 mg, 0.092 mmol) and K2CO3 (26 mg, 0.18 mmol) in MeOH (1.8 ml) and water (0.6 ml), 30% H2O2 (0.09 ml) was added. The reaction mixture was vigorously stirred at RT for 2 days. Then, more 30% H2O2 (0.19 ml) was added, and the reaction mixture was vigorously stirred at RT for a further 24 hours. Subsequently, the mixture was concentrated to remove the organic solvent, and the residue was extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated to yield the title compound 145 as a dirty white solid (17 mg, 46% yield).

[00361] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 7.81 (s, 2H), 7.357.21 (m, 6H), 7.17 (bs, 1H), 6.63 (bs, 1H), 2.77-2.59 (m, 3H), 2.50-2.48 (m, 1H), 2.16-2.08 (m, 1H), 2.01-1.90 (m, 4H), 0.64-0.58 (m, 2H), 0.50-0.45 (m, 2H). LC-MS: rt = 1.05 min, MS: 397.2 (calculated), 398.3 (M+H+, found). Example 86 Petition 870250103125, dated 11 / 11 / 2025, p. 186 / 470 181 / 431 2-Amino-6-methyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (146) Scheme 27 ΊΊ9 146: Example 86 Table 4

[00362] Compound 119 (Table 4) (50 mg, 0.17 mmol) was dissolved in a 0.4 M NH3 solution in THF (17 ml), and HATU (126 mg, 0.33 mmol) and N,N-diisopropylethylamine (0.058 ml, 0.33 mmol) were added to the mixture. The reaction mixture was then stirred at RT for 16 hours. Subsequently, the reaction mixture was rapidly cooled with a saturated NH4Cl solution and extracted with EA. The organic layer was washed with water and brine, then dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (40% to 100% EA eluent gradient in hexane), then purified again by semi-preparative HPLC-MS (35% to 100% CH3CN eluent gradient in 10 mM ammonium bicarbonate) to yield the title compound 146 as a white solid (22 mg, 44% yield).

[00363] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.32-7.28 (m, 4H), 7.24-7.19 (m, 1H), 2.95-2.89 (m, 1H), 2.68-2.58 (m, 2H), 2.28-2.21 (m, 1H), 1.48 (s, 3H). LC-MS: rt = 1.13, MS: 300.1 (calculated), 301.1 (M+H+, found). Example 87 2-Amino-6-benzyl-6-cyano-7-oxo-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide (147) Scheme 28 Petition 870250103125, dated 11 / 11 / 2025, p. 187 / 470 182 / 431

[00364] To a suspension of 120 (Table 4) (50 mg, 0.153 mmol) and ammonium chloride (164 mg, 3.06 mmol) in anhydrous THF (2.0 ml), HATU (87 mg, 0.230 mmol) and N,N-diisopropylethylamine (0.053 ml, 0.306 mmol) were added. Then, a saturated solution of NH3 in CHCl3 (0.25 ml) (prepared internally) was added dropwise, and the reaction mixture was stirred at RT for 16 hours. Subsequently, the reaction mixture was rapidly cooled with a saturated solution of NH4Cl and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 147 as a white solid (35 mg, 70% yield).

[00365] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 8.34 (bs, 2H), 7.40-7.30 (m, 5H), 7.13 (bs, 2H), 3.25-3.16 (m, 2H), 3.10-2.98 (m, 2H), 2,232.16 (m, 1H), 2.11-2.04 (m, 1H). LC-MS: rt = 1.15 min, MS: 325.1 (calculated), 326.1 (M+H+, found). Example 88 2-Amino-6-(cyclopropylmethyl)-6-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (148)

[00366] Compound 148 (example 88) was synthesized in a similar manner. Petition 870250103125, dated 11 / 11 / 2025, pp. 188 / 470 183 / 431 for compound 140 (example 80, diagram 24) starting from compound 124 (Table 4) instead of compound 138.

[00367] 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.67-3.56 (m, 2H), 3.03 (t, J = 6.1 Hz, 2H), 2.28 (dt, J = 13.8, 5.9 Hz, 1H), 2.17-2.10 (m, 1H), 2.05 (ddd, J = 13.7, 8.9, 6.1 Hz, 1H), 1.85 (ddd, J = 13.7, 8.9, 6.2 Hz, 1H), 1.74 (dd, J = 14.1, 6.1 Hz, 1H), 1.41 (dd, J = 14.2, 7.2 Hz, 1H), 0.74-0.64 (m, 1H), 0.50-0.42 (m, 2H), 0.11-0.00 (m, 2H). LC-MS: rt = 0.92 min, MS: 308.1 (calculated), 309.2 (M+H+, found). Example 89 2-Amino-6-(cyclopropylmethyl)-6-(hydroxymethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (149) o Znh2vjf ΤΥνη2 HO149: Example 89

[00368] Compound 149 (example 89) was synthesized similarly to compound 140 (example 80, scheme 24) starting from compound 125 (Table 4) instead of compound 138.

[00369] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.97 (s, 2H), 6.92 (bs, 2H), 4.54 (t, J = 5.4 Hz, 1H), 3.71 (dd, J = 10.5, 5.5 Hz, 1H), 3.39 (dd, J = 10.5, 5.3 Hz, 1H), 3.03-2.87 (m, 2H), 2.17-2.10 (m, 1H), 2.07-2.01 (m, 1H), 1.54 (dd, J = 14.0, 6.5 Hz, 1H), 1.32 (dd, J = 14.0, 7.0 Hz, 1H), 0.64-0.55 (m, 1H), 0.40-0.32 (m, 2H), 0.07-0.01 (m, 1H), -0.05 - -0.09 (m, 1H). LC-MS: rt = 0.88 min, MS: 294.1 (calculated), 295.0 (M+H+, found). Example 90 2-Amino-6-(cyanomethyl)-6-(cyclopropylmethyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (150) Petition 870250103125, dated 11 / 11 / 2025, p. 189 / 470 184 / 431

[00370] Compound 150 (example 90) was synthesized similarly to compound 109 (example 59, scheme 19) starting from compound 126 (Table 4) instead of compound 108.

[00371] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 8.06 (s, 2H), 6.97 (bs, 2H), 3.16-3.03 (m, 1H), 2.99-2.81 (m, 3H), 2.16-2.02 (m, 2H), 1.60-1.44 (m, 2H), 0.66-0.57 (m, 1H), 0.47-0.35 (m, 2H), 0.13-0.07 (m, 1H), -0.01 -0.07 (m, 1H). LC-MS: rt = 0.94 min. MS: 303.1 (calculated), 304.0 (M+H+, found). Example 91 2-Amino-7-oxo-4,7-dihydro-5H-spiro[benzo[ b ]thiophene-6,1'-cyclopentane]-3carboxamide (155) Scheme 29 Step 1. Ethyl 2-Amino-4,7-dihydro-5H-spiro[benzo[ b ]thiophene-6,1'-cyclopentane]3-carboxylate (152)

[00372] To a solution of spiro[4.5]decan-8-one (151) (199 mg, 1.31 mmol) and ethyl 2-cyanoacetate (0.139 ml, 1.31 mmol) in EtOH (1.3 ml), morpholine (0.126 ml, 1.44 mmol) and sulfur (46 mg, 0.18 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, then, Petition 870250103125, dated 11 / 11 / 2025, pp. 190 / 470 185 / 431 allowed to cool to RT and concentrated to dry. The residue was purified by flash column chromatography to yield compound 152 (270 mg, 74% yield). LC-MS: rt = 1.98 min, MS: 279.1 (calculated), 280.1 (M+H+, found). Step 2. Ethyl 2-Amino-7-oxo-4,7-dihydro-5H-spiro[benzo[ b ]thiophene-6,1'cyclopentane]-3-carboxylate (153)

[00373] To a mixture of 152 (100 mg, 0.358 mmol) in THF (1.2 ml) and water (0.2 ml) at 0 °C, a solution of DDQ (81 mg, 0.358 mmol) in THF (1.0 ml) was added dropwise, and the reaction mixture was stirred at 0 °C for 30 min. Then, the reaction mixture was rapidly cooled with saturated NaHCO3 solution and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography to yield the title compound 153 (15 mg, 14% yield). LC-MS: rt = 1.63 min, MS: 293.1 (calculated), 294.1 (M+H+, found). Step 3. 2-amino-7-oxo-4,7-dihydro-5H-spiro[benzo[b]thiophene-6,1'-cyclopentane]-3-carboxylic acid (154)

[00374] To a solution of 153 (15 mg, 0.051 mmol) in MeOH (1.1 ml), a solution of lithium hydroxide monohydrate (7 mg, 0.283 mmol) in water (1.1 ml) was added. The reaction mixture was stirred under reflux for 16 hours, then allowed to cool to RT. The mixture was diluted with water and concentrated to remove most of the organic solvent. The aqueous layer was acidified by slowly adding 1 N HCl and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated to yield the title compound 154 as a white solid (6 mg, 44% yield). (see Table 6 for characterization) Step 4. 2-Amino-7-oxo-4,7-dihydro-5H-spiro[benzo[ b ]thiophene-6,1'cyclopentane]-3-carboxamide (155)

[00375] Compound 154 (6 mg, 0.023 mmol) was dissolved in a Petition 870250103125, dated 11 / 11 / 2025, p. 191 / 470 186 / 431 0.4 M NH3 solution in THF (1.5 ml), and HATU (17 mg, 0.045 mmol) and N,N-diisopropylethylamine (0.008 ml, 0.045 mmol) were added to the mixture. Then, the reaction mixture was stirred at RT for 16 hours. Subsequently, the reaction mixture was rapidly cooled with a saturated NH4Cl solution and extracted with EA. The organic layer was washed with water and brine, then dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography to yield the title compound 155 as a white solid (3.7 mg, 62% yield).

[00376] 1H NMR: 400 MHz, CD3OD, δ (ppm): 2.99 (t, J = 6.0 Hz, 2H), 2.06 (t, J = 6.0 Hz, 2H), 2.03-1.97 (m, 2H), 1.79-1.68 (m, 4H), 1.62-1.56 (m, 2H). LC-MS: rt = 1.07 min, MS: 264.1 (calculated), 265.1 (M-H+, found). Example 92 2-Amino-6-(3-hydroxypropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (163) Scheme 30 Petition 870250103125, dated 11 / 11 / 2025, p. 192 / 470 187 / 431 Step 1. 3-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propanoic acid (157)

[00377] To a solution of 3-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propanonitrile (156) (2.30 g, 8.48 mmol) (Bioorg Med. Chem Lett. 21, p. 405, 2011) in ethylene glycol (40.0 ml), potassium hydroxide (3.80 g, 67.8 mmol) and water (0.030 ml, 1.70 mmol) were added. The reaction mixture was stirred at 170 °C for 16 hours, then allowed to cool to RT and diluted with water and DCM. The layers were separated, and the aqueous phase was acidified by slowly adding 2 N HCl and extracted with DCM. This organic layer was dried with MgSO4, filtered, and concentrated to yield compound 157 (2.03 g, 82% yield) as a brown solid. LC-MS: rt = 0.84 min, MS: 290.2 (calculated), 289.2 ([MH]-, found). Step 2. Methyl 3-(8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propanoate (158)

[00378] A solution of 157 (1.30 g, 4.48 mmol) in anhydrous DMF (10.0 ml) at 0 °C, potassium carbonate (1.86 g, 13.4 mmol) and iodomethane (0.418 ml, 6.72 mmol). The reaction mixture was stirred at RT for 16 hours, then diluted with water and extracted with Et2U. This Petition 870250103125, dated 11 / 11 / 2025, p. 193 / 470 188 / 431 organic layer was washed with brine and dried with MgSÜ4, filtered and concentrated to produce compound 158 (1.35 g, 99% yield) as an oil. LC-MS: rt = 1.53 min, MS: 304.2 (calculated), 305.2 (M+H+, found). Step 3. 3-(8-Phenyl-1,4-dioxaspiroyl4.51decan-8-yl)propan-1-ol (159)

[00379] To a solution of lithium aluminum hydride (6.25 ml, 1 M in THF, 6.25 mmol) in anhydrous THF (7.0 ml) at 0 °C, a solution of 158 (865 mg, 2.84 mmol) in anhydrous THF (10.0 ml) was added dropwise. The reaction mixture was stirred at 0 °C for 1 hour before being carefully cooled with MeÜH and water to 0 °C. Then, the mixture was diluted with EA and Rochelle saturated saline solution and stirred at RT for 30 min. The layers were separated, and the aqueous phase was extracted with EA. The combined organic layers were dried with Na2SÜ4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 70% EA in hexane) to yield the title compound 159 (760 mg, 97% yield) as a yellow oil. LC-MS: rt = 1.28 min, MS: 276.2 (calculated), 277.2 (M+H+, found). Step 4. 4-(3-Hydroxypropyl)-4-phenylcyclohexan-1-one (160)

[00380] To a solution of 159 (368 mg, 1.33 mmol) in acetone (18.0 ml), 2 N HCl (3.33 ml, 6.66 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized by slowly adding saturated aqueous solution of NaHCl3 and concentrated to remove the organic solvent. The residue was extracted with EA, and the organic layer was washed with brine, dried with Na2SU4, filtered, and concentrated to dryness to yield the title compound 160 (289 mg, 94% yield) as a yellow oil, which was not characterized and used directly for the next step. Step 5. 4-(3-(( ter-Butyldimethylsilyl)oxy)propyl)-4-phenylcyclohexan-1-one (161) Petition 870250103125, dated 11 / 11 / 2025, p. 194 / 470 189 / 431

[00381] To a solution of 160 (196 mg, 0.84 mmol) in anhydrous DMF (4.2 ml), tert-butyldimethylsilyl chloride (162 mg, 1.08 mmol) and imidazole (144 mg, 2.11 mmol) were added. The reaction mixture was stirred at RT for 16 hours, then diluted with water and EA. The layers were separated, and the organic phase was washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 30% EA in hexane) to yield the title compound 161 (259 mg, 89% yield) as a pale yellow oil, which was not characterized and used directly for the next step. Step 6. 2-Amino-6-(3-((tert-butyldimethylsilyl)oxy)propyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxamide (162)

[00382] To a solution of 161 (259 mg, 0.747 mmol) and cyanoacetamide (57 mg, 0.679 mmol) in EtOH (1.4 ml), morpholine (0.065 ml, 0.747 mmol) and sulfur (24 mg, 0.093 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, allowed to cool to RT, and concentrated to dryness. The residue was purified by flash column chromatography (eluent gradient from 0% to 10% MeOH in DCM) to yield the title compound 162 (200 mg, 60% yield). LC-MS: rt = 2.07 min, MS: 444.2 (calculated), 445.3 (M+H+, found). Step 7.2-Amino-6-(3-hydroxypropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (163)

[00383] To a mixture of 162 (200 mg, 0.450 mmol) in THF (1.5 ml) and water (0.25 ml) at 0 °C, a solution of DDQ (306 mg, 1.35 mmol) in THF (1.25 ml) was added dropwise. The reaction mixture was allowed to reach RT slowly and stirred for 16 hours. Then, the mixture was rapidly cooled with saturated NaHCO3 solution and extracted with EA. The organic layer was washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography. Petition 870250103125, dated 11 / 11 / 2025, pp. 195 / 470 190 / 431 (2% to 10% MeOH eluent gradient in DCM) was then purified again by semi-preparatory HPLC-MS (30% to 100% MeOH eluent gradient in 10 mM ammonium bicarbonate) to yield the title compound 163 as a white solid (10 mg, 6% yield).

[00384] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.34-7.28 (m, 4H), 7.23-7.19 (m, 1H), 3.54-3.43 (m, 2H), 2.96 (ddd, J = 17.1, 4.4, 3.1 Hz, 1H), 2.75-2.69 (m, 1H), 2.67-2.60 (m, 1H), 2.41-2.33 (m, 1H), 2.00-1.83 (m, 2H), 1.58-1.44 (m, 2H). LC-MS: rt = 0.96 min, MS: 344.1 (calculated), 345.1 (M+H+, found). Example 93 2-amino-6-(3-hydroxypropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (168) and Example 94 2-Amino-N-cyclopropyl-6-(3-hydroxypropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (169) Scheme 31 Petition 870250103125, dated 11 / 11 / 2025, pp. 196 / 470 191 / 431 Step 1 2-Amino-6-(3-hydroxypropyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (164)

[00385] To a solution of 160 (scheme 30) (289 mg, 1.24 mmol) and 2 ethyl cyanoacetate (0.149 ml, 1.37 mmol) in EtOH (10.0 ml), morpholine (0.120 ml, 1.37 mmol) and sulfur (44 mg, 0.172 mmol) were added. The reaction mixture was stirred at 60 °C for 24 hours, then allowed to cool to RT and concentrated to dryness. The residue was partitioned between EA and water. The layers were separated, and the aqueous phase was extracted with EA. The combined organic layers were dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 164 as a white solid (336 mg, 75% of Petition 870250103125, dated 11 / 11 / 2025, page 197 / 470 192 / 431 yield). LC-MS: rt = 1.53 min, MS: 359.2 (calculated), 360.2 (M+H+, found). Step 2 2-Acetamido-6-(3-acetoxypropyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (165)

[00386] To a suspension of 164 (336 mg, 0.935 mmol) in anhydrous DCM (3.0 ml), acetic anhydride (0.265 ml, 2.80 mmol) and acetic acid (0.054 ml, 0.935 mmol) were added. The reaction mixture was stirred at RT for 4 days, then diluted with DCM and washed with saturated NaHCO3 solution, water, and brine. The organic layer was dried with Na2SU4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 165 as a white solid (208 mg, 50% yield). LC-MS: rt = 1.86 min, MS: 443.2 (calculated), 444.3 (M+H+, found). Step 3. 2-Acetamido-6-(3-acetoxypropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (166)

[00387] Intermediate 165 (208 mg, 0.469 mmol) and ceric sulfate (1.35 g, 4.05 mmol) were added to a 1:1:1 mixture of acetic acid / water / dioxane (15 ml). The flask was sonicated to make the suspension homogeneous, and the reaction mixture was vigorously stirred at RT for 16 hours. Subsequently, the mixture was diluted with water and extracted with EA. The organic layer was washed with 1 N NaOH, water, and brine, then dried with Na2SU4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 45% EA in hexane) to yield title compound 166 as a white solid (122 mg, 57% yield). LC-MS: rt = 1.73 min, MS: 457.2 (calculated), 458.3 (M+H+, found). Step 4 6-(3-acetoxypropyl)-2-amino-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl (167) Petition 870250103125, dated 11 / 11 / 2025, page 198 / 470 193 / 431

[00388] To a solution of 166 (122 mg, 0.267 mmol) in toluene (0.5 ml), pyrrolidine (0.35 ml, 4.26 mmol) was added, and the reaction mixture was stirred at RT for 1 hour. Subsequently, the mixture was diluted with brine and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated to yield the title compound 167 as a dark orange oil, which was used directly for the next step. LC-MS: rt = 1.64 min, MS: 415.2 (calculated), 416.3 (M+H+, found). Step 5. 2-amino-6-(3-hydroxypropyl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (168)

[00389] To a solution of 167 (0.267 mmol) in MeOH (4.0 ml), a solution of lithium hydroxide monohydrate (162 mg, 3.86 mmol) in water (2.0 ml) was added. The reaction mixture was stirred at 60 °C for 3 days, then allowed to cool to RT. The mixture was concentrated to remove most of the organic solvent. The aqueous layer was acidified by slowly adding 1 N HCl and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (50% to 100% EA eluent gradient in hexane) to yield the title compound 168 as a yellow solid (70 mg, 76% yield over two steps).

[00390] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.32-7.28 (m, 4H), 7.23-7.18 (m, 1H), 3.53-3.43 (m, 2H), 3.26-3.19 (m, 1H), 2.60-2.51 (m, 2H), 2.35-2.27 (m, 1H), 1.98-1.83 (m, 2H), 1.55-1.44 (m, 2H). LC-MS: rt = 1.09 min, MS: 345.1 (calculated), 346.0 (M+H+, found). Step 6. 2-Amino-N-cyclopropyl-6-(3-hydroxypropyl)-7-oxo-6-phenyl-4,5,6,7tetrahydrobenzo[b]thiophene-3-carboxamide (169)

[00391] To a solution of 168 (54 mg, 0.156 mmol) in anhydrous DMF (1.95 ml), HATU (119 mg, 0.313 mmol), N,N-diisopropylethylamine (0.082 ml, 0.469 mmol) and cyclopropylamine (0.012 ml, 0.172 mmol) were added. Then, the reaction mixture was stirred at RT for 16 hours. Petition 870250103125, dated 11 / 11 / 2025, p. 199 / 470 194 / 431 Subsequently, the reaction mixture was diluted with EA and washed with a saturated solution of NaHCO3 and brine. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 30% to 100% EA in hexane) to yield the title compound 169 as a dirty white solid (46 mg, 77% yield).

[00392] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.33-7.26 (m, 4H), 7.21-7.17 (m, 1H), 3.52-3.42 (m, 2H), 2.81 (ddd, J = 17.3, 4.4, 3.3 Hz, 1H), 2.70-2.62 (m, 2H), 2.58 (dt, J = 13.9, 3.7 Hz, 1H), 2.31 (ddd, J = 13.8, 11.2, 4.6 Hz, 1H), 1.98-1.81 (m, 2H), 1.56-1.41 (m, 2H), 0.76-0.68 (m, 2H), 0.570,50 (m, 2H). LC-MS: rt = 1.13 min, MS: 384.1 (calculated), 385.1 (M+H+, found). Example 95 2-Amino-6-cyano-N-cyclopropyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (170) Scheme 32

[00393] A solution of 59 (example 36, diagram 8) (2.03 g, 6.50 mmol) in anhydrous DMF (72 ml) at 0 °C, PyBOP (3.73 g, 7.15 mmol), N,N-diisopropylethylamine (2.26 ml, 13.0 mmol) and cyclopropylamine (2.25 ml, 32.5 mmol) was then stirred at RT for 16 hours. Subsequently, the reaction mixture was rapidly cooled with saturated NH4Cl solution and extracted with EA. The organic layer was dried with Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (eluent gradient from 40% to 100% of Petition 870250103125, dated 11 / 11 / 2025, pp. 200 / 470 195 / 431 EA in hexane), then it was purified again by flash chromatography on a reversed-phase column (10% to 100% eluent gradient of CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 170 as a dirty-white solid (1.48 g, 65% yield).

[00394] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 8.16 (s, 2H), 7.617.59 (m, 1H), 7.47-7.38 (m, 5H), 3.04-2.97 (m, 1H), 2.80-2.70 (m, 3H), 2,642.57 (m, 1H), 0.68-0.60 (m, 2H), 0.54-0.48 (m, 2H). LC-MS: rt = 1.25 min, MS: 351.1 (calculated), 352.2 (M+H+, found). Example 96 2-Amino-6-cyano-6-((1-methylcyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (174) Intermediate compound 172 8-((1-Methylcyclopropyl)methyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (172) Scheme 33 Step 1. 8-(2-Methylallyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (171)

[00395] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (40, Scheme 4) (0.696 ml, 4.44 mmol) in anhydrous THF (10 ml) at -78 °C, LDA (6.67 ml, 1 M in THF / hexane, 6.67 mmol) was added dropwise. The reaction mixture was stirred at -78 °C for 30 min before the dropwise addition of a solution of 3-bromo-2-methylpropene (0.448 ml, 4.44 mmol) in anhydrous THF (10 ml). Then, the reaction mixture was left in the open air until RT was reached and stirred for 3 days. Subsequently, the reaction mixture was rapidly cooled with a saturated NH4Cl solution and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography. Petition 870250103125, dated 11 / 11 / 2025, page 201 / 470 196 / 431 (eluent gradient from 0% to 50% EA in hexane) to produce the title compound 171 (753 mg, 77% yield) as a colorless oil, which was not characterized and used directly for the next step. Step 2.8-((1-Methylcyclopropyl)methyl)-1,4-dioxaspiro [4.5]decane-8carbonitrile (172)

[00396] To a solution of 171 (650 mg, 2.94 mmol) in anhydrous DCM (29 ml) at -10 °C, diethylzinc (5.87 ml, 1 M in hexane, 5.87 mmol) and diiodomethane (0.946 ml, 11.7 mmol) were added. The reaction mixture was stirred at -10 °C for 30 min, then left in the open air until RT was reached and stirred for 3 days. Subsequently, the reaction mixture was rapidly cooled with saturated NH4Cl solution, and the layers were separated. The organic phase was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 172 (233 mg, 34% yield) as a colorless oil, which was not characterized and used directly for the synthesis of the relevant examples. 2-Amino-6-cyano-6-((1-methylcyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (174) Scheme 34 o nh3, nh4ci DIPEA, HATU DMF / THF / CHCI3 THE 173: Example 165

[00397] To a suspension of 173 (see Table 6 for characterization) (synthesized similarly to compound 47 (scheme 4) starting from compound 172 (scheme 33) instead of compound 41) (46 mg, 0.151 mmol) and ammonium chloride (162 mg, 3.02 mmol) in anhydrous DMF (2.0 ml), HATU (88 mg, 0.227 mmol) and N,N-diisopropylethylamine (0.053 ml, 0.302 mmol) were added. Then, a saturated solution of NH3 in CHCl3 (0.9 Petition 870250103125, dated 11 / 11 / 2025, page 202 / 470 197 / 431 ml) (prepared internally) and 0.4 M NH3 in THF (0.9 ml) were added dropwise, and the reaction mixture was stirred at RT for 16 hours. Subsequently, the reaction mixture was rapidly cooled with a saturated NH4Cl solution and extracted with EA. The organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid) to yield the title compound 174 as a white solid (26 mg, 57% yield).

[00398] 1H NMR: 400 MHz, DMSO-do, δ (ppm): 8.24 (s, 2H), 7.09 (bs, 2H), 3.15-3.01 (m, 2H), 2.46-2.43 (m, 1H), 2.39-2.32 (m, 1H), 1.88 (s, 2H), 1.12 (s, 3H), 0.46-0.38 (m, 1H), 0.32-0.24 (m, 3H). LC-MS: rt = 1.12 min, MS: 303.1 (calculated), 304.1 (M+H+, found). Example 97 2-Amino-N3-cyclopropyl-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3,6dicarboxamide (175)

[00399] Compound 175 (example 97) was synthesized in a similar manner to compound 145 (example 85, scheme 26) starting from compound 170 (example 95, scheme 32) instead of compound 144.

[00400] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.35-7.33 (m, 4H), 7.32-7.28 (m, 1H), 2.92 (dt, J = 17.1, 4.8 Hz, 1H), 2.73-2.68 (m, 3H), 2.58 (ddd, J = 17.1, 7.9, 5.5 Hz, 1H), 0.76-0.71 (m, 2H), 0.57-0.53 (m, 2H). LCMS: rt = 1.02 min, MS: 369.1 (calculated), 370.2 (M+H+, found). Example 98 2-Amino-6-(but-3-yn-1-yl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-Petition 870250103125, dated 11 / 11 / 2025, p. 203 / 470 198 / 431 carboxamide (179) Intermediate compound 177 8-(But-3-yn-1-yl)-8-phenyl-1,4-dioxaspiro[4.5]decane (177) Scheme 35 Step 1. 3-(8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propanal (176)

[00401] To a solution of 3-(8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)propanenitrile (156, diagram 30) (1.40 g, 5.16 mmol) (Bioorg Med. Chem Lett. 21, p. 405, 2011) in anhydrous toluene (33 ml) at -78 °C, DIBALH (4.16 ml, 25% toluene, 6.19 mmol) was added dropwise. The reaction mixture was stirred at -78 °C for 5 min, then suddenly cooled with saturated NH4Cl solution. Subsequently, the mixture was left in the open air until RT was reached, and 2 N HCl (2.58 ml, 5.16 mmol) was added. The mixture was extracted with Et2U, and this organic layer was washed with a saturated solution of NaHCO3 and brine, dried with Na2SU4, filtered, and concentrated to produce compound 176 as a colorless oil, which was used directly for the next step without characterization. Step 2. 8-(But-3-yn-1-yl)-8-phenyl-1,4-dioxaspiro[4.5]decane (177)

[00402] To a solution of triphenylphosphine (3.59 g, 13.4 mmol) in anhydrous DCM (32 ml) at 0 °C, carbon tetrabromide (2.22 g, 6.71 mmol) was added. The reaction mixture was stirred at RT for 30 min, then cooled to 0 °C again, and a solution of 176 (5.16 mmol) in anhydrous DCM (8 ml) was added, and the reaction mixture was stirred at 0 °C for 30 min. Subsequently, the reaction mixture was diluted with hexane, filtered through a Celite filter, and concentrated. The residue was diluted with Petition 870250103125, dated 11 / 11 / 2025, p. 204 / 470 199 / 431 hexane, filtered through a Celite filter and concentrated again. This residue was dissolved in anhydrous THF (23 ml), and the solution was cooled to -78 °C. Then, n-butyllithium (4.13 ml, 2.5 M in hexane, 10.3 mmol) was added dropwise, and the reaction mixture was stirred at -78 °C for 1 hour. Subsequently, the reaction mixture was rapidly cooled with saturated NH4Cl solution and extracted with EA. The organic layer was washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 50% EA in hexane) to yield the title compound 177 as a white solid (734 mg, 53% yield over two steps), which was not characterized and used directly for the synthesis of the relevant examples. 2-Amino-6-(but-3-yn-1-yl)-7-oxo-6-phenyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide (179) Scheme 36

[00403] 178 (see A solution of Table 6 for characterization) (synthesized similarly to compound 47 (sch...

Claims

1. Compound with Formula (I), or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: Ra is -NH2, -NH-OH, -OH, -NHRb or -NRcRd; Rb is C1-C6 alkyl, C3-C6 cycloalkyl, or a 3- to 6-membered heterocycloalkyl, wherein C1-C6 alkyl is optionally substituted by 1 to 3 halogens, 1 to 3 -OH, -OC1-C3 alkyl, -COOH, or cyclopropyl optionally substituted by -OH, and wherein C3-C6 cycloalkyl is optionally substituted by -CN; Rc and Rd form with the nitrogen to which they are attached a 4-membered heterocycloalkyl, wherein the 4-membered heterocycloalkyl is optionally substituted by at least one of -OH and C1C3 alkyl; O represents one of the following residues: Ao a A12 o R2 R2 f O Ao R Ai O a2 R A3 O A4 OR A5 o Ae O o R A7 R2fVy o Ag OR Ag O A10 OR An , or RJ A12 ; ; where: Petition 870250103125, dated 11 / 11 / 2025, page 438 / 470 2 / 30 R is H, C1-C6 alkyl or phenyl;R1 and R2 are independently -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein each C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents, each C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents, with the condition that when Ra is OH, CT represents Ao, and R1 is ^^^7, then R2 in the Ao residue is different γ-γOH from o; each R5 is independently C1-C6 alkyl, and each C1-C6 alkyl is optionally substituted by 1 to 3 R9 substituents; each R6 is independently C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl or C6-Cwaryl;Each R7 is independently -OH, -C(O)Rn, C3C6cycloalkyl, -CN, C6-Cwaryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), -N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC1C6alkyl, -NH2, -NH(C1-C4alkyl), or -N(C1-C4alkyl)2, wherein each C3C6cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl or oxo; each R8 is independently halogen, C1-C6 alkyl, -OC1-C6 alkyl, C3-C6 cycloalkyl, or 5- to 10-membered heteroaryl, wherein each -OC1-C6 alkyl is optionally substituted by -OC1-C4 alkyl, and each 5- to 10-membered heteroaryl is optionally substituted by C1-C4 alkyl; each R22 is independently C1-C6 alkyl optionally substituted by phenyl;Petition 870250103125, dated 11 / 11 / 2025, p. 439 / 470 3 / 30 each R9 is independently -OH, -C(O)R15, C3C-cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C-alkyl), -OC1-C-alkyl, -SC1-C-alkyl, -NH2, -NH(C1-C4-alkyl), or -N(C1-C4-alkyl)2, wherein each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4-alkyl, and each -OC1-C-alkyl is optionally substituted by -OC1-C4-alkyl; each Rn is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or a 4- to 6-membered heterocycloalkyl; each R20 is independently a 5- to 10-membered C1-C4alkyl or heteroaryl, wherein each C1-C4alkyl is optionally substituted by 3 Ri4 substituents and each 5- to 10-membered heteroaryl is optionally substituted by -OH or -NH(cyclopropyl); each Ri2 is independently a C1-C4alkyl, -SC1-C4alkyl, Ph, -OC1-C4alkyl, or -SPh, and each C1-C4alkyl is optionally substituted by -OH;each Ri3 is independently halogen, C1-C4 alkyl, C3-C6 cycloalkyl, -OH, -OCi-C6 alkyl, -SCi-C6 alkyl, -S(O)2Ci-C6 alkyl, NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, wherein each -OCi-C6 alkyl, -SCi-C6 alkyl, -S(O)2Ci-C6 alkyl, -NH(C1-C4 alkyl), and -N(C1-C4 alkyl)2 is optionally substituted by 3 substituents R9; each Ri4 is independently halogen, -OCi-C4 alkyl or C3-C6 cycloalkyl; each Ri5 is independently -NH2, -NH(C1-C4 alkyl), N(C1-C4 alkyl)2 or 4- to 6-membered heterocycloalkyl;R4 is C1-C6 alkyl, C3-C5 cycloalkyl, C6-C10 aryl, a partially unsaturated heterocyclic group of 7 to 10 members or a heteroaryl group of 5 to 10 members, wherein C1-C6 alkyl and C3-C5 cycloalkyl are optionally substituted by 1a 3 substituents R9, and C6-C10 aryl and heteroaryl groups of 5 to 10 members are optionally substituted by 1a 3 substituents R10, under Petition 870250103125, dated 2 / 2 / 2025, p. 440 / 470 4 / 30 η Λ condition that: (i) when Ra is -OH, -NH2, or > , and >—' represents A2, then R4 in residue A2 is different from -CH3; and (ii) when Ra is -NH2 and represents A3, then R4 in residue A3 is different from -C(CH3)3; each R10 is independently C1-C4 alkyl, halogen, -OC1C6 alkyl, -NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, and each C1C4 alkyl is optionally substituted by 1 to 3 halogens;R2a is C1-C6 alkyl, C3-C8 cycloalkyl, or C6-C10 aryl, wherein C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl is optionally substituted by 1 to 3 R10 substituents; R1a and R2b are independently -CN, C6-C10 aryl, C1C6 alkyl, C3-C8 cycloalkyl, -C(O)NH2, -C(O)NHR5, or -C(O)OC1-C6 alkyl, wherein each C1-C6 alkyl is optionally substituted by 1 to 3 R16 substituents and each C6-C10 aryl is optionally substituted by 1 to 3 R17 substituents;each R16 is independently -OH, -C(O)NH2, -C(O)NH(C1C4alkyl), C3-C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl) or -OC1-C4alkyl(OC1C4alkyl), wherein each C3-C6cycloalkyl is optionally substituted by 1 to 3 R18 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R21 substituents and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl; Each R17 is independently halogen, C1-C6 alkyl, -OC1C6 alkyl, or 5- to 10-membered heteroaryl, and each 5- to 10-membered heteroaryl is optionally substituted for C1-C4 alkyl; each R18 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, or -OC1-C4 alkyl; each R21 is independently halogen or C1-C4 alkyl;Petition 870250103125, dated 11 / 11 / 2025, page 441 / 470 5 / 30 R4a is C1-C6 alkyl or C3-C5 cycloalkyl, wherein each C1-C6 alkyl and C3-C5 cycloalkyl are optionally substituted by 1 to 3 R19 substituents; each R19 is independently halogen, -OH, -C1-C4 alkyl, -C1-C4 alkyl, -NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2;R1b and R2c, together with the carbon atom to which they are attached, form a C3-C8cycloalkyl, a 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group, wherein the C3C8cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and wherein the 4- to 14-membered heterocycloalkyl, an 8- to 14-membered partially unsaturated heterocyclic group, or an 8- to 14-membered partially unsaturated carbocyclic group is optionally substituted by oxo (=O), oxime (=NOH), C1-C3 alkoxyoxime (=N-OC i-C3alkyl), or 1 to 3 substituents independently selected from -OH and -CF3; R2d and R4b, together with the carbon atoms to which they are attached, form a 4- to 14-membered C3-C8 cycloalkyl or heterocycloalkyl, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents;and R1c and R3 together with the carbon atoms to which they are attached form a 4- to 14-membered C3-C8 cycloalkyl or heterocycloalkyl, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R19 substituents.

2. Compound according to claim 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R is H.

3. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by formula (Ia) or (Ia'): Petition 870250103125, dated 11 / 11 / 2025, page 442 / 470 6 / 30 (Ia') where R1, R2, R and Ra are as defined in claim 1 or 2.

4. Compound according to claim 3, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by formula (Ia): wherein R1, R2 and Ra are as defined in claim 1.

5. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, C6-C10aryl, C1-C6alkyl, C2-C6alkynyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein each C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents, each C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R22 substituents, and R5, R6, R7, R8 and R22 are as defined in claim 1.

6. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, C6-C10aryl, C1-C6alkyl, C2-C6alkynyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein each C1-C6alkyl is optionally substituted by 1 to 3 substituents R7, each C6-C10aryl is optionally substituted by 1 to 3 substituents R8, and each Petition 870250103125, dated 11 / 11 / 2025, p. 443 / 470 7 / 30 a 5- to 10-membered heteroaryl group is optionally substituted by 1 to 3 R22 substituents, wherein: each R5 is independently a C1-C6 alkyl group; each R6 is independently a 4- to 6-membered heterocycloalkyl group;each R7 is independently -OH, -C(O)Rn, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6alkyl), -N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OR20, -SC1C6alkyl, -NH2, or -N(C1-C4alkyl)2, and each C3-C6cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1C4alkyl or oxo; each R8 is independently halogen, C1-C6 alkyl or OC1-C6 alkyl, and each -OC1-C6 alkyl is optionally substituted by -OC1-C4 alkyl; each R22 is independently C1-C6 alkyl optionally substituted by phenyl; each R11 is independently -NH2, -NH(C1-C4 alkyl), or a 4- to 6-membered heterocycloalkyl;Each R20 is independently a 5- to 10-membered C1-C6 alkyl or heteroaryl, and each C1-C6 alkyl is optionally substituted by 1 to 3 R14 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by -OH or -NH(cyclopropyl); each R12 is independently a C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, or -SPh, and each C1-C4 alkyl is optionally substituted by -OH; each R13 is independently a halogen, C1-C4 alkyl, or C3-C6 cycloalkyl; and each R14 is independently a halogen, -OC1-C4 alkyl, or C3-C6 cycloalkyl.

7. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, C-Cioaryl, C1-Coalkyl, C2-Coalkyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, or -C(O)NH2, wherein each C1-Coalkyl is optionally substituted by 1 to 3 R7 substituents, each C-Cioaryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R22 substituents, and R7, R8, and R22 are as defined in claim 1.

8. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, C-C1-C1-Aryl, C1-C1-C1-Alkyl, C2-C2-C3-C8 ... 10-membered, -NH(C(O)OC1-C-alkyl), -N(C1-C4-alkyl)(C(O)OC1-C-alkyl), NH(C(O)C1-C-alkyl), 4- to 6-membered heterocycloalkyl, -OR20, -SC1C-alkyl, -NH2, or -N(C1-C4-alkyl)2, wherein each C3-C-cycloalkyl is optionally substituted by 1 to 3 R12 substituents,each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1 C4 alkyl or oxo; each R8 is independently halogen, C1-C4 alkyl or OC1-C4 alkyl, with each -OC1-C4 alkyl optionally substituted by -OC1-C4 alkyl; each R11 is independently -NH2, -NH(C1-C4 alkyl), or a 4- to 6-membered heterocycloalkyl; Each R20 is independently a 5- to 10-membered C1-C-alkyl or heteroaryl group, wherein each C1-C-alkyl group is optionally substituted by 1 to 3 R14 substituents and each 5- to 10-membered heteroaryl group is optionally substituted by -OH or -NH(cyclopropyl); each R12 is independently a C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, or -SPh group, wherein each C1-C4 alkyl group is optionally substituted by -OH; each R13 is independently a halogen,C1-C4 alkyl or C3-C-cycloalkyl; each R14 is independently halogen, -C1-C4 alkyl or C3-C-cycloalkyl; and each R22 is independently C1-C4 alkyl.

9. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, C-C10aryl, C1-C-alkyl, C2-C-alkyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, or -C(O)NH2, wherein each C1-C-alkyl is optionally substituted by 1 to 3 R7 substituents, each C1-C-aryl is optionally substituted by 1 to 3 R8 substituents, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 R2 substituents, and wherein: each R7 is independently -OH, -C(O)R11, -OR20, C3C-cycloalkyl, -CN, C-C10aryl, halogen, -C(O)OH or heteroaryl of 5 to 10 Petition 870250103125, dated 11 / 11 / 2025, page.446 / 470 10 / 30 members, wherein each C3-C-cycloalkyl is optionally substituted by 1 to 3 R12 substituents and each 5 to 10 membered heteroaryl is optionally substituted by 1 to 3 R13 substituents; each R8 is a halogen; each R11 is -NH2; each R20 is a 5 or 6 membered C1-C-alkyl or heteroaryl, wherein each C1-C6 alkyl is optionally substituted by 1 to 3 R14 substituents and each 5 or 6 membered heteroaryl is optionally substituted by -OH or -NH(cyclopropyl); each R12 is a C1-C4 alkyl; each R13 is independently a halogen or C1-C4 alkyl; each R14 is a halogen; and each R22 is independently a C1-C4 alkyl.

10. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, phenyl, C1-C4 alkyl, C2-C4 alkynyl, C3-C6 cycloalkyl, 5-membered heteroaryl or -C(O)NH2, wherein each C1-C4 alkyl is optionally substituted by 1 or 2 R7 substituents, each phenyl is optionally substituted by 1 or 2 halogens and each 5-membered heteroaryl is optionally substituted by 1 or 2 -CH3, and wherein: each R7 is independently -OH, -C(O)NH2, -OR20, C3C6 cycloalkyl, -CN, phenyl, halogen, -C(O)OH or 5-membered heteroaryl, wherein each C3-C6 cycloalkyl is optionally substituted by -CH3; and each R20 is a 5- or 6-membered C1-C6 alkyl or heteroaryl group, wherein each C1-C6 alkyl group is optionally substituted with 1 to 3 halogens and each 5- or 6-membered heteroaryl group is optionally substituted with -OH.

11. Compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug of Petition 870250103125, dated 11 / 11 / 2025, p. 447 / 470 11 / 30, characterized in that R1 and R2 independently represent: -CN, -CH3, VX», ; Λ!H, VX , , F , 4y\ Ly oo , , , y ,, , ς £ ,N, ς / γAH NH FAn N—NN=NA , , , yyyn=ny l0- < , , yy-N _ ^4 / )— XA O~n N; , N Π N , , fy .0 / Y Zxy-o^FF<y , , yyF rj , o rs 1 1 ·. í / í '' . AFs.l( rZsrf F4 ? A X / ° > X- 7' J (Ay yx . yyy Petition 870250103125, dated 11 / 11 / 2025, p. 448 / 470 12 / 30 12. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent: -CN, -CH3, V^oh or 13. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent: -CN, -CH3, OH Petition 870250103125, dated 11 / 11 / 2025, p. 449 / 470 13 / 30 FFV^OF, '''SZq^f, or 14. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent: -CN, -CH3,x 15. Compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are independently CN, C6-C10aryl, C1-C6alkyl, C3-C8cycloalkyl, 5-membered heteroaryl or -C(O)NH2, wherein each C1-C6alkyl is optionally substituted by 1 to 2 R7 substituents; each R7 is independently -OH, -C(O)NH2, C3 Petition 870250103125, dated 11 / 11 / 2025, p. 450 / 470 14 / 30 C6cycloalkyl, -CN, C6-C10aryl, halogen or heteroaryl of 5 to 8 members, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 2 C1C4alkyl, and each heteroaryl of 5 to 8 members is optionally substituted by 1 to 2 R13 substituents; and each R13 is independently halogen or C1-C4alkyl.

16. A compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are different.

17. A compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that one of R1 and R2 is -CN.

18. A compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that one of R1 and R2 is 19. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ib) or (Ib'): R' ο Ra NH2 R (Ib') wherein R4, R and Ra are as defined in claim 1 or 2.

20. Compound according to claim 19, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by formula (Ib): Petition 870250103125, dated 11 / 11 / 2025, page 451 / 470 15 / 30 where R4 and Ra are as defined in claim 1.

21. A compound according to any one of claims 1, 2, 19 and 20, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R4 is a C1-C6 alkyl, C6-C10 aryl, 7- to 10-membered partially unsaturated heterocyclic group, or 5- to 10-membered heteroaryl group, wherein the C1-C6 alkyl group is optionally substituted by 1 to 3 R9 substituents, and the C6-C10 aryl and 5- to 10-membered heteroaryl groups are optionally substituted by 1 to 3 R10 substituents, and wherein R9 and R10 are as defined in claim 1.

22. A compound according to any one of claims 1, 2, 19 and 20, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R4 is C1-C6 alkyl, C6-Cwaryl, a 7- to 10-membered partially unsaturated heterocyclic group, or a 5- to 10-membered heteroaryl group, wherein C6-Cwaryl and the 5- to 10-membered heteroaryl group are optionally substituted by 1 to 3 substituents R10, and wherein: each R10 is independently C1-C4 alkyl, halogen, -OC1C6 alkyl, -NH2, -NH(C1-C4 alkyl), or -N(C1-C4 alkyl)2, wherein each C1C4 alkyl group is optionally substituted by 1 to 3 halogens.

23. A compound according to any one of claims 1, 2, 19 and 20, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R4 is a C1-C6 alkyl, C6-Cwaryl, 7- to 10-membered partially unsaturated heterocyclic group, or a 5- to 10-membered heteroaryl group, wherein the C6-Cwaryl and 5- to 10-membered heteroaryl groups are optionally substituted by 1 to 3 R10 substituents, and wherein: Petition 870250103125, dated 11 / 11 / 2025, p. 452 / 470 16 / 30 each R10 is independently C1-C4 alkyl, halogen, -C1-C6 alkyl, or -N(C1-C4 alkyl)2, wherein each C1-C4 alkyl is optionally substituted by 1 to 3 halogens.

24. A compound according to any one of claims 1, 2, 19 and 20, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R4 is a C1-C4 alkyl, phenyl, 9-membered partially unsaturated heterocyclic group or a 5- to 6-membered heteroaryl group, wherein the phenyl and 5- to 6-membered heteroaryl groups are optionally substituted by 1 or 2 R10 substituents, and wherein: each R10 is independently -CF3, halogen, -OCH3, or N(CH3)2.

25. A compound according to any one of claims 1, 2, 19 and 20, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R4 stands for: or 26. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ic) or (Ic'): Petition 870250103125, dated 11 / 11 / 2025, p. 453 / 470 17 / 30 wherein R2a, R and Ra are as defined in claim 1 or 2.

27. Compound according to claim 26, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ic): wherein R2a and Ra are as defined in claim 1.

28. A compound according to any one of claims 1, 2, 26 and 27, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2a is C1-C-alkyl or C-C10aryl, wherein C-C-alkyl is optionally substituted by 1 to 3 R9 substituents and C-C10aryl is optionally substituted by 1 to 3 R10 substituents, and R9 and R10 are as defined in claim 1.

29. Compound according to any one of claims 1, 2, 26 and 27, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2a is Q-Cealkyl or C-C10aryl, wherein Q-Cealkyl is optionally substituted by 1 to 3 halogens.

30. Compound according to any one of claims 1, 2, 26 and 27, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2a is C1-C6 alkyl.

31. A compound according to any one of claims 1, 2, 26 and 27, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2a is C1-C4 alkyl. Petition 870250103125, dated 11 / 11 / 2025, p. 454 / 470 18 / 30 32. Compound according to any one of claims 1, 2, 26 and 27, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2a is ethyl.

33. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Id) or (Id'): wherein R1a, R2b, R4a, R and Ra are as defined in claim 1 or 2.

34. Compound according to claim 33, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Id): wherein R1a, R2b, R4a and Ra are as defined in claim 1.

35. Compound according to any one of claims 1, 2, 33 and 34, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1a and R2b are independently -CN, C-C10aryl, C1-C1-C1-alkyl, C3-C8cycloalkyl, or -C(O)NH2, wherein each C1-C1-alkyl is optionally substituted by 1 to 2 R16 substituents; each R16 is independently -OH, -C(O)NH2, C3C6cycloalkyl, -CN, C6-C10aryl, halogen or heteroaryl of 5 to 8 members, wherein each C3-C6cycloalkyl is optionally substituted by 1 to 2 C1 Petition 870250103125, dated 11 / 11 / 2025, p. 455 / 470 19 / 30 C1-C4 alkyl, and each 5- to 10-membered heteroaryl is optionally substituted by 1 to 2 R21 substituents; and each R21 is independently halogen or C1-C4 alkyl.

36. A compound according to any one of claims 1, 2, 33 and 34, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1a and R2b are independently C6-C1a or C6-C1aryl.

37. Compound according to any one of claims 1, 2, 33, 34, 35 and 36, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R4a is C1-C6 alkyl.

38. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ie) or (Ie'): (Ie') wherein R, R a, R1b and R2c are as defined in claim 1 or 2.

39. Compound according to claim 38, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ie): wherein Ra, R1b and R2c are as defined in claim 1.

40. Compound according to any of claims 1, 2, 38 and 39, or a pharmaceutically acceptable salt, solvate or prodrug. Petition 870250103125, dated 11 / 11 / 2025, page 1. 456 / 470 20 / 30 of the same, characterized in that R1b and R2c together with the carbon atom to which they are attached form a C3-C8 cycloalkyl, 4- to 14-membered heterocycloalkyl, 8- to 14-membered partially unsaturated heterocyclic group or 8- to 14-membered partially unsaturated carbocyclic group, wherein each 4- to 14-membered heterocycloalkyl, 8- to 14-membered partially unsaturated heterocyclic group or 8- to 14-membered partially unsaturated carbocyclic group is optionally substituted by oxo (=O), oxime (=N-OH), C1-C3 alkoxyoxime (=N-OC1C3alkyl) or 1 to 3 substituents independently selected from -OH and CF3.

41. A compound according to any one of claims 1, 2, 38 and 39, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1b and R2c together with the carbon atom to which they are attached form a C3-C8 cycloalkyl or an 8 to 10 membered partially unsaturated carbocyclic group, wherein the 8 to 10 membered partially unsaturated carbocyclic group is optionally substituted by oxo (=O), oxime (=N-OH), methoxyoxime (=NOCH3) or 1 to 2 substituents independently selected from -OH and -CF3.

42. Compound according to any one of claims 1, 2, 38 and 39, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1b and R2c form, together with the carbon atom to which they are attached, a C4-C6 cycloalkyl, or a group selected from HO cf3 N OH or N 'O / wherein the dashed lines represent the cyclohexanone fraction of the compound of formula (Ie) or (Ie') containing R1b and R2c.

43. Compound according to any one of claims 1, 2, 38 and 39, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1b and R2c together with the carbon atom to which they are attached form a cyclopentyl group, or a group selected from N o or / , wherein the dashed lines represent the cyclohexanone fraction of the compound of formula (Ie) or (Ie') containing R1b and R2c.

44. Compound according to any one of claims 1, 2, 38 and 39, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1b and R2c together with the carbon atom to which they are attached form a group selected from, wherein the dashed lines represent the cyclohexanone fraction of the compound of formula (Ie) or (Ie') containing R1b and R2c.

45. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (If) or (If'): Petition 870250103125, dated 11 / 11 / 2025, page 458 / 470 22 / 30 (If) (If') where R, Ra, R4b and R2d are as defined in claim 1 or 2.

46. ​​Compound according to claim 45, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (If): wherein Ra, R4b and R2d are as defined in claim 1.

47. A compound according to any one of claims 1, 2, 45 and 46, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2d and R4b, together with the carbon atoms to which they are attached, form a C3-C8 cycloalkyl group, wherein each C3-C8 cycloalkyl group is optionally substituted by 1 to 3 R19 substituents, as defined in claim 1.

48. Compound according to any one of claims 1, 2, 45 and 46, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R2d and R4b form, together with the carbon atoms to which they are attached, a C3-C8 cycloalkyl.

49. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ig): Petition 870250103125, dated 11 / 11 / 2025, page 459 / 470 23 / 30 c> j? VRa 1 X / NH2 R1cR3 (Ig) where Ra, R1c and R3 are as defined in claim 1.

50. A compound according to any one of claims 1, 2 and 49, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1c and R3 together with the carbon atoms to which they are attached form a C3-C8 cycloalkyl group, wherein each C3-C8 cycloalkyl group is optionally substituted by 1 to 3 R19 substituents, as defined in claim 1.

51. A compound according to any one of claims 1, 2 and 49, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1c and R3 form, together with the carbon atoms to which they are attached, a C3-C8 cycloalkyl.

52. A compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is -NHRb and Rb stands for: -CH3 / V, or 53. A compound according to any one of claims 1 to 52, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is -NHRb and Rb stands for: -CH3, w, V, or 54. Compound according to any of the claims in Petition 870250103125, dated 11 / 11 / 2025, pp. 460 / 470 24 / 30 1 to 53, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra stands for -NHRb and Rb stands for V.

55. A compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is a ,^-, or 56. Compound according to any one of claims 1 to 51 and 55, or a pharmaceutically acceptable salt, solvate or prodrug 5 / nZj % / N— / OH thereof, characterized in that Ra is or.

57. A compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is -OH.

58. A compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is NH2.

59. A compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is -NH-OH.

60. A compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is in the form of a racemate or any enantiomer thereof.

61. Compound according to claim 1, characterized in that the Compound is 4, 8, 9, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60a, 60b, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 108, 109, 119, 120, 121, 122, 123, 124, 125, 126, 127, Petition 870250103125, dated 11 / 11 / 2025, page. 461 / 470 25 / 30 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 154, 155, 163, 168, 169, 170, 173, 174, 175, 178, 179, 180, 181, 183, 189, 190, 191, 192, 193, 194, 195, 197, 198, 199, 200, 201, 202, 211, 212, 213, 214, 215, 216, 219, 221, 227, 228, 229, 230, 231, 232, 237, 238, 239, 245, 246, 247, 248, 249, 250, 251, 253, 254, 255, 257, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 290, 291, 297, 298, 305, 306, 313, 314, 321, 322, 330, 331, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 352, 353, 354, 355, 356,357, 358, 360, 362, 371, 378, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 401, 402, 403, 406, 407, 408, 412, 413, 414, 416, 418, 422, 427, 428,429, 430, 431, 433, 434, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 462, 463, 464, 465, 466, 468, 469, 470, 471, 472, 473, 474, 475, 476, 478, 479, 480, 481, 482, 483, 486, 488, 489, 492, 495, 496, 497, 498, 511, 512, 513, 514, 515, 520, 523, 524, or 534 from Table 1 of the descriptive report, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

62. Compound according to claim 1, characterized in that the Compound is 4, 15, 16, 17, 20, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 59, 60b, 61, 62, 63, 64, 65, 66, 67, 71, 72, 75, 81, 82, 83, 84, 89, 91, 97, 101, 109, 119, 120, 121, 122, 123, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 155, 163, 168, 169, 170, 173, 174, 175, 179, 180, 181, 183, 191, 192, 194, 195, 198, 199, 201, 202, 212, 213, 214, 215, 216, 228, 230, 231, 232 237, 238, 239, 246, 248, 250, 251, 253, 254, 255, 258, 263, 264, 271, 272, 273, 278, 279, 280, 281, 287, 288, 291, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 352, 353, 354, 355, 356, 357, 358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 401, 402, 403, 406, 407, 408, 413, 414, 416, 418, 422, 428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451, 453, 454, 462, 463, 464, 465, 466, 468, 470,472, 474, 475, 476, 479, 480, 481, 482, 486, 489, Petition 870250103125, dated 11 / 11 / 2025, page 462 / 470 26 / 30 495, 496, 498, 511, 512, 513, 514, 515, 520, or 524 of Table 1 of the descriptive report, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

63. Compound according to claim 1, characterized in that the Compound is 4, 15, 25, 32, 33, 47, 48, 49, 50, 52, 54, 59, 60b, 61, 62, 63, 72, 75, 82, 83, 89, 97, 101, 109, 119, 121, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 150, 163, 169, 170, 174, 179, 181, 183, 191, 192, 194, 195, 212, 213, 214, 215, 230, 231, 232, 238, 239, 246, 248, 250, 251, 253, 254, 255, 258, 263, 264, 272, 273, 278, 279, 280, 281, 288, 291, 298, 305, 306, 313, 314, 321, 322, 331, 338, 339, 340, 341, 342, 343, 344, 345, 353, 355, 356,358, 391, 392, 393, 394a, 394b, 395a, 395b, 396, 397, 402, 403, 407, 408, 413, 418, 422, 428, 429, 430, 431, 434, 445, 446, 447, 448, 449, 450, 451,454, 463, 464, 465, 466, 472, 475, 476, 479, 481, 486, 489, 495, 498, 512, 514, 515, 520, or 524 of Table 1 of the descriptive report, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

64. Compound according to claim 1, characterized in that the Compound is 48, 50, 54, 60b, 61, 63, 72, 75, 83, 97, 101, 109, 127, 135, 140, 141, 143, 144, 145, 146, 147, 149, 163, 169, 170, 174, 179, 181, 191, 194, 195, 212, 215, 230, 231, 232, 238, 246, 248, 250, 251, 255, 258, 272, 273, 279, 281, 291, 306, 314, 321, 322, 331, 338, 339, 340, 341, 342, 345, 353, 355, 356, 391, 393, 395a, 395b, 397, 402, 428, 430, 431, 434, 446, 447, 448, 450, 463, 464, 465, 466, 489, 512, 514, 515, or 524 from Table 1 of the descriptive report, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

65. Compound according to claim 1, characterized in that it is Compound 54, 61, 63, 75, 140, 143, 146, 174, 215, 230, 250, 251, 273, 306, 322, 430, 446, 463 or 512 of Table 1 of the descriptive report, or a pharmaceutically acceptable salt, solvate or prodrug thereof. Petition 870250103125, dated 11 / 11 / 2025, pp. 463 / 470 27 / 30 66. Pharmaceutical composition, characterized in that it comprises: a compound according to any one of claims 1 to 65, or a pharmaceutically acceptable salt, solvate or prodrug thereof; and a pharmaceutically acceptable carrier, diluent or excipient.

67. Use of a compound, as defined in any one of claims 1 to 65, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that it is for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASIC inhibitor is indicated.

68. Use according to claim 67, characterized in that the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

69. Use according to claim 67 or 68, characterized in that the ASIC inhibitor is an ASIC1a inhibitor.

70. Use according to claim 67 or 68, characterized in that the ASIC inhibitor is an ASIC1b inhibitor.

71. Use of a compound as defined in any one of claims 1 to 65, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that it is for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder selected from pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough and acute lung injury.

72. Use in accordance with any of claims 67 to 71, characterized in that the disorder is pain.

73. Use in accordance with any of claims 67 to 72, characterized in that the disorder is inflammatory pain or neuropathic pain. Petition 870250103125, dated 11 / 11 / 2025, pp. 464 / 470 28 / 30 74. Use in accordance with any of claims 67 to 72, characterized in that the disorder is inflammatory pain.

75. Use in accordance with any of claims 67 to 72, characterized in that the disorder is neuropathic pain.

76. A method for treating or preventing a disorder for which an ASIC inhibitor is indicated, characterized in that it comprises administering to a patient in need thereof a compound as defined in any of claims 1 to 65, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

77. Method according to claim 76, characterized in that the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

78. Method according to claim 76 or 77, characterized in that the ASIC inhibitor is an ASIC1a inhibitor.

79. Method according to claim 76 or 77, characterized in that the ASIC inhibitor is an ASIC1b inhibitor.

80. A method for treating or preventing a selected disorder among pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough, and acute lung injury, characterized in that it comprises administering to a patient in need thereof a compound as defined in any of claims 1 to 65, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

81. A method according to any one of claims 76 to 80, characterized in that the disorder is pain.

82. Method according to any of claims 76 to 81, characterized in that the disorder is inflammatory pain or neuropathic pain. Petition 870250103125, dated 11 / 11 / 2025, pp. 465 / 470 29 / 30 83. Method according to any one of claims 76 to 81, characterized in that the disorder is inflammatory pain.

84. Method according to any one of claims 76 to 81, characterized in that the disorder is neuropathic pain.

85. A compound according to any one of claims 1 to 65, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that it is for use in the treatment or prevention of a disorder for which an ASIC inhibitor is indicated.

86. A pharmaceutically acceptable compound, salt, solvate, or prodrug for use according to claim 85, characterized in that the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

87. A pharmaceutically acceptable compound, salt, solvate, or prodrug for use according to claim 85 or 86, characterized in that the ASIC inhibitor is an ASIC1a inhibitor.

88. A pharmaceutically acceptable compound, salt, solvate, or prodrug for use according to claim 85 or 86, characterized in that the ASIC inhibitor is an ASIC1b inhibitor.

89. A compound according to any one of claims 1 to 65, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that it is for use in the treatment or prevention of a selected disorder among pain, arthritis, stroke, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough and acute lung injury.

90. A compound, salt, solvate, or prodrug that is pharmaceutically acceptable for use according to any of claims 85 to 89, characterized in that the disorder is pain.

91. Compound, salt, solvate or prodrug pharmaceutically acceptable for use in accordance with any of claims 85 to 90, characterized in that the disorder is inflammatory pain or neuropathic pain. Petition 870250103125, dated 11 / 11 / 2025, pp. 466 / 470 30 / 30 92. A compound, salt, solvate, or prodrug that is pharmaceutically acceptable for use according to any of claims 85 to 90, characterized in that the disorder is inflammatory pain.

93. A compound, salt, solvate, or prodrug that is pharmaceutically acceptable for use according to any of claims 85 to 90, characterized in that the disorder is neuropathic pain.

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