N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamides, compositions comprising them, and uses thereof

Description

N-(2-(4-CYANOTHIAZOLIDIN-3-YL)-2-OXOETHYL)-QUINOLINE-4-CARBOXAMIDES, COMPOSITIONS COMPRISING THEM, AND USES THEREOF Divided from BR112023012022-5, deposited on 12 / 16 / 2021. FIELD

[0001] This disclosure refers generally to A / -(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamides and pharmaceutically acceptable salts thereof. The descriptive report further refers to pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent conditions mediated by Fibroblast activating protein prolyl endopeptidase (FAP); kits comprising such compounds and salts; and methods of manufacturing such compounds and salts. BACKGROUND

[0002] FAP, a type II transmembrane serine protease, is expressed by fibroblast-like cells involved in tissue remodeling and healing. In the context of non-alcoholic steatohepatitis (NASH), FAP is upregulated on the cell surface of activated hepatic stellate cells involved in fibrosis formation (Hepatology 1999, 29, 1768), an important aspect of NASH that predicts disease outcome (Gastroenterology 2020, 158, 1611). FAP may also be present as a released plasma protease. Increased circulating FAP levels are associated with NASH disease severity (Diabetes Res Clin Pract 2015, 108, 466).

[0003] FAP has a consensus cleavage motif after GlyPro and exhibits endopeptidase and exopeptidase activity. Known enzymatic activities include collagen cleavage (Hepatology 1999, 29, 1768), α2-antiplasmin (α2AP) (Blood 2004, 103, 3783), and fibroblast growth factor 21 (FGF21) (Biochem J 2016, 473, 605). Petition 870260043157, dated 07 / 05 / 2026, page 11 / 1284 2 / 598 FAP activity on the cell surface of activated fibroblasts (including collagen cleavage) generates a pro-fibrotic environment. FAP cleavage of α2AP leads to more efficient α2AP cross-linking into fibrin and results in reduced fibrin shedding. FAP cleavage of FGF21 inactivates the metabolic effects of FGF21 (Biochem J2016, 473, 605). All these activities are associated with an exacerbation of NASH disease, and FAP inhibition has the potential to treat NASH and other clinical conditions by affecting multiple mechanisms.

[0004] Inhibition of FAP activity is a currently unexplored therapeutic approach for treating NASH and other diseases associated with such activity. There are currently no approved pharmacological agents available that inhibit FAP activity in general, or that inhibit FAP activity specifically. Accordingly, FAP inhibitors are needed, particularly FAP inhibitors that have pharmacologically appropriate selectivity and bioavailability and, consequently, are suitable for administration to an individual in need of such treatment. This disclosure addresses this significant unmet need by providing such compounds together with corresponding pharmaceutical compositions and methods for the treatment or prevention of NASH and related conditions. SUMMARY

[0005] In one aspect, the present disclosure provides compounds having the structure of Formula (I): and pharmaceutically acceptable salts thereof, wherein: Petition 870260043157, dated 07 / 05 / 2026, page 12 / 1284 3 / 598 X1 is selected from the group consisting of -S-, -S(O)-, and S(O)2-; R1 is selected from the group consisting of hydrogen, halogen, hydroxyl, C1-3-alkyl, and C1-6-alkoxy; R2 is selected from the group consisting of: (a) heterocyclyl containing a total of 4 to 10 ring atoms, wherein the heterocyclyl ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has one, two, or three ring nitrogen atoms, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-e-alkyl, C3-6-cycloalkyl, Cs-s-cycloalkyl-C1-s-alkyl, C1-6-alkoxy, Cs-e-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydro-oxepanil,And where: C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenylC1-3-alkyl, Cy-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and tetrahydrooxepanyl may be additionally substituted with one or more halogens, and (b) the C1-s-alkyl group may be additionally substituted with one or more hydroxyl groups; (b) heterocycline containing a total of 5 to 10 ring atoms, wherein the heterocycline ring: (i) is a monocyclic or bicyclic ring Petition 870260043157, dated 07 / 05 / 2026, p. 13 / 1284 4 / 598 saturated, partially saturated, or completely unsaturated cast iron, (ii) has (a) one ring nitrogen atom and one ring oxygen atom, with the remaining ring atoms being carbon, or (b) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-e-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-e-alkyl, C1-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C13-alkylsulfonyl-C13-alkyl can be additionally substituted with one or more halogens;and (c) spiro-heterocyclyl containing a total of 6 to 11 ring atoms, wherein the spiro-heterocyclyl: (i) comprises two saturated rings, (ii) has: (a) one or two ring nitrogen atoms, with the remaining ring atoms being carbon, (b) one or two ring nitrogen atoms and one or two ring oxygen atoms, with the remaining ring atoms being carbon, or (c) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-e-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl; R3 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; R4 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; R5 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; and Petition 870260043157, dated 07 / 05 / 2026, p. 14 / 1284 5 / 598 R6 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl.

[0006] In another aspect, the present disclosure provides compounds having the structure of Formulas (II), (III-A), (III-B), (III-C), (III-D), (III-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI) as further defined herein, and pharmaceutically acceptable salts thereof.

[0007] In another aspect, the present disclosure provides pharmaceutical compositions comprising a therapeutically effective amount of a compound having the structure of Formulas (I), (II), (IIIIA), (III-B), (III-C), (III-D), (III-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0008] In another aspect, the present disclosure provides pharmaceutical compositions comprising therapeutically effective amounts of a compound having the structure of Formulas (I), (II), (lll-A), (lll-B), (lll-C), (lll-D), (lll-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or a pharmaceutically acceptable salt thereof; a second pharmacological agent; and a pharmaceutically acceptable carrier.

[0009] In another aspect, the present disclosure provides methods for treating or preventing a FAP-mediated condition by administering a therapeutically effective amount of a compound having the structure of Formulas (I), (II), (III-A), (III-B), (III-C), (III-D), (IIIE), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or its pharmaceutically acceptable salt, to a needy individual. In a further aspect, the FAP-mediated condition is selected from the group consisting of liver disease, type 2 diabetes mellitus, cardiovascular conditions, obesity, obesity-related conditions, fibrosis, keloid formation, inflammation, and cancer. In yet another aspect, the FAP-mediated condition is liver disease, particularly non-alcoholic steatohepatitis (NASH). Petition 870260043157, dated 07 / 05 / 2026, p. 15 / 1284 6 / 598

[0010] In another aspect, the present disclosure provides compounds having the structure of Formulas (I), (II), (lll-A), (lll-B), (lll-C), (IIID), (lll-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or pharmaceutically acceptable salts thereof, for use as medicaments to treat or prevent a FAP-mediated condition.

[0011] In another aspect, the present disclosure provides the use of compounds having the structure of Formulas (I), (II), (lll-A), (lll-B), (IIIC), (lll-D), (lll-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or pharmaceutically acceptable salts thereof, to prepare medicaments for treating or preventing a FAP-mediated condition.

[0012] In another aspect, the present disclosure provides kits comprising a compound having the structure of Formulas (I), (II), (IIIA), (lll-B), (lll-C), (lll-D), (lll-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or a pharmaceutically acceptable salt thereof.

[0013] In another aspect, the present disclosure provides methods for preparing compounds having the structure of Formulas (I), (II), (IIIIA), (IIII-B), (IIII-C), (IIII-D), (IIII-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), or (XI), or pharmaceutically acceptable salts thereof. DETAILED DESCRIPTION

[0014] Many embodiments are detailed throughout the descriptive report and will be evident to the reader skilled in the art. The descriptive report should not be interpreted as limited to any particular embodiment(s) described herein. I. Definitions

[0015] Regarding the modalities disclosed in this descriptive report, the following terms have the meanings presented below: Referring to “a” or “an” means “one or more”. Throughout the document, plural and singular should be treated interchangeably, rather than indicating a number. Petition 870260043157, dated 07 / 05 / 2026, page 16 / 1284 7 / 598

[0016] Unless the context requires otherwise, the words “comprise” or “comprises” or “comprising” are used on the basis and clear understanding that they should be interpreted inclusively, rather than exclusively, and that the Applicants intend that each of these words be interpreted in this way when considering this patent, including the claims below.

[0017] The term “halogen” (alone or in combination with other term(s)) means a fluorine radical (which may be represented as -F), a chlorine radical (which may be represented as -Cl), a bromine radical (which may be represented as -Br), or an iodine radical (which may be represented as -I).

[0018] The term “hydroxy” (alone or in combination with other term(s)) means -OH.

[0019] The term “cyan” (alone or in combination with other term(s)) means -CN.

[0020] The term “oxo” (alone or in combination with other term(s)) means an oxo radical, and can be represented as =0.

[0021] The term “alkyl” (alone or in combination with other term(s)) means a saturated linear or branched chain hydrocarbyl substituent (that is, a substituent containing only carbon and hydrogen). Alkyl typically contains from 1 to about 20 carbon atoms, more typically from 1 to about 12 carbon atoms, even more typically from 1 to about 8 carbon atoms, and even more typically from 1 to about 6 carbon atoms. Examples of such substituents include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, fec-butyl, pentyl, isoamyl, 2,2-dimethylpropyl, hexyl, heptyl, and octyl.

[0022] The term “cycloalkyl” (alone or in combination with Petition 870260043157, dated 07 / 05 / 2026, p. 17 / 1284 8 / 598 other term(s)) means a saturated carbocyclyl substituent containing from 3 to about 14 ring carbon atoms, more typically from 3 to about 12 ring carbon atoms, and even more typically from 3 to about 8 ring carbon atoms. A cycloalkyl includes a single ring of carbons, which typically contains from 3 to 6 ring carbon atoms. Examples of single-ring cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0023] The term “cycloalkylalkyl” (alone or in combination with other term(s)) means an alkyl substituted with cycloalkyl. Examples of such substituents include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, and cyclohexylmethyl.

[0024] The term “alkoxy” (alone or in combination with other term(s)) means an alkyl ether substituent, that is, alkyl-O-. Examples of alkoxy include methoxy (CH3-O-), ethoxy, n-propoxy, / so-propoxy, n-butoxy, / so-butoxy, sec-butoxy, and ferc-butoxy. Thus, for example: (i) The term “alkoxyalkyl” (alone or in combination with other term(s)) means alkyl substituted with alkoxy, such as “methoxymethyl” which can be represented as: H3C J (ii) The term “cycloalkylalkoxy” (alone or in combination with other term(s)) means alkoxy substituted with cycloalkyl, such as “cyclopropylmethoxy” which can be represented as: (iii) The term “alkoxyalkoxy” (alone or in combination with other term(s)) means alkoxy replaced with another alkoxy, such as “methoxyethoxy” which can be represented as: H,C. -f J (iv) 0 term “alkoxyalkoxyalkyl” (alone or in combination) Petition 870260043157, dated 07 / 05 / 2026, p. 18 / 1284 9 / 598 nation with other term(s)) means alkyl substituted with alkoxy alkoxy, such as “methoxyethoxymethyl” which can be represented as: (v) the term “alkoxyphenyl” (alone or in combination with other term(s)) means phenyl substituted with alkoxy, such as “4-methoxyphenyl” which can be represented as: (vi) the term “alkoxyphenylalkyl” (alone or in combination with other term(s)) means alkyl substituted with alkoxyphenyl, such as “4-methoxyphenylmethyl” which may be represented as:

[0025] In some cases, the number of carbon atoms in a substituent (e.g., alkyl, cycloalkyl, etc.) is indicated by the prefix “Cx-y-”, where x is the minimum number and y is the maximum number of carbon atoms in the substituent. Thus, for example, “C1-6-alkyl” refers to an alkyl substituent containing from 1 to 6 carbon atoms. As another illustration, C3-6-cycloalkyl refers to a cycloalkyl substituent containing from 3 to 6 ring carbon atoms.

[0026] The prefix “halo” indicates that the substituent to which the prefix is ​​attached is substituted with one or more independently selected halogen radicals. For example, haloalkyl means an alkyl substituent in which at least one hydrogen radical is substituted by a halogen radical. When there is more than one hydrogen substituted by a halogen, the halogens may be the same or different. Examples of haloalkyls include fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, 1,1,1-trifluoroethyl, pentafluoroethyl, difluoropropyl, Petition 870260043157, dated 07 / 05 / 2026, page 19 / 1284 10 / 598 heptafluoropropyl, chloromethyl, dichloromethyl, trichloromethyl, difluorochloromethyl, dichlorofluoromethyl, and dichloropropyl. Similarly, “haloalkoxy” means an alkoxy substituent in which at least one hydrogen radical is substituted by a halogen radical. When there is more than one hydrogen substituted by a halogen, the halogens may be the same or different. Examples of haloalkoxy substituents include fluoromethoxy, difluoromethoxy, trifluoromethoxy (also known as “perfluoromethyloxy”), 1,1,1-trifluoroethoxy, and chloromethoxy.

[0027] The term “carbonyl” (alone or in combination with other term(s)) means -C(O)-, which can also be represented as: the

[0028] Thus, for example: (i) the term “alkylcarbonyl” (alone or in combination with other term(s)) means alkyl-C(O)-, such as “methylcarbonyl” (i.e., acetyl) which can be represented as: the other alkylcarbonyl substituents, such as ethylcarbonyl, propylcarbonyl, butylcarbonyl, pentylcarbonyl, and hexylcarbonyl; (ii) the term “alkylcarbonylalkyl” (alone or in combination with other term(s)) means alkyl substituted with alkylcarbonyl, such as “methylcarbonylmethyl” which can be represented as: h3c J (iii) the term “cycloalkylcarbonyl” (alone or in combination with Petition 870260043157, dated 07 / 05 / 2026, p. 20 / 1284 11 / 598 (combination with other term(s)) means cycloalkyl-C(O)-, such as “cyclopropylcarbonyl” which can be represented as: (iv) the term “cycloalkylcarbonylalkyl” (alone or in combination with other term(s)) means alkyl substituted with cycloalkylcarbonyl, such as “cyclopropylcarbonylmethyl” which can be represented as: the

[0029] The term “tio” or “tia” (alone or in combination with other term(s)) means a divalent sulfur atom, which can also be represented as -S-.

[0030] The term “sulfinyl” or “sulfoxide” (alone or in combination with other term(s)) means -S(O)-, which can also be represented as:

[0031] The term “sulfonyl” (alone or in combination with other term(s)) means -S(O)2-, which can also be represented as:

[0032] Thus, for example, “alkylsulfonyl” (alone or in combination with other term(s)) means alkyl-S(O)2-. Examples of Petition 870260043157, dated 07 / 05 / 2026, p. 21 / 1284 12 / 598 Alkylsulfonyl substituents include methylsulfonyl, ethylsulfonyl, and propylsulfonyl. Similarly, the term "alkylsulfonylalkyl" (alone or in combination with other term(s)) means alkyl substituted with alkylsulfonyl, such as "methylsulfonylmethyl" which can be represented as:

[0033] The term “alkylearbonylaminoalkyl” (alone or in combination with other term(s)) means alkyl-C(O)-N(H)-alkyl-, such as “methylearbonylaminomethyl” which can also be represented as:

[0034] The term “heterocyclyl” (alone or in combination with other term(s)) means a saturated, partially saturated, or completely unsaturated (i.e., heteroaryl) ring structure containing a total of 3 to 14 ring atoms. At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

[0035] Heterocyclyl includes saturated, partially unsaturated, and completely unsaturated monocyclic ring structures having, for example, 3 to 7 members, such as 3 to 6 members, 5 to 7 members, such as 5 or 6 members, wherein at least one member and up to 4 members, particularly 1, 2, or 3 members of the ring are heteroatoms selected from N, O, and S, and the remaining ring atoms are atoms of carbon, in stable combinations known to those skilled in the art.Examples of monocyclic heterocyclics include furanila, dihydrofura. Petition 870260043157, de 07 / 05 / 2026, pág. 22 / 1284 13 / 598 nila, tetra-hydrofuranyl, thiophenyl, di-hydrothiophenyl, tetra-hydrothiophenyl, pyrrolyl, isopyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, isoimidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, dithiolyl, oxathiolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl, thiazolidinyl, isothiazolidinyl, thiazolidinyl, thiodiazolidinyl, oxathiazolyl, dioxazolyl, oxathiazolyl, oxathiazolyl, oxathiazolyl, oxathiolyl, oxatiolanyl, pyranyl, di-hydropyranyl, pyridinyl, piperidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, triazinyl, oxazinyl, isoxazinyl, oxazolidinyl, isoxazolidinyl, oxathiazinyl, morpholinyl, azepinyl, oxepinila, tiepinila, and diazepinila.

[0036] Heterocyclyl additionally includes fused bicyclic ring structures (i.e., fused bicyclics) or two rings with only one atom in common (i.e., spiro), wherein at least one of these rings contains a heteroatom as a ring atom (i.e., nitrogen, oxygen, or sulfur). Examples of heterocyclyls having two ring structures fused together include indolizinyl, pyrindinyl, pyranopyrrolyl, 4H-quinolizinyl, purinyl, naphthyridinyl, pyridopyridinyl, pteridinyl, indolyl, isoindolyl, indoleninyl, isoindazolyl, benzazinyl, phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl, benzopyranyl, benzothiopyranyl, benzoxazolyl, indoxazinyl, anthranilyl, benzodioxolyl, benzodioxanyl, benzoxadiazolyl, benzofuranyl, isobenzofuranyl, benzothienyl, isobenzotienyl, benzothiazolyl, benzothiadiazolyl, benzimidazolyl, benzotriazolyl, benzoxazinyl, benzisoxazinyl, and tetrahydroisoquinolinyl.

[0037] A substituent is “substitutable” if it comprises at least one carbon or nitrogen atom that is bonded to one or more hydrogen atoms. Thus, for example, hydrogen, halogen, and cyano do not fall within the scope of this definition.

[0038] If a substituent is described as being “substituted,” a radical other than hydrogen is in place of a hydrogen radical on a carbon or nitrogen of the substituent. Thus, for example, Petition 870260043157, dated 07 / 05 / 2026, page 23 / 1284 14 / 598 A substituted alkyl substituent is an alkyl substituent in which at least one non-hydrogen radical is in place of a hydrogen radical in the alkyl substituent. To illustrate, monofluoroalkyl is alkyl substituted with a fluoro radical and difluoroalkyl is alkyl substituted with two fluorine radicals. It should be recognized that if there is more than one substitution in a substituent, each non-hydrogen radical may be the same or different (unless stated otherwise).

[0039] If a substituent is described as being “optionally substituted”, the substituent may (1) not be substituted or (2) be substituted. If a carbon of a substituent is described as being optionally substituted with one or more from a list of substituents, one or more of the hydrogens on the carbon (as far as there are any) may be substituted, separately and / or together, by an independently selected optional substituent. If a nitrogen of a substituent is described as being optionally substituted with one or more from a list of substituents, one or more of the hydrogens on the nitrogen (as far as there are any) may each be substituted by an independently selected optional substituent.

[0040] If substituents are described as being “independently selected” from a group, each substituent is selected independently of the others. Consequently, each substituent may be the same as or different from the other substituent(s).

[0041] The term “pharmaceutically acceptable” is used as an adjective in this descriptive report to mean that the modified name is appropriate for use as a pharmaceutical product or as part of a pharmaceutical product. For example, “pharmaceutically acceptable salts” are salts that are suitable for use in mammals, particularly humans, and include salts with an inorganic base. Petition 870260043157, dated 07 / 05 / 2026, page 24 / 1284 15 / 598 organic, inorganic acid, organic acid, or basic or acidic amino acid that are suitable for use in mammals, particularly humans.

[0042] A “therapeutically effective amount” of a pharmacological agent is an amount that is sufficient to provide beneficial or desired results, including clinical results, and as such will depend on the situation in which it is being administered. When the pharmacological agent is being administered to treat liver disease, for example, a therapeutically effective amount of the agent is an amount of the agent that is sufficient, alone or in combination with additional therapies, to provide an anti-liver disease effect in an individual compared to the response obtained without administration of the agent.

[0043] The term “prevent” is easily understood by a usually expert physician and, in relation to the treatment of a particular condition, it may include primary prophylaxis to prevent the development of the condition and secondary prophylaxis where the condition has already developed and the patient is temporarily or permanently protected against exacerbation or worsening of the disease or the development of new symptoms associated with the condition.

[0044] The term “treat” is easily understood by a usually expert physician and, in relation to the treatment of a particular condition, may include (1) reducing the extent or cause of the condition being treated, and / or (2) relieving or improving one or more symptoms associated with that condition. Treatment of liver disease, for example, may include stabilizing (i.e., not worsening), delaying, or slowing the spread or progression of liver disease; prolonging survival compared to survival expected if no treatment were received; and / or otherwise improving or mitigating the effects of cancer or Petition 870260043157, dated 07 / 05 / 2026, p. 25 / 1284 16 / 598 the severity of liver disease, in whole or in part. II. Compounds

[0045] In one embodiment, the present disclosure provides compounds having the structure of Formula (I): and pharmaceutically acceptable salts thereof, where: X1 is selected from the group consisting of -S-, -S(O)-, and S(O)2-; R1 is selected from the group consisting of hydrogen, halogen, hydroxyl, C1-S-alkyl, and C1-6-alkoxy; R2 is selected from the group consisting of: (a) heterocyclyl containing a total of 4 to 10 ring atoms, wherein the heterocyclyl ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has one, two, or three ring nitrogen atoms, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-e-alkyl, C3-6-cycloalkyl, Cs-s-cycloalkyl-C1-s-alkyl, C1-6-alkoxy, Cs-e-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydro-oxepanil,and em que: (a) 0 C1 -e-alquila, Cs e-cicloalquila, C3-6, Petition 870260043157, 07 / 05 / 2026, pág. 26 / 1284 17 / 598 cycloalkoxy-C1-3-alkoxy, C1-6-alkoxy, Cs-e-cycloalkoxy, C1-3-alkoxy-C1-3-alkoxy, C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy-C1-3-alkoxy, C ... tetra-hidrofuranila, tetra-hidropyranila, and tetra-hidrooxepanila can be optionally substituted with either halogênios, and (b) Ci-s-alquila can be optionally substituted with either hydroxis; (b) heterocyclyl containing a total of 5 to 10 ring atoms, wherein the heterocyclyl ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has (a) one ring nitrogen atom and one ring oxygen atom, with the remaining ring atoms being carbon, or (b) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-e-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-e-alkyl, C1-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens;and (c) spiroheterocyclyl containing a total of 6 to 11 ring atoms, wherein the spiroheterocyclyl: (i) comprises two saturated rings, (ii) has: (a) one or two ring nitrogen atoms, with the remaining ring atoms being carbon, (b) one or two ring nitrogen atoms and one or two ring oxygen atoms, with the remaining ring atoms being carbon, or (c) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms; Petition 870260043157, dated 07 / 05 / 2026, page 27 / 1284 18 / 598 being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-e-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl; R3 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; R4 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; R5 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; and R6 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl.

[0046] In some embodiments, the present disclosure provides compounds having the structure of Formula (II): and pharmaceutically acceptable salts thereof, wherein X1, R1, R2, R3, R4, R5, and R6 are as defined above for the compounds of Formula (I). In one aspect, X1 is -S-. In another aspect, X1 is -S(O)-. In another aspect, X1 is -S(O)2-.

[0047] In some embodiments, R1 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl. In one aspect, R1 is selected from the group consisting of hydrogen, chlorine, fluorine, and methyl. In another aspect, R1 is hydrogen. In another aspect, R1 is chlorine. In another aspect, R1 is fluorine. In another aspect, R1 is methyl.

[0048] In some embodiments, R3 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl. In one aspect, R3 is Petition 870260043157, dated 07 / 05 / 2026, page 28 / 1284 19 / 598 selected from the group consisting of hydrogen, chlorine, fluorine, and methyl. In another aspect, R3 is hydrogen. In another aspect, R3 is chlorine. In another aspect, R3 is fluorine. In another aspect, R3 is methyl.

[0049] In some embodiments, R4 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl. In one aspect, R4 is hydrogen. In another aspect, R4 is chlorine. In another aspect, R4 is fluorine. In another aspect, R4 is methyl.

[0050] In some embodiments, R5 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl. In one aspect, R5 is selected from the group consisting of hydrogen, chlorine, fluorine, and methyl. In another aspect, R5 is hydrogen. In another aspect, R5 is fluorine. In another aspect, R5 is chlorine. In another aspect, R5 is methyl.

[0051] In some embodiments, R6 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl. In one aspect, R6 is selected from the group consisting of hydrogen, chlorine, fluorine, and methyl. In another aspect, R6 is hydrogen. In another aspect, R6 is chlorine. In another aspect, R6 is fluorine. In another aspect, R6 is methyl.

[0052] In some embodiments, one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of halogen and ci-s-alkyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine and fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro, and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is Petition 870260043157, dated 07 / 05 / 2026, p. 29 / 1284 20 / 598 methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0053] In some embodiments, at least two of the substituents R1, R3, R4, R5, and R6 are independently selected from the group consisting of halogen and ci-s-alkyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, two of the substituents R1, R3, R4, R5, and R6 are independently selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0054] In some embodiments, at least one of the substituents R1, R3, R4, R5, and R6 is chlorine.

[0055] In some embodiments, at least one of the substituents R1, R3, R4, R5, and R6 is fluorine.

[0056] In some embodiments, at least one of the substituents R1, R3, R4, R5, and R6 is methyl.

[0057] In some embodiments, the present disclosure provides compounds having the structure of Formula (lll-A): and pharmaceutically acceptable salts thereof, wherein R1 and R2 are as defined in the various embodiments above.

[0058] In some embodiments, the present disclosure provides compounds having the structure of Formula (lll-B): Petition 870260043157, dated 07 / 05 / 2026, p. 30 / 1284 21 / 598 and pharmaceutically acceptable salts thereof, wherein R2 and R3 are as defined in the various embodiments above.

[0059] In some embodiments, the present disclosure provides compounds having the structure of Formula (lll-C): and pharmaceutically acceptable salts thereof, wherein R2 and R4 are as defined in the various embodiments above.

[0060] In some embodiments, the present disclosure provides compounds having the structure of Formula (lll-D): and pharmaceutically acceptable salts thereof, wherein R2 and R5 are as defined in the various embodiments above.

[0061] In some embodiments, the present disclosure provides compounds having the structure of Formula (lll-E): Petition 870260043157, dated 07 / 05 / 2026, p. 31 / 1284 22 / 598 and pharmaceutically acceptable salts thereof, wherein R2 and R6 are as defined in the various embodiments above.

[0062] In some embodiments, the present disclosure provides compounds having the structure of Formula (IV): and pharmaceutically acceptable salts thereof, where R2 is as defined above for compounds of Formula (I).

[0063] In some embodiments, the present disclosure provides compounds having the structure of Formula (IV-A): or pharmaceutically acceptable salts thereof, where R2 is as defined above for compounds of Formula (I). A. R2 is Heterocyclic (Nitrogen and Carbon Ring Atoms) Monocyclic or Fused Bicyclic

[0064] In some embodiments, the present disclosure provides compounds having the structure of Formulas (I), (II), (lll-A), (lll-B), (IIIC), (lll-D), (lll-E), (IV), or (IV-A), and pharmaceutically acceptable salts. Petition 870260043157, dated 07 / 05 / 2026, p. 32 / 1284 23 / 598 of the same, wherein R2 is a heterocycline containing a total of 4 to 10 ring atoms, wherein the heterocycline ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has one, two, or three ring nitrogen atoms, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-6-alkyl, C3-6-cycloalkyl, C1-6-cycloalkyl-C1-6-alkyl, C1-6-alkoxy, C1-e-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydro-oxepanil,and where: (a) the C1-e-alkyl, Cs-e-cycloalkyl, Cs-s-cycloalkyl-C1-s-alkyl, C1-6-alkoxy, Cs-e-cycloalkoxy, C1-3alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, Cy-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, (a) tetrahydropyranyl and tetrahydro-oxepanyl may be additionally substituted with one or more halogens, and (b) the C1-e-alkyl group may be additionally substituted with one or more hydroxyl groups. In one aspect, the heterocyclyl ring R2 is a saturated monocyclic ring. In another aspect, the heterocyclyl ring R2 is a partially saturated monocyclic ring. In another aspect, the heterocyclyl ring R2 is a completely unsaturated monocyclic ring. In another aspect,The heterocyclyl ring R2 is a saturated fused bicyclic ring. In another aspect, the heterocyclyl ring R2 is a partially saturated fused bicyclic ring. In another aspect, the heterocyclyl ring R2 is a completely unsaturated fused bicyclic ring. In another aspect, Petition 870260043157, dated 07 / 05 / 2026, page 33 / 1284 24 / 598 The heterocyclyl ring R2 has one ring nitrogen atom, with the remaining ring atoms being carbon. Alternatively, the heterocyclyl ring R2 has two ring nitrogen atoms, with the remaining ring atoms being carbon. Alternatively, the heterocyclyl ring R2 has three ring nitrogen atoms, with the remaining ring atoms being carbon.

[0065] In some embodiments, the heterocyclyl ring R2 is selected from the group consisting of: Petition 870260043157, dated 07 / 05 / 2026, page 34 / 1284 25 / 598 where the heterocyclic ring is optionally replaced with one or more independently selected substitutions from the group consisting of halogênio, hidróxi, oxo, cyan, Ci-s-alquila, Cse-cycloalquila, C36-cycloalquil-Ci-3-alquila, Ci-6-alquila, Cs-e-cycloalcoxi, Ci-3-alcoxi-Ci-3-alquila, Ci-3-alcoxi-C2-3-alcoxi, Ci-3-alcoxi-C2-3-alcoxi-Ci-3-alquila, Ci-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, Ci-3-alquil-carbonylamino-Ci-3-alquila, Ci-3-alquilsulfonyl-Ci-3-alquila, phenyla, tolyla, Ci-3-alcoxifenila, phenylCi-3-alquila, Ci-3-alcoxifenil-Ci-3-alquila, azetidinila, pyrrolidinila, piperidinila, morpholinila, tetra-hidrofuranila, tetra-hidropiranila, e tetra-hidrooxepanila, e em que: (a) 0 Ci-e-alquila, Cse-cicloalquila, Cs-e-cicloalquilCi-3-alquila, Ci-6-alkóxi, Cs-e-cicloalkóxi, Ci-3-alcóxi-Ci-3-alquila, C1-3alcóxi-C2-3-alcóxi, Ci-3-alkóxi-C2-3-alkóxi-Ci-3-alquila, Ci-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, Ci-3-alkyl-carbonylamino-Ci-3-alquila,(a) C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl may be additionally substituted with one or more halogens, and (b) C1-6-alkyl may be additionally substituted with one or more hydroxyls.

[0066] In some embodiments, the heterocyclyl ring R2 is selected from the group consisting of: the Petition 870260043157, dated 07 / 05 / 2026, p. 35 / 1284 26 / 598 where the heterocyclic ring is optionally replaced with one or more independently selected substitutions from the group consisting of halogênio, hidróxi, oxo, cyan, Ci-s-alquila, Cse-cycloalquila, C36-cycloalquil-Ci-3-alquila, Ci-6-alquila, Cs-e-cycloalcoxi, Ci-3-alcoxi-Ci-3-alquila, Ci-3-alcoxi-C2-3-alcoxi, Ci-3-alcoxi-C2-3-alcoxi-Ci-3-alquila, Ci-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, Ci-3-alquil-carbonylamino-Ci-3-alquila, Ci-3-alquilsulfonyl-Ci-3-alquila, phenyla, tolyla, Ci-3-alcoxifenila, phenylCi-3-alquila, Ci-3-alcoxifenil-Ci-3-alquila, azetidinila, pyrrolidinila, piperidinila, morpholinila, tetra-hidrofuranila, tetra-hidropiranila, e tetra-hidrooxepanila, e em que: (a) 0 Ci-e-alquila, Cse-cicloalquila, Cs-e-cicloalquilCi-3-alquila, Ci-6-alkóxi, Cs-e-cicloalkóxi, Ci-3-alcóxi-Ci-3-alquila, C1-3alcóxi-C2-3-alcóxi, Ci-3-alkóxi-C2-3-alkóxi-Ci-3-alquila, Ci-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, Ci-3-alkyl-carbonylamino-Ci-3-alquila,(a) C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl may be additionally substituted with one or more halogens, and (b) C1-6-alkyl may be additionally substituted with one or more hydroxyls.

[0067] In some embodiments, the heterocyclyl ring R2 is selected from the group consisting of: Petition 870260043157, dated 07 / 05 / 2026, p. 36 / 1284 27 / 598 where the heterocyclic ring is optionally replaced with one or more independently selected substitutions from the group consisting of halogênio, hidróxi, oxo, cyan, Ci-s-alquila, Cse-cycloalquila, C36-cycloalquil-Ci-3-alquila, Ci-6-alquila, Cs-e-cycloalcoxi, Ci-3-alcoxi-Ci-3-alquila, Ci-3-alcoxi-C2-3-alcoxi, Ci-3-alcoxi-C2-3-alcoxi-Ci-3-alquila, Ci-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, Ci-3-alquil-carbonylamino-Ci-3-alquila, Ci-3-alquilsulfonyl-Ci-3-alquila, phenyla, tolyla, Ci-3-alcoxifenila, phenylCi-3-alquila, Ci-3-alcoxifenil-Ci-3-alquila, azetidinila, pyrrolidinila, piperidinila, morpholinila, tetra-hidrofuranila, tetra-hidropiranila, e tetra-hidrooxepanila, e em que: (a) 0 Ci-e-alquila, Cse-cicloalquila, Cs-e-cicloalquilCi-3-alquila, Ci-6-alkóxi, Cs-e-cicloalkóxi, Ci-3-alcóxi-Ci-3-alquila, C1-3alcóxi-C2-3-alcóxi, Ci-3-alkóxi-C2-3-alkóxi-Ci-3-alquila, Ci-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, Ci-3-alkyl-carbonylamino-Ci-3-alquila,(a) C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl may be additionally substituted with one or more halogens, and (b) C1-6-alkyl may be additionally substituted with one or more hydroxyls.

[0068] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, oxo, cyano, C13-alkyl, C15-cycloalkyl, C13-alkoxy, C13-alkylcarbonyl, C15-cycloalkylcarbonyl, C13-alkoxy-C13-alkyl, C13-alkoxy-C23-alkoxy, C13-alkoxy Petition 870260043157, dated 07 / 05 / 2026, p. 37 / 1284 28 / 598 C2-3-alkoxy-C1-3-alkyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydro-oxepanyl, wherein C1-3-alkyl, Cse-cycloalkyl, C1-3-alkoxy, C1-3-alkylcarbonyl, Cse-cycloalkylcarbonyl, C1-3-alkoxy-C1-3-alkyl, C13-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylsulfonylC1-3-alkyl, tetrahydrofuranyl, tetrahydropyranyl, and Tetrahydro-oxepanyl may be additionally substituted with one or more halogens.

[0069] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more halogens.

[0070] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, and morpholinyl, wherein the azetidinyl, pyrrolidinyl, piperidinyl, and morpholinyl groups may be additionally substituted with one or more halogens.

[0071] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl, wherein tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl may be additionally substituted with one or more halogens.

[0072] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more chlorines. In another aspect, the heterocyclyl ring R2 is optionally Petition 870260043157, dated 07 / 05 / 2026, p. 38 / 1284 29 / 598 replaced with one or more fluorocarbons.

[0073] In some embodiments, the heterocyclyl ring R2 is optionally replaced with one or more hydroxyl groups.

[0074] In some embodiments, the heterocyclyl ring R2 is optionally replaced with one or more oxos.

[0075] In some embodiments, the heterocyclyl ring R2 is optionally replaced with one or more cyano groups.

[0076] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkyl groups, wherein C1-5-alkyl groups may be further substituted with one or more independently selected halogen and hydroxyl substituents.

[0077] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more Cse-cycloalkyls, wherein the C3-6-cycloalkyl may be additionally substituted with one or more halogens.

[0078] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C3-6-cycloalkyl-C1-3-alkyls, wherein C5-s-cycloalkyl-C1-s-alkyl may be additionally substituted with one or more halogens.

[0079] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkoxy groups, wherein C1-3-alkoxy groups may be additionally substituted with one or more halogens.

[0080] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C3-6-cycloalkoxy groups, wherein C3-6-cycloalkoxy may be additionally substituted with one or more halogens.

[0081] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkoxy-C1-3-alkyl groups, wherein C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more halogens. Petition 870260043157, dated 07 / 05 / 2026, p. 39 / 1284 30 / 598

[0082] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkoxy-C2-3-alkoxy groups, wherein C1-3-alkoxy-C2-3-alkoxy groups may be further substituted with one or more halogens.

[0083] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl groups, wherein C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl group may be additionally substituted with one or more halogens.

[0084] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkylcarbonyls, wherein C1-3-alkylcarbonyl may be additionally substituted with one or more halogens.

[0085] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C3-6-cycloalkylcarbonyls, wherein C3-6-cycloalkylcarbonyl may be additionally substituted with one or more halogens.

[0086] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkyl-carbonylamino-C1-3-alkyls, wherein C1-3-alkyl-carbonylamino-C1-3-alkyl may be additionally substituted with one or more halogens.

[0087] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkylsulfonyl-C1-3-alkyls, wherein C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.

[0088] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, and C1-3-alkoxyphenyl-C1-3-alkyl, wherein the phenyl, tolyl, phenyl-C1-3-alkyl, and C1-3-alkoxyphenyl-C1-3-alkyl may be additionally substituted with one or more halogens. Petition 870260043157, dated 07 / 05 / 2026, p. 40 / 1284 31 / 598

[0089] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, and morpholinyl, wherein the azetidinyl, pyrrolidinyl, piperidinyl, and morpholinyl groups may be additionally substituted with one or more halogens.

[0090] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl, wherein tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl may be additionally substituted with one or more halogens.

[0091] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, oxo, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, trifluoropropyl, methoxy, ethoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, methoxymethyl, trifluoromethoxymethyl, methylcarbonylaminomethyl, methylsulfonylmethyl, morpholinyl, and tetrahydropyranyl.

[0092] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, difluoropropyl, cyclopropyl, methoxy, trifluoromethoxy, ethoxy, and methoxymethyl.

[0093] In some embodiments, the heterocyclyl ring R2 is: N'\ / > J in which the heterocyclyl ring R2 is optionally replaced with a Petition 870260043157, dated 07 / 05 / 2026, p. 41 / 1284 32 / 598 or more substituents independently selected from the group consisting of halogen, hydroxy, C1-e-alkyl, Cs e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, and morpholinyl, and wherein C1-e-alkyl, Cse-cycloalkyl, C1-6-alkoxy, C1-3alkoxy-C1-3-alkyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, Cy-3-alkoxyphenyl, phenyl-C1-3-alkyl, and Morpholinyl groups may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more fluoros.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, trifluoropropyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, methylamidomethyl, methylsulfonylmethyl, and morpholinyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, trifluoroethyl, difluoropropyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoromethoxymethyl, methoxymethyl, methylamidomethyl, and morpholinyl.

[0094] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylazetidin-1-yl)quinoline-4-carboxamide (Example 20); Petition 870260043157, dated 07 / 05 / 2026, page 42 / 1284 33 / 598 (R)-A / -(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Example 21); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylazetidin-1-yl)quinoline-4-carboxamide (Example 22); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoroazetidin-1-yl)quinoline-4-carboxamide (Example 23); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 24); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methylazetidin-1-yl)quinoline-4-carboxamide (Example 25); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 26); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 27); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 28); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(methoxymethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamida (Exemplo 29); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3 / ?)-3-methoxy-2-methylazetidin-1-yl)quinoline-4-carboxamida (Exemplo 30); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 31); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxiazetidin-1-yl)quinoline-4-carboxamida (Exemplo 66); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 113); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-morfolinoazetidin-1-yl)quinoline-4-carboxamide (Exemplo 122); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-((trifluoromethoxy)methyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 130); Petition 870260043157, 07 / 05 / 2026, pág. 43 / 1284 34 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-3-(2,2,2-trifluoroethyl)-azetidin-1-yl)quinoline-4-carboxamide (Exemplo 131); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethoxy)azetidin1-yl)quinoline-4-carboxamide (Exemplo 132); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoroethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 133); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 134); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 135); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethoxy)azetidin1-yl)quinoline-4-carboxamide (Exemplo 136); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 137); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-fluoroazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 138); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoropropyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 140); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(3,3,3-trifluoropropyl)azetidin-1-yl)quinoline-4-carboxamida (Exemplo 142); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(trifluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Example 143); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoroethyl)azetidin1-yl)-quinoline-4-carboxamide (Example 144); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropylazetidin-1 -yl)quinoline-4-carboxamide (Example 145); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2-fluoroethyl)azetidin-1yl)-quinoline-4-carboxamide (Example 146); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(1,1 -d if luroet il)azetid in1-yl)-quinoline-4-carboxamide (Example 147); Petition 870260043157, dated 07 / 05 / 2026, p. 44 / 1284 35 / 598 (R)-A / -(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-isopropylazetidin-1-yl)quinoline-4-carboxamide (Example 148); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxy-3-methylazetidin-1yl)-quinoline-4-carboxamide (Example 151); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethoxy-3-methylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 152); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-hidroxiazetidin-1 yl)-quinoline-4-carboxamida (Exemplo 154); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(fluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 157); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2,2-trifluoroethyl)azetidin-1-yl)quinoline-4-carboxamida (Exemplo 158); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoro-2-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 159); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-hidróxi-3-methylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 165); (R)-6-(3-(Acetamidomethyl)-3-methylazetidin-1-yl)- / \ / -(2-(4-cyanothiazolidin-3yl)-2-oxoethyl)quinoline-4-carboxamida (Exemplo 181); ( / ?)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-phenylazetidin-1-yl)-quinoline-4-carboxamide (Example 182); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(p-tolyl)azetidin-1-yl)quinoline-4-carboxamide (Example 183); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(4-fluorophenyl)azetidin-1yl)-quinoline-4-carboxamide (Example 185); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(n'-tolyl)azetidin-1-yl)quinoline-4-carboxamide (Example 186); ( / ?)-6-(3-(4-Chlorobenzyl)azetidin-1-yl)- / \ / -(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamide (Example 187); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-3-((methylsulfonyl)methyl)azetidin-1-yl)quinoline-4-carboxamide (Example 188); Petition 870260043157, dated 07 / 05 / 2026, page 45 / 1284 36 / 598 and pharmaceutically acceptable salts thereof.

[0095] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylazetidin-1-yl)quinoline-4-carboxamide (Example 22); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 24); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Example 27); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)azetidin-1yl)-quinoline-4-carboxamide (Example 28); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(methoxymethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Example 29); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3 / ?)-3-methoxy-2-methylazetidin-1-yl)quinoline-4-carboxamide (Example 30); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 31); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxiazetidin-1-yl)quinoline-4-carboxamida (Exemplo 66); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 113); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 135); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 138); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoropropyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 140); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(trifluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 143); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(1,1 -d if luoroethyl)azetid in Petition 870260043157, of 05 / 07 / 2026, page 46 / 1284 37 / 598 1-yl)-quinoline-4-carboxamide (Example 147); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxy-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 151); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethoxy-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 152); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(fluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Example 157); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-hydroxy-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 165); and pharmaceutically acceptable salts thereof.

[0096] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, C1-e-alkyl, hydroxy-C1-3-alkyl, C36-cycloalkyl, C16-alkoxy, and C13-alkoxy-C13-alkyl, wherein C1-e-alkyl, hydroxy-C13-alkyl, C16-e-cycloalkyl, C16-alkoxy, and C13-alkoxy-C13-alkyl may be further substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, hydroxy-C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, hydroxy-C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more fluoros.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl. Petition 870260043157, dated 07 / 05 / 2026, page 47 / 1284 38 / 598 pila, hydroxymethyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxy, methyl, ethyl, fluoromethyl, hydroxymethyl, methoxy, and trifluoromethoxy.

[0097] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Example 47); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 48); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R,4S)-3,4-difluoropyrrolidin-1-yl)-quinoline-4-carboxamida (Exemplo 50); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-fluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 51); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-fluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 52); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 54); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 55); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 56); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 57); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 65); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-methoxypyrrolidin-1-yl)quinoline-4-carboxamide (Example 161); Petition 870260043157, dated 07 / 05 / 2026, page 48 / 1284 39 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-hydroxy-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 167); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-hydroxy-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 168); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?S)-3-fluoro-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 198); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-2-cyclopropylpyrrolidin1-yl)quinoline-4-carboxamida Isômero 1 (Exemplo 199); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-2-cyclopropylpyrrolidin1-yl)quinoline-4-carboxamida Isômero 2 (Exemplo 200); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methoxipyrrolidin-1 -yl)quinoline-4-carboxamida (Exemplo 207); A / -(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-methylpyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 211); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamida (Exemplo 212); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 213); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,4 / ?)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 214); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Example 220); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Example 221); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?S)-3,3-difluoro-4-hydroxypyrrolidin-1-yl)quinoline-4-carboxamide (Example 224); / V-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R*,4R*)-3,4-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 225); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R*,4 / ?*)-3,4-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 226); Petition 870260043157, dated 07 / 05 / 2026, page 49 / 1284 40 / 598 and pharmaceutically acceptable salts thereof.

[0098] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, C1-s-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, and C1-3-alkoxy-C1-3-alkyl, and wherein C1-s-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be further substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more fluoros.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, fluoromethyl, methoxy, and trifluoromethoxy.

[0099] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxopyrrolidin-1-yl)quinoline-4-carboxamide (Example 11); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2-oxopyrrolidinPetition 870260043157, of 05 / 07 / 2026, page 50 / 1284 41 / 598 1-yl)quinoline-4-carboxamide (Example 12); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R*)-3-methyl-2-oxopyrrolidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 201); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R*)-3-methyl-2-oxopyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 202); and pharmaceutically acceptable salts thereof.

[0100] In some embodiments, the heterocyclyl ring R2 is: NI NH That the heterocyclic ring R2 is optionally substituted with one or more independently selected substitutions from the group consisting of halogênio, hidróxi, Ci-e-alquila, hidróxi-Ci-3-alquila, C3-6-CÍcloalquila, Cs-s-cycloalquil-Ci-s-alquila, Ci-6-alcóxi, Ci-3-alcóxi-Ci-3-alquila, Ci-3-alcóxi-C2-3-alcóxi, Ci-3-alcóxi-C2-3-alcóxi-Ci-3-alquila, Ci-3-alkyl-carbonylamino-Ci-3-alquila, Ci-3-alquilsulfonyl-Ci-3-alquila, fenila, tetra-hidrofuranila, tetra-hidropiranila, e tetra-hidro-oxepanila, e em que Ci-6-alquila, hidróxi-Ci-3-alquila, Cs-e-cicloalquila, C3-6-cicloalquil-Ci-3-alquila, Ci-6-alcóxi, Ci-3-alcóxi-Ci-3-alquila, Ci-3-alcóxi-C2-3-alcóxi, C1-3alcóxi-C2-3-alcóxi-Ci-3-alquila, Ci-3-alquil-carbonilamino-Ci-3-alquila, C13-alquilsulfonil-Ci-3-alquila, fenila, tetra-hidrofuranila, tetra-hidropiranila, e tetra-hidro-oxepanila podem estar adicionalmente replaced with any halogênios.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, C1-3-alkyl, C1-3-cycloalkyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl, wherein C1-3-alkyl, C1-3-cycloalkyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, and tetrahydropyranyl may be further substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more. Petition 870260043157, dated 07 / 05 / 2026, p. 51 / 1284 42 / 598 independently selected substituents from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and tetrahydropyranyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more independently selected substituents from the group consisting of methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, cyclopropyl, and tetrahydropyranyl.

[0101] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-methyl-1 / - / -pyrazol-4-yl)-quinoline-4-carboxamide (Example 129); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 -cyclopropyl-1 H-pyrazol-4yl)-quinoline-4-carboxamide (Example 170); (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,3-dimethyl-1 / - / -pyrazol-4-yl)quinoline-4-carboxamide (Example 171); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,5-dimethyl-1-(tetra-hydro2H-pyran-4-yl)-1 / - / -pyrazol-4-yl)quinoline-4-carboxamide (Example 172); (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-(tetra-hydro-2 / - / -pyran-4yl)-1 / - / -pyrazol-4-yl)quinoline-4-carboxamide (Example 173); and are pharmaceutically acceptable of the same.

[0102] In some embodiments, the R2é heterocyclyl ring: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, C1-S-alkyl, C1-S-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, Petition 870260043157, dated 07 / 05 / 2026, page 52 / 1284 43 / 598 phenyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydro-oxepanyl, and in which C1-e-alkyl, Cs-e-cycloalkyl, Cs-s-cycloalkyl-Ci-s-alkyl, C1-6alkoxy, C1-3-alkoxy-Ci-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3alkoxy-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydro-oxepanyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-3-alkyl, Cs-e-cycloalkyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrooxepanyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, and tetrahydropyranyl may be additionally substituted with one or more halogens.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and tetrahydropyranyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, cyclopropyl, and tetrahydropyranyl.

[0103] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-methyl-1 / - / -pyrazol-5-yl)-quinoline-4-carboxamide (Example 174); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-(tetrahydro-2 / - / -pyran-2yl)-1 / - / -pyrazol-5-yl)quinoline-4-carboxamide (Example 176); Petition 870260043157, dated 07 / 05 / 2026, page 53 / 1284 44 / 598 (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 / - / -pyrazol-5-yl)quinoline-4carboxamide (Example 196); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-isopropyl-1H-pyrazol-5-yl)quinoline-4-carboxamide (Example 197); and pharmaceutically acceptable salts thereof.

[0104] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, C1-e-alkyl, C1-s-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, phenyl, tolyl, and C1-3-alkoxyphenyl, and wherein C1-e-alkyl, C1-s-e-cycloalkyl, C1-s-cycloalkyl-C1-s-alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C23-alkoxy-C1-3-alkyl, phenyl, tolyl, and C1-3-alkoxyphenyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, cyclopropyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be further substituted with one or more fluoros. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl. In another aspect, the ring he. Petition 870260043157, dated 07 / 05 / 2026, p. 54 / 1284 45 / 598 terociclila R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, and trifluoroethoxy.

[0105] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidin-1-yl)quinoline-4-carboxamide (Example 7); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxypiperidin-1-yl)-quinoline-4-carboxamide (Example 8); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(piperidin-1-yl)quinoline-4carboxamide (Example 32); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-dimethylpiperidin-1-yl)quinoline-4-carboxamide (Example 33); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-methylpiperidin-1-yl)quinoline-4-carboxamide (Example 34); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoropiperidin-1-yl)quinoline-4-carboxamide (Example 35); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoropiperidin-1-yl)quinoline-4-carboxamide (Example 36); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-(fluoromethyl)-4-methyl-piperidin-1-yl)quinoline-4-carboxamide (Example 37); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoro-3,3-dimethyl-piperidin-1-yl)quinoline-4-carboxamide (Example 38); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-(trifluoromethyl)piperidin1-yl)-quinoline-4-carboxamide (Example 39); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoropiperidin-1-yl)quinoline-4-carboxamide (Example 40); Petition 870260043157, dated 07 / 05 / 2026, page 55 / 1284 46 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxipiperidin-1-yl)-quinoline-4-carboxamida (Exemplo 41); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxy-4-methylpiperidin1-yl)quinoline-4-carboxamida (Exemplo 42); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-isopropoxypiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 43); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoro-2-methylpiperidin-1-yl)quinoline-4-carboxamide (Exemplo 44); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)piperidin-1-yl)quinoline-4-carboxamide (Exemplo 45); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-hidroxipiperidin-1 yl)quinoline-4-carboxamida (Exemplo 189); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hidróxi-4-methylpiperidin1-yl)quinoline-4-carboxamida (Exemplo 190); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-methoxypiperidin-1yl)-quinoline-4-carboxamide (Example 191); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hydroxy-4-isopropylpiperidin-1-yl)quinoline-4-carboxamide (Example 192); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,4S,5S)-4-hydroxy3,4,5-trimethylpiperidin-1-yl)quinoline-4-carboxamide (Example 193); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoropiperidin-1-yl)quinoline-4-carboxamide (Example 205); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-phenylpiperidin-1yl)-quinoline-4-carboxamide (Example 223); and pharmaceutically acceptable salts thereof.

[0106] In some embodiments, the heterocyclyl ring R2 is:

[0107] In some forms, the pharmaceutical compound or salt Petition 870260043157, dated 07 / 05 / 2026, page 56 / 1284 47 / 598 acceptable is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-oxopiperidin-1-yl)quinoline-4-carboxamide (Example 230), or a pharmaceutically acceptable salt thereof.

[0108] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, oxo, C1-6-alkyl, C1-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, and phenyl, and wherein C1-6-alkyl, C1-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, and phenyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, oxo, C1-3-alkyl, cyclopropyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, cyclopropyl-C1-3-alkyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be further substituted with one or more fluoros. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, oxo, methyl, ethyl, isopropyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, propoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, oxo, methyl, etc. Petition 870260043157, dated 07 / 05 / 2026, p. 57 / 1284 48 / 598 ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, and methoxymethyl.

[0109] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-1-methylpiperidin-4-yl)quinoline-4-carboxamide (Example 195), or its pharmaceutically acceptable salt.

[0110] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, and C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, and wherein C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, and C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more fluoros.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxime. Petition 870260043157, dated 07 / 05 / 2026, page 58 / 1284 49 / 598 tila. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, trifluoroethoxy, and methoxymethyl.

[0111] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxopiperidin-1-yl)quinoline-4-carboxamide (Example 14); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2-oxopiperidin1-yl)-quinoline-4-carboxamide (Example 15); / V-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R*)-3-methyl-2-oxopiperidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 203); / V-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R*)-3-methyl-2-oxopiperidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 204); and pharmaceutically acceptable salts thereof.

[0112] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-S-alkyl, hydroxy-C1-3-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkyloxy, and C1-3-alkoxy-C2-3-alkyloxy-C1-3alkyl, and wherein C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkyloxy-C1-3alkyl may be further substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3 Petition 870260043157, dated 07 / 05 / 2026, p. 59 / 1284 50 / 598 alkyl, hydroxy-Ci-s-alkyl, cyclopropyl, Ci-3-alkoxy, and Ci-3-alkoxy-Ci-3-alkyl, wherein Ci-s-alkyl, cyclopropyl, Ci-3-alkoxy, and Ci-3-alkoxy-Ci-3-alkyl may be additionally substituted with one or more fluoros. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxy, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, propoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, and methoxymethyl.

[0113] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(pyridin-3-yl)quinoline-4-carboxamide (Example 126); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-methylpyridin-3-yl)quinoline-4-carboxamide (Example 128); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(difluoromethyl)pyridin-3yl)-quinoline-4-carboxamide (Example 169); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methylpyridin-3-yl)quinoline-4-carboxamide (Example 177); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methoxypyridin-3-yl)quinoline-4-carboxamide (Example 178); and pharmaceutically acceptable salts thereof.

[0114] In some embodiments, the heterocyclyl ring R2 is: Petition 870260043157, dated 07 / 05 / 2026, p. 60 / 1284 51 / 598 wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-e-alkyl, hydroxy-C1-3-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, and C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, and wherein C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl may be further substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, hydroxy-C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be further substituted with one or more fluoros.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, propoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, and methoxymethyl.

[0115] In some embodiments, the pharmaceutical compound or salt Petition 870260043157, dated 07 / 05 / 2026, page 61 / 1284 52 / 598 acceptable is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-dimethyl-5,6-dihydro-4 / - / -pyrrolo[1,2-b]pyrazol-3-yl)quinoline-4-carboxamide (Example 123), or a pharmaceutically acceptable salt thereof.

[0116] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-e-alkyl, hydroxy-C1-3-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, and C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, and wherein C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl may be further substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, C1-3-alkyl, hydroxy-C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl, wherein C1-3-alkyl, cyclopropyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be further substituted with one or more fluoros.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, propoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, and trifluoromethoxymethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, hydroxyl, methyl. Petition 870260043157, dated 07 / 05 / 2026, page 62 / 1284 53 / 598 ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, cyclopropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, and methoxymethyl.

[0117] In some embodiments, the pharmaceutically acceptable compound or salt is ( / ?)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,6,7,8tetrahydroimidazo[1,2-a]pyridin-3-yl)quinoline-4-carboxamide (Example 175) or a pharmaceutically acceptable salt thereof.

[0118] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S,5 / ?)-4-hydroxy-3,5-dimethylpiperidin-1-yl)quinoline-4-carboxamide (Example 7); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxypiperidin-1-yl)-quinoline-4-carboxamide (Example 8); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxopyrrolidin-1-yl)quinoline-4-carboxamide (Example 11); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2-oxopyrrolidin1-yl)quinoline-4-carboxamide (Example 12); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxopiperidin-1-yl)quinoline-4-carboxamida (Exemplo 14); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2-oxopiperidin1-yl)-quinoline-4-carboxamida (Exemplo 15); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 20); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 21); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 22); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 23); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-methylazetidin-1 Petition 870260043157, 07 / 05 / 2026, pág. 63 / 1284 54 / 598 il)-quinoline-4-carboxamida (Exemplo 24); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 25); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 26); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 27); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 28); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(methoxymethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamida (Exemplo 29); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3 / ?)-3-methoxy-2-methylazetidin-1-yl)quinoline-4-carboxamida (Exemplo 30); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 31); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(piperidin-1-yl)quinoline-4carboxamide (Exemplo 32); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-dimethylpiperidin-1-yl)quinoline-4-carboxamide (Exemplo 33); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-methylpiperidin-1yl)quinoline-4-carboxamida (Exemplo 34); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoropiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 35); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoropiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 36); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-(fluoromethyl)-4-methyl-piperidin-1-yl)quinoline-4-carboxamide (Exemplo 37); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoro-3,3-dimethyl-piperidin-1-yl)quinoline-4-carboxamide (Exemplo 38); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-(trifluoromethyl)piperidinPetição 870260043157, dated 07 / 05 / 2026, pág. 64 / 1284 55 / 598 1-yl)-quinoline-4-carboxamida (Exemplo 39); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoropiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 40); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxipiperidin-1-yl)-quinoline-4-carboxamida (Exemplo 41); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxy-4-methylpiperidin1-yl)quinoline-4-carboxamida (Exemplo 42); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-isopropoxypiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 43); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoro-2-methylpiperidin-1-yl)quinoline-4-carboxamide (Exemplo 44); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)piperidin-1-yl)quinoline-4-carboxamide (Exemplo 45); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoropyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 47); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylpyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 48); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 50); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-fluoropyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 51); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-fluoropyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 52); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(hexa-hidrocyclopenta[c]pyrrol-2(1 / - / )-yl)quinoline-4-carboxamida (Exemplo 53); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methylpyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 54); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 55); Petition 870260043157, dated 07 / 05 / 2026, page 65 / 1284 56 / 598 / V-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Example 56); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 57); / V-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-fluoroazepan-1yl)quinoline-4-carboxamide (Example 59); / V-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-fluoroazepan-1yl)quinoline-4-carboxamide (Example 60); / V-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 65); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxyazetidin-1-yl)quinoline-4-carboxamide (Example 66); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 113); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,5,6,7-tetra-hidro-1 / - / -indazol-1-yl)quinolina-4-carboxamida (Exemplo 114); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,5,6,7-tetra-hidro-2H-indazol-2-yl)quinolina-4-carboxamida (Exemplo 115); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-methyl-3-(trifluoromethyl)1 / - / -pyrazol-1-yl)quinoline-4-carboxamida (Exemplo 116); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-dimethyl-5,6-di-hidrociclopenta[c]pyrazol-2(4 / - / )-yl)quinoline-4-carboxamida (Exemplo 117); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethyl)-1 / - / -pyrazol-1-yl)quinoline-4-carboxamida (Exemplo 118); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,6-difluoro-1 / - / -indol-1 -yl)quinoline-4-carboxamida (Exemplo 119); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-fluoro-1 / - / -indol-1 -yl)quinoline-4-carboxamida (Exemplo 120); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-1 / - / -pyrrol-1 -yl)-quinoline-4-carboxamida (Exemplo 121); Petition 870260043157, 07 / 05 / 2026, pág. 66 / 1284 57 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-morpholinoazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 122); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-dimethyl-5,6-di-hidro4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-4-carboxamida (Exemplo 123); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-fluoropyridin-4-yl)quinoline-4-carboxamida (Exemplo 124); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-fluoropyridin-2-yl)quinoline-4-carboxamide (Exemplo 125); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(pyridin-3-yl)quinoline-4-carboxamide (Exemplo 126); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(pyrimidin-5-yl)quinoline-4carboxamide (Exemplo 127); / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-methylpyridin-3-yl)quinoline4-carboxamide (Exemplo 128); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 -methyl-1 / - / -pyrazol-4-yl)-quinoline-4-carboxamida (Exemplo 129); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-((trifluoromethoxy)methyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 130); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-3-(2,2,2-trifluoroethyl)-azetidin-1-yl)quinoline-4-carboxamide (Exemplo 131); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethoxy)azetidin1-yl)quinoline-4-carboxamide (Exemplo 132); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoroethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 133); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 134); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 135); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethoxy)azetidin1-yl)-quinoline-4-carboxamide (Exemplo 136); Petition 870260043157, 07 / 05 / 2026, pág. 67 / 1284 58 / 598 (R)-A / -(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 137); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-fluoroazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 138); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoropropyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 140); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(3,3,3-trifluoropropyl)azetidin-1-yl)quinoline-4-carboxamida (Exemplo 142); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(trifluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 143); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoroethyl)azetidin1-yl)-quinoline-4-carboxamide (Exemplo 144); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropylazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 145); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2-fluoroethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 146); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(1,1 -d if luoroet il)azetid in1-yl)-quinolina-4-carboxamida (Exemplo 147); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-isopropylazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 148); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-metóxi-3-methylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 151); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethoxy-3-methylazetidin-1yl)-quinoline-4-carboxamide (Example 152); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-hydroxyazetidin-1 il)-quinoline-4-carboxamide (Example 154); 6-(6-Azabicyclo[3.2.0]heptan-6-yl)- / \ / -(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamide (Example 156); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(fluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Example 157); Petition 870260043157, dated 07 / 05 / 2026, p. 68 / 1284 59 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2,2-trifluoroethyl)azetidin-1-yl)quinoline-4-carboxamide (Example 158); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoro-2-methylazetidin-1-yl)quinoline-4-carboxamide (Example 159); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)quinoline-4-carboxamida (Exemplo 160); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-methoxipyrrolidin-1 -yl)quinoline-4-carboxamida (Exemplo 161); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-hidróxi-3-methylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 165); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-hidróxi-3-methylpyrrolidin-1-yl)quinoline-4-carboxamida (Exemplo 167); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-hidróxi-3-methylpyrrolidin-1-yl)quinoline-4-carboxamida (Exemplo 168); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(difluoromethyl)pyridin-3yl)-quinoline-4-carboxamida (Exemplo 169); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 -cyclopropyl-1 H-pyrazol-4yl)-quinoline-4-carboxamida (Exemplo 170); ( / ?)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,3-dimethyl-1 / - / -pyrazol-4-yl)quinoline-4-carboxamide (Example 171); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,5-dimethyl-1-(tetra-hydro2H-pyran-4-yl)-1 H-pyrazol-4-yl)quinoline-4-carboxamide (Example 172); ( / ?)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-(tetra-hydro-2 / - / -pyran-4yl)-1H-pyrazol-4-yl)quinoline-4-carboxamide (Example 173); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 -methyl-1 / - / -pyrazol-5-yl)-quinoline-4-carboxamide (Example 174); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,6,7,8-tetra-hydroimidazo[1,2-a]-pyridin-3-yl)quinoline-4-carboxamide (Example 175); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-(tetra-hydro-2 / - / -pyran-2yl)-1H-pyrazol-5-yl)quinoline-4-carboxamide (Example 176); Petition 870260043157, of 07 / 05 / 2026, p. 69 / 1284 60 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methylpyridin-3-yl)quinoline-4-carboxamide (Exemplo 177); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methoxipyridin-3-yl)quinoline-4-carboxamida (Exemplo 178); ( / ?)-6-(3-(Acetamidomethyl)-3-methylazetidin-1-yl)- / \ / -(2-(4-cyanothiazolidin-3yl)-2-oxoethyl)quinoline-4-carboxamida (Exemplo 181); ( / ?)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-phenylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 182); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(p-tolyl)azetidin-1-yl)quinoline-4-carboxamida (Exemplo 183); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(4-fluorophenyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 185); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(n?-tolyl)azetidin-1 -yl)quinoline-4-carboxamide (Exemplo 186); ( / ?)-6-(3-(4-Chlorobenzil)azetidin-1-yl)- / \ / -(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamida (Exemplo 187); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-3-((methylsulfonyl)methyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 188); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-hidroxipiperidin-1 yl)-quinoline-4-carboxamida (Exemplo 189); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hidróxi-4-methylpiperidin1-yl)quinoline-4-carboxamida (Exemplo 190); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-methoxipiperidin-1yl)-quinoline-4-carboxamida (Exemplo 191); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hidróxi-4-isopropylpiperidin-1-yl)quinoline-4-carboxamida (Exemplo 192); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,4S,5S)-4-hydroxy3,4,5-trimethyl I piperidin-1 -yl)quinolina-4-carboxamida (Exemplo 193); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-1-metilpiperidin-4yl)-quinolina-4-carboxamida (Exemplo 195); Petition 870260043157, 07 / 05 / 2026, pág. 70 / 1284 61 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 / - / -pyrazol-5-yl)quinoline-4carboxamida (Exemplo 196); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1 -isopropyl-1 / - / -pyrazol-5-yl)quinoline-4-carboxamida (Exemplo 197); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?S)-3-fluoro-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 198); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-2-cyclopropylpyrrolidin1-yl)quinoline-4-carboxamida Isômero 1 (Exemplo 199); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-2-cyclopropylpyrrolidin1-yl)quinoline-4-carboxamida Isômero 2 (Exemplo 200); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopyrrolidin-1-yl)quinoline-4-carboxamida Isômero 1 (Exemplo 201); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopyrrolidin-1-yl)quinoline-4-carboxamida Isômero 2 (Exemplo 202); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopiperidin-1-yl)quinoline-4-carboxamida Isômero 1 (Exemplo 203); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopiperidin-1-yl)quinoline-4-carboxamida Isômero 2 (Exemplo 204); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoropiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 205); 6-(3-Azabicyclo[3.1.0]hexan-3-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamide (Exemplo 206); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methoxipyrrolidin-1 -yl)quinoline-4-carboxamida (Exemplo 207); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((1 / ?,5S,6 / ?)-6-(trifluoromethyl)-3-azabicyclo[3.1.0]hexan-3-yl)quinoline-4-carboxamida (Exemplo 208); ( / ?)-6-(7-Azabiciclo[2.2.1]heptan-7-yl)- / \ / -(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamida (Exemplo 209); Petition 870260043157, 07 / 05 / 2026, pág. 71 / 1284 62 / 598 6-(2-Azabicyclo[2.2.1 ]heptan-2-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamide (Exemplo 210); A / -(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-methylpyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 211); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamida (Exemplo 212); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 213); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,4 / ?)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 214); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-phenyl-1 / - / -imidazol-1 -yl)quinoline-4-carboxamida (Exemplo 217); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-phenyl-1 H-pyrrol-1 -yl)-quinoline-4-carboxamida (Exemplo 218); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,5,6,7-tetra-hidro-1 / - / -indol-1-yl)quinolina-4-carboxamida (Exemplo 219); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 220); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 221); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-phenylpiperidin-1yl)-quinoline-4-carboxamide (Example 223); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?S)-3,3-difluoro-4-hydroxypyrrolidin-1-yl)quinoline-4-carboxamide (Example 224); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R*,4 / ?*)-3,4-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 225); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R*,4 / ?*)-3,4-dimethylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 226); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-oxopiperidin-1-yl)quinoline-4-carboxamide (Example 230); Petition 870260043157, dated 07 / 05 / 2026, page 72 / 1284 63 / 598 and pharmaceutically acceptable salts thereof.

[0119] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S,5 / ?)-4-hydroxy-3,5-dimethylpiperidin-1-yl)quinoline-4-carboxamide (Example 7); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxypiperidin-1-yl)-quinoline-4-carboxamide (Example 8); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2-oxopyrrolidin1-yl)quinoline-4-carboxamide (Example 12); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2-oxopiperidin1-yl)quinoline-4-carboxamide (Example 15); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylazetidin-1-yl)quinoline-4-carboxamide (Example 22); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 24); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 27); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)azetidin-1yl)quinoline-4-carboxamida (Exemplo 28); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(methoxymethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamida (Exemplo 29); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3 / ?)-3-methoxy-2-methylazetidin-1-yl)quinoline-4-carboxamida (Exemplo 30); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3-fluoroazetidin-1-yl)quinoline-4-carboxamide (Exemplo 31); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(piperidin-1-yl)quinoline-4carboxamide (Exemplo 32); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-methylpiperidin-1yl)quinoline-4-carboxamida (Exemplo 34); Petition 870260043157, 07 / 05 / 2026, pág. 73 / 1284 64 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxipiperidin-1 -yl)-quinoline-4-carboxamida (Exemplo 41); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxy-4-methylpiperidin1-yl)quinoline-4-carboxamida (Exemplo 42); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-isopropoxypiperidin-1 -yl)quinoline-4-carboxamide (Exemplo 43); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 50); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-fluoropyrrolidin-1 -yl)quinoline-4-carboxamide (Exemplo 52); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxiazetidin-1-yl)quinoline-4-carboxamida (Exemplo 66); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)azetidin-1yl)-quinoline-4-carboxamida (Exemplo 113); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 135); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-fluoroazetidin-1 -yl)quinoline-4-carboxamide (Exemplo 138); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoropropyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 140); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(trifluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 143); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(1,1 -d if luoroet il)azetid in1-yl)quinolina-4-carboxamida (Exemplo 147); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxy-3-methylazetidin-1yl)quinoline-4-carboxamida (Exemplo 151); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethoxy-3-methylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 152); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(fluoromethyl)azetidin-1-yl)quinoline-4-carboxamide (Exemplo 157); Petition 870260043157, 07 / 05 / 2026, pág. 74 / 1284 65 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-methoxipyrrolidin-1 -yl)quinoline-4-carboxamida (Exemplo 161); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-hidróxi-3-methylazetidin-1yl)-quinoline-4-carboxamida (Exemplo 165); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(difluoromethyl)pyridin-3yl)-quinoline-4-carboxamida (Exemplo 169); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,5-dimethyl-1-(tetra-hidro2H-pyran-4-yl)-1 H-pyrazol-4-yl)quinoline-4-carboxamida (Exemplo 172); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,6,7,8-tetra-hidroimidazo[1,2-a]pyridin-3-yl)quinoline-4-carboxamida (Exemplo 175); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-hydroxypiperidin-1yl)quinoline-4-carboxamide (Example 189); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hydroxy-4-methylpiperidin-1-yl)quinoline-4-carboxamide (Example 190); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-1-methylpiperidin-4yl)-quinoline-4-carboxamide (Example 195); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?S)-3-fluoro-3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 198); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopyrrolidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 201); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 202); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopiperidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 203); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-methyl-2-oxopiperidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 204); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoropiperidin-1-yl)quinoline-4-carboxamide (Example 205); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methoxypyrrolidin-1-yl)quinoline-4-carboxamide (Example 207); Petition 870260043157, dated 07 / 05 / 2026, page 75 / 1284 66 / 598 A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Example 213); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Example 221); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((RS)-3,3-difluoro-4-hydroxypyrrolidin-1-yl)quinoline-4-carboxamide (Example 224); and pharmaceutically acceptable salts thereof. B. R2 is a fused monocyclic or bicyclic heterocyclic compound (ring atoms of nitrogen, oxygen (or sulfur), and carbon).

[0120] In some embodiments, the present disclosure provides compounds having the structure of Formulas (I), (II), (IIIl-A), (IIIl-B), (IIIC), (IIIl-D), (IIIl-E), (IV), or (IV-A), and pharmaceutically acceptable salts thereof, wherein R2 is a heterocycline containing a total of 5 to 10 ring atoms, wherein the heterocycline ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has (a) one ring nitrogen atom and one ring oxygen atom, with the remaining ring atoms being carbon, or (b) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C3-6cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and where C1-s-alkyl,C3-6-C1I0 alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is a saturated monocyclic ring. In another aspect, the heterocyclyl ring R2 is a partially saturated monocyclic ring. In another aspect, the heterocyclyl ring R2 is a completely unsaturated monocyclic ring. Petition 870260043157, dated 07 / 05 / 2026, p. 76 / 1284 67 / 598 In another aspect, the heterocyclyl ring R2 is a saturated fused bicyclic ring. In another aspect, the heterocyclyl ring R2 is a partially saturated fused bicyclic ring. In another aspect, the heterocyclyl ring R2 is a completely unsaturated fused bicyclic ring. In another aspect, the heterocyclyl ring R2 has one ring nitrogen atom and one ring oxygen atom, with the remaining ring atoms being carbon. In another aspect, the heterocyclyl ring R2 has one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon.

[0121] In some embodiments, the heterocyclyl ring R2 contains a total of 6 to 10 ring atoms.

[0122] In some embodiments, the heterocyclyl ring R2 is selected from the group consisting of: the wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-ε-alkyl, C2-ε-cycloalkyl, C1-6-alkoxy, C1-Petition 870260043157, dated 07 / 05 / 2026, page 77 / 1284 68 / 598 3-alkoxy-Ci-3-alkyl, Ci-3-alkylcarbonyl-Ci-3-alkyl, and Ci-3-alkylsulfonyl-Ci-3-alkyl, wherein Ci-s-alkyl, Ci-6-alkoxy, Ci-3-alkoxy-Ci-3-alkyl, C36-cycloalkyl, Ci-3-alkylcarbonyl-Ci-3-alkyl, and Ci-3-alkylsulfonyl-Ci-3-alkyl may be further substituted with one or more halogens.

[0123] In some embodiments, the heterocyclyl ring R2 is selected from the group consisting of: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-ε-alkyl, C3-ε-cycloalkyl, C1-6-alkoxy, C13-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-ε-alkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C36-cycloalkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.

[0124] In some embodiments, the heterocyclyl ring R2 is selected from the group consisting of: in which the heterocyclyl ring is optionally replaced with an or Petition 870260043157, dated 07 / 05 / 2026, p. 78 / 1284 69 / 598 plus substituents independently selected from the group consisting of halogen, cyano, C1-e-alkyl, C1-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl, wherein C1-e-alkyl, C1-6-cycloalkyl, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl may be additionally substituted with one or more halogens.

[0125] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, C35-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, C5-5-cycloalkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.

[0126] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-2-alkyl, C3-4-cycloalkyl, C1-2-alkoxy, C1-2-alkoxy-C1-3-alkyl, C1-2-alkylcarbonyl-C1-2-alkyl, and C1-2-alkylsulfonyl-C1-2-alkyl, wherein C1-2-alkyl, C3-4-cycloalkyl, C1-2-alkoxy, C1-2-alkoxy-C1-2-alkyl, C1-2-alkylcarbonyl-C1-2-alkyl, and C1-2-alkylsulfonyl-C1-2-alkyl may be additionally substituted with one or more halogens.

[0127] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more fluoros.

[0128] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkyls, wherein C1-3-alkyl may be additionally substituted with one or more halogens. Petition 870260043157, dated 07 / 05 / 2026, p. 79 / 1284 70 / 598

[0129] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more Cse-cycloalkyls, wherein the C3-6cycloalkyl may be additionally substituted with one or more halogens.

[0130] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkoxy-C1-3-alkyls, wherein C1-3-alkoxy-C1-3-alkyl may be additionally substituted with one or more halogens.

[0131] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkylsulfonyl-C1-3-alkyls, wherein C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.

[0132] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, methoxyethyl, trifluoromethoxymethyl, and methylsulfonylmethyl.

[0133] In some embodiments, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, isopropyl, cyclopropyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0134] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-ε-alkyl, C1-ε-cycloalkyl, C1-ε-6 Petition 870260043157, dated 07 / 05 / 2026, p. 80 / 1284 71 / 598 alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-6-alkyl, C1-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, C3-5-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, C3-5-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, cyano, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, methoxyethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, trifluoromethyl, difluoropropyl, methoxy, trifluoromethoxy, and methoxymethyl.

[0135] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-3-fluoro-6-morpholinoquinoline4-carboxamide (Example 2); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-difluoromorpholino)quinoline-4-carboxamide (Example 4); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2,6,6-tetrafluoromorpholino)-quinoline-4-carboxamide (Example 5); Petition 870260043157, dated 07 / 05 / 2026, page 81 / 1284 72 / 598 (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-8-methyl-6-morpholinoquinoline4-carboxamide (Example 9); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-7-methyl-6-morpholinoquinoline4-carboxamide (Example 10); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethyl-3-oxomorpholino)-quinoline-4-carboxamide (Example 16); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 67); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 68); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamida (Exemplo 69); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Exemplo 70); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamida (Exemplo 71); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 72); / V-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 73); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 74); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Exemplo 78); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylmorpholino)-quinoline-4-carboxamide (Example 80); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,3S)-2,3-dimethyl-morpholino)quinoline-4-carboxamide (Example 81); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-2,3-dimethylmorpholino)quinoline-4-carboxamide (Example 82); Petition 870260043157, dated 07 / 05 / 2026, page 82 / 1284 73 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3 / ?)-2,3-dimethyl-morpholino)quinoline-4-carboxamide (Example 83); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-(trifluoromethyl)-morpholino)quinoline-4-carboxamide Isomer 1 (Example 84); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-(trifluoromethyl)-morpholino)quinoline-4-carboxamide Isomer 2 (Example 85); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,5 / ?)-2,5-dimethylmorpholino)quinoline-4-carboxamide (Example 87); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylmorpholino)-quinolina-4-carboxamide (Examplo 88); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 89); N-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5 / ?)-3,5-dimethyl-morpholino)quinolina-4-carboxamide (Example 90); N-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-((methylsulfonyl)-methyl)morpholino)quinolina-4-carboxamide (Exemplo 92); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 93); N-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-((methylsulfonyl)-methyl)morpholino)quinolina-4-carboxamide (Exemplo 94); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-(2-methoxyethyl)-morpholino)quinoline-4-carboxamide (Example 95); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-3-(methoxymethyl)-2methylmorpholino)quinoline-4-carboxamide (Example 96); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3 / ?)-3-(methoxymethyl)-2methylmorpholino)quinoline-4-carboxamide (Example 97); 7-Bromo- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5 / ?)-3,5-dimethylmorpholino)quinoline-4-carboxamide (Example 100); ( / ?)-5-Chloro- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 101); Petition 870260043157, dated 07 / 05 / 2026, page 83 / 1284 74 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methylmorpholino)-quinoline-4-carboxamide (Example 102); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5S)-3,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 103); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,5 / ?)-3,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 105); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-ethylmorpholino)quinoline-4-carboxamide (Example 106); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylmorpholino)-quinoline-4-carboxamide (Example 107); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-methylmorpholino)-quinoline-4-carboxamide (Example 108); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-2-methyl-6-morpholinoquinoline4-carboxamide (Example 109); ( / ?)-7-Chloro- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 179); ( / ?)-8-Chloro- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 180); and pharmaceutically acceptable salts thereof.

[0136] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-8-methyl-6-morpholinoquinoline4-carboxamide (Example 9); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 67); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 68); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamide (Example 69); Petition 870260043157, dated 07 / 05 / 2026, page 84 / 1284 75 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,6 / ?)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 70); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamide (Example 71); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 72); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 73); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 74); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Exemplo 78); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 80); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 81); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 82); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylmorpholino)-quinoline-4-carboxamide (Example 88); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 89); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 93); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3 / ?)-3-(methoxymethyl)-2methylmorpholino)-quinoline-4-carboxamide (Example 97); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methylmorpholino)-quinoline-4-carboxamide (Example 102); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-ethylmorpholino)quinoline-4-carboxamide (Example 106); Petition 870260043157, dated 07 / 05 / 2026, page 85 / 1284 76 / 598 (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylmorpholino)-quinoline-4-carboxamide (Example 107); and pharmaceutically acceptable salts thereof.

[0137] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-3-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, etc. Petition 870260043157, dated 07 / 05 / 2026, p. 86 / 1284 77 / 598 ethyl, isopropyl, cyclopropyl, fluoromethyl, difluoropropyl, methoxy, etrifluoromethoxy.

[0138] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-thiomorpholinoquinoline-4-carboxamide (Example 3), or its pharmaceutically acceptable salt.

[0139] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl, and wherein C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and. Petition 870260043157, dated 07 / 05 / 2026, p. 87 / 1284 78 / 598 methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, isopropyl, cyclopropyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0140] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethyl-3-oxomorpholino)quinoline-4-carboxamide (Example 16), or its pharmaceutically acceptable salt.

[0141] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl, and wherein C1-e-alkyl, C1-e-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, etc. Petition 870260043157, dated 07 / 05 / 2026, p. 88 / 1284 79 / 598 ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, isopropyl, cyclopropyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0142] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-dimethyl-2-oxo-1,3-oxazinan-3-yl)quinoline-4-carboxamide (Example 112), or a pharmaceutically acceptable salt thereof.

[0143] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-3-C1-3-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-S-alkyl, C1-S-3-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, C5-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl Petition 870260043157, dated 07 / 05 / 2026, p. 89 / 1284 80 / 598 quila, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, C1-3-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, isopropyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0144] In some embodiments, the pharmaceutically acceptable compound or salt is 6-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)- / V-(2-((R)-4cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 77), or its pharmaceutically acceptable salt.

[0145] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected Petition 870260043157, dated 07 / 05 / 2026, p. 90 / 1284 81 / 598 compounds of the group consisting of halogen, cyano, C1-S-alkyl, C1-E-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, C1-E-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0146] In some embodiments, pharmaceutically acceptable compounds and salts are selected from the group consisting of: 6-((1S,4S)-2-oxa-5-azabicyclo[2.2.1 ]heptan-5-yl)- / V-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 75); 6-((1R,4R)-2-oxa-5-azabicyclo[2.2.1 ]heptan-5-yl)- / V-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 76); and pharmaceutically acceptable salts thereof.

[0147] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3 Petition 870260043157, dated 07 / 05 / 2026, p. 91 / 1284 82 / 598 alkoxy-Ci-3-alkyl, Ci-3-alkylcarbonyl-Ci-3-alkyl, and Ci-3-alkylsulfonyl-Ci-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-S-alkyl, C1-E-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, C1-E-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0148] In some embodiments, the pharmaceutically acceptable compound or salt is 6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)- / V-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 98), or a pharmaceutically acceptable salt thereof.

[0149] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, Petition 870260043157, dated 07 / 05 / 2026, p. 92 / 1284 83 / 598 C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-e-alkyl, Cs-e-cycloalkyl, C1-6-alkoxy, C1-3alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonylC1-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, isopropyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0150] In some embodiments, the pharmaceutically acceptable compound or salt is 6-((1 R,5S)-9-oxa-3-azabicyclo[3.3.1 ]nonan-3-yl)- / V-(2((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 194), or a pharmaceutically acceptable salt thereof.

[0151] In some embodiments, the heterocyclyl ring R2 is: in which the heterocyclyl ring is optionally replaced with an or Petition 870260043157, dated 07 / 05 / 2026, p. 93 / 1284 84 / 598 plus substituents independently selected from the group consisting of halogen, cyano, oxo, C1-s-alkyl, C1-3-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-s-alkyl, C1-s-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens. In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0152] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,2-oxazinan-2-yl)quinoline-4-carboxamide (Example 1), or a pharmaceutically acceptable salt thereof.

[0153] In some embodiments, the heterocyclyl ring R2 is: Petition 870260043157, dated 07 / 05 / 2026, p. 94 / 1284 85 / 598 wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-3-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl.In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0154] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-7-methyl-1,4-oxazepam Petition 870260043157, dated 07 / 05 / 2026, page 95 / 1284 86 / 598 4-yl)quinoline-4-carboxamide (Example 61); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-7-methyl-1,4-oxazepan4-yl)quinoline-4-carboxamide (Example 62); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methyl-1,4-oxazepan4-yl)quinoline-4-carboxamide (Example 63); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-methyl-1,4-oxazepan4-yl)quinoline-4-carboxamide (Example 64); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,4-oxazepan-4-yl)quinoline-4-carboxamide (Example 91); and pharmaceutically acceptable salts thereof.

[0155] In some embodiments, the heterocyclyl ring R2 is: wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-S-alkyl, C1-3-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-S-alkyl, C1-S-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be additionally substituted with one or more halogens.In one aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-3-alkyl, Cs-e-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens. In another aspect, the heterocyclyl ring R2... Petition 870260043157, dated 07 / 05 / 2026, p. 96 / 1284 87 / 598 is optionally substituted with one or more substituents independently selected from the group consisting of cyano, fluorine, methyl, ethyl, propyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methoxymethyl, trifluoromethoxymethyl, and methylsulfonylmethyl. In another aspect, the heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoropropyl, methoxy, and trifluoromethoxy.

[0156] In some embodiments, the pharmaceutically acceptable compound or salt is 6-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)- / V-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 79), or a pharmaceutically acceptable salt thereof.

[0157] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,2-oxazinan-2-yl)quinoline-4-carboxamide (Example 1); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-3-fluoro-6-morpholinoquinoline4-carboxamide (Example 2); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-thiomorpholinoquinoline-4-carboxamide (Example 3); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-difluoromorpholino)quinoline-4-carboxamide (Example 4); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2,6,6-tetrafluoromorpholino)-quinoline-4-carboxamide (Example 5); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,3-dihydro-4 / - / benzo[b][1,4]oxazin-4-yl)quinoline-4-carboxamide (Example 6); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-8-methyl-6-morpholinoquinoline4-carboxamide (Example 9); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-7-methyl-6-morpholinoquinoline Petition 870260043157, dated 07 / 05 / 2026, p. 97 / 1284 88 / 598 4-carboxamide (Example 10); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-dimethyl-2-oxo-oxazolidin-3-yl)quinoline-4-carboxamide (Example 13); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethyl-3-oxomorpholino)-quinoline-4-carboxamide (Example 16); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-7-methyl-1,4-oxazepan4-yl)-quinoline-4-carboxamide (Example 61); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-7-methyl-1,4-oxazepan4-yl)-quinoline-4-carboxamide (Example 62); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methyl-1,4-oxazepan4-yl)-quinoline-4-carboxamide (Example 63); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-methyl-1,4-oxazepan4-yl)-quinoline-4-carboxamide (Example 64); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamida (Exemplo 67); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Exemplo 68); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-(fluoromethyl)-morpholino)quinoline-4-carboxamida (Exemplo 69); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,6 / ?)-2,6-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 70); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)-morpholino)quinoline-4-carboxamida (Exemplo 71); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 72); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 73); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 74); Petition 870260043157, 07 / 05 / 2026, pág. 98 / 1284 89 / 598 6-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1 ]heptan-5-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamida (Exemplo 75); 6-((1 R, 4 / ?)-2-Oxa-5-azabicyclo[2.2.1 ]heptan-5-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Exemplo 76); 6-(6-Oxa-3-azabicyclo[3.1.1 ]he ptan-3-yl)- / V-(2-(( / ?)-4-cyanothiaz I id in-3-i I)2-oxoethyl)quinoline-4-carboxamida (Exemplo 77); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Exemplo 78); 6-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)- / \ / -(2-(( / ?)-4-cyanothiazolidin-3-yl)2-oxoethyl)quinoline-4-carboxamide (Exemplo 79); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 80); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 81); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 82); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3 / ?)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 83); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-(trifluoromethyl)-morpholino)quinoline-4-carboxamida Isômero 1 (Exemplo 84); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?*)-3-(trifluoromethyl)-morpholino)quinoline-4-carboxamida Isômero 2 (Exemplo 85); 6-(3-Oxa-9-azabicyclo[3.3.1]nonan-9-yl)- / \ / -(2-(( / ?)-4-cyanothiazolidin-3-yl)2-oxoethyl)quinoline-4-carboxamide (Exemplo 86); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,5 / ?)-2,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 87); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylmorpholino)-quinoline-4-carboxamide (Example 88); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 89); Petition 870260043157, dated 07 / 05 / 2026, page 99 / 1284 90 / 598 A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5 / ?)-3,5-dimethyl-morpholino)quinoline-4-carboxamide (Example 90); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,4-oxazepan-4-yl)quinoline-4-carboxamide (Example 91); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-((methylsulfonyl)-methyl)morpholino)quinoline-4-carboxamide (Example 92); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 93); N-(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-((methylsulfonyl)-methyl)morpholino)quinolina-4-carboxamide (Exemplo 94); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-(2-methoxyethyl)-morpholino)quinoline-4-carboxamide (Example 95); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-3-(methoxymethyl)-2methylmorpholino)quinoline-4-carboxamide (Example 96); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,3R)-3-(methoxymethyl)-2methylmorpholino)quinoline-4-carboxamide (Example 97); 6-(3-Oxa-8-azabiciclo[3.2.1]octan-8-yl)- / \ / -(2-(( / ?)-4-cyanothiazolidin-3-yl)2-oxoethyl)quinolina-4-carboxamide (Exemplo 98); 7-Bromo-[V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5 / ?)-3,5-dimethyl-morpholino)quinolina-4-carboxamide (Exemplo 100); ( / ?)-5-Chloro-[V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinolina4-carboxamide (Example 101); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methylmorpholino)-quinoline-4-carboxamide (Example 102); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5S)-3,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 103); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3 / ?,5 / ?)-3,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 105); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-ethylmorpholino)quinoline-4-carboxamide (Example 106); Petition 870260043157, dated 07 / 05 / 2026, pp. 100 / 1284 91 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylmorpholino)-quinoline-4-carboxamide (Example 107); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-3-methylmorpholino)-quinoline-4-carboxamide (Example 108); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-2-methyl-6-morpholinoquinoline4-carboxamide (Example 109); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-dimethyl-2-oxo-1,3-oxazinan-3-yl)quinoline-4-carboxamide (Example 112); ( / ?)-7-Chloro- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 179); ( / ?)-8-Chloro- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 180); 6-((1 / ?,5S)-9-Oxa-3-azabicyclo[3.3.1 ]nonan-3-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 194); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,4-dimethyloxazol-5-yl)quinoline-4-carboxamide (Example 215); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,5-dimethylisoxazol-4-yl)quinoline-4-carboxamide (Example 216); and pharmaceutically acceptable salts thereof.

[0158] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,2-oxazinan-2-yl)quinoline-4-carboxamide (Example 1); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-3-fluoro-6-morpholinoquinoline4-carboxamide (Example 2); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-difluoromorpholino)quinoline-4-carboxamide (Example 4); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-8-methyl-6-morpholinoquinoline4-carboxamide (Example 9); Petition 870260043157, dated 07 / 05 / 2026, page 101 / 1284 92 / 598 ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 67); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 68); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamida (Exemplo 69); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,6 / ?)-2,6-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 70); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamida (Exemplo 71); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 72); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( / ?)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 73); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (Exemplo 74); 6-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1 ]heptan-5-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamida (Exemplo 75); 6-((1 R, 4 / ?)-2-Oxa-5-azabicyclo[2.2.1 ]heptan-5-yl)- / V-(2-(( / ?)-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Exemplo 76); 6-(6-Oxa-3-azabicyclo[3.1.1 ]he ptan-3-yl)- / V-(2-(( / ?)-4-cyanothiaz I id in-3-i I)2-oxoethyl)quinoline-4-carboxamida (Exemplo 77); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Exemplo 78); 6-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)- / \ / -(2-(( / ?)-4-cyanothiazolidin-3-yl)2-oxoethyl)quinoline-4-carboxamide (Exemplo 79); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylmorpholino)-quinoline-4-carboxamida (Exemplo 80); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 81); Petition 870260043157, 07 / 05 / 2026, pág. 102 / 1284 93 / 598 A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 82); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylmorpholino)-quinoline-4-carboxamida (Exemplo 88); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(methoxymethyl)-morpholino)quinoline-4-carboxamida (Exemplo 89); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)-morpholino)quinoline-4-carboxamida (Exemplo 93); A / -(2-(( / ?)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2 / ?,3 / ?)-3-(methoxymethyl)-2methylmorpholino)quinoline-4-carboxamida (Exemplo 97); 6-(3-Oxa-8-azabicyclo[3.2.1]octan-8-yl)- / V-(2-((R)-4-cyanothiazolidin-3-yl)2-oxoethyl)quinoline-4-carboxamide (Exemplo 98); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-methylmorpholino)-quinoline-4-carboxamida (Exemplo 102); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-ethylmorpholino)quinoline-4-carboxamide (Example 106); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylmorpholino)-quinoline-4-carboxamide (Example 107); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-2-methyl-6-morpholinoquinoline4-carboxamide (Example 109); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-dimethyl-2-oxo-1,3-oxazinan-3-yl)quinoline-4-carboxamide (Example 112); and pharmaceutically acceptable salts thereof. C. R2 is Spiro-Heterocycline

[0159] In some embodiments, the present disclosure provides compounds having the structure of Formulas (I), (II), (III-A), (III-B), (IIIC), (III-D), (III-E), (IV), or (IV-A), or pharmaceutically acceptable salts thereof, wherein R2 is a spiro-heterocyclyl containing a total of 6 to 11 ring atoms, wherein the spiro-heterocyclyl: (i) comprises two saturated rings, (ii) has: (a) one or two nitrogen atoms of Petition 870260043157, dated 07 / 05 / 2026, p. 103 / 1284 94 / 598 ring, with the remaining ring atoms being carbon, (b) one or two ring nitrogen atoms and one or two ring oxygen atoms, with the remaining ring atoms being carbon, or (c) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, Oe-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiroheterocyclyl R2 has: (a) one or two ring nitrogen atoms, with the remaining ring atoms being carbon, or (b) one or two ring nitrogen atoms and one or two ring oxygen atoms, with the remaining ring atoms being carbon. In another aspect, the spiroheterocyclyl R2 has one or two ring nitrogen atoms and, optionally, one or two ring oxygen atoms, with the remaining ring atoms being carbon.In another aspect, the spiroheterocyclyl R2 has one ring nitrogen atom, with the remaining ring atoms being carbon. In another aspect, the spiroheterocyclyl R2 has two ring nitrogen atoms, with the remaining ring atoms being carbon. In another aspect, the spiroheterocyclyl R2 has one ring nitrogen atom and one ring oxygen atom, with the remaining ring atoms being carbon. In another aspect, the spiroheterocyclyl R2 has one ring nitrogen atom and two ring oxygen atoms, with the remaining ring atoms being carbon.

[0160] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are selected from the group consisting of: Petition 870260043157, dated 07 / 05 / 2026, page 104 / 1284 95 / 598 wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-S-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C1-6-alkylcarbonyl.

[0161] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are selected from the group consisting of: Petition 870260043157, dated 07 / 05 / 2026, p. 105 / 1284 96 / 598 wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-S-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C1-6-alkylcarbonyl.

[0162] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are selected from the group consisting of: o , e ozem that one or both rings are optionally replaced with one or more substituents independently selected from the group Petition 870260043157, dated 07 / 05 / 2026, p. 106 / 1284 97 / 598 consisting of halogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl.

[0163] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are selected from the group consisting of: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-S-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C1-6-alkylcarbonyl.

[0164] In some embodiments, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-s-alkyl, C13-haloalkyl, C13-alkoxy, C13-haloalkoxy, and C13-alkylcarbonyl.

[0165] In some embodiments, the spiro-heterocyclyl ring R2 is optionally replaced with one or more halogens. In one aspect, the spiro-heterocyclyl ring R2 is optionally replaced with one or more fluoros.

[0166] In some embodiments, the spiro-heterocyclyl ring R2 is optionally replaced with one or more C1-3-alkyl groups.

[0167] In some embodiments, the spiro-heterocyclyl ring R2 is optionally replaced with one or more C1-3-haloalkyls.

[0168] In some embodiments, the spiro-heterocyclyl R2e ring Petition 870260043157, dated 07 / 05 / 2026, p. 107 / 1284 98 / 598 optionally replaced with one or more Ci-3-alkoxy compounds.

[0169] In some embodiments, the spiro-heterocyclyl R2 ring is optionally replaced with one or more Ci-3-haloalkoxy rings.

[0170] In some embodiments, the spiro-heterocyclyl ring R2 is optionally substituted with one or more C1-3-alkylcarbonyls. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more methylcarbonyls.

[0171] In some embodiments, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, ethylcarbonyl, and isopropylcarbonyl.

[0172] In some embodiments, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0173] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiroheterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiroheterocyclyl ring R2 is optionally Petition 870260043157, dated 07 / 05 / 2026, p. 108 / 1284 99 / 598 optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, and trifluoroethoxy. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0174] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-azaespiro[3.3]heptan-2yl)-quinoline-4-carboxamide (Example 17); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-fluoro-2-azaspiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 155); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(trifluoromethyl)-2-azaspiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 150); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methyl-2-azaespiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 149); and pharmaceutically acceptable salts thereof.

[0175] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: in which one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-alkoxy, C1-6-alkyl ... 100 / 598 haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, and methylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, and methylcarbonyl.

[0176] In some embodiments, the pharmaceutically acceptable compound or salt is ( / ?)-6-(6-acetyl-2,6-diazaespiro[3.3]heptan-2-yl)- / V-(2(4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 184), or its pharmaceutically acceptable salt.

[0177] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiroheterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiroheterocyclyl ring R2 is optionally Petition 870260043157, dated 07 / 05 / 2026, p. 110 / 1284 101 / 598 optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0178] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-thia-6azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 222), or a pharmaceutically acceptable salt thereof.

[0179] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl. In another aspect, the spiro-heterocyclyl ring Petition 870260043157, dated 07 / 05 / 2026, p. 111 / 1284 102 / 598 R2 is optionally replaced with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0180] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-1-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 18); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 153); and pharmaceutically acceptable salts thereof.

[0181] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl. Petition 870260043157, dated 07 / 05 / 2026, p. 112 / 1284 103 / 598

[0182] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-6azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 166), or its pharmaceutically acceptable salt.

[0183] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0184] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-azaespiro[3.4]octan-2yl)quinoline-4-carboxamide (Example 139); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-difluoro-2-azaspiro[3.4]octan-2-yl)quinoline-4-carboxamide (Example 141); Petition 870260043157, dated 07 / 05 / 2026, page 113 / 1284 104 / 598 and pharmaceutically acceptable salts thereof.

[0185] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0186] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,8dioxa-2-azaespiro[3.4]octan-2-yl)quinoline-4-carboxamide (Example 163), or its pharmaceutically acceptable salt.

[0187] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: Petition 870260043157, dated 07 / 05 / 2026, p. 114 / 1284 105 / 598 wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, and trifluoroethoxy.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0188] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiroheterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiroheterocyclyl ring R2 is optionally Petition 870260043157, dated 07 / 05 / 2026, pp. 115 / 1284 106 / 598 optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0189] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(8-oxa-5azaespiro[3.5]nonan-5-yl)quinoline-4-carboxamide (Example 104), or a pharmaceutically acceptable salt thereof.

[0190] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: μOO J in which one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl. In another aspect, the spiro-heterocyclyl ring Petition 870260043157, dated 07 / 05 / 2026, p. 116 / 1284 107 / 598 R2 is optionally replaced with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0191] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-oxa-9azaespiro[5.5]undecan-9-yl)quinoline-4-carboxamide (Example 162), or a pharmaceutically acceptable salt thereof.

[0192] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl. Petition 870260043157, dated 07 / 05 / 2026, p. 117 / 1284 108 / 598

[0193] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,9dioxa-4-azaespiro[5.5]undecan-4-yl)quinoline-4-carboxamide (Example 99), or its pharmaceutically acceptable salt.

[0194] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, and trifluoroethoxy.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0195] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(7-oxo-6oxa-8-azaespiro[4.5]decan-8-yl)quinoline-4-carboxamide (Example 111), or its pharmaceutically acceptable salt. Petition 870260043157, dated 07 / 05 / 2026, pp. 118 / 1284 109 / 598

[0196] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, and trifluoroethoxy.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0197] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxo-1oxa-3-azaespiro[5.5]undecan-3-yl)quinoline-4-carboxamide (Example 110), or its pharmaceutically acceptable salt.

[0198] In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: where one or both rings are optionally replaced with Petition 870260043157, dated 07 / 05 / 2026, pp. 119 / 1284 110 / 598 one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0199] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-7azaespiro[3.5]nonan-7-yl)quinoline-4-carboxamide (Example 229), or a pharmaceutically acceptable salt thereof.

[0200] In some embodiments, the two saturated rings of the spiroheterocycline R2 are: oo J in which one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, Petition 870260043157, dated 07 / 05 / 2026, pp. 120 / 1284 111 / 598 C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl. In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0201] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,4-dioxa-8-azaespiro[4.5]decan-8-yl)quinoline-4-carboxamide (Example 228), or its pharmaceutically acceptable salt. In some embodiments, the two saturated rings of the spiro-heterocyclyl R2 are: w J wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-5-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl. In one aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-haloalkyl, C1-3-alkoxy, C1-3-haloalkoxy, and C1-3-alkylcarbonyl.In another aspect, the spiro-heterocyclyl ring R2 is optionally substituted with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylcarbonyl, and ethylcarbonyl. In another aspect, the spiro-heterocyclyl ring. Petition 870260043157, dated 07 / 05 / 2026, pages 121 / 1284 112 / 598 R2 is optionally replaced with one or more substituents independently selected from the group consisting of fluorine, methyl, ethyl, fluoromethyl, difluoromethyl, and trifluoromethyl.

[0202] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,5dioxa-9-azaespiro[5.5]undecan-9-yl)quinoline-4-carboxamide (Example 227), or a pharmaceutically acceptable salt thereof.

[0203] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-azaespiro[3.3]heptan-2yl)quinoline-4-carboxamide (Example 17); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-1-oxa-6-azaspiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 18); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-azaspiro[3.3]heptan-1yl)quinoline-4-carboxamide (Example 19); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-azaespiro[2.5]octan-5yl)quinoline-4-carboxamide (Example 46); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-azaspiro[2.4]heptan-5yl)quinoline-4-carboxamide (Example 49); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-6-(fluoromethyl)-5-azaespiro[2.4]heptan-5-yl)quinoline-4-carboxamide (Example 58); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,9-dioxa-4-azaespiro[5.5]undecan-4-yl)quinoline-4-carboxamide (Example 99); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(8-oxa-5-azaespiro[3.5]nonan-5-yl)quinoline-4-carboxamide (Example 104); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxo-1-oxa-3-azaespiro[5.5]undecan-3-yl)quinoline-4-carboxamide (Example 110); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(7-oxo-6-oxa-8-azaespiro[4.5]decan-8-yl)quinoline-4-carboxamide (Example 111); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-azaespiro[3.4]octan-2 Petition 870260043157, dated 07 / 05 / 2026, p. 122 / 1284 113 / 598 il)quinoline-4-carboxamide (Example 139); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-difluoro-2-azaespiro[3.4]octan-2-yl)quinoline-4-carboxamide (Example 141); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methyl-2-azaespiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 149); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(trifluoromethyl)-2-azaespiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 150); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 153); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-fluoro-2-azaespiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 155); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-oxa-9-azaespiro[5.5]undecan-9-yl)quinoline-4-carboxamide (Example 162); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,8-dioxa-2-azaespiro[3.4]octan-2-yl)quinoline-4-carboxamide (Example 163); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-azaespiro[2.3]hexan-5yl)quinoline-4-carboxamide (Example 164); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 166); ( / ?)-6-(6-Acetyl-2,6-diazaespiro[3.3]heptan-2-yl)- / V-(2-(4-cyanothiazolidin3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 184); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-thia-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 222); ( / ?)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,5-dioxa-9-azaespiro[5.5]undecan-9-yl)quinoline-4-carboxamide (Example 227); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,4-dioxa-8-azaespiro[4.5]decan-8-yl)quinoline-4-carboxamide (Example 228); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-7-azaespiro[3.5]nonan-7-yl)quinoline-4-carboxamide (Example 229); and pharmaceutically acceptable salts thereof. Petition 870260043157, dated 07 / 05 / 2026, pages 123 / 1284 114 / 598

[0204] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-1-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 18); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,9-dioxa-4-azaespiro[5.5]undecan-4-yl)quinoline-4-carboxamide (Example 99); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxo-1-oxa-3-azaespiro[5.5]undecan-3-yl)quinoline-4-carboxamide (Example 110); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(trifluoromethyl)-2-azaespiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 150); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 153); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,8-dioxa-2-azaespiro[3.4]octan-2-yl)quinoline-4-carboxamide (Example 163); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 166); ( / ?)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-thia-6-azaespiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 222); and pharmaceutically acceptable salts thereof. D. R2 is Azetidinil

[0205] In some embodiments, the present disclosure provides compounds having the structure of Formula (V): Petition 870260043157, dated 07 / 05 / 2026, pages 124 / 1284 115 / 598 and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R2°ae R20bsã0independently selected from the group consisting of hydrogen and C1-s-alkyl; R20ce R20dsão independentemente selecionados do grupo consistindo em hidrogênio, flúor, hidróxi, Ci-3-alquila, Cse-cicloalquila, C3-6-cicloalquil-Ci-3-alquila, Ci-3-alcóxi, Cs-e-cicloalcóxi, Ci-3-alcóxi-Ci-3alquila, fenila, tolila, fenil-Ci-3-alquila, morfolinila, Ci-3-alquilsulfonil-Ci-3alquila, e Ci-3-alquil-carbonilamino-Ci-3-alquila; and that Ci-3-alquila, C3-6-cycloalquila, Cs-s-cycloalquil-Ci-s-alquila, Ci-3-alcoxi, Cs-e-cycloalcoxi, Ci-3-alcoxi-Ci-3-alquila, phenyl, and phenyl-Ci-s-alquila can be additionally replaced with either one or more halogênios; And R20ee R20fsão independently selected by the group consisting of hydrogênio and Ci-s-alquila.

[0206] In some embodiments of compounds having the structure of Formula (V), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0207] In some embodiments of compounds having the structure of Formula (V), R1, R3, R4, R5, and R6 are all hydrogen.

[0208] In some embodiments of compounds having the structure of Formula (V): R2°ae R20bsã0independently selected from the group Petition 870260043157, dated 07 / 05 / 2026, pages 125 / 1284 116 / 598 consisting of hydrogen and methyl; R20ce R20d are independently selected from the group consisting of hydrogen, fluorine, hydroxyl, C1-s-alkyl, C1-cycloalkyl, C1-3-alkoxy, C1-3-alkoxy-C1-3-alkyl, morpholinyl, C1-3-alkylsulfonyl-C1-3-alkyl, and C1-3-alkyl-carbonylamino-C1-3-alkyl; and wherein C1-3-alkyl, C36-cycloalkyl, C1-3-alkoxy, and C1-3-alkoxy-C1-3-alkyl may be further substituted with one or more halogens; and R20ee and R20f are independently selected from the group consisting of hydrogen and methyl.

[0209] In some embodiments of compounds having the structure of Formula (V), R20ce R20d are independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, C1-3-alkoxy, morpholinyl, and C1-3-alkyl-carbonylamino-C1-3-alkyl; and wherein C1-3-alkyl and C13-alkoxy may be additionally substituted with one or more halogens.

[0210] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)-3-methylazetidin-1-yl)quinoline-4-carboxamide (Example 27); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)azetidin-1yl)quinoline-4-carboxamide (Example 113); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxy-3-methylazetidin-1-yl)quinoline-4-carboxamide (Example 151); and pharmaceutically acceptable salts thereof. E. R2e Morfolinila

[0211] In some embodiments, the present disclosure provides compounds having the structure of Formula (VI): Petition 870260043157, dated 07 / 05 / 2026, pages 126 / 1284 117 / 598 and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R3°ae R30bsã0independently selected from the group consisting of hydrogen, C1-S-alkyl, halo-C1-3-alkyl, and C1-3-alkoxyC1-3-alkyl; R30ce and R30d are independently selected from the group consisting of hydrogen, halogen, C1-3-alkyl, halo-C1-3-alkyl, C1-3-alkoxy-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-5-alkyl; R30ee R30f are independently selected from the group consisting of hydrogen, halogen, C1-3-alkyl, halo-C1-3-alkyl, C1-3-alkoxy-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-5-alkyl; and R3°ge R30hsã0independently selected from the group consisting of hydrogen, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxyC1-3-alkyl.

[0212] In some embodiments of compounds having the structure of Formula (VI), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents Petition 870260043157, dated 07 / 05 / 2026, pp. 127 / 1284 118 / 598 R1, R3, R4, R5, and R6 are methyl groups, and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen groups.

[0213] In some embodiments of compounds having the structure of Formula (VI), R1, R3, R4, R5, and R6 are all hydrogen.

[0214] In some embodiments of compounds having the structure of Formula (VI): R3°ae R30bsã0independently selected from the group consisting of hydrogen, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxyC1-2-alkyl; R30ce and R30d are independently selected from the group consisting of hydrogen, halogen, C1-2-alkyl, halo-C1-2-alkyl, C1-2-alkoxy-C1-2-alkyl, and C1-2-alkylsulfonyl-C1-2-alkyl; R30ee R30f are independently selected from the group consisting of hydrogen, halogen, C1-2-alkyl, halo-C1-2-alkyl, C1-2-alkoxy-C1-2-alkyl, and C1-2-alkylsulfonyl-C1-2-alkyl; and R3°ge R30hsã0independently selected from the group consisting of hydrogen, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxyC1-2-alkyl.

[0215] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-8-methyl-6-morpholinoquinoline4-carboxamide (Example 9); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide (Example 67); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 68); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamide (Example 69); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 70); Petition 870260043157, dated 07 / 05 / 2026, pages 128 / 1284 119 / 598 A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)morpholino)-quinoline-4-carboxamide (Example 71); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-methylmorpholino)-quinoline-4-carboxamide (Example 72); A / -(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylmorpholino)-quinoline-4-carboxamide (Example 80); and pharmaceutically acceptable salts thereof. F. R2é Piperidin-1-ila

[0216] In some embodiments, the present disclosure provides compounds having the structure of Formula (VII): and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R4°ae R40bsã0independently selected from the group consisting of hydrogen, C1-s-alkyl, and halo-C1-s-alkyl; R40ce and R40d are independently selected from the group consisting of hydrogen, fluorine, C1-S-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; R40ee and R40f are independently selected from the group consisting of hydrogen, fluorine, hydroxyl, oxo, C1-3-alkyl, halo-C1-3-alkyl, cyclopropyl, and C1-3-alkoxy; R4°ge R40hsã0independently selected from the group Petition 870260043157, dated 07 / 05 / 2026, pages 129 / 1284 120 / 598 consisting of hydrogen, fluorine, C1-5-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; and R40ie and R40j are independently selected from the group consisting of hydrogen, C1-3-alkyl, and halo-C1-3-alkyl.

[0217] In some embodiments of compounds having the structure of Formula (VII), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0218] In some embodiments of compounds having the structure of Formula (VII), R1, R3, R4, R5, and R6 are all hydrogen.

[0219] In some embodiments of compounds having the structure of Formula (VII): R4°ae R40bsã0independently selected from the group consisting of hydrogen, C1-3-alkyl, and halo-C1-3-alkyl; R40ce and R40d are independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; R40ee and R40f are independently selected from the group consisting of hydrogen, fluorine, hydroxyl, C1-3-alkyl, halo-C1-3-alkyl, cyclopropyl, and C1-3-alkoxy; R4°ge R40hsã0independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; and R40ie R40jsão independently selected from the group Petition 870260043157, dated 07 / 05 / 2026, page 130 / 1284 121 / 598 consisting of hydrogen, C1-3-alkyl, and halo-C1-3-alkyl.

[0220] In some embodiments of compounds having the structure of Formula (VII): R40ae and R40b are independently selected from the group consisting of hydrogen, C1-2-alkyl, and halo-C1-2-alkyl; R40ce and R40d are independently selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; R40ee and R40f are independently selected from the group consisting of hydrogen, fluorine, hydroxyl, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; R4°ge R40hsã0independently selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; and R40ie and R40j are independently selected from the group consisting of hydrogen, C1-2-alkyl, and halo-C1-2-alkyl.

[0221] In some embodiments, the pharmaceutically acceptable compounds and salts are selected from the group consisting of: (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxypiperidin-1-yl)quinoline-4-carboxamide (Example 8); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxy-4-methylpiperidin-1-yl)quinoline-4-carboxamide (Example 42); (R)- / V-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoropiperidin-1-yl)quinoline-4-carboxamide (Example 205); (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-oxopiperidin-1-yl)quinoline-4-carboxamide (Example 230) and pharmaceutically acceptable salts thereof. G. R2e Piperidin-4-ila

[0222] In some embodiments, the present disclosure provides compounds having the structure of Formula (VIII): Petition 870260043157, dated 07 / 05 / 2026, page 131 / 1284 122 / 598 and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R5°ae R50bsã0independently selected from the group consisting of hydrogen, fluorine, C1-5-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; R50ce and R50d are independently selected from the group consisting of hydrogen, C1-3-alkyl, and halo-C1-3-alkyl, or collectively are oxo; R50e is selected from the group consisting of hydrogen, C1-3-alkyl, halo-C1-3-alkyl, C1-3-alkoxy-C2-3-alkyl, C1-3-alkyl-carbonyl, and C3-6-cycloalkyl-carbonyl; R50fe R50gsão are independently selected from the group consisting of hydrogen, C1-3-alkyl, and halo-C1-3-alkyl, or collectively are oxo; R50he R50isão independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; and R50 is selected from the group consisting of hydrogen and fluorine.

[0223] In some embodiments of compounds having the structure of Formula (VIII), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents Petition 870260043157, dated 07 / 05 / 2026, p. 132 / 1284 123 / 598 R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0224] In some embodiments of compounds having the structure of Formula (VIII), R1, R3, R4, R5, and R6 are all hydrogen.

[0225] In some embodiments of compounds having the structure of Formula (VIII): R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, fluorine, and methyl; R5°ae R50bsã0independently selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; R50ce and R50d are independently selected from the group consisting of hydrogen, C1-2-alkyl, and halo-C1-2-alkyl; R50e is selected from the group consisting of hydrogen, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy-C2-3-alkyl; R50fe R50gsão independently selected from the group consisting of hydrogen, C1-2-alkyl, and halo-C1-2-alkyl; R50he R50isão independently selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; and R50 is selected from the group consisting of hydrogen and fluorine.

[0226] In some embodiments of compounds having the structure of Formula (VIII), at least one of R50a, R50b, R50h, R50i, and R50j is fluorine. H. R2 is 3-Oxomorpholinine Petition 870260043157, dated 07 / 05 / 2026, page 133 / 1284 124 / 598

[0227] In some embodiments, the present disclosure provides compounds having the structure of Formula (IX): and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R6°ae R60bsã0independently selected from the group consisting of hydrogen and C1-s-alkyl; r6°ce R60dsã0independently selected from the group consisting of hydrogen and C1-S-alkyl; and R6°ee R6oísã0independently selected from the group consisting of hydrogen and C1-S-alkyl.

[0228] In some embodiments of compounds having the structure of Formula (IX), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0229] In some embodiments of compounds having the structure of Formula (IX), R1, R3, R4, R5, and R6 are all hydrogen.

[0230] In some embodiments of compounds having the structure Petition 870260043157, dated 07 / 05 / 2026, p. 134 / 1284 125 / 598 of Formula (IX): R4 is methyl; and R1, R3, R5, and R6 are all hydrogen.

[0231] In some embodiments of compounds having the structure of Formula (IX): R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, fluorine, and methyl; R6°ae R60bsã0independently selected from the group consisting of hydrogen and C1-2-alkyl; r6°ce R60dsã0independently selected from the group consisting of hydrogen and C1-2-alkyl; and R6°ee R60fsã0independently selected from the group consisting of hydrogen and C1-2-alkyl. I. R2 is 5,8-Dioxa-2-azaspiro[3.41octan-2-yl

[0232] In some embodiments, the present disclosure provides compounds having the structure of Formula (X): and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R7°ae R70bsã0independently selected from the group consisting of hydrogen and C1-s-alkyl; R70ce and R70d are independently selected from the group consisting of hydrogen and C1-S-alkyl; Petition 870260043157, dated 07 / 05 / 2026, page 135 / 1284 126 / 598 R70ee and R70f are independently selected from the group consisting of hydrogen and C1-3-alkyl; and R7°ge R70hsã0independently selected from the group consisting of hydrogen and C1-3-alkyl.

[0233] In some embodiments of compounds having the structure of Formula (X), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen.

[0234] In some embodiments of compounds having the structure of Formula (X), R1, R3, R4, R5, and R6 are all hydrogen.

[0235] In some embodiments of compounds having the structure of Formula (X): R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, fluorine, and methyl; R7°ae R70bsã0independently selected from the group consisting of hydrogen and C1-2-alkyl; R70ce and R70d are independently selected from the group consisting of hydrogen and C1-2-alkyl; R70ee and R70f are independently selected from the group consisting of hydrogen and C1-2-alkyl; and R7°ge R70hsã0independently selected from the group consisting of hydrogen and C1-2-alkyl. J. R2é Piridin-3-ila Petition 870260043157, dated 07 / 05 / 2026, page 136 / 1284 127 / 598

[0236] In some embodiments, the present disclosure provides compounds having the structure of Formula (XI): R5 R80b(XI), and pharmaceutically acceptable salts thereof, wherein: R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine, and methyl; R8°a£ selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; R80bé selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; R80 is selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy; and R80 is selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl, and C1-3-alkoxy.

[0237] In some embodiments of compounds having the structure of Formula (XI), one of the substituents R1, R3, R4, R5, and R6 is selected from the group consisting of chlorine, fluorine, and methyl and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In one aspect, one of the substituents R1, R3, R4, R5, and R6 is chlorine and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is fluoro and the remaining substituents R1, R3, R4, R5, and R6 are all hydrogen. In another aspect, one of the substituents R1, R3, R4, R5, and R6 is methyl and the remaining substituents R1, R3, R4, R5, Petition 870260043157, dated 07 / 05 / 2026, p. 137 / 1284 128 / 598 and R6 are all hydrogen.

[0238] In some embodiments of compounds having the structure of Formula (XI), R1, R3, R4, R5, and R6 are all hydrogen.

[0239] In some embodiments of compounds having the structure of Formula (XI): R1, R3, R4, R5, and R6 are independently selected from the group consisting of hydrogen, fluorine, and methyl; R8°a£ selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; R80bé selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; R80 is selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy; and R80 is selected from the group consisting of hydrogen, fluorine, C1-2-alkyl, halo-C1-2-alkyl, and C1-2-alkoxy.

[0240] In some embodiments, the pharmaceutically acceptable compound or salt is (R)- / V-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(difluoromethyl)pyridin-3-yl)quinoline-4-carboxamide (Example 169), or a pharmaceutically acceptable salt thereof. K. Additional Options

[0241] Any embodiment of the compounds described in this disclosure may be combined with any other suitable embodiment described herein to provide additional embodiments. For example, where an embodiment, individually or collectively, describes possible groups for R1, R3, R4, R5, and / or R6 and a separate embodiment describes possible groups for R2, it is understood that these embodiments may be combined to provide an additional embodiment describing the possible groups described for R1, R3, R4, R5, and / or R6 together with the possible groups described for R2. In other words, for any of the embodiments of the compounds Petition 870260043157, dated 07 / 05 / 2026, pp. 138 / 1284 129 / 598 described in this disclosure, the substitute R2 may be as defined in any of the embodiments of R2 described below.

[0242] The compounds of this disclosure have pharmaceutically acceptable FAP inhibitory activity as measured as described for the hFAP (strong ligands) inhibition assay reported in the Examples below. In one aspect, the compounds have FAP inhibitory activity at ICso concentrations less than about 100 nM. In another aspect, the compounds have FAP inhibitory activity at ICso concentrations less than about 50 nM. In another aspect, the compounds have FAP inhibitory activity at ICso concentrations less than about 10 nM. In another aspect, the compounds have FAP inhibitory activity at ICso concentrations less than about 1 nM.

[0243] In some embodiments, the compounds of this disclosure have a pharmaceutically acceptable surface plasmon resonance (SPR) pKd value measured as described for the SPR assay reported in the Examples below. In one aspect, the compounds have a surface plasmon resonance (SPR) pKd value greater than about 7. In another aspect, the compounds have a surface plasmon resonance (SPR) pKd value greater than about 8. In another aspect, the compounds have an SPR pKd value greater than about 9. In another aspect, the compounds have an SPR pKd value greater than about 10.

[0244] In some embodiments, the compounds of this disclosure have pharmaceutically acceptable selectivity for FAP relative to PREP as measured as described for the hFAP (strong ligands) inhibition assay and the hPREP inhibition assay reported in the Examples below. In one aspect, the compounds are at least about 50 times more selective for FAP relative to PREP. In another Petition 870260043157, dated 07 / 05 / 2026, p. 139 / 1284 In one aspect, the compounds are at least about 100 times more selective for FAP compared to PREP. In another aspect, the compounds are at least about 1,000 times more selective for FAP relative to PREP. In another aspect, the compounds are at least about 10,000 times more selective for FAP relative to PREP. In another aspect, the compounds have an ICso value for PREP greater than about 0.1 μM. In another aspect, the compounds have an ICso value for PREP greater than about 1.0 μM. In another aspect, the compounds have an ICso value for PREP greater than about 10.0 μM.

[0245] In some embodiments, the compounds of the present disclosure have pharmaceutically acceptable selectivity for FAP relative to DPP7 as measured as described for the hFAP (strong ligands) inhibition assay and the DPP7 selectivity assay reported in the Examples below. In one aspect, the compounds are at least about 50 times more selective for FAP relative to DPP7. In another aspect, the compounds are at least about 100 times more selective for FAP relative to DPP7. In another aspect, the compounds are at least about 1,000 times more selective for FAP relative to DPP7. In another aspect, the compounds are at least about 10,000 times more selective for FAP relative to DPP7. In another aspect, the compounds have an ICso value for DPP7 that is greater than about 0.1 μM. In another aspect, the compounds have an ICso value for DPP7 that is greater than about 1 μM.In another aspect, the compounds have an ICso value for DPP7 that is greater than about 10 μM.

[0246] In some embodiments, the compounds of this disclosure have pharmaceutically acceptable selectivity for FAP with respect to DPP8 and / or DPP9 as measured as described for the hFAP (strong ligands) inhibition assay, DPP8 selectivity assay, and DPP9 selectivity assay reported in the Examples below. In Petition 870260043157, dated 07 / 05 / 2026, pp. 140 / 1284 131 / 598 In one aspect, the compounds are selective for FAP relative to DPP8. In another aspect, the compounds are selective for FAP relative to DPP9. In another aspect, the compounds are selective for FAP relative to both DPP8 and DPP9. In one aspect, the compounds are at least about 50 times more selective for FAP relative to DPP8 and / or DPP9. In another aspect, the compounds are at least about 100 times more selective for FAP relative to DPP8 and / or DPP9. In another aspect, the compounds are at least about 500 times more selective for FAP relative to DPP8 and / or DPP9. In another aspect, the compounds are at least about 1,000 times more selective for FAP relative to DPP8 and / or DPP9. In another aspect, the compounds have an ICso value for DPP8 and / or DPP9 that is greater than about 0.01 μM. In another aspect, the compounds have an ICso value for DPP8 and / or DPP9 that is greater than approximately 0.1 pM.In another aspect, the compounds have an ICso value for DPP8 and / or DPP9 that is greater than approximately 0.4 pM.

[0247] In some embodiments, the compounds of this disclosure have pharmaceutically acceptable metabolic stability as measured as described for the human liver microsome (HLM) assay reported in the Examples below. In one aspect, the compounds have an HLM CLnt value of less than about 300 pL / min / mg. In another aspect, the compounds have an HLM CLnt value of less than about 100 pL / min / mg. In another aspect, the compounds have an HLM CLnt value of less than about 50 pL / min / mg.

[0248] In some embodiments, the compounds of the present disclosure have pharmaceutically acceptable metabolic stability as measured as described for the rat hepatocyte assay (rHep) reported in the Examples below. In one aspect, the compounds have an rHep CLnt value of less than about 300 pL / min / 106 cells. In another aspect, the compounds have an rHep CLnt value of less than about Petition 870260043157, dated 07 / 05 / 2026, p. 141 / 1284 132 / 598 of 100 pL / min / 106 cells. In another aspect, the compounds have a lower rHep CLint value of about 50 pL / min / 106 cells.

[0249] In some embodiments, the compounds of the present disclosure have a pharmaceutically acceptable intrinsic permeability AB in Caco-2 measured as described for the intrinsic permeability AB in Caco-2 assay reported in the Examples below. In one aspect, the compounds have an apparent intrinsic permeability in Caco-2 of at least about 0.1 x 10⁶ cm / s. In another aspect, the compounds have an apparent intrinsic permeability in Caco-2 of at least about 0.5 x 10⁶ cm / s. In another aspect, the compounds have an apparent intrinsic permeability in Caco-2 of at least about 1 x 10⁶ cm / s.

[0250] In some embodiments, the compounds of the present disclosure have a pharmaceutically acceptable apparent permeability in bidirectional Caco-2 (ABBA) A to B measured as described for the apparent permeability test in bidirectional Caco-2 (ABBA) A to B reported in the Examples below. In one aspect, the compounds have an apparent permeability in bidirectional Caco-2 (ABBA) A to B of at least about 0.1 x 10⁶ cm / s. In another aspect, the compounds have an apparent permeability in bidirectional Caco-2 (ABBA) A to B of at least about 0.25 x 10⁶ cm / s. In another aspect, the compounds have an apparent permeability in bidirectional Caco-2 (ABBA) A to B of at least about 0.5 x 10⁶ cm / s.

[0251] In some embodiments, the compounds of the present disclosure have a pharmaceutically acceptable kinetic solubility measured as described for the kinetic solubility assay reported in the Examples below. In one aspect, the compounds have a kinetic solubility of at least about 1 μM. In another aspect, the compounds have a kinetic solubility of at least about 10 μM. In another Petition 870260043157, dated 07 / 05 / 2026, p. 142 / 1284 133 / 598 aspect, the compounds have a kinetic solubility of at least about 25 μM. In another aspect, the compounds have a kinetic solubility of at least about 50 μM. L. Sais

[0252] The compounds of this disclosure may exist in salt form or in non-salt form (i.e., as a free base), and this disclosure covers both salt and non-salt forms. The compounds may form acid addition salts or base addition salts. In general, an acid addition salt can be prepared using various inorganic or organic acids. Such salts can typically be formed, for example, by mixing the compound with an acid (e.g., a stoichiometric amount of acid) using various methods known in the art. This mixing may occur in water, an organic solvent (e.g., ether, ethyl acetate, ethanol, methanol, isopropanol, or acetonitrile), or an aqueous / organic mixture. In another aspect, acid addition salts are, for example, trifluoroacetate, formate, acetate, or hydrochloric acid.In general, a base addition salt can be prepared using various inorganic or organic bases, for example, an alkali or alkaline earth metal salt such as a sodium, calcium, or magnesium salt, or other metallic salts such as potassium or zinc, or an ammonium salt, or a salt with an organic base such as methylamine, dimethylamine, trimethylamine, piperidine, or morpholine. Those skilled in the art will be aware of the general principles and techniques for preparing pharmaceutical salts, such as those described, for example, in J Pharm Sci. 1977 66, 1. Examples of pharmaceutically acceptable salts are also described in “Handbook of Pharmaceutical Salts: Properties, Selection, and Use” by Stahl and Wermut (Wiley-VCH, Weinheim, Germany, 2002). M. Isomers

[0253] The compounds and salts of this disclosure may exist Petition 870260043157, dated 07 / 05 / 2026, pages 143 / 1284 134 / 598 in one or more geometric, optical, enantiomeric and diastereomeric forms, including, but not limited to, cis and trans forms, Ee and Ze forms, R, Se and meso forms. Unless otherwise indicated, a reference to a particular compound includes all such isomeric forms, including their racemic and other mixtures. Where appropriate, such isomers may be separated from their mixtures by applying or adapting known methods (e.g., chromatographic techniques and recrystallization techniques). Where appropriate, such isomers may be prepared by applying or adapting known methods. In some embodiments, a single stereoisomer is obtained by isolating it from a mixture of isomers (e.g., a racemate) using, for example, chiral chromatographic separation. In other embodiments, a single stereoisomer is obtained by direct synthesis, for example, from a chiral starting material.

[0254] A particular enantiomer of a compound described herein may be more active than other enantiomers of the same compound. In one embodiment, the compound, or a pharmaceutically acceptable salt thereof, is a single enantiomer being in an enantiomeric excess (%ee) > 90, > 95%, > 96%, > 97, > 98% or > 99%. In another aspect, the single enantiomer is present in an enantiomeric excess (%ee) > 99%.

[0255] In another embodiment, the present disclosure relates to a pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, which is a single enantiomer being in an enantiomeric excess (%ee) > 90, > 95%, > 96%, > 97, > 98% or > 99%, or a pharmaceutically acceptable salt thereof, in association with one or more pharmaceutically acceptable excipients. In one aspect, the single enantiomer is present in an enantiomeric excess (%ee) > 99%. N. Additional Forms Petition 870260043157, dated 07 / 05 / 2026, p. 144 / 1284 135 / 598

[0256] The compounds and salts of this disclosure may exist in various tautomeric forms and the descriptive report covers all such tautomeric forms. Tautomers are structural isomers that exist in equilibrium resulting from the migration of a hydrogen atom.

[0257] The compounds of this disclosure, and pharmaceutically acceptable salts thereof, may exist as solvates (such as hydrates) as well as non-solvated forms, and this descriptive report covers all such solvates.

[0258] The compounds of this disclosure, and pharmaceutically acceptable salts thereof, may exist in crystalline or amorphous form, and this descriptive report covers all such forms.

[0259] Compounds and salts of the present disclosure may be isotopically labeled (or “radiolabeled”). In this case, one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number typically present in nature. The descriptive report covers isotopically labeled forms of compounds disclosed herein. Examples of isotopes that may be incorporated include 2H (also written as “D” for deuterium), 3H (also written as “T” for tritium), 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, and 36Ci. The isotope that is used will depend on the specific application of this radiolabeled derivative. For example, for in vitro receptor labeling and competition assays, 3H or 14C are often useful. For radioimaging applications, 11C is often useful. In some modalities, the radionuclide is 3H. In some forms, the radionuclide is 14C. In some forms, the radionuclide is 11C. O. Intermediaries

[0260] In some modalities, the present disclosure provides Petition 870260043157, dated 07 / 05 / 2026, pages 145 / 1284 136 / 598 ona additional compounds that are useful as intermediates for preparing the compounds of the present disclosure, and pharmaceutically acceptable salts thereof. III. Methods of Use

[0261] The compounds disclosed in this disclosure, and pharmaceutically acceptable salts thereof, are inhibitors of the activity of fibroblast activating protein prolyl endopeptidase (FAP). FAP is an endopeptidase that performs the enzymatic cleavage of substrates involved in glucose and lipid metabolism, fibrinolysis, and collagen production.

[0262] FAP is believed to cleaves and inactivate human Fibroblast Growth Factor 21 (FGF-21) (Biochem J 2016, 473, 605), a protein involved in the regulation of glucose and lipid metabolism. It is hypothesized that FAP inhibition increases levels and signaling of endogenous FGF-21, and may result in, for example, decreased steatosis, improved insulin sensitivity, improved glucose tolerance, reduced body weight, and / or reduced mortality from cardiovascular disease.

[0263] It is also believed that FAP proceeds with the cleavage of human α2-Antiplasmin (α2AP) (Blood 2004 103, 3783), a protein involved in the regulation of fibrosis and fibrinolysis. Tissue repair involves coagulation, which results in fibrin deposition. The fibrin in a clot usually undergoes lysis, mainly by plasmin when converted from its inactive form (plasminogen) by plasminogen activators. Fibrinolysis is inhibited by Plasminogen Activator Inhibitor 1 (PAI-1), Plasminogen Activator Inhibitor-2 (PAI-2), and α2AP (Experimental & Molecular Medicine 2020, 52, 367), all of which are induced by tissue trauma. FAP converts α2AP into a more active form that decreases plasmin activity and increases fibrin deposition at the site of injury. It is hypothesized that the inhibition of... Petition 870260043157, dated 07 / 05 / 2026, pages 146 / 1284 137 / 598 FAP increases fibrinolysis and improves tissue regeneration at the injury site (J Thromb Haemost 2013, 11, 2029; Proteomics Clin. Appl. 2014, 8, 454).

[0264] It is also believed that FAP promotes collagen production and deposition and plays a role in increased fibrosis through altered extracellular matrix (ECM) turnover (J Biol Chem 2016, 8, 291). It is hypothesized that FAP inhibition leads to a decrease in collagen deposition and a reduction in inflammation (Inflamm Bowel Dis. 2018, 18, 332).

[0265] Considering the above, it is hypothesized that FAP inhibition collectively reduces fibrosis and inflammation by decreasing hepatic stellate cell activity and increasing fibrinolysis, and additionally provides positive metabolic effects through increased FGF21 signaling and improved glucose tolerance.

[0266] In some embodiments, therefore, the present disclosure provides a method for treating or preventing a FAP-mediated condition in an individual in need by administering to the individual a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof.

[0267] In some embodiments, the present disclosure provides a method for treating or preventing a condition characterized by overexpression of FAP in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof.

[0268] In some embodiments, the present disclosure provides a method for treating or preventing liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a Petition 870260043157, dated 07 / 05 / 2026, p. 147 / 1284 138 / 598 its pharmaceutically acceptable salt. In one aspect, the liver disease is fatty liver disease. In another aspect, the liver disease is Non-Alcoholic Fatty Liver Disease (NAFLD). In another aspect, NAFLD is selected from the group consisting of isolated steatosis, Non-Alcoholic Steatohepatitis (NASH), liver fibrosis, and cirrhosis. In another aspect, the liver disease is end-stage liver disease. In another aspect, the individual is also suffering from or is susceptible to one or more conditions selected from the group consisting of obesity, dyslipidemia, insulin resistance, Type 2 diabetes, and renal failure.

[0269] In some embodiments, the present disclosure provides a method for treating liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, wherein the individual has a body mass index (BMI) of 27 kg / m2 to 40 kg / m2. In one aspect, the individual has a BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight. In another aspect, the individual is obese. In another aspect, the liver disease is NAFLD. In another aspect, the liver disease is NASH. In another aspect, the liver disease is liver fibrosis. In another aspect, the liver disease is cirrhosis.

[0270] In some embodiments, the present disclosure provides a method for treating liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, wherein the individual is also suffering from or is susceptible to dyslipidemia. In another aspect, the liver disease is NAFLD. In another aspect, the liver disease is NASH. In another aspect, the liver disease is NAFLD. Petition 870260043157, dated 07 / 05 / 2026, pp. 148 / 1284 139 / 598 aspect, the liver disease is liver fibrosis. In another aspect, the liver disease is cirrhosis.

[0271] In some embodiments, the present disclosure provides a method for treating liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, wherein the individual is also suffering from or susceptible to insulin resistance. In another aspect, the liver disease is NAFLD. In another aspect, the liver disease is NASH. In another aspect, the liver disease is liver fibrosis. In another aspect, the liver disease is cirrhosis.

[0272] In some embodiments, the present disclosure provides a method for treating liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, wherein the individual is also suffering from or is susceptible to at least one of Type 2 diabetes and renal insufficiency. In another embodiment, the liver disease is NAFLD. In another embodiment, the liver disease is NASH. In another embodiment, the liver disease is liver fibrosis. In another embodiment, the liver disease is cirrhosis.

[0273] In some embodiments, the present disclosure provides a method for treating liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, wherein the individual is also suffering from or is susceptible to Type 2 diabetes. In another aspect, the liver disease is NAFLD. In another aspect, the liver disease is NASH. In another aspect, the liver disease is liver fibrosis. In another aspect, the liver disease is cirrhosis. Petition 870260043157, dated 07 / 05 / 2026, pp. 149 / 1284 140 / 598

[0274] In some embodiments, the present disclosure provides a method for treating liver disease in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, wherein the individual is also suffering from or susceptible to renal insufficiency. In another aspect, the liver disease is NAFLD. In another aspect, the liver disease is NASH. In another aspect, the liver disease is liver fibrosis. In another aspect, the liver disease is cirrhosis.

[0275] In some embodiments, the present disclosure provides a method for reducing liver fat in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is suffering from or is susceptible to NAFLD. In another aspect, the individual is suffering from or is susceptible to NASH. In another aspect, the individual is suffering from or is susceptible to liver fibrosis. In another aspect, the individual is suffering from or is susceptible to cirrhosis. In another aspect, the individual is also suffering from or is susceptible to one or more of the selected conditions from the group consisting of obesity, dyslipidemia, insulin resistance, Type 2 diabetes, and renal insufficiency.

[0276] In some embodiments, the present disclosure provides a method for treating or preventing Non-Alcoholic Fatty Liver Disease (NAFLD) in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the NAFLD is Stage 1 NAFLD. In another aspect, the NAFLD is Stage 2 NAFLD. In another aspect, the NAFLD is Stage 3 NAFLD. In another aspect, the NAFLD is Stage 4 NAFLD. See, for example, “The Diagnosis and Management of Nonalcoholic Fatty Liver Disease.” Petition 870260043157, dated 07 / 05 / 2026, pp. 150 / 1284 141 / 598 Disease: Practice Guidance From the American Association for the Study of Liver Diseases”, Hepatology, 2018, Vol. 67, No. 1. In another aspect, the individual is also suffering from or is susceptible to one or more conditions selected from the group consisting of obesity, dyslipidemia, insulin resistance, Type 2 diabetes, and renal failure.

[0277] In some embodiments, the present disclosure provides a method for treating or preventing Non-Alcoholic Steatohepatitis (NASH) in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the NASH is Stage 1 NASH. In another aspect, the NASH is Stage 2 NASH. In another aspect, the NASH is Stage 3 NASH. In another aspect, the NASH is Stage 4 NASH. In another aspect, the individual is also suffering from or is susceptible to one or more conditions selected from the group consisting of obesity, dyslipidemia, insulin resistance, Type 2 diabetes, and renal insufficiency.

[0278] In some embodiments, the present disclosure provides a method for treating or preventing liver fibrosis in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is suffering from Stage 3 liver fibrosis. In another aspect, the individual is also suffering from or is susceptible to one or more conditions selected from the group consisting of obesity, dyslipidemia, insulin resistance, Type 2 diabetes, and renal insufficiency.

[0279] In some embodiments, the present disclosure provides a method for treating or preventing cirrhosis in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is suffering Petition 870260043157, dated 07 / 05 / 2026, pp. 151 / 1284 142 / 598 of stage F4 cirrhosis. In another aspect, the individual is also suffering from or is susceptible to one or more conditions selected from the group consisting of obesity, dyslipidemia, insulin resistance, Type 2 diabetes, and renal failure.

[0280] In some embodiments, the present disclosure provides a method for treating or preventing type 2 diabetes mellitus in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is suffering from diabetic kidney disease. In another aspect, the individual is suffering from renal failure. In another aspect, administration of the compound is an adjunct to diet and exercise. In another aspect, administration of the compound also reduces body weight and / or treats obesity. In another aspect, the individual has a BMI of 27 kg / m2 to 40 kg / m2. In another aspect, the individual has a BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight. In another aspect, the individual is obese.

[0281] In some embodiments, the present disclosure provides a method for improving glycemic control in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is an individual suffering from type 2 diabetes. In another aspect, the individual is an individual suffering from diabetic kidney disease. In another aspect, the individual is suffering from renal failure. In another aspect, administration of the compound is an adjunct to diet and exercise. In another aspect, administration of the compound also reduces body weight and / or treats obesity. In another aspect, the individual has a BMI of 27 kg / m2 to 40 kg / m2. In another aspect, the individual has a Petition 870260043157, dated 07 / 05 / 2026, p. 152 / 1284 143 / 598 BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight. In another aspect, the individual is obese.

[0282] In some embodiments, the present disclosure provides a method for improving glycemic control in an individual with type 2 diabetes and diabetic kidney disease by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, administration of the compound is an adjunct to diet and exercise. In another aspect, administration of the compound also reduces body weight and / or treats obesity. In another aspect, the individual has a BMI of 27 kg / m2 to 40 kg / m2. In another aspect, the individual has a BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight. In another aspect, the individual is obese.

[0283] In some embodiments, the present disclosure provides a method for improving glycemic control in an individual with type 2 diabetes and renal insufficiency by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, administration of the compound is an adjunct to diet and exercise. In another aspect, administration of the compound also reduces body weight and / or treats obesity. In another aspect, the individual has a BMI of 27 kg / m2 to 40 kg / m2. In another aspect, the individual has a BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight. In another aspect, the individual is obese.

[0284] In some embodiments, the present disclosure provides a method for treating or preventing insulin resistance in an in Petition 870260043157, dated 07 / 05 / 2026, p. 153 / 1284 144 / 598 divided by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In another aspect, the individual is an individual suffering from type 2 diabetes. In another aspect, the individual is an individual suffering from diabetic kidney disease. In another aspect, the individual is suffering from renal failure. Insulin resistance can be measured, for example, using the Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR) and / or the MATSUDA index. HOMA-IR is explained, for example, in Diabetologia 1985, 28, 412, which is incorporated herein by reference in its entirety. The MATSUDA index is explained, for example, in Diabetes Care 1999, 22, 1462, which is incorporated herein by reference in its entirety.

[0285] In some embodiments, the present disclosure provides a method for treating or preventing glucose intolerance in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is an individual suffering from type 2 diabetes. In another aspect, the individual is an individual suffering from diabetic kidney disease. In another aspect, the individual is suffering from renal failure.

[0286] In some embodiments, the present disclosure provides a method for treating a cardiovascular condition in an individual in need of treatment by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the cardiovascular condition is selected from the group consisting of heart failure, cardiomyopathy, atherosclerosis, venous thromboembolism, and atrial fibrillation. In one aspect, the cardiovascular condition is heart failure. In another aspect, the cardiovascular condition is heart failure. Petition 870260043157, dated 07 / 05 / 2026, p. 154 / 1284 145 / 598 with preserved ejection fraction (HFpEF). In another aspect, the cardiovascular condition is cardiomyopathy. In another aspect, the cardiomyopathy is selected from the group consisting of hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, hypertrophic cardiomyopathy, ischemic cardiomyopathy, ischemic cardiomyopathy, dilated cardiomyopathy, and idiopathic cardiomyopathy. In another aspect, the cardiovascular condition is atherosclerosis. In another aspect, the cardiovascular condition is venous thromboembolism. In another aspect, the cardiovascular condition is atrial fibrillation.

[0287] In some embodiments, the present disclosure provides a method for treating obesity or an obesity-related condition in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the obesity-related condition is a metabolic condition related to obesity. In another aspect, the obesity-related condition is selected from the group consisting of insulin resistance, prediabetes, type 2 diabetes, glucose intolerance, elevated fasting glucose, and glucagonomas. In another aspect, the obesity-related condition is dyslipidemia. In another aspect, the obesity-related condition is a cardiovascular condition selected from the group consisting of heart failure, cardiomyopathy, atherosclerosis, venous thromboembolism, and atrial fibrillation. In another aspect, the obesity-related condition is kidney disease.

[0288] In some embodiments, the present disclosure provides a method for reducing body weight in a needy individual by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual is an individual suffering from type 2 diabetes. In another aspect, the individual Petition 870260043157, dated 07 / 05 / 2026, page 155 / 1284 146 / 598 is an individual suffering from diabetic kidney disease. In another aspect, the individual is suffering from kidney failure. In another aspect, the administration of the compound is an adjunct to diet and exercise. In another aspect, the administration of the compound also reduces body weight and / or treats obesity. In another aspect, the individual has a BMI of 27 kg / m2 to 40 kg / m2. In another aspect, the individual has a BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight. In another aspect, the individual is obese. In another aspect, the individual's weight is reduced, for example, by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40%.

[0289] In some embodiments, the present disclosure provides a method for reducing body fat in a treatment-impaired individual by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In another aspect, the individual is suffering from type 2 diabetes. In another aspect, the individual is suffering from diabetic kidney disease. In another aspect, the individual is suffering from renal failure. In another aspect, administration of the compound is an adjunct to diet and exercise. In another aspect, administration of the compound also reduces body weight and / or treats obesity. In another aspect, the individual has a BMI of 27 kg / m2 to 40 kg / m2. In another aspect, the individual has a BMI of 30 kg / m2 to 39.9 kg / m2. In another aspect, the individual has a BMI of at least 40 kg / m2. In another aspect, the individual is overweight.In another aspect, the individual is obese. In another aspect, the fat is liver fat.

[0290] In some forms, the present disclosure provides a method for treating or preventing fibrosis in an individual needing it. Petition 870260043157, dated 07 / 05 / 2026, page 156 / 1284 147 / 598 cited by administering to an individual a therapeutically effective amount of a compound of this disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, fibrosis is interstitial lung disease. In another aspect, fibrosis is interstitial lung disease with progressive fibrosis. In another aspect, interstitial lung disease is pulmonary fibrosis. In another aspect, interstitial lung disease is idiopathic pulmonary fibrosis (IPF).

[0291] In some embodiments, the present disclosure provides a method for promoting tissue remodeling in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the individual suffered cardiac tissue damage due to myocardial infarction.

[0292] In some embodiments, the present disclosure provides a method for promoting wound healing and / or reducing adhesions in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, administration of the compound promotes wound healing and / or reduces adhesions through enhanced fibrinolysis.

[0293] In some embodiments, the present disclosure provides a method for treating or preventing a keloid condition in an individual in need by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the keloid condition is selected from the group consisting of scar formation, keloid tumors, and keloid scars.

[0294] In some embodiments, the present disclosure provides a method for treating or preventing inflammation in an individual ne Petition 870260043157, dated 07 / 05 / 2026, p. 157 / 1284 148 / 598 required by administering to an individual a therapeutically effective amount of a compound of this disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, inflammation is chronic inflammation. In one aspect, chronic inflammation is selected from the group consisting of rheumatoid arthritis, osteoarthritis, and Crohn's disease. In another aspect, chronic inflammation is rheumatoid arthritis.

[0295] In some embodiments, the present disclosure provides a method for treating cancer in an individual in need of treatment by administering to the individual a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof. In one aspect, the cancer is selected from the group consisting of breast cancer, pancreatic cancer, small bowel cancer, colon cancer, rectal cancer, lung cancer, head and neck cancer, ovarian cancer, hepatocellular carcinoma, esophageal cancer, hypopharyngeal cancer, nasopharyngeal cancer, laryngeal cancer, myeloma cells, bladder cancer, cholangiocellular carcinoma, clear cell renal carcinoma, neuroendocrine tumor, oncogenic osteomalacia, sarcoma, CUP (carcinoma of unknown primary), dothymic carcinoma, desmoid tumors, glioma, astrocytoma, cervical carcinoma, and prostate cancer. In another aspect, the cancer is hepatocellular carcinoma.

[0296] The subject will typically be a human or non-human mammal, particularly a human. Suitable subjects may also include domestic or wild animals; companion animals (including dogs, cats and similar animals); livestock (including horses, cows and other ruminants, pigs, poultry, rabbits and similar animals); primates (including monkeys such as rhesus monkeys, cynomolgus monkeys (also known as crab-eating or long-tailed monkeys), marmosets, tamarins, chimpanzees, macaques, and similar animals); Petition 870260043157, dated 07 / 05 / 2026, pages 158 / 1284 149 / 598 and rodents (including rats, mice, gerbils, guinea pigs, and similar animals).

[0297] In some embodiments, the present disclosure provides the compounds of the present disclosure, or pharmaceutically acceptable salts thereof, for use as medicaments.

[0298] In some embodiments, the present disclosure provides for the use of the compounds of Formula I, or pharmaceutically acceptable salts thereof, to treat or prevent a FAP-mediated condition as discussed above.

[0299] In some embodiments, the present disclosure provides for the use of the compounds of Formula I, or pharmaceutically acceptable salts thereof, for the manufacture of medicaments to treat or prevent a FAP-mediated condition as discussed above. IV. Combination Therapies and Fixed-Dose Combinations

[0300] The compounds of this disclosure may be used in the methods described above as single pharmacological agents or in combination with other pharmacological agents or techniques. Such combination therapies may be achieved by simultaneous, sequential or separate dosing of the individual components of the treatment. These combination therapies (and corresponding combination products) employ the compounds of this disclosure within the dosage ranges described in this application and the other pharmacological agent(s), typically within their approved dosage range(s).

[0301] In some embodiments, the present disclosure provides a combination suitable for use in the treatment of a selected condition from the conditions previously discussed, wherein the combination comprises a compound of the present disclosure, or its pharmaceutically acceptable salt, and a sodium-glucose transporter protein 2 (SGLT2) inhibitor. In one aspect, the SGLT2 inhibitor Petition 870260043157, dated 07 / 05 / 2026, p. 159 / 1284 150 / 598 is selected from the group consisting of canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, and remogliflozin. In another aspect, the SGLT2 inhibitor is dapagliflozin.

[0302] In some embodiments, the present disclosure provides a suitable combination for use in the treatment of a selected condition from those previously discussed, wherein the combination comprises a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and metformin.

[0303] In some embodiments, the present disclosure provides a suitable combination for use in the treatment of a selected condition from those previously discussed, wherein the combination comprises a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and a glucagon-like peptide-1 (GLP-1) receptor agonist. In one aspect, the SGLT2 inhibitor is selected from the group consisting of exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and semaglutide.

[0304] In some embodiments, the present disclosure provides a suitable combination for use in the treatment of a selected condition from those previously discussed, wherein the combination comprises a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and a dipeptidyl peptidase 4 (DPP4) inhibitor. In one aspect, the DPP4 inhibitor is selected from the group consisting of sitagliptin, vildagliptin, saxagliptin, linagliptin, gemigliptin, anagliptin, teneligliptin, alogliptin, trelagliptin, omarigliptin, evogliptin, gosogliptin, and dutogliptin.

[0305] In some embodiments, the present disclosure provides a suitable combination for use in the treatment of a selected condition from those previously discussed, wherein the combination comprises a compound of the present disclosure, or a salt thereof. Petition 870260043157, dated 07 / 05 / 2026, page 160 / 1284 151 / 598 pharmaceutically acceptable, and a peroxisome proliferator-activated receptor (PPAR) agonist. In one aspect, the PPAR agonist is a PPARα agonist. In another aspect, the PPAR agonist is a PPARγ agonist. In another aspect, the PPAR agonist is a PPARα / γ agonist. In another aspect, the PPAR agonist is selected from the group consisting of clofibrate, gemfibrozil, ciprofibrate, bezafibrate, and fenofibrate. In another aspect, the PPAR agonist is a thiazolidinedione. In another aspect, the thiazolidinedione is selected from the group consisting of pioglitazone, rosiglitazone, lobeglitazone, and rivoglitazone. In another aspect, the PPAR agonist stimulates liver expression of FGF21.

[0306] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof; one or more pharmacological agents selected from SGLT2 inhibitors, metformin, GLP1 agonists, DPP4 inhibitors, and PPAR agonists; and a pharmaceutically acceptable diluent or carrier. Such a combination may be used to manufacture a medicament for use in the treatment of a selected condition from those previously discussed. In one aspect, the pharmaceutical composition comprises an SGLT2 inhibitor. In another aspect, the pharmaceutical composition comprises metformin. In another aspect, the pharmaceutical composition comprises a GLP1 agonist. In another aspect, the pharmaceutical composition comprises a DPP4 inhibitor. In another aspect, the pharmaceutical composition comprises a PPAR agonist.

[0307] In some embodiments, the present disclosure provides a combination suitable for use in the treatment of cancer, wherein the combination comprises a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and an immune checkpoint inhibitor. In one aspect, the checkpoint inhibitor Petition 870260043157, dated 07 / 05 / 2026, page 161 / 1284 152 / 598 immune checkpoint inhibitors are selected from the group consisting of anti-PD-1 antibodies, anti-PD-LI antibodies, anti-CTLA4 antibodies, TLR7 agonists, CD40 agonists, Lag-3 antagonists, and OX40 agonists. Alternatively, an immune checkpoint inhibitor is an anti-PD-1 antibody (e.g., pembrolizumab (Keytruda), nivolumab (Opdivo), cemiplimab (Libtayo), etc.). Alternatively, an immune checkpoint inhibitor is an anti-PD-LI antibody (e.g., atezolizumab (Tecentriq), avelumab (Bavencio), durvalumab (Imfinzi), etc.). Alternatively, an immune checkpoint inhibitor is an anti-CTLA4 antibody (e.g., ipilimumab (Yervoy), tremelimumab, etc.). In another aspect, the cancer is selected from the group consisting of pancreatic cancer, colon cancer, and rectal cancer. V. Pharmaceutical compositions

[0308] The compounds of this disclosure, and pharmaceutically acceptable salts thereof, may be administered as pharmaceutical compositions comprising one or more pharmaceutically acceptable excipients. Consequently, in some embodiments, this disclosure provides pharmaceutical compositions comprising a compound of this disclosure, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

[0309] The excipient(s) selected for inclusion in a particular composition will depend on factors such as the route of administration and the form of the composition provided. Suitable pharmaceutically acceptable excipients are well known to those skilled in the art and are described, for example, in the “Handbook of Pharmaceutical Excipients”, Sixth Edition, Pharmaceutical Press, edited by Rowe, Ray C; Sheskey, Paul J; Quinn, Marian. Pharmaceutically acceptable excipients may function as, for example, adjuvants, diluents, carriers, stabilizers, flavorings, colorants, Petition 870260043157, dated 07 / 05 / 2026, page 162 / 1284 153 / 598 fillers, binders, disintegrants, lubricants, glidants, thickening agents and coating agents. As those skilled in the art will appreciate, certain pharmaceutically acceptable excipients may serve more than one function and may serve alternative functions depending on how much of the excipient is present in the composition and what other excipients are present in the composition.

[0310] The compositions may be in a form suitable for oral use (for example, as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example, as creams, ointments, gels or aqueous or oily solutions or suspensions), for administration by inhalation (for example, as a finely divided powder or a liquid aerosol), for administration by insufflation (for example, as a finely divided powder) or for parenteral administration (for example, as a sterile aqueous or oily solution for intravenous, subcutaneous or intramuscular dosing) or as a suppository for rectal dosing. The compositions may be obtained by conventional procedures using conventional pharmaceutical excipients well known in the art. Thus, compositions intended for oral use may contain, for example, one or more coloring agents, sweeteners, flavorings and / or preservatives.

[0311] The total daily dose will necessarily vary depending on the individual being treated, the particular route of administration, any co-administered therapies, and the severity of the disease being treated, and may include a single dose or multiple doses. Specific dosages may be adjusted, for example, depending on the condition being treated; the individual's age, body weight, general health status, sex, and diet; routes of administration; dosing intervals; excretion rate; and other drugs being co-administered to the individual. Petition 870260043157, dated 07 / 05 / 2026, page 163 / 1284 154 / 598 duo. A physician usually skilled in the art, possessing the disclosure of this application, will be able to determine appropriate dosages and regimens for administering the therapeutic agent to the individual, and to adjust such dosages and regimens as necessary during treatment, in accordance with methods well known in therapeutic techniques. The compound of this disclosure, or a pharmaceutically acceptable salt thereof, will typically be administered to a warm-blooded animal at a unit dose within the range of 2.5 to 5000 mg / m2 of the animal's body surface area, or approximately 0.05 to 100 mg / kg, and this normally provides a therapeutically effective dose. A unit dose form, such as a tablet or capsule, may contain, for example, 0.1 to 500 mg, 0.1 to 250 mg, or 0.1 to 100 mg of the active ingredient.

[0312] In some embodiments, the present disclosure provides pharmaceutical compositions for use in therapy, comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

[0313] In some embodiments, the present disclosure provides pharmaceutical compositions for use in the treatment of a FAP-mediated condition, comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. In one aspect, the FAP-mediated condition is selected from the group consisting of liver disease, type 2 diabetes mellitus, cardiovascular conditions, obesity, obesity-related conditions, fibrosis, keloid formation, inflammation, and cancer. VI. Kits

[0314] The present disclosure further provides kits comprising a unit dosage form comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, contained within packaging material and a label or Petition 870260043157, dated 07 / 05 / 2026, page 164 / 1284 155 / 598 leaflet indicating that the single-dose form can be used to treat one or more of the conditions previously described.

[0315] In some embodiments, the kit comprises a unit dosage form comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, contained within a packaging material and a label or leaflet indicating that the pharmaceutical composition can be used to treat a FAP-mediated condition. In another aspect, the FAP-mediated condition is liver disease. In another aspect, the liver disease is selected from the group consisting of fatty liver disease, end-stage liver disease, and cirrhosis. In another aspect, the liver disease is selected from the group consisting of Non-Alcoholic Steatohepatitis (NASH) and Non-Alcoholic Fatty Liver Disease (NAFLD).

[0316] In some embodiments, the kit comprises: (a) a first unit dosage form comprising a compound of the present disclosure, or its pharmaceutically acceptable salt; (b) a second unit dosage form comprising a pharmacological agent selected from the group consisting of SGLT2 inhibitors, metformin, GLP1 agonists, DPP4 inhibitors, and PPAR agonists; (c) a containment means for containing said first and second dosage forms; and (d) a label or leaflet indicating that the first unit dosage form and second unit dosage form can be used to treat a FAP-mediated condition. VII. Preparation Methods

[0317] The present disclosure further provides processes for the preparation of the compounds of Formulas (I), (II), (III-A), (IIIB), (III-C), (III-D), (III-E), (IV), (IV-A), (V), (VI), (VII), (VIII), (IX), (X), and (XI), and pharmaceutically acceptable salts thereof.

[0318] Schemes 1 through 14 below illustrate synthesis routes for compounds of Formula (II) wherein R1, R2, R3, R4, R5, R6 and X1 are as Petition 870260043157, dated 07 / 05 / 2026, p. 165 / 1284 156 / 598 defined in formula (I), R7 is an alkyl group (e.g., methyl, ethyl, or ferc-butyl), and X2, X3, and X4 are labile groups (e.g., Cl, Br, I, or OTf). Those skilled in the art will appreciate that these methods are representative and do not include all possible methods for preparing the compounds of the present disclosure. The substituents Rx in each Scheme are as defined for the compounds of the present disclosure unless otherwise stated. It is understood that the preparation processes described in Schemes 1 to 14 can be carried out starting from any enantiomer, or a racemic mixture, of compounds of formula (2), (4), (6), (8), (9), (10), (11), (12), (13), or (14) to originate compounds of Formula (II) or any stereoisomer of Formula (II). SCHEME 1

[0319] Scheme 1 illustrates synthesis routes for certain compounds of formula (II). A compound of formula (2) can react with a compound of formula (3) to give a compound of formula (II). The reaction can be carried out using suitable coupling reagents (e.g., HATU, HOBt / EDC, or T3P) in the presence of a base (typically an organic base such as DIPEA or TEA) using a solvent such as DCM, DMF, EtOAc, or MeCN, or mixtures thereof, and at temperatures typically ranging from 0 °C to 60 °C. Petition 870260043157, dated 07 / 05 / 2026, page 166 / 1284 157 / 598

[0320] Scheme 2 illustrates additional synthesis routes for certain compounds of formula (II). A compound of formula (4) can react with a compound of formula (5) to give a compound of formula (II). The reaction can be carried out using suitable coupling reagents (e.g., HATU, HOBt / EDC, or T3P) in the presence of a base (typically an organic base such as DIPEA or TEA) using a solvent such as DCM, DMF, EtOAc, or MeCN, or mixtures thereof, and at temperatures typically ranging from 0 °C to 60 °C. SCHEME 3

[0321] Scheme 3 illustrates additional synthesis routes for certain compounds of formula (II). A compound of formula (6) can be transformed into a compound of formula (II) by dehydration using a suitable reagent (typically TFAA or T3P) in a solvent such as DCM, DMF, EtOAc or MeCN, or mixtures thereof, and at a temperature typically ranging from 0 °C to 120 °C. SCHEME 4 (4) (8) (2)

[0322] Scheme 4 illustrates synthesis pathways for certain compounds Petition 870260043157, dated 07 / 05 / 2026, page 167 / 1284 158 / 598 of formula (2). A compound of formula (4) can react with (ferc-butoxycarbonyl)-glycine (7) to give a compound of formula (8). The reaction can be carried out using suitable coupling reagents (e.g., HATU, HOBt / EDC, or T3P) in the presence of a base (typically an organic base such as DIPEA or TEA) using a solvent such as DCM, DMF, EtOAc, or MeCN, or mixtures thereof, and at temperatures typically ranging from 0 °C to 120 °C.

[0323] A compound of formula (2) can be formed by reacting a compound of formula (8) with a suitable acid (e.g., HCl) in a solvent such as 1,4-dioxane, EtOAc, MeOH or water, or mixtures thereof. Alternatively, the reaction can be carried out using acids such as TFA, pure or in a solvent such as DCM, at temperatures typically ranging from 0 °C to 60 °C. SCHEME 5 (9) (10) (11) (4)

[0324] Scheme 5 illustrates synthesis routes for certain compounds of formula (4). A compound of formula (10) can be formed by reacting a compound of formula (9) with NH3, pure or as a solution, for example, in water or MeOH, or with a synthetic equivalent of ammonia (for example, NH4Cl). The reaction can be carried out using suitable coupling reagents (for example, HATU, HOBt / EDC, T3P or BOC2O) in the presence of a base (typically an organic base, such as DIPEA or TEA) using a solvent such as THF, DMF, EtOAc or MeCN, or mixtures thereof, and at temperatures typically ranging from 0 °C to 120 °C.

[0325] A compound of formula (10) can be transformed into a compound of formula (11) by dehydration using a suitable reagent (typically TFAA or T3P) in a solvent such as DCM, DMF, Petition 870260043157, dated 07 / 05 / 2026, pages 168 / 1284 159 / 598 EtOAc or MeCN, or mixtures thereof, and at a temperature typically ranging from 0 °C to 120 °C.

[0326] A compound of formula (4) can be formed by reacting a compound of formula (11) with a suitable acid (e.g., HCl or TsOH) in a solvent such as MeCN, 1,4-dioxane, EtOAc, MeOH or water, or mixtures thereof. Alternatively, the reaction can be carried out using acids such as TFA, pure or in a solvent such as DCM, at temperatures typically ranging from 0 °C to 60 °C. SCHEME 6

[0327] Scheme 6 illustrates synthesis routes for certain compounds of formula (6). A compound of formula (12) can react with a compound of formula (3) to give a compound of formula (6). The reaction can be carried out under conditions described for the analogous reaction described in Scheme 1. SCHEME 7 (13) (14) (12)

[0328] Scheme 7 illustrates synthesis routes for certain compounds of formula (12). A compound of formula (12) can be formed from compounds of formula (13) and (7), via a compound of formula (14). The reactions can be carried out under conditions described for the analogous reactions described in Scheme 4. Petition 870260043157, dated 07 / 05 / 2026, page 169 / 1284 160 / 598 SCHEME 8

[0329] Scheme 8 illustrates synthesis routes for certain compounds of formula (5). A compound of formula (3) can react with a compound of formula (15) to give a compound of formula (16). The reaction can be carried out using suitable coupling reagents (e.g., HATU, HOBt / EDC, or T3P) in the presence of a base (typically an organic base such as DIPEA or TEA) using a solvent such as DCM, DMF, EtOAc, or MeCN, or mixtures thereof, and at temperatures typically ranging from 0 °C to 120 °C.

[0330] A compound of formula (5) can be formed by reacting a compound of formula (16) with a base (e.g., NaOH or LiOH) in an organic solvent (e.g., dioxane, THF, or MeOH, or mixtures thereof), and optionally in the presence of water. The reaction can be carried out in a temperature range between 0 °C and reflux. Alternatively, for compounds of formula (16) where R7 = ferc-butyl, the reaction can be carried out with a suitable acid (e.g., HCl) in a solvent such as 1,4-dioxane, EtOAc, MeOH, or water, or mixtures thereof. Alternatively, the reaction can be carried out using acids such as TFA, pure or in a solvent such as DCM, at temperatures typically ranging from 0 °C to 60 °C. SCHEME 9 W. (17) (18) Petition 870260043157, dated 07 / 05 / 2026, p. 170 / 1284 161 / 598

[0331] Scheme 9 illustrates synthesis routes for certain compounds of formula (3). A compound of formula (18) can be formed by reacting a compound of formula (17) with an alcohol (e.g., MeOH or EtOH) in the presence of an acid (e.g., HCl or H2SO4) in a suitable solvent, or using alcohol as solvent. Alternatively, the reaction can be promoted by reagents such as SOCl2 in a suitable solvent, or using alcohol (e.g., MeOH or EtOH) as solvent. Alternatively, a compound of formula (18) can react with an alcohol (e.g., MeOH or EtOH) promoted by coupling reagents (e.g., EDO or TBTU) in the presence of a base (such as DIPEA, TEA, or DMAP) using a solvent such as DCM, DMF, EtOAc, or MeCN, or mixtures thereof, and at temperatures typically ranging from 0 °C to 120 °C.

[0332] A compound of formula (19) wherein R2 is as defined in Formula (I), and wherein the quinoline attachment point is through a nitrogen atom, can be formed by the reaction of a compound of formula (18) with an amine H-R2(20), wherein R2 is as defined in Formula (I). The reaction can be catalyzed with a suitable Pd reagent, for example, Pd2(dba)s with a suitable phosphine ligand (for example, XPhos, CPhos, SPhos, RuPhos, DavePhos or XantPhos) in the presence of a base (such as CS2CO3) in a suitable solvent (such as 1,4-dioxane), optionally in the presence of water, at temperatures ranging from room temperature to reflux.

[0333] A compound of formula (19) in which R2 is as defined in formula (I), and in which the point of attachment to quinoline is through a nitrogen atom, can be formed by the reaction of a compound of formula (18) with an amine H-R2(20), in which R2 is as defined in formula (I). The reaction can be catalyzed with a suitable Cu reagent (e.g., Cul or Cu2O) in the presence of a base (such as Petition 870260043157, dated 07 / 05 / 2026, p. 171 / 1284 162 / 598 K2CO3 or CS2CO3) in a suitable solvent (such as DMF) at temperatures ranging from room temperature up to 160 °C.

[0334] A compound of formula (3) can be formed by reacting a compound of formula (19) with a base (e.g., NaOH or LiOH) in an organic solvent (e.g., 1,4-dioxane, THF, or MeOH, or mixtures thereof), and optionally in the presence of water. The reaction can be carried out in a temperature range between 0 °C and 0 °F reflux. Alternatively, for compounds of formula (19) where R7 = ferc-butyl, the reaction can be carried out with a suitable acid (e.g., HCl) in a solvent such as 1,4-dioxane, EtOAc, MeOH, or water, or mixtures thereof. Alternatively, for compounds of formula (19) where R7 = ferc-butyl, the reaction can be carried out using acids such as TFA, pure or in a solvent such as DCM, at temperatures typically ranging from 0 °C to 60 °C.

[0335] Alternatively, a compound of formula (3) wherein R2 is as defined in Formula (I), and wherein the point of attachment to quinoline is through a nitrogen atom, can be formed directly from a compound of formula (17) by reaction with an amine HR2(20), wherein R2 is as defined in formula (I). The reaction can be carried out under conditions described for the analogous reactions described above in Scheme 9. SCHEME 10

[0336] Scheme 10 illustrates synthesis routes for certain compounds of formula (3). A compound of formula (19) in which R2 is as defined in formula (I), and in which the point of attachment to quinoline is through a carbon atom, can be formed by the reaction of a compound of Petition 870260043157, dated 07 / 05 / 2026, p. 172 / 1284 163 / 598 formula (18) with a compound B-R2(21), wherein B is a boronic acid, boronate ester or trifluoroborate salt, and wherein R2 is as defined in formula (I). The reaction can be catalyzed with a suitable Pd reagent (e.g., Pd(dppf)Cb) in the presence of a base (such as Na2COs or K2CO3) in a suitable solvent (such as 1,4-dioxane), optionally in the presence of water, at temperatures ranging from room temperature to reflux.

[0337] A compound of formula (3) can be formed by reacting a compound of formula (19) under conditions described for the analogous reactions described in Scheme 9. Alternatively, a compound of formula (3) where R2 is as defined in Formula (I), and where the point of attachment to quinoline is through a carbon atom, can be formed directly from a compound of formula (17) by reaction with a compound B-R2(21), where B is a boronic acid, boronate ester or trifluoroborate salt, and where R2 is as defined in formula (I). The reaction can be carried out under conditions described for the analogous reaction described above in Scheme 10. SCHEME 11

[0338] Scheme 11 illustrates synthesis routes for certain compounds of formula (19). A compound of formula (22), wherein B is a boronic acid, boronate ester or trifluoroborate salt, can be formed by reacting a compound of formula (18) with a bis-boronic species (e.g., B2(OH)4 (hypodiboric acid) or B2pin2 (4,4,4',4',5,5,5',5'octamethyl-2,2'-bi(1,3,2-dioxaborolane)). The reaction can be catalyzed with a suitable Pd reagent (e.g., Pd(dppf)Cb) in the presence of a base (such as Na2COs or K2CO3) in a suitable solvent. Petition 870260043157, dated 07 / 05 / 2026, page 173 / 1284 164 / 598 (as ethanol or 1,4-dioxane), optionally in the presence of water, at temperatures ranging from room temperature to reflux.

[0339] A compound of formula (19) where R2 is as defined in formula (I), and where the point of attachment to quinoline is through a carbon atom, can be formed by the reaction of a compound of formula (22) with an aryl halide or aryl pseudo-halide of formula (23), where R2 is as defined in formula (I) and X3 is linked to R2 via a carbon atom. The reaction can be catalyzed with a suitable Pd reagent (e.g., Pd(dppf)Cb) in the presence of a base (such as Na2COs or K2CO3) in a suitable solvent (such as 1,4-dioxane), optionally in the presence of water, at temperatures ranging from room temperature to reflux. SCHEME 12

[0340] Scheme 12 illustrates synthesis routes for certain compounds of formula (17). A compound of formula (26) can be formed by reacting a compound of formula (24) with a 2-ketocarboxylic acid of formula (25), or a salt thereof (e.g., a sodium salt), in the presence of a base (e.g., NaOH) in water at reflux temperature, or at elevated temperatures typically ranging from 100 °C to 160 °C in a sealed container, or in a sealed tube in a microwave reactor. A compound of formula (17) can be formed by heating a compound of formula (26), pure, or in a suitable solvent (e.g., water) at elevated temperatures typically ranging from 150 °C to 250 °C in a sealed container, or in a sealed tube in a microwave reactor. Petition 870260043157, dated 07 / 05 / 2026, p. 174 / 1284 165 / 598

[0341] Scheme 13 illustrates synthesis routes for certain compounds of formula (19). A compound of formula (28) in which R2 is as defined in formula (I), and in which the point of attachment to quinoline is through a nitrogen atom or a carbon atom, can be formed from a compound of formula (27) using synthesis methodology carried out under conditions described for the analogous reactions described in Scheme 9, 10 and 11.

[0342] A compound of formula (19) can be formed by reacting a compound of formula (28) with carbon monoxide (1-10 atm), typically at a pressure of 10 atm, at a temperature ranging from typically 80 °C to 120 °C in a sealed container. The reaction can be catalyzed with a suitable Pd reagent (e.g., Pd(dppf)Cb) in the presence of a base (e.g., TEA) in the presence of a suitable alcohol (such as MeOH or EtOH) in a suitable solvent, or by using the alcohol as a solvent. SCHEME 14 p50e p50e (29) (31)

[0343] Scheme 14 illustrates synthesis pathways for certain compounds Petition 870260043157, dated 07 / 05 / 2026, pages 175 / 1284 166 / 598 of formula (31). A compound of formula (29) wherein R50 is as defined in Formula (VIII) can be formed from a compound of formula (27) by metal-halogen exchange using an organometallic reagent (e.g., BuLi) followed by reaction with an electrophile such as a ketone of formula (30). The reaction can be carried out in a solvent such as THF at a temperature typically ranging from -78 °C to room temperature.

[0344] A compound of formula (31) in which R50j is a fluorine, can be formed by reacting a compound of formula (29) with a fluorinating agent (e.g., DAST) in a solvent such as DCM at a temperature ranging from typically -20 °C to reflux.

[0345] A compound of formula (31) can be converted into a compound of formula (VIII) using synthesis methodology analogous to those described in Schemes 13, 10 and 1.

[0346] It should be understood that: (i) the organic reactions described in this disclosure are carried out in accordance with laboratory practice known to those skilled in the art; (ii) some of the reactions described in this disclosure may optionally be carried out in a different order than that presented herein; (iii) chiral isomers of compounds in this disclosure may be resolved at any stage of the synthesis process using chiral resolving agents described in the literature and known to those skilled in the art, or using chiral chromatography methods described in the literature and known to those skilled in the art, or as further described in the Examples; (iv) additional protecting groups and / or others may optionally be required in some of the steps described above, and (v) consequently, a deprotection step may optionally be carried out using methods described in the literature and known to those skilled in the art.The protection and deprotection of functional groups are described in "Protecting Groups in Organic Synthesis," 3rd ed., T.W. Greene and P.G.M. Wutz, Wiley-Interscience. Petition 870260043157, dated 07 / 05 / 2026, p. 176 / 1284 167 / 598 (1999), the publication of which is incorporated here by reference. VIII. Examples

[0347] The following descriptions of experiments, procedures, examples, and intermediates are intended to exemplify embodiments of the disclosure and are in no way intended to be limiting. Other compounds in this disclosure may be prepared using the methods illustrated in these examples, either alone or in combination with techniques generally known in the art. A. General Conditions

[0348] Unless stated otherwise: (i) the operations were carried out at ambient temperature (ta), i.e., in the range of 17 to 25 DCe under an atmosphere of an inert gas such as N2, unless otherwise specified. (ii) when the reactions refer to the use of a microwave reactor, one of the following microwave reactors was used: Biotage Initiator, Personal Chemistry Emrys Optimizer, Personal Chemistry Smith Creator or CEM Explorer; (iii) In general, the course of the reactions was followed by analytical thin layer chromatography (TLC) and / or high performance liquid chromatography (HPLC or UPLC) which was usually coupled to a mass spectrometer (LCMS). (iv) when necessary, organic solutions were dried in anhydrous MgSO4 or Na2SO4, or using ISOLUTE® Phase Separator, and handling procedures were conducted using traditional phase separation techniques. (v) the evaporations were carried out by rotary evaporation in vacuum or in a Genevac HT-4 / EZ-2 or Biotage V10; (vi) Unless otherwise stated, flash column chromatography was performed on direct-phase silica using Merck Silica. Petition 870260043157, dated 07 / 05 / 2026, page 177 / 1284 168 / 598 Gel (Art. 9385) or pre-packaged cartridges, such as Biotage® SNAP cartridges (silica 40-63 pm, 4-330 g), Biotage® Star Silica HC D cartridges (20 pm, 10-100 g), Interchim puriFlash™ cartridges (25 pm, 4-120 g), Interchim puriFlash™ cartridges (50 pm, 25-330 g), Grace™ GraceResolv™ Silica Flash cartridges (4-120 g) or Agela Flash Colum Silica-CS cartridges (80-330 g), or in reverse phase silica using Agela Technologies C-18 spherical cartridges (20-35 pm, 100 A, 80-330 g), manually or in an automated manner using a Grace Resolv™ X2 Flash system or similar system; (vii) Reverse-phase preparative HPLC and reverse-phase preparative SFC were conducted using standard HPLC and SFC instruments, respectively, equipped with an MS and / or UV driven fraction collection instrument, using an isocratic process or a mobile phase gradient as described in the experimental section, and one of the following methods as described below; HPLC Preparation Methods: Prep Method A: The compound was purified by preparative HPLC on a YMC-Actus Triart C18 ExRS column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / NH4HCO3 (10 mM) as the mobile phase; Prep Method B: The compound was purified by preparative HPLC on an XBridge™ C18 OBD column (5 pm, 150x30 mm Dl) using a MeCN gradient in a H2O / NH4HCO3 (10 mM) / NH3 (0.1%, aq) buffer system as the mobile phase; Prep Method C: The compound was purified by preparative HPLC on an XSelect CSH OBD column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / FA ​​(0.1%) as the mobile phase; Method Prep D: The compound was purified by preparative HPLC on an XSelect CSH C18 OBD column (5 µm, 250x19 mm Δl) using a MeCN gradient in H2O / FA ​​(0.1%) as the mobile phase; Method Prep E: The compound was purified by preparative HPLC on a Kromasil C8 column (10 µm, 250x20 mm Δl) using a MeCN gradient in H2O / MeCN / FA Petition 870260043157, dated 07 / 05 / 2026, pages 178 / 1284169 / 598 (95 / 5 / 0.2) as mobile phase; Prep Method F: The compound was purified by preparative HPLC on a Waters™ Sunfire™ C18 OBD column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / FA ​​(0.1%) as mobile phase; Prep Method G: The compound was purified by preparative HPLC on a Kromasil C8 column (10 pm, 250x50 mm Dl) using a MeCN gradient in H2O / MeCN / FA (95 / 5 / 0.2) as mobile phase; Prep Method H: The compound was purified by preparative HPLC on an XBridge™ C18 column (10 pm, 250x50 mm Dl) using a MeCN gradient in H2O / MeCN / NH3 (95 / 5 / 0.2) as mobile phase; Prep Method I: The compound was purified by preparative HPLC on an XBridge™ C18 OBD column (5 pm, 250x19 mm Dl) using a MeCN gradient in H2O / NH4HCO3 (10 mM) as the mobile phase; Prep Method N: The compound was purified by preparative HPLC on an XBridge™ C18 column (10 pm, 250x19 mm Dl) using a MeCN gradient in H2O / MeCN / NH3 (95 / 5 / 0.2) as the mobile phase;Prep Method O: The compound was purified by preparative HPLC on an XBridge™ C18 column (5 pm, 250x19 mm Dl) using a MeOH gradient in H2O / NH4HCO3 (10 mM) as the mobile phase; Prep Method P: The compound was purified by preparative HPLC on an XBridge™ Shield C18 column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / FA ​​(0.1%) as the mobile phase; Prep Method Q: The compound was purified by preparative HPLC on an Xbridge™ C18 ODB column (5 pm, 150x19 mm Dl) using a MeCN gradient in a H2O / NH3 buffer system (0.2%, pH 10) as the mobile phase; Prep R Method: The compound was purified by preparative HPLC on an XBridge™ C18 OBD column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / NH4HCO3 (10 mM) as the mobile phase; Prep T Method: The compound was purified by preparative HPLC on an XBridge™ Shield C18 column (5 pm, 150x30 mm Dl) using a MeCN gradient in a system; Petition 870260043157, dated 07 / 05 / 2026, page 179 / 1284 170 / 598 H2O / NH4CO3 (10 mM) / NH3 (0.1%, aq) buffer as mobile phase; Prep Method U: The compound was purified by preparative HPLC on an Xselect CSH F-Phenyl OBD column (5 pm, 250x19 mm Dl) using a MeCN gradient in H2O / FA ​​(0.1%) as mobile phase; Prep Method V: The compound was purified by preparative HPLC on a Waters™ Sunfire™ C18 OBD column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / FA ​​(0.1 M) as mobile phase; Prep Method X: The compound was purified by preparative HPLC on an Xselect CSH OBD column (5 pm, 150x30 mm Dl) using a MeCN gradient in H2O / FA ​​(0.1%) as mobile phase; SFC Preparation Methods: SFC Prep-A Method: The compound was purified by preparative SFC on a Phenomenex Luna® HILIC column (5 pm, 250x30 mm Dl) using EtOH / FA (20 mM) in CO2 as the mobile phase; SFC Prep-B Method: The compound was purified by preparative SFC on a DAICEL DCpak® P4VP (5 pm, 250x20 mm Dl) using 2 M MeOH / NH3 in MeOH (99.5 / 0.5) in CO2 as the mobile phase; SFC Prep-C Method: The compound was purified by preparative SFC on a Waters™ BEH (5 pm, 250x30 mm Dl) using MeOH / H2O (NH350 mM) (97 / 3) in CO2 as the mobile phase; SFC Prep-D Method: The compound was purified by preparative SFC in a Waters™ BEH (5 pm, 30x250 mm Dl) using EtOH / FA (20 mM) in CO2 as the mobile phase; SFC Prep-E Method: The compound was purified by preparative SFC in a Waters™ BEH (5 pm, 250x30 mm Dl) using MeOH / NH3 (20 mM) in CO2 as the mobile phase; SFC Prep-G Method: The compound was purified by preparative SFC in a Waters™ BEH (3.5 pm, 100x3 mm Dl) using MeOH / NH3 (20 mM) in CO2 as the mobile phase;SFC Prep-H Method: The compound was purified by preparative SFC on a Phenomenex Luna® HILIC column (5 pm, 250x30 mm DL) using MeOH / NH3 (20 mM) in CO2 as the mobile phase. Petition 870260043157, dated 07 / 05 / 2026, pages 180 / 1284 171 / 598

[0349] Relevant fractions were collected, combined and lyophilized to obtain the purified compound or relevant fractions were collected, combined and concentrated under reduced pressure, extracted with DCM or EtOAc, and the organic phase was dried over Na2SO4 or using a phase separator, and then concentrated under reduced pressure to obtain the purified compound; (viii) Chiral preparative chromatography was performed using HPLC or SFC on standard HPLC or SFC instruments, respectively, and using an isocratic or gradient process applied with mobile phase as described in the experimental section; (x) yields, when present, are not necessarily the maximum achievable and, when necessary, reactions were repeated when a larger quantity of the reaction product was required; (xi) when certain compounds were obtained as an acid addition salt, for example, a monohydrochloride salt or a dihydrochloride salt, the stoichiometry of the salt was based on the number and nature of the basic groups in the compound, the exact stoichiometry of the salt was not generally determined, for example, by means of elemental analysis data; (xii) In general, the structures of the final products of Formula (I) were confirmed by nuclear magnetic resonance (NMR) and / or mass spectral techniques; the proton NMR chemical shift values ​​were measured on the delta scale using Bruker Avance III 300, 400, 500 and 600 spectrometers, operating at 1H frequencies of 300, 400, 500 and 600 MHz, respectively. Experiments were typically recorded at 25 °C. Chemical shifts are presented in ppm, with the solvent as the internal standard. Protons in heteroatoms such as NH and OH protons are reported only when detected Petition 870260043157, dated 07 / 05 / 2026, pages 181 / 1284 172 / 598 of the NMR spectrum and may therefore be absent. In certain cases, protons may be masked or partially masked by solvent peaks and consequently will not be present and will not be reported or will be reported as multiplets superimposed with solvent. The following abbreviations have been used (and their derivatives, e.g., dd, doublet of doublets, etc.): s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, large; qn, quintet; p, pentet. In some cases, the structures of the final products of Formula (I) may appear as rotamers in the NMR spectrum, in which cases only peaks of the main rotamer are reported.Electrospray mass spectral data were obtained using a Waters Acquity UPLC coupled to a Waters single quadripole mass spectrometer or similar equipment, acquiring positive and negative ion data, and generally only ions relating to the parent structure are reported; high-resolution electrosp...

Claims

1. Compound, characterized in that it has the structure of Formula (I): X1 is selected from the group consisting of -S-, -S(O)- and S(O)2-; R1 is selected from the group consisting of hydrogen, halogen, hydroxyl, C1-3-alkyl and C1-6-alkoxy; R2 is selected from the group consisting of: (a) heterocyclyls containing a total of 5 to 10 ring atoms, wherein the heterocyclyl ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has (a) one ring nitrogen atom and one ring oxygen atom, with the remaining ring atoms being carbon, or (b) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl,C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl, wherein C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted with one or more halogens; and (b) heterocyclyl, containing a total of 4 to 10 ring atoms, wherein the heterocyclyl ring: (i) is a monocyclic or bicyclic ring Petition 870260082974, dated 17 / 08 / 2026, p. 6 / 77 2 / 33 saturated, partially saturated, or completely unsaturated cast iron, (ii) has one, two, or three ring nitrogen atoms, with the remaining ring atoms being carbon and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-6-alkyl, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C3-6-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl,C1-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and tetrahydrooxepanil, and in which: (a) C1-6-alkyl, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C3-6-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl-C1-3-alkyl, C1-3-alkoxyphenyl-C1-3-alkyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholiniyl, tetrahydrofuranyl(a) tetrahydropyranyl and tetrahydro-oxepanyl may be further substituted with one or more halogens and (b) C1-6-alkyl may be further substituted with one or more hydroxyls; and (c) spiroheterocyclyl, containing a total of 6 to 11 ring atoms, wherein the spiroheterocyclyl: (i) comprises two saturated rings, (ii) has: (a) one or two ring nitrogen atoms, with the remaining ring atoms being carbon, (b) one or two ring nitrogen atoms and one or two ring oxygen atoms, with the remaining ring atoms being carbon, or (c) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of Petition 870260082974, dated 17 / 08 / 2026, page 7 / 77 3 / 33 halogen, oxo, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy,R3 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; R4 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; R5 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl; and R6 is selected from the group consisting of hydrogen, halogen, and C1-3-alkyl.

2. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that it is a compound having the structure of Formula (II): R3, R4, R5 and R6 are as defined in claim 1.

3. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that X1 is -S-.

4. Compound according to claim 2, or a pharmaceutically acceptable salt thereof, characterized in that it is a compound having the structure of Formula (IV-A): Petition 870260082974, dated 17 / 08 / 2026, page 8 / 77 4 / 33 or a pharmaceutically acceptable salt thereof, where R2 is as defined in claim 1.

5. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, characterized in that R2 is a heterocycline containing a total of 5 to 10 ring atoms, wherein the heterocycline ring: (i) is a saturated, partially saturated or completely unsaturated fused monocyclic or bicyclic ring, (ii) has (a) one ring nitrogen atom and one ring oxygen atom with the remaining ring atoms being carbon, or (b) one ring nitrogen atom and one ring sulfur atom with the remaining ring atoms being carbon, and (iii) is optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl, and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl,C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted by one or more halogens.

6. A compound according to claim 5, or a pharmaceutically acceptable salt thereof, characterized in that: a) the heterocyclyl ring is a saturated monocyclic ring and / or b) the heterocyclyl ring has one nitrogen atom in the ring and one oxygen atom in the ring with the remaining ring atoms being carbon.

7. Compound, according to claim 5, or a pharmaceutically acceptable salt thereof, characterized in that Petition 870260082974, dated 08 / 17 / 2026, p.9 / 77 5 / 33 the heterocyclyl ring is selected from the group consisting of: wherein the heterocyclyl ring is optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl, and wherein C1-6-alkyl, C1-6-alkoxy, C1-3-alkoxyC1-3-alkyl, C3-6-cycloalkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted by one or more halogens; optionally where the heterocyclyl ring is selected from the group consisting of: λ-------, , x-------f , and x-------f ; wherein the heterocyclyl ring is optionally replaced by one or more substituents selected independently from the group Petition 870260082974, of 17 / 08 / 2026, p.10 / 77 6 / 33 which consists of halogen, cyano, Ci-6-alkyl, C3-6-cycloalkyl, C1-6alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl, and in which C1-6-alkyl, C3-6-cycloalkyl, C1-6alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl can be substituted by one or more halogens.

8. A compound according to claim 5, or a pharmaceutically acceptable salt thereof, characterized in that the heterocyclyl ring is: wherein the heterocyclyl ring is optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, oxo, C1-6-alkyl, C3-6-cycloalkyl, C16-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl, and where C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl may be further substituted by one or more halogens.

9. Compound according to claim 5, or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of: (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,2-oxazinan-2yl)quinoline-4-carboxamide (Example 1); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-3-fluoro-6-morpholinoquinoline-4-carboxamide (Example 2); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-thiomorpholinoline-4-carboxamide (Example 3); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-difluoromorpholino)quinoline-4-carboxamide (example 4); Petition 870260082974, dated 17 / 08 / 2026, page 11 / 77 7 / 33 (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2,6,6-tetrafluoromorpholino)-quinoline-4-carboxamide (example 5); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,3-dihydro-4Hbenzo[b][1,4]oxazine-4-yl)quinoline-4-carboxamide (Example 6); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-8-methyl-6-morpholinoline-4-carboxamide (example 9);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-7-methyl-6-morpholinolin-4-carboxamida (example 10); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-dimethyl-2oxoxazolidin-3-yl)quinolin-4-carboxamida (example 13); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethyl-3-oxomorpholino)-quinolin-4-carboxamida (example 16); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R )-7-methyl-1,4oxazepan-4-yl)-quinoline-4-carboxamida (example 61); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-7-methyl-1,4oxazepan-4-yl)-quinoline-4-carboxamida (example 62); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-3-methyl-1,4oxazepan-4-yl)-quinoline-4-carboxamida (example 63); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R )-2-methyl-1,4oxazepan-4-yl)-quinoline-4-carboxamida (example 64); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamida (example 67);N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (example 68); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-(fluoromethyl)-morpholino)quinoline-4-carboxamide (example 69); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,6R)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (example 70); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(fluoromethyl)-morpholino)quinoline-4-carboxamide (example 71); Petition 870260082974, dated 17 / 08 / 2026, page 12 / 77 8 / 33 N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-methylmorpholino)-quinoline-4-carboxamide (example 72); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (example 73); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(trifluoromethyl)-morpholino)quinoline-4-carboxamide (example 74);6-((1S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptane-5-yl)-N-(2-(( R)4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamida (exemplo 75); 6-((1 R,4R)-2-Oxa-5-azabicyclo[2.2.1 ]heptane[2.2.1 ]heptano5-yl)-N-(2-( (R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamida (example 76); 6-(6-Oxa-3-azabicyclo[3.

1. 1 ]heptane-3-yl)-N-(2-(( R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 77); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,6S)-2,6-dimethylmorpholino)-quinoline-4-carboxamide (Example 78); 6-(8-Oxa-3-azabicyclo[3.2.1 ]octano-3-yl)-N-(2-(( R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Example 79); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-2-methylmorpholino)-quinoline-4-carboxamida (example 80); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,3S)-2,3-dimethylmorpholino)-quinoline-4-carboxamida (example 81);N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-2,3-dimethylmorpholino)-quinolina-4-carboxamida (example 82); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,3R)-2,3-dimethylmorpholino)-quinolina-4-carboxamida (example 83); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-3-(trifluoromethyl)-morpholino)quinolina-4-carboxamida Isomer 1 (Example 84); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-3-(trifluoromethyl)-morpholino)quinoline-4-carboxamida Isomer 2 (Exemplo 85); Petition 870260082974, 17 / 08 / 2026, pág. 13 / 77 9 / 33 6-(3-Oxa-9-azabicyclo[3.3.1 ]nonan-9-yl)-N-(2-(( R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamida (exemplo 86); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,5R)-2,5-dimethylmorpholino)-quinoline-4-carboxamida (example 87); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylmorpholino)-quinoline-4-carboxamida (example 88);N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-3-(methoxymetil)-morpholino)quinolina-4-carboxamide (example 89); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5R)-3,5-dimethyl-morpholino)quinolina-4-carboxamide (example 90); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,4-oxazepan4-yl)quinolina-4-carboxamide (example 91); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R )-2-((methylsulfonyl)-methyl)morpholino)quinoline-4-carboxamide (Example 92); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)-morpholino)quinoline-4-carboxamide (Example 93); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-((methylsulfonyl)-methyl)morpholino)quinoline-4-carboxamide (Example 94); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-(2-methoxyethyl)-morpholino)quinoline-4-carboxamide (Example 95); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3S)-3-(methoxymethyl)-2-methylmorpholino)quinoline-4-carboxamide (Example 96);N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2R,3R)-3-(methoxymethyl)-2-methylmorpholino)quinoline-4-carboxamide (example 97); 6-(3-Oxa-8-azabicyclo[3.2.1 ]octano-8-yl)-N-(2-(( R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (example 98); 7-Bromo-N-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6((3S,5R)-3,5-dimethyl-morpholino)quinoline-4-carboxamide (example 100); (R )-5-Chloro-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoline-4-carboxamida (Exemplo 101); Petition 870260082974, 17 / 08 / 2026, pág. 14 / 77 10 / 33 N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-3-methylmorpholino)-quinoline-4-carboxamida (exemplo 102); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,5S)-3,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 103); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R,5R)-3,5-dimethylmorpholino)-quinoline-4-carboxamide (Example 105); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-ethylmorpholino)quinoline-4-carboxamide (Example 106);(R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylmorpholino)-quinoline-4-carboxamida (example 107); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-methylmorpholino)-quinoline-4-carboxamida (example 108); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-2-methyl-6-morpholinoline-4-carboxamida (example 109); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-dimethyl-2oxo-1,3-oxazinan-3-yl)quinoline-4-carboxamida (exemplo 112); (R )-7-Chloro-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamida (Exemplo 179); (R)-8-Chloro-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamida (Exemplo 180); 6-((1 R,5S)-9-Oxa-3-azabicyclo[3.3.1 ]nonan-3-yl)-N-(2-(( R )-4cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Exemplo 194); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,4-dimethyloxazol-5-yl)quinoline-4-carboxamide (Exemplo 215);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,5-dimethylisoxazol-4-yl)-quinoline-4-carboxamide (example 216); or a pharmaceutically acceptable salt thereof.

10. Compound, according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, characterized in that R2 is a heterocycline containing a total of 4 to 10 Petition 870260082974, dated 17 / 08 / 2026, p. 15 / 77 11 / 33 ring atoms, wherein the heterocyclyl ring: (i) is a saturated, partially saturated, or completely unsaturated fused monocyclic or bicyclic ring, (ii) has one, two, or three ring nitrogen atoms, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-6-alkyl, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C3-6-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, C1-3-alkylcarbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl,phenyl-C1-3-alquila, C1-3-alkoxyphenyl-C1-3-alquila, azetidinila, pyrrolidinila, piperidinila, morpholinila, tetra-hidrofuranila, tetra-hidropyranila and tetra-hidro-oxepanila, and thus: (a) C1-6-alquila, C3-6-cycloalquila, C3-6-cycloalkyl-C1-3-alkyl, C1-6-alkóxi, C3-6-cycloalkóxi, C1-3-alkóxiC1-3-alkóxi, C1-3-alkóxi-C2-3-alkóxi, C1-3-alkóxi-C2-3-alkóxi-C1-3-alkóxi, Ci3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3alquila, C1-3-alkylsulfonyl-C1-3-alquila, phenyl, tolyla, C1-3-alkoxyphenyl, phenylC1-3-alquila, C1-3-alkoxyphenyl-C1-3-alquila, azetidinyl, pyrrolidinyl, piperidinila, morpholinila, tetra-hidrofuranila, tetra-hidropyranila and tetra-hidrooxepanila can be optionally substituted with either halogênios and (b) C1-6-alquila can be optionally substituted with either hydroxis., 11. Compound according to claim 10, or a pharmaceutically acceptable salt thereof, characterized in that the heterocyclyl ring is selected from the group consisting of: Petition 870260082974, dated 08 / 17 / 2026, p. 16 / 77 12 / 33, and wherein the heterocyclyl ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-6-alkyl, C3-6-cycloalkyl, C36-cycloalkyl-C1-3-alkyl, C1-6-alkoxy, C3-6-cycloalkoxy, C1-3-alkoxy-C1-3-alkyl, C1-3-alkoxy-C2-3-alkoxy, C1-3-alkoxy-C2-3-alkoxy-C1-3-alkyl, C1-3-alkylcarbonyl, C3-6-cycloalkylcarbonyl, C1-3-alkyl-carbonylamino-C1-3-alkyl, C1-3-alkylsulfonyl-C1-3-alkyl, phenyl, tolyl, C1-3-alkoxyphenyl, phenyl Petition 870260082974, dated 08 / 17 / 2026, p.17 / 77 13 / 33 Ci-3-alquila, Ci—3-alcoxifenil-Ci—3-alquila, azetidinila, pyrrolidinila, piperidinila, morfolinila, tetra-hidrofuranila, tetra-hidropiranila e tetra-hidrooxepanila, e em que: (a) Ci-6-alquila, C3-6-cicloalquila, C3-6-cicloalquil-Ci3-alquila, Ci-6-alkóxi, C3-6-cicloalkóxi, Ci-3-alkóxi-Ci-3-alquila, Ci-3-alkóxiC2-3-alkóxi, Ci-3-alkóxi-C2-3-alkóxi-Ci-3-alquila, Ci-3-alquilcarbonila, C3-6cicloalquilcarbonila, Ci-3-alkyl-carbonylamino-Ci-3-alquila, Ci-3-alkylsulfonyl-Ci-3-alquila, phenyl, tolyla, Ci-3-alkoxyphenyl, phenyl-Ci-3-alquila, Ci-3-alkoxyphenyl-Ci-3-alquila, azetidinila, pyrrolidinila, piperidinila, morpholinila, tetra-hidrofuranila, tetra-hydropyranyl and tetra-hydro-oxepanila can be additionally substituted with or with halogênios and (b) Ci-6-alquila can be additionally replaced with with or without hydrochlorides.

12. Compound according to claim 10, or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of: N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S,5R)-4-hydroxy-3,5-dimethylpiperidine-1-yl)quinoline-4-carboxamide (Example 7); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxypiperidine-1-yl)-quinoline-4-carboxamide (Example 8); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxopyrrolidin-1-yl)quinoline-4-carboxamide (Example 11); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2oxopyrrolidin-1-yl)quinoline-4-carboxamide (example 12); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxopiperidin1-yl)quinoline-4-carboxamide (example 14); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-2oxopiperidin-1-yl)-quinoline-4-carboxamide (example 15); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylazetidin-1-yl)-quinoline-4-carboxamide (Example 20);(R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoroazetidine-1-yl)quinoline-4-carboxamida (exemplo 21); Petition 870260082974, 17 / 08 / 2026, pág. 18 / 77 14 / 33 (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylazetidin-1-yl)-quinoline-4-carboxamida (exemplo 22); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoroazetidine-1-yl)-quinoline-4-carboxamida (Exemplo 23); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-metilazetidine-1-yl)-quinoline-4-carboxamida (Exemplo 24); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-metilazetidine-1-yl)quinoline-4-carboxamida (Exemplo 25); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethyl)azetidine-1-yl)-quinoline-4-carboxamide (Exemplo 26); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)3-methylazetidine-1-yl)quinoline-4-carboxamide (Exemplo 27); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)azetidine-1-yl)-quinoline-4-carboxamide (Exemplo 28);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(methoxymethyl)3-methyl-azetidine-1-yl)quinoline-4-carboxamide (Exemplo 29); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((2S,3R)-3-methoxy-2-methyl-azetidine-1-yl)quinoline-4-carboxamide (Exemplo 30); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3fluoroazetidine-1-yl)quinoline-4-carboxamide (Exemplo 31); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(piperidine-1yl)quinoline-4-carboxamide (Example 32); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-dimethylpiperidine-1-yl)-quinoline-4-carboxamide (Example 33); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-methylpiperidine-1-yl)quinoline-4-carboxamide (Example 34); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoropiperidine-1-yl)-quinoline-4-carboxamida (Exemplo 35); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoropiperidine-1-yl)-quinoline-4-carboxamida (Exemplo 36);Petition 870260082974, 17 / 08 / 2026, pág. 19 / 77 15 / 33 (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-(fluoromethyl)4-methyl-piperidine-1-yl)quinoline-4-carboxamida (Exemplo 37); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoro3,3-dimethyl-piperidine-1-yl)quinoline-4-carboxamida (Exemplo 38); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-(trifluoromethyl)piperidine-1-yl)-quinoline-4-carboxamida (Exemplo 39); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoropiperidine-1-yl)quinoline-4-carboxamida (Exemplo 40); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxypiperidine-1-yl)-quinoline-4-carboxamida (Exemplo 41); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-methoxy-4-methylpiperidine-1-yl)quinoline-4-carboxamida (exemplo 42); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-isopropoxypiperidine-1-yl)-quinoline-4-carboxamida (Exemplo 43);N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,4-difluoro-2methylpiperidine-1-yl)quinoline-4-carboxamida (example 44); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-2-(fluoromethyl)piperidine-1-yl)quinoline-4-carboxamida (example 45); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoropyrrolidin-1-yl)-quinoline-4-carboxamida (example 47); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethylpyrrolidin-1-yl)-quinoline-4-carboxamida (Example 48); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamida (Example 50); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-fluoropyrrolidin-1-yl)-quinoline-4-carboxamida (Example 51); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-fluoropyrrolidin-1-yl)-quinolina-4-carboxamida (Exemplo 52); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(hexahydrocyclopenta[ c ]pyrrol-2(1H)-yl)quinolina-4-carboxamida (Exemplo 53);Petition 870260082974, 17 / 08 / 2026, pág. 20 / 77 16 / 33 N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-3-methylpyrrolidin-1-yl)-quinoline-4-carboxamida (Exemplo 54); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-( (R )-3-methylpyrrolidin-1-yl)-quinoline-4-carboxamida (exemplo 55); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-2-(trifluoromethyl)pyrrolidin-1-yl)quinoline-4-carboxamida (Exemplo 56); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2,2-dimethylpyrrolidin-1-yl)-quinoline-4-carboxamida (Exemplo 57); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-fluoroazepan-1-yl)quinoline-4-carboxamida (Exemplo 59); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-fluoroazepan-1-yl)quinoline-4-carboxamide (Exemplo 60); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-methylpyrrolidin-1-yl)-quinoline-4-carboxamide (Exemplo 65); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-metoxiazetidine-1-yl)quinoline-4-carboxamide (Exemplo 66);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(fluoromethyl)azetidine-1-yl)-quinoline-4-carboxamida (Exemplo 113); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,5,6,7-tetrahidro-1H-indazol-1-yl)quinoline-4-carboxamida (Exemplo 114); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,5,6,7-tetrahidro-2H-indazol-2-yl)quinoline-4-carboxamida (Exemplo 115); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)quinoline-4-carboxamida (Exemplo 116); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-dimethyl-5,6dihidrocyclopenta[ c ]pyrazol-2(4H)-yl)quinoline-4-carboxamida (exemplo 117); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethyl)-1H-pyrazol-1-yl)quinoline-4-carboxamida (exemplo 118); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,6-difluoro-1H Request 870260082974, dated 17 / 08 / 2026, pág. 21 / 77 17 / 33 indole-1-yl)-quinolina-4-carboxamida (Exemplo 119);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-fluoro-1H-indol-1-yl)quinoline-4-carboxamida (Exemplo 120); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-1H-pyrrol-1-yl)-quinoline-4-carboxamida (Exemplo 121); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-morfolinazetidin-1-yl)-quinoline-4-carboxamida (Exemplo 122); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-dimethyl-5,6dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-4-carboxamide (Example 123); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-fluoropyridin4-yl)quinoline-4-carboxamide (Example 124); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-fluoropyridin2-yl)quinoline-4-carboxamide (Example 125); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(pyridine-3-yl)quinoline-4-carboxamida (exemplo 126); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(pyrimidine-5yl)quinoline-4-carboxamida (Exemplo 127); R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-methylpyridin-3yl)quinoline-4-carboxamida (Exemplo 128);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-methyl-1H-pyrazol-4-yl)-quinoline-4-carboxamida (Exemplo 129); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-((trifluoromethoxy)methyl)-azetidin-1-yl)quinoline-4-carboxamida (Exemplo 130); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-3(2,2,2-trifluoroethyl)-azetidin-1-yl)quinoline-4-carboxamida (Exemplo 131); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(trifluoromethoxy)azetidine-1-yl)quinoline-4-carboxamida (Exemplo 132); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoroethyl)-3-methyl-azetidine-1-yl)quinoline-4-carboxamida (exemplo 133); Petition 870260082974, 17 / 08 / 2026, pág. 22 / 77 18 / 33 (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropyl-3methylazetidin-1-yl)quinoline-4-carboxamide (Exemplo 134); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethyl)-3-methyl-azetidin-1-yl)quinoline-4-carboxamide (Exemplo 135);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(difluoromethoxy)azetidine-1-yl)-quinoline-4-carboxamida (Exemplo 136); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-methylazetidin-1-yl)-quinoline-4-carboxamida (Exemplo 137); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-fluoroazetidine-1-yl)-quinoline-4-carboxamida (Exemplo 138); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoropropyl)azetidine-1-yl)quinoline-4-carboxamide (Exemplo 140); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(3,3,3-trifluoropropyl)azetidine-1-yl)quinoline-4-carboxamide (Exemplo 142); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(trifluoromethyl)-azetidine-1-yl)quinoline-4-carboxamide (Exemplo 143); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2-difluoroethyl)azetidin-1-yl)-quinoline-4-carboxamida (Exemplo 144); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-cyclopropylazetidin-1-yl)-quinoline-4-carboxamida (Exemplo 145);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2-fluoroethyl)azetidine-1-yl)-quinoline-4-carboxamide (Example 146); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(1, 1 -difluoroethyl)azetidine-1-yl)-quinoline-4-carboxamide (Example 147); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-isopropylazetidin-1-yl)quinoline-4-carboxamide (example 148); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methoxy-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 151); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethoxy-3-methylazetidin-1-yl)-quinoline-4-carboxamide (Example 152); Petition 870260082974, dated 08 / 17 / 2026, p. 23 / 77 19 / 33 (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-ethyl-3-hydroxyazetidin-1-yl)-quinoline-4-carboxamide (Example 154); 6-(6-Azabicyclo[3.2.0]heptane-6-yl)-N-(2-(( R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamide (Example 156);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-(fluoromethyl)azetidine-1-yl)quinoline-4-carboxamida (Exemplo 157); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(2,2,2-trifluoroethyl)azetidine-1-yl)quinoline-4-carboxamida (Exemplo 158); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-difluoro-2metilazetidine-1-yl)quinoline-4-carboxamida (Exemplo 159); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6,6-difluoro-3azabicyclo[3.1.0]hexan-3-yl)quinolina-4-carboxamida (Exemplo 160); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-methoxypyrrolidin-1-yl)-quinolina-4-carboxamida (Exemplo 161); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-hydroxy-3-methylazetidine-1-yl)-quinolina-4-carboxamida (Exemplo 165); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-hydroxy-3methylpyrrolidin-1-yl)quinolina-4-carboxamida (example 167); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-3-hydroxy-3methylpyrrolidin-1-yl)quinolina-4-carboxamida (example 168);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(difluoromethyl)pyridin-3-yl)-quinoline-4-carboxamida (Exemplo 169); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-cyclopropyl1H-pyrazol-4-yl)-quinoline-4-carboxamida (Exemplo 170); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,3-dimethyl-1H-pyrazol-4-yl)-quinoline-4-carboxamida (Exemplo 171); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,5-dimethyl-1(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)quinoline-4-carboxamida (exemplo 172); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-(tetrahidroPetição 870260082974, de 17 / 08 / 2026, pág. 24 / 77 20 / 33 2H-piran-4-il)-1 H-pyrazol-4-yl)quinoline-4-carboxamida (Exemplo 173); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-methyl-1H-pyrazol-5-yl)-quinoline-4-carboxamida (Exemplo 174); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,6,7,8-tetrahidroimidazo[1,2-a]-pyridin-3-yl)quinoline-4-carboxamida (Exemplo 175);N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-(tetrahidro2H-pyran-2-yl)-1H-pyrazol-5-yl)quinoline-4-carboxamida (Exemplo 176); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methylpyridin-3yl)quinoline-4-carboxamida (Exemplo 177); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methoxipyridin3-yl)quinoline-4-carboxamida (Exemplo 178); (R)-6-(3-(acetamidomethyl)-3-methylazetidin-1-yl)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamide (Exemplo 181); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-fluoro-3-phenylazetidin-1-yl)-quinoline-4-carboxamide (Exemplo 182); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(p-tolyl)azetidine-1-yl)quinoline-4-carboxamide (Exemplo 183); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(4-fluorophenyl)azetidine-1-yl)-quinoline-4-carboxamida (Exemplo 185); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-(m-tolyl)azetidine-1-yl)quinoline-4-carboxamida (Exemplo 186);(R)-6-(3-(4-chlorobenzyl)azetidine-1-yl)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamida (Exemplo 187); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-methyl-3-((methylsulfonyl)-methyl)azetidine-1-yl)quinoline-4-carboxamida (Exemplo 188); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-hydroxypiperidine-1-yl)-quinoline-4-carboxamida (Exemplo 189); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hidroxy-4-methylpiperidine-1-yl)quinoline-4-carboxamida (exemplo 190); Petition 870260082974, 17 / 08 / 2026, pág. 25 / 77 21 / 33 (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-ethyl-4-methoxypiperidine-1-yl)-quinoline-4-carboxamida (Exemplo 191); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-hidroxy-4-isopropylpiperidin-1-yl)quinoline-4-carboxamida (Exemplo 192); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R,4S,5S)-4hidroxi-3,4,5-trimethylpiperidine-1-yl)quinoline-4-carboxamida (Exemplo 193);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-1-methylpiperidine-4-yl)-quinoline-4-carboxamida (Exemplo 195); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1H-pyrazol-5yl)quinoline-4-carboxamida (Exemplo 196); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-isopropyl-1Hpyrazol-5-yl)-quinoline-4-carboxamida (Exemplo 197); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( RS )-3-fluoro3-methylpyrrolidin-1-yl)quinoline-4-carboxamide (Example 198); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-2-cyclopropylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 199); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-2-cyclopropylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 200); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-3-methyl-2oxopyrrolidin-1-yl)quinoline-4-carboxamida Isomer 1 (Exemplo 201);N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-3-methyl-2oxopyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 202); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-3-methyl-2oxopiperidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 203); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( R *)-3-methyl-2oxopiperidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 204); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoropiperidine-1-yl)quinoline-4-carboxamide (Example 205); 6-(3-Azabiciclo[3.1.0]hexane-3-yl)-N-(2-(( R )-4-cyanothiazolidin Petition 870260082974, dated 17 / 08 / 2026, p. 26 / 77 22 / 33 3-yl)-2-oxoethyl)-quinoline-4-carboxamide (Example 206); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( S )-3-methoxypyrrolidin-1-yl)-quinoline-4-carboxamide (Example 207); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((1R,5S,6R)-6(trifluoromethyl)-3-azabicyclo[3.1.0]hexane-3-yl)quinoline-4-carboxamide (example 208);(R )-6-(7-Azabicyclo[2.2.1 ]heptane-7-yl)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamida (Exemplo 209); 6-(2-Azabicyclo[2.2.1]heptane-2-yl)-N-(2-(( R )-4-cyanothiazolidin-3-yl)-2-oxoethyl)-quinoline-4-carboxamida (Exemplo 210); N-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-methylpyrrolidin-1-yl)-quinoline-4-carboxamida (Exemplo 211); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-2-(methoxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 212); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3S,4S)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 213); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R,4R)-3,4-difluoropyrrolidin-1-yl)quinoline-4-carboxamide (Exemplo 214); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-phenyl-1H-imidazol-1-yl)-quinoline-4-carboxamida (Example 217); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-phenyl-1H-pyrrol-1-yl)-quinoline-4-carboxamida (Example 218);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4,5,6,7-tetrahydro-1H-indol-1-yl)quinoline-4-carboxamide (Example 219); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (example 220); N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((S)-3-(hydroxymethyl)pyrrolidin-1-yl)quinoline-4-carboxamide (Example 221); (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-fluoro-4-phenylpiperidine-1-yl)-quinoline-4-carboxamide (Example 223); Petition 870260082974, dated 17 / 08 / 2026, page 27 / 77 23 / 33 N-(2-( (R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(( RS )-3,3-difluoro-4-hydroxy-pyrrolidin-1-yl)quinoline-4-carboxamide (Example 224); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R*,4R*)-3,4dimethylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 1 (Example 225); N-(2-(( R )-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((3R*,4R*)-3,4dimethylpyrrolidin-1-yl)quinoline-4-carboxamide Isomer 2 (Example 226);(R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(4-oxopiperidine-1-yl)quinoline-4-carboxamide (example 230); or a pharmaceutically acceptable salt thereof.

13. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, characterized in that R2 is a spiro-heterocyclyl containing a total of 6 to 11 ring atoms, wherein the spiro-heterocyclyl: (i) comprises two saturated rings, (ii) has: (a) one or two ring nitrogen atoms, with the remaining ring atoms being carbon, (b) one or two ring nitrogen atoms and one or two ring oxygen atoms, with the remaining ring atoms being carbon, or (c) one ring nitrogen atom and one ring sulfur atom, with the remaining ring atoms being carbon, and (iii) is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy and C1-6-alkylcarbonyl.

14. Compound according to claim 13, or a pharmaceutically acceptable salt thereof, characterized in that the two saturated rings are selected from the group consisting of: Petition 870260082974, dated 17 / 08 / 2026, p. 28 / 77 24 / 33, and J wherein one or both rings are optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, and C1-6-alkylcarbonyl.

15. Compound according to claim 13, or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of: (R)-N-(2-(4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-azaspiro[3.3]heptan-2-yl)quinoline-4-carboxamide (Example 17); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3,3-dimethyl-1-oxa-6-azaspiro[3.3]heptan-6-yl)quinoline-4-carboxamide (Example 18); Petition 870260082974, dated 17 / 08 / 2026, p. 29 / 77 25 / 33 (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-azaspiro[3.3]heptan-1-yl)quinoline-4-carboxamide (Example 19); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-azaspiro[2.5]octan-5-yl)quinoline-4-carboxamide (Example 46); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-azaspiro[2.4]heptan-5-yl)quinoline-4-carboxamide (Example 49); N-(2-((R)-4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-6-(fluoromethyl)-5-azaspiro[2.4]heptan-5-yl)quinolina-4-carboxamida (Exemplo 58); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,9-dioxa-4azaspiro[5.5]undecan-4-yl)quinolina-4-carboxamida (Exemplo 99); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(8-oxa-5-azaspiro[3.5]nonan-5-yl)quinolina-4-carboxamida (Exemplo 104); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxo-1-oxa-3azaspiro[5.5]undecan-3-yl)quinolina-4-carboxamida (Exemplo 110); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(7-oxo-6-oxa-8azaspiro[4.5]decan-8-yl)quinolina-4-carboxamida (Exemplo 111); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-azaspiro[3.4]octan-2-yl)quinolina-4-carboxamida (Exemplo 139); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,5-difluoro-2azaspiro[3.4]octan-2-yl)quinolina-4-carboxamida (Exemplo 141); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-methyl-2-azaspiro[3.3]heptan-2-yl)quinolina-4-carboxamida (Exemplo 149); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-(trifluoromethyl)-2-azaspiro[3.3]heptan-2-yl)quinolina-4-carboxamida (Exemplo 150); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-oxa-6-azaspiro[3.3]heptan-6-yl)quinolina-4-carboxamida (Exemplo 153); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(6-fluoro-2-azaspiro[3.3]heptan-2-yl)quinolina-4-carboxamida (Exemplo 155); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(3-oxa-9-azaspiro[5.5]undecan-9-yl)quinoline-4-carboxamida (Exemplo 162); Petition 870260082974, 17 / 08 / 2026, pág. 30 / 77 26 / 33 (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5,8-dioxa-2azaspiro[3.4]octan-2-yl)quinoline-4-carboxamida (Exemplo 163); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(5-azaspiro[2.3]hexan-5-yl)quinolina-4-carboxamida (Exemplo 164); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)quinolina-4-carboxamida (Exemplo 166); (R)-6-(6-Acetyl-2,6-diazaspiro[3.3]heptan-2-yl)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)quinoline-4-carboxamida (Exemplo 184); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1-thia-6-azaspiro[3.3]heptan-6-yl)quinoline-4-carboxamida (Exemplo 222); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,5-dioxa-9azaspiro[5.5]undecan-9-yl)quinoline-4-carboxamida (Exemplo 227); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(1,4-dioxa-8azaspiro[4.5]decan-8-yl)quinoline-4-carboxamida (Exemplo 228); (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-(2-oxa-7-azaspiro[3.5]nonan-7-yl)quinoline-4-carboxamida (Exemplo 229); or a sal pharmaceutically aceitável do mesmo.

16. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (V): or a pharmaceutically acceptable salt thereof, wherein: R1, R3, R4, R5 and R6 are independently selected from Petition 870260082974, dated 17 / 08 / 2026, p.31 / 77 27 / 33 group consisting of hydrogen, chlorine, fluorine and methyl; R20a and R20b are independently selected from the group consisting of hydrogen and C1-3-alkyl; R20c and R20d are independently selected from the group consisting of hydrogen, fluorine, hydroxyl, C1-3-alkyl, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-3-alkoxy, C3-6-cycloalkoxy, C1-3-alkoxy-C1-3alkyl, phenyl, tolyl, phenyl-C1-3-alkyl, morpholinyl, C1-3-alkylsulfonyl-C1-3alkyl and C1-3-alkyl-carbonylamino-C1-3-alkyl; and wherein C1-3-alkyl, C36-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, C1-3-alkoxy, C3-6-cycloalkoxy, C13-alkoxy-C1-3-alkyl, phenyl and phenyl-C1-3-alkyl may be additionally substituted with one or more halogens; and R20e and R20f are independently selected from the group consisting of hydrogen and C1-3-alkyl.

17. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (VI): or a pharmaceutically acceptable salt thereof, wherein: R1, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine and methyl; R30a and R30b are independently selected from the group consisting of hydrogen, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy-C13-alkyl; R30c and R30d are independently selected from the group consisting of hydrogen, halogen, C1-3-alkyl, halo-C1-3-alkyl, C1-3-alkyl. Petition 870260082974, dated 17 / 08 / 2026, page 1.32 / 77 28 / 33 3-alkoxy-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl; R30e and R30f are independently selected from the group consisting of hydrogen, halogen, C1-3-alkyl, halo-C1-3-alkyl, C1-3-alkoxy-C1-3-alkyl and C1-3-alkylsulfonyl-C1-3-alkyl; and R30g and R30h are independently selected from the group consisting of hydrogen, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy-C13-alkyl.

18. Compound according to claim 17, or a pharmaceutically acceptable salt thereof, characterized in that R1, R3, R4, R5 and R6 are all hydrogen.

19. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (VII): or a pharmaceutically acceptable salt thereof, wherein: R1, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine and methyl; R40a and R40b are independently selected from the group consisting of hydrogen, C1-3-alkyl and halo-C1-3-alkyl; R40c and R40d are independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; R40e and R40f are independently selected from the group consisting of hydrogen, fluorine, hydroxy, oxo, C1-3-alkyl, halo-C1-3-alkyl, cyclopropyl and C1-3-alkoxy; Petition 870260082974, dated 08 / 17 / 2026, page.33 / 77 29 / 33 R40g and R40h are independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; and R40i and R40j are independently selected from the group consisting of hydrogen, C1-3-alkyl and halo-C1-3-alkyl.

20. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (VIII): or a pharmaceutically acceptable salt thereof, wherein: R1, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine and methyl; R50a and R50b are independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; R50c and R50d are independently selected from the group consisting of hydrogen, C1-3-alkyl and halo-C1-3-alkyl, or together are oxo; R50e is selected from the group consisting of hydrogen, C1-3-alkyl, halo-C1-3-alkyl, C1-3-alkoxy-C2-3-alkyl, C1-3-alkyl-carbonyl and C3-6-cycloalkyl-carbonyl; R50f and R50g are independently selected from the group Petition 870260082974, dated 17 / 08 / 2026, page.34 / 77 30 / 33 consisting of hydrogen, C1-3-alkyl and halo-C1-3-alkyl, or together are oxo; R50h and R50i are independently selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; and R50j is selected from the group consisting of hydrogen and fluorine.

21. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (IX): or a pharmaceutically acceptable salt thereof, wherein: R1, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine and methyl; R60a and R60b are independently selected from the group consisting of hydrogen and C1-3-alkyl; R60c and R60d are independently selected from the group consisting of hydrogen and C1-3-alkyl; and R60e and R60f are independently selected from the group consisting of hydrogen and C1-3-alkyl.

22. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (X): Petition 870260082974, 17 / 08 / 2026, p. 35 / 77 31 / 33 or a pharmaceutically acceptable salt thereof, wherein: R1, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine and methyl; R70a and R70b are independently selected from the group consisting of hydrogen and C1-3-alkyl; R70c and R70d are independently selected from the group consisting of hydrogen and C1-3-alkyl; R70e and R70f are independently selected from the group consisting of hydrogen and C1-3-alkyl; R70g and R70h are independently selected from the group consisting of hydrogen and C1-3-alkyl.

23. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound has the structure of Formula (XI): NO (XI), or a pharmaceutically acceptable salt thereof, wherein: Petition 870260082974, dated 17 / 08 / 2026, page 36 / 77 32 / 33 R1, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, chlorine, fluorine and methyl; Rsoa is selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; R80b is selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; R80c is selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy; and R80d is selected from the group consisting of hydrogen, fluorine, C1-3-alkyl, halo-C1-3-alkyl and C1-3-alkoxy.

24. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that it is N-(2-((R)-4-Cyanothiazolidin-3-yl)-2-oxoethyl)-6-((R)-2-(fluoromethyl)morpholino)quinoline-4-carboxamide having the structure: or a pharmaceutically acceptable salt thereof.

25. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that it is (R)-N-(2-(4-cyanothiazolidin-3-yl)-2-oxoethyl)-6-morpholinoquinoline-4-carboxamide having the structure: or a pharmaceutically acceptable salt thereof. Petition 870260082974, dated 17 / 08 / 2026, p. 37 / 77 33 / 33 26. Pharmaceutical composition, characterized in that it comprises a compound, as defined in any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

27. Use of a compound as defined in any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, or of the composition as defined in claim 26, characterized in that it is for the manufacture of a medicament for the treatment or prevention of a FAP-mediated condition in an individual suffering from or susceptible to the FAP-mediated condition.

28. Use according to claim 27, characterized in that the FAP-mediated condition is selected from the group consisting of liver disease, type 2 diabetes mellitus, cardiovascular conditions, obesity, obesity-related conditions, fibrosis, keloid formation, inflammation, and cancer.

29. Use according to claim 28, characterized in that the FAP-mediated condition is liver disease.

30. Use, according to claim 29, characterized in that the liver disease is non-alcoholic fatty liver disease (NAFLD), optionally wherein the NAFLD is selected from isolated steatosis, non-alcoholic steatohepatitis (NASH), hepatic fibrosis and cirrhosis.

31. Use, according to claim 29, characterized in that the liver disease is non-alcoholic steatohepatitis.

32. Combination, characterized by comprising a compound as defined in any one of claims 1 to 25, and at least one additional pharmacological agent.

33. Kit, characterized by comprising a unit dosage form comprising a compound as defined in any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, packaging material, and a label or package insert.