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. The compound or pharmaceutically acceptable salt, solvate, or prodrug thereof can be used for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated. There is also provided a use of a compound C having the Formula (I') or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASICs inhibitor is indicated. In some embodiments, the compound Formula (I) or the pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition prepared using compound C is 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] This application claims priority over US Provisional Application No. 63 / 491,493, filed 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 inhibition of acid-sensitive ion channels, also called ASICs, is indicated. For example, the application refers to substituted thiophene fused derivatives, pharmaceutical compositions comprising them and their use as ASIC inhibitors. Background

[003] Since the discovery of acid-sensing ion channels (ASICs) in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant significance. ASICs play important roles in mediating pain sensation, 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 870250100355, dated 03 / 11 / 2025, p. 7 / 282 / 236 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 having formula (I), or a salt, solvate or pharmaceutically acceptable prodrug thereof, provided that: Raé -NH2, -NH-OH, -OH or -NHRb; 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; represents one of the following residues Ao a Aó or given that: R is H or C1-C6 alkyl; Petition 870250100355, dated 03 / 11 / 2025, p. 8 / 282 / 236 R' is H or C2-C6 alkyl; R1 is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2C6alkynyl, F, Cl, Br, I, -N(R)2, 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 C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents and C6-C10aryl is optionally substituted by 1 to 3 R8 substituents; R2 is C6-C10 aryl, unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted with 1 to 3 substituents; R7 is C2-C6 alkenyl, C2-C6 alkynyl, Cl, Br, I, -N(R)2, C3-C8 cycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6 or C(O)OR5, where C6-C10 aryl is optionally substituted by 1 to 3 R8 substituents, provided that: (i) when Ra is -NH2, CZ represents residue A0, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, Z··' represents residue A0, R is H and R1 is -CN, then R2 is different from or each R is independently C1-C4 alkyl; each R5 is independently C1-C6 alkyl, and each C1-C6 alkyl is optionally replaced by 1 to 3 R9 substituents; each R6 is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl or C6-C10aryl, and the 4- to 6-membered heterocycloalkyl is optionally replaced by -OH; each R7 is independently -OH, -C(O)Rn, C3C5cycloalkyl, -CN, C6-Cwaryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, Petition 870250100355, dated 03 / 11 / 2025, p. 9 / 282 / 236 NH(C(O)C1-C6alkyl), -OR20, -SCi-C6alkyl, -NH2, -NH(C1-C4alkyl), N(Ci-C4alkyl)2 or 4-oxo-1,4-dihydro-1-pyridinyl, wherein each C3C5cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- or 6-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl or oxo; each R8 is independently a 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 R9 is independently -OH, -C(O)R15, C3-C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, NH(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 -OC1-C6alkyl is optionally substituted by -OC1-C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, a 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or a 4- to 6-membered heterocycloalkyl substituted with -OH; each R20 is independently a 5- to 10-membered C2-C6 alkyl or heteroaryl group, wherein each C2-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents; each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, -SPh or -S(O)2Ph, with each C1-C4 alkyl group optionally replaced by -OH; each R13 is independently halogen, C1-C4 alkyl, C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2, -OH, -OC1-C6 alkyl, SC1-C6 alkyl, -S(O)2C1-C6 alkyl, -NH2, -NH(C1-C4 alkyl) or -N(C1C4 alkyl)2, wherein each -OC1-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1 Petition 870250100355, dated 03 / 11 / 2025, page 10 / 282 / 236 C6alkyl, -NH(C1-C4alkyl) and -N(C1-C4alkyl)2 is optionally replaced by 1 to 3 R9 substituents; Each R14 is independently halogen, -OCi-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 group; R4 is unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted by 1a 3 R9 substituents, C3-C5 cycloalkyl, C6-C6 ioaryl, a partially unsaturated heterocyclic group of 7 to 10 members or a heteroaryl group of 5 to 10 members, wherein C3-C5 cycloalkyl is optionally substituted by 1a 3 R9 substituents, and C6-C6 ioaryl and heteroaryl groups of 5 to 10 members are optionally substituted by 1a 3 Ri0 substituents, provided that when Ra is -OH, it represents the residue Ai, and R' is H, then R4 is different from -CH2CH3 or -C(CH3)3; each Ri0 is independently Ci-C4 alkyl, halogen, -OCiC6 alkyl, -NH2, -NH(Ci-C4 alkyl) or -N(Ci-C4 alkyl)2, wherein each CiC4 alkyl is optionally substituted by ia 3 halogens; R2a is unsubstituted C3-C6 alkyl, C1-C6 alkyl substituted by 1a 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl, C3C5 cycloalkyl or C6-C10aryl, wherein C3-C5 cycloalkyl is optionally substituted by 1a 3 R9 substituents, and C6-C10aryl is optionally substituted by 1a 3 R2 substituents, provided that: (i) when Ra is -NH2, - represents residue A2, and R is H, then R2a is different from CH2CH2CH3, -CH(CHs)2, -C(CH3)3, -C(CH3)2CH2CH3, -CH2OH, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH, - represents residue A2, and R is H, then R2 is different from -C(CH3)3, -C(CH3)2CH2CH3, NHC(O)OC(CH3)3 or unsubstituted phenyl; (iii) when Ra is -NHCH3 or NHCH2CH3 / -—- represents residue A2, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl Petition 870250100355, of 03 / 11 / 2025, p. 11 / 282 / 236 replaced; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3 or NHcyclopropyl, Z··' represents residue A2, and Ré is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3 or -CF3; and (v) when Ra is -NHcyclopentyl or -NHcyclohexyl, CZ represents residue A2, and R is H, then R2 is different from -C(CH3)3 or C(CH3)2CH2CH3; Each R22 is independently unsubstituted C2-C4 alkyl, C1-C4 alkyl substituted with 1 to 3 halogens, F, Br, I, -OC3-C6 alkyl, -NH2, NH(C1-C4 alkyl) or -N(C1-C4 alkyl)2; 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 substituents R16 and each C6-C10aryl is optionally substituted by 1 to 3 substituents R17; each R16 is independently -OH, -C(O)NH2, -C(O)NH(C1-C4 alkyl), C3-C6 cycloalkyl, -CN, C6-C10 aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6 alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6 alkyl) or -OC1-C4 alkyl(OC1-C4 alkyl), wherein each C3-C6 cycloalkyl 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-C4 alkyl; 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, where each C1 Petition 870250100355, dated 03 / 11 / 2025, p. 12 / 282 / 236 C3-C8 cycloalkyl 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 cyclic structure selected from a C3-Cs-cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the C3-Cs-cycloalkyl is optionally substituted by 1 to 3 substituents R9, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted by oxo, provided that: (i) when Ra is -NH2, CZ represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl or 1,3-dioxolane; and (ii) when Rae -NHCH3, NHCH2CH3, -NHcyclopropyl, -NHCH(CH3)2 or -NHCH2CH2CH3, C represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl; 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.

[008] In some embodiments, the compound of formula (I) may be a compound of formula (Ia), formula (Ib), formula (Ic), formula (Id), formula (Ie), formula (If) or formula (Ig), as described herein, or a pharmaceutically acceptable salt, solvate or prodrug. Petition 870250100355, dated 03 / 11 / 2025, p. 13 / 282 / 236 of the same.

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

[0010] According to another aspect, the present application relates to the use of a compound C which has the formula (I'): 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, wherein: Raé -NH2, -NH-OH, -OH or -NHRb; 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; represents one of the following residues Ao a Aó or given that: R is H or C1-C6 alkyl; R' is H, C1-C6 alkyl or phenyl; R1 is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2C6alkynyl, F, Cl, Br, I, -N(R)2, C3-C8cycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, Petition 870250100355, dated 03 / 11 / 2025, p. 14 / 282 / 236 C(O)R6 or -C(O)OR5, where C1-CWquila is optionally replaced by 1 to 3 R7 substituents and C6-C1oarila is optionally replaced by 1 to 3 R8 substituents; R2 is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted by 1 to 3 R7 substituents, C2-C6alkenyl, C2-C6alkynyl, F, Cl, Br, I, -N(R)2, 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, where C6-C1aryl is optionally substituted by 1 to 3 R8 substituents; provided that when Ra is -NH2, CZ represents the If N is residue Ao, R is H and R1 is -CN, then R2 is different from N, each R is independently C1-C4 alkyl; each R5 is independently C1-C6 alkyl, with each C1-C6 alkyl optionally replaced by 1 to 3 R9 substituents; each R6 is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl or C6-C10aryl, wherein the 4- to 6-membered heterocycloalkyl is optionally replaced by -OH; Each R7 is independently -OH, -C(O)R11, C3C5cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6alkyl), -OR20, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or 4-oxo-1,4-dihydro-1-pyridinyl, wherein each C3C5cycloalkyl is optionally substituted by 1 to 3 substituents. R12, each 5- or 6-membered heteroaryl is optionally substituted by 1 to 3 substituents. R13, and each 4- to 6-membered heterocycloalkyl group is optionally replaced by C1-C4 alkyl or oxo; Each R8 is independently a halogen, C1-C6 alkyl, -OC1C6 alkyl, C3-C6 cycloalkyl, or heteroaryl group of 5 to 10 members, with Petition 870250100355, dated 03 / 11 / 2025, p. 15 / 282 / 236 each -OCi-C6alkyl is optionally replaced by -OCi-C4alkyl, and each 5- to 10-membered heteroaryl is optionally replaced by C1-C4alkyl; each R9 is independently -OH, -C(O)R15, C3C6cycloalkyl, -CN, C6-C1aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(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 C1C4alkyl, and each -OC1-C6alkyl is optionally substituted by -OC1C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, a 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or a 4- to 6-membered heterocycloalkyl substituted with -OH; each R20 is independently a 5- to 10-membered C2-C6 alkyl or heteroaryl group, wherein each C2-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents; each R12 is independently C1-C4alkyl, -SC1-C4alkyl, Ph, -OC1-C4alkyl, -SPh or -S(O)2Ph, each C1-C4alkyl being optionally replaced by -OH; each R13 is independently halogen, C1-C4 alkyl, C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2, -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-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1C6 alkyl, -NH(C1-C4 alkyl) and -N(C1-C4 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 C1-C6 alkyl, C3-C5 cycloalkyl, C6-C1 aryl group Petition 870250100355, dated 03 / 11 / 2025, p. 16 / 282 / 236 partially unsaturated heterocyclic group of 7 to 10 members or heteroaryl group of 5 to 10 members, wherein C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-Cwaryl and heteroaryl groups of 5 to 10 members are optionally substituted by 1 to 3 R10 substituents; 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 unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted with 1 to 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl, C3-C8 cycloalkyl or C6-C10 aryl, wherein C3-C8 cycloalkyl is optionally substituted with 1 to 3 R9 substituents, and C6-Cwaryl is optionally substituted with 1 to 3 R22 substituents; Each R22 is independently C1-C4 alkyl, halogen, -OC1C6 alkyl, -NH2, -NH(C1-C4 alkyl) or -N(C1-C4 alkyl)2, with each C1C4 alkyl group optionally substituted by 1 to 3 halogens; R1 and R2 are independently -CN, C6-Cwaryl, 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(C1-C4 alkyl), C3-C6 cycloalkyl, -CN, C6-C10 aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6 alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6 alkyl) or -OC1-C4 alkyl(OC1-C4 alkyl), wherein each C3-C6 cycloalkyl 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-C4 alkyl; Each R17 is independently halogen, C1-C6 alkyl, -OC1 Petition 870250100355, dated 03 / 11 / 2025, p. 17 / 282 / 236 5- to 10-membered coalkyl or heteroaryl groups, wherein each 5- to 10-membered heteroaryl group is optionally replaced by a C1-C4 alkyl group; 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 cyclic structure selected from a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted by oxo; provided that when Ra is NH2, CZ represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than 1,3-dioxolane; 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.

[0011] In some embodiments, compound C may be a compound of formula (I), formula (Ia), formula (Ib), formula (Ic), Petition 870250100355, dated 03 / 11 / 2025, p. 18 / 282 / 236 formula (Id), of formula (Ie), of formula (If), of formula (Ig), as described herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0012] In some embodiments, compound C may be a compound from Table 2 of this description, or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[0013] 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.

[0014] An additional aspect relates to the use of a compound, as defined herein, or a pharmaceutically acceptable salt, solvate, or 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 pharmaceutically acceptable salt, solvate, or 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, as defined herein, or a pharmaceutically acceptable salt, solvate, or prodrug thereof. In one embodiment, the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

[0015] 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 selected disorder from among pain, arthritis, stroke, epileptic disorder, Petition 870250100355, dated 03 / 11 / 2025, page 19 / 282 / 236 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 salt, solvate or pharmaceutically acceptable 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. 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 Petition 870250100355, dated 03 / 11 / 2025, page 20 / 282 / 236. If any definitions contrary to those presented in this descriptive report are found to be true, 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.

[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, these 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 respect 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" means within a range. Petition 870250100355, dated 03 / 11 / 2025, page 21 / 282 / 236, an acceptable error for the specific value should be presumed. Compounds and compounds for use

[0020] This application relates to innovative compounds of the following general formula (I) and Compounds C for use of the general formula (I') or pharmaceutically acceptable salts, solvates or prodrugs thereof, Rae CZZ being defined in more detail below.

[0021] Thus, the compounds described in this application include those represented by the chemical structure of formula (I), with reference to any of the applicable embodiments described below, and exemplary compounds.

[0022] The compounds described in this application may also include compounds such as Compounds 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 of Table 1, as well as their pharmaceutically acceptable salts, solvates and prodrugs, when applicable.

[0023] The compounds for use described in this application also include those represented by the chemical structure of formula (I'), with Petition 870250100355, dated 03 / 11 / 2025, p. 22 / 282 / 236 refers to any of the applicable modalities described below, and exemplary compounds.

[0024] The compounds for use described in this application also include compounds such as Compounds 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 or 294, 295, 296 or 297 of Table 2, as well as their pharmaceutically acceptable salts, solvates and prodrugs, when applicable.

[0025] 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.

[0026] 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 (or conformational) mixtures 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 Petition 870250100355, dated 03 / 11 / 2025, page 23 / 282 / 236, which, as indicated otherwise, the structures represented in the present invention must 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. These compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents according to the present description.

[0027] In some embodiments, the compounds defined herein, or the salt, solvate, or pharmaceutically acceptable prodrug thereof, the compound being in the form of a racemate or any enantiomer thereof.

[0028] Definitions of specific functional groups and chemical terms are provided below.

[0029] 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.

[0030] 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). Petition 870250100355, dated 03 / 11 / 2025, page 24 / 282 / 236

[0031] The term halogen, as used herein, refers to an atom selected from among fluorine (fluoro, -F), chlorine (chlorine, -Cl), bromine (bromine, -Br) and iodine (iodine, -I).

[0032] The term heteroatom means one or more of the following: oxygen, sulfur, nitrogen, phosphorus or silicon, more particularly, oxygen, sulfur or nitrogen.

[0033] 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.

[0034] 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, C2-C6 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.

[0035] 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, C2-C6 alkynyl 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 870250100355, dated 03 / 11 / 2025, p. 25 / 282 / 236

[0036] 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.

[0037] 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.

[0038] 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.

[0039] The term heterocycloalkyl used alone or as part of Petition 870250100355, dated 03 / 11 / 2025, p. 26 / 282 / 236, 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.

[0040] 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 heteroaryl groups Petition 870250100355, dated 03 / 11 / 2025, p. 27 / 282 / 236 com more than 10 non anel 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.

[0041] 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 870250100355, dated 03 / 11 / 2025, page 28 / 282 / 236: 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]l, 4-oxazin-3(4H)-one, and . 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).

[0042] 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 at any Petition 870250100355, dated 03 / 11 / 2025, p. 29 / 282 / 236. A given structure may be replaced 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 this description are preferably those that result in the formation of chemically stable or chemically viable compounds. The term chemically stable, as used herein, refers to compounds that are not substantially altered when subjected to conditions to permit their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0043] 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, -Cl, -Br, -I), -OH, -CO2H, alkoxy, such as methoxy, ethoxy or propyloxy, -OCHF2, -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 groups, cycloalkyl, as defined above, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, oxo, thio-oxo, -NO2, -CN, -NH2, -NHMe, -NHEt, N(Me)2, -NHCOMe, -NH(COOtBu), -N(Et)(COOtBu), protected amino acid, CH2OH, -COOH, -COOMe, -COOEt, -CONH2, -CONHMe, -CONHEt, -CF-3, -CHF2, -CH2F, -Si(Me), -OSi(Me)2(tBu), -SMe, -SO2NH(CH2)3OH, -SO2Me, SO2Ph, -SPh, pirazolila, pyrrolila, piridila, piperidila, triazolila, tetrazolila, morphinila, isoxazolila, oxazolila, tiazolila, imidazolila, benzotiazolila, benzimidazolila, Petition 870250100355, of 03 / 11 / 2025, p. 30 / 282 / 236

[0044] The term pharmaceutically acceptable salt refers to salts 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, and are proportionate to a reasonable risk / benefit ratio. Pharmaceutically acceptable salts are well known in the art. 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, and 2-naphthalenesulfonate. Petition 870250100355, dated 03 / 11 / 2025, page 31 / 282 / 236 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 formed using counterions, such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, sulfonate, and aryl sulfonate.

[0045] 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.

[0046] 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. Petition 870250100355, dated 03 / 11 / 2025, page 32 / 282 / 236

[0047] 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 146, for example. As can be recognized by those skilled in the art, other methods of synthesis of the compounds of the formulas in the present invention will be evident to those skilled in the art. Furthermore, the various synthetic steps can be performed in an alternative sequence or order to yield the desired compounds. In addition, 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.

[0048] 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. These 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.

[0049] In some embodiments, the present disclosure thus provides a compound having formula (I), Petition 870250100355, dated 03 / 11 / 2025, p. 33 / 282 / 236 or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, wherein: Raé -NH2, -NH-OH, -OH or -NHRb; Rb is C1-C6 alkyl, C3-C6 cycloalkyl or 3- to 6-membered heterocycloalkyl, and C1-C6 alkyl is optionally substituted by 1 to 3 halogens; ^ZZZ represents one of the following residues: Ao a Aó or given that: R is H or C1-C6 alkyl; R' is H or C2-C6 alkyl; R1 is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2C6alkynyl, F, Cl, Br, I, -N(R)2, 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 C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents and C6-C10aryl is optionally substituted by 1 to 3 R8 substituents; R2 is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted by 1 to 3 substituents R7, C2-C6alkenyl, C2-C6alkynyl, Cl, Br, I, -N(R)2, 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, where C6-C10aryl is optionally substituted by 1 to 3 substituents R8, provided that: (i) when Ra is -NH2, ZZZ represents residue A0, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, ZZZ represents the Petition 870250100355, dated 03 / 11 / 2025, p. 34 / 282 / 236 residue Ao, R is H and R1 is -CN, then R2 is different from or each R is independently C1-C4 alkyl; Each R5 is independently C1-C6 alkyl, and each C1-C6 alkyl is optionally replaced by 1 to 3 R9 substituents; each R6 is independently C3-C6cycloalkyl, 4- to 6-membered heterocycloalkyl or C6-C10aryl, and the 4- to 6-membered heterocycloalkyl is optionally replaced by -OH; Each R7 is independently -OH, -C(O)Rn, C3C5cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6alkyl), -OR20, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or 4-oxo-1,4-dihydro-1-pyridinyl, wherein each C3C5cycloalkyl is optionally substituted by 1 to 3 substituents. R12, each 5- or 6-membered heteroaryl is optionally substituted by 1 to 3 substituents. R13, each 4- to 6-membered heterocycloalkyl is optionally replaced by C1-C4 alkyl or oxo; each R8 is independently a 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 R9 is independently -OH, -C(O)R15, C3C6cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6alkyl), -OC1-C6alkyl, -SC1-C6alkyl, NH2, -NH(C1-C4alkyl) or -N(C1-C4alkyl)2, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1 Petition 870250100355, dated 03 / 11 / 2025, p. 35 / 282 / 236 C4alkyl, and each -OC1-C6alkyl is optionally replaced by -OC1C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, a 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or a 4- to 6-membered heterocycloalkyl substituted with -OH; each R20 is independently a 5- to 10-membered C2-C6 alkyl or heteroaryl group, wherein each C2-C6 alkyl group is optionally substituted by 1 to 3 R14 substituents; each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, -SPh or -S(O)2Ph, with each C1-C4 alkyl group optionally replaced by -OH; each R13 is independently halogen, C1-C4 alkyl, C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2, -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-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1C6 alkyl, -NH(C1-C4 alkyl) and -N(C1-C4 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 unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted with 1 to 3 R9 substituents, C3-C8 cycloalkyl, C6-Cwaryl, a 7- to 10-membered partially unsaturated heterocyclic group or a 5- to 10-membered heteroaryl group, wherein C3-C8 cycloalkyl is optionally substituted with 1 to 3 R9 substituents, and C6-Cwaryl and 5- to 10-membered heteroaryl groups are optionally substituted with 1 to 3 R10 substituents, provided that when Ra is -OH, CZ represents residue A1, and R' is H, then R4 is different from -CH2CH3 or -C(CH3)3; Petition 870250100355, dated 03 / 11 / 2025, p. 36 / 282 / 236 each R10 is independently Ci-C4 alkyl, halogen, -OC1C6 alkyl, -NH2, -NH(C1-C4 alkyl) or -N(C1-C4 alkyl)2, wherein each C1C4 alkyl is optionally substituted by 1 to 3 halogens; R2a is unsubstituted C3-C6 alkyl, C1-C6 alkyl substituted with 1 to 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl, C3-C8 cycloalkyl or C6-Cwaryl, wherein C3-C8 cycloalkyl is optionally substituted with 1 to 3 R9 substituents, and C6-C10 aryl is optionally substituted with 1 to 3 R2 substituents, provided that: (i) when Ra is -NH2, it represents residue A2, and R is H, then R2a is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CH2OH, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH, '- represents residue A2, and R is H, then R2 is different from -C(CH3)3, -C(CH3)2CH2CH3, NHC(O)OC(CH3)3 or unsubstituted phenyl; (iii) when Ra is -NHCH3 or NHCH2CH3, CZZ represents residue A2, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl;(iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3 or NHcyclopropyl, represents residue A2, and Ré is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3 or -CF3; and (v) when Ra is -NHcyclopentyl or -NHcyclohexyl, represents residue A2, and R is H, then R2 is different from -C(CH3)3 or C(CH3)2CH2CH3; Each R22 is independently unsubstituted C2-C4 alkyl, C1-C4 alkyl substituted with 1 to 3 halogens, F, Br, I, -OC3-C6 alkyl, -NH2, NH(C1-C4 alkyl) or -N(C1-C4 alkyl)2; R1 and R2 are independently -CN, C6-Cwaryl, 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; Petition 870250100355, dated 03 / 11 / 2025, p. 37 / 282 / 236 each R16 is independently -OH, -C(O)NH2, -C(O)NH(C1-C4 alkyl), C3-C6 cycloalkyl, -CN, C6-C10 aryl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)OC1-C6 alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6 alkyl) or -OC1-C4 alkyl(OC1-C4 alkyl), and each C3-C6 cycloalkyl is optionally substituted by 1 to 3 substituents R18, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 substituents R21 and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4 alkyl; 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 cyclic structure selected from a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl, and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted by oxo, provided that: (i) when Rae is -NH2, CZ represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl, or 1,3-dioxolane; and (ii) when Rae is -NHCH3, Petition 870250100355, dated 03 / 11 / 2025, p. 38 / 282 / 236 NHCH2CH3, -NHcyclopropyl, -NHCH(CH3)2 or -NHCH2CH2CH3, where C represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl; 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.

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

[0051] In some embodiments, the compound of formula (I), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Let R' be H.

[0052] In some embodiments, the compound of formula (I), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raseja is selected from the group consisting of -NH2, -NH-OH, -OH or -NHRb, with Rb representing: -CH3, or

[0053] In some embodiments, the compound of formula (I), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raseja -NHRbe Rbrepresents 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. Petition 870250100355, dated 03 / 11 / 2025, p. 39 / 282 / 236

[0054] In some embodiments, the compound of formula (I) or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raseja -NHRb and Rbre is present:

[0055] In some embodiments, the compound of formula (I), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raseja selected from the group consisting of -NH2, -OH, or -NHRb, with Rbrepresenta: -CH3, or

[0056] In some embodiments, the compound of formula (I) or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, is such that Raseja -NHRbe Rbrepresente: A Aύ -CH3, , 'ΧχΆ / , A, A or V .

[0057] In some modalities, Raé -NHRb and Rb represents

[0058] In other Raé NH2 modalities.

[0059] In other forms, Raé -OH

[0060] In other forms, Raé -NH-OH.

[0061] In some embodiments, the compound of formula (I) may have the following structures (Ia), (Ib), (Ic), (Id), (Ie), (If) or (Ig), a salt, a solvate or a pharmaceutically acceptable prodrug thereof: Petition 870250100355, dated 03 / 11 / 2025, p. 40 / 282 35 / 236 where R1, R2, R3, R4, Rla, Rlb, Rlc, R2a, R2b, R2c, R2d, R4a, R4b, R, R and Ratio as defined herein. Compound of formula (Ia)

[0062] In some embodiments, the compound of formula (I) may be a compound of formula (Ia), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. (Ia)

[0063] The groups R, Ra, R1 and R2 can be as defined for the general formula (I) above.

[0064] In some embodiments, the compound with the following general formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 is -CN, C-Cioaryl, C1-Cealkyl, C1-Cealquinyl, F, -N(R)2, Cs-Cgcycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, C(O)NHR5, -C(O)R6 or -C(O)OR5, where C1-Cealkyl is optionally substituted by 1 to 3 substituents R7 and C-Cioaryl is optionally substituted by 1 to 3 substituents R8; and R2 is C-Cioaryl, unsubstituted C2-C6alkyl, C1-Coalkyl substituted by 1 to 3 substituents R7, -N(R)2, Cs-Cgcycloalkyl, Petition 870250100355, dated 03 / 11 / 2025, p. 41 / 282 / 236 5- to 10-membered heteroaryl groups, -C(O)NH2, -C(O)NHR5, -C(O)R6 or C(O)OR5, where C6-Cwaryl is optionally substituted by 1 to 3 R8 substituents, provided that: (i) when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, R is H and R1 is -CN, then R2 is different from or

[0065] Ni== / ; and R, R5, R6, R7 and R8 are as defined here. In some embodiments, the compound with the following general formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 is -CN, C6-C10aryl, C1-C-6alkyl, C2-C6alkynyl, F, -N(R)2, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, C(O)NHR5, -C(O)R6 or -C(O)OR5, where C1-C-6alkyl is optionally substituted by 1 to 3 substituents R7 and C6-C10aryl is optionally substituted by 1 to 3 substituents R8; and R2 is C6-C10aryl, unsubstituted C2-C6alkyl, C1C6alkyl substituted by 1 to 3 R7 substituents, -N(R)2, C3-C8cycloalkyl, 5 to 10 membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6 or C(O)OR5, wherein C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, provided that: (i) when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, R is H and R1 is -CN, then R2 is different from or N; where each R is C1-C2 alkyl; each R5 is C1-C-6 alkyl; Each R6 is a 4- to 6-membered heterocycloalkyl group or C6 Petition 870250100355, dated 03 / 11 / 2025, p. 42 / 282 / 236 Cioarila, and the 4- to 6-membered heterocycloalkyl is optionally replaced by -OH; each R7 is independently -OH, -C(O)R11, C3C5cycloalkyl, -CN, C6-C6-C6-alkyl, halogen, -C(O)OH, 5-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1-C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6alkyl), -OR20, -C1-C6alkyl, -NH2, -NH(C1-C4alkyl) or N(C1-C4alkyl)2, wherein each C3-C5cycloalkyl is optionally substituted by 1a3 substituents R12, each 5-membered heteroaryl is optionally substituted by 1a3 substituents R13, and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4alkyl or oxo; each R8 is independently a halogen, C1-C6 alkyl, -C1-C6 alkyl or 5- to 10-membered heteroaryl, wherein each 5- to 10-membered heteroaryl is optionally substituted by C1-C4 alkyl; each R11 is independently -NH2, -NH(C1-C4 alkyl) or a 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms; each R2oé independently C2-C6alkyl or heteroaryl of 5 to 10 members, wherein each C2-C6alkyl is optionally substituted by 1 to 3 R14 substituents; each R12 is independently Ci-C4alkyl, -SCi-C4alkyl, Ph, -OCi-C4alkyl, -S(O)2Ph or -SPh, with each Ci-C4alkyl optionally replaced by -OH; Each R13 is independently C1-C4 alkyl, -C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2 or -OH; and each R14 is independently halogen or -OC1-C4 alkyl.

[0066] In some embodiments, the compound with the following general formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 is -CN, phenyl, C1-C5 alkyl, C3 alkynyl, F, C3 Petition 870250100355, 03 / 11 / 2025, p. 43 / 282 / 236 C-cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, C(O)R6 or -C(O)OR5, and C1-C5 alkyl is optionally substituted by 1 to 2 R7 substituents and phenyl is optionally substituted by 1 R8 substituent; R2 is phenyl, unsubstituted C2-C4 alkyl, C1-C5 alkyl substituted by 1 to 2 R7 substituents, C3-C6 cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6 or -C(O)OR5, wherein phenyl is optionally substituted by 1 R8 substituent, provided that when Ra is -NH2, R is H, and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; R5, R6, R7, and R8 are as defined here.

[0067] In some embodiments, the compound with the following general formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 is -CN, phenyl, C1-C5 alkyl, C3 alkynyl, F, C3C6 cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, C(O)R6 or -C(O)OR5, where C1-C5 alkyl is optionally substituted by 1 to 2 substituents R7 and phenyl is optionally substituted by 1 substituent R8; R2 is phenyl, unsubstituted C2-C4 alkyl, C1-C5 alkyl substituted by 1 to 2 substituents R7, C3-C6 cycloalkyl, 5 to 10 membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6 or -C(O)OR5, wherein phenyl is optionally substituted by 1 substituent R8, provided that: (i) when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, R is H and R1 is -CN, then R2 N1 is different from Ne, wherein each R5 is a C1-C2 alkyl; each R6 is a 6-membered heterocycloalkyl or phenyl, and the 6-membered heterocycloalkyl is optionally substituted with -OH; Petition 870250100355, dated 03 / 11 / 2025, p. 44 / 282 / 236 each R7 is independently -OH, -C(O)R11, C3-C5cycloalkyl, -CN, phenyl, F, -C(O)OH, 5-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC4alkyl), -N(CH2CH3)(C(O)OC4alkyl), 6-membered heterocycloalkyl, -NH(C(O)CH3), -OR20, -NH2, -NHCH2CH3 or -N(Me)2, with each C3-C5cycloalkyl being optionally substituted by 1 to 3 substituents R12, each 5-membered heteroaryl is optionally substituted by 1 to 3 substituents R13, and each 6-membered heterocycloalkyl is optionally substituted by propyl or oxo; Each R8 is independently -F, -Cl, -Br, -CH3, -OCH3, or a 5-membered heteroaryl, with each 5-membered heteroaryl optionally replaced by -CH3; Each R11 is independently -NH2, -NHCH2CH3, or a 6-membered heterocycloalkyl group containing at least 2 heteroatoms; each R20 is independently a 6-membered C2 alkyl or heteroaryl, and each C2 alkyl is optionally replaced by 1 R14 substituent; each R12 is independently C1-C4 alkyl, -SCH3, -Ph, OCH3, -S(O)2Ph or -SPh, and C1 alkyl is optionally replaced by -OH; Each R13 is independently C1-C3 alkyl, -C(O)OCH2CH3, C3-C4 cycloalkyl, -C(O)NH2, or -OH; and each R14 is independently halogen or -OCH3.

[0068] In some embodiments, the compound with the following formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 and R2 independently represent R23, or R1 represents -F, -CN or -CH3 and R2 represents R23; wherein R23 represents: -CH2CH3, -CH2CH2CH3, , , , v , Petition 870250100355, dated 03 / 11 / 2025, p. 45 / 282 / 236 X, -N(CH3)2, Petition 870250100355, dated 03 / 11 / 2025, p. 46 / 282 / 236 or; on the condition that when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

[0069] In some embodiments, the compound with the following formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 and R2 independently represent R23, or R1 represents -F, -CN or -CH3 and R2 represents R23; wherein R23 represents: -CH2CH3, -CH2CH2CH3, , -N(CH3)2, Petition 870250100355, dated 03 / 11 / 2025, p. 47 / 282 / 236 or under the condition that when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

[0070] In some forms, the compound with the following formula Petition 870250100355, dated 03 / 11 / 2025, p. 48 / 282 / 236 (Ia), or the pharmaceutically acceptable salt, solvate or prodrug thereof, is such that R1 and R2 independently represent R23, or R1 represents -CN or -CH3 and R2 represents R23; wherein R23 represents: CH2CH2CH3 ^, , , 'ou ; under the condition that when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

[0071] In some embodiments, the compound with the following formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 and R2 independently represent R23, or R1 represents -CN or -CH3 and R2 represents R23; wherein R23 represents: CH2CH2CH31, δδ or ' ; under the condition that when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

[0072] In some embodiments, the compound with the following formula (Ia), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 and R2 independently represent R23, or R1 represents -CN or -CH3 and R2 represents R23; wherein R23 represents: with the condition that when Ra is -NH2, R is H and R1 is phenyl Petition 870250100355, dated 03 / 11 / 2025, p. 49 / 282 / 236 not replaced, so R2 is different from unsubstituted phenyl.

[0073] In some specific embodiments, R1 and R2 in the compound of formula (Ia) or the salt, solvate or pharmaceutically acceptable prodrug thereof, are different. In another specific embodiment, R1 is -CN.

[0074] Other embodiments include compounds of formula (Ia), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, wherein one of R1 and R2 is V

[0075] Additional embodiments include compounds of formula (Ia), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, wherein one of R1 and R2 is or no.

[0076] Additional embodiments include compounds of formula (Ia), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof, wherein one of R1 and R2 is . Compounds of formula (Ib)

[0077] In some embodiments, the compound of formula (I) may be a compound of formula (Ib), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof. (Ib)

[0078] The Ra, R' and R4 groups can be as defined for the general formula (I) above.

[0079] In some embodiments, the compound of formula (Ib), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R' is H, on the condition that when Ra is -OH, then R4 is different from CH2CH3 or -C(CH3>.

[0080] In some forms, the compound of formula (Ib), or the Petition 870250100355, dated 03 / 11 / 2025, p. 50 / 282 / 236 salt, the solvate or the pharmaceutically acceptable prodrug thereof, is such that R4 is C2-C-6 alkyl or C6-Cwaryl unsubstituted, provided that when Ra is -OH, and R' is H, then R4 is different from -CH2CH3 or C(CH3)3.

[0081] In some embodiments, the compound of formula (Ib), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R4 is unsubstituted C4 alkyl or phenyl, provided that when Ra is -OH and R' is H, then R4 is different from -C(CH3)3.

[0082] In some embodiments, the compound of formula (Ib), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R4 is -C(CH3)3, on the condition that when Ra is -OH, then R' is different from H.

[0083] In some embodiments, the compound of formula (Ib), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R4 is phenyl. Compounds of formula (Ic)

[0084] In some embodiments, the compound of formula (I) may be a compound of formula (Ic), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[0085] The Rae R2a groups can be as defined for the general formula (I) above.

[0086] In some embodiments, the compound of formula (Ic), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R2 is unsubstituted C3-C6 alkyl, C1-C6 alkyl substituted by 1 to 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl or C6-C10 aryl, and Petition 870250100355, dated 03 / 11 / 2025, page. 51 / 282 / 236 each R9 is a halogen, with the condition that: (i) when Ra is -NH2, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3), C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2 is different from -C(CH3)3, -C(CH3)2CH2CH3 or unsubstituted phenyl; (iii) when Ra is -NHCH3 or -NHCH2CH3, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3 or -NHcyclopropyl, and R (v) when Ra is NHcyclopentyl or -NHcyclohexyl, and R is H, then R2 is different from -CH2CH2CH3, CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3 or -CF3; and (v) when Ra is NHcyclopentyl or -NHcyclohexyl, and R is H, then R2 is different from C(CH3)3 or -C(CH3)2CH2CH3.

[0087] In some embodiments, the compound of formula (Ic), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R2 is unsubstituted C3-C5 alkyl, C1-C2 alkyl substituted by 1 to 3 substituents R9, -CECH, -NHC(O)OC(CH3)3 or phenyl; and each R9 is F, provided that: (i) when Ra is -NH2, and R is H, then R2 is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2 is different from C(CH3)3, -C(CH3)2CH2CH3 or unsubstituted phenyl; (iii) when Ra is NHCH3 or -NHCH2CH3, and R is H, then R2 is different from -CH2CH2CH3, CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3 or -NHcyclopropyl, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3), C(CH3)2CH2CH3 or -CF3; and (v) when Ra is -NHcyclopentyl or -NHcyclohexyl, and R is H, then R2 is different from -C(CH3)3 or -C(CH3)2CH2CH3.

[0088] In some embodiments, the compound of formula (Ic), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R2 represents: or on the condition that Petition 870250100355, dated 03 / 11 / 2025, page 52 / 282 / 236 stating that: (i) when Ra is -NH2, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2 is different from -C(CH3)3, C(CH3)2CH2CH3 or unsubstituted phenyl; (iii) when Ra is -NHCH3 or NHCH2CH3, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (iv) when Ra is NHCH(CH3)2, -NHCH2CH2CH3 or -NHcyclopropyl, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3 or -CF3; and (v) when Ra is -NHcyclopentyl or -NHcyclohexyl, and R is H, then R2 is different from -C(CH3)3 or -C(CH3)2CH2CH3.

[0089] In some embodiments, the compound of formula (Ic) or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R is -H or -CH3, and R2 represents: or on the condition that: (i) when Ra is -NH2, and R is H, then R2 is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2 is different from C(CH3)3, -C(CH3)2CH2CH3 or unsubstituted phenyl; (iii) when Ra is NHCH3 or -NHCH2CH3, and R is H, then R2 is different from -CH2CH2CH3, CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3 or -NHcyclopropyl, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3>, C(CH3)2CH2CH3 or -CF3; and (v) when Ra is -NHcyclopentyl or -NHcyclohexyl, and R is H, then R2 is different from -C(CH3)3 or -C(CH3)2CH2CH3.

[0090] In some embodiments, the compound of formula (Ic), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R is H, and R2 represents: or with Petition 870250100355, dated 03 / 11 / 2025, page 53 / 282 / 236, the condition that: (i) when Ra is -NH2, and R is H, then R2 is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2 is different from C(CH3)3, -C(CH3)2CH2CH3 or unsubstituted phenyl; (iii) when Ra is NHCH3 or -NHCH2CH3, and R is H, then R2 is different from -CH2CH2CH3, CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3 or unsubstituted phenyl; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3 or -NHcyclopropyl, and R is H, then R2 is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3>, C(CH3)2CH2CH3 or -CF3; and (v) when Ra is -NHcyclopentyl or -NHcyclohexyl, and R is H, then R2 is different from -C(CH3)3 or -C(CH3)2CH2CH3. Compounds of the formula (Id)

[0091] In some embodiments, the compound of formula (I) may be a compound of formula (Id), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[0092] The groups R, Ra, R1a, R2b and R4a can be as defined for the general Formula (I) above.

[0093] In some embodiments, the compound of formula (Id), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1a and R2b are independently -CN, C6-C10aryl or C1-C-6alkyl; and R4a is C1-C6alkyl.

[0094] In some embodiments, the compound of formula (Id), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1a and R2b are independently -CN, phenyl or methyl; and R4a is CH2CH(CH3)2. Compounds of the formula (Ie) Petition 870250100355, dated 03 / 11 / 2025, p. 54 / 282 / 236

[0095] In some embodiments, the compound of formula (I) is of formula (Ie), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[0096] The groups R, Ra, R1b and R2c can be as defined for the general formula (I) above.

[0097] In some embodiments, the compound of formula (Ie), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1b and R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo, provided that: (i) when Ra is -NH2, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl or 1,3-dioxolane; and (ii) when Rae -NHCH3, -NHCH2CH3, -NHcyclopropyl, -NHCH(CH3)2 or NHCH2CH2CH3, and Ré H, then R1be R2c form a cyclic structure other than unsubstituted cyclopentyl.

[0098] In some embodiments, the compound of formula (Ie), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1b and R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a C5-C7 cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo, provided that: (i) when Ra Petition 870250100355, dated 03 / 11 / 2025, p. 55 / 282 / 236 is -NH2, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl or 1,3-dioxolane; and (ii) when Ra is -NHCH3, -NHCH2CH3, -NHcyclopropyl, -NHCH(CH3)2 or NHCH2CH2CH3, and Ré is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl.

[0099] In some embodiments, the compound of formula (Ie), or the pharmaceutically acceptable salt, solvate or prodrug thereof, is such that R1b and R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from unsubstituted cyclopentyl, unsubstituted cyclohexyl and unsubstituted cycloheptyl, provided that: (i) when Ra is -NH2, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl or unsubstituted cyclohexyl; and (ii) when Ra is -NHCH3, -NHCH2CH3, -NHcyclopropyl, NHCH(CH3)2 or -NHCH2CH2CH3, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl.

[00100] In some embodiments, the compound of formula (Ie), or the pharmaceutically acceptable salt, solvate or prodrug thereof, is such that R is H, and R1b and R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from unsubstituted cyclopentyl, unsubstituted cyclohexyl and unsubstituted cycloheptyl, provided that: (i) when Ra is -NH2, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl or unsubstituted cyclohexyl; and (ii) when Ra is -NHCH3, -NHCH2CH3, -NHcyclopropyl, NHCH(CH3)2 or -NHCH2CH2CH3, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl.

[00101] In some embodiments, the compound of formula (Ie), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1b and R2c, together with the carbon atom to which they are attached, form a partially unsaturated heterocyclic group of 9 or 13 members, Petition 870250100355, dated 03 / 11 / 2025, p. 56 / 282 / 236, which is optionally replaced by oxo.

[00102] In some embodiments, the compound of formula (Ie), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R is H, and R1b and R2c, together with the carbon atom to which they are attached, form a partially unsaturated heterocyclic group of 9 or 13 members, which is optionally substituted by oxo.

[00103] In some embodiments, the compound of formula (Ie), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1b and R2c, together with the carbon atom to which they are attached, form a partially unsaturated 13-membered heterocyclic group, which is substituted by oxo.

[00104] In some embodiments, the compound of formula (Ie), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R is H, and R1b and R2c, together with the carbon atom to which they are attached, form a partially unsaturated 13-membered heterocyclic group, which is substituted by oxo. Compounds of the formula (If)

[00105] In some embodiments, the compound of formula (I) may be a compound of formula (If), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[00106] The groups R, Ra, R2 and R4b can be as defined for the general formula (I) above.

[00107] In some embodiments, the compound of formula (If), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R2dR4b, together with the carbon atoms to which they are attached, form Petition 870250100355, dated 03 / 11 / 2025, p. 57 / 282 / 236 a C3-C8 cycloalkyl.

[00108] In some embodiments, the compound of formula (Ib), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R2dR4b, together with the carbon atoms to which they are attached, form a cyclohexane. Compound of the formula (Ig)

[00109] In some embodiments, the compound of formula (I) may be a compound of formula (Ig), or a salt, a solvate or a pharmaceutically acceptable prodrug thereof.

[00110] The Ra, R1 and R3 groups can be as defined for the general formula (I) above.

[00111] In some embodiments, the compound of formula (Ig), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 and R3, together with the carbon atoms to which they are attached, form a C3-C8 cycloalkyl.

[00112] In some embodiments, the compound of formula (Ig), or the salt, solvate or pharmaceutically acceptable prodrug thereof, is such that R1 and R3, together with the carbon atoms to which they are attached, form a cyclohexane. Examples of compounds

[00113] In some forms, the compound may be Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, Petition 870250100355, dated 03 / 11 / 2025, p. 58 / 282 / 236 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 or 294, 295, 296 or 297 of Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00114] In some forms, the compound may be Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 223, 229, 233, 234, 235, 236, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258 or 294, 295, 296 or 297 of Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00115] In some forms, the compound may be Compound 4, 6, 12, 20, 46, 76, 77, 78, 80, 81, 84, 85, 86, 87, 98, 99, 100, 101, 105, 109, 120, 121, 125, 127, 128, 129, 132, 134, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 169, 170, 176, 177, 183, 186, 187, 188, 190, 191, 192, 195, 198, 223, 229, 235, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 294, 295 or 296 of Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00116] In some forms, the compound may be Compound 4, 6, 12, 20, 46, 76, 77, 78, 80, 84, 85, 86, 87, 98, 99, 100, 101, 120, 121, 127, Petition 870250100355, dated 03 / 11 / 2025, p. 59 / 282 / 236 128, 129, 134, 137, 139, 140, 142, 143, 144, 146, 147, 148, 149, 150, 151, 152, 153, 155, 156, 158, 159, 160, 161, 170, 176, 183, 186, 187, 188, 190, 192, 195, 198, 229, 235, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 252, 254, 255, 256, 257, 258, 294, 295 or 296 from Table 1 below, or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00117] In some forms, the compound may be Compound 4, 6, 12, 76, 78, 80, 84, 85, 98, 99, 120, 127, 128, 129, 137, 139, 140, 142, 143, 144, 146, 147, 148, 151, 152, 153, 155, 156, 158, 160, 161, 183, 186, 187, 198, 229, 235, 240, 241, 244, 245, 246, 247, 250, 252, 254, 255, 257, 258, 294 or 295 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00118] In some embodiments, the compound may be Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161, 198, 235, 245, 247, 252, 254, 255, 257 or 258 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00119] In some embodiments, the compound may be Compound 6, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 152, 153, 156, 158, 235, 245, 252, 254 or 255 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00120] In some embodiments, the compound may be Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158 or 235 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00121] In some embodiments, the compound may be Compound 4 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 12 from Table 1 below or may be any Petition 870250100355, dated 03 / 11 / 2025, p. 60 / 282 / 236 salt, solvate or pharmaceutically acceptable prodrug thereof. In some embodiments, the compound may be Compound 78 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 80 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 84 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 85 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 99 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 139 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 140 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 142 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 151 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 155 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 183 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 186 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. Petition 870250100355, dated 03 / 11 / 2025, p. 61 / 282 / 236 In some embodiments, the compound may be Compound 187 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 229 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 240 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 241 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 244 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 246 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 250 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 294 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 295 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 6 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 76 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 98 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 120 from Table 1. Petition 870250100355, dated 03 / 11 / 2025, p. 62 / 282 / 236 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 127 of Table 1 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 128 of Table 1 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 129 of Table 1 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 137 of Table 1 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 143 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 144 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 146 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 147 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 148 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 152 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 153 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 156 from Table 1 below, or it may be any pharmaceutically available salt, solvate, or prodrug. Petition 870250100355, dated 03 / 11 / 2025, p. 63 / 282 / 236 acceptable thereof. In some embodiments, the compound may be Compound 158 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 160 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 161 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 198 from Table 1 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, the compound may be Compound 235 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 245 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 247 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 252 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 254 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 255 from Table 1 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, the compound may be Compound 257 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, the compound may be Compound 258 from Table 1 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. Petition 870250100355, dated 03 / 11 / 2025, page 64 / 282 / 236 Table 1 Compound 4 Compound 6 O vQrV- Compound 12 O ÍZ ZZQiV Compound 16 OjCzí- Compound 20 Or^QrX Compound 24 CXxjZxX Compound 25 O^Oo- Compound 28 Compound 29 Compound 46 Compound 76 Compound 77 \ y- CXCxX Compound 78 z Compound 79 oXxX Compound 80 Petition 870250100355, dated 03 / 11 / 2025, page 65 / 282 / 236 Compound 100 Compound 101 Opt- Compound 105 O^OcZ- = Opt- Compound 106 Compound 109 Compound 113 Opt- \ V oog Compound 114 1 Compound 117 Compound 118 \ V GZG oot Compound 119 Compound 120 Compound 121 O x QX - G3O Compound 122 Compound 123 Compound 124 tot- pOt Compound 125 Compound 126 Compound 127 ^OOG Compound 128 Compound 129 Compound 131 Q > yp / J> OjG Compound 132 Compound 133 Compound 134 Petition 870250100355, 03 / 11 / 2025, pág. 66 / 282 / 236 Compound 135 X^X^- Compound 136 x Χχί- Compound 137 CXXX^ Compound 139 Compound 140 )000 Compound 142 Vqc^· Compound 143 Compound 144 ^jCX^· Compound 145 Compound 146 Compound 147 Compound 148 Compound 149 CXXX^ Compound 150 O^X“ Compound 151 Compound 152 Compound 153 CA-cX Compound 154 C0CX^ Compound 155 X0X>- Compound 156 \ j> 7^ 00 Compound 157 Compound 158 Compound 159 Compound 160 Petition 870250100355, 03 / 11 / 2025, pág. 67 / 282 / 236 F o-oX Compound 161 Compound 162 OhCX^ Compound 163 / Compound 164 Compound 165 Compound 169 θχΧ- Compound 170 Compound XX2n Compound 172 °8^NH2 \ XX Xx^nh2 SO oO Compound 176 Compound 177 Q, _r Compound 181 o^qX Compound 183 xQxCX^ Compound 186 Compound ί7-χθ 188 Compound 189 Compound 190 χΟ^· Compound 191 Petition 870250100355, dated 03 / 11 / 2025, p. 68 / 282 / 236 CX X ^ΧΧΧ Compound 192 Compound 194 oexí Compound 195 Compound 223 Compound 224 _χχί- χΧ^- hoX Compound 227 Compound wχ> 228 ó Compound 230 Compound 231 Compound 233 'V rXX^ <χχΧ Afv Qi (X Compound 234 Compound 235 Compound 236 V- O^X^- ^X^ Οχχ> o 9 Compound Οχχζ caX OA Compound 240 Compound 241 Compound 242 Petition 870250100355, dated 03 / 11 / 2025, p. 69 / 282 / 236 ΟΧχν Compound 243 Compound 244 Compound 245 Compound 246 Compound 247 Compound 248 Compound 249 Compound 250 Compound 251 Compound 252 c^oí“ ' J\ Compound 253 Compound 254 Compound 255 Compound 256 CMOl^ L / Compound 257 Compound 258 Compound 259 ΓΎυ- c Compound 260 Petition 870250100355, dated 03 / 11 / 2025, p. 70 / 282 / 236 a compound C for a use as defined herein, which is a compound of formula (I') (I') 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, wherein: Raé -NH2, -NH-OH, -OH or -NHRb; Petition 870250100355, dated 03 / 11 / 2025, p. 71 / 282 / 236 Rbé C1-C6 alkyl, C3-C6 cycloalkyl or 3-membered heterocycloalkyl represents one of the following residues Ao to Aó to 6 members, wherein C1-C6 alkyl is optionally substituted by 1 to 3 halogens; or given that: R is H or C1-C6 alkyl; R' is H, C1-C6 alkyl or phenyl; R1 is -CN, C6-C10aryl, C1-C6alkyl, C2-C6alkenyl, C2C6alkynyl, F, Cl, Br, I, -N(R)2, 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 C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents and C6-C10aryl is optionally substituted by 1 to 3 R8 substituents; R2 is C6-C10aryl, unsubstituted C2-C6alkyl, C1-C6alkyl substituted by 1 to 3 substituents R7, C2-C6alkenyl, C2-C6alkynyl, F, Cl, Br, I, -N(R)2, 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, where C6-C10aryl is optionally substituted by 1 to 3 substituents R8, with the condition that when Ra is -NH2, - represents the residue Ao, R is H, and R1 is -CN, then R2 is different from each R is independently C1-C4alkyl; each R5 is independently C1-C6 alkyl, and each C1-C6 alkyl is optionally replaced by 1 to 3 R9 substituents; each R6 is independently C3-C6 cycloalkyl, Petition 870250100355, dated 03 / 11 / 2025, p. 72 / 282 / 236 4- to 6-membered heterocycloalkyl or C6-Cioaryl, and the 4- to 6-membered heterocycloalkyl is optionally replaced by -OH; Each R7 is independently -OH, -C(O)R11, C3C5cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6alkyl), -OR20, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2 or 4-oxo-1,4-dihydro-1-pyridinyl, wherein each C3C5cycloalkyl is optionally substituted by 1 to 3 substituents; R12, each 5- or 6-membered heteroaryl is optionally substituted by 1 to 3 substituents. R13, and each 4- to 6-membered heterocycloalkyl group is optionally replaced by C1-C4 alkyl or oxo; each R8 is independently a 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 R9 is independently -OH, -C(O)R15, C3C6cycloalkyl, -CN, C6-Cwaryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(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 C1C4alkyl, and each -OC1-C6alkyl is optionally substituted by -OC1C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, a 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or a 4- to 6-membered heterocycloalkyl substituted with -OH; each R20 is independently a 5- to 10-membered C2-C6 alkyl or heteroaryl, and each C2-C6 alkyl is optionally substituted by 1 to 3 R14 substituents; Petition 870250100355, dated 03 / 11 / 2025, page 73 / 282 / 236 each R12 is independently Ci-C4alkyl, -SCi-C4alkyl, Ph, -OC1-C4alkyl, -SPh or -S(O)2Ph where each C1-C4alkyl is optionally replaced by -OH; each R13 is independently halogen, C1-C4 alkyl, C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2, -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-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1C6 alkyl, -NH(C1-C4 alkyl) and -N(C1-C4 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-Cwaryl, 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-Cwaryl and heteroaryl of 5 to 10 members are optionally substituted by 1 to 3 R10 substituents; 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 replaced by 1 to 3 halogens; R2a is unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted with 1 to 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl, C3-C8 cycloalkyl or C6-Cwaryl, wherein C3-C8 cycloalkyl is optionally substituted with 1 to 3 R9 substituents, and C6-Cwaryl is optionally substituted with 1 to 3 R22 substituents; Each R22 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; Petition 870250100355, dated 03 / 11 / 2025, p. 74 / 282 / 236 R1 and R2 are independently -CN, C6-Cioaryl, C1-C6 alkyl, C3-C8 cycloalkyl, -C(O)NH2, -C(O)NHR5 or -C(O)C1-C6 alkyl, wherein each C1-C6 alkyl is optionally substituted by 1 to 3 substituents R16 and each C6-Cioaryl is optionally substituted by 1 to 3 substituents R17; each R16 is independently -OH, -C(O)NH2, -C(O)NH(C1-C4 alkyl), C3-C6 cycloalkyl, -CN, C6-C1-C6 cycloalkyl, halogen, -C(O)OH, 5- to 10-membered heteroaryl, -NH(C(O)C1-C6 alkyl), 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C6 alkyl) or -C1-C4 alkyl(C1-C4 alkyl), wherein each C3-C6 cycloalkyl is optionally substituted by 1 to 3 substituents R18, each 5- to 10-membered heteroaryl is optionally substituted by 1 to 3 substituents R2i and each 4- to 6-membered heterocycloalkyl is optionally substituted by C1-C4 alkyl; each R17 is independently a halogen, C1-C6 alkyl, -C1-C6 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; R4 is a C1-C6 alkyl or C3-C8 cycloalkyl, and each C1-C6 alkyl and C3-C8 cycloalkyl are optionally replaced by 3 Ri9 substituents; each R19 is independently halogen, -OH, -OCiC4alkyl, -SCi-C4alkyl, -NH2, -NH(Ci-C4alkyl) or -N(Ci-C4alkyl)2; R1b and R2c, together with the carbon atom to which they are attached, form a cyclic structure selected from a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 3 substituents R9, and the 4- to 14-membered heterocycloalkyl Petition 870250100355, dated 03 / 11 / 2025, p. 75 / 282 / 236 members and the partially unsaturated heterocyclic group of 8 to 14 members are optionally replaced by oxo; with the condition that when Ra is NH2, ZZ represents the residue A4, and R is H, then R1b and R2c form a cyclic structure other than 1,3-dioxolane; 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.

[00123] In some embodiments, compound C may be a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt, solvate, or prodrug thereof. Therefore, in some embodiments, compound C may be a compound of formula (Ia) to (Ig), as defined herein, or any pharmaceutically acceptable salt, solvate, or prodrug thereof. In further embodiments, compound C may be a compound from Table 2 below, or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.

[00124] In other forms, compound C may be Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, Petition 870250100355, dated 03 / 11 / 2025, p. 76 / 282 / 236 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261 or 294, 295, 296 or 297 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00125] In some embodiments, compound C may be Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 of Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00126] In some embodiments, compound C may be Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 207, 208, 209, 210, 211, 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate or prodrug. Petition 870250100355, dated 03 / 11 / 2025, p. 77 / 282 / 236 of the same.

[00127] In some embodiments, compound C may be Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 207, 208, 209, 210, 211, 212, 213, 217, 219, 220, 223, 229, 233, 234, 236, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 294, 295, 296 or 297 of Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00128] In some embodiments, compound C may be Compound 4, 6, 12, 20, 46, 76, 77, 78, 80, 81, 84, 85, 86, 87, 98, 99, 100, 101, 105, 109, 120, 121, 125, 127, 128, 129, 132, 134, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 169, 170, 176, 177, 183, 186, 187, 188, 190, 191, 192, 195, 198, 209, 210, 211, 212, 213, 217, 219, 220, 223, 229, 235, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 294, 295 or 296 of Table 2 below or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00129] In some embodiments, compound C may be Compound 4, 6, 12, 20, 46, 76, 77, 78, 80, 84, 85, 86, 87, 98, 99, 100, 101, 120, 121, 127, 128, 129, 134, 137, 139, 140, 142, 143, 144, 146, 147, 148, 149, 150, 151, 152, 153, 155, 156, 158, 159, 160, 161, 170, 176, 183, 186, 187, 188, 190, 192, 195, 198, 212, 213, 217, 219, 220, 229, 235, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 252, 254, 255, 256, 257, 258, 294, 295 or 296 from Table 2 below, or it may be any salt, solvate or prodrug. Petition 870250100355, dated 03 / 11 / 2025, p. 78 / 282 / 236 pharmaceutically acceptable of the same.

[00130] In some embodiments, compound C may be Compound 4, 6, 12, 76, 78, 80, 84, 85, 98, 99, 120, 127, 128, 129, 137, 139, 140, 142, 143, 144, 146, 147, 148, 151, 152, 153, 155, 156, 158, 160, 161, 183, 186, 187, 198, 217, 219, 220, 229, 235, 240, 241, 244, 245, 246, 247, 250, 252, 254, 255, 257, 258, 294 or 295 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00131] In some embodiments, compound C may be Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161, 198, 220, 235, 245, 247, 252, 254, 255, 257 or 258 from Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00132] In some embodiments, compound C may be Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220 or 235 from Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof.

[00133] In some embodiments, compound C may be Compound 4 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 6 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 12 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 76 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 78 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 80 from Table 2 Petition 870250100355, dated 03 / 11 / 2025, p. 79 / 282 / 236 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 84 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 85 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 98 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 99 from Table 2 below, or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 120 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 127 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 128 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 129 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 137 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 139 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 140 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 142 from Table 2 below or it may be any pharmaceutically available salt, solvate, or prodrug. Petition 870250100355, dated 03 / 11 / 2025, p. 80 / 282 / 236 acceptable thereof. In some embodiments, compound C may be Compound 143 from Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 144 from Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 146 from Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 147 from Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 148 from Table 2 below or it may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 151 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 152 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 153 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 155 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 156 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 158 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 160 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be... Petition 870250100355, dated 03 / 11 / 2025, p. 81 / 282 / 236 Compound 161 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 183 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 186 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 187 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 198 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 217 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 218 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 219 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 220 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 229 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 235 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 240 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 241 in Table 2 below or it may be any salt, solvate or proton. Petition 870250100355, dated 03 / 11 / 2025, p. 82 / 282 / 236 pharmaceutically acceptable drug thereof. In some embodiments, compound C may be Compound 244 of Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 245 of Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 246 of Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 247 of Table 2 below or may be any pharmaceutically acceptable salt, solvate or prodrug thereof. In some embodiments, compound C may be Compound 250 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 252 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 254 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 255 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 257 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 258 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. In some embodiments, compound C may be Compound 294 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof.In some embodiments, compound C may be Compound 295 from Table 2 below or may be any pharmaceutically acceptable salt, solvate, or prodrug thereof. Petition 870250100355, dated 03 / 11 / 2025, page 83 / 282 / 236 Table 2 Compound 4 Compound 6 O y Compound 12 O y χχχ>- Compound 16 0^0^ Compound 20 CX^Qr^- Compound 24 CXqQr^- Compound 25 CUOl^“ Compound 28 Compound 29 Compound 46 ^CX^- Compound 76 Compound 77 \y- CXCiX Compound 78 z ~CXOc^- Compound 79 CXjOcí- Compound 80 Compound 81 ^CHOc^ Compound 82 Compound 83 QXQü^- Compound 84 OXX^- Compound 85 Compound 86 Compound 87 XXOrl Compound 88 Compound 89 Compound 90 Compound 98 o^oí· / Compound 99 Petition 870250100355, dated 03 / 11 / 2025, page 84 / 282 / 236 Compound 100 χΖΧ^- Compound 101 ckoZ Compound 105 ckoZ Compound 106 Compound 109 Compound 113 \ V χγίΧ- Compound 114 1 Compound 117 Compound 118 \ V χχχΧ Compound 119 Compound 120 Compound 121 - OX XXX- Q ^X χχχχ Compound 122 Compound 123 Compound 124 Compound 125 XXct- Compound 126 Compound 127 ZX, X ί^χχί- ^<χχν- Compound 128 Compound 129 Compound 131 ^4>^r νχχ>- ^χχχ>- Compound 132 Compound 133 Compound 134 Petition 870250100355, 03 / 11 / 2025, pág. 85 / 282 / 236 Compound 135 Compound 136 x Compound 137 Compound 139 ooX Compound 140 o Compound 142 Compound 143 Compound 144 Compound 145 Compound 146 Compound 147 Compound 148 o^cx^· Compound 149 Compound 150 O^Cc^ Compound 151 Compound 152 ^02x^ Compound 153 JOãX Compound 154 C0CX^ Compound 155 X0x^ Compound 156 \ j> JC χχχν Compound 157 Compound 158 o^xx^- Compound 159 Compound 160 Petition 870250100355, 03 / 11 / 2025, pág. 86 / 282 / 236 Ϋ Compound 161 Compound 162 OhCx^ Compound 163 / Compound 164 oxx^ Compound 165 0^3^- Compound 166 0^3^- P Compound 167 Compound 169 Compound 170 0^3^ Compound 171 oVNh \ ]T;^nh2 ^ / y^ / ^s oQ / o Compound 172 °8^NH2 \ Vj jT / ^nh2 SO oO Compound 176 Compound 177 Q, y Compound 181 oyoZ - Compound 183 Compound 186 ChCX^ Compound 187 Compound 188 Compound 189 Compound 190 Compound 191 Petition 870250100355, 03 / 11 / 2025, pág. 87 / 282 / 236 X Compound 192 Compound 194 coí- Compound 195 θχχΡ Compound 198 θχχΧ- Compound 200 Compound 203 Compound 204 Compound 205 χχΐ Compound 206 P yOZ Compound 207 P Compound 208 P \XX^ Compound 209 γθ^ Compound 210 iQry- Compound 211 P Compound 212 Compound 213 yXp Compound 214 γΧ)Ρ Compound 215 Compound 216 Compound 217 Compound 218 Q\X^ Compound 219 cP^ Compound 220 Compound 223 Petition 870250100355, 03 / 11 / 2025, pág. 88 / 282 / 236 O Compound 224 Compound 227 Compound 228 v- οχΧ XQTy- CO ó Compound 231 Compound 229 Compound 230 V- / xCO CkÇO- ΓΎν O' Compound 234 Compound 233 Compound 235 o Compound 236 Compound 237 Compound 238 000¼ V o L'> Compound 239 Compound 240 Compound 241 θχχν O^Qrv Compound 242 Compound 243 Compound 244 Petition 870250100355, 03 / 11 / 2025, pág. 89 / 282 / 236 Compound 245 Compound 246 Compound 247 Compound 248 Compound 249 Compound 250 Compound 251 Compound 252 - Ί\ Compound 253 Compound 254 Compound 255 Compound 256 Compound 257 jyry Compound 258 Compound 259 XX^- Compound 260 XA χΧ Compound 261 o Compound 294 Petition 870250100355, 03 / 11 / 2025, pág. 90 / 282 / 236

[00134] The substituted thiophene fused 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), (Ia) to (Ig), the compound of formula (I') (compound C), or the compounds of Table 1 or Table 2 may be formulated into a pharmaceutical composition comprising an effective amount of one or more of the compounds, or their pharmaceutically acceptable salts, solvates, or prodrugs, and a pharmaceutically acceptable carrier, diluent, or excipient.

[00135] In certain embodiments, the present description thus provides a method for treating or preventing a disorder for which an ASIC inhibitor is indicated comprising administering to a patient or an individual identified as needing the same at least one compound of formula (I), (Ia) to (Ig), the compounds of formula (I') (compound C) or the compounds of Table 1 or Table 2, as defined herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[00136] Identifying those patients who need treatment Petition 870250100355, dated 03 / 11 / 2025, pp. 91 / 282 / 236, regarding the disorders described above, is well within the capacity and knowledge of one skilled in the art. Some of the methods for identifying patients at risk of developing the above disorders that 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 these candidate patients by using, for example, clinical tests, physical examination, and medical / family history.

[00137] 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.

[00138] 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 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, Petition 870250100355, dated 03 / 11 / 2025, pp. 92 / 282 / 236 to prevent or delay its recurrence.

[00139] 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.

[00140] 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, buffering 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.

[00141] As used herein, the term ASIC inhibitor denotes a compound that inhibits acid-sensitive ion channels, such as acid-sensitive ion channel 1a (ASIC1a) or acid-sensitive ion channel 1b (ASIC1b).

[00142] In some embodiments, the disorders or conditions that can be treated using the compounds of formula (I), (Ia) to (Ig), the compound of formula (I') (compound C), or the compounds of Table 1 or Table 2 described herein, or their pharmaceutically acceptable salts, solvates, or prodrugs, may include pain, arthritis, stroke. Petition 870250100355, dated 03 / 11 / 2025, page 93 / 282 / 236 cerebral, epileptic disorder, anxiety, post-traumatic stress disorder (PTSD), depression, multiple sclerosis, Alzheimer's disease, gastroesophageal reflux disease, cancer, migraine, cough and acute lung injury.

[00143] In some embodiments, the compounds of formula (I), (Ia) to (Ig), the compound of formula (I') (compound C) or the compounds of Table 1 or Table 2, or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising the same, may be used for the treatment or prevention of a disorder, the disorder being 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.

[00144] 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.

[00145] 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, osteoarthritis pain of the spine, osteoarthritis pain of the shoulder, osteoarthritis pain of the hand, osteoarthritis pain of the finger, osteoarthritis pain of the thumb, osteoarthritis pain of the foot, or osteoarthritis pain of the toe. In certain modalities, pain may include inflammatory rheumatoid arthritis pain or neuropathic rheumatoid arthritis pain. In certain modalities, pain may include Petition 870250100355, dated 03 / 11 / 2025, p. 94 / 282 / 236 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.

[00146] 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.

[00147] 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.

[00148] 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.

[00149] In certain modalities, pain may include postoperative pain. 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 Petition 870250100355, dated 03 / 11 / 2025, page 95 / 282 / 236 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.

[00150] In certain modalities, pain may include dysmenorrhea pain, episiotomy pain, endometriosis pain, or postpartum pain, including postpartum cramping pain.

[00151] 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.

[00152] 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.

[00153] 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, spinal cord injury pain, spinal cord compression pain, radicular pain, sciatica pain, spinal stenosis pain, cervical spine injury pain, brain injury pain, or post-stroke pain.

[00154] In some modalities, pain may include neuropathic pain. In certain modalities, pain may include neuropathic pain. Petition 870250100355, dated 03 / 11 / 2025, page 96 / 282 / 236 peripheral, 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, the pain may include diabetic neuropathy pain. In some modalities, the pain may include diabetic peripheral neuropathy pain, diabetic polyneuropathy pain, diabetic proximal neuropathy pain, or diabetic mononeuropathy pain. In certain modalities, the pain may include autoimmune disease neuropathy pain. In some modalities, the pain may include neuropathic pain from Sjögren's syndrome, neuropathic pain from Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy pain, or vasculitic neuropathy pain. In some modalities, the pain may include neuropathic pain from multiple sclerosis.In certain modalities, pain may include carpal tunnel syndrome pain. 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 Lyme disease neuropathy pain, Epstein-Barr virus neuropathy pain, hepatitis B virus neuropathy pain, hepatitis C virus neuropathy pain, leprosy neuropathy pain, diphtheria neuropathy pain, or human immunodeficiency virus (HIV) neuropathy pain, including HIV distal symmetrical polyneuropathy pain. In certain modalities, pain may include hereditary neuropathy pain. In some modalities, pain may include Charcot-Marie-Tooth disease neuropathy pain or hereditary neuropathy with pressure palsies (HNPP).In certain modalities, the pain may include neuropathic pain caused by a malignant tumor, neuropathic pain caused by a benign tumor, or paraneoplastic neuropathic pain. In some modalities, the pain may include myeloma neuropathic pain, lymphoma neuropathic pain, or neuropathic pain. Petition 870250100355, dated 03 / 11 / 2025, p. 97 / 282 / 236 amyloid. In certain modalities, pain may include neuropathy pain from liver disease, uremic neuropathy pain, neuropathic pain from connective tissue disorders, neuropathy pain from hypothyroidism, neuropathy pain from alcohol use, or neuropathy pain from vitamin deficiency. In some modalities, pain may include neuropathy pain from vitamin B deficiency, including neuropathy pain from vitamin B1, niacin, vitamin B6, or vitamin B12 deficiency, or neuropathy pain from vitamin E deficiency. In certain modalities, pain may include neuropathy pain from exposure to toxic substances, including neuropathy pain after lead exposure or neuropathy pain after mercury exposure. In certain modalities, pain may include neuropathy pain induced by antiretroviral therapy or neuropathic pain induced by neurotoxic drugs.In certain modalities, pain may include chemotherapy-induced neuropathy pain, including neuropathic pain induced by platinum-based antineoplastic drugs or chemotherapy-induced peripheral neuropathy (CIPN), radiation therapy-induced pain, including radiation therapy-induced neuropathy pain, cancer-targeted therapy-induced neuropathy pain, or immunotherapy-induced neuropathy pain. In some modalities, this pain may include central neuropathic pain. In certain modalities, pain may include post-stroke central pain, spinal cord injury-related central neuropathic pain, brain injury-related central neuropathic pain, or multiple sclerosis-related central neuropathic pain.

[00155] In certain modalities, pain may include cancer pain. 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 postmastectomy pain syndrome (PMPS). Petition 870250100355, dated 03 / 11 / 2025, page 98 / 282 / 236

[00156] In certain modalities, pain may include post-amputation pain. In some modalities, pain may include phantom pain, phantom limb pain, or residual limb pain.

[00157] 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.

[00158] 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.

[00159] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of arthritis, including rheumatoid arthritis (Xu, Y. et al., 2021).

[00160] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of stroke (Chassagnon, Petition 870250100355, dated 03 / 11 / 2025, p. 99 / 282 / 236 IR et al., 2017; Qi, X. et al., 2022).

[00161] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of an epileptic disorder (Cheng, Y. et al., 2021).

[00162] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, 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).

[00163] In some embodiments, the compounds described herein 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).

[00164] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of depression (Coryell, MW et al., 2009; Mango, D. et al., 2019).

[00165] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of multiple sclerosis (Vergo S. et al., 2011; Wei W. et al., 2021).

[00166] In some embodiments, the compounds described herein or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising them, may be used Petition 870250100355, dated 03 / 11 / 2025, p. 100 / 282 / 236 for the treatment or prevention of Alzheimer's disease (Mango, D. et al., 2023).

[00167] In some embodiments, the compounds described herein or their salts, solvates or pharmaceutically acceptable prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of gastroesophageal reflux disease (Han, X. et al., 2022).

[00168] In some embodiments, the compounds described herein 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).

[00169] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of a migraine (Holland, PR et al., 2012; Karsan, N. et al., 2018).

[00170] In some embodiments, the compounds described herein or their pharmaceutically acceptable salts, solvates or prodrugs, or pharmaceutical compositions comprising them, may be used for the treatment or prevention of cough (Reznikov, LR et al., 2016).

[00171] In some embodiments, the compounds described herein or their salts, solvates or pharmaceutically acceptable prodrugs, or those Petition 870250100355, dated 03 / 11 / 2025, p. 101 / 282 / 236 pharmaceutical compositions comprising the same, may be used for the treatment or prevention of acute lung injury (Liu, Y. et al., 2023).

[00172] 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 itching (Papalampropoulou-Tsiridou, M. et al., 2022; Jung, M. et al., 2023).

[00173] 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.

[00174] 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.

[00175] 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 inert diluents commonly used in the art, such as 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, alcohol Petition 870250100355, dated 03 / 11 / 2025, p. 102 / 282 / 236 tetrahydrofurfuryl, 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.

[00176] 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.

[00177] 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.

[00178] In order to prolong the effect of a supplied compound, 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 solubility in water. 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 form of Petition 870250100355, dated 03 / 11 / 2025, page 103 / 282 / 236. Parenterally administered compound release 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 polylactide-polyglycolide. Depending on the compound-to-polymer ratio and the nature of the specific polymer employed, the compound release rate can be controlled.

[00179] 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.

[00180] 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 into the rectum or vaginal cavity and release the active compound.

[00181] 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 and silicic acid, b) binders, such as, for example, 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, for example, cetyl alcohol and glycerol monostearate, h) Petition 870250100355, dated 03 / 11 / 2025, page 104 / 282 / 236 absorbents, such as kaolin and bentonite clay, and) 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.

[00182] 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 filled gelatin capsules using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like.

[00183] The supplied compounds may also be in microencapsulated form 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. These dosage forms may also comprise, as is common practice, substances Petition 870250100355, dated 03 / 11 / 2025, page 105 / 282 100 / 236 additional ingredients other than 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 include 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.

[00184] 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. These dosage forms may be made by dissolving or dispensing the compound in the appropriate medium. Absorption enhancers may 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 polymer matrix.

[00185] The pharmaceutically acceptable compositions provided herein may also be administered by nasal spray or inhalation. These compositions are prepared according to well-known techniques in the art of pharmaceutical formulation and may be prepared as solutions in saline solution, employing benzyl alcohol or other preservatives. Petition 870250100355, dated 03 / 11 / 2025, page 106 / 282 101 / 236 suitable, absorption enhancers to increase bioavailability, fluorocarbons and / or other conventional solubilizing or dispersing agents.

[00186] 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.

[00187] 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.

[00188] 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, timing of administration, excretion rate, drug combinations, the judgment 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.

[00189] The compounds or compositions described herein may be administered using any amount and any route of administration effective in treating or reducing 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, Petition 870250100355, dated 03 / 11 / 2025, page 107 / 282 102 / 236 severity of infection, specific agent, its route 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 this 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.

[00190] The pharmaceutically acceptable compositions of this disclosure may be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by means of powders, ointments or drops), buccally, as an oral or nasal spray, or similarly, depending on the severity of the infection to be treated. In certain embodiments, the compounds provided may be administered orally or parenterally at dosage levels of about 0.01 mg / kg to about 50 mg / kg and preferably from 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.

[00191] 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 Petition 870250100355, dated 03 / 11 / 2025, page 108 / 282 103 / 236 administration, or both, may be reduced, depending on the symptoms, to a level where the improved condition is maintained. When the symptoms are relieved to the desired level, treatment should cease. The individual, however, may need long-term intermittent treatment in case of recurrence of the disorder's symptoms.

[00192] 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 patient's age, body weight, general health, sex, and diet; 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.

[00193] 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 more commonly from 0.1 to 25 mg / kg of body weight. Single-dose compositions may contain these amounts or submultiples thereof to make up the daily dose. In one embodiment, the treatment regimens according to the description herein comprise administering to a patient requiring such treatment from about 10 mg to about 1000 mg of the compound(s) described herein per day in single or multiple doses. Compound testing methods

[00194] In some modalities, compounds can be tested for their effectiveness in treating inflammatory or neuropathic pain using an inflammatory or neuropathic pain model. The test can be performed Petition 870250100355, dated 03 / 11 / 2025, page 109 / 282 104 / 236 as detailed below. Animals

[00195] The animals to be used in the inflammatory or neuropathic pain model may be male Sprague-Dawley rats (~250 g, Charles River, St. Constant, Canada). Rats are group-housed on autoclaved corn cob bedding in individual HEPA-ventilated cages (Innocage® IVC, Innovive, San Diego, CA, USA) in a temperature-controlled environment (22±1.5 °C, 30 to 80% relative humidity, 12 h light / dark cycle) and receive irradiated feed (Harlan Teklad, Montreal, Canada) and filtered water ad libitum. Rats are acclimated to the animal facility (adMare BioInnovations, Montreal, Canada) for at least 5 days prior to use. Studies may be conducted under a protocol approved by the NEOMED Animal Care Committee and run during the light-dependent phase of the cycle. The number of rats to be used is the minimum necessary to achieve a statistical power of 80% to detect a change of 40%. Efficacy in an inflammatory pain model: Inflammation and carrageenan test

[00196] Lambda carrageenan (Sigma-Aldrich) is dissolved in sterile 0.9% saline solution at a concentration of 1% w / v. Rats are placed in a Plexiglass chamber with 2% isoflurane at a flow rate of 0.8 to 1 L / h with oxygen for approximately 60 to 90 seconds, until a mild average depth of anesthesia is achieved. One hundred microliters of carrageenan solution are injected into the subcutaneous space on the dorsal aspect of the left hind paw, in the center of the four pads.

[00197] The compound to be tested or the control (e.g., naproxen) is dissolved in 40% polyethylene glycol (PEG) 400 (in 0.9% sterile saline solution) and administered orally 2 h after carrageenan inoculation, once inflammation is established, at a volume of 5 mL / kg and can be tested 30 min later.

[00198] Thermal hyperalgesia can be assessed by the plantar test of Petition 870250100355, dated 03 / 11 / 2025, page 110 / 282 105 / 236 Hargreaves. Animals are placed on a glass surface, and a heat source is focused on the plantar surface of the affected paw. The time from the onset of heat until the animal withdraws its paw is recorded and defined as paw withdrawal latency (PWL). Mechanical allodynia is assessed using the dynamic Von Frey test. Animals are placed on a wire mesh surface, and the Von Frey filament is applied to the plantar surface of the affected paw with increasing force. The force (g) required for the animal to withdraw its paw is recorded. Statistical significance is determined using one-way ANOVA on raw data followed by a posthoc Holm-Sidak t-test. The level of statistical significance is set to p < 0.05. The raw data are normalized using the following formula: % efficacy = (Response(dose) Response(vehicle)) / (Response^m treatment) - Response(vehicle)) X 100. The data can be expressed as mean ± standard deviation of the mean. Efficacy in a neuropathic pain model: Chronic constriction injury (CCI) model of neuropathic pain and testing.

[00199] CCI is performed under anesthesia. A blunt dissection of approximately 3 cm in length is made in the skin overlying the area between the gluteus and biceps femoris muscles, and the common sciatic nerve of the hind leg is exposed at the mid-thigh level. Approximately 7 mm of the nerve are released proximal to the sciatic trifurcation, and four or three loose ligatures (spaced approximately 1 mm apart) of 4-0 chromic gut (or 4-0 silk) sutures are placed around the sciatic nerve until a brief contraction is observed. The wound is closed with sutures in the muscle and staples in the skin. The animal is then allowed to recover from surgery for 24 h before the start of the hypersensitivity pain test.

[00200] The compound to be tested is dissolved in 40% polyethylene glycol (PEG) 400 (in sterile 0.9% saline solution) and administered orally at a volume of 5 mL / kg and tested 30 minutes later.

[00201] Thermal hyperalgesia is assessed by the plantar test of Petition 870250100355, dated 03 / 11 / 2025, page 111 / 282 106 / 236 Hargreaves. The animals are placed on a glass surface, and a heat source is focused on the plantar surface of the affected paw. The time from the onset of heat until the animal withdraws its paw is recorded and defined as paw withdrawal latency (PWL). Mechanical allodynia is assessed by the dynamic Von Frey test. The animals are placed on a wire mesh surface, and the Von Frey filament is applied to the plantar surface of the affected paw with increasing force. The force (g) required for the animal to withdraw its paw is recorded.

[00202] Statistical significance is determined using one-way ANOVA on raw data followed by a post-hoc Holm-Sidak t-test. The level of statistical significance is set to p < 0.05. Raw data are normalized using the following formula: % efficacy = (Response(dose) Response(vehicle)) / (Response^treatment) - Response(vehicle)) X 100. Data can be expressed as mean ± standard deviation of the mean. Examples General methods Preparation of compounds

[00203] 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

[00204] Chromatographic separations were performed on: - Teledyne ISCO CombiFlash flash chromatography systems, using pre-packed SiO2 or C18 columns. Petition 870250100355, dated 03 / 11 / 2025, page 112 / 282 107 / 236 - Teledyne ISCO ACCQPrep high-pressure preparative liquid chromatography system; Column: Gemini 5 µm C18 110 Å, 150 x 30 mm - Biotage Isolera flash chromatography systems, using pre-packed SiO2 or C18 columns. - HPLC Semi-Prep Waters Mass Trigger; Column: Gemini 5 um NX-C18 110 Â, 100 x 30 mm. Analytical methods

[00205] 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. - Agilent HPLC-MS; Column: Kinetex EVO C18 100 Â 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. - Agilent UPLC-MS; Column: Kinetex EVO C18 100 Â 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.

[00206] 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 Angstrom Petition 870250100355, dated 03 / 11 / 2025, page 113 / 282 108 / 236 Ac Acetyl Bn Benzyl Boc ter-Butoxycarbonyl bs Broad singlet Bu Butyl Calcified d Doublet DAST Diethylaminosulfur trifluoride dd Doublet of doublets dt Doublet of triplets DCM Dichloromethane DDQ 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone DIBALH 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 1,1'-Bis(diphenylphosphino)ferrocene EA Ethyl acetate ee Enantiomeric excess Et Ethyl EtOH Ethanol eq Equivalents g Grams HATU Azabenzotriazole hexafluorophosphate tetramethyluronium Hz Hertz Petition 870250100355, dated 03 / 11 / 2025, page 114 / 282 109 / 236 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 mCPBA Meta-chloroperoxybenzoic acid; Me Methyl MeOH Methanol mg Milligram MHz Megahertz min Minutes mL Milliliter mm Millimeter mmol Millimol mol Mol MS Mass spectrography N Normal NBS N-bromosuccinimide PCC Pyridinium chlorochromate Pd(dppf)Cl2 Bis(diphenylphosphino)ferrocene]dichloropalladium(II) pH Potential of hydrogen Ph Phenyl PPh3 Triphenylphosphine ppm Parts per million PyBOP Benzotriazole-1-hexafluorophosphate Petition 870250100355, dated 03 / 11 / 2025, page 115 / 282 110 / 236 yloxytripyrolidinephosphonium q RT Quadruplet Room temperature rt Retention time NMR Nuclear magnetic resonance s Singlet sat Saturated SFC Supercritical fluid chromatography sxt sextuplet t er t Triplet tt Triplet of triplet t-But tert-Butyl TMS Trimethylsilyl TFA Trifluoroacetic acid THF Tetrahydrofuran Ts Tosyl pL pmol v / v Microliter Micromol Volume / volume ° Degree % Percentage Example 1 2-Amino-6-cyano-6-isopropyl-4,5,6,7-tetrahydrobenzorb1thiophene-3carboxamide (4) Scheme 1 Petition 870250100355, dated 03 / 11 / 2025, page 116 / 282 111 / 236 Step 1. 8-Isopropyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (2)

[00207] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1) (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 left in the open air until it slowly reached 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 title compound 2 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 (3)

[00208] To a solution of 2 (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 NaHCO3 solution and concentrated to remove the organic solvent. The residue was extracted with EA, and the organic layer was dried with Na2SU4, filtered, and concentrated to dryness to yield the title compound 3 (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 (4) Petition 870250100355, dated 03 / 11 / 2025, p. 117 / 282 112 / 236

[00209] To a solution of 3 (445 mg, 2.69 mmol) and cyanoacetamide (206 mg, 2.45 mmol) in EtOH (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 title compound 4 (477 mg, 74% yield) as a white solid.

[00210] 1H NMR: 400 MHz, CDCb, δ (ppm): 6.18 (bs, 2H), 5.38 (bs, 2H), 2.99-2.84 (m, 3H), 2.63 (dt, J = 16.0, 2.1 Hz, 1H), 2.27 (m, 1H), 1.89-1.78 (m, 1H), 1.75-1.63 (m, 1H), 1.18 (d, J = 6.6 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H). LC-MS: rt = 2.60 min, MS: 263.1 (calculated), 264.1 (M+H+, found). Example 2 2-Amino-6-cyano-6-isobutyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide (6) Scheme 2 Step 1. 1-Isobutyl-4-oxocyclohexane-1-carbonitrile (5)

[00211] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, Scheme 1) (221 μL, 1.50 mmol) 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 partitioned between hexane and water. The layers were separated, and the aqueous layer was extracted with EA. The combined organic layers were dried with N2SO4, filtered, and concentrated. The dry residue was dissolved in acetone (19.7 mL), and 2 N HCl (5.0 mL, 10.0 mmol) was... Petition 870250100355, dated 03 / 11 / 2025, page 118 / 282 113 / 236 added slowly. The mixture was stirred for 16 hours, then neutralized by slowly adding saturated NaHCO3 solution and concentrated to remove the organic solvent. The residual mixture was extracted with EA, and the organic layer was dried with Na2SO4, filtered, and concentrated to dryness to yield compound 5 (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 (6)

[00212] To a solution of 5 (141 mg, 0.784 mmol) and cyanoacetamide (59.9 mg, 0.713 mmol) in EtOH (713 gL), morpholine (67.6 gL, 0.784 mmol) and sulfur (25.2 mg, 98.3 gmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, allowed to cool naturally 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 6 as a beige solid (115 mg, 58% yield).

[00213] 1H NMR: 400 MHz, CD3OD, δ (ppm): 2.93 (d, J = 16.27 Hz, 1H), 2.85-2.80 (m, 2H), 2.63 (d, J = 16.11 Hz, 1H), 2.19 (d, J = 13.36 Hz, 1H), 2.00-1.92 (m, 1H), 1.76 (ddd, J = 13.43, 10.03, 6.18 Hz, 1H), 1.64 (d, J = 6.33 Hz, 2H), 1.09 (d, J = 6.66 Hz, 3H), 1.05 (d, J = 6.63 Hz, 3H). LC-MS: rt = 1.49 min, MS: 277.1 (calculated), 277.9 (M+H+, found). Example 3 2-Amino-6-cyano-6-(2-(pyridin-3-yl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (9) Scheme 3 Petition 870250100355, dated 03 / 11 / 2025, p. 119 / 282 114 / 236 Step 1. 8-(2-(Pyridin-3-yl)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (7)

[00214] A solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, Scheme 1) (126 mg, 0.752 mmol) in anhydrous THF (1 mL) was added at 78 °C to a solution of LDA (1.65 mL, 1 M in THF / hexane, 1.65 mmol) in anhydrous THF (3 mL). The reaction mixture was stirred at -78 °C for 45 minutes, then 3-(2-bromoethyl)pyridine hydrobromide (240 mg, 0.902 mmol) was added in portions and the reaction mixture was left in the open air until slowly reaching 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. The residue was purified by flash column chromatography (eluent gradient from 0.5% to 10% MeOH in DCM) to yield compound 7 (59 mg, 29% yield) as a white solid. LC-MS: rt = 1.13 min, MS: 272.1 (calculated), 273.1 (M+H+, found). Step 2. 4-Oxo-1-(2-(pyridin-3-yl)ethyl)cyclohexane-1-carbonitrile (8)

[00215] To a solution of 7 (59 mg, 0.220 mmol) in acetone (5 mL), 2 N HCl (1 mL, 2 mmol) was added, and the reaction mixture was stirred at RT for 18 hours. Then, the mixture was neutralized by slowly adding concentrated saturated NaHCO3 solution to remove the organic solvent. The residue was extracted with EA, and the organic layer was dried with Na2SO4, filtered, and concentrated to dryness to yield the title compound 8 (48 mg, 99% yield). LC-MS: rt = 0.37 min, MS: 228.1 Petition 870250100355, dated 03 / 11 / 2025, p. 120 / 282 115 / 236 (calculated), 229.1 (M+H+, found). Step 3.2-Amino-6-cyano-6-(2-(pyridin-3-yl)ethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (9)

[00216] To a suspension of 8 (48 mg, 0.21 mmol), sulfur (7 mg, 0.026 mmol) and cyanoacetamide (16 mg, 0.19 mmol) in EtOH (0.4 mL) morpholine (18 pL, 0.21 mmol) was added. The reaction mixture was stirred at 60 °C for 16 hours, and a precipitate was formed. This solid was collected by filtration, washed with EtOH, and dried to yield the title compound 9 as a dirty white solid (28 mg, 46% yield).

[00217] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.47 (d, J = 1.6 Hz, 1H), 8.39 (dd, J = 4.7, 1.6 Hz, 1H), 7.66 (dt, J = 7.8, 1.9 Hz, 1H), 7,347.25 (m, 1H), 6.97 (s, 2H), 6.69-6.47 (m, 2H), 2.92 (d, J = 16.0 Hz, 1H), 2.832.73 (m, 4H), 2.66 (d, J = 16.0 Hz, 1H), 2.16-2.06 (m, 1H), 2.01-1.86 (m, 2H), 1.72 (m, J = 13.6 Hz, 1H). LC-MS: rt = 1.00 min, MS: 326.1 (calculated), 327.0 (M+H+, found). Example 4 2-Amino-6-benzyl-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (12) Scheme 4 Step 1. 8-Benzyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (10)

[00218] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, Scheme 1) (1.0 g, 5.98 mmol) in anhydrous THF (24.0 mL) at -78 °C, LDA (6.58 mL, 1 M in THF / hexane, 6.58 mmol) was added dropwise. The reaction mixture was stirred at -78 °C for 45 min, then benzyl bromide (0.870 mL, 7.18 mmol) was added dropwise. The mixture of Petition 870250100355, dated 03 / 11 / 2025, pp. 121 / 282 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 NebSO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 30% EA in hexane) to yield compound 10 (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 (11)

[00219] To a solution of 10 (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 NaHCO3 solution and concentrated to remove the organic solvent. The residue was extracted with EA, and the organic layer was dried with Na2SO4, filtered, and concentrated to dryness to yield compound 11 (1.00 g, >99% yield). LC-MS: rt = 2.93 min, MS: 213.1 (calculated), 214.1 (M+H+, found). Step 3. 2-Amino-6-benzyl-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (12)

[00220] To a suspension of 11 (148 mg, 0.694 mmol), sulfur (22.3 mg, 0.0871 mmol) and cyanoacetamide (53 mg, 0.631 mmol) in EtOH (1.3 mL) was added morpholine (61 lI, 0.694 mmol). The reaction mixture was stirred at 60 °C for 16 hours, and a precipitate appeared. This solid was collected by filtration and purified by flash column chromatography (eluent gradient from 0.5% to 10% MeOH in DCM) to yield the title compound 12 (111 mg, 56% yield).

[00221] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.40-7.26 (m, 5H), 3.02 (s, 2H), 2.91-2.82 (m, 2H), 2.78-2.65 (m, 2H), 2.24-2.16 (m, 1H), 1,901.81 (m, 1H). LC-MS: rt = 1.27 min, MS: 311.1 (calculated), 312.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 122 / 282 117 / 236 Example 5 2-Amino-6-benzoyl-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide (16) Scheme 5 Step 1. 8-(Hydroxy(phenyl)methyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (13)

[00222] A solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, Scheme 1) (500 mg, 2.99 mmol) in anhydrous THF (2 mL) was added at -78 °C to a solution of LDA (3.3 mL, 1 M in THF / hexane, 3.3 mmol) in anhydrous THF (10 mL). The reaction mixture was stirred at -78 °C for 45 minutes, then benzaldehyde (239 pL, 1.97 mmol) was added and the reaction mixture was left in the open air until it slowly reached RT and stirred for 16 hours. Finally, the reaction mixture was rapidly cooled with water 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% EA in hexane) to yield compound 13 (616 mg, 76% yield) as a white solid, which was not characterized and used directly for the next step. Step 2. 8-Benzoyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (14)

[00223] To a solution of 13 (617 mg, 2.26 mmol) in DCM (45 mL), DMP (1.97 g, 4.51 mmol) was added, and the mixture was stirred at RT for 3 hours. Then, the mixture was rapidly cooled by slowly adding saturated NaHCO3 solution and concentrated to remove the organic solvent. The residue was extracted with EA, and the extract was dried with Petition 870250100355, dated 03 / 11 / 2025, pp. 123 / 282 118 / 236 NaiSOd, filtered and concentrated to dryness to produce compound 14 (499 mg, 82% yield). LC-MS: rt = 1.41 min, MS: 271.1 (calculated), 270.2 ([MH]-, found). Step 3. 1-Benzoyl-4-oxocyclohexane-1-carbonitrile (15)

[00224] To a solution of 14 (500 mg, 1.85 mmol) in acetone (19 mL), 2 N HCl (10 mL, 20 mmol) was added, and the reaction mixture was stirred at RT for 3 days. 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 extract was dried with Na2SO4, filtered, and concentrated to dryness to yield the title compound 15 as a colorless oil (416 mg, 99% yield), which was not characterized and used directly in the next step. Step 4. 2-Amino-6-benzoyl-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (16)

[00225] To a suspension of 15 (420 mg, 1.85 mmol), sulfur (65.4 mg, 0.255 mmol) and cyanoacetamide (155 mg, 1.85 mmol) in EtOH (4 mL) was added morpholine (178 pL, 1.85 mmol). The reaction mixture was stirred at 60 °C for 16 hours, and a precipitate was formed. This solid was collected by filtration, washed with EtOH and dried to yield the title compound 16 (411 mg, 68% yield).

[00226] 1H NMR: 400 MHz, DMSO-d6, d (ppm): 8.10-8.04 (m, 2H), 7.68 (d, J = 7.4 Hz, 1H), 7.61-7.54 (m, 2H), 6.99 (s, 2H), 6.63 (bs, 2H), 3.28-3.20 (m, 1H), 3.13-3.05 (m, 1H), 2.93-2.78 (m, 2H), 2.16-2.06 (m, 1H). LC-MS: rt = 1.23 min, MS: 325.1 (calculated), 326.0 (M+H+, found). Example 6 2-Amino-N6-ethyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3,6-dicarboxamide (20) Scheme 6 Petition 870250100355, dated 03 / 11 / 2025, pp. 124 / 282 119 / 236 Step 1. N-Ethyl-8-phenyl-1,4-dioxaspiro[4.5]decane-8-carboxamide (18)

[00227] To a solution of 8-phenyl-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (17) (49.7 mg, 189 pmol) (Bioorg. Med. Chem. Lett., 21, page 405, 2011) in DMF (2.37 mL) were added ethylamine (104 pL, 208 pmol), N,N-di-isopropylethylamine (99.0 pL, 568 pmol) and HATU (86.5 mg, 227 pmol). The resulting mixture was stirred at RT for 16 hours, then diluted with saturated aqueous NH4Cl solution (10 mL) and extracted with EA (3 x 10 mL). The combined organic compounds were washed with ice-cold brine (30 mL), dried with Na2SO4, filtered, and concentrated to produce the crude compound 18 as an orange liquid, which was used in Step 2 without purification. LC-MS: rt = 1.32 min, MS: 289.2 (calculated), 290.2 (M+H+, found). Step 2. N-Ethyl-4-oxo-1-phenylcyclohexane-1-carboxamide (19)

[00228] A solution of 18 (54.8 mg, 189 pmol, assuming quantitative yield in Step 1) in acetone (2.6 mL) was treated with 2 N HCl (480 pL, 960 pmol) and the resulting mixture was stirred at RT for 16 hours, then rapidly cooled with saturated aqueous NaHCO3 (5 mL) and concentrated by rotary evaporation to remove the acetone. The aqueous residue was partitioned between water and EA (10 mL each), the layers were separated, and the aqueous phase was extracted with a further 10 mL of EA. The combined organic compounds were dried with Na2SO4, filtered, and concentrated to yield the title compound 19 as a light orange oil (43.5 mg, 94% yield over two steps), which was used in Step 3 without purification. LC-MS: rt = 1.11 min, MS: 245.1 (calculated), 246.2 (M+H+, found). Step 3. 2-Amino-N6-ethyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3,6dicarboxamide (20) Petition 870250100355, dated 03 / 11 / 2025, pages 125 / 282 120 / 236

[00229] A suspension of cyanoacetamide (14.0 mg, 167 pmol), morpholine (15.8 pL, 183 pmol), sulfur (5.89 mg, 23.0 pmol) and 19 (42.5 mg, 173 pmol) in EtOH (167 pL) was stirred at 60 °C for 16 hours. The mixture was allowed to cool naturally to RT and concentrated by rotary evaporation, and the residue was purified by flash column chromatography (40% to 100% EA eluent gradient in hexane) to yield the title compound 20 as a light yellow solid (32.7 mg, 57% yield).

[00230] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.46 (t, J = 5.7 Hz, 1H), 7.37-7.26 (m, 4H), 7.26 -7.16 (m, 1H), 6.99 (s, 2H), 6.46 (bs, 2H), 0.89 (t, J = 7.1 Hz, 3H). LC-MS: rt = 1.17 min, MS: 343.1 (calculated), 344.1 (M+H+, found). Example 7 2-Amino-6-(1H-benzo[d]imidazol-2-yl)-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (24) Scheme 7 Step 1. Methyl 5-(1H-Benzo[d]imidazol-2-yl)-5-cyano-2-oxocyclohexane-1carboxylate (22)

[00231] To a solution of (2-benzimidazolyl)acetonitrile (21) (468 mg, 2.98 mmol) and methyl acrylate (546 pL, 5.96 mmol) in anhydrous THF (8.05 mL) at 0 °C, solid potassium tert-butoxide (401 mg, 3.58 mmol) was added. The reaction vessel was removed from the ice bath and the mixture was stirred at RT for 2 hours, then a further 200 mg of solid potassium tert-butoxide (1.79 mmol) was added and stirring continued at RT for 16 hours. Petition 870250100355, dated 03 / 11 / 2025, pp. 126 / 282 121 / 236 Subsequently, an additional 224 mg of potassium tert-butoxide (2.0 mmol) was added, the mixture was stirred for another 2 hours, then diluted with saturated aqueous NH4Cl solution (20 mL) and extracted with EA (2 x 20 mL). The combined organic compounds were dried with N2SO4, filtered, and concentrated to yield the crude compound 22 as a light brown solid (390.9 mg, 44% yield), which was used in Step 2 without purification. LC-MS: rt = 1.32 min, MS: 297.1 (calculated), 298.1 (M+H+, found). Step 2. 1-(1H-Benzo[d]imidazol-2-yl)-4-oxocyclohexane-1-carbonitrile (23)

[00232] To a solution of 22 (386 mg, 1.30 mmol) in DMSO (4.08 mL) were added NaCl (25.0 mg, 428 pmol) and water (40.8 pL). The resulting mixture was stirred at 160 °C for 4 hours, then a further 24 mg of NaCl (411 pmol) and 41 pL of water were added and stirring at 160 °C continued for a further 5 hours. The mixture was then allowed to cool naturally to RT, diluted with water (30 mL) and extracted with EA (3 x 15 mL). The combined organic compounds were washed with ice-cold brine (30 mL), dried with Na2SO4, filtered, and concentrated to produce the crude compound 23 as a dark brown solid, which was used in Step 3 without purification. LC-MS: rt = 0.97 min, MS: 239.1 (calculated), 240.1 (M+H+, found). Step 3. 2-Amino-6-(1H-benzo[d]imidazol-2-yl)-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (24)

[00233] A suspension of cyanoacetamide (110 mg, 1.31 mmol), morpholine (124 pL, 1.44 mmol), sulfur (46.4 mg, 181 pmol), and 23 (310 mg, 1.30 mmol) in EtOH (1.31 mL) was stirred at 60 °C for 16 hours. The mixture was allowed to cool naturally to RT, the precipitate was removed by filtration, and the filtrate was concentrated by rotary evaporation. The residue was first purified by flash column chromatography (eluent gradient from 5% to 100% EA in hexane, then from 0% to 15% MeOH). Petition 870250100355, dated 03 / 11 / 2025, pp. 127 / 282 122 / 236 in EA), then by semi-preparative HPLC-MS (20% to 100% CH3CN eluent gradient in 10 mM ammonium bicarbonate) to produce the title compound 24 as a dirty-white solid (1.3 mg, 0.3% yield over two steps).

[00234] 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.61 (bs, 2H), 7.29 (dd, J = 6.1, 3.2 Hz, 2H), 3.44-3.32 (m, 2H), 3.17-2.97 (m, 2H), 2.74-2.64 (m, 1H), 2.55-2.41 (m, 1H). LC-MS: rt = 1.01 min, MS: 337.1 (calculated), 338.1 (M+H+, found). Example 8 2-Amino-6-(benzo[d]thiazol-2-yl)-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (25)

[00235] Compound 25 (example 8) was synthesized similarly to compound 24 (example 7, scheme 7) starting from 2-benzothiazolacetonitrile instead of (2-benzimidazolyl)acetonitrile (21).

[00236] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.19 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.08 (s, 2H), 6.68 (bs, 2H), 3.45 (d, J = 16.1 Hz, 1H), 3.37 (d, J = 16.2 Hz, 1H), 3.06-2.94 (m, 1H), 2.93-2.84 (m, 1H), 2.66-2.57 (m, 1H), 2.48-2.38 (m, 1H). LC-MS: rt = 1.28 min, MS: 354.1 (calculated), 355.1 (M+H+, found). Example 9 2-Amino-6-phenyl-6-(piperidine-1-carbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (28) and Example 10 2-Amino-6-(morpholine-4-carbonyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophenePetition 870250100355, of 03 / 11 / 2025, p. 128 / 282 123 / 236 3-carboxamide (29) Scheme 8 Step 1. 2-amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzorb]thiophene-6-carboxylic acid (27)

[00237] A suspension of cyanoacetamide (35.0 mg, 416 pmol), morpholine (75.4 pL, 874 pmol), sulfur (14.7 mg, 57.4 pmol) and 4-oxo-1-phenylcyclohexanecarboxylic acid (26) (99.9 mg, 458 pmol) in EtOH (416 pL) was stirred at 60 °C for 16 hours. The mixture was allowed to cool naturally to RT and concentrated by rotary evaporation. The residue was purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O) to yield the title compound 27 as a light orange solid (70 mg, 53% yield). LC-MS: rt = 1.25 min, MS: 316.1 (calculated), 317.1 (M+H+, found). Step 2a.2-Amino-6-phenyl-6-(piperidine-1-carbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (28)

[00238] To a solution of 27 (10.0 mg, 31.6 pmol), piperidine (3.43 pL, 34.8 pmol) and N,N-diisopropylethylamine (16.5 pL, 94.8 pmol) in DMF (395 pL) was added HATU (14.4 mg, 37.9 pmol). The resulting mixture was stirred at RT for 16 hours, then diluted with saturated aqueous NH4Cl solution (5 mL) and extracted with EA (3 x 5 mL). The Petition 870250100355, dated 03 / 11 / 2025, pp. 129 / 282 124 / 236 combined organic compounds were washed with ice-cold brine (15 mL), dried with N2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (40% to 100% eluent gradient in hexane) to yield compound 28 as a white solid (4.6 mg, 38% yield).

[00239] 1H NMR: 400 MHz, CDCfe, δ (ppm): 7.35-7.14 (m, 5H), 6.16 (s, 2H), 5.27 (bs, 2H), 3.72-2.84 (m, 6H), 2.72-2.58 (m, 1H), 2.61-2.43 (m, 1H), 2.37-2.27 (m, 1H), 2.16-2.06 (m, 1H), 1.34-0.81 (m, 6H). LC-MS: rt = 1.34 min, MS: 383.2 (calculated), 384.3 (M+H+, found). Step 2b.2-Amino-6-(morpholine-4-carbonyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (29)

[00240] To a solution of 27 (11.3 mg, 35.7 pmol), morpholine (3.44 pL, 39.3 pmol) and NN-diisopropylethylamine (18.7 pL, 107 pmol) in DMF (446 pL) was added HATU (16.3 mg, 42.9 pmol). The resulting mixture was stirred at room temperature for 16 hours, then diluted with saturated aqueous NH4Q solution (5 mL) and extracted with EA (3 x 5 mL). The combined organic compounds were washed with ice-cold brine (15 mL), dried with N2SO4, 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 29 as a white solid (3.9 mg, 28% yield).

[00241] 1H NMR: 400 MHz, CDCfe, δ (ppm): 7.39-7.14 (m, 5H), 6.17 (s, 2H), 5.30 (bs, 2H), 3.85-2.89 (m, 10H), 2.73-2.60 (m, 1H), 2.53-2.42 (m, 1H), 2.39-2.30 (m, 1H), 2.20-2.05 (m, 1H). LC-MS: rt = 1.11 min, MS: 385.2 (calculated), 386.2 (M+H+, found). Example 11 2-Amino-6-(hydroxymethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (46) Petition 870250100355, dated 03 / 11 / 2025, page 130 / 282 125 / 236 Scheme 13 Step 1. 4-(((ter-Butyldimethylsilyl)oxy)methyl)-4-phenylcyclohexan-1-one (44)

[00242] To a solution of 4-(hydroxymethyl)-4-phenylcyclohexan-1-one (43) (Bioorg. Med. Chem. Lett., 21, page 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 compound 44 as a white solid (1.20 g, 86% yield), which was not characterized and used directly in the next step. Step 2. 2-amino-6-(((tert-butyldimethylsilyl)oxy)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (45)

[00243] To a solution of 44 (80 mg, 0.251 mmol) and cyanoacetamide (23 mg, 0.276 mmol) in EtOH (0.25 mL), morpholine (0.024 mL, 0.276 mmol) and sulfur powder (9 mg, 0.035 mmol) were added. The reaction was heated at 60 °C for 16 hours, cooled to RT, and concentrated to dryness. The residue was partitioned between water and EA. The layers were separated, and the organic layer was dried with Na2SO4, filtered, and evaporated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane) to yield the title compound 45 (54 mg, 52% yield) as a pale yellow solid. LC-MS: rt = 4.43 Petition 870250100355, dated 03 / 11 / 2025, pp. 131 / 282 126 / 236 min, MS: 416.2 (calculated), 417.2 (M+H+, found). Step 3. 2-Amino-6-(hydroxymethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (46)

[00244] To a solution of 45 (20 mg, 0.048 mmol) in MeOH (0.5 mL) at 0 °C, 2 N HCl (0.5 mL, 1.0 mmol) was added dropwise. The reaction mixture was stirred at 0 °C for 2 hours before being rapidly cooled with saturated NaHCO3 solution. Then, the mixture was extracted with EA, and the organic layer was dried with Na2SO4, filtered, and concentrated. The residue was ground with a 1:1 DCM / hexane mixture and collected by filtration. This solid was then redissolved in CHCl3, and insoluble impurities were removed by filtration. Finally, the solution was concentrated to yield the title compound 46 (4 mg, 28% yield) as a pale orange solid.

[00245] 1H NMR: 400 MHz, CDCb, δ (ppm): 7.35-7.34 (m, 5H), 6.15 (bs, 2H), 5.29 (bs, 2H), 4.68 (bs, 1H), 3.84 (d, J = 11.0 Hz, 1H), 3.68 (d, J = 11.0 Hz, 1H), 3.13 (d, J = 16.6 Hz, 1H), 2.84 (d, J = 16.6 Hz, 1H), 2.72-2.67 (m, 1H), 2.35-2.27 (m, 1H), 2.18-2.04 (m, 2H). LC-MS: rt = 2.22 min, MS: 302.1 (calculated), 303.1 (M+H+, found). Example 12 2-Amino-6-(2-amino-2-oxoethyl)-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (76) Intermediate compound 56 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acetonitrile (56) Scheme 16 Step 1. (8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)methanol (54) Petition 870250100355, dated 03 / 11 / 2025, pp. 132 / 282 127 / 236

[00246] Sodium borohydride (816 mg, 21.1 mmol) was added to a solution of 48 (scheme 14) (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 N2SO4, filtered, and concentrated to yield compound 54 (2.95 g, 93% yield) as a colorless oil, which was not characterized and used directly for the next step. Step 2. 4-Methylbenzenesulfonate of (8-(cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)methyl (55)

[00247] To a solution of 54 (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 N2SO4, 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 55 (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 (56)

[00248] To a solution of 55 (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 naturally to RT and diluted with a saturated aqueous solution of Petition 870250100355, dated 03 / 11 / 2025, p. 133 / 282 128 / 236 NaHCO3 (50 mL). The mixture was then diluted with EA (50 mL) and water (40 mL), the layers were 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 56 (2.5 g, 72% yield) as a yellow oil, which was not characterized and used directly for the synthesis of relevant examples. 2-Amino-6-(2-amino-2-oxoethyl)-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzofb1thiophene-3-carboxamide (76) Scheme 22 Step 1. 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiror4.51decan-8-yl)acetic acid (73

[00249] To a solution of compound 56 (scheme 16) (814 mg, 3.46 mmol) in ethylene glycol (18.3 mL) were added potassium hydroxide (1.55 g, 27.7 mmol) and water (1 mL). The resulting mixture was stirred at 170 °C for 24 hours, then more potassium hydroxide (1.55 g, 27.7 mmol) and water (1 mL) were added, and the reaction mixture was stirred at 170 °C for another 24 hours. The mixture was allowed to cool naturally to RT, diluted with water (50 mL) and washed with EA (2 x 50 mL). The aqueous phase was acidified with 2 N HCl to pH 4 to 5 and extracted with EA (3 x 50 mL). These organic compounds were washed with brine (50 mL), dried with Petition 870250100355, dated 03 / 11 / 2025, page 134 / 282 129 / 236 Na2SÜ4, filtered and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 20% MeOH in DCM) to yield the title compound 73 as a colorless oil (611 mg, 69% yield), which was not characterized and used directly in the next step. Step 2. 2-(1-(cyclopropylmethyl)-4-oxocyclohexyl)acetic acid (74)

[00250] To a solution of 73 (220 mg, 0.865 mmol) in acetone (10.7 mL), 2 N HCl (4.33 mL, 8.65 mmol) was added. The mixture was stirred at RT for 72 hours, then diluted with water and EA (20 mL each). The layers were separated, and the aqueous phase was extracted with EA (2 x 20 mL). The combined organic compounds were dried with N2SO4, filtered, and concentrated to dryness to yield the title compound 74 as a white solid (180 mg, >99% yield). LC-MS: rt = 1.07 min, MS: 210.1 (calculated), 209.1 ([MH]-, found). Step 3. 2-(2-Amino-3-carbamoyl-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)acetic acid (75)

[00251] To a solution of 74 (100 mg, 476 pmol) and cyanoacetamide (44.0 mg, 523 pmol) in EtOH (1.49 pL), morpholine (91.5 pL, 1.05 mmol) and sulfur (16.8 mg, 65.6 pmol) were added. The resulting mixture was stirred at 60 °C for 16 hours, then allowed to cool naturally to RT and concentrated to dryness. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane, then from 0% to 30% MeOH in DCM) to yield the title compound 75 as a red oil (90.0 mg, 61% yield). LC-MS: rt = 1.14 min, MS: 308.1 (calculated), 307.1 ([MH]-, found). Step 4. 2-Amino-6-(2-amino-2-oxoethyl)-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (76)

[00252] To a suspension of 75 (30.0 g, 97.3 pmol) and ammonium chloride (104 mg, 1.95 mmol) in anhydrous DMF (957 pL), were added Petition 870250100355, dated 03 / 11 / 2025, page 135 / 282 130 / 236 HATU (56.6 mg, 146 pmol) and N,N-diisopropylethylamine (33.9 pL, 195 pmol). The mixture was stirred at RT for 1 hour and purified directly by reversed-phase column chromatography (5% to 100% CH3CN eluent gradient in H2O with 0.1% (v / v) formic acid) to yield the title compound 76 as a dirty white solid (18.5 mg, 62% yield).

[00253] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.22 (s, 1H), 6.87 (s, 2H), 6.68 (s, 1H), 6.48 (bs, 2H), 2.58-2.54 (m, 2H), 2.49-2.48 (m, 1H), 2.41-2.37 (m, 1H), 2.18-2.09 (m, 2H), 1.67-1.60 (m, 1H), 1.63-1.55 (m, 1H), 1.51-1.43 (m, 1H), 1.20-1.15 (m, 1H), 0.74-0.67 (m, 1H), 0.38-0.34 (m, 2H), 0.00 - -0.06 (m, 2H). LC-MS: rt = 1.00 min, MS: 307.1 (calculated), 308.2 (M+H+, found). Examples 13 to 26

[00254] Compounds 77 to 90 (examples 13 to 26) were synthesized starting from commercially available cyanoketones that had been suitably substituted, following the procedure reported for the synthesis of compound 4 from cyanoketone 3 (example 1, scheme 1) or the procedure reported for the synthesis of compound 6 from cyanoketone 5 (example 2, scheme 2). The characterization of compounds 77 to 90 (examples 13 to 26) is given in Table 3. Table 3. Characterization of compounds 77 to 90 (examples 13 to 26). Ex. No. Compound No. Structure Characterization 13 77 ÒtcX 2-Amino-6-cyano-6-(m-tolyl)4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.39-7.29 (m, 3H), 7.19 (m, 1H), 7.05 (s, 2H), 6.64 (bs, 2H), 3.09 (m, 2H), 3.00-2.79 (m, 2H), 2.35 (s, 3H), 2.31-2.19 (m, 2H). LC-MS: rt = 1.34 min, MS: 311.1 (calculated), 312.2 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, p. 136 / 282 131 / 236 Example No. Compound No. Structure Characterization 14 78 \ 'X 2-Amino-6-cyano-6-(2-methoxyphenyl)4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.42-7.28 (m, 2H), 7.16 (d, J = 8.2 Hz, 1H), 7.06 (bs, 2H), 7.00 (t, J = 7.4 Hz, 1H), 6.58 (bs, 2H), 3.89 (s, 3H), 3.29-3.20 (m, 2H, partially overlapping with the water signal), 3.08-2.99 (m, 1H), 2.81-2.70 (m, 1H), 2.45-2.29 (m, 2H). LC-MS: rt = 1.25 min, MS: 327.1 (calculated), 328.2 (M+H+, found). 15 79 'Οχχχ 2-Amino-6-cyano-6-(4-methoxyphenyl)4,5,6,7-tetrahydrobenzo[ b ]thiophene3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.49 (d, J = 9.0 Hz, 2H), 7.05 (s, 2H), 6.99 (d, J = 9.0 Hz, 2H), 6.63 (bs, 2H), 3.77 (s, 3H), 3,162.99 (m, 2H), 2.99-2.76 (m, 2H), 2.33-2.15 (m, 2H). LC-MS: rt = 1.24 min, MS: 327.1 (calculated), 328.2 (M+H+, found).16 80 cXoZ 2-Amino-6-ciano-6-(o-tolil)-4,5,6,7tetra-hidrobenzo[b]tiofeno-3carboxamide RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7.37 (t, J = 8.0 Hz, 1H), 7.14 (d, J = 2.0 Hz, 2H), 7.05 (s, 2H), 6.95 (dd, J = 8.2, 1.6 Hz, 1H), 6.64 (bs, 2H), 3.78 (s, 3H), 3.173,04 (m, 2H), 3.00-2.79 (m, 2H), 2.29 (m, 2H). LC-MS: rt = 1.29 min, MS: 311.1 (calculator), 312.2 (M+H+, encontrado). 17 81 òoZ 2-Amino-6-cyano-6-(3-metoxifenil)4,5,6,7-tetra-hydrobenzo[ b ]tiofeno3-carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7.40-7.20 (m, 4H), 7.07 (s, 2H), 6.61 (bs, 2H), 3.08-2.91 (m, 2H), 2.85-2.74 (m, 1H), 2.62 (s, 3H), 2.48-2.40 (m, 1H), 2.38-2.27 (m, 1H). LC-MS: rt = 1.25 min, MS: 327.1 (calculator), 328.1 (M+H+, encontrado). 18 82 2-Amino-6-(4-chlorofenil)-6-cyano4,5,6,7-tetra-hydrobenzo[ b ]tiofeno3-carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7.64-7.56 (d, J = 8.6 Hz, 2H), 7.50 (d, J = 8.6 Hz, 2H), 7.03 (s, 2H), 6.62 (bs, 2H), 3.09 (m, 2H), 2.97-2.76 (m, 2H), 2.33-2.21 (m, 2H).LC-MS: rt = 1.37 min, MS: 331.1 (calculated), 332.2 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, p. 137 / 282 132 / 236 Example No. Compound No. Structure Characterization 19 83 C / sOc^ 2-Amino-6-cyano-6-(pyridin-2-yl)4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.64 (d, J = 5.1 Hz, 1H), 7.91 (td, J = 7.8, 1.9 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.42 (dd, J = 7.5, 4.8 Hz, 1H), 7.04 (s, 2H), 6.64 (bs, 2H), 3.24 (d, J = 16.3 Hz, 1H), 3.15 (d, J = 16.2 Hz, 1H), 3.02-2.88 (m, 1H), 2.88-2.81 (m, 1H), 2.43-2.34 (m, 1H), 2.34-2.24 (m, 1H). LC-MS: rt = 1.06 min, MS: 298.1 (calculated), 299.0 (M+H+, found). 20 84 2-Amino-6-(2-chlorophenyl)-6-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide. 1H NMR: 400 MHz, DMSO-d... d (ppm): 7.62-7.56 (m, 1H), 7.54-7.49 (m, 2H), 7.48-7.39 (m, 2H), 7.08 (s, 2H), 6.61 (bs., 2H), 3.46 (d, J = 15.6 Hz, 2H), 3.13 (d, J = 16.0 Hz, 1H), 3.02-2.91 (m, 1H), 2.82-2.73 (m, 1H), 2.60-2.39 (m, 2H). LC-MS: rt = 1.49 min, MS: 331.1 (calculated), 332.1 (M+H+, found).21 85 Οχχί- 2-Amino-6-cyano-6-phenyl-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, d (ppm): 7.59 (d, J = 7.8 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.41-7.34 (m, 1H), 7.05 (s, 2H), 6.64 (bs, 2H), 3.17-3.03 (m, 2H), 3.01-2.79 (m, 2H), 2.33-2.25 (m, 2H). LC-MS: rt = 1.43 min, MS: 297.1 (calculated), 297.9 (M+H+, found). 22 86 2-Amino-6-(3-bromophenyl)-6-cyano 4,5,6,7-tetrahydrobenzo[ b ]thiophene3-carboxamide 1H NMR: 400 MHz, CD3OD, d (ppm): 7.76 (t, J = 1.8 Hz, 1H), 7.60-7.52 (m, 2H), 7.37 (t, J = 7.8 Hz, 1H), 3.16-3.11 (m, 2H), 3.102.98 (m, 1H), 2.92 (dt, J = 16.8, 4.7 Hz, 1H), 2.43-2.30 (m, 2H). LC-MS: rt = 1.66 min, MS: 375.0 and 377.0 (calculated), 375.8 and 377.8 (M+H+, found). 23 87 2-Amino-6-cyano-6-cyclopropyl4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide 1H NMR: 400 MHz, DMSO-d6, d (ppm): 7.01 (s, 2H), 6.64 (bs, 2H), 2.89-2.64 (m, 4H), 2.06 (d, J = 13.3 Hz, 1H), 1.85-1.74 (m, 1H), 1.201.10 (m, 1H), 0.62-0.51 (m, 2H), 0.50-0.41 (m, 2H).LC-MS: rt = 1.28 min, MS: 261.1 (calculated), 262.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 138 / 282 133 / 236 Ex. No. Compound No. Structure Characterization 24 88 2-Amino-6-cyano-6-(p-tolyl)-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, d (ppm): 7.46 (d, J = 7.8 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 7.05 (s, 2H), 6.63 (bs, 2H), 3.15-3.00 (m, 2H), 3.00-2.77 (m, 2H), 2.31 (s, 3H), 2.26 (s, 2H). LC-MS: rt = 1.65 min, MS: 311.1 (calculated), 312.2 (M+H+, found). 25 89 2-Amino-6-cyano-6-(pyridin-4-yl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.80 (d, J = 2.43 Hz, 1H), 8.58 (d, J = 4.73 Hz, 1H), 8.00 (d, J = 8.16 Hz, 1 H), 7.48 (dd, J = 8.08, 4.76 Hz, 1H), 7.04 (s, 2H), 6.64 (bs, 2H), 3.21-3.10 (m, 2H), 2.96-2.91 (m, 1H), 2.87-2.77 (m, 1H), 2,392,30 (m, 2H). LC-MS: rt = 0.67 min, MS: 298.1 (calculated), 299.1 (M+H+, found).26 90 2-Amino-6-cyano-6-(pyridin-3-yl)4,5,6,7-tetrahydrobenzo[ b ]thiophene3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.64 (d, J = 5.22 Hz, 2H), 7.60 (d, J = 5.26 Hz, 2H), 7.04 (s, 2H), 6.64 (bs, 2H), 3.17-3.07 (m, 2H), 2.97-2.83 (m, 2H), 2.32-2.29 (m, 2H). LC-MS: rt = 0.57 min, MS: 298.1 (calculated), 299.1 (M+H+, found). Examples 27 to 30

[00255] Compounds 98 to 101 (examples 27 to 30) were synthesized from commercially available ketones suitably substituted, following the procedure reported for the synthesis of compound 4 from ketone 3 (example 1, scheme 1) or the procedure reported for the synthesis of compound 6 from ketone 5 (example 2, scheme 2). The characterization of compounds 98 to 101 (examples 27 to 30) is given in Table 4. Table 4. Characterization of compounds 98 to 101 (examples 27 to 30). Example No. Compound No. Structure Characterization 27 98 2-Amino-6-methyl-6-phenyl-4,5,6,7tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.36 (d, J = 7.3 Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H), 6.95 (s, 2H), 6.44 (bs, 2H), 2.93 (d, J = 16.0 Hz, 1H), 2.70-2.55 (m, 2H), 2.36-2.18 (m, 1H), 2.13-2.01 (m, 1H), 1.91-1.77 (m, 1H), 1.26 (s, 3H), LC-MS: rt = 1.71 min, MS: 286.1 (calculated), 287.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, p. 139 / 282 134 / 236 28 99 2-Amino-3-carbamoil-6-fenil4,5,6,7-tetra-hidrobenzo[ b ]tiofeno6-carboxilato de metila RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7,35 (d, J = 4,2 Hz, 4H), 7,27 (m, 1H), 6,96 (s, 2H), 6,50 (bs, 2H), 3,57 (s, 3H), 3,23 (d, J = 16,0 Hz, 1H), 2,88 (d, J = 16,1 Hz, 1H), 2,752,64 (m, 1H), 2,56-2,51 (m, 1H), 2,47-2,38 (m, 1H), 2,28-2,15 (m, 1H). LC-MS: rt = 1,51 min, MS: 330,1 (calculado), 331,1 (M+H+, encontrado). 29 100 2-Amino-4,7-di-hidro-5Hespiro[benzo[ b ]tiofeno-6,1'-cicloheptano] -3-carboxamida RMN de 1H: 400 MHz, CDCL, d (ppm): 6,15 (s, 2H), 5,43 (bs, 2H), 2,60 (t, J = 6,17 Hz, 2H), 2,30 (s, 2H), 1,63 (t, J = 6,25 Hz, 2H), 1,571,48 (m, 10H), 1,41-1,35 (m, 2H). LC-MS: rt = 2,02 min, MS: 278,2 (calculado), 279,2 (M+H+, encontrado). 30 101 YQry 2-Amino-6-etil-6-fluoro-4,5,6,7tetra-hidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-d6, d (ppm): 6,91 (s, 2H), 6,56 (bs, 2H), 2,77-2,58 (m, 4H), 2,01-1,90 (m, 1H), 1,80-1,60 (m, 3H), 0,94 (t, J = 7,4 Hz, 3H).19F NMR: 376 MHz, DMSO-d6 d (ppm): -156.2. LC-MS: rt = 1.29 min, MS: 242.1 (calculated), 243.1 (M+H+, found). Example 31 tert-butyl ((2-Amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophen-6yl)methyl)carbamate (105) and Example 32 2-Amino-6-(aminomethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (106) Scheme 26 Step 1. Tert-butyl ((8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)methyl)carbamate Petition 870250100355, dated 03 / 11 / 2025, pp. 140 / 282 135 / 236 (103)

[00256] To a solution of (8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)methanamine (102) (Biochemistry, 41, page 7781, 2002) (500 mg, 2.02 mmol) in anhydrous THF (10.0 mL) were added triethylamine (0.704 mL, 5.05 mmol) and di-tert-butyldicarbonate (668 mg, 3.03 mmol). The reaction mixture was stirred at RT for 16 hours and diluted with water and EA. The layers were separated and the organic phase was washed with brine, dried with MgSO4, filtered and concentrated to yield the title compound 103 as a colorless oil (702 mg, >99%). LC-MS: rt = 1.96 min, MS: 347.2 (calculated), 248.2 (M-Boc+H+, found). Step 2. tert-Butyl ((4-Oxo-1-phenylcyclohexyl)methyl)carbamate (104)

[00257] To a solution of 103 (250 mg, 0.720 mmol) in acetone (25 mL), 2 N HCl (2.0 mL, 4.0 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized with saturated NaHCO3 solution and concentrated to remove the organic solvent. The residue was partitioned between water and EA. The layers were separated, and the organic phase was washed with brine, dried with MgSO4, filtered, and concentrated to yield the title compound 104 as a white solid (201 mg, 92% yield). LC-MS: rt = 1.73 min, MS: 303.2 (calculated), 248.1 (M-tBu+H+, found). Step 3. Tert-butyl ((2-Amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophen-6yl)methyl)carbamate (105)

[00258] To a solution of 104 (104 mg, 0.343 mmol) and cyanoacetamide (32 mg, 0.377 mmol) in EtOH (0.35 mL), morpholine (0.033 mL, 0.377 mmol) and sulfur (12 mg, 0.047 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, allowed to cool naturally 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 chromatography. Petition 870250100355, dated 03 / 11 / 2025, pp. 141 / 282 136 / 236 flash in a column (eluent gradient from 0% to 100% EA in hexane) to produce the title compound 105 (65 mg, 47% yield) as a pale yellow solid.

[00259] 1H NMR: 400 MHz, CDCfe, δ (ppm): 7.33-7.23 (m, 5H), 6.14 (s, 2H), 5.25 (bs, 2H), 4.24 (bs, 1H), 3.45 (bs, 2H), 3.05 (d, J = 16.7 Hz, 1H), 2.78 (d, J = 16.7 Hz, 1H), 2.72-2.68 (m, 1H), 2.23-2.16 (m, 2H), 2,041.99 (m, 1H), 1.39 (s, 9H). LC-MS: rt = 3.22 min, MS: 401.2 (calculated), 346.1 (M-1Bu+H+, found). Step 4. 2-Amino-6-(aminomethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (106)

[00260] To a solution of 105 (10 mg, 0.025 mmol) in DCM (2.0 mL) at 0 °C, trifluoroacetic acid (1.0 mL) was added dropwise. The reaction mixture was stirred at RT for 30 min and then concentrated to dry. 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 106 as a formate salt (4 mg, 46% yield).

[00261] 1H NMR: 400 MHz, CD3OD, δ (ppm): 8.53 (s, 1H), 7,437.37 (m, 4H), 7.31-7.27 (m, 1H), 3.35-3.32 (m, 1H), 3.19 (d, J = 16.3 Hz, 1H), 3.14 (d, J = 13.1 Hz, 1H), 2.82 (d, J = 16.3 Hz, 1H), 2.71-2.66 (m, 1H), 2.28-2.20 (m, 2H), 2.08-2.01 (m, 1H). LC-MS: rt = 0.47 min, MS: 301.1 (calculated), 302.1 (M+H+, found). Example 33 6-(Acetamidomethyl)-2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide (109) Scheme 27 Petition 870250100355, dated 03 / 11 / 2025, pp. 142 / 282 137 / 236 Step 1. N-((8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)methyl)acetamide (107)

[00262] To a solution of (8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)methanamine (102, Scheme 26) (500 mg, 2.02 mmol) in anhydrous THF (10.0 mL) were added dropwise pyridine (5.0 mL) and acetic anhydride (0.290 mL, 3.07 mmol). The reaction mixture was stirred at 75 °C for 16 hours, then allowed to cool naturally to RT and diluted with water and EA. The layers were separated, and the aqueous phase was extracted with EA. The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated to yield compound 107 as a white solid (521 mg, 89%). LC-MS: rt = 1.24 min, MS: 289.2 (calculated), 290.2 (M+H+, found). Step 2. N-((4-Oxo-1-phenylcyclohexyl)methyl)acetamide (108)

[00263] To a solution of 107 (208 mg, 0.720 mmol) in acetone (25 mL), 2 N HCl (2.0 mL, 4.0 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized with concentrated saturated NaHCO3 solution to remove the organic solvent. The residue was partitioned between water and EA. The layers were separated, and the organic phase was washed with brine, dried with MgSO4, filtered, and concentrated to yield the title compound 108 as a white solid (165 mg, 93% yield). LC-MS: rt = 0.95 min, MS: 245.1 (calculated), 246.1 (M+H+, found). Step 3.6-(Acetamidomethyl)-2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (109) Petition 870250100355, dated 03 / 11 / 2025, pp. 143 / 282 138 / 236

[00264] To a solution of 108 (100 mg, 0.408 mmol) and cyanoacetamide (38 mg, 0.448 mmol) in EtOH (0.40 mL), morpholine (0.039 mL, 0.448 mmol) and sulfur (40 mg, 0.155 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, allowed to cool naturally 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 (eluent gradient from 0% to 10% MeOH in DCM) to yield the title compound 109 (74 mg, 53% yield) as a white solid.

[00265] 1H NMR: 400 MHz, CDCh, δ (ppm): 7.37-7.24 (m, 5H), 6.15 (s, 2H), 5.27 (bs, 2H), 5.06-5.03 (m, 1H), 3.65 (dd, J = 13.6, 7.1 Hz, 1H), 3.55 (dd, J = 13.6, 5.5 Hz, 1H), 3.01 (d, J = 16.6 Hz, 1H), 2.80 (d, J = 16.6 Hz, 1H), 2.75-2.71 (m, 1H), 2.27-2.13 (m, 2H), 2.07-2.01 (m, 1H), 1.88 (s, 3H). LC-MS: rt = 1.03 min, MS: 343.1 (calculated), 344.1 (M+H+, found). Example 34 ((2-Amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophen-6yl)methyl)(ethyl) tert-butyl carbamate (113) and Exemplo 35 2-Amino-6-((ethylamino)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide (114) Esquema 28 Petition 870250100355, dated 03 / 11 / 2025, pp. 144 / 282 139 / 236 Step 1. N-((8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)methyl)ethanamine (110)

[00266] A suspension of 107 (scheme 27) (100 mg, 0.346 mmol) in anhydrous THF (1.4 mL), lithium aluminum hydride (0.35 mL, 2 M in THF, 0.70 mmol), and the reaction mixture was stirred at RT for 5 hours. Then, more lithium aluminum hydride (0.35 mL, 2 M in THF, 0.70 mmol) was added and the reaction mixture was stirred at RT for 3 days. After that, the mixture was allowed to cool naturally to 0 °C and then rapidly cooled with 4 N NaOH (1.0 mL). The mixture was filtered through a MgSO4 filter and the filtrate was concentrated until dry to produce compound 110 as a colorless oil, which was used directly in the next step. LC-MS: rt = 1.06 min, MS: 275.2 (calculated), 276.2 (M+H+, found). Step 2. Tert-butyl ethyl((8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)methyl)carbamate (111)

[00267] To a solution of 110 (0.346 mmol) in anhydrous THF (5.0 mL) were added triethylamine (0.123 mL, 0.881 mmol) and di-tert-butyldicarbonate (115 mg, 0.528 mmol). The reaction mixture was stirred at RT Petition 870250100355, dated 03 / 11 / 2025, pp. 145 / 282 140 / 236 for 16 hours, then it was abruptly 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 0% to 30% EA in hexane) to yield the title compound 111 as a colorless oil (85 mg, 65% over two steps). LC-MS: rt = 3.54 min, MS: 375.2 (calculated), 398.2 (M+Na+, found). Step 3. tert-Butyl Ethyl((4-oxo-1-phenylcyclohexyl)methyl)carbamate (112)

[00268] To a solution of 111 (85 mg, 0.226 mmol) in acetone (3.0 mL), 2 N HCl (0.566 mL, 1.13 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized with saturated NaHCO3 solution and concentrated to remove the organic solvent. The residue was partitioned between water and EA. The layers were separated, and the organic phase was dried with Na2SO4, filtered, and concentrated to yield the title compound 112 as a colorless oil (62 mg, 83% yield). LC-MS: rt = 2.86 min, MS: 331.2 (calculated), 354.2 (M+Na+, found). Step 4. Tert-butyl ((2-Amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophen-6yl)methyl)(ethyl)carbamate (113)

[00269] To a solution of 112 (62 mg, 0.187 mmol) and cyanoacetamide (17 mg, 0.206 mmol) in EtOH (0.20 mL), morpholine (0.018 mL, 0.206 mmol) and sulfur (7 mg, 0.138 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, allowed to cool naturally 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 NebSO4.i, 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 113 (42 mg, 52% yield) as a pale yellow solid.

[00270] 1H NMR: 400 MHz, CDCb, δ (ppm) (mixture of Petition 870250100355, dated 03 / 11 / 2025, pp. 146 / 282 141 / 236 rotamers): 7.29-7.26 (m, 5H), 7.22-7.17 (m, 1H), 6.12 (s, 2H), 5.20 (bs, 2H), 3.67-3.57 (m, 1H), 3.32-3.27 (m, 1H), 3.07-3.02 (m, 1H), 2.95-2.81 (m, 2H), 2.68-2.64 (m, 1H), 2.52-2.45 (m, 1H), 2.34-2.31 (m, 1H), 2.14-2.07 (m, 1H), 2.01-1.93 (m, 1H), 1.45 (s, 9H), 0.84 (bs, 3H). LC-MS: rt = 3.64 min, MS: 429.2 (calculated), 430.2 (M+H+, found). Step_________5._________2-Amino-6-((ethylamino)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (114)

[00271] To a solution of 113 (20 mg, 0.047 mmol) in DCM (4.0 mL) at 0 °C, trifluoroacetic acid (2.0 mL) was added dropwise. The reaction mixture was stirred at 0 °C for 30 min and then concentrated to dry. 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 114 as a formate salt (8 mg, 52% yield).

[00272] 1H NMR: 400 MHz, CD3OD, δ (ppm): 8.54 (s, 1H), 7,447.38 (m, 4H), 7.32-7.30 (m, 1H), 3.44 (d, J = 12.8 Hz, 1H), 3.24-3.20 (m, 2H), 2.93-2.86 (m, 3H), 2.71-2.67 (m, 1H), 2.28-2.16 (m, 2H), 2.09-2.03 (m, 1H), 1.20 (t, J = 7.25 Hz, 3H). LC-MS: rt = 0.73 min, MS: 329.2 (calculated), 330.2 (M+H+, found). Example 36 2-Amino-6-((dimethylamino)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (117) Scheme 29 Petition 870250100355, dated 03 / 11 / 2025, pp. 147 / 282 142 / 236 Step 1. N,N-Dimethyl-1-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)methanamine (115)

[00273] To a solution of (8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)methanamine (102, Scheme 26) (100 mg, 0.404 mmol) in 2,2,2-trifluoroethanol (5.0 mL) were added paraformaldehyde (182 mg, 6.06 mmol) and sodium borohydride (46 mg, 1.21 mmol). The reaction mixture was stirred at RT for 16 hours, filtered, and concentrated. The residue was dissolved in EA and washed with saturated NaHCO3, water, and brine solution, then dried with Na2SO4, filtered, and concentrated to yield the compound of title 115 as a colorless oil, which was used directly in the next step. LCMS: rt = 1.07 min, MS: 275.2 (calculated), 276.2 (M+H+, found). Step 2. 4-((Dimethylamino)methyl)-4-phenylcyclohexan-1-one (116)

[00274] To a solution of 115 (0.404 mmol) in acetone (5.5 mL), 2 N HCl (1.0 mL, 2.0 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, the mixture was neutralized with concentrated saturated NaHCO3 solution to remove the organic solvent. The residue was partitioned between water and EA. The layers were separated, and the organic phase was dried with W2SO4, filtered, and concentrated to yield the title compound 116 as a colorless oil, which was used directly in the next step. LC-MS: rt = 0.33 min, MS: 231.2 (calculated), 232.2 (M+H+, found). Step 3.2-Amino-6-((dimethylamino)methyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (117) Petition 870250100355, dated 03 / 11 / 2025, pp. 148 / 282 143 / 236

[00275] To a solution of 116 (93 mg, 0.404 mmol) and cyanoacetamide (37 mg, 0.440 mmol) in EtOH (0.40 mL), morpholine (0.039 mL, 0.440 mmol) and sulfur (14 mg, 0.055 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, then allowed to cool naturally 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 chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in H2O with 0.1% (v / v) formic acid), then purified again by semi-preparative HPLC-MS (eluent gradient from 30% to 100% CH3CN in 10 mM ammonium bicarbonate) to yield the title compound 117 as a white solid (2 mg, 1.5% yield over two steps).

[00276] RMN de 1H: 400 MHz, CD3OD, δ (ppm): 7,41-7,39 (m, 2H), 7,35-7,32 (m, 2H), 7,25-7,21 (m, 1H), 3,20 (d, J = 16,3 Hz, 1H), 3,14-2,93 (m, 2H), 2,86 (d, J = 16,3 Hz, 1H), 2,66-2,60 (m, 1H), 2,34-2,10 (m, 8H), 2,04-1,97 (m, 1H). LC-MS: rt = 0,58 min, MS: 329,2 (calculado), 330,2 (M+H+, encontrado). Exemplos 37 a 48 e 50

[00277] Compounds 118 to 129, 131 (examples 37 to 48, 50) were synthesized similarly to compound 4 (example 1, scheme 1), similarly to compound 6 (example 2, scheme 2) or similarly to compound 9 (example 3, scheme 3), starting from 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, scheme 1) and using in the first step 1-bromo-2-methoxyethane (for 118), 1-bromo-2-(methylsulfanyl)ethane (for 119), iodopropane (for 120), iodoethane (for 121), chloromethyl methyl ether (for 122), 3-(bromomethyl)pyridine bromide (for 123), 4-(bromomethyl)pyridine bromide (for 124), 4-(bromomethyl)tetrahydropyran (for 125), 2-(chloromethyl)oxazole (for 126), (bromomethyl)cyclopropane (for Petition 870250100355, dated 03 / 11 / 2025, pp. 149 / 282 144 / 236 127), (bromomethyl)cyclobutane (for 128), (bromomethyl)cyclopentane (for 129) and 4-(2-bromoethyl)pyridine bromide (for 131), instead of 2-iodopropane, 1-bromo-2-methylpropane or 3-(2-bromoethyl)pyridine bromide. The characterization of compounds 118 to 129, 131 (examples 37 to 58, 50) is provided in Table 5. Table 5. Characterization of compounds 118 to 129, 131 (examples 37 to 48, 50). Example No. Compound No. Structure Characterization 37 118 2-Amino-6-cyano-6-(2-methoxyethyl)4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 6.99 (s, 2H), 6.61 (bs, 2H), 3.55 (t, J = 6.51 Hz, 2H), 3.25 (s, 3H), 2.87-2.81 (m, 1H), 2.78-2.73 (m, 2H), 2.66-2.62 (m, 1H), 2.11-2.06 (m, 1H), 1.95-1.86 (m, 2H), 1.73-1.66 (m, 1H). LC-MS: rt = 0.92 min, MS: 279.1 (calculated), 280.2 (M+H+, found). 38 119 2-Amino-6-cyano-6-(2(methylthio)ethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.01 (s, 2 H), 6.63 (s, 1H), 2.89 (d, J = 16.23 Hz, 1H), 2,792.73 (m, 2H), 2.67-2.60 (m, 3H), 2.14-2.08 (m, 4H), 1.99-1.88 (m, 2H), 1.76-1.65 (m, 1H). LC-MS: rt = 1.12 min, MS: 295.1 (calculated), 296.1 (M+H+, found).39 120 2-Amino-6-cyano-6-propyl-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 2.91-2.86 (m, 3H), 2.62 (d, J = 16.05 Hz, 1H), 2.18 (d, J = 13.42 Hz, 1H), 1.80-1.58 (m, 5H), 1.02 (t, J = 7.01 Hz, 3H). LC-MS: rt = 1.40 min, MS: 263.1 (calculated), 264.1 (M+H+, found). 40 121 2-Amino-6-cyano-6-ethyl-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CDCh δ (ppm): 6.17 (bs, 2H), 5.40 (bs, 2H), 2.95 (d, J = 16.8 Hz, 1H), 2.91-2.80 (m, 2H), 2.58 (dt, J = 16.0, 2.1 Hz, 1H), 2.26-2.17 (m, 1H), 1.85-1.67 (m, 3H), 1.17 (t, J = 7.4 Hz, 3H). LC-MS: rt = 1.13 min, MS: 249.1 (calculated), 250.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 150 / 282 145 / 236 Ex. No. Compound No. Structure Characterization 41 122 2-Amino-6-cyano-6-(methoxymethyl)4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide 1H NMR: 400 MHz, CDCh δ (ppm): 6.16 (bs, 2H), 5.41 (bs, 2H), 3.61-3.49 (m, 2H), 3.47 (s, 3H), 2.97 (d, J = 16.4 Hz, 1H), 2.91-2.81 (m, 2H), 2.72 (d, J = 16.0 Hz, 1H), 2.23 (d, J = 12.9 Hz, 1H), 1.90-1.77 (m, 1H). LC-MS: rt = 0.91 min, MS: 265.1 (calculated), 266.1 (M+H+, found). 42 123 2-Amino-6-cyano-6-(pyridin-3ylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 8.56 (d, J = 1.2 Hz, 1H), 8.51 (dd, J = 5.0, 1.2 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.47 (dd, J = 7.9, 4.9 Hz, 1H), 3.10 (s, 2H), 2.97-2.83 (m, 2H), 2.80 (d, J = 16.2 Hz, 1H), 2.74 (d, J = 16.2Hz, 1H), 2.20 (d, J = 13.2 Hz, 1H), 1.90 (ddd, J = 13.2, 10.0, 6.2 Hz, 1H). LC-MS: rt = 0.46 min, MS: 312.1 (calculated), 313.1 (M+H+, found).43 124 o 2-Amino-6-cyano-6-(pyridin-4ylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 8.54 (s, 2H), 7.44 (s, 2H), 3.09 (s, 2H), 2.97–2.70 (m, 4H), 2.25–2.13 (m, 1H), 1.97–1.79 (m, 1H). LC-MS: rt = 0.16 min, MS: 312.1 (calc.), 313.1 (M+H+, found). 44 125 2-Amino-6-cyano-6-((tetra-hydro2H-pyran-4-yl)methyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CDCh, δ (ppm): 6.17 (s, 2H), 5.39 (bs. 2H), 4.02–3.92 (m, 2H), 3.44 (td, J = 11.9, 1.9 Hz, 2H), 3.01 (d, J = 16.0 Hz, 1H), 2.94–2.81 (m, 2H), 2.63 (dt, J = 16.0, 2.1 Hz, 1H), 2.27–2.17 (m, 1H), 1.96–1.58 (m, 6H), 1.541.36 (m, 2H). LC-MS: rt = 1.00 min, MS: 319.1 (calc.), 320.1 (M+H+, found).45 126 2-Amino-6-cyano-6-(oxazol-2ylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.95 (d, J = 0.9 Hz, 1H), 7.19 (d, J = 0.9 Hz, 1H), 3.28 (s, 2H), 3.02-2.77 (m, 4H), 2.30 (dt, J = 14.4, 4.7 Hz, 1H), 1.91 (ddd, J = 13.4, 8.8, 6.8 Hz, 1H). LC-MS: rt = 0.85 min, MS: 302.1 (calculated), 302.9 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 151 / 282 146 / 236 Example No. Compound No. Structure Characterization 46 127 2-Amino-6-cyano-6(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.02 (s, 2H), 6.63 (bs, 2H), 2.92 (d, J = 16.1 Hz, 1H), 2.78 (bs, 2H), 2.65 (d, J = 16.1 Hz, 1H), 2.12 (d, J = 13.2 Hz, 1H), 1.74-1.54 (m, 3H), 0.91-0.84 (m, 1H), 0.53-0.51 (m, 2H), 0.21-0.17 (m, 2H). LC-MS: rt = 2.73 min, MS: 275.1 (calculated), 276.1 (M+H+, found). 47 128 2-Amino-6-cyano-6(cyclobutylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CDCb, δ (ppm): 6.16 (s, 2H), 5.37 (bs, 2H), 2.94-2.81 (m, 3H), 2.66 (p, J = 7.6 Hz, 1H), 2.57 (dt, J = 16.1, 2.2 Hz, 1H), 2.23-2.12 (m, 3H), 2.01-1.90 (m, 1H), 1.86- 1.67 (m, 6H). LC-MS: rt = 1.34 min, MS: 289.1 (calculated), 290.1 ​​(M+H+, found).48 129 2-Amino-6-cyano-6(cyclopentylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CDCh, δ (ppm): 6.16 (s, 2H), 5.37 (bs, 2H), 2.98 (d, J = 16.1 Hz, 1H), 2.91-2.84 (m, 2H), 2.61 (dt, J = 16.1, 2.2 Hz, 1H), 2.27-2.18 (m, 1H), 2.12-2.03 (m, 1H), 2.02-1.91 (m, 2H), 1,861.56 (m, 7H), 1.29-1.17 (m, 2H). LC-MS: rt = 1.39 min, MS: 303.1 (calculated), 304.1 (M+H+, found). 50 131 2-Amino-6-cyano-6-(2-(pyridin-4yl)ethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 8.51-8.45 (m, 2H), 7.33-7.29 (m, 2H), 7.00 (s, 2H), 6.63 (bs, 2H), 3.32-3.26 (m, 1H), 2.95 (d, J = 16.2 Hz, 1H), 2.89-2.75 (m, 3H), 2.69 (d, J = 16.2 Hz, 1H), 2.25-2.10 (m, 1H), 2.06-1.91 (m, 2H), 1.86-1.69 (m, 1H). LC-MS: rt = 0.41 min, MS: 326.1 (calculated), 327.1 (M+H+, found). Examples 51 to 56 Intermediate compound 64 4-(Bromomethyl)-4-propyltetrahydro-2H-pyran (64) Scheme 19 Step 1. Methyl 4-Propyltetrahydro-2H-pyran-4-carboxylate (62)

[00278] To a solution of LDA (8.32 mL, 1 M in THF / hexane, 8.32 Petition 870250100355, dated 03 / 11 / 2025, pp. 152 / 282 147 / 236 mmol) in anhydrous THF (20.8 mL) at -78 °C was added methyl tetrahydro-2H-pyran4-carboxylate (61) (0.926 mL, 6.94 mmol). The mixture was stirred at -78 °C for 45 min. Then, a mixture of hexamethylphosphoramide (0.673 mL, 3.87 mmol) and iodopropane (0.866 mL, 8.88 mmol) was added through a cannula. The resulting mixture was stirred for 20 minutes at -78 °C and then for 30 minutes at RT. The reaction mixture was poured into ice-cold water and Et2O. The two layers were separated, and the aqueous phase was extracted with Et2O. The combined organic layers were washed with brine, dried with NébSO.i, filtered, and concentrated to produce compound 62 as a yellow oil (736 mg, 57% yield), which was not characterized and used directly in the next step. Step 2. (4-Propyltetrahydro-2H-pyran-4-yl)methanol (63)

[00279] To a 1 M solution of LiAll 14 in THF (5.93 mL, 5.93 mmol) at 0 °C, a solution of 62 (736 mg, 3.95 mmol) in anhydrous Et2O (3.95 mL) was added dropwise. The reaction mixture was stirred at 0 °C for 2 hours. Then, EtOH was slowly added to the mixture until bubbling subsided. Next, water was slowly added and the mixture was stirred until a white precipitate appeared. The precipitate was removed by filtration and the filtrate was extracted with EA. The organic phase was dried with NebSO.i, filtered, and concentrated to yield the title compound 63 as a brown oil (511 mg, 82% yield), which was not characterized and used directly in the next step. Step 3. 4-(Bromomethyl)-4-propyltetrahydro-2H-pyran (64)

[00280] To a solution of 63 (511 mg, 3.23 mmol) in THF (0.807 mL) under Ar, carbon tetrabromide (1.18 g, 3.55 mmol) was added. The mixture was cooled to 0 °C and PPh3 (951 mg, 3.55 mmol) was added in portions. The reaction mixture was stirred for 16 hours, then slowly diluted with water. The two layers were separated, and the aqueous layer was extracted with Et2O. The combined organic layers were dried with Na2SO4, filtered, and Petition 870250100355, dated 03 / 11 / 2025, pp. 153 / 282 148 / 236 concentrated to produce the compound of title 64 as a transparent oil (270 mg, 38% yield), which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 66 (1-(Bromomethyl)cyclopropyl)(phenyl)sulfane (66) Scheme 20

[00281] To a solution of (1-(phenylthio)cyclopropyl)methanol (65) (J. Am. Chem. Soc. 99, 9, page 3080, 1977) (296 mg, 1.64 mmol) in anhydrous DCM (8.5 mL) at 0 °C, carbon tetrabromide (545 mg, 1.64 mmol) was added. Then, triphenylphosphine (527 mg, 1.97 mmol) was added in small portions and the reaction mixture was left in the open air until it slowly reached RT and stirred for 16 hours. The mixture was then rapidly cooled with a saturated 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 (eluent gradient from 0% to 30% EA in hexane) to yield title compound 66 (339 mg, 85% yield) as a colorless oil, which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 67 (1-(Bromomethyl)cyclopropyl)benzene (67)

[00282] Compound 67 was synthesized similarly to compound 66 (scheme 20) starting from (1-phenylcyclopropyl)methanol instead of (1-(phenylthio)cyclopropyl)methanol (65). Petition 870250100355, dated 03 / 11 / 2025, pp. 154 / 282 149 / 236 Intermediate compound 70 1-(Bromomethyl)-1-isobutylcyclopropane (70) Scheme 21 Step 1. (1-Isobutylcyclopropyl)methanol (69)

[00283] To a solution of 4-methyl-2-methylenepentan-1-ol (68) (J. Am. Chem. Soc. 140, 47, page 16152, 2018) (660 mg, 5.78 mmol) in anhydrous DCM (58 mL) at -10 °C, diethylzinc (11.6 mL, 1 M in hexane, 11.6 mmol) and diiodomethane (1.86 mL, 23.1 mmol) were added. The reaction mixture was stirred at -10 °C for 15 min, then at RT for 15 min, and finally under reflux for 16 hours. Subsequently, the reaction mixture was rapidly cooled with saturated NH4Cl solution, and the layers were separated. The organic phase was dried with Na2SÜ4, 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 69 (436 mg, 59% yield) as a colorless oil. Step 2. 1-(Bromomethyl)-1-isobutylcyclopropane (70)

[00284] To a solution of 69 (436 mg, 3.40 mmol) in anhydrous DCM (18 mL), triphenylphosphine (1.09 g, 4.08 mmol) and carbon tetrabromide (1.69 g, 5.10 mmol) were added. The reaction mixture was stirred at RT for 10 min, then rapidly cooled with saturated 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 (eluent gradient from 0% to 20% EA in hexane), then the oily product was removed from the excess carbon tetrabromide solid residue with a syringe and purified again by flash column chromatography (eluent gradient from 0% to 20% EA in hexane) to yield compound 70 (61 mg, 9% of Petition 870250100355, dated 03 / 11 / 2025, pp. 155 / 282 150 / 236 yield) as a colorless oil, which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 71 ((1-(Bromomethyl)cyclopropyl)methoxy)(tert-butyl)dimethylsilane (71)

[00285] Compound 71 was synthesized similarly to compound 66 (scheme 20) starting from (1-((( terbutyldimethylsilyl)oxy)methyl)cyclopropyl)methanol instead of (1(phenylthio)cyclopropyl)methanol (65). Intermediate compound 72 ((1-(Bromomethyl)cyclopropyl)methyl)(methyl)sulfane (72)

[00286] Compound 72 was synthesized similarly to compound 66 (scheme 20) starting from (1-(methylthio)cyclopropyl)methanol (WO 2017 / 055859) instead of (1-(phenylthio)cyclopropyl)methanol (65). Compounds 132 to 137

[00287] Compounds 132 to 137 (examples 51 to 56) were synthesized similarly to compound 4 (example 1, scheme 1), similarly to compound 6 (example 2, scheme 2) or similarly to compound 9 (example 3, scheme 3), starting from 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, scheme 1) and using in the first step 4-(bromomethyl)-4-propyltetrahydro-2H-pyran (Intermediate compound 64, scheme 19) (for 132), (1-(bromomethyl)cyclopropyl)(phenyl)sulfane (Intermediate compound 66, scheme 20) (for 133), (1-(bromomethyl)cyclopropyl)benzene (Intermediate compound 67) (for 134), 1-(bromomethyl)-1-isobutylcyclopropane (Intermediate compound 70, Scheme 21) (for 135), ((1-(bromomethyl)cyclopropyl)methoxy)(tert-butyl)dimethylsilane Petition 870250100355, dated 03 / 11 / 2025, pages 156 / 282 151 / 236 (Intermediate compound 71) (for 136) and ((1 (bromomethyl)cyclopropyl)methyl)(methyl)sulfane (Intermediate compound 72) (for 137), instead of 2-iodopropane, 1-bromo-2-methylpropane hydrobromide or 3-(2-bromoethyl)pyridine. The characterization of compounds 132 to 137 (examples 51 to 56) is given in Table 6. Table 6. Characterization of compounds 132 to 137 (examples 51 to 56). Ex. No. Compound number 132 Structure Characterization 133 134 2-Amino-6-cyano-6-((4-propyltetrahydro-2H-pyran-4-yl)methyl)-4,5,6,7tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.80-3.60 (m, 4H), 3.03 (d, J = 16.4 Hz, 1H), 2.95-2.80 (m, 2H), 2.77 (d, J = 16.0 Hz, 1H), 2.27-2.17 (m, 1H), 1.92-1.55 (m, 7H), 1,621.51 (m, 2H), 1.45-1.22 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H). LC-MS: rt = 1.27 min, MS: 361.2 (calculated), 362.2 (M+H+, found). 2-Amino-6-ciano-6-((1(feniltio)ciclopropil)metil)-4,5,6,7tetra-hidrobenzo[b]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7,45-7,42 (m, 2H), 7,38-7,34 (m, 2H), 7,24-7,20 (m, 1H), 7,02 (s, 2H), 6,58 (bs, 2H), 3,01 (d, J = 16,0 Hz, 1H), 2,79-2,67 (m, 3H), 2,252,19 (m, 1H), 2,09 (d, J = 15,0 Hz, 1H), 1,83 (d, J = 15,0 Hz, 1H), 1,761,68 (m, 1H), 1,15-1,12 (m, 2H), 1,04-1,01 (m, 2H). LC-MS: rt = 1,46 min, MS: 383,1 (calculado), 384,1 (M+H+, encontrado). 2-Amino-6-ciano-6-((1fenilciclopropil)metil)-4,5,6,7tetra-hidrobenzo[b]tiofeno-3RMN de1H: 400 MHz, CD3OD, δ (ppm): 7,50-7,47 (m, 2H), 7,32-7,28 (m, 2H), 7,24-7,19 (m, 1H), 2,772,64 (m, 2H), 2,56 (d, J = 16,2 Hz, 1H), 2,39 (dt, J = 16,2, 2,1 Hz, 1H), 2,13-2,05 (m, 2H), 1,94-1,88 (m, 1H), 1,60 (ddd, J = 13,4, 9,9, 6,0 Hz, 1H), 0,98-0,87 (m, 4H). LC-MS: rt = 1,41 min, MS: 351,1 (calculado), 352,2 (M+H+, encontrado). carboxamida 135 2-Amino-6-cyano-6-((1-isobutylcyclopropyl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CDCL. δ (ppm): 6.17 (s, 2H), 5.37 (bs, 2H), 3.03 (d, J = 16.2Hz, 1H), 2.95-2.81 (m, 2H), 2.69 (dt, J = 16.2, 2.1Hz, 1H), 2.31-2.25 (m, 1H), 2.09-1.99 (m, 1H), 1.86 (d, J = 14.7 Hz, 1H), 1.71 (ddd, J = 13.4, 10.1, 5.8 Hz, 1H), 1.60-1.55 (m, 1H), 1.47 (d, J = 14.7 Hz, 1H), 1.12 (dd, J = 14.5, 8.2 Hz, 1H), 0.96 (d, J = 4.5 Hz, 3H), 0.94 (d, J = 4.4 Hz, 3H), 0.42-0.37 Petition 870250100355, dated 03 / 11 / 2025, pp. 157 / 282 152 / 236 Example: No. Compound No. Structure Characterization (m, 4H). LC-MS: rt = 1.55 min, MS: 331.2 (calculated), 332.1 (M+H+, found). 55 136 2-Amin (hydroxymethyl 4,5,6,7-tetra3-c Of / o-6-cyano-6-((1Ll)cyclopropyl)methyl)hydrobenzo[ b ]thiophenearboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.01 (s, 2H), 6.59 (bs, 2H), 4.56 (t, J = 5.3 Hz, 1H), 3.44 (dd, J = 11.4, 5.3 Hz, 1H), 3.37 (dd, J = 11.4, 5.3 Hz, 1H), 2.93 (d, J = 16.1 Hz, 1H), 2.80-2.67 (m, 3H), 2,152.10 (m, 1H), 1.85 (d, J = 14.6 Hz, 1H), 1.74-1.67 (m, 1H), 1.66 (d, J = 14.6 Hz, 1H), 0.47-0.38 (m, 4H). LC-MS: rt = 0.89 min, MS: 305.1 (calculated), 306.1 (M+H+, found). 56 137 2-Amin (methylthio) 4,5,6,7-tetra3-c 00“ o-6-cyano-6-((1cyclopropyl)methyl)hydrobenzo[ b ]thiophenearboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.02 (s, 2H), 6.60 (bs, 2H), 3.02 (d, J = 15.9 Hz, 1H), 2.86-2.73 (m, 3H), 2.26-2.22 (m, 1H), 2.13 (s, 3H), 1.99 (d, J = 15.0 Hz, 1H), 1.811.71 (m, 2H), 0.88-0.77 (m, 4H).LC-MS: rt = 1.21 min, MS: 321.1 (calculated), 322.0 (M+H+, found). Example 57 2-Amino-6-(2-hydroxyethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (139) Scheme 30

[00288] To a solution of 138 (synthesized similarly to compound 45 (scheme 13) starting from 4-(2-hydroxyethyl)-4-phenylcyclohexan-1-one (Bioorg. Med. Chem. Lett., 21, page 405, 2011) instead of 4-(3-hydroxymethyl)-4-phenylcyclohexan-1-one) (8 mg, 0.019 mmol) in anhydrous THF (1.0 mL) was added TBAF (0.028 mL, 1 M in THF, 0.028 mmol) and the reaction mixture was stirred at RT for 2 hours. Then, the mixture was rapidly cooled with saturated NaHCO3 solution and extracted with EA. The organic layer was dried with Na2SO4, filtered and Petition 870250100355, dated 03 / 11 / 2025, pp. 158 / 282 153 / 236 concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane) to yield the title compound 139 (2 mg, 34% yield) as a white solid.

[00289] 1H NMR: 400 MHz, CDCb, δ (ppm): 7.29-7.20 (m, 5H), 6.15 (s, 2H), 5.25 (bs, 2H), 3.55-3.48 (m, 1H), 3.44-3.38 (m, 1H), 3.12 (d, J = 16.4 Hz, 1H), 2.77 (d, J = 16.4 Hz, 1H), 2.66-2.61 (m, 1H), 2.23-2.12 (m, 3H), 2.08-2.02 (m, 1H), 1.96-1.89 (m, 1H). LC-MS: rt = 1.06 min, MS: 316.1 (calculated), 317.2 (M+H+, found). Example 58 2-Amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3,6-dicarboxamide (140) Scheme 31

[00290] To a suspension of 85 (example 21, Table 3) (100 mg, 0.336 mmol) and K2CO3 (93 mg, 0.673 mmol) in DMSO (2.5 mL) was added 30% H2O2 (0.5 mL). The reaction was vigorously stirred at RT for 16 hours. Then, more 30% H2O2 (0.5 mL) was added, and the reaction was stirred at RT for 6 hours. Subsequently, the mixture was diluted with water and extracted with EA. The organic layer was dried with Na2SO4, filtered, and evaporated. The residue was ground in CHCl3 and collected by filtration to yield the compound of title 140 as a pale orange solid (29 mg, 27% yield). 10 mg were further purified by flash chromatography on a reversed-phase column (eluent gradient from 0% to 100% CH3CN in 0.1% (v / v) formic acid in water) to yield 5 mg of highly pure material (96% purity by HPLC).

[00291] 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.37-7.35 (m, 2H), 7.33-7.29 (m, 2H), 7.23-7.20 (m, 1H), 7.03 (s, 1H), 6.98 (s, 2H), 6.87 (s, 1H), Petition 870250100355, dated 03 / 11 / 2025, pp. 159 / 282 154 / 236 6.43 (bs, 2H), 3.14 (d, J = 16.1 Hz, 1H), 2.93 (d, J = 16.1 Hz, 1H), 2.72-2.66 (m, 1H), 2.39-2.32 (m, 2H), 2.24-2.18 (m, 1H). LC-MS: rt = 0.93 min, MS: 315.1 (calculated), 316.1 (M+H+, found). Examples 59 to 74 Intermediate compound 34 4-(3-Hydroxypropyl)-4-phenylcyclohexan-1-one (34) Scheme 9 Step 1. 3-(8-phenyl-1,4-dioxaspiror[4.5]decan-8-yl)propanoic acid (31)

[00292] To a solution of 3-(8-phenyl-1,4-dioxaspiror[4.5]decan-8-yl)propanonitrile (30) (2.30 g, 8.48 mmol) (Bioorg Med. Chem Lett. 21, page 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 naturally 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 produce compound 31 (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 (32)

[00293] To a solution of 31 (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 Petition 870250100355, dated 03 / 11 / 2025, pp. 160 / 282 155 / 236 at RT for 16 hours, then diluted with water and extracted with Et2U. This organic layer was washed with brine and dried with MgSO4, filtered and concentrated to produce compound title 32 (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-dioxaspiro[4.5]decan-8-yl)propan-1-ol (33)

[00294] 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 32 (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 MeOH 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 Na2SO4, 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 33 (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 (34)

[00295] To a solution of 33 (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 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 N2SO4, filtered, and concentrated to dryness to yield the title compound 34 (289 mg, 94% yield) as a yellow oil. The product was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 38 Petition 870250100355, dated 03 / 11 / 2025, pp. 161 / 282 156 / 236 4-(2,2-Difluoroethyl)-4-phenylcyclohexan-1-one (38) Scheme 10 Step 1. 2-(8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)acetaldehyde (36)

[00296] To a solution of 2-(8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)acetonitrile (35) (1.0 g, 3.89 mmol) (Bioorg Med. Chem Lett. 21, page 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 W2SO4, filtered, and concentrated.The residue was purified by flash column chromatography (5% to 100% EA eluent gradient in hexane) to yield compound 36 (605 mg, 60% yield) as a colorless oil, which was not characterized and used directly in the next step. Step 2. 8-(2,2-Difluoroethyl)-8-phenyl-1,4-dioxaspiro[4.5]decane (37)

[00297] To a solution of 36 (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 solution Petition 870250100355, dated 03 / 11 / 2025, pages 162 / 282 157 / 236 saturated with NaHCO3e extracted with DCM. The organic layer was dried with Na2SO4, filtered and concentrated to produce compound 37 (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 (38)

[00298] To a solution of 37 (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 concentrated saturated NaHCO3 solution to remove the organic solvent. The residue was extracted with EA, and the organic layer was washed with brine, dried with W2SO4, filtered, and concentrated to dryness to yield the title compound 38 (169 mg, 94% yield) as a colorless oil. The product was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 40 8-((1-Methylcyclopropyl)methyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (40) Scheme 11 Step 1. 8-(2-Methylallyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (39)

[00299] To a solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1, Scheme 1) (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 solution of NH4Cl. Petition 870250100355, dated 03 / 11 / 2025, pp. 163 / 282 158 / 236 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 50% EA in hexane) to yield compound 39 (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 (40)

[00300] To a solution of 39 (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 W2SO4, 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 40 (233 mg, 34% yield) as a colorless oil, which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 51 3-(1-(Cyclopropylmethyl)-4-oxocyclohexyl)propanenitrile (51) Scheme 14 Step 1. 8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbaldehyde (48)

[00301] Diisobutylaluminum hydride (25% solution in toluene; 121 Petition 870250100355, dated 03 / 11 / 2025, pp. 164 / 282 159 / 236 mL, 180.0 mmol) was added dropwise to a solution of 8(cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (47) (24.3 g, 110 mmol) (ACS Med. Chem. Lett. 2010, 350 to 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) at -78 °C and partitioned between aqueous saturated NH4Cl solution (200 mL) and diethyl ether (300 mL). The mixture was left in the open air until it slowly reached RT, and an aqueous saturated 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 saturated aqueous NaHCO3 and concentrated to remove the organic solvent.The aqueous residue was extracted with diethyl ether, and the organic compounds were dried with NebSO4, filtered, and concentrated to produce compound 48 as a colorless oil (24.6 g, >99% yield), which was not characterized and used directly for the next step. Step 2. 3-(8-(cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acrylonitrile (49)

[00302] To a mixture of sodium hydride (2.14 g, 53.5 mmol) and DMPU (11.3 mL, 93.6 mmol) in anhydrous THF (40 mL) at 0 °C, diethylcyanomethylphosphonate (8.65 mL, 53.5 mmol) was slowly added. The mixture was stirred at 0 °C for 1 hour, then a solution of 48 (10.0 g, 44.6 mmol) in anhydrous THF (65 mL) was added dropwise, and the reaction mixture was stirred at RT for 24 hours. The mixture was partitioned between water and EA (200 mL each). The layers were separated, and the organic phase was washed with brine (150 mL), dried with MgSO4, filtered, and concentrated. The residue was purified by column chromatography (mixture of eluents at 50% Et2O in hexane) to yield the title compound 49 as a colorless oil. Petition 870250100355, dated 03 / 11 / 2025, pages 165 / 282 160 / 236 (10.0 g, 91% yield), which was not characterized and used directly for the next step. Step 3. 3-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)propanenitrile (50)

[00303] A suspension of 49 (10.0 g, 40.4 mmol) and 10% Pd / C (215 mg) in EA (189 mL) and EtOH (246 mL) was stirred under a hydrogen atmosphere (flask) at RT for 24 hours. The mixture was then filtered, and the filtrate was concentrated to yield the title compound 50 as a colorless oil (9.90 g, 98% yield), which was used in Step 4 without purification and without characterization. Step 4. 3-(1-(Cyclopropylmethyl)-4-oxocyclohexyl)propanenitrile (51)

[00304] 2 N aqueous HCl (186 mL, 372 mmol) was added to a solution of 50 (9.30 g, 37.3 mmol) in acetone (460 mL), and the resulting mixture was stirred at 40 °C for 24 hours, then rapidly cooled with aqueous saturated NaHCO3 (200 mL) and concentrated to remove the organic solvent. The residue was extracted with EA (2 x 250 mL). The combined organic compounds were washed with brine, dried with Na2SO4, filtered, and concentrated to yield the title compound 51 as a colorless oil (6.90 g, 90% yield), which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 53 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)ethan-1-ol (53) Scheme 15 Step 1. 8-(Cyclopropylmethyl)-8-vinyl-1,4-dioxaspiro[4.5]decane (52)

[00305] For a 1 M solution of LHMDS in THF (10 mL, 10.0 mmol) Petition 870250100355, dated 03 / 11 / 2025, pp. 166 / 282 161 / 236 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, 48 (scheme 14) (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, abruptly cooled with a saturated NH4Q solution (40 mL) and extracted twice with EA (2 x 50 mL). The combined organic compounds were dried with Na2SO4, filtered and concentrated, and the residue was purified by flash column chromatography (eluent gradient from 0% to 30% Et2O in hexane) to yield the title compound 52 as a colorless oil (527 mg, 76% yield), which was not characterized and used directly for the next step. Step 2. 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)ethan-1-ol (53)

[00306] To a solution of 52 (1.39 g, 6.27 mmol) in anhydrous THF (32 mL) at 0 °C, 9-BBN (25 mL, 0.5 M in THF, 12.5 mmol) was added dropwise. The reaction mixture was stirred at RT for 2.5 hours, then cooled to 0 °C again, and water (0.113 mL, 6.27 mmol), 1 N NaOH (18.8 mL, 18.8 mmol) and 30% H2O2 (32 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 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 53 as a colorless oil (1.28 g, 85% yield), which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 59 2-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acetamide (59) Petition 870250100355, dated 03 / 11 / 2025, pp. 167 / 282 162 / 236 Scheme 17 Step 1. 3-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8yl)propanoic acid (57)

[00307] To a solution of 50 (scheme 14) (2.14 g, 8.58 mmol) in ethylene glycol (45.5 mL), potassium hydroxide (3.85 g, 68.7 mmol) and water (31.0 pL, 1.72 mmol) were added. The resulting mixture was stirred at 170 °C for 24 hours. The mixture was allowed to cool to RT, diluted with water (50 mL) and washed with DCM (2 x 50 mL). The aqueous phase was acidified to pH 2 by adding 2 N HCl and extracted with DCM (3 x 10 mL). These organic compounds were dried with MgSO4, filtered and concentrated to yield the compound of title 57 as a red oil, which was used directly in Step 2 without purification and characterization. Step 2. 3-(8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decan-8-yl)propan-1-ol (58)

[00308] To a solution of 57 (8.58 mmol) in anhydrous THF (54 mL) at 0 °C, lithium aluminum hydride (9.55 mL, 2 M in THF, 19.1 mmol) was added dropwise. The resulting mixture was stirred at 0 °C for 1 hour, left in the open air until RT was reached, and stirred for 16 hours. Saturated aqueous solution of Rochelle salt (30 mL) was added dropwise, then the mixture was diluted with EA (50 mL), stirred at RT for 30 min, and filtered through a Celite filter. The layers were separated, and the aqueous phase was extracted with EA (2 x 50 mL). The combined organic compounds were dried with MgSO4, filtered, and concentrated to yield the title compound 58 as a yellow oil (2.07 g, 95% yield over two Petition 870250100355, dated 03 / 11 / 2025, pp. 168 / 282 163 / 236 steps), which was used in Step 3 without purification and characterization. Step 3. 4-(Cyclopropylmethyl)-4-(3-hydroxypropyl)cyclohexan-1-one (59)

[00309] To a solution of 58 (2.07 g, 8.14 mmol) in acetone (125 mL), 2 N aqueous HCl (22.9 mL, 45.7 mmol) was added, and the resulting mixture was stirred at RT for 70 hours. Then, the mixture was neutralized with a saturated aqueous solution of NaHCO3 (50 mL) and concentrated to remove the organic solvent. The residue was then partitioned between EA (50 mL) and water (40 mL), the layers were separated, and the organic phase was dried with Na2SO4, filtered, and concentrated. The residue was absorbed in DCM (30 mL), and the insoluble impurity was removed by filtration and washed with DCM (50 mL). The filtrate and washings were combined and concentrated to produce compound 59 as a thick, pale yellow oil (1.53 g, 89% yield), which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 60 8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carboxamide (60) Scheme 18

[00310] To a suspension of 47 (scheme 14) (200 mg, 0.90 mmol) and potassium carbonate (250 mg, 1.81 mmol) in DMSO (6.6 mL) was added H2O2 (3 mL) and the reaction was stirred for 16 hours at RT. Then, the mixture was diluted with water and extracted with EA. The organic layers were dried with Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography (eluent gradient from 0% to 20% MeOH in DCM) to yield the title compound 60, which was not characterized and used directly for the synthesis of relevant examples. Petition 870250100355, dated 03 / 11 / 2025, pp. 169 / 282 164 / 236 Intermediate compound 93 1-(3-(1-Methyl-1H-pyrazol-4-yl)phenyl)-4-oxocyclohexane-1-carbonitrile (93) Scheme 23

[00311] To a solution of 1-(3-bromophenyl)-4-oxocyclohexanecarbonitrile (91) (20.0 mg, 71.9 μmol) in dioxane (338 pL) and water (84.6 pL) under Ar were added (1-methyl-1H-pyrazol-4-yl)boronic acid (92) (11.1 mg, 86.3 pmol), Pd(dppf)Cl2 (8.81 mg, 10.8 pmol) and tripotassium phosphate (45.8 mg, 216 pmol). The reaction mixture was stirred at 80 °C for 24 hours, then cooled to RT and diluted with EA. The layers were separated, the aqueous phase was extracted with EA, and the combined organics were dried with Na2SO4, filtered, and concentrated to dryness to produce the compound of title 93. LC-MS: rt = 1.33 min, MS: 279.1 (calculated), 280.0 (M+H+, found). Intermediate compound 95 8-Ethyl-8-phenyl-1,4-dioxaspiro[4.5]decane (95) Scheme 24

[00312] To a solution of 8-phenyl-8-vinyl-1,4-dioxaspiro[4.5]decane (94) (WO 2018 / 081384) (174 mg, 0.712 mmol) in EA (48 mL) was added 10% Pd / C (20 mg). Then, the reaction mixture was stirred at RT for 2 hours under a hydrogen atmosphere (flask). Subsequently, the mixture was filtered through a Celite filter and concentrated to yield the compound of title 95 (167 mg, 95% yield) as a colorless oil. LC-MS: rt = 3.37 min, MS: 246.2 (calculated), 247.2 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 170 / 282 165 / 236 Intermediate compound 97 8-Fluoro-8-(fluoro(phenyl)methyl)-1,4-dioxaspiro[4.5]decane (97) Scheme 25

[00313] To a solution of 8-phenyl-1,4-dioxaspiro[4.5]decane-8 carbaldehyde (96) (Bioorg Med. Chem Lett. 21, page 405, 2011) (200 mg, 0.812 mmol) in anhydrous DCM (10 mL) at 0 °C, DAST (0.20 mL, 1.62 mmol) was added. The reaction mixture was then stirred at RT for 16 hours and cooled to 0 °C again, before being rapidly cooled with saturated NaHCO3 solution. The mixture was extracted with DCM, and the organic layer was dried with Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 20% EA in hexane) to yield the title compound 97 (53 mg, 24% yield) as a colorless oil, which was not characterized and used directly for the synthesis of relevant examples. Intermediate compound 141 8-((1-Methoxycyclopropyl)methyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (141)

[00314] Compound 141 was synthesized similarly to intermediate compound 40 (scheme 11) starting from 1,4dioxaspiro[4.5]decane-8-carbonitrile (1) and using in the first step 3-bromo-2-methoxyprop-1-ene (J. Org. Chem. 42, 15, page 2545, 1977) instead of 3-bromo-2-methylpropene. The product was not characterized and used directly for the synthesis of relevant examples. Compounds 142 to 157

[00315] Compounds 142 to 157 (examples 59 to 74) were Petition 870250100355, dated 03 / 11 / 2025, pages 171 / 282 166 / 236 synthesized following the procedure reported for the synthesis of compound 4 (example 1, scheme 1) or the procedure reported for the synthesis of compound 6 (example 2, scheme 2) and starting from the following suitably substituted ketones or dioxolanes: intermediate compound 97 (scheme 25) (for 142), intermediate compound 51 (scheme 14) (for 143), 54 (scheme 16) (for 144), 57 (scheme 17) (for 145), intermediate compound 56 (scheme 16) (for 146), intermediate compound 59 (scheme 17) (for 147), intermediate compound 60 (scheme 18) (for 148), 2-(4-oxo-1-phenylcyclohexyl)acetonitrile (Bioorg. Med. Chem. Lett., 21, page 405, 2011) (for 149), 30 (scheme 9) (for 150), intermediate compound 34 (scheme 9) (for 151), intermediate compound 38 (scheme 10) (for 152), intermediate compound 53 (scheme 15) (for 153), intermediate compound 93 (scheme 23) (for 154), intermediate compound 95 (scheme 24) (for 155), intermediate compound 40 (scheme 11) (for 156) and intermediate compound 141 (for 157). The characterization of compounds 142 to 157 (examples 59 to 74) is provided in Table 7. Table 7. Characterization of compounds 142 to 157 (examples 59 to 74). Ex. No. Compound No. Structure Characterization 59 142 2-Amino-6-fluoro-6(fluoro(phenyl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.46-7.44 (m, 5H), 6.95-6.89 (m, 2H), 6.59 (bs, 2H), 5.67 (ddd, J = 44.2, 20.6, 2.8 Hz, 1H), 3.01-2.61 (m, 4H), 2.36-2.22 (m, 1H), 1.80-1.76 (m, 1H). 19F NMR: 376 MHz, CD3OD, δ (ppm): -172.9 - -173.2 (m, 0.5F), -173.3 - -173.6 (m, 0.5F), -190.5 (dd, J = 44.2, 11.3 Hz, 0.5F), -191.4 (dd, J = 44.2, 9.7Hz, 0.5F). LC-MS: rt = 3.05 min, MS: 322.1 (calculated), 323.1 (M+H+, found). 60 143 2-Amino-6-(2-cyanoethyl)-6(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 6.86 (s, 2 H), 6.51 (bs, 2H), 2,652.49 (m, 2H), 2.44-2.39 (m, 2H), 2,392.23 (m, 2H), 1.78-1.63 (m, 2H), 1,561.44 (m, 2H), 1.30 (dd, J = 14.39, 6.23 Hz, 1 H), 1.09-1.04 (m, 1H), 0.64-0.57 (m, 1H), 0.41-0.37 (m, 2H), 0.03-0.00 (m, 2H).LC-MS: rt = 1.29 min, MS: 303.1 (calculated), 304.3 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 172 / 282 167 / 236 Example No. Compound No. Structure Characterization 61 144 VoP- 2-Amino-6-(cyclopropylmethyl)-6(hydroxymethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 6.89 (s, 2H), 6.49 (bs, 1H), 4.44 (t, J = 5.12 Hz, 1H), 3.37-3.34 (m, 2H), 2.55 (t, J = 6.15 Hz, 2H), 2.31-2.28 (m, 2H), 1.50-1.60 (m, 2H), 1.33 (dd, J = 13.98, 6.19 Hz, 1H), 1.14-1.08 (m, 1H), 0.690.62 (m, 1H), 0.39-0.35 (m, 2H), 0.02 -0.08 (m, 2H). LC-MS: rt = 1.09 min, MS: 280.1 (calculated), 281.2 (M+H+, found). 62 145 3-(2-Amino-3-carbamoyl-6(cyclopropylmethyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophen-6-yl)propanoic acid 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 6.90 (s, 2H), 6.51 (bs, 2H), 2,582.52 (m, 2H), 2.34-2.21 (m, 2H), 2,192.13 (m, 2H), 1.72-1.44 (m, 4H), 1,341.27 (m, 1H), 1.07 (dd, J = 14.35, 7.18 Hz, 1H), 0.66-0.59 (m, 1H), 0.42-0.38 (m, 2H), 0.03 - -0.05 (m, 2H). LC-MS: rt = 1.20 min, MS: 322.1 (calculated), 321.1 ([MH]-, found).63 146 2-Amino-6-(cianometil)-6(ciclopropilmetil)-4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3-carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 6,90 (s, 2H), 6,56 (bs, 2H), 2,662,60 (m, 4H), 2,56 (d, J = 14,31 Hz, 1H), 2,38 (d, J = 16,18 Hz, 1H), 1,65 (t, J = 6,31 Hz, 2H), 1,41 (dd, J = 14,32, 6,43 Hz, 1H), 1,27 (dd, J = 14,34, 7,05 Hz, 1H), 0,74-0,68 (m, 1H), 0,48-0,43 (m, 2H), 0,11-0,00 (m, 2H). LC-MS: rt = 1,22 min, MS: 289,1 (calculado), 290,1 (M+H+, encontrado). 64 147 2-Amino-6-(ciclopropilmetil)-6-(3hidroxipropil)-4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3-carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 6,89 (s, 2H), 6,50 (bs, 1 H), 4,34 (t, J = 5,18 Hz, 1 H), 3,39-3,32 (m, 2H), 2,56-2,51 (m, 2H), 2,40-2,19 (m, 2H), 1,55-1,46 (m, 2H), 1,47-1,27 (m, 5H), 1,09-1,02 (m, 1H), 0,67-0,60 (m, 1H), 0,41-0,35 (m, 2H), -0,02 - -0,06 (m, 2H). LC-MS: rt = 1,21 min, MS: 308,2 (calculado), 309,1 (M+H+, encontrado).65 148 Ppi 2-Amino-6-(cyclopropylmethyl)-4,5,6,7tetrahydrobenzo[b]thiophene-3,6dicarboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.08 (s, 1H), 6.88 (s, 2H), 6.81 (s, 1H), 6.44 (bs, 2H), 2.88 (d, J = 16.02 Hz, 1H), 2.60-2.50 (m, 2H), 2.38 (d, J = 16.03 Hz, 1H), 1.96-1.93 (m, 1H), 1.70-1.67 (m, 1H), 1.57 (dd, J = 13.92, 6.13 Hz, 1H), 1.27 (dd, J = 13.94, 7.29 Hz, 1H), 0.640.52 (m, 1H), 0.40-0.36 (m, 2H), 0.00 -0.04 (m, 2H). LC-MS: rt = 0.93 min, MS: 293.1 (calculated), 294.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 173 / 282 168 / 236 Example No. Compound No. Structure Characterization 66 149 OγΖ 2-Amino-6-(cyanomethyl)-6-phenyl4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide 1H NMR: 400 MHz, CDCh. δ (ppm): 7.39-7.36 (m, 4H), 7.31-7.28 (m, 1H), 6.18 (s, 2H), 5.28 (bs, 2H), 3.20 (d, J = 16.4 Hz, 1H), 2.91 (d, J = 16.4 Hz, 1H), 2.81-2.66 (m, 3H), 2.47-2.39 (m, 1H), 2.29-2.27 (m, 2H). LC-MS: rt = 1.16 min, MS: 311.1 (calculated), 295.1 (M-NH3+H+, found). 67 150 OjqX 2-Amino-6-(2-cyanoethyl)-6-phenyl4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide 1H NMR: 400 MHz, CDCh. δ (ppm) 3H), 2.11-1.88 (m, 4H). LC-MS: rt = 1.24 min, MS: 325.1 (calculated), 326.2 (M+H+, found).68 151 ΟγΖ 2-Amino-6-(3-hidroxipropil)-6-fenil4,5,6,7-tetra-hidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7,30-7,26 (m, 4H), 7,17-7,13 (m, 1H), 6,97 (s, 2H), 6,42 (bs, 2H), 4,28 (t, J = 5,1 Hz, 1H), 3,23-3,19 (m, 2H), 2,95 (d, J = 16,2 Hz, 1H), 2,62-2,56 (m, 2H), 2,21-2,15 (m, 1H), 2,09-2,05 (m, 1H), 1,93-1,87 (m, 1H), 1,72 (td, J = 12,8, 4,2 Hz, 1H), 1,52 (td, J = 12,8, 4,2 Hz, 1H), 1,23-1,14 (m, 1H), 1,04-0,95 (m, 1H). LC-MS: rt = 1,12 min, MS: 330,1 (calculado), 331,1 (M+H+, encontrado). 69 152 2-Amino-6-(2,2-difluoroetil)-6-fenil4,5,6,7-tetra-hidrobenzo[ b ]tiofeno-3carboxamida RMN de 1H: 400 MHz, CDCh, δ (ppm): 7,34-7,20 (m, 5H), 6,15 (s, 2H), 5,40 (tdd, J = 56,3, 6,2, 3,5 Hz, 1H), 5,26 (bs, 2H), 3,14 (d, J = 16,6 Hz, 1H), 2,80 (d, J = 16,6 Hz, 1H), 2,68-2,61 (m, 1H), 2,442,30 (m, 1H), 2,27-2,05 (m, 4H). RMN de 19F 376 MHz, CDCl3, δ (ppm): -111,9 -112,2 (m, 2F). LC-MS: rt = 1,39 min, MS: 336,1 (calculado), 337,0 (M+H+, encontrado).70 153 2-Amino-6-(cyclopropylmethyl)-6-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 3.71-3.64 (m, 2H), 2.68-2.64 (m, 2H), 2.49 (d, J = 16.0 Hz, 1H), 2.40 (d, J = 16.0 Hz, 1H), 1.81-1.69 (m, 4H), 1.45 (dd, J = 14.3, 5.9 Hz, 1H), 1.16 (dd, J = 14.3, 7.4 Hz, 1H), 0.77-0.68 (m, 1H), 0.50-0.46 (m, 2H), 0.06-0.03 (m, 2H). LC-MS: rt = 1.12 min, MS: 294.1 (calculated), 295.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 174 / 282 169 / 236 Ex. No. Compound number Structure Characterization 154 2-Amino-6-cyano-6-(3-(1-methyl-1Hpyrazol-4-yl)phenyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxamide RMN de 1H: 400 MHz, CDCh, d (ppm): 7,78 (s, 1H), 7,67 (s, 1H), 7,63 (s, 1H), 7,50-7,45 (m, 1H), 7,42 (t, J = 7,6 Hz, 1H), 7,37-7,31 (m, 1H), 6,22 (s, 2H), 5,42 (bs, 2H), 3,97 (s, 3H), 3,24-3,13 (m, 2H), 3,13-3,00 (m, 1H), 2,98-2,89 (m, 1H), 2,50-2,42 (m, 1H), 2,41-2,31 (m, 1H). LC-MS: rt = 1,35 min, MS: 377,1 (calculado), 377,9 (M+H+, encontrado). 155 2-Amino-6-etil-6-fenil-4,5,6,7-tetrahidrobenzo[ b ]tiofeno-3-carboxamida RMN de 1H: 400 MHz, CDCl3, δ (ppm): 7,30-7,23 (m, 4H), 7,19-7,16 (m, 1H), 6,15 (bs, 2H), 6,29 (bs, 2H), 3,07 (d, J = 16,4 Hz, 1H), 2,65-2,57 (m, 2H), 2,212,13 (m, 2H), 2,02-1,95 (m, 1H), 1,921,83 (m, 1H), 1,67-1,58 (m, 1H), 0,64 (t, J = 7,4 Hz, 3H). LC-MS: rt = 1,52 min, MS: 300,1 (calculado), 301,1 (M+H+, encontrado). 156 2-Amino-6-ciano-6-((1metilciclopropil)metil)-4,5,6,7-tetrahidrobenzo[b]tiofeno-3-carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7,01 (s, 2H), 6,60 (bs, 2H), 2,91 (d, J = 16,1 Hz, 1H), 2,81-2,76 (m, 2H), 2,69 (d, J = 16,1 Hz, 1H), 2,14-2,08 (m, 1H), 1,79 (d, J = 14,5 Hz, 1H), 1,72-1,65 (m, 1H), 1,53 (d, J = 14,5 Hz, 1H), 1,21 (s, 3H), 0,43-0,28 (m, 4H). LC-MS: rt = 1,26 min, MS: 289,1 (calculado), 290,2 (M+H+, encontrado). 157 2-Amino-6-ciano-6-((1metoxiciclopropil)metil)-4,5,6,7tetra-hidrobenzo[b]tiofeno-3carboxamida RMN de 1H: 400 MHz, DMSO-d6, δ (ppm): 7,02 (s, 2H), 6,61 (bs, 2H), 3,20 (s, 3H), 2,95 (d, J = 16,1 Hz, 1H), 2,812,76 (m, 3H), 2,21-2,16 (m, 1H), 2,08 (d, J = 15,1 Hz, 1H), 1,86 (d, J = 15,1 Hz, 1H), 1,80-1,73 (m, 1H), 0,78-0,71 (m, 2H), 0,59-0,51 (m, 2H). LC-MS: rt = 1,04 min, MS: 305,1 (calculado), 306,2 (M+H+, encontrado). Exemplo 75 2-Amino-6-(3-amino-3-oxopropil)-6-(ciclopropilmetil)-4,5,6,7-tetrahidrobenzorb]tiofeno-3-carboxamida (158)

[00316] Compound 158 (example 75) was synthesized in a similar manner to compound 76 (example 12, scheme 22) starting from compound Petition 870250100355, dated 03 / 11 / 2025, pp. 175 / 282 170 / 236 145 (example 62, table 7) instead of 75.

[00317] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.20 (s, 1 H), 6.88 (s, 2H), 6.64 (s, 1H), 6.48 (bs, 1H), 2.57-2.50 (m, 2H), 2.34 (d, J = 16.02 Hz, 1H), 2.22 (d, J = 15.97 Hz, 1H), 1.99-1.97 (m, 2H), 1.62-1.51 (m, 3H), 1.461.43 (m, 1H), 1.28 (dd, J = 14.23, 6.11 Hz, 1H), 1.03 (dd, J = 14.23, 7.22 Hz, 1H), 0.68-0.58 (m, 1H), 0.43-0.31 (m, 2H), -0.03 - -0.08 (m, 2H). LC-MS: rt = 1.05 min, MS: 321.2 (calculated), 322.2 (M+H+, found). Example 76 2-Amino-6-(2-ammo-2-oxoethyl)-6-feml-4,5,6,7-tetrahydrobenzo[b]thiophene-3carboxamide (159)

[00318] Compound 159 (example 76) was synthesized similarly to compound 140 (example 58, scheme 31) starting from compound 149 (example 66, table 7) instead of 85.

[00319] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.32-7.30 (m, 2H), 7.27-7.23 (m, 2H), 7.15-7.12 (m, 1H), 7.04 (s, 1H), 6.97 (s, 2H), 6.59 (s, 1H), 6.41 (bs, 2H), 3.09 (d, J = 16.5 Hz, 1H), 2.95 (d, J = 16.5 Hz, 1H), 2,672.59 (m, 1H), 2.46 (d, J = 13.9 Hz, 1H), 2.39 (d, J = 13.9 Hz, 1H), 2.13-2.00 (m, 3H). LC-MS: rt = 2.04 min. MS: 329.1 (calculated), 330.1 (M+H+, found). Example 77 2-Amino-6-(3-amino-3-oxopropyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene3-carboxamide (160) Petition 870250100355, dated 03 / 11 / 2025, pp. 176 / 282 171 / 236

[00320] Compound 160 (example 77) was synthesized in a similar manner to compound 140 (example 58, scheme 31) starting from 150 (example 67, table 7) instead of 85.

[00321] 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.30-7.27 (m, 4H), 7.19-7.15 (m, 1H), 7.12 (s, 1H), 6.98 (s, 2H), 6.64 (s, 1H), 6.43 (bs, 2H), 2.93 (d, J = 16.2 Hz, 1H), 2.67-2.58 (m, 2H), 2.18-2.08 (m, 2H), 2.00-1.88 (m, 2H), 1.84-1.74 (m, 2H), 1.62-1.54 (m, 1H). LC-MS: rt = 1.06 min, MS: 343.1 (calculated), 343.9 (M+H+, found). Examples 78 to 82

[00322] Compounds 161 to 165 (examples 78 to 82) were synthesized similarly to compound 85 (example 21, Table 3) and using 2-cyano-N-cyclopropylacetamide, 2-cyano-N-isopropylacetamide, 2-cyano-N-ethylacetamide, 2-cyano-N-methylacetamide and 2-cyano-N-propylacetamide, respectively, instead of 2-cyanoacetamide. The characterization of compounds 161 to 165 (examples 78 to 82) is given in Table 8. Table 8. Characterization of compounds 161 to 165 (examples 78 to 82). Example No. Compound No. Structure Characterization 78 161 oxoX 2-Amino-6-cyano-N-cyclopropyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.57 (d, J = 7.74 Hz, 2H), 7.44 (t, J = 7.53 Hz, 2H), 7.36 (t, J = 7.22 Hz, 1H), 7.05 (d, J = 3.68 Hz, 1H), 6.67 (s, 2H), 3.10-3.03 (m, 2H), 2.92-2.87 (m, 1H), 2.74-2.67 (m, 2H), 2.25 (t, J = 5.17 Hz, 2H), 0.65-0.57 (m, 2H), 0.51 (t, J = 3.98 Hz, 2H). LC-MS: rt = 1.68 min, MS: 337.1 (calculated), 338.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 177 / 282 172 / 236 79 162 o ~ ü 7.59 Hz, 2H), 7.36 (t, J = 7.27 Hz, 1H), 4.12 (t, J = 6.62 Hz, 1H), 3.14 (s, 2H), 2.98 (t, J = 8.55 Hz, 1H), 2.87 (d, J = 16.77 Hz, 1H), 2.36 (dd, J = 8.01, 4.37 Hz, 2H), 1.23 (d, J = 6.58 Hz, 6H). LC-MS: rt = 1.80 min, MS: 339.1 (calculated), 340.1 (M+H+, found). 80 163 · 2-Amino-6-cyano-N-ethyl-6-phenyl4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, d ppm 7.58 (d, J = 7.8 Hz, 2H), 7.44 (t, J = 8.6 Hz, 2H), 7.40-7.32 (m, 1H), 3.42-3.33 (m, 2H), 3.14 (s, 2H), 3.06-2.96 (m, 1H), 2.92-2.81 (m, 1H), 2.37 (dd, J = 8.2, 4.3 Hz, 2H), 1.20 (t, J = 7.0Hz, 3H). LC-MS: rt = 1.66 min, MS: 325.1 (calculated), 326.1 (M+H+, found).81 164 / οχΧ 2-Amino-6-cyano- N-methyl-6phenyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, d (ppm): 7.58 (d, J = 7.8 Hz, 2H), 7.44 (t, J = 7.4 Hz, 2H), 7.40-7.31 (m, 1H), 3.14 (s, 2H), 3.01 (d, J = 8.2 Hz, 1H), 2.91-2.77 (m, 4H), 2.40-2.33 (m, 2H). LC-MS: rt = 1.58 min, MS: 311.1 (calculated), 312.1 (M+H+, found). 82 165 θχχ>- 2-Amino-6-cyano-6-phenyl-Npropyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, d (ppm): 7.59 (d, J = 7.8 Hz, 2H), 7.50-7.430 (m, 2H), 7.39 (s, 1H), 6.98 (t, J = 5.3 Hz, 1H), 6.74 (s, 2H), 3.23-3.07 (m, 4H), 3.03-2.91 (m, 1H), 2.87-2.74 (m, 1H), 2,362.23 (m, 2H), 1.50 (sxt, J = 1.0 Hz, 2H), 0.87 (t, J = 7.4 Hz, 3H). LC-MS: rt = 1.81 min, MS: 339.1 (calculated), 340.2 (M+H+, found). Example 83 2-Amino-6-(2-(ethylamino)-2-oxoethyl)-6-phenyl-4,5,6,7-tetrahydrobenzorb]thiophene-3-carboxamide (166)

[00323] Compound 166 (example 83) was synthesized in a similar manner. Petition 870250100355, dated 03 / 11 / 2025, pp. 178 / 282 173 / 236 to compound 20 (scheme 6) starting from 2-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)acetic acid (Biochemistry, 41, page 7781, 2002) instead of 8-phenyl-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (17).

[00324] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.51-7.49 (m, 1H), 7.31-7.23 (m, 4H), 7.16-7.12 (m, 1H), 6.97 (s, 2H), 6.40 (bs, 2H), 3.07 (d, J = 16.6 Hz, 1H), 2.96 (d, J = 16.6 Hz, 1H), 2.89-2.83 (m, 2H), 2.67-2.59 (m, 1H), 2.43-2.33 (m, 2H), 2.16-2.09 (m, 2H), 2.05-1.98 (m, 1H), 0.77 (t, J = 7.2 Hz, 3H). LC-MS: rt = 2.42 min, MS: 357.2 (calculated), 358.2 (M+H+, found). Example 84 2-Amino-6-(2-(4-hydroxypiperidin-1-yl)-2-oxoethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (167)

[00325] Compound 167 (example 84) was synthesized similarly to compound 166 (example 83) and using 4-hydroxypiperidine instead of ethylamine in the first step.

[00326] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.33-7.31 (m, 2H), 7.26-7.22 (m, 2H), 7.15-7.12 (m, 1H), 6.97 (s, 2H), 6.42 (bs, 2H), 4.62 (bs, 1H), 3.73-3.69 (m, 1H), 3.51-3.48 (m, 1H), 3.21-3.15 (m, 1H), 2.89-2.73 (m, 4H), 2.67-2.54 (m, 3H), 2.21-2.06 (m, 3H), 1.52-1.45 (m, 1H), 1.41-1.32 (m, 1H), 1.08-0.85 (m, 2H). LC-MS: rt = 2.22 min, MS: 413.2 (calculated), 414.2 (M+H+, found). Example 85 3-(2-amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophen-6-acid) Petition 870250100355, dated 03 / 11 / 2025, pp. 179 / 282 174 / 236 yl)propanoic (169) and Example 86 2-Amino-6-(3-(ethylamino)-3-oxopropyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (170) Scheme 32 Step 1. 3-(4-oxo-1-phenylcyclohexyl)propanoic acid (168)

[00327] To a solution of 3-(8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)propanoic acid (31, Scheme 9) (100 mg, 0.344 mmol) in THF (3.0 mL), 2 N HCl (0.861 mL, 1.72 mmol) was added, and the reaction mixture was stirred at RT for 24 hours. Then, the mixture was diluted with DCM and water. The aqueous phase was extracted with DCM, and the combined organics were dried with MgSO4, filtered, and concentrated to yield the title compound 168 as a white solid (85 mg, >99% yield). LC-MS: rt = 0.73 min, MS: 246.1 (calculated), 245.2 ([MH]-, found). Step 2. 3-(2-Amino-3-carbamoyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)propanoic acid (169)

[00328] To a solution of 168 (85 mg, 0.344 mmol) and cyanoacetamide (32 mg, 0.379 mmol) in EtOH (2.0 mL), morpholine (0.066 mL, 0.758 mmol) and sulfur (12 mg, 0.047 mmol) were added. The reaction mixture was stirred at 80 °C for 16 hours and allowed to cool. Petition 870250100355, dated 03 / 11 / 2025, pages 180 / 282 175 / 236 naturally to RT and concentrated to dry. The residue was purified by flash column chromatography (eluent gradient from 0% to 90% EA in hexane with 0.1% (v / v) formic acid) to yield the title compound 169 (44 mg, 37% yield) as a brown solid. 24 mg were further purified by semi-preparatory HPLC-MS (eluent gradient from 40% to 100% MeOH in 10 mM ammonium formate) to yield 13 mg of highly pure material (>99% purity by HPLC).

[00329] RMN at 1H: 400 MHz, DMSO-d6, δ (ppm): 7.32-7.27 (m, 4H), 7.19-7.16 (m, 1H), 6.98 (s, 2H), 6.43 (bs, 2H), 2.95 (d, J = 16.1 Hz, 1H), 2.67-2.56 (m, 2H), 2.20-2.09 (m, 2H), 2.01-1.87 (m, 3H), 1.82-1.67 (m, 2H). LC-MS: rt = 0.80 min, MS: 344.1 (calculator), 345.2 (M+H+, encontrado). Etapa 3. 2-Amino-6-(3-(etilamino)-3-oxopropil)-6-fenil-4,5,6,7-tetrahidrobenzo[b]tiofeno-3-carboxamida (170)

[00330] To a solution of 169 (15 mg, 0.044 mmol) in anhydrous DMF (0.8 mL), HATU (20 mg, 0.052 mmol), N,N-diisopropylethylamine (0.023 mL, 0.131 mmol) and ethylamine (0.024 mL, 2 M in THF, 0.048 mmol) were added. The reaction mixture was stirred at RT for 16 hours, then the mixture was concentrated. The residue was dissolved in EA and washed with brine, dried with MgSO4, filtered and concentrated. The residue was purified by flash column chromatography (eluent gradient from 0% to 100% EA in hexane), then purified again by semi-preparative HPLC-MS (eluent gradient from 35% to 100% MeOH in 10 mM ammonium bicarbonate) to yield the title compound 170 (3 mg, 20% yield) as a white solid.

[00331] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.64 (t, J = 5.4 Hz, 1H), 7.30-7.26 (m, 4H), 7.20-7.14 (m, 1H), 6.98 (s, 2H), 6.43 (bs, 2H), 2.98-2.92 (m, 3H), 2.67-2.57 (m, 2H), 2.18-2.08 (m, 2H), 2.00-1.86 (m, 2H), 1.82-1.73 (m, 2H), 1.62-1.55 (m, 1H), 0.92 (t, J = 7.2 Hz, 3H). LC-MS: rt = 1.25 min, MS: 371.2 (calculated), 372.1 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 181 / 282 176 / 236 Example 87 2-Amino-6-(3-oxo-3-(piperidin-1-yl)propyl)-6-phenyl-4,5,6,7-tetrahydrobenzorb]thiophene-3-carboxamide (171)

[00332] Compound 171 (example 87) was synthesized similarly to compound 28 (example 9, scheme 8) starting from 3-(4-oxo-1-phenylcyclohexyl)propanoic acid (168, scheme 32) instead of 4-oxo-1-phenylcyclohexanecarboxylic acid (26).

[00333] 1H NMR: 400 MHz, CDCb, δ (ppm): 7.33-7.25 (m, 4H), 7.21-7.17 (m, 1H), 6.16 (s, 2H), 5.29 (bs, 2H), 3.50-3.41 (m, 2H), 3.11-3.04 (m, 3H), 2.71-2.61 (m, 2H), 2.23-2.11 (m, 3H), 2.08-1.86 (m, 4H), 1.61-1.52 (2H), 1.48-1.44 (m, 2H), 1.43-1.38 (m, 2H). LC-MS: rt = 1.33 min, MS: 411.2 (calculated), 412.3 (M+H+, found). Example 88 2-Amino-6-(3-morpholino-3-oxopropyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (172)

[00334] Compound 172 (example 88) was synthesized similarly to compound 29 (example 10, scheme 8) starting from 3-(4-oxo-1-phenylcyclohexyl)propanoic acid (168, scheme 32) instead of 4-oxo-1-phenylcyclohexanecarboxylic acid (26).

[00335] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.33-7.27 (m, Petition 870250100355, dated 03 / 11 / 2025, pp. 182 / 282 177 / 236 4H), 7.19-7.15 (m, 1H), 6.98 (s, 2H), 6.43 (bs, 2H), 3.46-3.43 (m, 5H), 3,233.09 (m, 3H), 3.00 (d, J = 16.2 Hz, 1H), 2.67-2.57 (m, 2H), 2.18-2.08 (m, 3H), 1.99-1.89 (m, 2H), 1.80-1.71 (m, 2H). LC-MS: rt = 1.11 min, MS: 413.2 (calculator), 414.3 (M+H+, encontrado). Exemplo 89 2-Amino-6-(2-(2-metoxietoxi)etil)-6-fenil-4,5,6,7-tetra-hydrobenzo[b]tiofeno3-carboxamida (176) Esquema 33 Step 1. 8-(2-(2-Methoxyethoxy)ethyl)-8-phenyl-1,4-dioxaspiro[4.5]decane (174)

[00336] To a solution of 2-(8-phenyl-1,4-dioxaspiro[4.5]decan-8yl)ethan-1-ol (173) (Bioorg Med. Chem Lett. 21, page 405, 2011) (100 mg, 0.381 mmol) in anhydrous DMF (3.0 mL) at 0 °C was added NaH (30 mg, 60% in mineral oil, 0.76 mmol). The mixture was stirred at 0 °C for 30 min before the addition of 2-bromoethyl methyl ether (0.11 mL, 1.14 mmol). Then, the reaction mixture was stirred at RT for 3 days. The reaction mixture was rapidly cooled with saturated NH4Cl solution, diluted with water, 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 100% EA in hexane) to yield compound 174 (57 mg, 47% yield) as a colorless oil. LC-MS: rt = 3.44 min, MS: 320.2 (calculated), 321.2 (M+H+, found). Step 2. 4-(2-(2-Methoxyethoxy)ethyl)-4-phenylcyclohexan-1-one (175) Petition 870250100355, dated 03 / 11 / 2025, pp. 183 / 282 178 / 236

[00337] To a solution of 174 (57 mg, 0.178 mmol) in acetone (2.4 mL), 2 N HCl (0.45 mL, 0.90 mmol) was added, and the reaction mixture was stirred at RT for 16 hours. Then, more 2 N HCl (0.225 mL, 0.45 mmol) was added, and the reaction mixture was stirred for 3 days. Subsequently, the mixture was neutralized with saturated NaHCO3 solution and concentrated to remove the organic solvent. The residue was partitioned between water and EA. The layers were separated, and the organic phase was dried with N2SO4, filtered, and concentrated to yield the title compound 175 as a colorless oil (49 mg, >99% yield). LC-MS: rt = 3.07 min, MS: 276.2 (calculated), 277.2 (M+H+, found). Step 3.2-Amino-6-(2-(2-methoxyethoxy)ethyl)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (176)

[00338] To a solution of 175 (49 mg, 0.177 mmol) and cyanoacetamide (16 mg, 0.195 mmol) in EtOH (0.2 mL), morpholine (0.017 mL, 0.195 mmol) and sulfur (6 mg, 0.024 mmol) were added. The reaction mixture was stirred at 60 °C for 16 hours, then allowed to cool naturally 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 N2SO4, filtered, and concentrated. The residue was purified by flash column chromatography (50% to 100% EA eluent gradient in hexane) to yield the title compound 176 (30 mg, 45% yield) as a pale yellow solid. 15 mg of the material were further purified by semi-preparatory HPLC-MS (50% to 100% MeOH eluent gradient in 10 mM ammonium bicarbonate) to yield 9.5 mg of highly pure material (98% purity by HPLC).

[00339] 1H NMR: 400 MHz, CDCh, δ (ppm): 7.30-7.25 (m, 4H), 7.21-7.16 (m, 1H), 6.16 (s, 2H), 5.24 (bs, 2H), 3.45-3.43 (m, 2H), 3.41-3.39 (m, 2H), 3.34 (s, 3H), 3.30-3.24 (m, 1H), 3.16-3.07 (m, 2H), 2.76 (d, J = 16.5 Hz, 1H), 2.65-2.60 (m, 1H), 2.20-2.13 (m, 3H), 2.07-1.93 (m, 2H). LC-MS: rt = 2.98 min, MS: 374.2 (calculated), 375.2 (M+H+, found). Petition 870250100355, dated 03 / 11 / 2025, pp. 184 / 282 179 / 236 Example 90 2-Amino-6-(3-(2-methoxyethoxy)propyl)-6-phenyl-4,5,6,7-tetrahydrobenzorb]thiophene-3-carboxamide (177)

[00340] Compound 177 (example 90) was synthesized similarly to compound 176 (example 89, scheme 33) starting from 3-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propan-1-ol (33, scheme 9) instead of 2-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)ethan-1-ol (173).

[00341] 1H NMR: 400 MHz, DMSO-de, δ (ppm): 7.31-7.26 (m, 4H), 7.17-7.14 (m, 1H), 6.98 (s, 2H), 6.43 (bs, 2H), 3.34-3.32 (m, 4H), 3.21-3.18 (m, 5H), 2.96 (d, J = 16.2 Hz, 1H), 2.61-2.57 (m, 2H), 2.22-2.14 (m, 1H), 2.11-2.05 (m, 1H), 1.93-1.86 (m, 1H), 1.73 (td, J = 12.7, 4.2Hz, 1H), 1.54 (td, J = 12.7, 4.2 Hz, 1H), 1.29-1.19 (m, 1H), 1.08-0.99 (m, 1H). LC-MS: rt = 1.37 min, MS: 388.2 (calculated), 389.3 (M+H+, found). Example 91 2-Amino-6-cyano-6-((1-(phenylsulfonyl)cyclopropyl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (181) Scheme 34 Step 1. 8-((1-(Phenylsulfonyl)cyclopropyl)methyl)-1,4-dioxaspiro[4.5]decane-8 Petition 870250100355, dated 03 / 11 / 2025, pp. 185 / 282 180 / 236 carbonitrile (179)

[00342] To a solution of 178 (synthesized similarly to compound 7 (scheme 3) starting from 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1) and using intermediate compound 66 (scheme 20) instead of 3-(2-bromoethyl)pyridine hydrobromide) (100 mg, 0.304 mmol) in anhydrous DCM (10 mL) was added in small portions 3-chloroperoxybenzoic acid (105 mg, 0.608 mmol) and the reaction mixture was stirred at RT for 2 hours. Then, the mixture was rapidly cooled with saturated NaHCO3 solution and extracted with DCM. The organic layer was dried with Na2SO4, filtered, and concentrated to produce compound 179 (101 mg, 92% yield) as a white solid, which was not characterized and used directly in the next step. Step 2. 4-Oxo-1-((1-(phenylsulfonyl)cyclopropyl)methyl)cyclohexane-1-carbonitrile (180)

[00343] To a solution of 179 (101 mg, 0.279 mmol) in acetone (3.5 mL), 1 N HCl (1.40 mL, 2.80 mmol) was added, and the reaction mixture was stirred at RT for 3 days. Then, the mixture was neutralized with concentrated saturated NaHCO3 solution to remove the organic solvent. The residue was partitioned between 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 100% EA in hexane) to yield the title compound 180 as a colorless oil (52 mg, 59% yield), which was not characterized and used directly for the next step. Step 3. 2-Amino-6-cyano-6-((1-(phenylsulfonyl)cyclopropyl)methyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (181)

[00344] To a solution of 180 (52 mg, 0.164 mmol) and cyanoacetamide (15 mg, 0.180 mmol) in EtOH (0.2 mL), morpholine (0.016 mL, 0.180 mmol) and sulfur (6 mg, 0.023 mmol) were added. The reaction mixture was Petition 870250100355, dated 03 / 11 / 2025, pages 186 / 282 181 / 236 was stirred at 60 °C for 16 hours, then allowed to cool naturally 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 (20% to 100% EA eluent gradient in hexane) to yield the title compound 181 (41 mg, 60% yield) as a dirty white solid.

[00345] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.98-7.95 (m, 2H), 7.80-7.76 (m, 1H), 7.69-7.65 (m, 2H), 7.01 (s, 2H), (bs, 2.89), (bs, 2.79) (d, J = 16.1 Hz, 1H), 2.75–2.67 (m, 2H), 2.58 (d, J = 16.1 Hz, 1H), 2.16 (d, J = 16.1 Hz, 1H), 2.10–2.06 (m, 2H), 1.39-1.26 (m, 2H). LC-MS: rt = 1.16 min, MS: 415.1 (calculated), 416.3 (M+H+, found). Example 92 6-(2-(1H-1,2,3-Triazol-5-yl)ethyl)-2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (183) Intermediate Compound 42 8-(But-3-in-1-yl)-8-phenyl-1,4-dioxaspiro[4.5]decane (42) Scheme 12 Step 1. 3-(8-Phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propanal (41)

[00346] To a solution of 3-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propanenitrile (30, diagram 9) (1.40 g, 5.16 mmol) (Bioorg Med. Chem Lett. 21, page 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 rapidly cooled with saturated NH4Cl solution. Subsequently, the Petition 870250100355, dated 03 / 11 / 2025, pp. 187 / 282 182 / 236 of 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 Et2O, and this organic layer was washed with a saturated solution of NaHCO3 and brine, dried with NebSO4, filtered, and concentrated to yield the compound of title 41 as a colorless oil, which was used directly in the next step without characterization. Step 2. 8-(But-3-yn-1-yl)-8-phenyl-1,4-dioxaspiro[4.5]decane (42)

[00347] 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 41 (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 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 NibSC)4, 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 42 as a white solid (734 mg, 53% yield over two steps), which was not characterized and used directly for the synthesis of relevant examples. 6-(2-(1H-1,2,3-Triazol-5-yl)ethyl)-2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (183) Scheme 35 Petition 870250100355, dated 03 / 11 / 2025, pp. 188 / 282 183 / 236

[00348] To a suspension of 182 (synthesized similarly to compound 9 (example 3, scheme 3) starting from intermediate compound 42 (scheme 12) instead of 7) (10 mg, 0.031 mmol) in DMF (0.3 mL) and water (0.15 mL) were added copper(II) sulfate pentahydrate (16 mg, 0.062 mmol) and sodium ascorbate (12 mg, 0.062 mmol). The flask was evacuated and refilled with nitrogen, then trimethylsilyl azide (0.033 mL, 0.247 mmol) was added and the reaction mixture was stirred at RT for 2 hours. Subsequently, the mixture 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 183 as a white solid (4 mg, 35% yield).

[00349] 1H NMR: 400 MHz, DMSO-d6, δ (ppm): 7.47 (bs, 1H), 7.38-7.36 (m, 2H), 7.33-7.29 (m, 2H), 7.21-7.17 (m, 1H), 6.96 (s, 2H), 6.41 (bs, 2H), 3.05 (d, J = 16.2 Hz, 1H), 2.73-2.62 (m, 2H), 2.43-2.32 (m, 1H), 2.23-2.04 (m, 4H), 2.00-1.86 (m, 2H). LC-MS: rt = 1.12 min, MS: 367.2 (calculated), 368.2 (M+H+, found). Examples 93 to 99 and 101 to 102 Intermediate compound 185 2-Isobutyl-4-oxo-1-phenylcyclohexane-1-carbonitrile (185) Scheme 36

[00350] A solution of CuCl (120 mg, 1.22 mmol) under Ar in THF Petition 870250100355, dated 03 / 11 / 2025, pp. 189 / 282 Anhydrous 184 / 236 (15.3 mL) isobutylmagnesium bromide (1.22 mL, 2 M in THF, 2.44 mmol) was added dropwise. The mixture was stirred at RT for 30 min, then cooled to 0 °C. A solution of 4-oxo-3,4-dihydro-[1,1'-biphenyl]-1(2H)-carbonitrile (184) (200 mg, 1.01 mmol) (ACS Catalysis, 10(9), page 5057, 2020) in anhydrous THF (5.0 mL) was added dropwise and the reaction mixture was stirred at 0 °C for 12 hours. 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 layers were dried with Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash column chromatography (eluent gradient from 0% to 70% EA in hexane) to yield the compound of title 185 as a clear oil (177 mg, 68% yield). LC-MS: rt = 2.02 min, MS: 255.2 (calculated), 256.0 (M+H+, found). Compounds 186 to 192, 194 and 195

[00351] Compounds 186 to 192, 194, 195 (examples 93 to 99, 101, 102) were synthesized starting from appropriately substituted ketones, following the procedure reported for the synthesis of compound 4 from ketone 3 (example 1, scheme 1) or the procedure reported for the synthesis of compound 6 from ketone 5 (example 2, scheme 2). Compound 189 (example 96) was synthesized starting from intermediate compound 185 (scheme 36). The remaining ketones were commercially available. The characterization of compounds 186 to 192, 194, 195 (examples 93 to 99, 101, 102) is given in Table 9. Table 9. Characterization of compounds 186 to 192, 194, 195 (examples 93 to 99, 101, 102). Example: No. Compound Number Structure Characterization Petition 870250100355, dated 03 / 11 / 2025, pp. 190 / 282 185 / 236 Example No. Compound No. Structure Characterization 93 186 χχχΧ 2-Amino-6-cyano-6-(4-fluorophenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 7.61 (t, J = 6.50 Hz, 2H), 7.17 (t, J = 8.49 Hz, 2H), 3.01 (bs, 1H), 3.13 (s, 2H), 2.90 (d, J = 16.79 Hz, 1H), 2.37 (d, J = 6.43 Hz, 2H). 19F NMR: 376 MHz, DMSO-d6, d (ppm): -116.3. LC-MS: rt = 1.54 min, MS: 315.1 (calculated), 316.1 (M+H+, found). 94 187 2-Amino-6-cyano-6-(2fluorophenyl)-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, d (ppm): 7.51-7.42 (m, 2H), 7.37-7.23 (m, 2H), 7.05 (s, 2H), 6.61 (bs, 2H), 3.24 (d, J = 15.6 Hz, 1H), 3.12 (d, J = 16.8 Hz, 1H), 2.99-2.87 (m, 1H), 2.82-2.72 (m, 1H), 2.46-2.25 (m, 2H). 19F NMR: 376 MHz, DMSO-d6, d (ppm): -111.7. LC-MS: rt = 1.46 min, MS: 315.1 (calculated), 316.1 (M+H+, found).95 188 xxxX 2-Amino-6-(3-chlorophenyl)-6cyano-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, d (ppm): 7.61 (s, 1H), 7.54 (d, J = 7.4 Hz, 1H), 7.48-7.36 (m, 2H), 3.13 (s, 2H), 3.05-2.99 (m, 1H), 2.94-2.90 (m, 1H), 2.37 (dd, J = 7.98, 4.43, 2H). LC-MS: rt = 1.62 min, MS: 331.1 (calculated), 332.2 (M+H+, found). 96 189 χχχ o 2-Amino-6-cyano-5-isobutyl-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, d (ppm): 7.54-7.50 (m, 2H), 7.47-7.41 (m, 2H), 7.39-7.35 (m, 1H), 3.36 (s, 1H), 3.24 (d, J = 16.16 Hz, 1H), 2.58 (d, J = 17.16 Hz, 2H), 1.58 (d, J = 9.90 Hz, 1H), 1.07 (t, J = 11.80 Hz, 1H), 0.93 (t, J = 12.01 Hz, 1H), 0.79 (d, J = 6.62 Hz, 3H), 0.69 (d, J = 6.49 Hz, 3H). LC-MS: rt = 1.52 min, MS: 353.2 (calculated), 354.1 (M+H+, found).97 190 2-Amino-5-(tert-butyl)-4,5,6,7tetrahydrobenzo[b]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, d (ppm): 2.74-2.64 (m, 1H), 2.63-2.45 (m, 2H), 2.42-2.31 (m, 1H), 2092.00 (m, 1H), 1.45-1.32 (m, 2H), 0.97 (s, 9H). LC-MS: rt = 1.81 min, MS: 252.1 (calculated), 253.1 (M+H+, found). 98,191 2.04-1.92 (m, 1H), 1.63 (t, J = 19.5 Hz, 3H), 1.48-1.35 (m, 1H). 19F NMR: 376 MHz, DMSO-d6, d (ppm): —156.2. Petition 870250100355, dated 03 / 11 / 2025, pp. 191 / 282 186 / 236 Example No. Compound No. Structure Characterization 2-Amino-6-(1,1-difluoroethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide LC-MS: rt = 1.34 min, MS: 260.1 (calculated), 261.1 (M+H+, found). 99 192 2-Amino-5-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, d (ppm): 7.35-7.25 (m, 4H), 7.21-7.14 (m, 1H), 2.93 (d, J = 12.5 Hz, 2H), 2.79-2.54 (m, 3H), 2.14-1.91 (m, 2H). LC-MS: rt = 1.67 min, MS: 272.1 (calculated), 273.1 (M+H+, found). 101 194 2-Amino-6-ethynyl-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3carboxamide 1H NMR: 400 MHz, DMSO-d6, d (ppm): 6.93 (s, 2H), 6.53 (bs, 2H), 2.92 (d, J = 2.1 Hz, 1H), 2.83-2.59 (m, 4H), 2.50-2.42 (m, 1H), 1,991.85 (m, 1H), 1.77-1.64 (m, 1H). LC-MS: rt = 1.02 min, MS: 220.1 (calculated), 221.1 (M+H+, found). 102 195 2-Amino-4,4a,5,6,7,8,8a,9-octahydronaphtho[2,3- b ]thiophene-3carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 2.76-2.43 (m, 3H), 2.03-1.86 (m, 2H), 1.66-1.37 (m, 9H).LC-MS: rt = 1.71 min, MS: 250.1 (calculated), 251.1 (M+H+, found). Example 104 2-Amino-6-cyano-6-cyclohexyl-7-oxo-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide (198) Scheme 37

[00352] 8-Cyclohexyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (2a): A 250 mL dry round-bottom flask fitted with a stirring bar was charged with 1,4-dioxaspiro[4.5]decane-8-carbonitrile (1) (3 g, 17.9 mmol, 1 equiv.) and 70 mL of dry THF. The solution was sprayed with argon for 10 minutes using an argon balloon and cooled to -78 °C with a dry ice-acetone bath under a positive argon atmosphere. Petition 870250100355, dated 03 / 11 / 2025, pp. 192 / 282 187 / 236 A 1 M lithium diisopropylamide solution in THF / heptanes (19.7 mL, 19.7 mmol, 1.1 equiv.) was added dropwise to the flask, and the reaction was stirred at -78 °C for 1 hour. A degassed cyclohexyl bromide solution (4.39 g, 26.9 mmol, 1.5 equiv.) in 20 mL of dry THF was added to the flask by syringe, and the reaction was heated to 60 °C during stirring for 36 hours. Note: The reaction did not exceed 50% completion. The reaction was cooled to room temperature, sharply cooled with 50 mL of saturated ammonium chloride solution, and extracted with diethyl ether (2 x 50 mL). The organic fractions were combined, dried with sodium sulfate, filtered, and the volatiles were removed under vacuum.The crude material was purified by automated column chromatography using silica gel and a 0 to 100% ethyl acetate gradient in hexanes as eluent to yield the title compound as a pale yellow oil (783 mg, 3.14 mmol, 18% yield). 1H NMR (400 MHz, CDCl3): δ 4.11 - 3.67 (m, 4H), 2.16 - 1.47 (m, 15H), 13.0 - 1.09 (m, 5H).

[00353] Ethyl 2-Amino-6-cyano-6-cyclohexyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate (198): A 20 mL flask fitted with a stirring bar was charged with 8-cyclohexyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (2a), aqueous HCl (12 M) and acetone (3.81 mL). The reaction was stirred at room temperature for 48 hours and the volatiles were removed under vacuum to yield the intermediate 1-cyclohexyl4-oxocyclohexane-1-carbonitrile (197) which was proceeded without further purification or characterization. A 20 mL flask fitted with a stirring bar was loaded with 1-cyclohexyl-4-oxocyclohexane-1-carbonitrile (197) (400 mg, 1.95 mmol, 1 equiv.), ethyl 2-cyanoacetate (164 mg, 1.95 mmol, 1 equiv.), elemental sulfur (69 mg, 269 pmol, 0.138 equiv.), morpholine (187 mg, 2.14 mmol, 1.1 equiv.), and ethanol (3.1 mL, 0.63 M). The flask was sealed with a pressure-relieving septum stopper, and the reaction was stirred at 60 °C for 18 hours. The reaction was then cooled to the Petition 870250100355, dated 03 / 11 / 2025, pp. 193 / 282 188 / 236 room temperature, and the product was isolated by vacuum filtration. The solids were washed with diethyl ether (2 x 5 mL) to yield the title compound as a pale yellow solid (392 mg, 1.29 mmol, 66% yield). 1H NMR (500 MHz, DMSO-d6): δ 7.00 (s, 2H), 6.59 (s, 2H), 2.85 - 2.71 (m, 3H), 2.63 (d, J = 16.0 Hz, 1H), 2.15 (d, J = 13.5 Hz, 1H), 1.96 (d, J = 12.5 Hz, 1H), 1.88 (d, J = 12.3 Hz, 2H), 1.82 - 1.75 (m, 2H), 1.68 1.59 (m, 2H), 1.50 (t, J = 12.3 Hz, 1H), 1.33 - 0.94 (m, 4H). LC-MS: Calculated 303.4, found (M+H) 304.3, retention time 0.32 min. Example 105

[00354] Compounds 200, 203 to 220, provided in Table 10, were obtained from a commercial supplier or were prepared according to synthetic protocols known in the literature, as per reported references. Table 10. Structures of compounds 200, 203 to 220 No. of the compound Structure Source or reference of preparation 200 o Schweizer, Ernst; Schmidt, Paul; Eichenberger, Kurt, DE1934172 203 9 Commercial supplier 204 Commercial supplier 205 Commercial supplier 206 χί- Commercial supplier 207 yC^ Commercial supplier Petition 870250100355, dated 03 / 11 / 2025, pp. 194 / 282 189 / 236 Compound No. Structure Source or reference of preparation 208 Y Commercial supplier 209 Y Commercial supplier 210 γθί· Ravindranathan, KP; Mandiyan, V.; Ekkati, AR; Bae, JH; Schlessinger, J.; Jorgensen, WLJ Med. Chem. (2010), 53(4), 1662 to 1672. https: / / doi.org / 10.1021 / jm901386e 211 (Χ^ Commercial supplier 212 y γθί· Commercial supplier 213 γθ^ Commercial supplier 214 Commercial supplier 215 γΧΧ^ Commercial supplier 216 χΧΧ^ Commercial supplier 217 yCX^ Commercial supplier Petition 870250100355, dated 03 / 11 / 2025, pages 195 / 282 190 / 236 Compound No. Structure Source or preparation reference 218 Commercial supplier 219 Commercial supplier 220 Commercial supplier Examples 107 to 111

[00355] Compounds 223, 224, 228, 233, and 261 (examples 107 to 111) were synthesized starting from appropriately substituted ketones, following the procedure reported for the synthesis of compound 4 from ketone 3 (example 1, scheme 1) or the procedure reported for the synthesis of compound 6 from ketone 5 (example 2, scheme 2). Compound 233 (example 110) was synthesized starting from intermediate compound 185 (scheme 36). The remaining ketones were commercially available. The characterization of compounds 223, 224, 228, 233 and 261 (examples 107 to 111) are provided in Table 11. Table 11. Characterization of compounds 223, 224, 228, 233 and 261 (examples 107 to 111). Ex. No. Compound No. Structure Characterization 107 223 2-Amino-4,5,5a,6,7,8,9,9a-octahydronaphtho[1,2-b]thiophene-3-carboxamide 1H NMR: 400 MHz, CD3OD, δ (ppm): 2.71 (dd, J = 15.5, 4.6 Hz, 1H), 2.53-2.48 (m, 1H), 2.25-2.12 (m, 2H), 1.86 (t, J = 12.1 Hz, 2H), 1.77 (s, 2H), 1.44-1.29 (m, 4H), 1.20-1.03 (m, 2H). LC-MS: rt = 1.77 min, MS: 250.1 (calculated), 251.1 (M+H+, found). 108,224 Hz, 2H), 7.03-7.00 (m, 2H), 6.62 (s, 2H), 3.16-3.04 (m, 2H), 2.98-2.75 (m, 2H), 2.27 (s, 2H). LC-MS: rt = 1.69 min, MS: Petition 870250100355, dated 03 / 11 / 2025, pp. 196 / 282 191 / 236 ...

Claims

1. Compound with Formula (I), or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: Ra is -NHz, -NH-OH, -OH or -NHRb; 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; represents one of the following residues Ao to Aó, or wherein: R is H or C1-C6-alkyl; R' is H or C1-C6-alkyl; R1 is -CN, C6-C1-C6alkyl, C1-C6alkenyl, C2C6alkynyl, F, Cl, Br, I, -N(R”)2, C3-C5-cycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, C(O)R6, or -C(O)OR5, wherein C1-C6alkyl is optionally substituted by 1 to 3 R7 substituents and C6-C1-C6-Aryl is optionally substituted by 1 to 3 R8 substituents;R2 is C6-C1oaryl, unsubstituted C6-C6alkyl, C1-C6alkyl substituted by 1 to 3 substituents R7, C2-C6alkenyl, C2-C6alkynyl, Cl, Br, Petition 870250100355, dated 03 / 11 / 2025, p. 243 / 282 2 / 39 I, -N(R”)2, CyCscycloalkyl, 4- to 14-membered heterocycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or C(O)OR5, wherein C6-C10aryl is optionally substituted by 1 to 3 R8 substituents, provided that: (i) when Ra is -NH2, XX represents residue Ao, Ré H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, XX represents residue Ao, Ré H and R1 is -CN, then R2 is different from or each R” is independently C1-C4alkyl; each R5 is independently C1-C6alkyl, and each C1C6alkyl is optionally substituted by 1 to 3 R9 substituents;Each R6 is independently C3-C6cycloalkyl, a 4- to 6-membered heterocycloalkyl, or a C6-C1aryl, and the 4- to 6-membered heterocycloalkyl is optionally replaced by -OH; Each R7 is independently -OH, -C(O)Rn, C3C5cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6alkyl), -OR20, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, or 4-oxo-1,4-dihydro-1-pyridinyl, and each C3C5cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5- or 6-membered heteroaryl is optionally substituted by 1 to 3 R13 In the substituents, each 4- to 6-membered heterocycloalkyl group is optionally replaced by a C1-C4 alkyl or oxo group;each R8 is independently halogen, C1-C6 alkyl, -OC1C6 alkyl, C3-C6 cycloalkyl, or 5- to 10-membered heteroaryl, wherein each -OC1-C6 alkyl is optionally replaced by -OC1-C4 alkyl, and each 5- to 10-membered heteroaryl is optionally replaced by C1-C4 alkyl; Each R9 is independently -OH, -C(O)R15, C3C6cycloalkyl, -CN, C6-Cwaryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(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, 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms or 4- to 6-membered heterocycloalkyl substituted by -OH;each R20 is independently a 5- to 10-membered C2-C6 alkyl or heteroaryl, wherein each C2-C6 alkyl is optionally substituted by 1 to 3 R14 substituents; each R12 is independently a C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, -SPh, or -S(O)2Ph, wherein each C1-C4 alkyl is optionally substituted by -OH; each R13 is independently halogen, C1-C4 alkyl, C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2, -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-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1C6 alkyl, -NH(C1-C4 alkyl), and -N(C1-C4 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 unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted by 1 to 3 R9 substituents, C3-C8 cycloalkyl, C6-C1 cycloaryl, a partially unsaturated heterocyclic group of 7 to 10 members, or a heteroaryl group of 5 to 10 members, wherein C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and C6-C8 cycloalkyl and heteroaryl groups of 5 to 10 members are optionally substituted by 1 to 3 R10 substituents, provided that when R a is -OH, ZZZ represents the residue Ai, and R' is H, then R4 is different from -CH2CH3 or -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 unsubstituted C3-C6 alkyl, C1-C6 alkyl substituted with 1 to 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl, C3Cs cycloalkyl, or C6-Cwaryl, wherein C3-Cs cycloalkyl is optionally substituted with 1 to 3 R9 substituents, and C6-Cwaryl is optionally substituted with 1 to 3 R22 substituents, provided that: (i) when R a is -NH2, ZZZ represents residue A2, and R is H, then R2a is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CH2OH, -CF3, or unsubstituted phenyl; (ii) when R a is -OH, ZZZ represents residue A2, and R is H, then R2a is different from -C(CH3)3, -C(CH3)2CH2CH3, NHC(O)OC(CH3)3, or unsubstituted phenyl; (iii) when R a is -NHCH3 or NHCH2CH3 / ZZZ represents residue A2, and R is H, then R2a is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl;(iv) when R a is -NHCH(CH3)2, -NHCH2CH2CH3, or NHcyclopropyl, ΖΞΖ represents residue A2, and R is H, then R2a is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, or -CF3; and (v) when R a is -NHcyclopentyl or -NHcyclohexyl, ΖΞΖ represents residue A2, and R is H, then R2a is different from -C(CH3)3 or -C(CH3)2CH2CH3; each R22 is independently unsubstituted C2-C4alkyl, C1-C4alkyl substituted with 1 to 3 halogens, F, Br, I, -OC3-C6alkyl, -NH2, NH(C1-C4alkyl), or -N(C1-C4alkyl)2; R1a and R2b are independently -CN, C6-Cwarila, C1 Petition 870250100355, dated 03 / 11 / 2025, p. 246 / 282 5 / 39 C-alkyl, C3-C8cycloalkyl, -C(O)NH2,-C(O)NHR5, or -C(O)OCi-C6alkyl, wherein each C1-C6alkyl is optionally substituted by 1 to 3 substituents R16 and each C6-Cwarila is optionally substituted by 1 to 3 substituents R17;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 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;R4a is C1-C6 alkyl or C3-C8 cycloalkyl, wherein each C1-C6 alkyl and C3-C8 cycloalkyl are optionally substituted by 1 to 3 R19 substituents; each R19 is independently halogen, -OH, -OC1C4 alkyl, -SC1-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 cyclic structure selected from a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group. Petition 870250100355, dated 03 / 11 / 2025, p. 247 / 282 6 / 39 members are optionally replaced by oxo, with the condition that: (i) when Ra is -NH2, ZZ represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl or 1,3-dioxolane; and (ii) when Ra is -NHCH3, NHCH2CH3, -NHcyclopropyl, -NHCH(CH3)2, or -NHCH2CH2CH3, ZZ represents residue A4, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl;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 R1c 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.

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): wherein R1, R2, and Ra are as defined in claim 1 and R is 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: Petition 870250100355, dated 03 / 11 / 2025, p.248 / 282 7 / 39 R1 being -CN, C-Cyoaryl, C1-Cyoalkyl, C2-Cyoalkyl, F, N(R”)2, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C1-Cyoalkyl is optionally substituted by 1 to 3 R7 substituents and C-Cyoaryl is optionally substituted by 1 to 3 R8 substituents; R2 being C-Cyoaryl, unsubstituted C2-Cyoalkyl, C1-Cyoalkyl substituted by 1 to 3 R7 substituents, -N(R”)2, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, where C-C1oaryl is optionally replaced by 1 to 3 substituents R8, provided that: (i) when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, R is H and R1 is -CN, then R2 is different from or ; and R”, R5, R6, R7 and R8 are as defined in claim 1.

5. Compound according to claim 3 or 4, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R1 is -CN, C-C1-C1-alkyl, C1-C1-alkyl, C2-C1-alkyl, F, N(R”)2, C3-C8-cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C1-C1-alkyl is optionally substituted by 1 to 3 R7 substituents and C6-C1-alkyl is optionally substituted by 1 to 3 R8 substituents; substituents R7, -N(R”)2, C3-C8-cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein C6-C1oaryl is optionally replaced by 1 to 3 R8 substituents, provided that: (i) when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl;and (ii) when Ra is -NH2, R is H and Petition 870250100355, dated 03 / 11 / 2025, p. 249 / 282 8 / 39 R1 is -CN, then R2 is different from and where: each R” is C1-C2 alkyl; each R5 is C1-C6 alkyl; each R6 is a 4- to 6-membered heterocycloalkyl, or C1-C6 aryl, the 4- to 6-membered heterocycloalkyl being optionally substituted with -OH; each R7 is independently -OH, -C(O)Rn, C3C5 cycloalkyl, -CN, C6-C6 aryl, halogen, -C(O)OH, 5-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6 alkyl), -N(C1C4 alkyl)(C(O)OC1-C6 alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6 alkyl), -OR20, -SC1-C6 alkyl, -NH2, -NH(C1-C4alkyl), or N(C1-C4alkyl)2, and each C3-C5cycloalkyl is optionally substituted by 1 to 3 R12 substituents, each 5-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 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 R11 is independently -NH2, -NH(C1-C4 alkyl), or 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms; each R20 is independently a C2-C6 alkyl or 5- to 10-membered heteroaryl, wherein each C2-C6 alkyl is optionally substituted by 1 to 3 R14 substituents; each R12 is independently C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, -S(O)2Ph, or -SPh, wherein each C1-C4 alkyl is optionally substituted by -OH; Petition 870250100355, dated 03 / 11 / 2025, page 250 / 282 9 / 39 each R13 is independently C1-C4 alkyl, -C(O)OC1C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2 or -OH; and each R14 is independently halogen or -OC1-C4 alkyl.; 6. Compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt thereof, characterized in that: R1 is -CN, phenyl, C1-C5 alkyl, C3 alkynyl, F, C3C6 cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, C(O)R6, or -C(O)OR5, wherein C1-C5 alkyl is optionally substituted by 1 to 2 substituents R7 and phenyl is optionally substituted by 1 substituent R8; R2 being phenyl, unsubstituted C2-C4 alkyl, C1-C5 alkyl substituted by 1 to 2 substituents R7, C3-C6 cycloalkyl, 5 to 10 membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein phenyl is optionally substituted by 1 substituent R8, provided that when Ra is -NH2, R is H, and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and R5, R6, R7 and R8 are as defined in claim 1.

7. Compound according to any one of claims 3 to 6, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R1 is -CN, phenyl, C1-C5 alkyl, C3 alkynyl, F, C3C6 cycloalkyl, 5- to 10-membered heteroaryl, -C(O)NH2, -C(O)NHR5, C(O)R6, or -C(O)OR5, wherein C1-C5 alkyl is optionally substituted by 1 to 2 substituents R7 and phenyl is optionally substituted by 1 substituent R8; and R2 being phenyl, unsubstituted C2-C4 alkyl, C1-C5 alkyl substituted by 1 to 2 R7 substituents, C3-C6 cycloalkyl, 5 to 10 membered heteroaryl, -C(O)NH2, -C(O)NHR5, -C(O)R6, or -C(O)OR5, wherein phenyl is Petition 870250100355, dated 03 / 11 / 2025, p. 251 / 282 10 / 39 optionally substituted by 1 R8 substituent, on the condition that: (i) when Ra is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl; and (ii) when Ra is -NH2, R is H and R1 is -CN, then R2 is 1 / different from ;Whereas: each R5 is C1-C2 alkyl; each R6 is a 6-membered phenyl heterocycloalkyl, and the 6-membered heterocycloalkyl is optionally substituted with -OH; each R7 is independently -OH, -C(O)R11, C3C5cycloalkyl, -CN, phenyl, F, -C(O)OH, 5-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC4alkyl), -N(CH2CH3)(C(O)OC4alkyl), 6-membered heterocycloalkyl, -NH(C(O)CH3), -OR20, -NH2, -NHCH2CH3, or -N(Me)2, with each C3-C5cycloalkyl being optionally substituted by 1 to 3 R12 substituents, each 5-membered heteroaryl is optionally substituted by 1 to 3 R13 substituents, and each 6-membered heterocycloalkyl is optionally substituted by propyl or oxo; each R8 is independently -F, -Cl, -Br, -CH3, -OCH3 or a 5-membered heteroaryl, with each 5-membered heteroaryl optionally substituted for -CH3; each R11 is independently -NH2, -NHCH2CH3, or a 6-membered cycloalkyl heteroatom containing at least 2 heteroatoms;each R20 is independently a 6-membered C2-alkyl or heteroaryl, and each C2-alkyl is optionally substituted by 1 R14 substituent; each R12 is independently C1-C4 alkyl, -SCH3, -Ph, OCH3, -S(O)2Ph or -SPh, and C1-alkyl is optionally substituted by -OH; Petition 870250100355, dated 11 / 03 / 2025, p. 252 / 282 11 / 39 each R13 is independently C1-C3 alkyl, -C(O)OCH2CH3, C3-C4 cycloalkyl, -C(O)NH2 or -OH; and each R14 is independently halogen or -OCH3.

8. A compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent R23, or R1 represents -F, -CN or -CH3 and R2 represents R23; wherein R23 represents: -CH2CH3, -CH2CH2CH3, -N(CH3)2, or on the condition that when R is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

9. A compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent R23, or R1 represents -CN or -CH3 and R2 represents R23; wherein R23 represents: Petition 870250100355, dated 03 / 11 / 2025, page 254 / 282 13 / 39 CH2CH2CH3,V^ X' or on the condition that when R a is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

10. A compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent R23, or R1 represents -CN or -CH3 and R2 represents R23; wherein R23 represents: CH2CH2CH3,V^ with the condition that when R is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

11. A compound according to any one of claims 3 to 5, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 independently represent R23, or R1 represents -CN or -CH3 and R2 represents R23; wherein R23 represents: Petition 870250100355, dated 03 / 11 / 2025, page 255 / 282 14 / 39 on the condition that when R a is -NH2, R is H and R1 is unsubstituted phenyl, then R2 is different from unsubstituted phenyl.

12. A compound according to any one of claims 3 to 11, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 and R2 are different.

13. A compound according to any one of claims 3 to 12, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 is -CN.

14. A compound according to any one of claims 3 to 13, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that one of R1 and R2 is Z.

15. A compound according to any one of claims 3 to 14, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that one of R1 and R2 is either .

16. A compound according to any one of claims 3 to 15, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that one of R1 and R2 is ♭♭♭.

17. Compound according to claim 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ib): (Ib) wherein R4, R' and Ra are as defined in claim 1.

18. Compound according to claim 17, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R' is H, with the condition that when Ra is -OH, then R4 is different from -CH2CH3 or -C(CH3)3.

19. Compound according to claim 17 or 18, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R4 is unsubstituted C2-C6 alkyl or C6-Cwaryl, provided that when Ra is -OH and R' is H, then R4 is different from -CH2CH3 or -C(CH3)3.

20. A compound according to any one of claims 17 to 19, or a pharmaceutically acceptable salt thereof, characterized in that: R4 is unsubstituted C4 alkyl or phenyl, provided that when Ra is -OH and R' is H, then R4 is different from -C(CH3)3.

21. 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): wherein R2a and Ra are as defined in claim 1 and R is as defined in claim 1 or 2.

22. Compound according to claim 21, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R2a is unsubstituted C3-C6 alkyl, C1-C6 alkyl substituted by 1 to 3 substituents R9, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl or C10 aryl, and each R9 is a halogen, provided that: (i) when Ra is -NH2, and R is H, then R2a is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, Petition 870250100355, dated 03 / 11 / 2025, p.257 / 282 16 / 39 CF3, or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2a is different from -C(CH3)3, -C(CH3)2CH2CH3, or unsubstituted phenyl; (iii) when Ra is -NHCH3 or -NHCH2CH3, and R is H, then R2a is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3, or NHcyclopropyl, and R is H, then R2a is different from -CH2CH2CH3, -CH(CH3)2, C(CH3)3, -C(CH3)2CH2CH3, or -CF3; and (v) when Ra is -NHcyclopentyl or NHcyclohexyl, and R is H, then R2a is different from -C(CH3)3 or C(CH3)2CH2CH3.

23. Compound according to claim 21 or 22, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R2a is unsubstituted C3-C5 alkyl, C1-C2 alkyl substituted by 1 to 3 substituents R9, -C1CH, -NHC(O)OC(CH3)3 or phenyl, and each R9 is F, provided that: (i) when Ra is -NH2, and R is H, then R2a is different from -CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, CF3, or unsubstituted phenyl; (ii) when Ra is -OH and R is H, then R2a is different from -C(CH3)3, -C(CH3)2CH2CH3, or unsubstituted phenyl; (iii) when R a is -NHCH3 or -NHCH2CH3, and R is H, then R2a is different from CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2CH2CH3, -CF3, or unsubstituted phenyl; (iv) when Ra is -NHCH(CH3)2, -NHCH2CH2CH3, or NHcyclopropyl, and R is H, then R2a is different from -CH2CH2CH3, -CH(CH3)2, C(CH3)3, -C(CH3)2CH2CH3, or -CF3; and (v) when Ra is -NHcyclopentyl or NHcyclohexyl, and R is H, then R2a is different from -C(CH3)3 or C(CH3)2CH2CH3.

24. 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): Petition 870250100355, dated 03 / 11 / 2025, page 258 / 282 17 / 39 where R1a, R2b, R4a and R a are as defined in claim 1 and R is as defined in claim 1 or 2.

25. Compound according to claim 24, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R1a and R2b are independently C-CN, C6-C10 aryl or C1C6 alkyl; and R4a is C1-C6 alkyl.

26. Compound according to claim 24 or 25, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that: R1a and R2b are independently -CN, phenyl or methyl; and R4a is -CH2CH(CH3)2.

27. 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): wherein Ra, R1b and R2c are as defined in claim 1 and R is as defined in claim 1 or 2.

28. Compound according to claim 27, 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, are attached. Petition 870250100355, dated 03 / 11 / 2025, page 1. 259 / 282 18 / 39 linked, form a cyclic structure selected from a C3C8cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, with the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group being optionally substituted by oxo, provided that: (i) when Ra is -NH2, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl or 1,3-dioxolane; and (ii) when Ra is -NHCH3, -NHCH2CH3, NHcyclopropyl, -NHCH(CH3)2, or -NHCH2CH2CH3, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl.

29. Compound according to claim 27 or 28, 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 cyclic structure selected from a C5C7cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted with oxo, provided that: (i) when Ra is -NH2, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl, unsubstituted cyclohexyl or 1,3-dioxolane; and (ii) when Ra is -NHCH3, -NHCH2CH3, NHcyclopropyl, -NHCH(CH3)2, or -NHCH2CH2CH3, and R is H, then R1b and R2c form a cyclic structure other than unsubstituted cyclopentyl.

30. 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): Petition 870250100355, dated 03 / 11 / 2025, page 260 / 282 19 / 39 (If) where Ra, R4b and R2d are as defined in claim 1 and R is as defined in claim 1 or 2.

31. Compound according to claim 30, 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.

32. Compound according to claim 30 or 31, 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 cyclohexane.

33. Compound according to claim 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is represented by the formula (Ig): wherein Ra, R1c and R3 are as defined in claim 1.

34. Compound according to claim 33, 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.

35. Compound according to claim 33 or 34, 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 cyclohexane.

36. A compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is selected from the group consisting of -NH2, -NH-OH, -OH or -NHRb and Rb stands for: CH3, or 37. A compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra is selected from the group consisting of -NH2, -OH or -NHRb and Rb stands for: -CH3, , or 38. A compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that Ra stands for -NHRb and Rb stands for V.

39. A compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that R1 is NH2.

40. Pharmaceutically acceptable compound or salt, solvate, or prodrug thereof, characterized in that the compound is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, Petition 870250100355, dated 03 / 11 / 2025, page. 262 / 282 21 / 39 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296, or 297 from Table 1.

41. Compound according to claim 40, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, characterized in that the compound is Compound 4, 6, 12, 20, 46, 76, 77, 78, 80, 81, 84, 85, 86, 87, 98, 99, 100, 101, 105, 109, 120, 121, 125, 127, 128, 129, 132, 134, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 169, 170, 176, 177, 183, 186, 187, 188, 190, 191, 192, 195, 198, 223, 229, 235, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 294, 295, or 296 from Table 1.

42. Compound according to claim 40 or 41, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is Compound 6, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 152, 153, 156, 158, 235, 245, 252, 254 or 255 of Table 1.

43. A compound according to any one of claims 40 to 42, or a pharmaceutically acceptable salt, solvate or prodrug thereof, characterized in that the compound is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158 or 235 of Table 1.

44. A compound according to any one of claims 1 to 43, 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. Petition 870250100355, dated 03 / 11 / 2025, p. 263 / 282 22 / 39 45. Pharmaceutical composition, characterized in that it comprises: a compound, as defined in any one of claims 1 to 44, or a pharmaceutically acceptable salt, solvate or prodrug thereof; and a pharmaceutically acceptable carrier, diluent or excipient.

46. ​​Use of a compound C with Formula (I'): or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASIC inhibitor is indicated, characterized in that: Ra is -NH2, -NH-OH, -OH or -NHRb; Rb is C1-C1-C1-alkyl, C3-C1-C1-cycloalkyl or 3- to 6-membered heterocycloalkyl, wherein C1-C1-alkyl is optionally substituted by 1 to 3 halogens; represents one of the following residues Ao to Aó wherein: R is H or C1-C1-C1-alkyl; R' is H, C1-C1-C1-alkyl or phenyl;R1 is -CN, C-C10aryl, C1-C1-alkyl, C2-C2-alkenyl, C2-C2-alkynyl, F, Cl, Br, I, -N(R”)2, 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 C1-C1-alkyl is optionally substituted by 1 to 3 R7 substituents and C6-C1-aryl is optionally substituted by 1 to 3 R8 substituents; unsubstituted C2-C6alkyl, C1-C6alkyl substituted by 1 to 3 substituents R7, C2-C6alkenyl, C2-C6alkynyl, F, Cl, Br, I, -N(R”)2, 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, where C6-C1oaryl is optionally substituted by 1 to 3 R8 substituents; with the condition that when Ra is -NH2, CX represents the residue Ao, R is H and R1 is -CN, then R2 is different from ; each R” is independently C1-C4alkyl;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-C1-aryl, and the 4- to 6-membered heterocycloalkyl is optionally substituted by -OH; Each R7 is independently -OH, -C(O)Rn, C3C5cycloalkyl, -CN, C6-C10aryl, halogen, -C(O)OH, 5- or 6-membered heteroaryl containing 2 or 3 heteroatoms, -NH(C(O)OC1-C6alkyl), -N(C1C4alkyl)(C(O)OC1-C6alkyl), 4- to 6-membered heterocycloalkyl, NH(C(O)C1-C6alkyl), -OR20, -SC1-C6alkyl, -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, or 4-oxo-1,4-dihydro-1-pyridinyl, wherein each C3C5cycloalkyl is optionally substituted by 1 to 3 substituents. R12, each 5- or 6-membered heteroaryl is optionally substituted by 1 to 3 substituents. R13, and each 4- to 6-membered heterocycloalkyl group is optionally replaced by C1-C4 alkyl or oxo;each R8 is independently halogen, C1-C6 alkyl, -OC1 Petition 870250100355, dated 03 / 11 / 2025, page 265 / 282 24 / 39 C-alkyl, CYC-cycloalkyl, or 5- to 10-membered heteroaryl, wherein each -OC1-C-alkyl is optionally replaced by -OC1-C4 alkyl, and each 5- to 10-membered heteroaryl is optionally replaced by C1-C4 alkyl; Each R9 is independently -OH, -C(O)R15, C3C-cycloalkyl, -CN, C1-C^aryl, halogen, -C(O)OH, 4- to 6-membered heterocycloalkyl, -NH(C(O)C1-C-alkyl), -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 -OC1C-alkyl is optionally substituted by -OC1-C4alkyl; each R11 is independently -NH2, -NH(C1-C4alkyl), N(C1-C4alkyl)2, 4- to 6-membered heterocycloalkyl containing at least 2 heteroatoms, or 4- to 6-membered heterocycloalkyl substituted by -OH;each R20 is independently a 5- to 10-membered C2-C6 alkyl or heteroaryl, wherein each C2-C6 alkyl is optionally substituted by 1 to 3 R14 substituents; each R12 is independently a C1-C4 alkyl, -SC1-C4 alkyl, Ph, -OC1-C4 alkyl, -SPh, or -S(O)2Ph, wherein each C1-C4 alkyl is optionally substituted by -OH; each R13 is independently halogen, C1-C4 alkyl, C(O)OC1-C4 alkyl, C3-C6 cycloalkyl, -C(O)NH2, -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-C6 alkyl, -SC1-C6 alkyl, -S(O)2C1C6 alkyl, -NH(C1-C4 alkyl), and -N(C1-C4 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-C1 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-C8 cycloalkyl are optionally substituted by 1 to 3 R9 substituents, and C6-C8 aryl and heteroaryl groups of 5 to 10 members are optionally substituted by 1 to 3 R10 substituents; 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 unsubstituted C2-C6 alkyl, C1-C6 alkyl substituted by 1 to 3 R9 substituents, C2-C6 alkynyl, -NHC(O)OC1-C6 alkyl, C3C8 cycloalkyl, or C6-C10 aryl, wherein C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and C6-C10 aryl is optionally substituted by 1 to 3 R2 substituents;Each R22 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; 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, 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 substituted by 1 to 3 R19 substituents; each R19 is independently halogen, -OH, -OC1C4 alkyl, -SC1-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 cyclic structure selected from a C3-C8 cycloalkyl, a 4- to 14-membered heterocycloalkyl and an 8- to 14-membered partially unsaturated heterocyclic group, wherein the C3-C8 cycloalkyl is optionally substituted by 1 to 3 R9 substituents, and the 4- to 14-membered heterocycloalkyl and the 8- to 14-membered partially unsaturated heterocyclic group are optionally substituted by oxo; with the condition that when R a is -NH2, C3 represents the residue A4, and R is H, then R1b and R2c form a cyclic structure other than 1,3-dioxolane;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 R1c 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.

47. Use according to claim 46, characterized in that compound C is a compound as defined in any of claims 1 to 44 or a pharmaceutically acceptable salt, solvate or prodrug thereof.

48. Use of a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for the treatment or prevention of a disorder for which an ASIC inhibitor is indicated, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244 245, 246, 247, 248, 249, 250, 251,252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 from Table 2.

49. Use according to claim 48, characterized in that compound C or the pharmaceutically acceptable salt, solvate or prodrug thereof is in the form of a racemate or any enantiomer thereof.

50. Use in accordance with any one of claims 46 to 49, characterized in that the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

51. Use in accordance with any one of claims 46 to 50, characterized in that the ASIC inhibitor is an ASIC1a inhibitor.

52. Use in accordance with any of claims 46 to 50, characterized in that the ASIC inhibitor is an inhibitor of Petition 870250100355, dated 03 / 11 / 2025, page 269 / 282 28 / 39 ASIClb.

53. Use of a compound C or a pharmaceutically acceptable salt, solvate or prodrug thereof according to claim 46, characterized in that it is intended for the preparation of a pharmaceutical composition for 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.

54. Use according to claim 53, characterized in that compound C is a compound as defined in any of the claims 1a 44 or a pharmaceutically acceptable salt, solvate or prodrug thereof.

55. Use of a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for the preparation of a pharmaceutical composition for 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, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, l06, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160,161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194,195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, Petition 870250100355, dated 03 / 11 / 2025, page. 270 / 282 29 / 39 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296, or 297 from Table 2.

56. Use according to claim 55, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254 255, 256, 257, 258, 259, 260, 261, 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

57. Use according to claim 55 or 56, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194 195, 198, 200, 203, 204, 205, 207, 208, 209, 210, 211, 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258 259, 260, 261, 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

58. Use in accordance with any of the claims in Petition 870250100355, dated 11 / 03 / 2025, pp. 271 / 282 30 / 39 57, characterized in that compound C is Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161, 198, 220, 235, 245, 247, 252, 254, 255, 257 or 258 of Table 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

59. Use in accordance with any one of claims 55 to 58, characterized in that compound C is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220 or 235 of Table 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

60. Use in accordance with any of claims 55 to 59, characterized in that compound C or the pharmaceutically acceptable salt, solvate or prodrug thereof is in the form of a racemate or any enantiomer thereof.

61. Use in accordance with any of claims 46 to 60, characterized in that the disorder is pain.

62. Use in accordance with any of claims 46 to 61, characterized in that the disorder is inflammatory pain or neuropathic pain.

63. Use in accordance with any of claims 46 to 61, characterized in that the disorder is inflammatory pain.

64. Use in accordance with any of claims 46 to 61, characterized in that the disorder is neuropathic pain.

65. 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 C as defined in claim 46, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

66. Method according to claim 65, characterized in that compound C is a compound as defined in any of claims 1 to 44 or a pharmaceutically acceptable salt, solvate or prodrug thereof.

67. Method for treating or preventing a disorder for which an ASIC inhibitor is indicated comprising administering to a patient in need thereof a compound C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243 244, 245, 246, 247, 248, 249,250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 from Table 2.

68. Method according to claim 67, characterized in that compound C or the pharmaceutically acceptable salt, solvate or prodrug thereof is in the form of a racemate or any enantiomer thereof.

69. Method according to any one of claims 65 to 68, characterized in that the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

70. Method according to any one of claims 65 to 69, characterized in that the ASIC inhibitor is an ASIC1a inhibitor.

71. Method according to any one of claims 65 to 69, characterized in that the ASIC inhibitor is an ASIC1b inhibitor. Petition 870250100355, dated 03 / 11 / 2025, p. 273 / 282 32 / 39 72. 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 C, as defined in claim 46, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

73. Method according to claim 72, characterized in that compound C is a compound as defined in any of claims 1 to 44 or a pharmaceutically acceptable salt, solvate or prodrug thereof.

74. 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 C, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191,192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251 252, 253, 254, 255, Petition 870250100355, dated 03 / 11 / 2025, pages 274 / 282 33 / 39 256, 257, 258, 259, 260, 261, 294, 295, 296, or 297 of Table 2., 75. Method according to claim 74, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254 255, 256, 257, 258, 259, 260, 261, 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

76. Method according to claim 74 or 75, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189, 190, 191, 192, 194 195, 198, 200, 203, 204, 205, 207, 208, 209, 210, 211, 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259 260, 261, 294, 295, 296, or 297 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

77. Method according to any one of claims 74 to 76, characterized in that compound C is Compound 6, 76, Petition 870250100355, 03 / 11 / 2025, p. 275 / 282 34 / 39 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161, 198, 220, 235, 245, 247, 252, 254, 255, 257 or 258 of Table 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

78. Method according to any one of claims 74 to 77, characterized in that compound C is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220 or 235 of Table 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

79. Method according to any one of claims 74 to 78, characterized in that compound C or the pharmaceutically acceptable salt, solvate or prodrug thereof is in the form of a racemate or any enantiomer thereof.

80. Method according to any one of claims 65 to 79, characterized in that the disorder is pain.

81. A method according to any one of claims 65 to 80, characterized in that the disorder is inflammatory pain or neuropathic pain.

82. Method according to any one of claims 65 to 80, characterized in that the disorder is inflammatory pain.

83. A method according to any one of claims 65 to 80, characterized in that the disorder is neuropathic pain.

84. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for use in the treatment or prevention of a disorder for which an ASIC inhibitor is indicated, characterized in that the compound is a C compound as defined in claim 46.

85. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof according to claim 84, characterized in that compound C is a compound as defined in any one of claims 1 to 44. Petition 870250100355, dated 03 / 11 / 2025, p. 276 / 282 35 / 39 86. A compound, 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, characterized in that the compound is a C compound, with Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259,260, 261, 294, 295, 296 or 297 from Table 2.

87. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof according to claim 86, characterized in that compound C is in the form of a racemate or any enantiomer thereof.

88. A pharmaceutically acceptable compound, or salt, solvate, or prodrug thereof according to any one of claims 84 to 87, characterized in that the ASIC inhibitor is an ASIC1a or ASIC1b inhibitor.

89. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for use in accordance with any of claims 84 to 88, characterized in that the ASIC inhibitor is an ASIC1a inhibitor.

90. Compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for use in accordance with any of claims 84 to 88, characterized in that the ASIC inhibitor is an ASIC1b inhibitor.

91. A compound, 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, characterized in that the compound is a compound C as defined in claim 46.

92. A pharmaceutically acceptable compound, or salt, solvate, or prodrug thereof according to claim 91, characterized in that compound C is a compound as defined in any one of claims 1 to 44.

93. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, for use in the treatment or prevention of a selected disorder of 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 the compound is a compound C being a Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 182, 183, 186, 187, 188, 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 223, 224, 227, 228, 229, Petition 870250100355, dated 03 / 11 / 2025, page. 278 / 282 37 / 39 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296, or 297 from Table 2.

94. Compound, or pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 93, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188, 189 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 from Table 2.

95. Compound, or pharmaceutically acceptable salt, solvate, or prodrug thereof for use according to claim 93 or 94, characterized in that compound C is Compound 4, 6, 12, 16, 20, 24, 25, 28, 29, 46, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 98, 99, 100, 101, 105, 106, 109, 113, 114, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 131, 132, 133, 134, 135, 136, 137, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 176, 177, 181, 183, 186, 187, 188 189, 190, 191, 192, 194, 195, 198, 200, 203, 204, 205, 207, 208, 209, 210, 211, 212, 213, 217, 219, 220, 223, 224, 227, 228, 229, 230, 231, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 254, 255, 256, 257, 258, 259, 260, 261, 294, 295, 296 or 297 of Table 2 Petition 870250100355, dated 03 / 11 / 2025, pages 279 / 282 38 / 39 96. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof according to any one of claims 93 to 95, characterized in that compound C is Compound 6, 76, 98, 120, 127, 128, 129, 137, 143, 144, 146, 147, 148, 152, 153, 156, 158, 160, 161, 198, 220, 235, 245, 247, 252, 254, 255, 257, or 258 of Table 2, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

97. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 93 to 96, characterized in that compound C is Compound 6, 98, 127, 143, 144, 146, 147, 153, 156, 158, 220 or 235 of Table 2, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

98. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 93 to 97, characterized in that compound C is in the form of a racemate or any enantiomer thereof.

99. A compound, or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 84 to 98, characterized in that the disorder is pain.

100. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof according to any one of claims 84 to 99, characterized in that the disorder is inflammatory pain or neuropathic pain.

101. A compound, or a pharmaceutically acceptable salt, solvate, or prodrug thereof according to any one of claims 84 to 99, characterized in that the disorder is inflammatory pain.

102. Compound, or a salt, solvate or prodrug Petition 870250100355, dated 03 / 11 / 2025, p. 280 / 282 39 / 39 pharmaceutically acceptable thereof according to any of claims 84 to 99, characterized in that the disorder is neuropathic pain.