Compound, e, pharmaceutical composition for the prevention or treatment of movement disorder

Description

62 PHARMACEUTICAL COMPOUND AND COMPOSITION FOR THE PREVENTION OR TREATMENT OF MOVEMENT DISORDERS TECHNICAL FIELD

[001] A dual antagonist of mGluR5 and HDAC6 and its use are described. More specifically, a compound that acts as an antagonist of both mGluR5 and HDAC6 is described, and its use as a therapeutic agent for movement disorders is described. FUNDAMENTALS OF THE TECHNIQUE

[002] Movement disorders are a group of conditions that affect the ability to produce and control body movements and are often associated with neurological disorders or conditions associated with neurological dysfunction. Movement disorders may manifest as abnormal proficiency or speed of movements, excessive or involuntary movements, or slowness or absence of voluntary movements.

[003] Movement disorders are frequently caused by impaired regulation of dopaminergic neurotransmission. Parkinson's disease (PD) is an example of a movement disorder associated with dysfunction in the regulation of dopaminergic neurotransmission caused by the progressive degeneration of dopaminergic neurons. Tardive dyskinesia is another example of a movement disorder associated with dysfunction in the regulation of dopaminergic neurotransmission.

[004] To replace lost dopamine, PD is currently treated with, for example, levodopa (L-DOPA, a precursor of dopamine). Unfortunately, treatment of PD with L-DOPA usually results in a specific form of dyskinesia called L-DOPA-induced dyskinesia (LID), which is caused in part by excessive levels of dopamine in the synapse.

[005] Glutamate receptors are broadly divided into ionotropic glutamate receptors (iGluR) and metabotropic receptors. Petition 870250084318, dated 09 / 18 / 2025, page 10 / 79 / 62 glutamate (mGluR). Among them, the metabotropic glutamate receptor is a type of G protein-coupled receptor (GPCR) and is classified into three groups — I, II, and III, according to the characteristics of the signal transduction process. Group I is composed of mGluR1 and mGluR5 and acts as postsynaptic receptors involved in increasing neuronal excitability.

[006] Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues of histone proteins that make up chromatin. In humans, 18 HDACs are known and classified into Class I (HDAC1, 2, 3, 8), Class II (IIa: HDAC4, 5, 7, 9; IIb: HDAC6, 10), Class III (SIRT 1-7), and Class IV (HDAC11). HDAC6—which is one of the Class IIb HDACs—exists primarily in the cytoplasm and plays an important role in the microtubule network, regulating the balance of tubulin acetylation and deacetylation, as well as histones. DESCRIPTION OF THE INVENTION TECHNICAL PROBLEM

[007] One objective of the present invention is to provide a compound that modulates mGluR5 and HDAC6 simultaneously.

[008] Another objective of the present invention is to provide the use of said compound for the prevention or treatment of movement disorders. SOLUTION TO THE PROBLEM

[009] To achieve the above objective, a compound of the following Formula 1 or a pharmaceutically acceptable salt thereof is provided: [Formula 1] In Formula 1, Ar, Ri, R2, X1, X2, X3, Y1, Y2, Y3 and are the same as those defined here.

[0010] In addition, a pharmaceutical composition is provided for the Petition 870250084318, dated 09 / 18 / 2025, page 11 / 79 3 / 62 prevention or treatment of movement disorders, comprising a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof as the active ingredient, together with a pharmaceutically acceptable vehicle or excipient.

[0011] In addition, a method is provided for treating movement disorders, comprising administering to a mammal the compound of Formula 1 or a pharmaceutically acceptable salt thereof.

[0012] In addition, the use of the compound of Formula 1 or a pharmaceutically acceptable salt thereof is provided for in the prevention or treatment of movement disorders. EFFECTS OF THE INVENTION

[0013] The compound of formula 1 or a pharmaceutically acceptable salt thereof according to the present invention acts as a dual antagonist of mGluR5 and HDAC6. The dual antagonism against mGluR5 and HDAC6 may have synergistic effects in the prevention or treatment of movement disorders. Due to these properties, the compound of Formula 1 or a pharmaceutically acceptable salt thereof may exhibit preventive or therapeutic effects in movement disorders without specific side effects, even at low doses. METHOD FOR THE INVENTION

[0014] The present invention is described in detail below.

[0015] According to one aspect of the present invention, a compound of the following Formula 1 or a pharmaceutically acceptable salt thereof is provided: [Formula 1] in Formula 1, Petition 870250084318, dated 09 / 18 / 2025, page 12 / 79 / 62 Ar is aryl or heteroaryl, wherein aryl and heteroaryl are optionally replaced by one or more substituents selected from the group consisting of halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy and alkylsulfonyl; Ri is alkyl or haloalkyl; R2 is H or alkyl; One of Xi, X2, and X3 is C, and the others are N; Y1, Y2, and Y3 are each independently CR3 or N; where R3 is H, halo, or alkyl; n is an integer from 0 to 2; and the heteroaryl group has one or more heteroatoms selected from N, O, and S.

[0016] Here, the following concepts defined for substituents are used to define the Formula 1 compound.

[0017] As used herein, the term “halo” or halogen, alone or in combination with additional terms (e.g., haloalkyl or haloalkoxy), refers to a fluorine (F), chlorine (Cl), bromine (Br), or iodine (I) radical.

[0018] As used herein, the term “cyan” refers to -CN.

[0019] As used herein, the term “sulfonyl” refers to -S(=O)2-.

[0020] As used herein, the term “alkyl”, alone or in combination with additional terms (e.g., haloalkyl), refers to a radical of a saturated aliphatic hydrocarbon group having, for example, 1 to 7 carbon atoms in a linear or branched chain. Representative examples of alkyl may include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl and the like.

[0021] As used herein, the term “alkoxy” refers to alkyloxy (Petition 870250084318, dated 09 / 18 / 2025, p. 13 / 79 / 62) O-alkyl) having, for example, 1 to 7 carbon atoms.

[0022] As used herein, the term “aryl” refers to an aromatic hydrocarbon group having, for example, 6 to 10 carbon atoms. For example, aryl may include phenyl and naphthyl, but is not limited to them.

[0023] As used herein, the term “heteroaryl” refers, for example, to 5- to 10-membered aromatic hydrocarbons that include one or more heteroatoms selected from N, O, and S as a ring member.

[0024] According to one embodiment of the present invention, in Formula 1 above, Ar is a 5- to 10-membered C6-C10 aryl or heteroaryl group, wherein aryl and heteroaryl groups are optionally substituted by one or more substituents selected from the group consisting of halo, cyano, C1-C7 alkyl, C1-C7 halo-alkyl, C1-C7 alkoxy, C1-C7 halo-alkoxy and C1-C7 alkylsulfonyl; R1 is C1-C7 alkyl or C1-C7 haloalkyl; R2 is H or C1-C7 alkyl; One of X1, X2, and X3 is C, and the others are N; Y1, Y2, and Y3 are each independently CR3 or N; where R3 is H, halo, or C1-C7 alkyl; n is an integer between 1 and 2; and the heteroaryl group has 1 to 3 heteroatoms selected from N, O, and S.

[0025] According to another embodiment of the present invention, X1 can be C and X2 and X3 can be N. At this point, Formula 1 above can be represented by the following Formula 2: [Formula 2] In Formula 2, Ar, R1, R2, Y1, Y2, and Y3 are defined the same way. Petition 870250084318, dated 09 / 18 / 2025, p. 14 / 79 / 62 in Formula 1, en can be an integer from 0 to 2, specifically 1 or 2, and more specifically 1.

[0026] According to another embodiment of the present invention, X2 can be C and Xi and X3 can be N. At this point, Formula 1 above can be represented by the following Formula 3: [Formula 3] R1 In Formula 3, Ar, R1, R2, Y1, Y2, and Y3 are the same as defined in Formula 1, and can be an integer from 0 to 2, specifically 1 or 2. 2, and more specifically 1.

[0027] According to another embodiment of the present invention, aryl may be phenyl; and heteroaryl may be pyridyl, thienyl, imidazolyl or benzothiazolyl.

[0028] According to another embodiment of the present invention, Ar can be phenyl or pyridyl. At this point, Formula 1 above can be represented by the following Formula 4: [Formula 4] In Formula 4, Z is CH or N; R4 is halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, or alkylsulfonyl; m is an integer from 0 to 3; R1, R2, X1, X2, X3, Y1, Y2, Y3, and n are the same as defined in Formula 1.

[0029] According to another embodiment of the present invention, all Y1, Y2 and Y3 can be CR3. According to another embodiment of the present invention, R3 can be H. Petition 870250084318, dated 09 / 18 / 2025, page 15 / 79 / 62

[0030] In any of Formulas 1 to 4, Ri can be C1 haloalkyl and, more specifically, Ri can be CF2H or CF3.

[0031] According to another embodiment of the present invention, representative examples of the Formula 1 compound may include, but are not limited to, the following compounds: 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-phenylprop-2-yn1-yl)pyridin-2(1H)-one; 1-(3-phenylprop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol3-yl)pyridin-2(1H)-one; 1-(3-(pyridin-4-yl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1-(3-(pyridin-3-yl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1-(3-(pyridin-2-yl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; -(3-(2-fluorophenyl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridine-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-4yl)prop-2-yl-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-3yl)prop-2-in-1-yl)pyridin-2(1H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-2yl)prop-2-yl-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(4fluorophenyl)prop-2-yl-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3fluorophenyl)prop-2-yl-1-yl)pyridin-2(1H)-one; Petition 870250084318, 18 / 09 / 2025, pág. 16 / 79 / 62 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2fluorophenyl)prop-2-yl-1 -yl)pyridin-2( 1 H)-one; 1-(3-(4-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2(1H)-one; -(3-(2-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(p-tolyl)prop-2in-1 -yl)pyridin-2( 1 H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(m-tolyl)prop-2in-1 -yl)pyridin-2( 1 H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethyl)phenyl)prop-2-yl-1 -yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethoxy)phenyl)prop-2-yl-1 -yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3methoxyphenyl)prop-2-yl-1 -yl)pyridin-2(1H)-one; 1-(3-(6-chloropyridin-2-yl)prop-2-yl-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2( 1 H)-one; -(3-(2-chloropyridin-4-yl)prop-2-in- 1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(6-methylpyridin2-yl)prop-2-yl-1 -yl)pyridin-2(1H)-one; 1-(3-(3-bromophenyl)prop-2-yl-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(difluoromethyl)phenyl)prop-2-yl-1 -yl)pyridin-2( 1H)-one; 1-(3-(3-(difluoromethoxy)phenyl)prop-2-in-1-yl)-4-(5Petição 870250084318, de 18 / 09 / 2025, pág. 17 / 79 / 62 (difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-ona; 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(5-methylpyridin3-yl)prop-2-yl-1 -yl)pyridin-2( 1 H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 3-(3-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-2-oxopyridin1 (2H)-yl)prop- 1-in-1 -yl)benzonitrile; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(methylsulfonyl)phenyl)prop-2-ylene-1-yl)pyridin-2(1H)-one; -(3-(3-chloro-2-fluorophenyl)prop-2-in-1 -yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chloro-4-fluorophenyl)prop-2-yl-1 -yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chloro-5-fluorophenyl)prop-2-in-1 -yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(5-chloro-2-fluorophenyl)prop-2-yl-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 2-(3-(3-chlorophenyl)prop-2-yn-1-yl)-5-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridazin-3(2H)-one; 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyrimidin-2(1H)-one; 3-(3-(3-chlorophenyl)prop-2-yn-1-yl)-6-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyrimidin-4(3H)-one; 1-(3-(benzo]thiazol-5-yl)prop-2-yl-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2methylbenzo[ d ]thiazol-6-yl)prop-2-yl-1 -yl)pyridin-2( 1H)-one; Petition 870250084318, 18 / 09 / 2025, pág. 18 / 79 / 62 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2-methyl-1Himidazol-5-yl)prop-2-yl-1 -yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(thiophen-3yl)prop-2-in-1 -yl)pyridin-2(1H)-ona; 1-(1 -(3-chlorophenyl)pent-1 -yn-3-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-6-methylpyridin-2(1H)-one; and 5-bromo-1 -(3-(3-chlorophenyl)prop-2-yl-1 -yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one.

[0032] According to another method of this invention, more specific examples of the compounds of Formula 1 may include the following compounds: 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(p-tolyl)prop-2yn-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(m-tolyl)prop-2in-1-yl)pyridin-2(1H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethyl)phenyl)prop-2-yl-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethoxy)phenyl)prop-2-yl-1-yl)pyridin-2(1H)-one; 1-(3-(2-chloropyridin-4-yl)prop-2-yl-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(6-methylpyridin2-yl)prop-2-yl-1-yl)pyridin-2(1H)-one; Petition 870250084318, 18 / 09 / 2025, pág. 19 / 79 / 62 1-(3-(3-bromophenyl)prop-2-yl-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 1-(3-(3-(difluoromethoxy)phenyl)prop-2-yl-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 3-(3-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-2-oxopyridin1 (2H)-yl)prop- 1-in-1 -yl)benzonitrile; -(3-(5-chloro-2-fluorophenyl)prop-2-in-1 -yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(1 -(3-chlorophenyl)pent-1 -yn-3-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; and -(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-6-methylpyridin-2(1H)-one. Preparation methods

[0033] The compound of Formula 1 according to one embodiment can be prepared by anyone with common knowledge of compound synthesis in this technical field using known compounds or compounds that can be easily prepared from them. For example, the compound of Formula 1 can be synthesized according to the methods of Reaction Schemes 1 to 3 below, but this presents only an exemplary method and the order of unit operations can be selectively altered as required. This is not intended to limit the scope of the invention. Petition 870250084318, dated 09 / 18 / 2025, p. 20 / 79 / 62 [Reaction Scheme 1]

[0034] In Reaction Scheme 1, X is a leaving group, such as mesylate (MsO). Intermediate 3 can be prepared, for example, as shown in Reaction Scheme 1' below. [Reaction Scheme 1'] 12

[0035] Intermediate 10 or 12 is obtained from each ester- or cyano-containing starting material by the addition of hydrazine or hydroxylamine, and then Intermediate 3 is obtained by means of a cyclization reaction by the addition of trifluoroacetic anhydride. If necessary, Intermediate 5 containing acetylene can also be obtained by an additional nucleophilic addition reaction. [Reaction Scheme 2] oo

[0036] In Reaction Scheme 2, Compound 1 can be obtained from acetylene Intermediate 5 and a halogen-containing reagent via Sonogashira coupling. Intermediate 5 can be prepared by various methods, including Scheme 1' above or Scheme Petition 870250084318, dated 09 / 18 / 2025, page 21 / 79 / 62 2 minutes below. [Reaction Scheme 2']

[0037] Acetylene-containing intermediate 13 is obtained from cyano-containing starting material 11 via a nucleophilic addition reaction, and then hydroxylamine is added to obtain intermediate 14. Then, intermediate 5 can be obtained via a cyclization reaction with the addition of trifluoroacetic anhydride. [Reaction Scheme 3]

[0038] Acetylene-containing Intermediate 7 is obtained from ester-containing starting material 6 via a nucleophilic addition reaction, and Intermediate 8 is obtained via Sonogashira coupling. Consequently, intermediate compound 9 is obtained by the addition of hydrazine, and then compound 1 can be obtained via a cyclization reaction by the addition of trifluoroacetic anhydride. Pharmaceutical Composition

[0039] According to another aspect of the present invention, a pharmaceutical composition is provided for the prevention or treatment of movement disorders, comprising a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof as Petition 870250084318, dated 09 / 18 / 2025, page 22 / 79 / 62 active ingredient, together with a pharmaceutically acceptable vehicle or excipient.

[0040] The pharmaceutical composition can be formulated in various oral or parenteral dosage forms. For example, the pharmaceutical composition can be formulated in any dosage form for oral administration, such as tablets, pills, hard / soft capsules, solutions, suspensions, emulsifiers, syrups, granules, or elixirs.

[0041] When the pharmaceutical composition is formulated in a parenteral dosage form, the pharmaceutical composition may be administered by a parenteral administration method such as subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. The pharmaceutical composition may be prepared as a solution or a suspension by mixing an active ingredient—that is, the compound of Formula 1 or a pharmaceutically acceptable salt thereof—with a stabilizer or buffer in water, and the solution or suspension may be prepared as a unit dosage form in an ampoule or vial. Medical Utility

[0042] According to another aspect of the present invention, a method is provided for preventing or treating movement disorders in a subject, comprising administering to the subject in need a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof. The movement disorder may include, for example, Huntington's disease, Parkinson's disease and levodopa-induced dyskinesia (LID), but is not limited to them.

[0043] The symptoms of Parkinson's disease appear when ionotropic glutamate receptors (iGlu) and metabotropic glutamate receptors (mGlu)—glutamate is an excitatory neurotransmitter in the brain—are activated. Among them, the metabotropic glutamate receptor 5 Petition 870250084318, dated 09 / 18 / 2025, page 23 / 79 / 62 (mGluR5) is expressed primarily on postsynaptic cell membranes (Shigemoto et al., 1997), and is also found on presynaptic cell membranes and glial cells. Therefore, in Parkinson's disease and levodopa-induced complications (PD-LID), pharmacological inhibition of the metabotropic glutamate receptor 5 (mGluR5) regulates excitatory postsynaptic synaptic transmission and glutamatergic hyperactivity, thus showing potential as a therapeutic target (Huber et al., 2002).

[0044] The mechanism of HDAC6 (histone deacetylase 6) is unclear, but it is known to have a protective effect on the brain in neurological diseases such as Huntington's disease and Parkinson's disease. In general, HDAC6 is believed to affect the development of neurological diseases through several pathways, such as the formation of aggressors, increased autophagy, and the removal of misfolded proteins (de Zoeten et al., 2011, d'Ydewalle et al., 2011, Fukuda et al., 2012, Govindarajan et al., 2013).

[0045] Alterations in cytoprotective activity are associated with several neurodegenerative pathologies, such as Parkinson's disease (Outerio et al., Science (2007), (5837), 516-519) and Huntington's disease (Dompierre et al., J. Neurosci. (2007), 27(13), 3571-3583), and it is known that HDAC6 inhibition has a protective effect and prevents the death of α-synuclein neurons. At the same time, it can inhibit α-synuclein aggregation and protect nerve cells by increasing autophagy activity, which is involved in regulating α-synuclein accumulation.

[0046] The Formula 1 compound acts as a dual antagonist of mGluR5 and HDAC. These compounds may have effects in reducing damage to excitatory neurons and inhibiting microglial activity by inhibiting metabotropic glutamate receptors (mGluR5) among the various mechanisms of Parkinson's disease, and have neuroprotective effects by inhibiting HDAC6. Therefore, the Formula 1 compound may be Petition 870250084318, dated 09 / 18 / 2025, page 24 / 79 / 62, effectively used as a pharmaceutical composition to treat Parkinson's disease and suppress levodopa-induced complications.

[0047] In another embodiment according to the present invention, a method for preventing or treating movement disorders comprises administering to an animal a pharmaceutical composition comprising an effective amount of the compound of Formula 1 and a pharmaceutically acceptable vehicle or excipient. The method is particularly suitable for use in humans, but can also be used in other animals, particularly mammals.

[0048] The specific method of administration and the therapeutically effective amount of the Formula 1 compound or of a pharmaceutically acceptable salt thereof may be determined by a person skilled in the art, taking into account the type of target mammal, the type of disease and the type of Formula 1 compound, and are not specifically limited.

[0049] For example, the compound of Formula 1 or a pharmaceutically acceptable salt thereof may be included in the pharmaceutical composition at an effective dose of 0.1 to 1,000 mg / kg (body weight), preferably 0.5 to 500 mg / kg (body weight) per day for mammals, including humans. The pharmaceutical composition may be administered once or divided into two or more doses per day and administered orally or parenterally. Examples

[0050] The present invention is explained in more detail below with the following examples. However, it should be understood that the scope of protection of the present invention is not limited to the examples. Example 1: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3phenylprop-2-yn-1-yl)pyridin-2(1H)-one Step 1: Synthesis of methyl 2-oxo-1-(prop-2-yn-1-yl)-1,2-dihydropyridine-4-Petition 870250084318, dated 09 / 18 / 2025, p. 25 / 79 17 / 62 carboxylate o o

[0051] Methyl 2-o-1,2-dihydropyridine-4-carboxylate (1.000 g, 6.530 mmol), 3-bromoprop-1-yne (80.00% solution in toluene, 0.618 mL, 6.530 mmol) and potassium carbonate (1.805 g, 13.060 mmol) were dissolved in M / V-dimethylformamide (30 mL) at room temperature and stirred at the same temperature for 18 hours. Water was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain methyl 2-oxo-l-(prop-2-yn-l-yl)-l,2-dihydropyridine-4-carboxylate (0.720 g, 57.7%) in the form of a white solid. Step 2: Synthesis of methyl 2-oxo-l-(3-phenylprop-2-yn-l-yl)-1,2-dihydropyridine4-carboxylate

[0052] Methyl 2-oxo-l-(prop-2-yn-l-yl)-l,2-dihydropyridine-4-carboxylate (0.720 g, 3.766 mmol) and triethylamine (2.624 mL, 18.829 mmol) were dissolved in tetrahydrofuran (10 mL) at room temperature, and bis(triphenylphosphine)palladium(II) dichloride (0.132 g, 0.188 mmol) and copper iodide (Cul, 0.086 g, 0.452 mmol) were added and stirred at the same temperature for 10 minutes. Iodobenzene (0.462 mL, 4.142 mmol) was added to the reaction mixture and stirred at the same temperature for a further 18 hours. The reaction mixture was filtered through a Celite pad to remove solids, the filtrate was treated under reduced pressure to remove solvent, and the concentrate was purified and concentrated by column chromatography to obtain methyl 2-oxo-1-(3-phenylprop-2-yn-1-yl)-1,2-dihydropyridine-4 Petition 870250084318, dated 09 / 18 / 2025, p. 26 / 79 18 / 62 carboxylate (0.658 g, 65.4%) in the form of a yellow solid. Step 3: Synthesis of 2-oxo-l-(3-phenylprop-2-yn-l-yl)-1,2-dihydropyridine-4carbohydrazide oo

[0053] Methyl 2-oxo-l-(3-phenylprop-2-yn-l-yl)-l,2-dihydropyridine-4-carboxylate (0.658 g, 2.462 mmol) and hydrazine monohydrate (1.197 mL, 24.618 mmol) were dissolved in ethanol (20 mL) at room temperature, stirred at 80°C for 5 hours, and then the temperature was reduced to room temperature to stop the reaction. Water was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 2-oxo-l-(3-phenylprop-2-yn-l-yl)-l,2-dihydropyridine-4-carbohydrazide (0.414 g, 62.9%) as a yellow solid: LRMS (ES) m / z 268.06 [M+H]+, calculated MW 267.29. Step 4: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-phenylprop2-yn-1-ippyridin-2(17 / )-one oo

[0054] 2-oxo-1-(3-phenylprop-2-yn-1-yl)-1,2-dihydropyridine-4-carbohydrazide (0.414 g, 1.549 mmol), 2,2-difluoroacetic anhydride (0.578 mL, 4.647 mmol), and triethylamine (0.648 mL, 4.647 mmol) were mixed with tetrahydrofuran (10 mL) at room temperature. The resulting mixture was heated under reflux for 1 hour and then reduced to room temperature, and a saturated aqueous solution of sodium bicarbonate was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with Petition 870250084318, dated 09 / 18 / 2025, p. 27 / 79 19 / 62 Saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-phenylprop-2-yn-1-yl)pyridin-2(1H)one (0.300 g, 59.2%) in the form of a white solid: LRMS (ES) m / z 328.11 [M+H]+, calculated MW 327.29; Ή NMR (400 MHz, CD3OD) d 8.09 (d, J = 7.6 Hz, 1 H), 7.44 (dd, J = 7.8, 1.8 Hz, 2 H), 7.35 ~ 7.31 (m, 3 H), 7.22 (t, J = 51.8 Hz, 1 H), 7.21 (d, J = 1.6 Hz, 1 H), 7.03 (dd, J = 7.4, 1.8 Hz, 1 H), 5.06 (s, 2 H). Example 2: Synthesis of 1-(3-phenylprop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1 / / )-one Step 1: Synthesis of 2-oxo-l-(prop-2-yn-l-yl)-1,2-dihydropyridine-4carbonitrile

[0055] 2-Oxo-1,2-dihydropyridine-4-carbonitrile (3.000 g, 24.977 mmol), 3-bromoprop-1-yne (80.00% solution in toluene, 2.366 mL, 24.977 mmol) and potassium carbonate (6.904 g, 49.954 mmol) dissolved in N,N-dimethylformamide (30 mL) at room temperature and stirred at the same temperature for 18 hours. Water was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 2-oxo-1-(prop-2-yn-1-yl)-1,2-dihydropyridine-4-carbonitrile (3.000 g, 75.9%) in the form of an ivory solid. Step 2: Synthesis of V-hydroxy-2-oxo-1-(prop-2-yn-1-yl)-1,2-dihydropyridine-4-carboximidamide Petition 870250084318, dated 09 / 18 / 2025, p. 28 / 79 20 / 62

[0056] 2-Oxo-l-(prop-2-yn-l-yl)-l,2-dihydropyridine-4-carbonitrile (3.000 g, 18.968 mmol), hydroxylamine (50.00% solution, 6.265 mL, 94.841 mmol) and triethylamine (13.219 mL, 94.841 mmol) were mixed with ethanol (100 mL) at room temperature. The resulting mixture was heated under reflux for 2 hours and then reduced to room temperature, and water was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The precipitated solid was filtered, washed with ethanol, and dried to obtain 2V-hydroxy-2-oxo-l-(prop-2yn-l-yl)-l,2-dihydropyridine-4-carboximidamide (2.250 g, 62.0%) in the form of a white solid. Step 3: Synthesis of 1-(prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3yl)pyridin-2(1H)-one

[0057] iV-hydroxy-2-oxo-1-(prop-2-yn-1-yl)-1,2-dihydropyridine-4-carboximidamide (2.250 g, 11.768 mmol), trifluoroacetic anhydride (2.493 mL, 17.653 mmol), and triethylamine (2.460 mL, 17.653 mmol) were mixed with tetrahydrofuran (50 mL) at room temperature. The resulting mixture was refluxed for 1 hour and then reduced to room temperature, and a saturated aqueous solution of sodium bicarbonate was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain l-(prop-2 Petition 870250084318, dated 09 / 18 / 2025, page 29 / 79 21 / 62 in-1-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2(17 / )-one (2,000 g, 63.1%) as an ivory solid. Etapa 4: Síntese de l-(3-fenilprop-2-in-l-yl)-4-(5-(trifluorometil)-l,2,4oxadiazol-3-il)piridin-2( 17 / )-ona

[0058] l-(Prop-2-yn-l-yl)-4-(5-(trifluoromethyl)-l,2,4-oxadiazol-3yl)pyridin-2(l / / )-one (0.100 g, 0.371 mmol), triethylamine (0.259 mL, 1.857 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.013 g, 0.019 mmol) and copper iodide (Cui, 0.008 g, 0.045 mmol) were dissolved in tetrahydrofuran (5 mL) and stirred at room temperature for 10 minutes, and iodobenzene (0.046 mL, 0.409 mmol) was added and stirred at the same temperature for a further 18 hours. The reaction mixture was filtered through a Celite pad to remove solids, and water was added to the filtrate and extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure.The concentrate was purified and concentrated by chromatography in a column to obtain l-(3phenylprop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2( 1H)ona (0.065 g, 50.7%) in the form of a solid batch: LRMS (ES) m / z 346.04 [M+H]+, MW calculated 345.28; NMR de Ή (400 MHz, CD3OD) d 8.07 (d, J = 6.8 Hz, 1 H), 7.45 ~ 7.43 (m, 2 H), 7.35 ~ 7.28 (m, 4 H), 7.03 (dd, J = 7.2, 2.0 Hz, 1 H), 5.06 (s, 2 H). Example 3: Synthesis of l-(3-(pyridin-4-yl)prop-2-ml-yl)-4-(5(trifluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2( l / / )-ona oo

[0059] 1-(Prop-2-in-1-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3 Petition 870250084318, 18 / 09 / 2025, pág. 30 / 79 22 / 62 il)pyridin-2(l / / )-ona (0.100 g, 0.371 mmol), triethylamine (0.259 mL, 1.857 mmol), bis(triphenylphosphine)paládio(II) dicloreto (0.013 g, 0.019 mmol), cobre iodeto (Cui, 0.008 g, 0.045 mmol) and 4-iodopyridine (0.084 g, 0.409 mmol) as batch materials for use in the same way as Stage 4 in Example 2 to read l-(3-(pyridin-4-yl)prop-2-in-l-yl)-4-(5(trifluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(l / / )-one (0.059 g, 45.9%) in the form of a bitter solid: LRMS (ES) m / z 347.02 [M+H]+, MW calculated 346.27; NMR de Ή (400 MHz, CD3OD) d 8.51 (d, J = 4.0 Hz, 2 H), 8.03 (d, J = 7.2 Hz, 1 H), 7.44 (d, J = 6.0 Hz, 2 H), 7.28 (d, J = 2.0 Hz, 1 H), 7.01 (dd, J = 7.0, 2.2 Hz, 1 H), 5.12 (s, 2 H). Example 4: Synthesis of l-(3-(pyridin-3-yl)prop-2-in-l-yl)-4-(5(triíliioromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2( l / / )-one

[0060] l-(Prop-2-in-l-yl)-4-(5-(trifluoromethyl)-l,2,4-oxadiazol-3yl)pyridin-2(lH)-one (0.100 g, 0.371 mmol), triethylamine (0.259 mL, 1.857 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.013 g, 0.019 mmol), copper iodide (Cul, 0.008 g, 0.045 mmol) and 3-iodopyridine (0.084 g, 0.409 mmol) were used as starting materials as shown in Example 24 to obtain l-(3-(pyridin-3-yl)prop-2-in-l-yl)-4-(5(trifluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(lH)-one (0.030 g, 23.3%) in the form of a yellow solid: LRMS (3-m / 3-mW, MW++ calculated 346.27; Ή NMR (400 MHz, CD3OD) d 8.62 (d, J = 1.2 Hz, 1 H), 8.49 (dd, J = 4.6, 1.4 Hz, 1 H), 8.06 (d, J = 7.2 Hz, 1 H), 7.90 (dt, J = 7.6, 2 Hz, 1 H), 7.41 (dd, J = 7.8, 5.0 Hz, 1 H), 7.28 (d, J = 1.2 Hz, 1 H), 7.02 (dd, J = 7.0, 2.2 Hz, 1 H), 5.12 (s, 2 H). Example 5: Synthesis of l-(3-(pyridin-2-yl)prop-2-in-l-yl)-4-(5(trifluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(lH)-one Petition 870250084318, of 18 / 09 / 2025, p. 31 / 79 23 / 62

[0061] 1 -(Prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3yl)pyridin-2(17 / )-one (0.100 g, 0.371 mmol), triethylamine (0.259 mL, 1.857 mmol), dichloro demol bis(triphenylphosphine)palladium(II) (0.013 g, 0.019 mmol), copper iodate (Cui, 0.008 g, 0.045 mmol) and 2-iodopyridine (0.084 g, 0.409 mmol) were used as starting materials as shown in Example 24 to obtain l-(3-(pyridin-2-yl)prop-2-in-l-yl)-4-(5(trifluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(17 / )-one (0.080 g, 62.2%) in the form of a yellow solid (ES) m LRMS / M / H, 37++ calculated MW 346.27; Ή NMR (400 MHz, CD3OD) d 8.09 (d, J = 6.8 Hz, 1 H), 7.83 (t, J = 7.0 Hz, 1 H), 7.65 ~ 7.53 (m, 2 H), 7.41 (t, J = 6.0 Hz, 1 H), J Hz, 1 H), 7.02 (dd, J = 7.2, 1.6 Hz, 1 H), 5.13 (s, 2 H). Example 6: Synthesis of l-(3-(2-phiorophenyl)prop-2-ml-yl)-4-(5(triyliioromethyl)-l,2,4-oxadiazol-2-yl)pyridin-2( l / / )-one

[0062] 1 -(Prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3yl)pyridin-2(l / f)-one (0.100 g, 0.371 mmol), triethylamine (0.259 mL, 1.857 mmol), dichloride bis(triphenylphosphine)palladium(II) (0.013 g, 0.019 mmol), copper iodide (Cul, 0.008 g, 0.045 mmol) and l-fluoro-2-iodobenzene (0.091 g, 0.409 mmol) were used as starting materials in a similar way to Step 4 Example 2 to obtain l-(3-(2-fluorophenyl)prop-2-in1 -yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2( lH)-one (0.045 g, 33.3%) as a white solid: m / ESMS (ESMS) 36.03 [M+H]+, calculated MW 363.27; Ή NMR (400 MHz, CD3OD) d 8.07 (d, J = 6.8 Hz, 1 H), 7.47 (td, J = 7.5, 1.7 Hz, 1 H), 7.41 ~ 7.35 (m, 1 H), 7.29 (d, J = 1.6, 16 Hz), ~ Hz 7.10 (m, 2 H), 7.03 (dd, J = 7.2, 1.6 Hz, 1 H), 5.12 (s, 2 H). Petition 870250084318, of 18 / 09 / 2025, p. 32 / 79 24 / 62 Example 7: Synthesis of l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5(triyl ioromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2( l / / )-one

[0063] 1 -(Prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3yl)pyridin-2(17 / )-one (0.100 g, 0.371 mmol), triethylamine (0.259 mL, 1.857 mmol), dichloride bis(triphenylphosphine)palladium(II) (0.013 g, 0.019 mmol), copper iodide (Cul, 0.008 g, 0.045 mmol) and l-chloro-3-iodobenzene (0.097 g, 0.409 mmol) were used as starting materials in the same way Example 2 to obtain l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5(trifluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(17 / )-one (0.082 g, 58.1%) as a white solid: LRMS (38.000 m / s) [M+H]+, calculated MW 379.72; Ή NMR (400 MHz, CD3OD) of 8.05 (d, J = 6.8 Hz, 1 H), 7.46 (s, 1 H), 7.38 (dd, J = 2.6, 1.4 Hz, 1H), 7.36 (dd, J = 3.2, 1.2 Hz, 1.2 Hz), J 7.6 Hz, 1 H), 7.28 (d, J = 2.0 Hz, 1 H), 7.02 (dd, J = 7.4, 1.8 Hz, 1 H), 5.07 (s,2H). Example 8: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3(pyridin-4-yl)prop-2-in-l-yl)pyridin-2(lH)-one Step 1: Synthesis of 2-oxo-l,2-dihydropyridine-4-carbohydrazide

[0064] Methyl 2-oxo-1,2-dihydropyridine-4-carboxylate (3.000 g, 19.590 mmol) and hydrazine monohydrate (1.143 mL, 23.508 mmol) were dissolved in ethanol (100 mL) at room temperature. The resulting solution was stirred at 80°C for 18 hours, and the temperature was reduced to room temperature to stop the reaction. The precipitated solid was filtered and dried to obtain 2-oxo-1,2-dihydropyridine-4-carbohydrazide (2.610 g, 87.0%) in the form Petition 870250084318, dated 09 / 18 / 2025, page 33 / 79 25 / 62 of a solid ivory: LRMS (ES) m / z 153.98 [M+ / / ]+, MW calculated 153.14. Step 2: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(l / Dona

[0065] 2-oxo-l,2-dihydropyridine-4-carbohydrazide (2.610 g, 17.043 mmol), 2,2-difluoroacetic anhydride (6.357 mL, 51.130 mmol) and imidazole (3.481 g, 51.130 mmol) were dissolved in dichloromethane (30 mL) at room temperature. The resulting solution was heated and refluxed for 18 hours, and then the temperature was reduced to room temperature to stop the reaction. The reaction mixture was filtered through filter paper to remove solids, a saturated aqueous solution of sodium bicarbonate was poured onto the filtrate and extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridine-2(1 / f)-one (1,800 g, 49.6%) as a white solid: LRMS (ES) m / z 213.96 [M+H]+, calculated MW 213.14. Step 3: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(prop-2-yn-lyl)pyridin-2(17 / )-one oo

[0066] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1 / f)-one (2.500 g, 11.729 mmol), 3-bromoprop-1-yne (2.093 g, 17.594 mmol) and potassium carbonate (4.863 g, 35.188 mmol) were dissolved in N,N-dimethylformamide (50 mL) at room temperature, and the resulting solution was Petition 870250084318, dated 09 / 18 / 2025, page 34 / 79 26 / 62 stirred at the same temperature for 18 hours. The reaction mixture was filtered through a Celite pad to remove solids, and water was added to the filtrate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(prop-2-yn-1-yl)pyridin-2(17 / )-one (2.000 g, 67.9%) as a yellow solid: LRMS (ES) m / z 293.16 [M+ACN+H]+, calculated MW 251.19. Step 4: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-4yl)prop-2-yn-1-yl)pyridin-2(17 / )-one oo

[0067] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro demol bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and 4-iodopyridine (0.033 g, 0.159 mmol) were used as starting materials as shown in Example 24 to obtain 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l(3-(pyridin-4-yl)prop-2-in-l-yl)pyridin-2(l / / )-one (0.028 g, 53.6%) in the form of a yellow solid (ES) [3,3,30] mL / H calculated MW 328.28; Ή NMR (400 MHz, CD3OD) is 8.54 (m, 2 Hz), 8.07 (d, J = 7.2 Hz, 1 H), 7.47 (m, 2 H), 7.23 (t, J = 51.6 Hz, 1H), 7.23 (d, J = 51.6 Hz, 1H), = 7.0, 1.8 Hz, 1 H). Example 9: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3(pyridin-3-yl)prop-2-in-l-yl)pyridm-2( l / / )-one Petition 870250084318, of 18 / 09 / 2025, p. 35 / 79 27 / 62

[0068] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodate (Cul, 0.004 g, 0.019 mmol) and 3-iodopyridine (0.033 g, 0.159 mmol) were used as starting materials as shown in Example 24 to obtain 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l(3-(pyridin-3-yl)prop-2-in-l-yl)pyridin-2(lH)-one (0.030 g, 57.4%) in the form of a yellow solid (ES) m LRMS / 3,3,+H calculated MW 328.28; Ή NMR (400 MHz, DMSO-76) d 8.64 ~ 8.52 (m, 2 H), 8.09 (d, J = 7.6 Hz, 1H), 7.91 (d, J = 6.8 Hz, 1 H), 7.42 (m, 1 H), t 7.23 (m, 1 H), 7.04 (dd, 7= 7.4, 1.8 Hz, 1 H), 5.11 (s, 2 H). Example 10: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3(pyridin-2-yl)prop-2-in-l-yl)pyridin-2(lH)-one

[0069] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and 2-iodopyridine (0.033 g, 0.159 mmol) were used as starting materials as shown in Example 24 to obtain 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l(3-(pyridin-2-yl)prop-2-in-l-yl)pyridin-2(lH)-one (0.020 g, 38.3%) in the form of a yellow solid (ES) m LRMS / 3,3,+H calculated MW 328.28; Ή NMR (400 MHz, DMSO-in / 6) d 8.51 (m, 1H), 8.13 (d, J = 7.2 Hz, 1 H), 7.85 (t, J = 7.8 Hz, 1 H), 7.67 ~ 7.56 (m, 2 Hz, 1 H), 7.67 ~ 7.56 (m, 2 Hz), Hz, 1 H), 7.24 (t, J = 51.8 Hz, 1 H), 7.24 (m, 1 H), 7.05 (d, J = 6.8 Hz, 1 H), 5.14 (s, 2 H). Example 11: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(4fluorophenyl)prop-2-in-1 -yl) pyr id in-2( 1 / / )-one Petition 870250084318, 18 / 09 / 2025, pág. 36 / 79 28 / 62 o o

[0070] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-ona (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), bis(triphenylphosphine)paládio(II) dicloreto (0.006 g, 0.008 mmol), cobre iodine (Cul, 0.004 g, 0.019 mmol) and l-fluoro-4-iodobenzene (0.035 g, 0.159 mmol) as part materials for use in the preparation phase 4 of Example 2 below obter4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3-(4-fluorophenyl)prop-2-in-1 -yl)pyridin-2( 17 / )-one (0.010 g, 18.2%) in the form of a marine solid: LRMS (ES) m / z 346.04 [M+H]+, MW calculated 345.28; NMR de Ή (400 MHz, CD3OD) d 8.12 (dd, J = 6.8, 3.6 Hz, 1 H), 7.52 ~ 7.49 (m, 2 H), 7.25 (t, J = 51.8 Hz, 1 H), 7.26 ~ 7.23 (m, 1 H), 7.13 ~ 7.04 (m, 3 H), 5.08 (d, J = 3.6 Hz, 2 H). Example 12: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3fluoropheml)prop-2-in-l-yl)pyridm-2(lH)-one

[0071] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro demol bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and l-fluoro-3-iodobenzene (0.035 g, 0.159 mmol) were used as starting materials in a similar way to Step 4 Example 2 to obtain 4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3-(3-fluorophenyl)prop-2-in-1 -yl)pyridin-2( 1 H)-one (0.012 g, 21.8%) in the form of an ivory solid: LRMS (34.4 m / s) [M+H]+, calculated MW 345.28; Ή NMR (400 MHz, CD3OD) d 8.11 (d, J = 7.2 Hz, 1 H), 7.40 ~ 7.34 (m, 1 H), 7.28 (d, J = 19.6 Hz, 1 H), 7.25 (t, J = 51.8 Hz, 1 Hz, 7.21 ~ Hz), 2 H), 7.16 ~ 7.11 (m, 1 H), 7.06 (dd, J = 7.4, 1.8 Petition 870250084318, of 18 / 09 / 2025, p. 37 / 79 29 / 62 Hz, 1 Η), 5.10 (s, 2 Η). Example 13: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(2fluorophenyl)prop-2-in- l-yl)pyridin-2( l / / )-one

[0072] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro demol bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and l-fluoro-2-iodobenzene (0.035 g, 0.159 mmol) were used as starting materials in a similar way to Step 4 Example 2 to obtain 4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3-(2-fluorophenyl)prop-2-in-1 -yl)pyridin-2( 17 / )-one (0.010 g, 18.2%) in the form of an ivory solid: 34 m / m MS / MS [M+H]+, calculated MW 345.28; Ή NMR (400 MHz, CD3OD) d 8.12 (d, J = 6.8 Hz, 1 H), 7.50 ~ 7.49 (m, 1 H), 7.40 ~ 7.38 (m, 1 H), 7.25 (m, 1 H), 7.25 (t, 18, 18 H), ~ z 7.12 (m, 2 H), 7.08 ~ 7.06 (m, 1 H), 5.15 (s, 2 H). Example 14: Synthesis of l-(3-(4-chlorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lZ / )-one

[0073] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro demol bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and l-chloro-4-iodobenzene (0.038 g, 0.159 mmol) were used as starting materials in the same way Example 2 to obtain l-(3-(4-chlorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one (0.010 g, 17.4%) in the form of an ivory solid: LRMS (LRMS) m / 00000 [M+H]+, MW Petition 870250084318, of 18 / 09 / 2025, p. 38 / 79 30 / 62 calculated 361.73; Ή NMR (400 MHz, CD3OD) d 8.10 (d, J = 6.8 Hz, 1 H), 7.46 ~ 7.44 (m, 2 H), 7.35 (m, 2 H), 7.25 (t, J = 51.8 Hz, 1 H), 7.25 (m, J = 51.8 Hz, 1 H), 6.8, 2.0 Hz, 1 H), 5.08 (s, 2 H). Example 15: Synthesis of l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one oo

[0074] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.040 g, 0.159 nunol), triethylamine (0.111 mL, 0.796 mmol dichloro), bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 nunol), copper iodide (Cul, 0.004 g, 0.019 mmol) and l-chloro-3-iodobenzene (0.038 g, 0.159 mmol) were used as starting materials in the same way Example 2 to obtain l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one (0.010 g, 17.4%) in the form of an ivory solid: LRMS (LRMS) m / 000000 [M+H]+, calculated MW 361.73; Ή NMR (400 MHz, CD3DO) d 8.11 (d, J = 7.6 Hz, 1 H), 7.50 (t, J = 1.6 Hz, 1 H), 7.41 ~ 7.36 (m, 2 H), 7.25 (t, J = 51.8 Hz, 1, 7.2 Hz), J Hz, 2 H), 7.06 (dd, J = 7.0, 2.2 Hz, 1 H), 5.10 (s, 2 H). Example 16: Synthesis of l-(3-(2-chlorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lZ / )-one

[0075] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro demol bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and l-chloro-2-iodobenzene (0.038 g, 0.159 mmol) were used as starting materials in the same way Example 2 to obtain l-(3-(2-chlorophenyl)prop-2-in-l-yl)-4-(5 Petition 870250084318, of 18 / 09 / 2025, p. 39 / 79 31 / 62 (difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one (0.008 g, 13.9%) in the form of an ivory solid: LRMS (ES) m / z 362.00 [M+H]+, calculated MW 361.73; Ή NMR (400 MHz, CD3OD) is 8.17 (m, 1 H), 7.56 ~ 7.08 (m.7H), 5.16 (s, 2 H). Example 17: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(ptolyl)prop-2-in-l-yl)pyridin-2(lH)-one

[0076] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cui, 0.004 g, 0.019 mmol) and l-iodo-4-methylbenzene (0.035 g, 0.159 mmol) were used as starting materials in a similar way to Epa 4 Example 2 to obtain 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)l-(3-(p-tolyl)prop-2-in-l-yl)pyridin-2(17 / )-one (0.010 g, 18.4%) in the form of an ivory solid: LRMS (LRMS) 32.19 m / 4 [M+H]+, calculated MW 341.32; Ή NMR (400 MHz, CD3OD) d 8.12 (d, J = 7.2 Hz, 1 H), 7.25 (t, J = 51.8 Hz, 1H), 7.34 (d, J = 7.6 Hz, 2 H), 7.25 ~ 7.23 (d, J = 7.6 Hz, 2 H), Hz, 2 H), 7.05 (dd, J = 7.0, 2.2 Hz, 1 H), 5.07 (s, 2 H), 2.34 (s, 3 H). Example 18: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(mtolyl)prop-2-in-l-yl)pyridin-2(lH)-one

[0077] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(17 / )-one (0.040 g, 0.159 mmol), triethylamine (0.111 mL, 0.796 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol), copper iodide (Cul, 0.004 g, 0.019 mmol) and l-iodo-3-methylbenzene (0.035 g, 0.159 mmol) were used as starting materials in a similar manner Petition 870250084318, of 18 / 09 / 2025, p. 40 / 79 32 / 62 to Step 4 of Example 2 to obtain 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)l-(3-(m-tolyl)prop-2-in-l-yl)pyridin-2(l / / )-one (0.015 g, 27.6%) in the form of a solid: LR (ES) m / z 342.05 [M+H]+, calculated MW 341.32; Ή NMR (400 MHz, CD3DO) d 8.13 (d, J = 7.2 Hz, 1 H), 7.25 (t, J = 51.6 Hz, 1 H), 7.30 ~ 7.21 (m, 5 H), 7.07 (d, J = 7.2 Hz, 1 H), 2.32 (s, 3 H). Example 19: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3(trill iioromethyl)phenyl)prop-2-in-1-yl)pyridin-2( l / / )-one

[0078] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 mmol dichloro), bis(triphenylphosphine)palladium(II) (0.007 g, 0.010 mmol), copper iodide (Cul, 0.005 g, 0.024 mmol) and l-iodo-3(trifluoromethyl)benzene (0.032 mL, 0.219 mmol) were used as starting materials in a similar way Step 4 of Example 2 to obtain 4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3-(3-(trifluoromethyl)phenyl)prop-2-in-lyl)pyridin-2(l / f)-one (0.030 g, 38.1%) in a solid form using LRMS: m / z 396.27 [M+H]+, calculated MW 395.29; Ή NMR (400 MHz, DMSO-in / o) d 8.12 (d, J = 6.8 Hz, 1 H), 7.79 (s, 1 H), 7.75 (d, J = 7.6 Hz, 2 H), 7.53 (t, J = 51.2 Hz, 1,600 Hz), 1 H), 7.01 (d, J = 1.6 Hz, 1 H), 6.84 (dd, J = 7.4, 1.8 Hz, 1 H), 5.06 (s, 2 H). Example 20: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3(trilliioromethoxy)phenyl)prop-2-in-l-yl)pyridin-2( l / / )-one

[0079] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-yn-1yl)pyridin-2(1H)-one (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 Petition 870250084318, dated 09 / 18 / 2025, p. 41 / 79 33 / 62 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.007 g, 0.010 mmol), copper iodide (Cui, 0.005 g, 0.024 mmol) and l-iodo-3(trifluoromethoxy)benzene (0.034 mL, 0.219 mmol) as starting materials were used similarly to Step 4 of Example 2 to obtain 4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3-(trifluoromethoxy)phenyl)prop-2-ynl-yl)pyridin-2(l / / )-one (0.030 g, 36.6%) in the form of an ivory solid: LRMS (ES) m / z 411.93 [M+H]+, calculated MW 411.29; Ή 400 MHz NMR, DMSO-íZô) d 8.10 (d, J = 7.2 Hz, 1 H), 7.53 (t, J = 51.4 Hz, 1 H), 7.50 ~ 7.40 (m, 4 H), 7.01 (d, J = 2.4 Hz, 1 H), 6.84 (dd, J = 7.2, 2.0Hz, 1H), 5.05 (s.2H). Example 21: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3methoxyphenyl)prop-2-in-l-yl)pyridin-2(lH)-one oo

[0080] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(17 / )-one (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.007 g, 0.010 mmol), copper iodide (Cul, 0.005 g, 0.024 mmol) and l-iodo-3-methoxybenzene (0.029 mL, 0.219 mmol) were used as starting materials in a separate way. of Example 2 to obtain 4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3-(3-methoxyphenyl)prop-2-in-1 -yl)pyridin-2( l / / )-one (0.013 g, 18.3%) in the form of an ivory solid: 18.3 m / s (ES) MS [M+H]+, calculated MW 357.32; Ή NMR (400 MHz, DMSO-in / 6) d 8.10 (d, J = 7.2 Hz, 1 H), 7.53 (t, J = 51.6 Hz, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.01 ~ 6.93 (d, J = 6.84 Hz), 7.0, 2.2 Hz, 1 H), 5.02 (s, 2 H), 3.72 (s, 3 H). Example 22: Synthesis of l-(3-(6-chloropyridin-2-yl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one Petition 870250084318, of 18 / 09 / 2025, p. 42 / 79 34 / 62

[0081] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 mmol dichloro), bis(triphenylphosphine)palladium(II) (0.007 g, 0.010 mmol), copper iodide (Cul, 0.005 g, 0.024 mmol) and 2-chloro-6-iodopyridine (0.026 mL, 0.219 mmol) were used as the starting materials for the EPA method. 4 of Example 2 to obtain l-(3-(6-chloropyridin-2-yl)prop2-in-l-yl)-4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(l / / )-one (0.028 g, 38.8%) in the form of a yellow solid (ES: m / LMS) 363.12 [M+H]+, calculated MW 362.72; Ή NMR (400 MHz, DMSO-in / 6) d 8.09 (d, J = 6.4 Hz, 1 H), 7.85 (t, J = 7.8 Hz, 1 H), 7.53 (t, J = 51.2 Hz, 1 H), 7.57 ~ 7.50 (m, J = 7.02 Hz), 1.6 Hz, 1 H), 6.85 (dd, J = 7.0, 2.2 Hz, 1 H), 5.08 (s, 2 H). Example 23: Synthesis of l-(3-(2-chloropyridin-4-yl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one oo

[0082] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-ona (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 mmol), bis(triphenylphosphine)paládio(II) dicloreto (0.007 g, 0.010 mmol), cobre iodeto (Cul, 0.005 g, 0.024 mmol) and 2-chloro-4-iodopyridine (0.026 mL, 0.219 mmol) as part materials used in the preparation stage 4 in Example 2 to obtain l-(3-(2-cloropiridin-4-yl)prop2-in-l-yl)-4-(5-(difluorometil)-l,3,4-oxadiazol-2-il)piridin-2(l / r)-ona (0,015 g, 20,8%) na forma de um sólido amarelo: LRMS (ES) m / z 363,12 [M+H]+, MW calculado 362,72; NMR de Ή (400 MHz, DMSO-í / 6) d 8.40 (d, J = 6.0 Hz, 1H), 8.09 (d, J = 6.4 Hz, 1 H), 7.53 (t, J = 51.2 Hz, 1H), 7.61 (m, 1H), 7.44 (dd, J = 5.0, 1.4 Hz, 1 H), 7.02 (d, J = 1.2 Hz, 1 H), 6.84 (dd, J = 7.4, 1.8 Petition 870250084318, 18 / 09 / 2025, pág. 43 / 79 35 / 62 Hz, 1 Η), 5.10 (s, 2 Η). Example 24: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(6methylpyridine-2-yl)prop-2-ml-yl)pyridin-2( l / / )-one oo

[0083] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.007 g, 0.010 mmol), copper iodide (Cul, 0.005 g, 0.024 mmol) and 2-iodo-6-methylpyridine (0.026 mL, 0.219 mmol) were used as starting materials in a separate manner. of Example 2 to obtain 4-(5-(difluoromethyl)-l,3,4oxadiazol-2-yl)-1 -(3 -(6-methylpyridin-2-yl)prop-2-in-1 -yl)pyridin-2( 17 / )-one (0.020 g, 29.4%) in the form of a brown solid (LRMS) m / z 343.17 [M+H]+, calculated at MW 342.31; Ή NMR (400 MHz, DMSO-in / 6) d 8.09 (d, J = 7.2 Hz, 1 H), 7.68 ~ 7.64 (m, 1 H), 7.53 (t, J = 51.8 Hz, 1 H), 7.31 (d, J = 7.2 Hz, 1 H), J 8.0 Hz, 1 H), 7.02 (d, J = 1.2 Hz, 1 H), 6.85 (dd, J = 7.0, 2.2 Hz, 1 H), 5.05 (s, 2 H), 2.40 (s, 3 H). Example 25: Synthesis of l-(3-(3-bromophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyrimidin-2(lH)-one oo

[0084] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(lH)-one (0.050 g, 0.199 mmol), triethylamine (0.139 mL, 0.995 mmol dichloro), bis(triphenylphosphine)palladium(II) (0.007 g, 0.010 mmol), copper iodide (Cul, 0.005 g, 0.024 mmol) and l-bromo-3-iodobenzene (0.028 mL, 0.219 mmol) were used as starting materials in the same way as Eta 4 Example 2 to obtain l-(3-(3-bromophenyl)prop-2-in1 -yl)-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2( 1 H)-one (0.019 g, Petition 870250084318, of 18 / 09 / 2025, p. 44 / 79 36 / 62 23.5%) in the form of a white solid: LRMS (ES [M+2H]) m / z 408.10 [M+H]+, calculated MW 406.19; Ή NMR (400 MHz, DMSO-in / 6) d 8.10 (d, J = 6.8 Hz, 1 H), 7.65 (d, J = 1.6 Hz, 1 H), 7.59 (dt, J = 6.8, 1.3 Hz, 1 H), t 7.45 (dd, J = 7.6, 1.2 Hz, 1 H), 7.31 (t, J = 8.0 Hz, 1 H), 7.01 (d, J = 1.2 Hz, 1 H), 6.84 (dd, J = 7.2, 2.0 Hz, 1 H), 5.04 (s, 2 H). Example 26: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(difluoromethyl)phenyl)prop-2-yn-1-yl)pyridin-2(1H)-one Step 1: Synthesis of 3-(3-(difluoromethyl)phenyl)prop-2-yn-l-ol

[0085] 3-(3-(Difluoromethoxy)phenyl)prop-2-yn-1-ol (0.550 g, 2.775 mmol), methanesulfonyl chloride (0.322 mL, 4.163 mmol) and triethylamine (0.774 mL, 5.551 mmol) were dissolved in dichloromethane (10 mL) at room temperature and stirred at the same temperature for 1 hour. Water was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 3-(3-(difluoromethoxy)phenyl)prop-2-yn-1-yl methanesulfonate (0.430 g, 56.1%) in the form of a yellow liquid: LRMS (ES) m / z no detection [M+H]+, calculated MW 182.17. Step 2: Synthesis of 3-(3-(difluoromethyl)phenyl)prop-2-yn-l-yl methanesulfonate

[0086] 3-(3-(Difluoromethyl)phenyl)prop-2-yn-1-ol (0.750 g, 4.117 mmol), methanesulfonyl chloride (0.478 mL, 6.176 mmol) and triethylamine (1.148 mL, 8.234 mmol) were dissolved in dichloromethane (10 mL) at room temperature and stirred at the same temperature for 1 hour. Water was added to the reaction mixture and extracted with dichloromethane. The layer Petition 870250084318, dated 09 / 18 / 2025, page 45 / 79 37 / 62 organic material was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 3-(3-(difluoromethyl)phenyl)prop-2-yn-1-yl methanesulfonate (0.975 g, 91.0%) as a clear liquid: LRMS (ES) m / z no detection [M+H]+, calculated MW 260.25. Stage 3: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(3(difluoromethyl)phenyl)prop-2-in-1 -yl)pyridin-2( 17 / )-on a 0

[0087] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1 / f)-one (0.050 g, 0.235 mmol), 3-(3-(difluoromethyl)phenyl)prop-2-yn-1-yl methanesulfonate (0.092 g, 0.352 mmol) and cesium carbonate (CS2CO3, 0.115 g, 0.352 mmol) were dissolved in acetonitrile (2 mL) at room temperature and stirred at the same temperature for 10 minutes. Water was added to the reaction mixture and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure.The concentrate was purified and concentrated by column chromatography to obtain 4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3-(difluoromethyl)phenyl)prop-2-yn-lyl)pyridin-2(1 / f)-one (0.037 g, 41.5%) as a white solid: LRMS (ES) m / z 378.17 [M+H]+, calculated MW 377.3; Ή 400 MHz NMR, CD3OD) d 8.09 (d, J = 7.2 Hz, 1 H), 7.61 (s, 1 H), 7.58 (d, J = 7.2 Hz, 1 H), 7.53 (d, J = 7.6 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 1H), 7.23 (t, J = 51.8 Hz, 1 H), 7.22 (s, 1 H), 7.03 (dd, J = 7.0, 1.4 Hz, 1 H), 6.73 (t, J = 56.2 Hz, 1 H), 5.08 (s, 2H). Example 27: Synthesis of 1-(3-(3-(difluoromethoxy)feml)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one Step 1: Synthesis of 3-(3-(difluoromethoxy)phenyl)prop-2-yn-l-ol Petition 870250084318, dated 09 / 18 / 2025, p. 46 / 79 38 / 62

[0088] l-Bromo-3-(difluoromethoxy)benzene (1.000 g, 4.484 mmol), 2,3,4,6,7,8,9,10-octahydropyrimido[l,2-a]azepine (DBU, 0.805 mL, 5.381 mmol), tetrakis(triphenylphosphine)palladium (0.155 g, 0.135 mmol) and copper iodide (Cui, 0.026 g, 0.135 mmol) as starting materials were used similarly to Step 1 of Example 26 to obtain 3-(3(difluoromethoxy)phenyl)prop-2-yn-l-ol (0.550 g, 61.9%) in the form of a yellow solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 198.17. Step 2: Synthesis of 3-(3-(difluoromethoxy)phenyl)prop-2-yn-l-yl methanesulfonate

[0089] 3-(3-(difluoromethoxy)phenyl)prop-2-yn-1-ol (0.550 g, 2.775 mmol), methanesulfonyl chloride (0.322 mL, 4.163 mmol) and triethylamine (0.774 mL, 5.551 mmol) as starting materials were used similarly to Step 2 of Example 26 to obtain 3-(3(difluoromethoxy)phenyl)prop-2-yn-1-yl methanesulfonate (0.430 g, 56.1%) in the form of a yellow liquid: LRMS (ES) m / z no detection [M+H]+, calculated MW 276.25. Step 3: Synthesis of 1-(3-(3-(difluoromethoxy)phenyl)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(l / f)-one 0

[0090] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(l / f)-one (0.050 g, 0.235 mmol), 3-(3-(difluoromethoxy)phenyl)prop-2-yn-l-yl methanesulfonate (0.097 g, 0.352 mmol) and cesium carbonate (Cs2CO3, 0.153 g, 0.469 mmol) as starting materials were used in a Petition 870250084318, dated 09 / 18 / 2025, p. 47 / 79 39 / 62 similar to Step 3 of Example 26 to yield 1-(3-(3(difluoromethoxy)phenyl)prop-2-in-l-yl)-4-(5-(difluoromethyl)-l,3,4-oxadiazol-2yl)pyridin-2(l / / )-one (0.07 g, 7.6%) in solid form. brown: LRMS (ES) m / z 394.29 [M+H]+, calculated MW 393.3; Ή NMR (400 MHz, CD3OD) d 8.08 (d, J = 7.2 Hz, 1 H), 7.22 (t, J = 51.6 Hz, 1 H), 7.38 ~ 7.29 (m, 2 H), Hz, 1 H), 7.03 (dd, J = 7.2, 2.0 Hz, 1 H), 6.82 (t, J = 73.8 Hz, 1 H), 5.07 (s, 2 H). Example 28: Synthesis of l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5(trifhioromethyl)-1,3,4-oxad iazol-2-yl )pi r id in-2( 1 / / )-one Step 1: Synthesis of 4-(5-(trifluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(l / Dona

[0091] 2-Oxo-1,2-dihydropyridine-4-carbohydrazide (1.730 g, 11.297 mmol), triethylamine (4.724 mL, 33.891 mmol) and trifluoroacetic anhydride (4.787 mL, 33.891 mmol) as starting materials were used similarly to Step 2 of Example 8 to obtain 4-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1 / / )-one (1.500 g, 57.4%) in the form of a light brown solid: Ή NMR (400 MHz, DMSO-1 / 6) δ 8.91 (s, 1H), 7.59 (s, 2 H). Step 2: Synthesis of 3-(3-chlorophenyl)prop-2-yn-l-ol

[0092] l-chloro-3-iodobenzene (1.000 g, 4.194 mmol), 2,3,4,6,7,8,9,10-octahydropyrimido[l,2-a]azepine (DBU, 0.753 mL, 5.033 mmol), tetrakis(triphenylphosphine)palladium (0.145 g, 0.126 mmol) and copper iodide (Cul, 0.024 g, 0.126 mmol) as starting materials were used similarly to Step 1 of Example 26 to obtain 3-(3-chlorophenyl)prop2-yn-l-ol (0.580 g, 83.0%) in the form of a yellow solid: LRMS (ES) m / z Petition 870250084318, dated 09 / 18 / 2025, page 48 / 79 40 / 62 no detection [M+H]+, calculated MW 166.60. Step 3: Synthesis of 3-(3-chlorophenyl)prop-2-yn-l-yl methanesulfonate

[0093] 3-(3-chlorophenyl)prop-2-yn-1-ol (0.580 g, 3.481 mmol), methanesulfonyl chloride (9.20 M solution in toluene, 0.568 mL, 5.222 mmol) and triethylamine (1.456 mL, 10.444 mmol) as starting materials were used similarly to Step 2 of Example 26 to obtain 3-(3-chlorophenyl)prop-2-yn-1-yl methanesulfonate (0.650 g, 76.3%) in the form of a clear liquid: LRMS (ES) m / z no detection [M+H]+, calculated MW 244.69. Step 4: Synthesis of 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2(1 / D-one oo

[0094] 4-(5-(Trifluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(l / / )-one (0.050 g, 0.216 mmol), 3-(3-chlorophenyl)prop-2-in-l-yl methanosulfonate (0.079 g, 32 mmol) and carbon cesium (CS2CO3, 0.141 g, 0.433 mmol) as starting materials were used in a manner similar to Step 3 of Example 26 to obtain l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5-(trifluoromethyl)l,3,4-oxadiazol-2-yl)pyridin-2(l / / )-one (0.066 g, 80.3%) in the form of a yellow solid: LRMS (ES) 38 m / m / m / MH+ calcd. 379.72; Ή NMR (400 MHz, CD3OD) d 8.09 (d, J = 6.8 Hz, 1 H), 7.46 (s, 1 H), 7.38 ~ 7.29 (m, 3 H), 7.03 (d, J = 1.6 Hz, 1 H), 7.03 (d, J = 1.8 Hz, 16 H), 5.07 (s, 2 H). Example 29: Synthesis of 4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)-l-(3-(5methylpyridin-3-yl)prop-2-in-l-yl)pyridin-2( l / / )-one Step 1: Synthesis of 3-(5-methylpyridin-3-yl)prop-2-in-l-ol Petition 870250084318, of 18 / 09 / 2025, p. 49 / 79 41 / 62

[0095] 3-Bromo-5-methylpyridine (1.000 g, 5.813 mmol), 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (DBU, 1.043 mL, 6.976 mmol), tetrakis(triphenylphosphine)palladium (0.202 g, 0.174 mmol), copper iodide (Cui, 0.033 g, 0.174 mmol) and prop-2-yn-1-ol (0.391 g, 6.976 mmol) as starting materials were used similarly to Step 1 of Example 26 to obtain 3-(5-methylpyridin-3-yl)prop-2-yn-1-ol (0.752 g, 87.9%) in the form of a yellow solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 147.18. Step 2: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(5methylpyridin-3-yl)prop-2-yn-1-yl)pyridin-2(1 / D-one

[0096] 3-(5-methylpyridin-3-yl)prop-2-yn-1-ol (0.050 g, 0.340 mmol), methanesulfonyl chloride (0.032 mL, 0.408 mmol) and triethylamine (0.057 mL, 0.408 mmol) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 1 hour, and 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2yl)pyridin-2(1 / / )-one (0.109 g, 0.510 mmol) and cesium carbonate (CS2CO3, 0.166 g, 0.510 mmol) were added and stirred at the same temperature for a further 0.5 hours. Water was poured into the reaction mixture and extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure.The concentrate was purified and concentrated by chromatography in a column to obtain 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2yl)-1-(3-(5-methylpyridin-3-yl)prop-2-in-1-yl)pyridin-2(1 / / )-one (0.020 g, 17.2%) in the form of a solid batch: LRMS (ES) m / z 343.23 [M+H]+, calculated MW 342.31; NMR de Ή (400 MHz, CD3OD) d 8.41 (s, 1 H), 8.35 (s, 1 H), 8.08 (d, J = 6.8 Hz, 1 H), 7.75 (s, 1 H), 7.62 ~ 7.56 (m, 1 H), 7.23 (t, J =. Petition 870250084318, 18 / 09 / 2025, pág. 50 / 79 42 / 62 51.6 Hz, 1 Η), 7.22 (d, J = 2.0 Hz, 1 Η), 7.03 (dd, J = 7.2, 2.0 Hz, 1 H), 5.10 (s, 2 H), 2.32 (s, 3 H). Example 30: Synthesis of l-(3-(3-chlorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(lH)-one Step 1: Summary of / V-hidroxi-2-oxo-l,2-di-hidropyridina-4-carboxymidida or

[0097] 2-Oxo-1,2-dihydropyridine-4-carbonitrile (2.000 g, 16.651 mmol) and hydroxylamine (50.00% solution in water, 3.300 mL, 49.954 mmol) as starting materials were used similarly to Step 1 of Example 8 to obtain 2V-hydroxy-2-oxo-1,2-dihydropyridine-4-carboximidamide (2.430 g, 95.3%) in the form of an ivory solid. Step 2: Synthesis of 4-(5-(difluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2(l / Dona

[0098] iV-hydroxy-2-oxo-1,2-dihydropyridine-4-carboximidamide (2.430 g, 15.868 mmol), triethylamine (6.635 mL, 47.604 mmol) and 2,2-difluoroacetic anhydride (5.918 mL, 47.604 mmol) as starting materials were used similarly to Step 2 of Example 8 to obtain 4-(5(difluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2(1 / f)-one (2.000 g, 59.1%) in the form of a white solid. Step 3: Synthesis of 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)1,2,4-oxadiazol-3-yl)pyridin-2( 1 / D-one oo

[0099] 4-(5-(Difluoromethyl)-l,2,4-oxadiazol-3-yl)pyridin-2(l / f)-one Petition 870250084318, of 18 / 09 / 2025, p. 51 / 79 / 62 (0.050 g, 0.235 mmol), 3-(3-chlorophenyl)prop-2-in-1-yl methanesulfonate (0.086 g, 0.352 mmol) and cesium carbonate (CS2CO3, 0.153 g, 0.469 mmol) were used as starting materials similar to Step 3 of Example 26 to obtain 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)1,2,4-oxadiazol-3-yl)pyridin-2(1 H)-one (0.052 g, 61.3%) as a white solid (LRMS: m / z 362.19 [MH], calculated MW 361.73; 1H NMR (400 MHz, CD3OD) d 8.02 (d, J = 7.2 Hz, 1 H), 7.43 (s, 1 H), 7.36 ~ 7.25 (m, 3 H), 7.25 (d, J = 1.2 Hz, 1 H), t 6.99 (dd, J = 7.2, 1.6 Hz, 1 H), 5.06 (s, 2 H). Example 31: Synthesis of 3-(3-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-2oxopyridin-1 (2 H)-yl)prop-1 -in-1-yl)benzonitrile Step 1: Synthesis of 3-(3-hydroxyprop-1-in-1-yl)benzonitrile

[00100] Prop-2-yn-1-ol (0.312 mL, 5.351 mmol), 3-iodobenzonitrile (1.226 g, 5.351 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.075 g, 0.107 mmol), copper iodide (CuI, 0.020 g, 0.107 mmol) and triethylamine (2.238 mL, 16.054 mmol) as starting materials were used similarly to Step 1 of Example 26 to obtain 3-(3-hydroxyprop-1-yn-1yl)benzonitrile (0.768 g, 91.3%) in the form of a yellow oil: LRMS (ES) m / z no detection [M+H]+, calculated MW 235.26. Step 2: Synthesis of 3-(3-cyanophenyl)prop-2-yn-1-yl methanesulfonate

[00101] 3-(3-hydroxyprop-1-yn-1-yl)benzonitrile (0.768 g, 4.886 mmol), triethylamine (2.043 mL, 14.659 mmol), and methanesulfonyl chloride (0.756 mL, 9.773 mmol) as starting materials were used similarly to Step 2 of Example 26 to obtain 3-(3-cyanophenyl)prop-2-yn-1-yl methanesulfonate (0.703 g, 61.2%) in the form of a yellow solid: LRMS Petition 870250084318, dated 09 / 18 / 2025, p. 52 / 79 / 62 (ES) m / z no detection [M+H]+, calculated MW 235.26. Step 3: Synthesis of 3-(3-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-2oxopyridin-1(2H)-yl)prop-1-yn-1-yl)benzonitrile O o

[00102] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2( 1H)-one (0.100 g, 0.469 mmol), 3-(3-cyanophenyl)prop-2-in-1-yl methanosulfonate (0.101 g, 490 mmol) and carbon dioxide cesium (Cs2CO3, 0.459 g, 1.408 mmol) as starting materials were used in a manner similar to Step 3 of Example 26 to obtain 3-(3-(4-(5-(difluoromethyl))-1,3,4-oxadiazol-2-yl)-2(oxopiridin-21) H)-yl)prop-1-in-1-yl)benzonitrile (0.027 g, 16.3%) as a yellow solid: LRMS (ES) m / z 353.14 [M+H]+, calculated MW 352.3; 1H NMR (400 MHz, CDCb) d 7.82 (d, J = 6.8 Hz, 1 H), 7.74 (t, J = 1.4 Hz, 1 H), 7.69 ~ 7.63 (m, 2 H), 7.46 (t, J = 7.8 Hz, 1 H), J Hz, 2 H), 6.95 (dd, J = 7.4, 1.8 Hz, 1 H), 6.92 (t, J = 51.6 Hz, 1 H), 5.03 (s, 2 H). Example 32: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(methylsulfonyl)phenyl)prop-2-in-1-yl)pyridin-2(1 H)-one Step 1: Synthesis of 3-(3-(methylsulfonyl)phenyl)prop-2-in-1-ol

[00103] Prop-2-in-1-ol (0.312 mL, 5.351 mmol), 1-bromo-3(methylsulfonyl)benzene (1.258 g, 5.351 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.075 g, 0.107 mmol), copper iodide (CuI, 0.020 g, 0.107 mmol) and triethylamine (2.238 mL, 16.054 mmol) as starting materials were used similarly to Step 1 of Example 26 to obtain 3-(3-(methylsulfonyl)phenyl)prop-2-in-1-ol (0.985 g, 87.5%) in the form of a yellow oil: LRMS (ES) m / z no detection [M+H]+, calculated MW 210.25. Step 2: Synthesis of 3-(3-(methylsulfonyl)phenyl)prop-2-yn-1-yl methanesulfonate Petition 870250084318, dated 09 / 18 / 2025, p. 53 / 79 45 / 62

[00104] 3-(3-(methylsulfonyl)phenyl)prop-2-yn-1-ol (0.985 g, 4.685 mmol), triethylamine (1.959 mL, 14.055 mmol) and methanesulfonyl chloride (0.725 mL, 9.370 mmol) as starting materials were used similarly to Step 2 of Example 26 to obtain 3-(3(methylsulfonyl)phenyl)prop-2-yn-1-yl methanesulfonate (0.812 g, 60.1%) in the form of a yellow solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 288.33. Step 3: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(methylsulfonyl)phenyl)prop-2-yn-1-yl)pyridin-2(l / D-one O o

[00105] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2( l / / )-one (0.100 g, 0.469 mmol) and 3-(3-(methylsulfonyl)phenyl)prop-2-in-l-methanosulfonate were prepared as particles in a similar manner à Step 3 of Example 26 to obtain 4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3 -(3 -(methylsulfonyl)phenyl)prop-2-in-1 -yl)pyridin-2( 17 / )-one (0.029 g, 15.2%) in the form of LR oil: (ES) m / z 406.05 [MH], calculated MW 405.38; NMR of Ή (400 MHz, CDC13) d 8.04 (s, 1 H), 7.94 ~ 7.91 (m, 1 H), 7.84 (d, J = 7.2 Hz, 1 H), 7.72 (d, J = 7.6 Hz, 1 H), t 7.30 (d, J = 2.0 Hz, 1 H), 6.96 (dd, J = 7.2, 2.0 Hz, 1 H), 6.92 (t, J = 51.6 Hz, 1 H), 5.04 (s, 2 H), 3.05 (s, 3 H). Example 33: Synthesis of l-(3-(3-chloro-2-fluorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lZ / )-one o

[00106] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.100 g, 0.398 mmol), triethylamine (0.277 mL, 1.991 Petition 870250084318, 18 / 09 / 2025, pág. 54 / 79 46 / 62 mmol), bis(triphenylphosphine)paládio(II) dicloreto (0.014 g, 0.020 mmol), cobre iodeto (Cul, 0.009 g, 0.048 mmol) and l-chloro-2-fluoro-3-iodobenzene (0.112 g, 0.438 mmol) as part material Foram used as follows in Step 4 of Example 2 to obtain l-(3-(3-chloro-2fluorophenyl)prop-2-in-l-yl)-4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin2(lH)-one (0.080 g, 52.9%) in the form of a solid love it: LRMS (ES) m / z 380.02 [M+H]+, calculated MW 379.72; RMN-1H (400 MHz, DMSO-í / 6) d 8.08 (d, J = 6.8 Hz, 1 H), 7.52 (t, J = 51.2 Hz, 1 H), 7.62 (td, J = Ί,Ί, 1.5 Hz, 1 Η), 7.49 ~ 7.48 (m, 1 H), 7.21 (td, J = 8.0, 0.8 Hz, 1 H), 7.02 (d, J = 1.6 Hz, 1 H), 6.84 (dd, J = 7.0, 1.8 Hz, 1 H), 5.10 (s, 2 H). Example 34: Synthesis of l-(3-(3-chloro-4-fluorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridine-2( l / / )-one oo

[00107] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.100 g, 0.398 mmol), triethylamine (0.277 mL, 1.991 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.014 g, 0.020 mmol), copper iodide (Cul, 0.004 g, 0.020 mmol) and 2-chloro-l-fluoro-4-iodobenzene (0.112 g, 0.438 mmol) were used as similar starting materials Step 4 of Example 2 to obtain l-(3-(3-chloro-4fluorophenyl)prop-2-in-l-yl)-4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin2(l / / )-one (0.092 g, 60.9% %) in bitter form (ESL / MS) only 380.09 [M+H]+, calculated MW 379.72; 1H NMR (400 MHz, DMSO-in / 6) d 8.09 (d, J = 7.2 Hz, 1 H), 7.72 (dd, J = 7.0, 1.8 Hz, 1 H), 7.52 (t, J = 51.2 Hz, 1 H), 7.47 (~ 7.46), ~ 7.46 Hz 7.39 (m, 1 H), 7.01 (d, J = 2.0 Hz, 1 H), 6.83 (dd, J = 7.2, 2.0 Hz, 1 H), 5.03 (s, 2 H). Example 35: Synthesis of l-(3-(3-chloro-5-fluorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one Petition 870250084318, of 18 / 09 / 2025, p. 55 / 79 47 / 62

[00108] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(l / / )-one (0.100 g, 0.398 mmol), triethylamine (0.277 mL, 1.991 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.014 g, 0.020 mmol), copper iodide (Cul, 0.004 g, 0.020 mmol) and l-chloro-3-fluoro-5-iodobenzene (0.112 g, 0.438 mmol) were used as the same formulation materials Step 4 of Example 2 to obtain l-(3-(3-chloro-5fluorophenyl)prop-2-in-l-yl)-4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin2(l / / )-one (0.083 g, 54.9%) in a solid form (ESL / MS) 380.09 [M+H]+, calculated MW 379.72; 1H NMR (400 MHz, DMSO-in / 6) d 8.09 (d, J = 7.6 Hz, 1 H), 7.52 (t, J = 51.2 Hz, 1 H), 7.50 (td, J = 5.5, 2.9 Hz, 1 H), 7.41 (s), 7.37 ~ 7.37 H (m, 1 H), 7.01 (d, J = 1.2 Hz, 1 H), 6.83 (dd, J = 7.0, 1.8 Hz, 1 H), 5.05 (s, 2 H). Example 36: Synthesis of l-(3-(5-chloro-2-fluorophenyl)prop-2-in-l-yl)-4-(5(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin-2(lH)-one oo

[00109] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 yl)pyridin-2(17 / )-one (0.100 g, 0.398 mmol), triethylamine (0.277 mL, 1.991 mmol), dichloro bis(triphenylphosphine)palladium(II) (0.014 g, 0.020 mmol), copper iodide (Cul, 0.004 g, 0.020 mmol) and 4-chloro-l-fluoro-2-iodobenzene (0.112 g, 0.438 mmol) were used as similar starting materials Step 4 of Example 2 to obtain l-(3-(5-chloro-2fluorophenyl)prop-2-in-l-yl)-4-(5-(difluoromethyl)-l,3,4-oxadiazol-2-yl)pyridin2(l / / )-one (0.095 g, 62.8%) in one ml form of bitter MS (MS) 380.09 [M+H]+, calculated MW 379.72; NMR dexH(400 MHz, DMSO-in / 6) d 8.08 (d, J = 7.2 Hz, 1 H), 7.52 (t, J = 51.2 Hz, 1 H), 7.63 (dd, J = 5.8, 2.6 Hz, Petition 870250084318, of 18 / 09 / 2025, p. 56 / 79 / 62 H), 7.50 ~ 7.49 (m, 1 H), 7.34 (t, J = 9.2 Hz, 1 H), 7.02 (d, J = 1.6 Hz, 1 H), 6.84 (dd, J = 7.0, 1.8 Hz, 1 H), 5.09 (s, 2 H). Example 37: Synthesis of 2-(3-(3-chlorophenyl)prop-2-yn-1-yl)-5-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridazin-3(2H)-one Step 1: Synthesis of 6-oxo-1,6-dihydropyridazine-4-carbohydrazide

[00110] A solution in which methyl 6-oxo-1,6-dihydropyridazine-4-carboxylate (1.000 g, 6.488 mmol) was dissolved in ethanol (50 mL) at room temperature, and hydrazine hydrate (1.532 mL, 32.440 mmol) as starting materials were used similarly to Step 1 of Example 8 to obtain 6-oxo-1,6-dihydropyridazine-4-carbohydrazide (0.966 g, 96.6%) in the form of a yellow solid: LRMS (ES) m / z 155.33 [M+H]+, calculated MW 154.13. Step 2: Synthesis of 5-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridazin-3(2H)one

[00111] 6-Oxo-1,6-dihydropyridazine-4-carbohydrazide (0.966 g, 6.267 mmol), imidazole (1.280 g, 18.802 mmol) and 2,2-difluoroacetic anhydride (2.338 mL, 18.802 mmol) as starting materials were used similarly to Step 2 of Example 8 to obtain 5-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridazin-3(2H)-one (0.435 g, 32.4%) in the form of a yellow solid: LRMS (ES) m / z 215.80 [M+H]+, calculated MW 214.13. Step 3: Synthesis of 2-(3-(3-chlorophenyl)prop-2-yn-1-yl)-5-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridazin-3(2H)-one Petition 870250084318, dated 09 / 18 / 2025, pages 57 / 79 / 62

[00112] 5-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridazin-3(2H)-one (0.100 g, 0.467 mmol), 3-(3-chlorophenyl)prop-2-yn-1-yl methanesulfonate (0.120 g, 0.490 mmol) and cesium carbonate (CS2CO3, 0.228 g, 0.701 mmol) as starting materials were used similarly to Step 3 of Example 26 to obtain 2-(3-(3-chlorophenyl)prop-2-yn-1-yl)-5-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridazin-3(2H)-one (0.032 g, 18.9%) as a light brown solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 362.72; 1H NMR (400 MHz, DMSO-d6) d 7.74 (s, 1 H), 7.53 ~ 7.53 (m, 1 H), 7.47 ~ 7.38 (m, 3 H), 7.27 (s, 1 H), 6.91 (s, 1 H), 5.16 (s, 2 H). Example 38: Synthesis of 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin-2(1H)-one Step 1: Synthesis of 2-oxo-1,2-dihydropyrimidine-4-carbohydrazide

[00113] A solution in which methyl 2-oxo-1,2-dihydropyrimidine-4-carboxylate (0.500 g, 3.244 mmol) was dissolved in ethanol (20 mL) at room temperature, and hydrazine hydrate (0.766 mL, 16.220 mmol) as starting materials were used similarly to Step 1 of Example 8 to obtain 2-oxo-1,2-dihydropyrimidine-4-carbohydrazide (0.494 g, 98.8%) in the form of a yellow liquid: LRMS (ES) m / z 155.04 [M+H]+, calculated MW 154.13. Step 2: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin-2(1H)one Petition 870250084318, dated 09 / 18 / 2025, pages 58 / 79 / 62

[00114] 2-oxo-1,2-dihydropyrimidine-4-carbohydrazide (0.570 g, 3.698 mmol) and imidazole (0.755 g, 11.095 mmol) were dissolved in dichloromethane (10 mL) and stirred at room temperature for 30 minutes. The resulting solution and 2,2-difluoroacetic anhydride (1.379 mL, 11.095 mmol) as starting materials were used similarly to Step 2 of Example 8 to obtain 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin2(1H)-one (0.710 g, 89.7%) as a yellow solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 214.13. Step 3: Synthesis of 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyrimidin-2(1H)-one

[00115] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin-2(1H)-one (0.100 g, 0.467 mmol), 3-(3-chlorophenyl)prop-2-yn-1-yl methanesulfonate (0.120 g, 0.490 mmol) and cesium carbonate (Cs2CÜ3, 0.228 g, 0.701 mmol) as starting materials were used similarly to Step 3 of Example 26 to obtain 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyrimidin-2(1H)-one (0.024 g, 14.2%) in the form of a light brown solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 362.72; 1H NMR (400 MHz, DMSO-d6) d 7.73 (s, 1 H), 7.53 ~ 7.53 (m, 1 H), 7.47 ~ 7.36 (m, 3 H), 7.27 (s, 1 H), 6.91 (s, 1 H), 5.16 (s, 2 H). Example 39: Synthesis of 3-(3-(3-chlorophenyl)prop-2-yn-1-yl)-6-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin-4(3H)-one Step 1: Synthesis of 6-oxo-1,6-dihydropyrimidine-4-carbohydrazide

[00116] A solution in which methyl 6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.000 g, 6.488 mmol) was dissolved in ethanol (50 mL) Petition 870250084318, dated 09 / 18 / 2025, page 59 / 79 / 62 at room temperature, and hydrazine hydrate (1.624 g, 32.440 mmol) as starting materials were used similarly to Step 1 of Example 8 to obtain 6-oxo-1,6-dihydropyrimidine-4-carbohydrazide (0.996 g, 99.6%) in the form of a white solid: LRMS (ES) m / z 155.30 [M+H]+, calculated MW 154.13. Step 2: Synthesis of 6-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin-4(3H)one

[00117] 6-Oxo-1,6-dihydropyrimidine-4-carbohydrazide (0.996 g, 6.462 mmol), imidazole (1.320 g, 19.386 mmol) and 2,2-difluoroacetic anhydride (2.410 mL, 19.386 mmol) as starting materials were used similarly to Step 2 of Example 8 to obtain 6-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidine-4(3H)-one (0.231 g, 16.7%) was obtained as a brown liquid: LRMS (ES) m / z 215.08 [M+H]+, calculated MW 214.13. Step 3: Synthesis of 3-(3-(3-chlorophenyl)prop-2-yn-1-yl)-6-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyrimidin-4(3H)-one

[00118] 6-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyrimidin-4(3H)-one (0.100 g, 0.467 mmol), 3-(3-chlorophenyl)prop-2-yn-1-yl methanesulfonate (0.120 g, 0.490 mmol) and cesium carbonate (Cs2CO3, 0.228 g, 0.701 mmol) as starting materials were used similarly to Step 3 of Example 26 to obtain 3-(3-(3-chlorophenyl)prop-2-yn-1-yl)-6-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyrimidin-4(3H)-one (0.021 g, 12.4%) in the form of a brown solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 362.72; 1H NMR (400 MHz, DMSO-d6) d 7.74 (s, 1 H), 7.53 ~ 7.53 (m, 1 H), 7.47 ~ 7.36 (m, 3 H), 7.27 (s, 1 H), 6.92 (s, 1 H), 5.16 (s, 2 H). Petition 870250084318, dated 09 / 18 / 2025, pages 60 / 79 / 62 Example 40: Synthesis of 1-(3-(benzo[D]thiazol-5-yl)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one Step 1: Synthesis of 3-(benzo[ d ]thiazol-5-yl)prop-2-yn-1-ol

[00119] Prop-2-yn-1-ol (0.100 g, 1.784 mmol), 5-bromobenzo[d-Ithiazol] (0.401 g, 1.873 mmol), tetrakis(triphenylphosphine)palladium (0.103 g, 0.089 mmol), copper iodide (CuI, 0.017 g, 0.089 mmol), and triethylamine (0.746 mL, 5.351 mmol) were mixed with N,N-dimethylformamide (4 mL) at room temperature. The resulting mixture was microwave-irradiated and heated to 120°C for 30 minutes, and the temperature was reduced to room temperature to stop the reaction. The solvent was removed from the reaction mixture under reduced pressure, and the resulting concentrate was poured with a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure.The concentrate was purified and concentrated by column chromatography to obtain 3-(benzo[d]thiazol-5-yl)prop-2-yn-1-ol (0.052 g, 15.4%) as a yellow solid: LRMS (ES) m / z 190.21 [M+H]+, calculated MW 189.23. Step 2: Synthesis of 1-(3-(benzo[ d ]thiazol-5-yl)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one

[00120] 3-(Benzo[d]thiazol-5-yl)prop-2-yn-1-ol (0.052 g, 0.275 mmol), triethylamine (0.046 mL, 0.330 mmol), 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one (0.070 g, 0.330 mmol), and cesium carbonate (Cs2CO3, 0.134 g, 0.412 mmol) as starting materials were used similarly to Step 2 of Example 29 to obtain 1-(3-(benzo[d]thiazol-5 Petition 870250084318, of 18 / 09 / 2025, p. 61 / 79 / 62 yl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1 H)-one (0.016 g, 15.1%) in the form of a brown solid: LRMS (ES) m / z 385 [M+H+] calculated 384.36; 1H NMR (400 MHz, DMSO-d 6) d 9.43 (s, 1 H), 8.19 ~ 8.14 (m, 3 H), 7.66 ~ 7.40 (m, 1 H), 7.53 (s, 1 H), 7.02 (d, J = 2.0 Hz, 1 Hz, Jdd = 6.85). 7.0, 2.2 Hz, 1 H), 5.08 (s, 2 H). Example 41: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2methylbenzo[D]thiazol-6-yl)prop-2-in-1-yl)pyridin-2(1 H)-one Step 1: Synthesis of 3-(2-methylbenzo[ d ]thiazol-6-yl)prop-2-in-1-ol

[00121] Prop-2-in-1-ol (0.025 g, 0.446 mmol), 6-bromo-2-methylbenzo[d]thiazole (0.107 g, 0.468 mmol), tetrakis(triphenylphosphine)palladium (0.026 g, 0.022 mmol), copper iodide (CuI, 0.004 g, 0.022 mmol) and triethylamine (0.186 mL, 1.338 mmol) were used similarly to Step 1 of Example 40 to obtain 3-(2-methylbenzo[d]thiazol-6-yl)prop-2-in-1-ol (0.068 g, 75.0%) in the form of a brown liquid: LRMS (ES) m / z 204.05 [M+H]+, calculated MW 203.26. Step 2: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2methylbenzo[ d ]thiazol-6-yl)prop-2-yn-1-yl)pyridin-2(1H)-one

[00122] 3-(2-Methylbenzo[d]thiazol-6-yl)prop-2-in-1-ol (0.060 g, 0.295 mmol), triethylamine (0.049 mL, 0.354 mmol), methanosulfonyl chlorate (0.027 mL, 0.354 mmol), 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin2(1 H)-one (0.075 g, 0.354 mmol) and cesium carbonate (Cs2CO3, 0.144 g, 0.443 mmol) were used as starting materials using the simple method of Example 2 29 to obtain 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2yl)-1 -(3-(2-methylbenzo [ d ] thiazol-6-yl)prop-2-in-1 -yl)pyridin-2( 1H)-one (0.005 g, 4.3%) in the form of a brown solid (MS: m / LR) 399.18 [M+H]+, MW Petition 870250084318, of 18 / 09 / 2025, p. 62 / 79 / 62 calculated 398.39; 1H NMR (400 MHz, DMSO-d6) and 8.43 (d, J = 5.2 Hz, 1 H), 8.00 (d, J = 2.0 Hz, 1 H), 7.81 (d, J = 8.4 Hz, 1 H), 7.63 (dd, J = 5.4, 1.4 Hz, 1 H), 7.52 ~ 7.49 (m, 2 H), 7.23 (t, J = 51.8 Hz, 1 H), 5.29 (s, 2 H), 2.80 (s, 3 H). Example 42: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2methyl-1 H -imidazol-5-yl)prop-2-in-1-yl)pyridin-2(1 H)-one

[00123] 5-Iodo-2-methyl-1 H-imidazole (0.050 g, 0.240 mmol), 4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1 -(prop-2-in-1 -yl)pyridin-2( 0.00.3.3 mmol), copper iodate (CuI, 0.005 g, 0.024 mmol), 1,1'bis(diphenylphosphine)ferrocene (0.013 g, 0.024 mmol) and methanosulfonate 1,1ferrocenodiyl-bis(diphemlphosphine)(2'-ammo '-biphenyl-2-yl)palladium(II) (0.022 g, 0.024 mmol) as starting materials were used in a manner similar to Step 4 of Example 2 to obtain 4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3-(2-methyl-1H-imidazol-5-yl)prop-2-in-1 -yl)pyridin-2(1 H) was (0.022 g, 27.6%) in the form of a brown solid: LRMS (ES) m / z 332.20 [M+H]+, MW calculated 331.28; 1H NMR (400 MHz, DMSO-d6) d 11.92 (s, 1 Hz), 8.04 (d, J = 6.8 Hz, 1 H), 7.65 ~ 7.29 (m, 2 H), 6.99 (d, J = 2.0 Hz, 1 H), 6.83 (dd, J = 6.8, 1.6 Hz, 1 H), 4.96 (s, 2 H), 2.18 (s, 3 H). Example 43: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3(thiophen-3-yl)prop-2-in-1-yl)pyridin-2(1 H) -one

[00124] 3-Iodothiophene (0.030 g, 0.143 mmol), 4-(5-(difluoromethyl) 1,3,4-oxadiazol-2-yl)-1-(prop-2-in-1-yl)pyridin-2(1 H)-one (0.047 g, 0.186 mmol), copper iodide (CuI, 0.003 g, 0.014 mmol), 1,1'-ferrocenedyl Petition 870250084318, of 18 / 09 / 2025, p. 63 / 79 / 62 bis(diphenylphosphine) (0.008 g, 0.014 mmol) and methanosulfonate 1,1ferrocenediyl-bis(diphenylphosphine)(2'-amino-1,1'-biphenyl-2-yl)palladium(n) (0.01 g, 0.014 mmol) as partial material were used in a manner similar to Step 4 of Example 2 to obtain 4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-1 -(3-(thiophen-3-yl)prop-2-in-1 -yl)pyridin-2( 1H)-one (0.01 g, 76%, only 5%) in the form of brown LRMS (ES) m / z 334.12 [M+H]+, calculated MW 333.31; 1H NMR (400 MHz, DMSO-d 6) d 8.07 (d, J = 7.2 Hz, 1 H), 7.81 (dd, J = 3.0, 1.0 Hz, 1 H), 7.65 ~ 7.40 (m, 1 H), 7.59 ~ 7.57 (m, J = 7.1 Hz), 5.2, 1.2 Hz, 1 H), 7.00 (d, J = 2.0 Hz, 1 H), 6.83 (dd, J = 7.2, 2.0 Hz, 1 H), 5.00 (s, 2 H). Example 44: Synthesis of 1-(1-(3-chlorophenyl)pent-1-in-3-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one Step 1: Synthesis of 1-(3-chlorophenyl)pent-1-in-3-ol

[00125] 1-chloro-3-iodobenzene (0.500 g, 2.097 mmol), pent-1-yn-3-ol (0.229 g, 2.726 mmol), tetrakis(triphenylphosphine)palladium (0.121 g, 0.105 mmol), copper iodide (CuI, 0.020 g, 0.105 mmol) and triethylamine (0.877 mL, 6.291 mmol) as starting materials were used similarly to Step 1 of Example 40 to obtain 1-(3-chlorophenyl)pent-1-yn-3-ol (0.190 g, 46.5%) in the form of a yellow liquid: LRMS (ES) m / z no detection [M+H]+, calculated MW 194.66; 1H NMR (400 MHz, DMSO-d 6) d 7.42 ~ 7.39 (m, 2 H), 7.38 ~ 7.32 (m, 2 H), 5.44 (d, J = 5.6 Hz, 1 H), 4.34 (q, J = 6.0 Hz, 1 H), 1.67 ~ 1.56 (m, 2 H), 0.93 (t, J = 7.4 Hz, 3 H). Step 2: Synthesis of 1-(3-bromopent-1-yn-1-yl)-3-chlorobenzene Petition 870250084318, dated 09 / 18 / 2025, pp. 64 / 79 / 62

[00126] 1-(3-chlorophenyl)pent-1-yn-3-ol (0.200 g, 1.027 mmol) was dissolved in dichloromethane (4 mL), and phosphorus tribromide (0.105 mL, 1.110 mmol) was added at 0°C and stirred at the same temperature for 1 hour and further stirred at room temperature for 3 hours. Water (0.555 mL, 30.823 mmol) was added to the reaction mixture at room temperature and stirred for 5 minutes to stop the reaction. A saturated aqueous solution of sodium bicarbonate was poured into the reaction mixture, and the resulting mixture was extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified and concentrated by column chromatography to obtain 1-(3-bromopent-1-yn-1-yl)-3-chlorobenzene (0.165 g, 62.4%) in the form of a brown solid: Rf 0.4; LRMS (ES) m / z no detection [M+H]+, calculated MW 257.56. Step 3: Synthesis of 1-(1-(3-chlorophenyl)pent-2-in-3-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2(1 H)-one

[00127] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1 H)-one (0.050 g, 0.235 mmol), 1-(3-bromopent-1-in-1-yl)-3-chlorobenzene (0.066 g, 0.062 mmol of potassium carbonate) and (0.097 g, 0.704 mmol) as starting materials were used in a manner similar to Step 3 of Example 26 to obtain 1-(1-(3-chlorophenyl)pent-1-in-3-yl)-4-(5-(difluoromethyl)-1,3,4-oxazole2-yl (2) (0.029 g, 31.7%) in the form of a brown solid: LRMS (ES) m / z 390.20 [M+H]+, calculated MW 389.79; Ή NMR (400 MHz, DMSO-d6) d 8.46 (d, J = 6.0 Hz, 1 H), 7.67 ~ 7.54 (m, 2 H), 7.45 ~ 7.40 (m, 3 H), 7.36 ~ 7.33 (m, 28 H), t H), 2.00 ~ 1.93 (m, 2 H), 1.07 (t, J = 7.2 Hz, 3 H). Petition 870250084318, of 18 / 09 / 2025, p. 65 / 79 / 62 Example 45: Synthesis of 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-6-methylpyridin-2(1H)-one Step 1: Synthesis of 6-methyl-2-oxo-1,2-dihydropyridine-4-carbohydrazide

[00128] Methyl 6-methyl-2-oxo-1,2-dihydropyridine-4-carboxylate (2.000 g, 11.965 mmol) and hydrazine monohydrate (0.756 mL, 15.554 mmol) as starting materials were used similarly to Step 1 of Example 8 to obtain 6-methyl-2-oxo-1,2-dihydropyridine-4-carbohydrazide (1.731 g, 86.5%) in the form of a beige solid: LRMS (ES) m / z 168.05 [M+H]+, calculated MW 167.17. Step 2: Synthesis of 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)6-methylpyridine-2(1H)-one

[00129] 6-Methyl-2-oxo-1,2-dihydropyridine-4-carbohydrazide (1.731 g, 10.355 mmol), imidazole (1.719 mL, 31.064 mmol) and 2,2-difluoroacetic anhydride (2.832 mL, 22.780 mmol) as starting materials were used similarly to Step 2 of Example 8 to obtain 4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-6-methylpyridin-2(1H)-one (1.821 g, 77.4%) in the form of an ivory solid: LRMS (ES) m / z 228.16 [M+H]+, calculated MW 227.17. Step 3: Synthesis of 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)-

[00130] 4-(5-(Difluoromethyl)-1,3,4-oxadiazol-2-yl)-6-methylpyridin Petition 870250084318, dated 09 / 18 / 2025, page 66 / 79 / 62 2(1 H)-one (0.100 g, 0.440 mmol), 3-(3-chlorophenyl)prop-2-in-1-yl methanesulfonate (0.118 g, 0.484 mmol) and potassium carbonate (0.122 g, 0.880 mmol) were used as separate form materials 3 of Example 26 to obtain 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)-6-methylpyridin-2(1H)-one (0.036 g, 21.8%) in beige solid formation (ES: LR / MS) 376.19 [M+H]+, calculated MW 375.76; 1H NMR (400 MHz, DMSO-d6) d 7.51 (t, J = 52.2 Hz, 1 H), 7.52 (m, 1 H), 7.46 ~ 7.43 (m, 1 H), 7.39 ~ 7.36 (m, 2 H), 6.90 ~ 7.36 (m, 2 H), 5.14 (s, 2 H), 2.63 (s, 3 H). Example 46: Synthesis of 5-bromo-1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1 H)-one Step 1: Synthesis of 5-bromo-2-oxo-1,2-di-hydropyridine-4-carbohydrazide oo

[00131] Methyl 5-bromo-2-oxo-1,2-dihydropyridine-4-carboxylate (2.000 g, 8.620 mmol) and hydrazine monohydrate (0.545 mL, 11.205 mmol) as starting materials were used similarly to Step 1 of Example 8 to obtain 5-bromo-2-oxo-1,2-dihydropyridine-4-carbohydrazide (1.619 g, 80.9%) in the form of a beige solid: LRMS (ES) m / z 232.06 [M+H]+, calculated MW 232.04. Step 2: Synthesis of 5-bromo-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin2(1H)-one

[00132] 5-Bromo-2-oxo-1,2-dihydropyridine-4-carbohydrazide (1.619 g, 6.977 mmol), imidazole (1.159 mL, 20.932 mmol) and 2,2-difluoroacetic anhydride (1.908 mL, 15.350 mmol) as starting materials were Petition 870250084318, dated 09 / 18 / 2025, pp. 67 / 79 / 62 used similarly to Step 2 of Example 8 to obtain 5-bromo-4(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one (0.589 g, 28.9%) in the form of a light yellow solid: LRMS (ES) m / z 292.04 [M+H]+, calculated MW 292.04. Step 3: Synthesis of 5-bromo-1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one

[00133] 5-Bromo-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one (0.100 g, 0.342 mmol), 3-(3-chlorophenyl)prop-2-yn-1-yl methanesulfonate (0.092 g, 0.377 mmol) and potassium carbonate (0.095 g, 0.685 mmol) as starting materials were used similarly to Step 3 of Example 26 to obtain 5-bromo-1-(3-(3-chlorophenyl)prop-2-yn-1yl)-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one (0.027 g, 17.9%) in the form of a brown solid: LRMS (ES) m / z no detection [M+H]+, calculated MW 440.63; 1H NMR (400 MHz, DMSO-d 6) d 8.28 (s, 1 H), 7.50 (s, 1 H), 7.44 (t, J = 21.4 Hz, 1 H), 7.46 ~ 7.43 (m, 1 H), 7.39 ~ 7.37 (m, 2 H), 6.78 (s, 1 H), 4.95 (s, 2 H). Experimental Example 1: Fluorescence-based enzyme activity assay

[00134] To measure the inhibitory effect of the compounds on histone deacetylase 6 (HDAC6) activity, an enzymatic activity assay was performed to evaluate enzymatic activity by reacting human HDAC6 enzyme with a substrate to which a fluorescent peptide of p53 residues 379-382 was attached. The test compounds were dissolved in 100% DMSO at a concentration of 10 mM to prepare a stock solution. An initial concentration of 30 pM was prepared from the stock solution, followed by serial 1 / 3 dilutions to prepare the test buffer solution. Trichostatin A (TSA)—which is the reference compound—was used. Petition 870250084318, dated 09 / 18 / 2025, pp. 68 / 79 / 62 used to confirm the validity of the experiment—was serially diluted by 1 / 3 with the test buffer solution, starting from the highest concentration of 1 μM. To react the test compounds and the TSA prepared in the test buffer with the HDAC6 enzyme, they were dispensed onto a 96-well black plate and the plate was centrifuged. Then, the reaction was carried out at room temperature for 10 minutes. After 10 minutes, the substrate was dispensed and the plate was sealed. The reaction was carried out at 30°C for 1 hour under light-blocking conditions. Fluorescence values ​​were measured using a plate reader (wavelength: excitation / emission = 360 / 460 nm). Fluorescence measurements were normalized for the group treated with the HDAC6 enzyme as 100% and the untreated group as 0%, respectively. The activity of the compounds was calculated as the IC50 value and represented in Table 1 (+: 500 - 1.000 nM, ++: 100 - 500 nM, +++: less than 100 nM). [Table 1] Example No. HDAC6 (IC50, nM) Example No. HDAC6 (IC50, nM) 1 +++ 21 +++ 2 + 22 +++ 3 ++ 23 +++ 4 ++ 24 +++ 5 ++ 25 ++ 6 + 27 +++ 7 + 28 + 8 +++ 29 +++ 9 +++ 30 + 10 +++ 31 +++ 11 +++ 32 +++ 12 +++ 33 +++ 13 +++ 34 +++ 14 +++ 35 +++ 15 +++ 36 ++ 16 +++ 40 ++ 17 ++ 41 + 18 +++ 42 +++ 19 ++ 43 +++ 20 ++ 45 ++ Experimental Example 2: Fluorescence-based Ca2+ mobilization assay

[00135] To measure the antagonist's activity on mGluR5, it was Petition 870250084318, dated 09 / 18 / 2025, pp. 69 / 79 61 / 62 An experiment was conducted to verify the alteration in intracellular Ca2+ levels using the HEK293 cell line, which permanently overexpresses mGluR5. Cells in cell culture medium were aliquoted into a 384-well plate coated with poly-D-lysine and cultured in a 37°C incubator supplied with 5% CO2. The following day, the medium was removed and a dye loading buffer—in which a reagent capable of measuring Ca2+ was dissolved—was added and then incubated at 37°C for 60 minutes. The test compounds were dissolved in 100% DMSO to a final concentration of 10 mM to form a stock solution. An initial concentration of 10 μM was prepared from the stock solution, followed by serial dilutions to prepare working solutions (working solutions of the test compound).Working solutions of the test compound were added to cells that were incubated in dye loading buffer, which were maintained for 30 minutes at room temperature in a light-protected state before measurement. The L-glutamate-induced change in Ca2+ level at ECso concentration was measured for 2 minutes using FLIPR Tetra (MDS Analytical Technologies). The values ​​of the fluorescent Ca2+ signal in the presence of the test compounds were normalized to the fluorescent signal elicited by the L-glutamate concentration at EC80 as 100% and that elicited by the vehicle as 0% to estimate the % inhibition of the test compounds. The antagonistic efficacy of the test compounds was calculated as IC50 values ​​and represented in Table 2 (+: 1,000-2,000 nM, ++: 500-1,000 nM, +++: 100-500 nM, ++++: less than 100 nM). [Table 2] Example No. mGluR5 human (ICso, nM) Example No. mGluR5 human (ICso, nM) 7 + 28 + 15 ++ 30 ++ 17 + 31 ++ 18 + 36 + 19 + 37 ++ 20 + 38 ++ 23 + 39 ++ Petition 870250084318, dated 09 / 18 / 2025, pp. 70 / 79 / 62 Example No. mGluR5 human (IC50, nM) Example No. mGluR5 human (IC50, nM) 24 ++ 44 + 25 ++ 45 ++

Claims

CLAIMS 1. Compound, characterized in that it is of the following Formula 1 or a pharmaceutically acceptable salt thereof: [Formula 1] In Formula 1, Ar is aryl or heteroaryl, wherein the aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy and alkylsulfonyl; Ri is alkyl or haloalkyl; R2 is H or alkyl; one of Xi, X2 and X3 is C, and the others are N; Yi, Y2 and Y3 are each independently CR3 or N; where R3 is H, halo or alkyl; n is an integer from 0 to 2; and the heteroaryl has one or more heteroatoms selected from N, O and S.

2. Pharmaceutically acceptable compound or salt thereof according to claim 1, characterized in that Ar is a 5- to 10-membered C6-C10 aryl or heteroaryl, wherein the aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of halo, cyano, C1-C7 alkyl, C1-C7 halo-alkyl, C1-C7 alkoxy, C1-C7 halo-alkoxy and C1-C7 alkylsulfonyl; Ri is C1-C7 alkyl or C1-C7 halo-alkyl; R2 is H or C1-C7 alkyl; one of Xi, X2 and X3 is C, and the others are N; Petition 870250084318, dated 09 / 18 / 2025, p. 72 / 79 2 / 7 Yi, Y2 and Y3 are each independently CR3 or N; where R3 is H, halo or C1-C7 alkyl; n is an integer of i or 2; and the heteroaryl has 1 to 3 heteroatoms selected from N, O and S.

3. A pharmaceutically acceptable compound or salt thereof according to claim 1, characterized in that the compound of Formula 1 is a compound of the following Formula 2: [Formula 2] O R2 yAnA. _ II I RivVy^ Ar \\ / / '2 NN in Formula 2, n is an integer from 1 to 2; and Ar, R1, R2, Y1, Y2 and Y3 are the same as defined in claim 1.

4. A pharmaceutically acceptable compound or salt thereof according to claim 1, characterized in that the compound of Formula 1 is a compound of the following Formula 3: in Formula 3, n is an integer from 1 to 2; and Ar, R1, R2, Y1, Y2 and Y3 are the same as defined in claim 1.

5. A pharmaceutically acceptable compound or salt thereof according to claim 1, characterized in that the aryl group is phenyl; and the heteroaryl group is pyridyl, thienyl, imidazolyl or benzothiazolyl.

6. Pharmaceutically acceptable compound or salt of the same as in Petition 870250084318, dated 09 / 18 / 2025, page 73 / 79 3 / 7 according to claim 1, characterized in that all Yi, Y2 and Y3 are CR3.

7. Pharmaceutically acceptable compound or salt thereof according to claim 6, characterized in that R3 is H.

8. Compound or pharmaceutically available according to indication 1, characterized by the fact that the compound of Formula 1 is selected from the group consisting of: 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-phenylprop-2-in1 -yl)pyridin-2(1H)-one; 1-(3-phenylprop-2-in-1-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol3-yl)pyridin-2(1H)-ona; 1 -(3-(pyridin-4-yl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1 -(3-(pyridin-3-yl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1 -(3-(pyridin-2-yl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1 -(3-(2-fluorophenyl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 1 -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(trifluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-4yl)prop-2-in-1-yl)pyridin-2(1H)-one;4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-3yl)prop-2-in-1-yl)pyridin-2(1H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(pyridin-2yl)prop-2-in-1-yl)pyridin-2(1H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(4fluorophenyl)prop-2-in-1-yl)pyridin-2(1H)-ona; Petition 870250084318, 18 / 09 / 2025, pág. 74 / 79 4 / 7 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3fluorophenyl)prop-2-in-1 -yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2fluorophenyl)prop-2-in-1 -yl)pyridin-2( 1 H)-one; 1-(3-(4-chlorophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 1-(3-(2-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(p-tolyl)prop-2in-1 -yl)pyridin-2( 1 H)-one;4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(m-tolyl)prop-2in-1 -yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethyl)phenyl)prop-2-in-1 -yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethoxy)phenyl)prop-2-in-1 -yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3-methoxyphenyl)prop-2-in-1 -yl)pyridin-2(1H)-one; 1-(3-(6-chloropyridin-2-yl)prop-2-in-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(2-chloropyridin-4-yl)prop-2-in-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(6-methylpyridin2-yl)prop-2-in-1 -yl)pyridin-2(1H)-ona; 1-(3-(3-bromophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-ona; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3Petição 870250084318, de 18 / 09 / 2025, pág. 75 / 79 5 / 7 (difluoromethyl)phenyl)prop-2-in-1 -yl)pyridin-2( 1H)-ona;1-(3-(3-(difluoromethoxy)phenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2( 1 H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(5-methylpyridin3-yl)prop-2-in-1 -yl)pyridin-2( 1 H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2( 1H)-one; 3-(3-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-2-oxopyridin1 (2H)-yl)prop- 1-in-1 -yl)benzonitrile; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(methylsulfonyl)phenyl)prop-2-in-1 -yl)pyridin-2( 1H)-one; 1-(3-(3-chloro-2-fluorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chloro-4-fluorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chloro-5-fluorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one;1-(3-(5-chloro-2-fluorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 2-(3-(3-chlorophenyl)prop-2-in-1-yl)-5-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridazin-3(2H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyrimidin-2( 1 H)-one; 3-(3-(3-chlorophenyl)prop-2-in-1-yl)-6-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyrimidin-4(3H)-ona; 1-(3-(benzo[ d ]thiazol-5-yl)prop-2-in-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2(1H)-ona; Petition 870250084318, 18 / 09 / 2025, pág. 76 / 79 6 / 7 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(2methylbenzo[ d ]thiazol-6-yl)prop-2-in-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)- 1-(3-(2-methyl-1Himidazol-5-yl)prop-2-in-1 -yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(thiophen-3yl)prop-2-in-1 -yl)pyridin-2(1H)-one; 1-(1 -(3-chlorophenyl)pent-1 -yn-3-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2(1H)-one;1 -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-6-methylpyridin-2(1H)-one; and 5-bromo-1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one.; 9. Pharmaceutically acceptable compound or salt thereof according to claim 8, characterized in that the compound of Formula 1 is selected from the group consisting of: 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2(1H)-one; 1-(3-(3-chlorophenyl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(p-tolyl)prop-2yn-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(m-tolyl)prop-2yn-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethyl)phenyl)prop-2-yn-1-yl)pyridin-2(1H)-one; 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(3(trifluoromethoxy)phenyl)prop-2-yn-1-yl)pyridin-2(1H)-one; 1-(3-(2-chloropyridin-4-yl)prop-2-yn-1-yl)-4-(5-(difluoromethyl)1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; Petition 870250084318, of 09 / 18 / 2025, p.77 / 79 7 / 7 4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-1-(3-(6-methylpyridin2-yl)prop-2-in-1 -yl)pyridin-2(1H)-one; 1-(3-(3-bromophenyl)prop-2-in-1-yl)-4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2( 1 H)-one; 1-(3-(3-(difluoromethoxy)phenyl)prop-2-in-1-yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1-yl)-4-(5-(trifluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; 1-(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,2,4oxadiazol-3-yl)pyridin-2(1H)-one; 3-(3-(4-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-2-oxopyridin1 (2H)-yl)prop- 1-in-1 -yl)benzonitrile; 1 -(3-(5-chloro-2-fluorophenyl)prop-2-in-1 -yl)-4-(5(difluoromethyl)-1,3,4-oxadiazol-2-yl)pyridin-2(1H)-one; 1-(1 -(3-chlorophenyl)pent-1 -in-3-yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)pyridin-2( 1 H)-one; and 1 -(3-(3-chlorophenyl)prop-2-in-1 -yl)-4-(5-(difluoromethyl)-1,3,4oxadiazol-2-yl)-6-methylpyridin-2(1H)-one.

10. Pharmaceutical composition for the prevention or treatment of movement disorders, characterized in that it comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof as defined in any one of claims 1 to 9 as the active ingredient, together with a pharmaceutically acceptable vehicle or excipient.

11. Pharmaceutical composition according to claim 10, characterized in that the movement disorder is Huntington's disease, Parkinson's disease, or levodopa-induced dyskinesia (LID). Petition 870250084318, dated 09 / 18 / 2025, pp. 78 / 79