RU2265015C2 - 1,2-dihydropyridine compounds, method for their preparing and their using - Google Patents

Abstract

FIELD: organic chemistry, medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to derivatives of 1,2-dihydropyridine of the general formula (I)

,

their salts or hydrates wherein Q means oxygen atom (O); R¹, R², R³, R⁴ and R⁵ are similar or different of one another and each radical means hydrogen atom, halogen atom, (C₁-C₆)-alkyl group or group represented by the formula: -X-A (wherein X means a simple bond, (C₁-C₆)-alkylene group); A means (C₆-C₁₄)-aromatic hydrocarbocyclic group or 5-14-membered aromatic heterocyclic group. Also, invention describes a method for preparing compounds and pharmaceutical composition. Compounds possess the strong inhibitory effect on AMPA receptors and/or kainate receptors.

EFFECT: improved preparing method, valuable properties of compounds and composition.

99 cl, 1 tbl, 414 ex

Description

The present invention relates to a new compound, its salt and its hydrates and to a method for their preparation. In particular, it relates to a compound of pyridone, its salt and its hydrates, which are used as inhibitors for non-NMDA receptors (not related to NMDA) and, in particular, as inhibitors for AMPA receptors.

Glutamate and aspartate are important amino acids that are involved in the functions of sensory nerves, such as recognition, memory, movement, respiration, regulation of cardiovascular activity and sensation, and are also called stimulating neurotransmitters. In the manifestation of their physiological activities, their interaction with a specific receptor is important, and, in general, two types of receptors are known - the type of ion channel and the type associated with the G-protein. The latter, in addition, is subdivided into the N-methyl-D-aspartate receptor (NMDA), the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA), the kainate receptor, etc. On the other hand, it is known that an amino acid, as an exciting neurotransmitter, induces neurotoxicity by, for example, abnormal excitation of the central nervous system. It was noted that the aforementioned toxicity is so serious that it entails the death of nerve cells, causing various nervous diseases. The main nervous diseases that are known are cerebral ischemia, head trauma, spinal cord injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's chorea; AIDS disorder (AIDS); epilepsy, neurodegeneration observed after hypoxia, mental disorder, impaired mobility, pain, muscle spasms; nervous breakdown caused by toxin during food poisoning; various neurodegenerative diseases, various mental illnesses, chronic pain, migraine, pain with a malignant disease; pain caused by diabetic breakdown. All these diseases are serious diseases, many of the mechanisms of occurrence of which, etc. they have not yet been clarified, and pharmaceutical agents that are effective in treating them have not yet been found, however, they believe that they are closely related to the excessive release / accumulation of exciting neurotransmitters, changes in the pattern of expression of receptors, etc. For example, it has been reported that glutamate concentration in cerebrospinal fluid and plasma increases with stroke, cerebral ischemia, head injury and spinal cord injury (Castillo, J., Dazalos, A. and Noya, M., Lancet, 1997, 346: 79-83 ; etc.). There is a message that neuropathy occurs when glutamate, NMDA, AMPA, kainat, etc. overexposure to nerve cells (Meldrum, B., Brain Res. Reviews, 18, 293, 1993). In Alzheimer's disease, there are reports that the α-amyloid protein enhances the neurotoxicity of glutamate and that it promotes the release of glutamate (Arias, C., Arrieta, I. and Tapia, R., J. Neurosci. Res., 1995, 41: 561-566 ; etc.). In the case of Parkinson's disease, there are reports that L-dopa hydroxide activates the AMPA receptor (Cha, JJ, et al., Neurosci. Lett., 1991, 132: 55-58) and enhances neurotoxicity (Olney, JW, et al., 1990, 108: 269-272; Rosenberg, PA, et al., Proc. Natl. Acad. Sci. USA, 1991, 88: 4865-4869). There is another report that L-dopa promotes the generation of free radicals, which leads to the development of oxidative stress (Smith, T. S., et al., Neuroreport, 1994, 5: 1009-1011). In the case of Huntington's chorea, it is reported that a substance that inhibits the release of glutamate is effective in alleviating the symptoms of the disease. In the case of ALS (ALS), there are many reports indicating the participation of glutamate in the pathology of this disease. There are several cases in which HIV-infected patients suffer from a deficiency in the sensory nerve function responsible for recognition, and even glutamate is assumed to be involved in the development of such a nervous disease. For example, gp 120, which is a glycoprotein in the envelope of an HIV virus, has been reported to inhibit glutamate uptake by astrocytes (Dreyer, E. B., Eur. J. Neurosci., 1995, 7: 2502-2507; Ushijima, H., et al., Eur. J. Neurosci., 1995, 7: 1353-1359), while a substance that inhibits glutamate release inhibits neurodegeneration of gp 120 (Sindou, P., et al., J. Neurosci. 1994, 126: 133-137; Muller, WEG, et al., Eur. J. Pharmacol. Molec. Pharmacol., 1992, 226: 209-214; Lipton, SA, Neurology, 1992, 42: 1403-1405). Regarding allergic encephalomyelitis, there is a report that in mice that have the aforementioned inflammation, an enzyme that breaks down glutamate, grouped outside the cells, is deficient (Hardin-Pouzet, H., Glia., 1997, 20: 79-85 ) Olivopontocerebellar atrophy is a disease that sometimes occurs in Parkinson's disease, and an anti-GluR2 antibody has been discovered that is a subunit of the AMPA receptor (Gahring, LC, Neurology, 1997, 48: 494-500), and there is a suggestion of a relationship between olivopontocerebellar atrophy and the AMPA receptor. Regarding the report regarding epilepsy, there is evidence that in mice that are unable to convert GluR2 in the AMPA receptor, Ca ²⁺ permeability in the AMPA receptor increases, whereby a sudden attack leading to death can be triggered (Brusa, R. Science, 1995, 270: 1677-1680). In addition to the foregoing, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenz [f] quinoxaline; Sheardown, et al., Science, 247, 571, 1990) and other compounds that inhibit AMPA receptors have been shown to have sedative effects. and anticonvulsant effects (J. Pharmacol. Exp. Ther., 260, 742, 1992; Pharmacol. Biochem. Behavior, 1998, 60: 119-124) and, in addition, there are reports regarding the association of the AMPA / Kainate receptor with urination impairment substance abuse, pain, etc. (J. Pharmacol. Exp. Ther., 280, 894-904, 1997; Neuroscience Letters, 268: 127-130, 1999).

It can be expected that substances exhibiting an antagonistic effect on excitatory neurotransmitter receptors will be useful in the treatment of the aforementioned nervous diseases. Particular attention is currently being paid to substances that antagonize non-NMDA receptors, such as the AMPA receptor and the kainate receptor. For example, international publication WO 00/01376 reports that inhibitors of the interaction of glutamate with AMPA and / or the kainate receptor or their complex are useful for treating demyelinating disorders such as encephalitis, acute disseminated encephalomyelitis, acute demyelinating polyneuropathy (Hyena-Barre syndrome) chronic inflammatory demyelinating polyneuropathy, multiple sclerosis, Markiafava-Binyami disease; demyelination of nerve fibers related to the central Varolian bridge; Devik's syndrome, Balo's disease; myelopathy due to HIV or HTLV (human T-cell leukemia virus), progressive multifocal leukoencephalopathy, secondary demyelinating disorder, such as secondary lupus erythematosus disorders, nodosa (nodular) polyarteritis, Sjogren's syndrome, isolated sarcoidosis cerebral) vasculitis. Regarding a compound having an inhibitory effect on the AMPA receptor and the kainate receptor, there are reports which disclose the following compounds.

 (1) Compounds competitively inhibiting the AMPA receptor represented by the following formulas

(2) Compounds that non-competitively inhibit the AMPA receptor represented by the following formulas

(3) In addition to the above, in international publications WO 94/25469, WO 96/10023, US patent 5356902, etc. reported compounds competitively inhibiting the AMPA receptor having the quinoxalindione structure, and in international publications WO 95/01357, WO 97/28135, WO 97/18163, WO 97/43276, WO 97/34878, WO 98/38173, European patent 802195 DE 19643037, etc. reported compounds that noncompetitively inhibit the AMPA receptor.

On the other hand, with regard to compounds of 1,2-dihydropyridine, there are several reports concerning compounds of a similar structure, as, for example, in the international publication WO 98/55480, compounds represented by the formula

[in the formula R represents a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, a C _1-6 alkoxy group, etc .; V represents CH or N; W represents O or S; X represents a phenyl group which is unsubstituted or substituted by one group or several groups selected from a C _1-6 alkyl group, CF ₃ , a cyano group, a nitro group, a halogen, etc. or an aromatic hetero group which is substituted with one group or several groups selected from a C _1-6 alkyl group, CF ₃ , halogen, etc .; Y represents a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, an aryl group, etc .; Z represents a halogen, a C _3-6 cycloalkyl group, a C _1-6 alkylthio group, a C _2-6 alkenylthio group, an aryl group, etc.], or their salts as a ligand for the subunit of GABA _A α, and in the international publication WO 00 / 07988 discloses compounds represented by the formula

[in the formula, n is 0, 1, 2, 3, 4 or 5; X represents a hydrogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, a trifluoromethyl group, a trifluoromethoxy group or halogen; A represents an amino group, a C _1-4 alkylamino group, a C _1-4 dialkylamino group, a morpholino group, a piperidino group or a pyrrolidino group] used to treat epilepsy, however, these publications do not mention the connection of the above compounds with the AMPA receptor and the kainate receptor.

There is a great demand for compounds that inhibit the DMPA / kainate receptor and which are useful as pharmaceuticals. However, no compounds have yet been discovered that exhibit a strong inhibitory effect on the AMPA receptor and / or kainate receptor and which would be extremely useful as pharmaceuticals that are effective in clinical practice. Thus, the object of the present invention is to investigate and find a compound that inhibits the AMPA receptor and / or the kainate receptor, which inhibits the neurotoxicity of excitatory neurotransmitters and provides the necessary neuroprotective effect as pharmaceuticals that are to be used as therapeutic / prophylactic / enhancing remedies for various nervous diseases.

Under the aforementioned circumstances, the applicants conducted an intensive study and, as a result of it, they were successful in the synthesis of a new compound represented by formula (I), its salt or its hydrates, and an excellent way was found to obtain the specified compound or its salt, and an intermediate suitable for receiving it. In addition, quite unexpectedly, the applicants found that the aforementioned compound (I), its salt or its hydrates show a strong antagonistic effect on the AMPA receptor, after which the present invention was completed.

The compound represented by the following formula, its salt or its hydrates

In the formula, Q means NH, O or S, and R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different from each other and each means a hydrogen atom, a halogen atom, a C _1-6 alkyl group or group, represented by the formula —X — A (where X is a single bond, an optionally substituted C _1-6 alkylene group, an optionally substituted C _2-6 alkenylene group, an optionally substituted C _2-6 alkynylene group, —O—, —S—, —CO -, -SO-, -SO ₂ -, -N (R ⁶ ) -, -N (R ⁷ ) -CO-, -CO-N (R ⁸ ) -, -N (R ⁹ ) -CH ₂ -, -CH ₂ -N (R ¹⁰ ) -, -CH ₂ -CO-, -CO-CH ₂ -, -N (R ¹¹ ) -S (O) _m -, -S (O) _n -N (R ¹² ) -, -CH ₂ -S (O) _p -, -S (O) _q -CH ₂ -, -CH ₂ -O-, -O-CH ₂ -, -N (R ¹³ ) -CO-N ( R ¹⁴ ) - or -N (R ¹⁵ ) -CS-N (R ¹⁶ ) - (where e R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ mean a hydrogen atom, a C _1-6 alkyl group or a C _1-6 alkoxy group and m, n, p and q are an integer of 0, 1 or 2, independently of each other); and A means a C _3-8 cycloalkyl group, a C _3-8 cycloalkenyl group, a 5-14 membered non-aromatic heterocyclic group, C _{6 A -14} aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group which may be substituted, respectively, provided that 3 groups of R ¹ , R ² , R ³ , R ⁴ and R ⁵ are always the same or different from dr uga and each means -X-A, and the remaining 2 groups always mean a hydrogen atom, a halogen atom or a C _1-6 alkyl group), provided that in the above definition there are no cases where (1) Q represents O; R ¹ and R ⁵ represent atoms other than hydrogen and R ² , R ³ and R ⁴ represent a phenyl group (2) Q represents O; R ¹ and R ⁴ represent hydrogen atoms and R ² , R ³ and R ⁵ represent phenyl groups and (3) Q represents O; R ¹ and R ² represent hydrogen atoms and R ³ , R ⁴ and R ⁵ represent phenyl groups.

Those. the present invention relates to (1) a compound represented by the above formula (I), a salt thereof or hydrates thereof; (2) the compound according to the above (1), its salt or its hydrates, which is represented by the formula

where Q is NH, O or S; X ¹ , X ^2, and X ³ are the same or different from each other and each represents a single bond, an optionally substituted C _1-6 alkylene group, an optionally substituted C _2-6 alkenylene group, an optionally substituted C _2-6 alkynylene group, —O -, -S-, -CO-, -SO-, -SO ₂ -, -N (R ⁶ ) -, -N (R ⁶ ) -CO-, -CO-N (R ⁸ ) -, -N ( R ⁹ ) -CH ₂ -, -CH ₂ -N (R ¹⁰ ) -, -CH ₂ -CO-, -CO-CH ₂ -, -N (R ¹¹ ) -S (О) _m -, -S ( O) _n -N (R ¹² ) -, -CH ₂ -S (O) _p -, -S (O) _q -CH ₂ -, -CH ₂ -O-, -O-CH ₂ -, -N ( R ¹³ ) —CO — N (R ¹⁴ ) - or —N (R ¹⁵ ) —CS-N (R ¹⁶ ) - (where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ represent a hydrogen atom, a C _1-6 alkyl group or a C _1-6 alkoxy group and m, n, p and q are independent and from each other and each means an integer 0, 1 or 2); A ¹ , A ² and A ³ are the same or different from each other and each means an optionally substituted C _3-8 cycloalkyl group, C _3-8 cycloalkenyl group, 5-14 membered non-aromatic heterocyclic group, C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group and R ¹⁷ and R ¹⁸ are the same or different from each other and each represents a hydrogen atom, a halogen atom or a C _1-6 alkyl group; (3) the compound according to the above (2), its salt or its hydrates, where X ¹ , X ² and X ³ represent (1) a single bond, (2) a C _1-6 alkylene group, a C _2-6 alkenylene group or C _2-6 alkynylene group, which may be optionally substituted, respectively, by one or more groups selected from the following substituent group a, (3) -O-, (4) -S-, (5) -CO-, (6 ) -SO-, (7) -SO ₂ -, (8) -N (R ⁶ ) -, (9) -N (R ⁷ ) -CO-, (10) -CO-N (R ⁸ ) -, (11) -N (R ⁹ ) -CH ₂ -, (12) -CH ₂ -N (R ¹⁰ ) -, (13) -CH ₂ -CO-, (14) -CO-CH ₂ -, (15 ) -N (R ¹¹ ) -S (O) _m -, (16) -S (O) _n -N (R ¹² ) -, (17) -CH ₂ -S (O) _p -, (18) - S (O) _q -CH ₂ -, (19) -CH ₂ -O-, (20) -O-CH ₂ -, (21) -N (R ¹³ ) -CO-N (R ¹⁴ ) - or ( 22) -N (R ¹⁵⁾ -CS-N (R ¹⁶⁾ - ( de R ^6, R ^7, R ^8, R ^9, R ^10, R ^11, R ^12, R ^13, R ^14, R ¹⁵ and R ^16, m, n, p and q have the same meanings as defined above; and A ¹ , A ² and A ³ represent a C _3-8 cycloalkyl group, a C _3-8 cycloalkenyl group, a 5-14 membered non-aromatic heterocyclic group, a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group, which may optionally be substituted with one or more groups selected from the following substituent group b (substituent a: a group consisting of a hydroxy group, a halogen atom and a nitrile g groups and substituent b: a group consisting of (1) a hydroxy group, (2) a halogen atom, (3) a nitrile group, (4) a nitro group, (5) a C _1-6 alkyl group, a C _2-6 alkenyl group, or C _{A 2-6} alkynyl group, which may optionally be substituted, respectively, by one or more groups selected from the group consisting of a hydroxy group, a nitrile group, a halogen atom, a C _1-6 alkylamino group, a di (C _1-6 alkyl) amino group, C _2-6 alkenylamino groups, di (C _2-6 alkenylamino) groups, C _2-6 alkynylamino groups, di (C _2-6 alkynylamino) groups, N — C _1-6 alkyl-N — C _2-6 alkenyl amino groups, N — C _1-6 alkyl-N — C _2-6 alkynylamino groups, N — C _2-6 alkenyl-N — C _2-6 alkynylamino groups, aralkyloxy groups, TBDMS hydroxy groups, C _1-6 alkylsulfonylamino groups, C _{1- 6} alkylcarbonyloxy groups, C _2-6 alkenylcarbonyloxy groups, C _2-6 alkynylcarbonyloxy groups, NC _1-6 alkylcarbamoyl groups and NC _2-6 alkenylcarbamoyl groups, and NC _1-6 alkynylcarbamoyl groups, (6) C _1-6 alkoxy groups, C _2-6 alkenyloxy C _2-6 alkynyloxy groups, which may optionally be substituted, respectively, by one or more groups selected from the group consisting of C _1-6 alkyl non-groups, aralkyloxy groups and hydroxy groups, (7) C _1-6 alkylthio groups, C _2-6 alkenylthio groups or C _2-6 alkynylthio groups, which may be optionally substituted by one or more groups selected from the group consisting of a hydroxy group, a nitrile group a halogen atom, a C _1-6 alkylamino group, an aralkyloxy group, a TBDMS oxy group, a C _1-6 alkylsulfonylamino group, a C _1-6 alkylcarbonyloxy group, and a C _1-6 alkylcarbamoyl group, (8) a carbonyl group substituted with a group selected from the group consisting of C _1-6 alkoxy Aminogen uppy, C _1-6 alkylamino, di (C _1-6 alkyl) amino, _C2-6 alkenylamino, di (C _2-6 alkenyl) amino, C _2-6 alkinilaminogruppy, di (C _2-6 alkynyl) amino group, NC _1-6 alkyl-N-C _2-6 alkenylamino, N-C _1-6 alkyl-N-C _2-6 alkinilaminogruppy and _N-C2-6 alkenyl-N-C _2-6 alkynylamino group, (9) an amino group which may optionally be substituted with one or two groups selected from the group consisting of a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylsulfonyl group, C _2-6 alkenylsulfonyl group, C _2-6 alkynylsulfonium ln group, C _1-6 alkylcarbonyl group, C _2-6 alkenylcarbonyl group and C _2-6 alkynylcarbonyl group, (10) C _1-6 alkylsulfonyl group, (11) C _2-6 alkenylsulfonyl group, (12) C _{2- 6} alkynylsulfonyl group, (13) C _1-6 alkylsulfinyl group, (14) C _2-6 alkenylsulfinyl group, (15) C _2-6 alkynylsulfinyl group, (16) formyl group, (17) C _3-8 cycloalkyl group or C _3-8 cycloalkenyl group, which may be optionally substituted, respectively, by one or more groups selected from the group consisting of hydroxy Rupp, a halogen atom, nitrile group, C _1-6 alkilnoygruppy, C _1-6 alkyloxy, C _1-6 alkyloxyC _1-6 alkyl group and aralkyl group, (18) 5-14-membered nonaromatic heterocyclic group which may optionally be substituted with one or more groups selected from the group consisting of hydroxy, halogen atom, nitrile group, C _1-6 alkyl group, C _1-6 alkyloxy, C _1-6 alkyloxyC _1-6 alkyl group and aralkyl group, (19) gidrokarbotsiklicheskoy C _6-14 aromatic group which may be optionally of meschena one or more groups selected from the group consisting of hydroxy, halogen atom, nitrile group, C _1-6 alkyl group, C _1-6 alkyloxy, C _1-6 alkyloxyC _1-6 alkyl group and aralkyl group, and (20 ) A 5-14 membered aromatic heterocyclic group which may optionally be substituted with one or more groups selected from the group consisting of a hydroxy group, a halogen atom, a nitrile group, a C _1-6 alkyl group, a C _1-6 alkyloxy group, a C _{1- 6} alkyloxyC _1-6 alkyl group and aralkyl group); (4) the compound according to the above (2), its salt or its hydrates, where A ¹ , A ² and / or A ³ are the same and / or different from each other and each represents an optionally substituted C _3-8 cycloalkyl, C _{3- 8} cycloalkenyl or 5-14 membered non-aromatic hetero ring; (5) the compound according to the above (2), its salt or its hydrates, where A ¹ , A ² and / or A ³ are the same or different from each other and each represents an optionally substituted C _6-14 aromatic hydrocarbon ring or 5-14 -membered aromatic hetero ring; (6) the compound according to the above (2), its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents a phenyl group, a pyrrolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group, carbazol an alkyl group, a cyclopentyl group, a cyclohexyl group, a cyclohexenyl group, a dioxinyl group, an adamantyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group or a morpholyl group, which may optionally have substituents, respectively; (7) the compound according to the above (2), its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents a group represented by the formula

which may be substituted; (8) the compound according to the above (2), its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each is optionally substituted with a hydroxy group, a halogen atom, an amino group or a nitrile group; (9) the compound according to the above (7), its salt or its hydrates, where the substituents A ¹ , A ² and A ³ are the same or different from each other and each represents a hydroxyl group, a halogen atom or an amino group, a nitrile group or a nitro group; (10) a compound according to the above (1) or (2), a salt thereof, hydrates thereof, wherein Q is oxygen; (11) the compound according to the above (1) or (2), its salt, its hydrates, where X ¹ , X ² and X ³ are the same or different from each other and each represents a simple bond, -CH ₂ -, -CH ( OH) -, -CH ₂ -CH ₂ -, -CH = CH-, -C≡C-, -O- or -CO-; (12) the compound according to the above (2), its salt or its hydrates, where X ¹ , X ² and X ³ represent simple bonds; (13) the compound according to the above (2), its salt or its hydrates, where R ¹⁷ and R ¹⁸ are the same or different from each other and each represents a hydrogen atom, fluorine, chlorine, bromine, iodine, methyl group, ethyl group, n a propyl group or an isopropyl group; (14) the compound according to the above (2), its salt or its hydrates, where R ¹⁷ and R ¹⁸ represent a hydrogen atom; (15) the compound according to the above (1) or (2), its salt or its hydrates, which is represented by the formula

where X ¹ , X ² , X ³ , A ¹ , A ² , A ³ , R ¹⁷ and R ¹⁸ have the same meanings as defined in the above (2); 16) the compound according to the above (15), its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents an optionally substituted C _6-14 aromatic hydrocarbon ring or 5-14 membered aromatic hetero ring; (16) the compound according to the above (15), its salt and its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents an optionally substituted C _6-14 aromatic hydrocarbon ring or 5-14 membered aromatic hetero ring; (17) the compound according to the above (15), its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents an optionally substituted phenyl group, pyrrolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazop ridilnuyu group, carbazolyl group, cyclopentyl group, cyclohexyl group, cyclohexenyl group, dioxinyl group, adamantyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group or morfolilnuyu group; (18) the compound according to the above (15), its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents a group represented by the following formula:

which may be substituted; (19) the compound according to the above (15), its salt or its hydrates, where the place of attachment of the substituent on A ¹ , A ² and / or A ³ is the α-position of the carbon atom, which is associated with the group X ¹ , X ² and X ³ , respectively; (20) a compound according to the above (15), a salt thereof or hydrates thereof, wherein X ¹ , X ² and X ³ are single bonds; (21) the compound according to the above (15), a salt thereof or hydrates thereof, wherein R ¹⁷ and R ¹⁸ are hydrogen atoms; (22) the compound according to the above (1), its salt or its hydrates, which is any one of the compounds selected from 3- (2-cyanophenyl) -5- (2-methylsulfonylaminophenyl) -1-phenyl-1,2-dihydropyridine -2-she; 3- (2-chloro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitrophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-dimethylaminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- [3- (5-methoxymethyl-2-oxazolidinon-3-yl) phenyl] -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxycarbonylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminocarbonylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyano-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-hydroxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-formylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-hydroxymethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-cyanomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetylaminomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetoxymethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylthiophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylsulfonylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-formylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-diethylaminomethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-hydroxymethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1-benzyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5-phenyl- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1,5-diphenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-methoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (3,4-dimethoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (thiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-fluorophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (thiophen-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (3-furyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-furyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-methoxycarbonylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3-phenyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-fluorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-methoxy-5-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one; 3-phenyl-5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-formylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-formylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-chlorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-tolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-trifluoromethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (thiophen-3-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-furyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-tolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-trifluoromethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (pyrimidin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-benzyloxymethylpyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-ethylthiopyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-chloropyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-fluoropyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-methoxyphenyl) -1,2-dihydropyridin-2-one; 3-phenyl-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (thiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2,6-dimethylphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanothiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-hydroxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminopropoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-hydroxymethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-cyanomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-cyanomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (6-diethylaminomethyl-2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-hydroxypyridin-6-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- (2-aminobenzothiazol-6-yl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-benzyl-1,2,5,6-tetrahydropyridin-3-yl) -1,2-dihydropyridin-2-one; 3- [2- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (6-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (5-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (3-hydroxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1-phenyl-5- (2-thiazolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (6-methoxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 1- (4-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- (3-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-amino-4-methylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-dimethylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-piperidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-pyrrolidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-diisopropylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- [3- (4-piperidinobutoxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (4-nitrophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1-phenyl-5- (2-pyridyl) -3- (2-thiazolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-pyridyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-fluoropyridin-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-nitrophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-nitrophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-formylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-naphthyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-naphthyl) -1,2-dihydropyridin-2-one; 5- (2-aminopyridin-6-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 5- (6-bromopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-morpholinopyridin-6-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-hydroxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- [3- (4-piperidyloxy)] phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- [3- (N-acetylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- [3- (1-methylsulfonylpiperidin-4-yl-hydroxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- [3- (N-methylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (6-chloro-1H-benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitro-4-methylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanothiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- [2- (5-oxazolyl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- [2- (5-oxazolyl) thiophen-3-yl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one and 3- (2-ethoxycarbonylvinylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; (23) a method for producing a compound represented by the formula

(where each A ^1a and A ^3a are the same or different from each other and each means an optionally substituted C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group; W ″ represents a halogen atom), or a salt thereof, which is that the compound represented by the formula

(where A ^1a and A ^3a have the same meanings as defined above), or its salt is subjected to a halogenation reaction; (24) a method for producing a compound represented by the formula

(where A ^1a and A ^3a have the same meanings as defined above), or its salt, which consists in the fact that the compound represented by the formula

(where A ^3a has the same meaning as defined above), or a salt thereof and a boronic acid derivative represented by the formula A ^1a B (OH) ₂ (where A ^1a represents an optionally substituted C _6-14 aromatic hydrocarbon ring or 5-14- membered aromatic hetero ring), subjected to a coupling reaction in the presence of a copper compound; (25) a production method according to the above (24), which consists in the fact that the compound represented by the aforementioned formula (VIII), or a salt thereof, obtained by a deprotection reaction of a compound represented by the formula

(where A ^3a has the same meaning as defined above, and Z ³ means a protective group of an alcohol hydroxy group), and a boronic acid derivative represented by the formula A ^1a B (OH) ₂ (where A ^1a has the same meaning as defined above) subject to a coupling reaction in the presence of a copper compound; (26) a production method according to the above (24), which comprises preparing a compound represented by the aforementioned formula (VIII) or a salt thereof by deprotecting a compound represented by the aforementioned formula (IX) or a salt thereof obtained by a reaction of combining a boronic acid derivative represented by the formula

(where Z ³ has the same meaning as defined above), or its salt and a compound represented by the formula A ^3a- Z ¹ (where A ^3a has the same meaning as defined above, and Z ¹ represents a halogen atom), or its salts in the presence of a palladium catalyst; and then subjecting compound (VIII) or a salt thereof and a boronic acid derivative represented by the formula A ^1a B (OH) ₂ (where A ^1a has the same meaning as defined above) to a coupling reaction in the presence of a copper compound; (27) a production method according to the above (24), which comprises preparing a compound represented by the aforementioned formula (X) or a salt thereof by reacting a compound represented by a formula

(where Z ³ has the same meaning as defined above; W 'represents a halogen atom), or its salt and trimethoxyborane in the presence of a base; obtaining a compound represented by the aforementioned formula (IX), or a salt thereof by subjecting a compound (X) or a salt thereof and a compound represented by the formula A ^3a -Z ¹ (wherein A ^3a and Z ¹ have the same meanings as defined above) or a a coupling reaction salt in the presence of a palladium catalyst; preparing a compound represented by the aforementioned formula (VIII) or a salt thereof by subjecting a compound (IX) or its salt to a deprotection reaction and then subjecting a compound (VIII) and a boronic acid derivative represented by formula A ^1a B (OH) ₂ (where A ^1a has the same meaning as defined above), coupling reactions in the presence of a copper compound; (28) a production method according to the above (24), which comprises preparing a compound represented by the aforementioned formula (X) or a salt thereof by reacting a compound represented by the aforementioned formula (XI) or a salt thereof obtained by reacting a compound represented by a formula

(where W 'and W''are the same or different from each other and each represents a halogen atom), or its salt and a compound represented by the formula Z ³ OM (where Z ³ has the same meaning as defined above and M represents an alkali atom metal), and trimethoxyborane in the presence of a base; obtaining a compound represented by the aforementioned formula (IX), or a salt thereof by subjecting a compound (X) or a salt thereof and a compound represented by the formula A ^3a -Z ¹ (wherein A ^3a and Z ¹ have the same meanings as defined above) or its combination reaction salt in the presence of a palladium catalyst; obtaining the compound represented by the above formula (VIII) or a salt thereof by subjecting the compound (IX) or its salt to a deprotection reaction and then subjecting the compound (VIII) and a boronic acid derivative represented by the formula A ^1a B (OH) ₂ (where A ^1a has the same meaning as defined above) a coupling reaction in the presence of a copper compound; (29) a production method according to the aforementioned (23), which consists in the fact that the compound represented by the aforementioned formula (VI) and obtained by the production method according to any of the aforementioned (24) to (28), or a salt thereof is subjected to a halogenation reaction; (30) a production method according to the above (23) or (29), where W is bromine or iodine; (31) the production method according to the above (23) or (29), where the halogenation reaction to obtain compound (VII) or a salt thereof is (1) a bromination reaction using N-bromosuccinimide or an acetic acid / bromine mixture or (2) an iodination reaction using N-iodosuccinimide or iodine; (32) a production method according to the above (23) or (29), wherein a halogenation reaction to obtain compound (VII) or a salt thereof is carried out using N, N-dimethylformamide as a solvent; (33) the production method according to the above (23) or (29), wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a thienyl group thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group or carbazolyl group y; (34) the production method according to any of the above (24) to (28), wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group or carbazole a silt group; (35) the production method according to any of the above (24) to (29), wherein the copper compound used for the coupling reaction using compound (VIII) or a salt thereof is copper acetate or di-μ-hydroxy bis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride; (36) a production method according to any of the above (24) to (29), wherein the coupling reaction using compound (VIII) or a salt thereof is carried out in the presence of a base; (37) a production method according to the above (36), wherein the base is triethylamine, pyridine or tetramethylethylenediamine; (38) a production method according to any of the above (24) to (29), wherein a coupling reaction using compound (VIII) or a salt thereof is carried out using N, N-dimethylformamide as a solvent; (39) a production method according to any of the above (25) to (29), wherein Z ³ represents a C _1-6 alkyl group or a C _1-6 aralkyl group; (40) a production method according to the above (25) to (29), wherein the deprotection reaction of compound (IX) or a salt thereof is carried out in the presence of an acid; (41) a production method according to the above (40), wherein the acid is hydrochloric acid; (42) the production method according to the above (26) to (29), wherein the catalyst in the coupling reaction using compound (X) or a salt thereof is palladium acetate and triphenylphosphine; (43) a production method according to the above (26) to (29), wherein a coupling reaction using compound (X) or a salt thereof is carried out in the presence of a base; (44) a production method according to the above (43), wherein the base is cesium carbonate, sodium carbonate or potassium carbonate; (45) a production method according to any one of the above (27) to (29), wherein W ′ is bromo; (46) the production method according to the above (27) to (29), wherein the base used for the reaction of compound (XI) or its salt with trimethoxyborane is n-butyllithium; (47) a production method according to the above (28) or (29), where W 'and W''arebromo; (48) a production method according to the above (28) or (29), wherein the compound represented by formula Z ³ OM is sodium methoxide or sodium ethoxide; (49) a method for producing a compound represented by the formula

(where the D ring means an optionally substituted pyridine ring; the E ring represents an optionally substituted benzene ring and W ″ has the same meaning as defined above), or a salt thereof, which consists in the fact that the compound represented by the formula

(where ring D and E have the same meanings as defined above), or its salt is subjected to a halogenation reaction; (50) a method for producing a compound represented by the formula

(where ring D and ring E have the same meanings as defined above), or its salt, which is that the compound represented by the formula

(where ring D has the same meaning as defined above), or a salt thereof and a boronic acid derivative represented by the formula PhB (OH) ₂ (where Ph is an optionally substituted phenyl group) are subjected to a coupling reaction in the presence of a copper compound; (51) a production method according to the above (50), which consists in the fact that the compound represented by the aforementioned formula (VIII) 'or a salt thereof obtained by deprotecting a compound represented by the formula

(where ring D and Z ³ have the same meanings as defined above), or a salt thereof, and a boronic acid derivative represented by the formula PhB (OH) ₂ (where Ph has the same meaning as defined above), undergo a coupling reaction in the presence of a copper compound; (52) a production method according to the above (50), which comprises preparing a compound represented by the aforementioned formula (VII) ', or a salt thereof, by subjecting a deprotection reaction to a compound represented by the aforementioned formula (IX)', or a salt thereof, obtained by combining a derivative boronic acid represented by the formula

(where Z ³ has the same meaning as defined above), or its salt and optionally substituted 2-halogen-pyridine or its salt in the presence of a palladium catalyst and then exposing compound (VIII) 'or its salt and a boronic acid derivative represented by the formula PhB ( OH) ₂ (where Ph has the same meaning as defined above), coupling reactions in the presence of a copper compound; (53) a production method according to the above (50), which comprises preparing a compound represented by formula (X) or a salt thereof by reacting a compound represented by formula

(where Z ³ has the same meaning as defined above and W 'represents a halogen atom), or its salt and trimethoxyborane in the presence of a base; preparing a compound represented by the aforementioned formula (IX) 'or a salt thereof by subjecting a compound (X) or a salt thereof and optionally substituted 2-halogen pyridine or a salt thereof to a coupling reaction in the presence of a palladium catalyst; preparing a compound represented by the above formula (VIII) 'or a salt thereof by subjecting a compound (IX)' or its salt to a deprotection reaction and then subjecting a compound (VIII) 'and a boronic acid derivative represented by the formula PhB (OH) ₂ (where Ph has the same meaning as defined above), coupling reactions in the presence of a copper compound; (54) a production method according to the above (50), which comprises preparing a compound represented by the aforementioned formula (X) or a salt thereof by reacting a compound represented by the aforementioned formula (XI) or a salt thereof obtained by reacting a compound represented by a formula

(where W 'and W''are the same or different from each other and each represents a halogen atom), or a salt thereof and a compound represented by the formula Z ³ OM (where Z ³ and M have the same meanings as defined above), and trimethoxyborane in the presence of a base; preparing a compound represented by the aforementioned formula (IX) 'or a salt thereof by subjecting a compound (X) or a salt thereof and optionally substituted 2-halogen pyridine or a salt thereof to a coupling reaction in the presence of a palladium catalyst; preparing a compound represented by the aforementioned formula (VIII) or a salt thereof by subjecting a compound (IX) 'or a salt thereof to a deprotection reaction and then subjecting a compound (VIII)' and a boronic acid derivative represented by the formula PhB (OH) ₂ (where Ph has the same meaning as defined above), a coupling reaction in the presence of a copper compound; (55) a production method according to the above (25), which consists in the fact that the compound represented by the above formula (VI) 'and obtained by the production method according to any of the above (29) to (32), or a salt thereof is subjected to a halogenation reaction; (56) a production method according to the above (49) or (55), where W represents bromine or iodine; (57) a production method according to the above (49) or (55), wherein the halogenation reaction to obtain compound (VII) or a salt thereof is (1) a bromination reaction using N-bromosuccinimide or an acetic acid / bromine mixture, or (2) a reaction iodination using N-iodosuccinimide or iodine; (58) a production method according to the above (49) or (55), wherein a halogenation reaction to produce compound (VII) or a salt thereof is carried out using N, N-dimethylformamide as a solvent; (59) the production method according to the above (49) or (55), wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a thienyl group thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group or carbazolyl group; (60) the production method according to any of the above (50) to (54), wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally phenyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group or carbazolyl group y; (61) the production method according to any of the above (50) to (55), wherein the copper compound used for the coupling reaction using compound (VIII) or a salt thereof is copper acetate or di-μ-hydroxy bis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride; (62) a production method according to any of the above (50) to (55), wherein the coupling reaction using compound (VIII) or a salt thereof is carried out in the presence of a base; (63) a production method according to the above (62), wherein the base is triethylamine, pyridine or tetramethylethylenediamine; (64) a production method according to any of the above (50) to (55), wherein a coupling reaction using compound (VIII) or a salt thereof is carried out using N, N-dimethylformamide as a solvent; (65) a production method according to any of the above (51) to (55), wherein Z ³ represents a C _1-6 alkyl group or an aralkyl group; (66) a production method according to the above (51) to (55), wherein the deprotection reaction of compound (IX) or a salt thereof is carried out in the presence of an acid; (67) a production method according to the above (66), wherein the acid is hydrochloric acid; (68) the production method according to the above (52) to (55), wherein the catalyst in the coupling reaction using compound (X) or a salt thereof is palladium acetate and triphenylphosphine; (69) a preparation method according to the above (52) to (55), wherein the coupling reaction using compound (X) or a salt thereof is carried out in the presence of a base; (70) a production method according to the above (69), wherein the base is cesium carbonate, sodium carbonate or potassium carbonate; (71) a production method according to any of the above (53) to (55), wherein W ′ is bromo; (72) a production method according to the above (53) to (55), wherein the base used for the reaction of compound (XI) or its salt with trimethoxyborane is n-butyllithium; (73) a production method according to the above (54) or (55), wherein W and W ′ are bromo; (74) a production method according to the above (54) or (55), wherein the compound represented by formula Z ³ OM is sodium methoxide or sodium ethoxide; (75) a production method according to any of the above (52) to (55), wherein the optionally substituted 2-halo-pyridine is optionally substituted 2-bromopyridine; (76) a compound represented by the following formula, or a salt thereof

where A ^1a and A ^3a are the same or different from each other and each means an optionally substituted C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group and R means a hydrogen atom or a halogen atom; (77) the compound according to the above (76) or a salt thereof, wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a thienyl group, a thiazolyl group group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group or carbazolyl group a group; (78) a compound according to the above (76) or a salt thereof, wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, a pyridyl group, a pyrimidinyl group, a thienyl or furyl group; (79) a compound according to the above (76), or a salt thereof, wherein R represents a hydrogen atom or bromine; (80) a pharmaceutical composition comprising a compound represented by the following formula, a salt thereof or hydrates thereof

in the formula, Q is NH, O or S; R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different from each other and each means a hydrogen atom, a halogen atom, a C _1-6 alkyl group or the formula —X — A (where X is a single bond, C _1-6 alkylene group, which may optionally have a substituent, C _2-6 alkenylene group, which may optionally have a substituent, C _2-6 alkynylene group, which may optionally have a substituent, -O-, -S-, -CO-, -SO-, -SO ₂ -, -N (R ⁶ ) -, -N (R ⁷ ) -CO-, -CO-N (R ⁸ ) -, -N (R ⁹ ) -CH ₂ -, -CH _2- N (R ¹⁰ ) -, -CH ₂ -CO-, -CO-CH ₂ -, -N (R ¹¹ -S (O) _m -, -S (O) _n -N (R ¹² ) -, -CH ₂ -S (O) _p -, -S (O) _q -CH ₂ -, -CH ₂ -O-, -O-CH ₂ -, -N (R ¹³ ) -CO-N (R ¹⁴ ) - or -N (R ¹⁵ ) -CS-N (R ¹⁶ ) - (where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ means a hydrogen atom, C _{A 1-6} alkyl group or a C _1-6 alkoxy group and m, n, p and q are independent of each other and each is an integer of 0, 1 or 2), and A is an optionally substituted C _3-8 cycloalkyl group, C _{3 -8} cycloalkenyl group, 5-14 membered non-aromatic heterocyclic group, C _6-14 aromatic hydrocarbocyclic group or 5-14 membered aromatic heterocyclic group), provided that 3 groups of R ¹ , R ² , R ³ , R ⁴ and R ⁵ are always the same or different from each other and each indicates -X-A, and the remaining two groups always represent a hydrogen atom, a halogen atom or a C _1-6 alkyl group; (81) a pharmaceutical composition according to the above (80), wherein it is an inhibitor of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (hereinafter referred to as AMPK and / or kainate receptor; ( 82) a pharmaceutical composition according to the above (80), where it is an inhibitor with respect to the AMPK receptor (AMPA); (83) a pharmaceutical composition according to the above (80) where it is an inhibitor with respect to the kainate receptor; (84) a pharmaceutical composition according to aforementioned mu (80), which is a therapeutic or prophylactic agent for treating diseases in which the AMPA or kainate receptor is involved (involved); (85) a pharmaceutical composition according to the above (80), which is a therapeutic or prophylactic agent for treating diseases, which involves the AMPA receptor; (86) a pharmaceutical composition according to the above (80), which is a therapeutic or prophylactic agent for the treatment of acute neurodegenerative disease Ania; (87) a pharmaceutical composition according to the above (80), which is a therapeutic or prophylactic agent for the treatment of acute cerebrovascular disorders, head injury, spinal cord injury, diseases of the nervous system (neuropathy) caused by hypoxia or hypoglycemia; (88) a pharmaceutical composition according to the above (80), which is a therapeutic or prophylactic agent for treating chronic neurodegenerative disease; (89) a pharmaceutical composition according to the above (80), which is a therapeutic or prophylactic agent for treating Alzheimer's disease, Parkinson's disease, Huntington’s chorea, amyotrophic lateral sclerosis or disorders associated with degeneration of the spinal cord and cerebellum; (90) a pharmaceutical composition according to the above (80), which is a means for treating or preventing epilepsy, hepatic encephalopathy, peripheral neuropathy, Parkinson's syndrome, spasticity, pain, neuralgia, schizophrenia, anxiety, drug abuse (substance abuse), nausea, vomiting, dysuria; visual impairment caused by glaucoma; hearing impairment caused by antibiotics or food poisoning; (91) a pharmaceutical composition according to the above (80), which is a means for treating or preventing infectious encephalomyelitis, cerebrovascular senile dementia or dementia or neurosis caused by cerebrospinal meningitis; (92) a pharmaceutical composition according to the above (91), wherein the infectious encephalomyelitis is HIV-related encephalomyelitis (HIV); (93) a pharmaceutical composition according to the above (80), which is an agent for treating or preventing a demyelinating disease; (94) a pharmaceutical composition according to the above (93), wherein the demyelinating disease is encephalitis, acute multiple disseminated encephalomyelitis, multiple (multiple) sclerosis, acute polyradiculoneuritis, Hyena-Barre syndrome; chronic inflammatory demyelinating polyneuropathy, Markiafava-Binyami disease; demyelination of nerve fibers related to the central Varolian bridge; optic neuromyelitis, Devic's disease, Balo's disease; HIV myelopathy HTLV (human T-cell leukemia virus) myelopathy; progressive multifocal leukoencephalopathy or secondary demyelinating disease; (95) a pharmaceutical composition according to the above (94), wherein the secondary demyelinating disease is a lupus erythematosus disorder, nodosa polyarteritis, Sjogren's syndrome, sarcoidosis or isolated cerebral vasculitis and the like.

The present invention relates to a method for the prevention or treatment of diseases in which the AMPA or kainate receptor is involved (involved) by administering to a patient a pharmacologically effective dose of a compound represented by formula (I), a salt thereof or its hydrates.

The present invention relates to a compound represented by formula (I), a salt thereof or a hydrate thereof, suitable for the manufacture of a therapeutic or prophylactic agent for diseases in which the AMPA receptor or kainate receptor is involved.

In the present invention, "diseases in which the AMPA or kainate receptor is involved" include acute neurodegenerative disease; cerebrovascular disorders in the acute stage; head injury; damage to the spinal cord, diseases of the nervous system (neuropathy) caused by hypoxia or hypoglycemia; chronic neurodegenerative disease; Alzheimer's disease; Parkinson's disease; Huntington's chorea; amyotrophic lateral sclerosis; a disorder associated with degeneration of the spinal cord and cerebellum; epilepsy hepatic encephalopathy; peripheral neuropathy; Parkinson's syndrome; spasticity; pain; neuralgia; schizophrenia; Anxiety drug abuse (substance abuse); nausea vomiting dysuria; visual impairment caused by glaucoma; hearing impairment caused by antibiotics; food poisoning; infectious encephalomyelitis; cerebrovascular senile dementia; dementia or neurosis caused by cerebrospinal meningitis, and demyelinating diseases.

DETAILED DESCRIPTION OF THE INVENTION

The meanings of the symbols, terms, etc. mentioned in the description of this application are explained below, whereby the present invention is illustrated in detail.

The term "acute neurodegenerative disease" in the present invention refers, for example, to cerebrovascular disorders in the acute stage (subarachnoid hemorrhage, cerebral infarction, etc.), head injury, spinal cord injury, diseases of the nervous system (neuropathy) due to hypoxia or hypoglycemia , etc. The term "chronic neurodegenerative disease" refers to, for example, Alzheimer's disease, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis; a disorder associated with degeneration of the spinal cord and cerebellum. The term “infectious encephalomyelitis” refers to, for example, HIV-related encephalomyelitis, and “demyelinating disease” refers to, for example, encephalitis, acute multiple disseminated encephalomyelitis, multiple (multiple) sclerosis, acute polyradiculoneuritis, Hyena-Barre syndrome; chronic inflammatory demyelinating polyneuropathy, Markiafava-Binyami disease; demyelination of nerve fibers related to the central pontine myelinolysis, optic neuromyelitis, Devic's disease, Balo's disease; HIV myelopathy myelopathy due to HTLV (human T-cell leukemia virus); progressive multifocal leukoencephalopathy, secondary demyelinating disease, etc. The "secondary demyelinating disease" referred to above includes, for example, demyelinating disorder with lupus erythematosus, nodular polyarteritis, Sjogren's syndrome, sarcoidosis, isolated cerebral vasculitis, and the like.

Used in the present invention, the term "and / or" is used to mean that both cases are included, in the case of "and" and in the case of "or" - one of them.

Incidentally, in the description of the present application, although the structural formula of the compound for the sake of convenience may display a particular isomer, the present invention covers all isomers, namely geometric isomers resulting from the structure of the compound, optical isomers due to asymmetric carbon, rotamers, stereoisomers and tautomers, as well as a mixture of isomers, and the present invention is not limited to the description of the presented formula, but may represent another isomer or may represent a mixture of (isomers). Accordingly, although an asymmetric carbon atom may be present in the molecule, and accordingly there may be an optically active substance and a racemic substance, this is not particularly specified in the present invention, it covers any of the aforementioned substances. In addition, crystalline polymorphism may be present, however, again there is no limitation, and any of the forms of a single crystal or a mixture of them may take place. Compound (I) or a salt thereof related to the present invention may be an anhydride or hydrate, and any of the above forms of the compound is included within the scope of the formula of the present invention. The metabolite that is generated by the decomposition of compound (I) related to the present invention in vivo, and the prodrug that is obtained from compound (I) or its salt, are also included in the scope of the present invention.

As used herein, the term “halogen atom” means fluoro, chloro, bromo, iodo and the like, and a preferred halogen atom is fluoro, chloro and bromo.

As used herein, the term “C _1-6 alkyl group” means an alkyl group having from 1 to 6 carbon atoms, and examples include straight or branched chain alkyl groups such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, 1-ethylpropyl group , 2-ethylpropyl group, n-hexyl group PA, 1-methyl-2-ethylpropyl group, 1-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group, 1-propylpropyl group, 1-methylbutyl group, 2-methylbutyl group, 1,1-dimethylbutyl group , 1,2-dimethylbutyl group, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group, 2-methylpentyl group, 3-methylpentyl group and the like.

Used in the present invention, the term "C _2-6 alkenyl group" means an alkenyl group having from 2 to 6 carbon atoms, and examples of the aforementioned preferred group include a vinyl group, an allyl group, a 1-propenyl group, a 2-propenyl group, an isopropenyl group, 2-methyl-1-propenyl group, 3-methyl-1-propenyl group, 2-methyl-2-propenyl group, 3-methyl-2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group , 1-pentenyl group, 1-hexenyl group, 1,3-hexadienyl group PUF, 1,6-hexadienyl group and the like

As used herein, the term “C _2-6 alkynyl group” means an alkynyl group having from 2 to 6 carbon atoms, and examples of the aforementioned preferred group include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, 2 -butynyl group, 3-butynyl group, 3-methyl-1-propynyl group, 1-ethynyl-2-propynyl group, 2-methyl-3-propynyl group, 1-pentinyl group, 1-hexynyl group, 1,3- hexadiinyl group; 1,6-hexadiinyl group and the like.

As used herein, the term “C _1-6 alkoxy group” means an alkoxy group having from 1 to 6 carbon atoms, and examples include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, a sec-propoxy group, an n-butoxy group, an isobutoxy group, sec-butoxy group tert-butoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy group, n-hexoxy group, isohexoxy group, 1,1-dimethylpropoxy group, 1,2-dimethylpropoxy group, 2,2-dimethylpropoxy group, 2-ethylpropyloxypropoxy group 1-ethyl-2-m ethyl propoxy group, 1,1,2-trimethylpropoxy group, 1,1-dimethylbutoxy group, 1,2-dimethylbutoxy group, 2,2-dimethylbutoxy group, 2,3-dimethylbutoxy group, 1,3-dimethylbutoxy group, 2-ethylbutoxy group, 1,3-dimethylbutoxy group 2-methylpentoxy group, 3-methylpentoxy group, hexyloxy group and the like.

As used herein, the term “C _2-6 alkenyloxy group” means an alkenyloxy group having from 2 to 6 carbon atoms, and examples of the aforementioned preferred group include vinyloxy group, allyloxy group, 1-propenyloxy group, 2-propenyloxy group, isopropenyloxy group, 2-methyl-1-propenyloxy , 3-methyl-1-propenyloxy group, 2-methyl-2-propenyloxy group, 3-methyl-2-propenyloxy group, 1-butenyloxy group, 2-butenyloxy group, 3-butenyloxy group, 1-pentenyloxy group, 1-hexenyloxy group, 1,3-hexadienyloxy group 1,6-ge xadienyloxy group and the like.

As used herein, the term “C _3-8 cycloalkyl group” means a cycloalkyl group of 3-8 carbon atoms, and examples include a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group and the like.

As used herein, the term “C _3-8 cycloalkenyl group” means a C _3-8 cycloalkenyl group consisting of 3-8 carbon atoms, and examples include cyclopropen-1-yl, cyclopropen-3-yl, cyclobuten-1-yl, cyclobuten-3-yl, 1,3-cyclobutadiene-1-yl, cyclopenten-1-yl, cyclopenten-3-yl, cyclopenten-4-yl, 1,3-cyclopentadiene-1-yl, 1,3-cyclopentadiene- 2-yl, 1,3-cyclopentadien-5-yl, cyclohexen-1-yl, cyclohexen-3-yl, cyclohexen-4-yl, 1,3-cyclohexadien-1-yl, 1,3-cyclohexadiene-2- yl, 1,3-cyclohexadiene-5-yl, 1,4-cyclohexadiene-3-yl, 1,4-cyclohexadiene-1-yl, cyclohepten-1 -yl, cyclohepten-3-yl, cyclohepten-4-yl, cyclohepten-5-yl, 1,3-cyclohepten-2-yl, 1,3-cyclohepten-1-yl, 1,3-cycloheptadien-5-yl , 1,3-cycloheptadien-6-yl, 1,4-cycloheptadien-3-yl, 1,4-cycloheptadien-2-yl, 1,4-cycloheptadien-1-yl, 1,4-cycloheptadien-6-yl 1,3,5-cycloheptatrien-3-yl, 1,3,5-cycloheptatrien-2-yl, 1,3,5-cycloheptatrien-1-yl, 1,3,5-cycloheptatrien-7-yl, cyclooctene -1-yl, cycloocten-3-yl, cycloocten-4-yl, cycloocten-5-yl, 1,3-cyclooctadiene-2-yl, 1,3-cyclooctadiene-1-yl, 1,3-cyclooctadiene-5 -yl, 1,3-cyclooctadiene-6-yl, 1,4-cyclooctadiene-3-yl, 1,4-cyclooctadiene-2-yl, 1,4-cyclooctadiene-1-yl, 1,4-cyclo ctadiene-6-yl, 1,4-cyclooctadiene-7-yl, 1,5-cyclooctadiene-3-yl, 1,5-cyclooctadiene-2-yl, 1,3,5-cyclooctatrien-3-yl, 1, 3,5-cyclooctatrien-2-yl, 1,3,5-cyclooctatrien-1-yl, 1,3,5-cyclooctatrien-7-yl, 1,3,6-cyclooctatrien-2-yl, 1,3, 6-cyclooctatrien-1-yl, 1,3,6-cyclooctatrien-5-yl, 1,3,6-cyclooctatrien-6-yl group and the like.

Used in the present invention, the term "5-14 membered non-aromatic heterocyclic group" means a 5-14 membered non-aromatic heterocyclic group of monocyclic type, dicyclic type or tricyclic type, which contains one or more heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom. Specific examples of the aforementioned group include, for example, a pyrrolidinyl group, a pyrrolinyl group, a piperidyl group, a piperazinyl group, an imidazolidinyl group, a pyrazolidinyl group, a morpholinyl group, a tetrahydrofuryl group, a tetrahydropyranyl group, a dihydrofuryl group, a dihydropyrazinyl group, a dihydropyrazinyl group, a dihydropyrazinyl group, a dihydrodiazinyl azinyl group In addition, the non-aromatic heterocyclic group also includes groups derived from the pyridone ring and non-aromatic condensation a ring (e.g., a group derived from a phthalimide ring, a succinimide ring, etc.).

As used in the present invention, the terms “C _6-14 aromatic hydrocarbocyclic group” and “aryl group” mean an aromatic hydrocarbocyclic group that consists of 6-14 carbon atoms, and it includes a monocyclic group and a fused group of a dicyclic type, tricyclic type, etc. P. Specific examples of the aforementioned group include a phenyl group, an indenyl group, a 1-naphthyl group, a 2-naphthyl group, an azulenyl group, a heptalenyl group, a biphenyl group, an indatenyl group, an acenaphthyl group, a fluorenyl group, a phenalenyl group, a phenanthrenyl group, an anthracenyl group, cyclopentenocyclo group , benzocyclooctenyl group, etc.

As used herein, the terms “5-14 membered aromatic heterocyclic group” and “heteroaryl group” mean a 5-14 membered aromatic heterocyclic group of monocyclic type, dicyclic type or tricyclic type, which contains one or more heteroatoms selected from the group which consists of a nitrogen atom, a sulfur atom and an oxygen atom. For example, specific examples of the aforementioned group include 1) aromatic heterocyclic groups containing nitrogen, such as a pyrrolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a triazolyl group, a tetrazolyl group, a benzotriazolyl group, a pyrazolyl group, an imidazolyl group, a benzimidazole group , indolyl group, isoindolyl group, indolysinyl group, prenyl group, indazolyl group, quinolyl group, isoquinolyl group, inolysyl group, phthalazyl group, naphthylidinyl group, quinoxalyl group, quinazolinyl group, cinnolinyl group, pteridinyl group, imidazotriazinyl group, pyrazinopyridazinyl group, acridinyl group, phenanthridinyl group, phenazyridinyl group, imidazinyl group, perimidinyl group, perimidinyl group an imidazopyrimidinyl group, a pyrazolopyridinyl group, a pyrazolopyridinyl group, etc .; 2) aromatic heterocyclic groups containing a sulfur atom, such as a thienyl group or a benzothienyl group; 3) aromatic heterocyclic groups containing an oxygen atom, such as a furyl group, a pyranyl group, a cyclopentapyranyl group, a benzofuryl group or an isobenzofuryl group, and 4) aromatic heterocyclic groups containing 2 or more different heteroatoms, such as a thiazolyl group, an isothiazolyl group, a benzothiazolyl group group, benzothiadiazolyl group, phenothiazinyl group, isoxazolyl group, furazanyl group, phenoxazinyl group, oxazolyl group, isoxazoyl group uppa, benzoxazolyl group, oxadiazolyl group, pyrazoloxadiazolyl group, imidazothiazolyl group, thienofuranyl group, furopyrrolyl group or pyridoxadinyl group.

The groups designated A, A ¹ , A ² and A ³ in formulas (I) and (II) in the present invention mean, independently, optionally substituted C _3-8 cycloalkyl group, optionally substituted C _3-8 cycloalkenyl group, optionally substituted 5-14-membered nonaromatic heterocyclic group, optionally substituted C _6-14 aromatic gidrokarbotsiklicheskuyu group or an optionally substituted 5-14-membered aromatic heterocyclic group, and each of said groups has the same meanings as defined in the above definitions, with tvetstvenno. The preferred group for A, A ¹ , A ² and A ³ is not specifically specified, but a more preferred group includes a phenyl group, a pyrrolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a thienyl group, a thiazolyl group, a furyl group, a naphthyl group a group, a quinolyl group, an isoquinolyl group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, an imidazopyridyl group, a carbazolyl group, a cyclopentyl group , A cyclohexyl group, cyclohexenyl group, dioxinyl group, adamantyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group and morpholinyl group which may be substituted, respectively, etc. A more preferred group includes a group represented by the formula

which optionally may have substituents, respectively, etc., and the most preferred group includes a group represented by the formula

which optionally may have substituents, respectively, etc.

Examples of a preferred group used as a “substituent” for the designated A, A ¹ , A ² and A ³ in formulas (I) and (II) include a group such as a hydroxyl group, a halogen atom, a nitrile group, a nitro group, C _{1- 6} alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _1-6 alkoxy, C _2-6 alkenyloxy, C _2-6 alkynyloxy, C _1-6 alkylthio, C _2-6 alkenylthio, C _{2 -6} alkynylthio group, amino group, substituted carbonyl group, C _1-6 alkylsulfonyl group, C _2-6 alkenylsulfonyl group, C _2-6 alkinilsulfonil nd group, C _1-6 alkylsulfinyl group, _C2-6 alkenylsulfinyl group, _C2-6 alkynylsulfinyl group, formyl group, aralkyl group, heteroarylalkyl group, aralkyloxy group, geteroarilalkiloksigruppa, _C3-8 cycloalkyl group, _C3-8 cycloalkenyl group A 5-14 membered non-aromatic heterocyclic group, a C _6-14 aromatic hydrocarbon group, a 5-14 membered aromatic heterocyclic group, etc., which may be substituted, respectively.

Examples of a preferred group designated as “halogen atom” include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc., and a more preferred example includes a fluorine atom, a chlorine atom, and a bromine atom.

Examples of a preferred group for the aforementioned “C _1-6 alkyl group which may optionally have substituents” include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, 1-methylpropyl group, 1,2-dimethylpropyl group, 2-ethylpropyl group, 1-methyl-2-ethylpropyl group, 1-ethyl-2-methylpropyl group, 1, 1,2-trimethylpropyl group, 1-methylbutyl th group, 2-methylbutyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 2-ethylbutyl group, 1,3-dimethylbutyl group, 2-methylpentyl group, 3-methylpentyl group, etc. Examples of a preferred group for the aforementioned “C _1-6 alkenyl group which may optionally have substituents” include a vinyl group, an allyl group, a 1-propenyl group, an isopropenyl group, a 1-buten-1-yl group, 1-buten-2-yl a group, a 1-buten-3-yl group, a 2-buten-1-yl group, a 2-buten-2-yl group, etc., which may be substituted, respectively. Examples of a preferred group for the aforementioned “C _2-6 alkynyl group, which optionally may have substituents, respectively,” include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a butynyl group, a pentinyl group, a hexynyl group, etc., which may be substituted, respectively. In addition, preferred examples of “substituents” in the term “which may optionally have substituents” include 1 or more groups selected from a hydroxy group, a nitrile group, a halogen atom, an NC _1-6 alkylamino group, an N, N-di-C _1-6 alkylamino group , NC _2-6 alkenylamino groups, N, N-di-C _2-6 alkenylamino groups, N-C _2-6 alkynylamino groups, N, N-di-C _2-6 alkynylamino groups, C _6-14 aromatic hydrocarbocyclic group (e.g. phenyl group, etc.), a 5-14 membered aromatic heterocyclic group (e.g., thienyl group, furyl group a, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group etc.), an aralkyloxy group, a heteroaryloxy group, TBDMS oxy group, C _1-6 alkylsulfonylamino, C _2-6 alkenilsulfonilaminogruppy, alkinilsulfonilaminogruppy C _2-6, C _1-6 alkylcarbonyloxy , C _2-6 alkenylcarbonyloxy groups, C _2-6 alkynylcarbonyloxy groups, C _1-6 alkylcarbamoyl groups, C _2-6 alkenylcarbamoyl groups, C _2-6 alkynylcarbamoyl groups and the like.

Preferred examples for the aforementioned “C _1-6 alkoxy group which optionally may have substituents” include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, a sec-propoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a t-butoxy group, n-tert-butoxy group, n , isopentoxy group, sec-pentoxy group, tert-pentoxy group, n-hexoxy group, isohexoxy group, 1,2-dimethylpropoxy group, 2-ethylpropoxy group, 1-methyl-2-ethylpropoxy group, 1-ethyl-2-methylpropoxy-group, 1,1-dime tilbutoxy group, 2,2-dimethylbutoxy group, 2-ethylbutoxy group, 1,3-dimethylbutoxy group, 2-methylpentoxy group, 3-methylpentoxy group, hexyloxy group, etc. Preferred examples for the aforementioned “C _2-6 alkenyloxy group, which optionally may have substituents” include a vinyloxy group, an allyloxy group, a 1-propenyloxy group, an isopropenyloxy group, 1-buten-1-yloxy group, 1-buten-2-yloxy group, 1-buten-3- iloxy group, 2-buten-1-yloxy group, 2-buten-2-yloxy group, etc. Preferred examples for the aforementioned “C _2-6 alkynyloxy group which optionally may have substituents” include an ethynyloxy group, a 1-propynyloxy group, a 2-propynyloxy group, a butynyloxy group, a pentynyloxy group, a hexynyloxy group, etc. In addition, preferred examples of “substituents” in the term “which may optionally have substituents” include 1 or more groups selected from a C _1-6 alkylamino group, an aralkyloxy group, a hydroxy group, and the like.

Accordingly, in that order, preferred examples for the aforementioned “C _1-6 alkylthio group which optionally may have substituents”, “C _2-6 alkenylthio group which optionally may have substituents” and “C _2-6 alkynylthio group which optionally may have substituents "include C _1-6 alkylthio (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio, isopentylthio, neopentylthio, n-hexylthio group and .d.), C _2-6 alkenylthio (e.g., viniltiogruppa, alliltiogruppa, 1-propenylthio group, izopropeniltiogruppa, 1-buten-1-iltiogruppa, 1-buten-2-iltiogruppa, 1-buten-3-iltiogruppa 2 -butene-1-ylthio group, 2-buten-2-ylthio group, etc.) and C _2-6 alkynylthio group (e.g. ethynylthio group, 1-propynylthio group, 2-propynylthio group, butynylthio group, pentynylthio group, hexynylthio group, etc.) which may optionally be substituted with one or more groups selected from the group consisting of a hydroxy group, a halogen atom, a nitrile group and n itrogroups.

Preferred examples for the aforementioned “carbonyl group which is substituted” include a group which is represented by the formula —CO — W (examples W in the formula include a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _{1 -6} alkoxy group, amino group, NC _1-6 alkylamino group, N, N-di (C _1-6 alkyl) amino group, N-C _2-6 alkenylamino group, N, N-di (C _2-6 alkenyl) amino group, N- C _2-6 alkynylamino group, N, N-di (C _2-6 alkynyl) amino group, N — C _1-6 alkyl-N — C _2-6 alkenylamino group, N — C _1-6 alkyl-N — C _2-6 alkynylamino group, N — C _2-6 alkenyl-N — C _2-6 alkynylamino group, etc.).

Examples of “substituents” in the term “amino group which optionally may have substituents” include 1 or 2 groups selected from a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylsulfonyl groups, a C _2-6 alkenylsulfonyl group, a C _2-6 acynylsulfonyl group, a C _1-6 alkylcarbonyl group, a C _2-6 alkenylcarbonyl group, a C _2-6 alkynylcarbonyl group, etc., which may be substituted, respectively. Preferred Examples for “Substituents” of a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylsulfonyl group, a C _2-6 alkenylsulfonyl group, a C _2-6 alkynylsulfonyl group, C _{1 -6} alkylcarbonyl groups, C _2-6 alkenylcarbonyl groups and C _2-6 alkynylcarbonyl groups include a hydroxy group, a halogen atom, a nitrile group, a C _1-6 alkoxy group, a C _1-6 alkylthio group, etc. Specifically, preferred examples for the aforementioned “amino group, which optionally may have substituents,” in particular, include a methylamino group, an ethylamino group, an n-propylamino group, an isopropylamino group, an n-butylamino group, an isobutylamino group, a tert-butylamino group, an n-pentylaminamino group, isopentylamino-amino-group, hexylamino group, 1-methylpropylamino group, 1,2-dimethylpropylamino group, 2-ethylpropylamino group, 1-methyl-2-ethylpropylamino group, 1-ethyl-2-methylpropylamino group, 1,1,2-trimethylpropylamino uppu, 1-methylbutylamino group, 2-methylbutylamino group, 1,1-dimethylbutylamino group, 2,2-dimethylbutylamino group, 2-ethylbutylamino group, 1,3-dimethylbutylamino group, 2-methylpentylamino group, 3-methylpentylamino group, N, N-dimethylamino diethylamino group, N, N-di (n-propyl) amino group, N, N-di (isopropyl) amino group, N, N-di (n-butyl) amino group, N, N-di (isobutyl) amino group, N, N- di (tert-butyl) amino group, N, N-di (n-pentyl) amino group, N, N-di (isopentyl) amino group, N, N-di (neopentyl) amino group, N, N-di (n-hexyl) amino group, N, N-di (1-methylpropyl) amino group, N, N-di (1,2-Dimethylpropyl) amino group, N-methyl-N-ethylamino group, N-ethyl-N- (n-propyl) amino group, N-ethyl-N- (isopropyl) amino group, vinylamino group, allylamino group, (1-propenyl) amino group, isopropenylamino group, (1-buten-1-yl) amino group, (1-buten-2-yl) amino group, (1-buten-3-yl) amino group, (2-buten-1-yl) amino group, (2 -buten-2-yl) amino group, N, N-divinylamino group, N, N-diallylamino group, N, N-di (1-propenyl) amino group, N, N-di (isopropenyl) amino group, N-vinyl-N-allylamino group , ethynylamino group, 1-propynylamino group, 2-propynylamino group, butynylamino group, ne ntinylamino group, hexynylamino group, N, N-diethylamino group, N, N-di (1-propynyl) amino group, N, N-di (2-propynyl) amino group, N, N-N-dibutinylamino group, N, N-dipentinylamino group, N, N- dihexinylamino group, hydroxymethylamino group, 1-hydroxyethylamino group, 2-hydroxyethylamino group, 3-hydroxy-n-propylamino group, methylsulfonylamino group, ethylsulfonylamino group, n-propylsulfonylamino-amino-amino-amino-butyl-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-amino-to-amino-amino-amino-amino-amino-amino-amino] -yl-amino-amino-amino-amino-amino-amino-amino] Rupp, izopropenilsulfonilaminogruppu, izopentenilsulfonilaminogruppu, etinilsulfonilaminogruppu, methylcarbonylamino, ethylcarbonylamino, n-propylcarbonylamino, isopropylcarbonylamino, n-butylcarbonylamino, tert-butylcarbonylamino, vinilkarbonilaminogruppu, allilkarbonilaminogruppu, izopropenilkarbonilaminogruppu, izopentenilkarbonilaminogruppu, etinilkarbonilaminogruppu etc.

Accordingly, preferred examples for the aforementioned “C _1-6 alkylsulfonyl group which optionally may have substituents”, “C _2-6 alkenylsulfonyl group which optionally may have substituents”, “C _2-6 alkynylsulfonyl group which optionally may have substituents” , "C _1-6 alkylsulfinyl group which may optionally have substituents" and "C _2-6 alkenylsulfinyl group which may optionally have substituents", "C _2-6 alkynylsulfinyl group which may optionally have a deputy "" include methylsulfonyl group, ethylsulfonyl group, n-propylsulfonyl group, isopropylsulfonyl group, n-butylsulfonyl group, tert-butylsulfonyl group, vinylsulfonyl group, allylsulfonyl group, isopropenylsulfonyl group, isopropenylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, isopropylsulfonyl group, -propylsulfinyl group, isopropylsulfinyl group, n-butylsulfinyl group, tert-butylsulfinyl group, vinylsulfini l group, allyl sulfinyl group, isopropenyl sulfinyl group, isopentenyl sulfinyl group, ethynyl sulfinyl group, etc.

Preferred examples for the “aralkyl group” and “heteroarylalkyl group” include a benzyl group, a phenethyl group, a naphthylmethyl group, a naphthylethyl group, a pyridylmethyl group, a pyridylethyl group, a thienylmethyl group, a thienylethyl group, etc., preferred examples for the “aralkyloxy group” include , phenethyloxy group, phenylpropoxy group, naphthylmethyloxy group, naphthylethyloxy group, naphthylpropyloxy group, etc., and preferred examples for a “heteroarylalkyloxy group” include dissolved piridilmetiloksigruppu, pirazinilmetiloksigruppu, pirimidinilmetiloksigruppu, pirrolilmetiloksigruppu, imidazolilmetiloksigruppu, pirazolilmetiloksigruppu, hinolilmetiloksigruppu, izohinolilmetiloksigruppu, furyloxy, tienilmetiloksigruppu, tiazolilmetiloksigruppu etc.

Preferred examples for the “C _3-8 cycloalkyl group which may optionally have substituents” and the “C _3-8 cycloalkenyl group which may optionally have a substituent” include a C _3-8 cycloalkyl group (e.g., cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, etc.) and C _3-8 cycloalkenyl group (e.g., tsiklopropenilnaya group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group and the like), which I may be optionally substituted respectively with one or more groups selected from hydroxy group, halogen atom, nitrile group, C _1-6 alkyl group (e.g., methyl group, ethyl group, n-propyl group, an isopropyl group, a n-butyl group , isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, etc.), C _1-6 alkoxy groups (e.g. methoxy group, ethoxy group, n-propoxy group, isopropoxy group, sec. propoxy group, n-butoxy oup, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, izopentoksigruppa, sec-pentoxy, tert-pentoxy, n-hexoxy, etc.), C _1-6 alkoxyC _1-6 alkyl group, an aralkyl group ( for example, a benzyl group, a phenethyl group, a naphthylmethyl group, a naphthylethyl group, etc.), and the like.

Preferred examples of the “5-14 membered non-aromatic heterocyclic group”, “C _6-14 aromatic hydrocarbocyclic group” and the “5-14 membered aromatic heterocyclic group” for the above terms “optionally substituted 5-14 membered non-aromatic heterocyclic group”, “ optionally substituted C _6-14 aromatic hydrocarbocyclic group "and" optionally substituted 5-14 membered aromatic heterocyclic group "are not particularly limited, however more preferred" 5-14 membered non-aromatic g the heterocyclic group "includes a pyrrolidinyl group, a pyrrolinyl group, a piperidinyl group, a piperazinyl group, an imidazolidinyl group, a pyrazolidinyl group, a morpholinyl group, a phthalimidoyl group, a succinimidoyl group, etc .; more preferred “C _6-14 aromatic hydrocarbocyclic group” includes a phenyl group, an indenyl group, a naphthyl group, an azulenyl group, a heptalenyl group, a biphenyl group, etc .; a more preferred “5-14 membered aromatic heterocyclic group” includes a pyrrolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a pyrazolyl group, an imidazolyl group, a thienyl group, a furyl group, a thiazolyl group, an isothiazolyl group, a quinine group, a quinine group, a group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, a carbazolyl group, a dioxinyl group, etc., respectively. In addition, preferred examples of “substituents” in the term “which may optionally have substituents” include one or more groups selected from a hydroxy group, a halogen atom (e.g., a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc.), a nitrile group, a C _1-6 alkyl group (e.g., methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, nonopentyl group, n-hexyl group, etc.), C _1-6 alkox igroups (methoxy group, ethoxy group, n-propoxy group, isopropoxy group, sec-propoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentoxy group, iso-pentoxy-group, sec-pentoxy pentoxy pentoxy pentoxy etc.), a C _1-6 alkoxyC _1-6 alkyl group (e.g., methoxymethyl group, methoxyethyl group, ethoxymethyl group, ethoxyethyl group, etc.), an aralkyl group (e.g., benzyl group, phenethyl group, naphthylmethyl group , naphthylethyl group, etc. .), Etc. In addition, an amino group, a cyclic amino group and an alkoxy amino group, which optionally may have substituents, are also preferred as substituents.

Q is NH, O or S in formulas (I) and (II) and is preferably O.

The groups designated X, X ¹ , X ² and X ³ in the present invention mean the same or different simple (single) bond, optionally substituted C _1-6 alkylene group, optionally substituted C _2-6 alkenylene group, optionally substituted C _{2- 6} alkynylene group, -O-, -S-, -CO-, -O-, -SO ₂ -, -N (R ⁶ ) -, -N (R ⁷ ) -CO-, -CO-N (R ⁸ ) -, -N (R ⁹ ) -CH ₂ -, -CH ₂ -N (R ¹⁰ ) -, -CH ₂ -CO-, -CO-CH ₂ -, -N (R ¹¹ ) -S (O) _m -, -S (O) _n -N (R ¹² ) -, -CH ₂ -S (O) _p -, -S (O) _q -CH ₂ -, -CH ₂ -O-, -O-CH ₂ -, -N (R ¹³ ) -CO-N (R ¹⁴ ) - or -N (R ¹⁵ ) -CS-N (R ¹⁶ ) - (where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ represent a hydrogen atom, a C _1-6 alkyl group or a C _1-6 alkoxy group and m, n, p and q represent an integer, independently of each other, 0, 1 or 2).

Particularly preferred examples for the aforementioned “C _1-6 alkylene group” are an alkylene group having from 1 to 3 carbon atoms, and these examples include —CH ₂ -, - (CH ₂ ) ₂ -, —CH (CH ₃ ) -, - (CH ₂ ) ₃ -, -CH (CH ₃ ) -CH ₂ -, -CH ₂ -CH (CH ₃ ) - etc. Particularly preferred examples for the aforementioned “C _2-6 alkenylene group” are an alkenylene group having 2 or 3 carbon atoms, and examples of such a group include —CH = CH—, —CH = CH — CH ₂ -, —CH ₂ —CH = CH-, —C (CH ₃ ) = CH—, —CH = C (CH ₃ ) - etc. Particularly preferred examples of the aforementioned “C _2-6 alkynylene group” are an alkynylene group having 2 or 3 carbon atoms, and examples of such a group include —C≡C—, —C≡C — CH ₂ -, —CH ₂ —C≡C - etc. Preferred examples of the substituents indicated by X, X ¹ , X ² and X ³ in the aforementioned “C _1-6 alkylene group which may optionally have substituents”, “C _2-6 alkenylene group, which optionally may have substituents”, or “C _{The 2-6} alkynylene group, which optionally may have substituents, "includes a halogen atom (e.g., a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc.), a hydroxy group, a nitrile group, a nitro group, etc.

A preferred C _1-6 alkyl group represented by R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ includes a methyl group, an ethyl group, n a propyl group, an isopropyl group, an n-butyl group, a tert-butyl group, etc., and a preferred C _1-6 alkoxy group includes a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a tert-butoxy group, etc. d.

A preferred group for X, X ¹ , X ² and X ³ in the above formulas (I) and (II) includes a single bond, —CH ₂ -, —CH (OH) -, —CH (CN) -, —CH ₂ - CH ₂ -, -CH (OH) -CH ₂ -, -CH (CN) -CH ₂ -, -CH ₂ -CH (OH) -, -CH ₂ -CH (CN) -, -CH = CH-, -CH = CH-CH ₂ -, -CH = CH-CH (OH) -, -CH = CH-CH (CN) -, -CH (OH) -CH = CH-, -CH (CN) -CH = CH-, -C≡C-, -O-, -S-, -SO-, -SO ₂ -, -CO-, -NH-CO-NH-, -NH-CS-NH- and the like. ; a more preferred group includes a single bond, —CH ₂ -, —CH (OH) -, —CH (CN) -, —CH ₂ —CH ₂ -, —CH (OH) —CH ₂ -, —CH (CN) - CH ₂ -, -CH ₂ -CH (OH) -, -CH ₂ -CH (CN) -, -CH = CH-, -C≡C-, -CO- and the like; even more preferable are —CH ₂ -, —CH (OH) -, —CO— and a single bond is most preferred.

A preferred type of the claimed compound represented by the formula

(where Q, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as defined above), its salt or its hydrates are not particularly limited. Among them, the preferred type includes the compound, its salt or its hydrates, where R ¹ (namely, the 1-position of the pyridone ring) is a group represented by the formula —X — A (X and A have the same meanings as defined above), two of the remaining R ² , R ³ , R ⁴ and R ⁵ mean a group represented by the formula —X — A (X and A have the same meanings as defined above), and the other two represent a hydrogen atom, a halogen atom or C _1-6 an alkyl group; namely a compound represented by the formula

(where Q, X ¹ , X ² , X ³ , A ¹ , A ² , A ³ , R ¹⁷ and R ¹⁸ have the same meanings as defined above), its salt or its hydrates. A more preferred type includes a compound, its salt or its hydrates, where Q is oxygen in the above formula (II), namely the pyridone compound represented by the formula

(where X ¹ , X ² , X ³ , A ¹ , A ² , A ³ , R ¹⁷ and R ¹⁸ have the same meanings as defined above), its salt or its hydrates. Another preferred type includes a compound, its salt or its hydrates, where R ¹⁷ and R ¹⁸ represent hydrogen atoms in the above formula (III), namely a 1,3,5-substituted pyridone compound represented by the formula

(where X ¹ , X ² , X ³ , A ¹ , A ² and A ³ have the same meanings as defined above), its salt or its hydrates. The most preferred type includes the compound, its salt or its hydrates, where X ¹ , X ² and X ³ represent simple bonds in the above formula (IV), namely the 1,3,5-substituted pyridone compound represented by the formula

(where A ¹ , A ² and A ³ have the same meanings as defined above), its salt or its hydrates. Preferred groups for A ¹ , A ² and A ³ are the same groups as those presented in the above description of examples.

In the description of the present application, there is no particular limitation on the “salt” if it is formed with a compound of the present invention and is pharmacologically acceptable. Preferably, it is a salt with hydrogen halide (such as hydrofluoride, hydrochloride, hydrobromide or hydroiodide), a salt with inorganic acid (such as sulfate, nitrate, perchlorate, phosphate, carbonate or bicarbonate), a salt with organic carboxylic acid (such as acetate, trifluoroacetate, oxalate, maleate, tartrate, fumarate or citrate), a salt with an organic sulfonic acid (such as methanesulfonate, trifluoromethanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate or camphorsulfonate), a salt with an amino acid (such as aspartate or glutamate), a quaternary amine salt, an alkali metal salt (such as a sodium salt or a potassium salt) and an alkaline earth metal salt (such as a magnesium salt or a calcium salt). More preferred examples of a “pharmacologically acceptable salt” are hydrochloride, oxalate, etc.

Representative methods for preparing the compounds represented by the above formulas (I) and (II) according to the present invention are illustrated below.

Method 1

where A ¹ , A ² and A ³ may be the same or different from each other and each means an optionally substituted C _3-8 cycloalkyl group, C _3-8 cycloalkenyl group, 5-14-membered non-aromatic heterocyclic group, C _6-14 aromatic a hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group; Z ¹ and Z ² are the same or different from each other and each represents a halogen atom and X ¹ , X ² and X ³ have the same meanings as defined above. In the present production method, it is most preferred that A ¹ , A ² and A ³ represent an optionally substituted C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group. The above method 1 is a method for producing compound (I-1), which is related to the present invention, by introducing A ¹ , A ² and A ³ into a pyridone compound that has substituents Z ¹ and Z ² . That is, the compound (I-1) that is related to the present invention can be obtained by a method which consists in the fact that the pyridone compound (i), which has the substituents Z ¹ and Z ² , and the aryl boronic acid derivative are subjected to coupling reactions using a copper compound, to give compound (ii), and then A ² and A ³ are introduced into compound (ii), performing a coupling reaction with an organometallic reagent, using a transition metal catalyst or an organoboron compound, preferably carrying out a coupling reaction with derivatives m of aryl tin, arylzinc derivative or arylboronic acid derivative using a palladium catalyst. The preferred arylboronic acid derivative that is used to prepare compound (ii) varies depending on the starting material, the solvent used, and the like, and the choice of this derivative is not particularly limited if the reaction is not disturbed, however, the arylboronic derivative can be used acid, which has a group corresponding to A ^1, represented as an aryl group such as preferably a phenyl boronic acid derivative which may be optionally substituted, geterotsiklich skoe boronic acid derivative which may be optionally substituted, or the like A preferred result can also be obtained by carrying out the present reaction in the presence of a base, in which case a base is selected depending on the starting material, the solvent used, and the like. When a base is used for the coupling reaction of the above reaction, its choice is not particularly limited, and triethylamine, pyridine, tetramethylethylenediamine and the like are preferably used. Preferred examples of the copper compound used include copper acetate, di-μ-hydroxybis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride and the like. A more preferred result can be obtained by carrying out the reaction for the preparation of compound (ii) from (i) in the presence of a solvent. The solvent used usually differs depending on the starting material, reagent and the like, and its choice is not particularly limited provided that it is inert in the reaction and that it dissolves the starting material to some extent. Preferably, dichloromethane, tetrahydrofuran, ethyl acetate and the like are provided. In addition, the present reaction is preferably carried out in an atmosphere of oxygen or in a stream of air, and optimal results can be achieved (reducing the reaction time and increasing yield, etc.). The aryl tin compound, an arylzinc compound or an arylboronic acid derivative that is used for the reaction for preparing compound (I-1) by introducing A ² and A ³ into compound (ii) differs depending on the starting material, solvent used, etc., and its selection is not particularly limited until the reaction progresses, however, it is preferable to use a phenyltin compound, which may be optionally substituted, a heterocyclic tin compound, which may be optionally substituted, enzinc, which may be optionally substituted, a heterocyclic zinc compound, which may be optionally substituted, a phenylboronic acid derivative, a heterocyclic boronic acid derivative, which may be optionally substituted, an aryl tin compound, an aryl zinc compound or an arylboronic acid derivative that has a group corresponding to A ² or A ³ represented as an aryl group. A preferred result can also be obtained by using the present reaction in the presence of a base, in which case the base used differs depending on the starting material, the solvent used, etc. In addition, the choice of base is not particularly limited until the reaction progresses, and cesium carbonate, sodium carbonate, potassium carbonate and the like are preferably used. The type of palladium catalyst used is not particularly limited, and known palladium catalysts such as tetrakistriphenylphosphine palladium and the like are preferably mentioned. The reaction to obtain compound (I-1) by introducing A ² and A ³ into compound (ii) is preferably carried out in the presence of a solvent to achieve optimal process conditions and the possibility of mixing, the choice of solvent used is usually not particularly limited, however, dimethylformamide, toluene is preferably used xylene, benzene and the like. The reaction temperature is not particularly limited, and usually the process is carried out at room temperature or by boiling under reflux, preferably from 50 to 160 ° C. In addition to this, the compound (I-1) related to the present invention can also be obtained by the method according to which the pyridone compound (iii) after the introduction of A ¹ and A ^{2 is} combined with an organoboron compound or an organometallic reagent, preferably a boronic acid derivative, a tin compound or a zinc compound, and the resulting derivative is coupled with a halogenated aryl derivative using a transition metal catalyst.

Method 2

where X ¹ , X ² , X ³ , A ¹ , A ² , A ³ , Z ¹ and Z ² have the same meanings as defined above, and Z ³ means a protecting group of an alcohol hydroxy group (for example, a C _1-6 alkyl group benzyl group, etc.). In the present method of the invention, it is most preferred that A ¹ , A ² and A ³ represent an optionally substituted C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group. The compound (I-1) according to the present invention can also be obtained by introducing A ¹ , A ² and A ³ into the pyridine compound (iv) having substituents Z ¹ and —OZ ³ . The reaction for preparing compound (v) by introducing A ³ into compound (iv) can be carried out by coupling with an organometallic reagent or an organoboron compound using a transition metal catalyst, preferably providing a coupling reaction of compound (iv) with an aryolol derivative, an arylzinc derivative or an arylboronic acid derivative in the presence of a base using a palladium catalyst. The arylol derivative used, the arylzinc derivative or the arylboronic acid derivative used in the present reaction differs depending on the starting material, the solvent used and the like, and its choice is not particularly limited if the reaction is not disturbed, nevertheless, it is preferable to use the phenyltin derivative, which may be optionally substituted, a heterocyclic tin derivative, which may be optionally substituted, a phenylzinc derivative, which may be optionally substituted, heter an cyclic zinc derivative, which may be optionally substituted, a phenylboronic acid derivative, a heterocyclic boronic acid derivative, which may be optionally substituted, an aryl tin derivative, an aryl zinc derivative or an arylboronic acid derivative that has a group corresponding to A ³ represented as an aryl group. The base used differs depending on the starting material, the solvent used, and the like, and its selection is not particularly limited until the reaction course is disturbed, nevertheless, cesium carbonate, sodium carbonate, potassium carbonate and the like are preferably used. The type of palladium catalyst used is not particularly limited, and a known palladium complex such as tetrakistriphenylphosphine palladium and the like is preferably referred to. In addition, the present reaction is preferably carried out in the presence of a solvent in order to achieve an optimal process mode and the possibility of stirring. The solvent used differs depending on the starting material, the solvent used and the like, and the choice of solvents that dissolve the starting material to a certain extent is not particularly limited, provided that the reaction is not disturbed, nevertheless, dimethylformamide, toluene, xylene, benzene, etc. The reaction temperature is not particularly limited, and usually it is room temperature or under boiling conditions (with reflux condenser), preferably from 50 to 160 ° C. The reaction to produce pyridone compound (vi) by deprotecting Z ³ can be carried out by several known methods, and, for example, the conventional method described by TWGreene and PGMWuts "Protecting groups in organic synthesis 2 ^nd Edition (1991)" is mentioned as a reference method. The reaction for preparing the pyridone compound (vii) by introducing a substituent Z ² into the compound (vi) can usually be carried out by a known halogenation method. The halogenating reagent varies depending on the starting material, the solvent used, and the like, and its choice is not particularly limited until the reaction progresses, however, a brominating reagent such as acetic acid / bromine, N-bromosuccinimide or etc., an iodinating reagent such as iodine, N-iodosuccinimide or the like. Compound (viii) can be prepared by subjecting compound (vii) and the arylboronic acid derivative to a coupling reaction using a copper compound and introducing A ¹ . The choice of the arylboronic acid derivative to be used is usually not particularly limited, and an arylboronic acid derivative, which may be optionally substituted, a heterocyclic boronic acid derivative, which may be optionally substituted, and an arylboronic acid derivative that has a group corresponding to A ¹ represented as aryl can be used. Group. A preferred result can also be obtained by using the present reaction in the presence of a base, in which case the base used differs depending on the starting material, the solvent used, and the like. In addition, the choice of base is not particularly specified and triethylamine, pyridine, tetramethylethylenediamine and the like are preferably used. Preferred examples of the copper compound used include copper acetate, di-μ-hydroxybis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride and the like. In addition, the above reaction is preferably carried out in the presence of a solvent. The solvent used is usually selected depending on the starting material, reagent, and the like. and its selection is not particularly limited provided that it is reactively inert and that it dissolves the starting materials in a certain amount, nevertheless, dichloromethane, tetrahydrofuran, ethyl acetate and the like are preferably used. Further, the present reaction is preferably carried out in an oxygen atmosphere or in a stream of air, while optimal results can be achieved (reducing the reaction time and increasing yield, etc.). The final step in the preparation of compound (I-1) related to the present invention can be carried out by subjecting compound (viii) to a coupling reaction with an organometallic reagent or an organoboron reagent using a transition metal catalyst, preferably providing a coupling reaction with an aryolol derivative, an arylzinc derivative or an arylboronic derivative acid using a palladium catalyst, and by introducing A ² into compound (viii). The choice of an arylol derivative, an arylzinc derivative or an arylboronic acid derivative is usually not particularly limited, and it is preferable to use a phenyltin derivative, which may be optionally substituted, a heterocyclic tin derivative, which may be optionally substituted, a phenylzinc derivative, which may be optionally substituted, a heterocyclic zinc derivative which may be optionally substituted, phenylboronic acid derivative, heterocyclic boron derivative nd acid, which may be optionally substituted, aryl tin derivative, aryl zinc derivative or aryl boronic acid derivative which has a group corresponding to A ^2, shown as the aryl group. The sequential reaction for producing (I-1) from (viii), referred to in Production Method 2, can also provide a preferred result in the presence of a base, in which case the base used differs depending on the starting material, the solvent used, and the like. In addition, his choice is not particularly limited if the course of the reaction is not disturbed, and cesium carbonate, sodium carbonate, potassium carbonate, and the like are preferably used. The choice of the palladium catalyst used is usually not particularly limited, and known palladium catalysts such as tetrakistriphenylphosphine palladium and the like are preferably mentioned. In addition, a more preferable result can be obtained by carrying out the present reaction in the presence of a solvent, and the choice of solvent used is usually not particularly limited, the solvent used differs depending on the starting material, reagent, etc. The choice of a solvent that does not interfere with the reaction and which dissolves the starting material to a certain extent is not specified, however, dimethylformamide, toluene, xylene, benzene, etc. are preferable. The reaction temperature is not particularly limited, and usually it is room temperature or under boiling conditions (with reflux condenser), and preferably from 50 to 160 ° C. In addition to this, the compound (I-1) related to the present invention can also be obtained by the method according to which the pyridone compound (viii) after the administration of A ^{1 is} reacted with an organoboron compound or an organometallic reagent, preferably a boronic acid derivative, a tin compound or a zinc compound, and the (resulting) derivative is coupled with a halogenated aryl derivative using a transition metal catalyst, preferably a palladium catalyst.

 Method 3

where X ¹ , X ² , X ³ , A ¹ , A ² , A ³ , Z ¹ and Z ² have the same meanings as defined above, and each of the most preferred groups A ¹ , A ² and A ³ in the above method the preparation represents a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group, which may optionally have substituents, respectively. The compound (I-1) according to the present invention can also be obtained by introducing A ¹ , A ² and A ³ into 2-hydroxypyridine. The reaction for the preparation of compound (ix) can be carried out by a coupling reaction with an arylboronic acid derivative using a copper compound, a Ullman reaction with a halogenated aryl derivative, or a substitution reaction with a halogenated aryl derivative, and by introducing A ¹ into 2-hydroxypyridine. The arylboronic acid derivative used in the coupling reaction usually differs depending on the starting material, reagent, and the like. and his choice is not particularly limited if the course of the reaction is not disturbed. Preferably, an arylboronic acid derivative having a group corresponding to A ¹ representing an aryl group, such as a phenylboronic acid derivative that may optionally be substituted, a heterocyclic boronic acid derivative that may optionally be substituted, and the like, can be used. A preferred result can also be obtained by using the present reaction in the presence of a base, in which case the base used differs depending on the starting material, the solvent used, and the like. In addition, the choice of base is not particularly limited as long as the reaction is not disturbed, however, triethylamine, pyridine, tetramethylethylenediamine and the like are preferable. Preferred examples of the copper compound used include copper acetate, di-μ-hydroxybis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride and the like. In addition, the above reaction is preferably carried out in the presence of a solvent. The solvent used usually differs depending on the starting material, reagent, and the like. and the choice of an inert solvent that dissolves the starting material to a certain extent is not particularly limited, but dichloromethane, tetrahydrofuran, ethyl acetate and the like are preferred. Further, the aforementioned reaction is preferably carried out in an oxygen atmosphere or in a stream of air, while optimal results can be achieved (reducing the reaction time and increasing yield, etc.). The Ullmann reaction is carried out at 60 ° C. until boiling (refluxing), preferably from 100 to 200 ° C., in the presence of a base such as potassium carbonate, sodium carbonate or sodium acetate, using copper or a copper compound, such as copper iodide , copper chloride, copper bromide or the like, the choice of which is not specifically specified. The solvent used differs depending on the starting material, reagent, and the like. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, dimethylformamide, toluene, xylene, tetralin, dichlorobenzene, nitrobenzene and the like are preferable. The conditions for carrying out the substitution reaction with a halogenated aryl derivative are not particularly limited, nevertheless, it is carried out under conditions of ice cooling to boiling (reflux), preferably at room temperature up to 60 ° C., in a solvent such as tetrahydrofuran or dimethylformamide or the like. using a base such as potassium carbonate, sodium hydride, potassium hydride, sodium butoxide or potassium butoxide or the like. The reaction for preparing compound (x) by introducing substituent Z ¹ into compound (ix) can usually be carried out by a known halogenation method. The halogenating agent used differs depending on the starting material, the solvent used, and the like. and its choice is not particularly limited, if it does not disrupt the reaction, nevertheless, a brominating agent such as a mixture of acetic acid / bromine, N-bromosuccinimide or the like, an iodinating agent such as iodine, N-iodosuccinimide or etc., etc. The reaction for preparing compound (xi) by introducing A ³ into compound (x) can usually be carried out by subjecting compound (x) to a coupling reaction with an organometallic reagent or an organoboron compound using a transition metal catalyst, preferably subjecting it to a coupling reaction with an aryolol derivative, an arylzinc derivative, or arylboronic acid derivative in the presence of a base using a palladium catalyst. An aryl tin derivative, an aryl zinc derivative or an aryl boronic acid derivative that is used for the above reaction is usually not particularly limited, however, an aryl tin derivative, an aryl zinc derivative or an aryl boronic acid derivative having a group corresponding to A ³ introduced as an aryl group can be preferably used. as a phenyltin derivative that may optionally be substituted, a heterocyclic tin derivative that may optionally be substituted, a derivative of enzinc, which may optionally be substituted, a heterocyclic zinc derivative, which may optionally be substituted, a phenylboronic acid derivative, a heterocyclic boronic acid derivative, which may optionally be substituted. The base used varies depending on the starting material, the solvent used, and the like. and his choice is not particularly limited if the course of the reaction is not disturbed, nevertheless, cesium carbonate, sodium carbonate, potassium carbonate, etc. are preferred. The choice of the palladium catalyst used is not particularly limited, and known palladium catalysts such as tetrakistriphenylphosphine palladium and the like are preferably mentioned. Further, the aforementioned reaction is preferably carried out in the presence of a solvent in order to achieve an optimum mode of operation and the possibility of stirring. The solvent used varies depending on the starting material, the solvent used, and the like. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, dimethylformamide, toluene, xylene, benzene and the like are preferable. The reaction temperature is not particularly limited, and it is usually room temperature or under boiling conditions (with reflux condenser), preferably 50-160 ° C. The reaction for preparing compound (xii) by introducing a substituent Z ² into compound (xi) can usually be carried out by a known halogenation method. The halogenating agent used differs depending on the starting material, the solvent used, and the like. and its choice is not particularly limited until the reaction progresses, nevertheless, a brominating agent, such as a mixture of acetic acid / bromine, N-bromosuccinimide or the like, an iodinating agent, such as iodine, N-iodosuccinimide or t .p., etc. The final step in the preparation of compound (I-1) related to the present invention can be carried out by subjecting compound (xii) to a coupling reaction with an organometallic reagent or an organoboron compound using a transition metal catalyst, preferably subjecting it to a coupling reaction with an aryolol derivative, an arylzinc derivative or a derivative arylboronic acid using a palladium catalyst, and by introducing A ² into compound (xii). The aryl tin derivative, the arylzinc derivative, or the arylboronic acid derivative that is used differs depending on the starting material, the solvent used, and the like. and his choice is not particularly limited until the course of the reaction is disrupted. An aryl tin derivative, an aryl zinc derivative or an aryl boronic acid derivative having a group corresponding to A ² introduced as an aryl group, such as a phenyl tin derivative that may optionally be substituted, a heterocyclic tin derivative that may optionally be substituted, a phenyl zinc derivative that may optionally be used, can be used. to be substituted, a heterocyclic zinc derivative, which may optionally be substituted, a phenylboronic acid derivative, heterocyclic roizvodnoe boronic acid derivative which may be optionally substituted. In this case, the base used differs depending on the starting material, the solvent used, and the like. and his choice is not particularly limited until the reaction course is disrupted, nevertheless, cesium carbonate, sodium carbonate, potassium carbonate, and the like are preferred. The palladium catalyst used varies depending on the starting material, the solvent used, and the like. and his choice is not particularly limited, if the reaction is not disturbed, nevertheless reference is made to known palladium catalysts such as tetrakistriphenylphosphine palladium and the like. Further, a more preferable result can be obtained by carrying out the above reaction in the presence of a solvent, and the solvent used is not usually specified, however, dimethylformamide, toluene, xylene, benzene and the like are preferably used. The reaction temperature is not particularly limited, and usually it is room temperature or under boiling conditions (with reflux condenser), preferably 50-160 ° C. In addition to the foregoing, compound (I-1) related to the present invention can also be prepared by a method according to which compound (xii) is introduced into an organoboron compound or organometallic reagent, preferably a boronic acid derivative, tin compound or zinc compound or the like. and the resulting derivative is coupled with a halogenated aryl derivative using a transition metal catalyst, preferably a palladium catalyst.

Method 4

where X ¹ , X ² , X ³ , A ¹ , A ² , A ³ , Z ¹ , Z ² and Z ³ have the same meanings as defined above, and each of the preferred groups A ¹ , A ² and A ³ in the above process method represents a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group, which optionally may have substituents, respectively. The compound (I-1) related to the present invention can also be obtained by introducing A ¹ , A ² and A ³ into the compound (xiii) having substituents Z ¹ , Z ² and —OZ ³ . The reaction of obtaining compound (xiv) by introducing A ² into compound (xiii) can be carried out by subjecting compound (xiii) to a coupling reaction with an organometallic reagent or an organoboron compound using a transition metal catalyst, preferably subjecting it to a coupling reaction with an aryolol derivative, an arylzinc derivative or an arylboronic derivative acids in the presence of a base using a palladium catalyst. The aryl tin compound, aryl zinc compound or arylboronic acid derivative used in the present reaction usually differs depending on the starting material, reagent, and the like. and his choice is not particularly limited until the course of the reaction is disrupted. An aryl tin compound, an aryl zinc compound or an aryl boronic acid derivative having a group corresponding to A ² represented as an aryl group, such as a phenyl tin derivative which may be optionally substituted, a heterocyclic tin derivative which may be optionally substituted, a phenyl zinc derivative that may be used can be used. optionally substituted, heterocyclic zinc derivative, which may be optionally substituted, phenylboronic acid derivative, heterocyclic nical boronic acid derivative which may be optionally substituted, and the like The base used differs depending on the starting material, the solvent used, and the like. and his choice is not particularly limited, if the course of the reaction is not disturbed, nevertheless, cesium carbonate, sodium carbonate, potassium carbonate, etc. are used. The palladium catalyst used varies depending on the starting material, the solvent used, and the like. and his choice is not particularly limited until the reaction course is disrupted, nevertheless, palladium catalysts such as tetrakistriphenylphosphine palladium and the like are mentioned. In addition, the aforementioned reaction is preferably carried out in the presence of a solvent in order to achieve an optimum mode of operation and the possibility of stirring. The solvent used varies depending on the starting material, the solvent used and the like, and the choice of a solvent that does not interrupt the reaction and which dissolves the starting material to some extent is not particularly limited, however, dimethylformamide, toluene, xylene, benzene are preferred etc. The reaction temperature is not particularly limited, and usually it is room temperature or under boiling conditions (with reflux condenser), preferably 50 to 160 ° C. The reaction of obtaining compound (xv) of the substituent A ³ represented in compound (xiv) can be carried out by subjecting the compound (xiv) to a coupling reaction with an organometallic reagent or an organoboron compound using a transition metal catalyst, preferably subjecting it to a coupling reaction with an aryolol compound, an arylzinc compound or derivative arylboronic acid in the presence of a base using a palladium catalyst. The aryl tin compound, aryl zinc compound or arylboronic acid derivative used in the above reaction usually differs depending on the starting material, reagent, and the like. and his choice is not particularly limited until the course of the reaction is disrupted. Preferably, an arylol compound, an arylzinc compound or an arylboronic acid derivative having a group corresponding to A ³ represented as an aryl group, such as a phenyltin derivative which may be optionally substituted, a heterocyclic tin derivative which may be optionally substituted, a phenylzinc derivative which can be used may be optionally substituted, a heterocyclic zinc derivative, which may be optionally substituted, a phenylboronic ki derivative slots, a heterocyclic derivative of boronic acid, which may be optionally substituted, and the like. The base used differs depending on the starting material, the solvent used, and the like. and its selection is not particularly limited until the reaction course is disrupted, nevertheless, cesium carbonate, sodium carbonate, potassium carbonate and the like are preferably used. The choice of the palladium catalyst used is usually not particularly limited, however, known palladium catalysts such as tetrakistriphenylphosphine palladium and the like are mentioned. In addition, the aforementioned reaction is preferably carried out in the presence of a solvent in order to achieve an optimum mode of operation and the possibility of stirring. The solvent used differs depending on the starting material, the solvent used and the like, and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, dimethylformamide, toluene, xylene, benzene are preferred etc. The reaction temperature is not particularly limited, and usually it is room temperature or at boiling (with reflux condenser), preferably 50-160 ° C. The reaction for producing a pyridone compound (xvi) by removing the Z ³ protecting group can be carried out by several known methods, and for example, the conventional method described in TWGreene and PGMWuts "Protecting groups in organic synthesis 2 ^nd Edition (1991)" is mentioned as a reference method. The final step in the preparation of compound (I-1) of the present invention can be carried out by combining a compound (xvi) with an arylboronic acid derivative using a copper compound, a Ulman reaction with a halogenated aryl derivative, or a substitution reaction with a halogenated aryl derivative and by introducing A ¹ . The arylboronic acid derivative used differs depending on the starting material, the solvent used, and the like. and his choice is not particularly limited until the course of the reaction is disrupted. An arylboronic acid derivative having a group corresponding to A ¹ represented as an aryl group, such as a phenylboronic acid derivative that may optionally be substituted, a heterocyclic boronic acid derivative that may optionally be substituted, and the like can be used. A preferred result can also be obtained by carrying out the present reaction in the presence of a base, in which case the base used differs depending on the starting material used, the solvent used, and the like. In addition, the choice of base is not particularly limited if it does not disrupt the reaction, however, triethylamine, pyridine, tetramethylethylenediamine and the like are preferable. Preferred examples of the copper compound used include copper acetate, di-μ-hydroxybis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride and the like. Further, the above reaction is preferably carried out in the presence of a solvent. The solvent used varies depending on the starting material, reagent, etc. used. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, dichloromethane, tetrahydrofuran, ethyl acetate and the like are preferable. Further, the aforementioned reaction is preferably carried out in an atmosphere of oxygen or in a stream of air, and optimal results can be obtained (reducing the reaction time and increasing the yield, etc.). The Ullman reaction is carried out at a temperature of from 60 ° C to reflux conditions, preferably 100-200 ° C, in the presence of a base such as potassium carbonate, sodium carbonate or sodium acetate, using copper or a copper compound such as copper iodide, chloride copper, copper bromide or the like, which is usually not particularly limited. The solvent used varies depending on the starting material, reagent, and the like. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, dimethylformamide, toluene, xylene, tetralin, dichlorobenzene, nitrobenzene and the like are preferable. The conditions for carrying out the substitution reaction with a halogenated aryl derivative are not particularly limited, however, it is carried out under ice cooling to reflux, preferably from room temperature to 60 ° C., in a solvent such as tetrahydrofuran or dimethylformamide or the like, using a base such as potassium carbonate, sodium hydride, potassium hydride, sodium butoxide or potassium butoxide and the like.

In the above method, an intermediate compound represented by the formula

(where A ^1a , A ^3a and W ″ have the same meanings as defined above) can also be obtained in the following way.

Method 5

W ', W' 'and W' '' in the above formula mean the same or different halogen atom and the most preferred atom is a bromine atom.

The compound (XII) can be easily obtained by known methods or appropriate methods, and in addition, it can be easily obtained as a commercially available substance. The step for preparing compound (XI) from compound (XII) is a step for reacting compound (XII) with a base represented by the formula Z ³ OM (M is an alkali metal atom). The base differs depending on the starting material used, the solvent used, and the like. and its choice is not particularly limited if the reaction is not disturbed, sodium alkoxide is nevertheless preferred, and in particular, the use of sodium methoxide, sodium ethoxide and the like is preferable. In this case, the reaction is preferably carried out in an alcohol corresponding to the alkoxide used, and, for example, it is preferable to carry out the reaction in methanol in the case of sodium methoxide and in ethanol in the case of sodium ethoxide, etc.

The step for preparing compound (X) from compound (XI) is a step for reacting compound (XI) with trimethoxyborane in the presence of a base. The base used varies depending on the starting material, the solvent used, and the like. and his choice is not particularly limited until the reaction course is violated, n-butyllithium and the like are nevertheless preferred. The solvent used varies depending on the starting material, the solvent used, and the like. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, ethers such as tetrahydrofuran and the like are preferred. When n-butyllithium is used as the base, the reaction can be terminated with an acid, such as hydrochloric acid, or the like. in accordance with the usual method.

The step for preparing compound (IX) from compound (X) is a step for carrying out a coupling reaction of compound (X) with haloaryl or haloheteroaryl, which corresponds to the introduced substituent A ^3a , in the presence of a base and a palladium catalyst, and to produce compound (IX). The palladium catalyst used is not particularly limited, however, a palladium acetate / triphenylphosphine catalyst is mentioned as a preferred example. The base used varies depending on the starting material, the solvent used, and the like. and its selection is not limited, provided that the selected base does not disrupt the reaction, nevertheless, cesium carbonate, sodium carbonate, potassium carbonate, and the like are preferred. In addition, the aforementioned step is preferably carried out in the presence of a solvent in order to achieve optimum operating conditions and the possibility of mixing. The solvent used varies depending on the starting material, the solvent used, and the like. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent is not particularly limited, however, 1,2-dimethoxyethane, dimethylformamide, toluene, xylene, benzene and the like are preferably used. The reaction temperature is not particularly limited, and usually it is room temperature or the reaction is carried out under reflux conditions and preferably at 50-160 ° C.

The step for preparing compound (VIII) from compound (IX) is a step consisting in removing the protective group Z ³ from compound (IX). This reaction can be carried out by several known methods, and, for example, a method for boiling (under reflux) of compound (IX) in the presence of an acid (preferably hydrochloric acid and the like) is mentioned. In addition to this, the conventional method described in TWGreene and PGMWuts "Protecting groups in organic synthesis 2 ^nd Edition (1991)" is mentioned as a reference method.

The step for preparing compound (VI) from compound (VIII) represents the step that the compound (VIII) and the arylboronic acid derivative represented by the formula A ^1a B (OH) ₂ are subjected to a coupling reaction using a copper compound and the introduction

A ^1a . The selection of the arylboronic acid derivative used is generally not particularly limited. An arylboronic acid derivative that has a group corresponding to A ^1a represented as an aryl group, such as a phenylboronic acid derivative that may optionally be substituted, a heterocyclic boronic acid derivative that may optionally be substituted, and the like can be used. A preferred result can also be obtained by carrying out the present reaction in the presence of a base, in which case the base used varies from the starting material, the solvent used, and the like. In addition, the choice of base is not particularly limited so long as this does not disrupt the reaction, however, triethylamine, pyridine, tetramethylethylenediamine and the like are preferable. Preferred examples of the copper compound used include copper acetate, di-μ-hydroxybis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride and the like. In addition, the present reaction is preferably carried out in the presence of a solvent. The solvent used varies depending on the starting material, reagent, etc. used. and the choice of a solvent that does not interfere with the reaction and which dissolves the starting material to some extent, is not particularly limited, however, N, N-dimethylformamide, dichloromethane, tetrahydrofuran, ethyl acetate and the like are preferable. Further, this reaction is preferably carried out in an atmosphere of oxygen or in a stream of air, while it is possible to obtain optimal results (reducing the reaction time and increasing yield, etc.).

The step for preparing compound (VII) from compound (VI) is a step in which compound (VI) is subjected to a halogenation reaction. The halogenation reaction can usually be carried out by known halogenation methods. The halogenating agent used varies depending on the starting material, the solvent used, and the like. and its choice is not particularly limited, provided that the reaction is not disturbed, however, a brominating agent, such as a mixture of acetic acid / bromine, N-bromosuccinimide or the like, an iodinating agent, such as iodine, N is preferred iodosuccinimide or the like and the like.

According to the above process method 5, intermediates (VI) and (VII) can be obtained in high yield. In addition, in the case where the intermediate compounds related to the present invention are obtained by the methods of the invention, it is possible to easily prevent contamination of the final product with a copper compound and thereby obtain compounds of the present invention that satisfy the requirements for their safe use (toxicity, etc.) . Thus, the proposed methods are highly ideal in terms of output and safety (experimentally and when used for industrial purposes).

The new compound represented by the formula

(where A ^1a and A ^3a are the same or different from each other and each means a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group, which optionally may have a substituent, respectively, and R means a hydrogen atom or a halogen atom ) or its salt is used as an intermediate to obtain the claimed compound (I) or its salt. In the formula (XIII), preferred examples (groups) for A ^1a and A ^3a may be the same or different from each other, and each group includes a phenyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a thienyl group, a thiazolyl group, a furyl group, a naphthyl group, a quinolyl group, an isoquinolyl group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, an imidazopyridyl group, a carbazolyl group, etc., which is optional o may have substituents, respectively. More preferred examples may be the same or different from each other, and each group includes a phenyl group, a pyridyl group, a pyrimidinyl group, a thienyl group, a furyl group, etc., which optionally may have substituents, respectively. In addition, preferred examples for R, in particular, represent a hydrogen atom or a bromine atom.

Substituents on A ¹ , A ² and A ³ in the compound represented by the formula

(where Q, X ¹ , X ² , X ³ , A ¹ , A ² and A ³ have the same meanings as defined above; Y ¹ , Y ² and Y ³ mean the same or different substituents and each of the most preferred groups for A ¹ , A ² and A ³ represents a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group, which optionally may have substituents, respectively) can undergo transformations by various reactions. For example, using the reference methods presented below. So, for example, in the case where 1) Y ¹ , Y ² and / or Y ³ represent / represents nitro group (s), there are various reactions for the conversion of a functional group based on the nitro group, and since there is no restriction on the method and in relation to the resulting substance, an example is the method of conversion to an amino derivative by a reduction reaction. Although, as a rule, there are no restrictions with respect to the conditions for the reduction, conditions that represent a process using iron, zinc or tin under acidic conditions are preferred; hydrogenation method, where palladium, rhodium, ruthenium, platinum or their complex are used as a catalyst. In the case where an amine derivative obtained by the aforementioned reduction reaction is used, it can then be easily converted to an amide derivative, a carbamate compound, a sulfonamide compound, a halide derivative, a substituted amine compound, etc. (2) When Y ¹ , Y ² and / or Y ³ represent / represents an alkoxy group (s), an example of the conversion of a functional group based on an alkoxy group is a method for converting it to an alcohol derivative by deprotection reaction. The alcohol derivative, which is obtained by the above method, can be easily converted to an ester compound by condensation, accompanied by the evolution of water, with a carboxylic acid derivative or by reaction with an acid chloride, or it can be easily converted into an ester compound by a Mitsunobu reaction or a condensation reaction with a halide compound. (3) When Y ¹ , Y ² and / or Y ³ represent / represents an aldehyde group (s), there are various reactions for converting a functional group based on the aldehyde group and, since there is no restriction with respect to the method and with respect to the substance formed in the result of this transformation, an example is the method of conversion to a carboxylic acid derivative by an oxidation reaction. The carboxylic acid derivative obtained by the above method can be easily converted further into an ester compound, a ketone compound, etc. In addition, based on the above aldehyde derivative, it is possible to easily obtain an alcohol derivative by a reduction reaction, an amine derivative by a reductive amination reaction, a secondary alcohol compound by an addition reaction with an organometallic reagent, and various alkyl derivatives by a Wittig reaction. (4) When Y ¹ , Y ² and / or Y ³ represent / represents a halogen atom (s), an example for converting a functional group based on a halogen atom as a substituent is a method for converting a nitrile derivative into a substitution reaction. In addition to the above, it is also possible quite easily to be converted into various other types of compounds (derivatives) using, for example, an organolithium compound, an organomagnesium compound, an organotin compound or an organoboronic acid derivative, etc.

The above methods are a process for preparing compound (I) of the present invention. The starting compound in the above methods can form a salt or hydrate and there is no restriction on such a salt and hydrate as long as they do not inhibit the reaction. In the case when the compound (I) of the present invention is obtained in the form of a free substance, it can be converted into its salt form by conventional methods. In addition, a variety of isomers (e.g., geometric isomer; asymmetric carbon based enantiomer; rotamer, stereoisomer, tautomer, etc.) which are obtained in the case of compound (I) of the present invention are purified using conventional separation methods for example, such as recrystallization, diastereomeric salt method, enzymatic method, various chromatographic methods (for example, thin layer chromatography, column chromatography, gas chromatography, etc.), and they can be separated using ny above methods.

The compound of the present invention represented by the above formula (I), its salt or its hydrates by conventional methods can be included in pharmaceutical formulations presented in various dosage forms, such as tablets, diluted powders, micronized granules, granules, coated tablets, capsules , syrup, lozenges, inhalation preparation, suppositories, injections, ointments, eye ointments, eye drops, nasal preparations, ear drops, poultices or lotions. In the manufacture of pharmaceutical preparations, commonly used excipients, binders, disintegrating agents, lubricants, colorants, flavoring agents and, if necessary, stabilizers, emulsifiers, absorption promoters, surfactants can be used; pH adjusting agents; antiseptics, antioxidants, etc. and, after compounding (mixing) with components usually used as (auxiliary) substances for the preparation of pharmaceutical preparations, pharmaceutical preparations are prepared in the usual manner from a mixture. Examples of components used for this are 1) animal and vegetable oil, such as soybean oil, beef tallow or synthetic glyceride; 2) a hydrocarbon such as liquid paraffin, squalane or paraffin wax; 3) an ester oil such as octyldodecyl myristate or isopropyl myristate; 4) a higher alcohol, such as cetostearyl alcohol or behenyl alcohol; 5) silicone resin; 6) silicone oil; 7) a surfactant such as a condensation product of ethylene oxide with various high molecular weight fatty acids, ester of sorbitan and fatty acids, ester of glycerol and fatty acids, ester of polyoxyethylene sorbitan and fatty acids, polyoxyethylene hydrogenated castor oil or polyoxyethylene polyoxypropylene block copolymer ; 8) a water-soluble high molecular weight substance such as hydroxyethyl cellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinylpyrrolidone or methyl cellulose; 9) a lower alcohol such as ethanol or isopropanol; 10) a polyhydric alcohol such as glycerol, propylene glycol, dipropylene glycol or sorbitol; 11) a saccharide such as glucose or sucrose; 12) an inorganic powder, such as silicic anhydride, aluminum, magnesium, silicate or aluminum silicate; 13) pure water, etc. Suitable examples of excipients are (1) excipients: lactose, corn starch, pure sugar, glucose, mannitol, sorbitol, crystalline cellulose, silicon dioxide, etc .; (2) a binder: polyvinyl alcohol, polyvinyl ether, methyl cellulose, ethyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, block copolymer polypropylene glycol polyoxy ethylene polymethine, calcium, mega-calcium polymethylene citrate, mega-polytin ethylene polymethylene, mega-polythenecide, calcium (3) a disintegrant: starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, calcium citrate, dextrin, pectin, calcium carboxymethyl cellulose, etc .; (4) lubricants: magnesium stearate, talc, polyethylene glycol, silicon oxide, hydrogenated vegetable oil, etc .; (5) colorant: colorants that are allowed to be added to pharmaceuticals; (6) flavoring agent: cocoa powder, menthol, aromatic powder, peppermint essential oil, borneol and cinnamon powder; (7) antioxidant: antioxidants that are allowed to be added to pharmaceuticals, such as ascorbic acid, α-tocopherol and the like, and are used accordingly.

(1) To prepare preparations for oral use, a compound of the present invention or a pharmacologically acceptable salt thereof is mixed with an excipient and, if necessary, then with a binder, disintegrant, lubricant, dye, flavoring agent, etc. and a diluted powder, fine particles, granules, tablets, coated tablets, capsules, etc. are prepared from the mixture in the usual way. (2) In the case of tablets and coated tablets, of course, there is no problem that, if necessary, they can be coated with a sugar coating, a gelatin coating or other suitable coating. (3) In the case of liquid preparations such as syrup, injectable preparations and eye drops, a pH adjusting agent, a solubilizer and an isotonic agent, etc. are added. and, if necessary, a solubilizing additive, stabilizer, buffer, suspending agent, antioxidant, etc. and then pharmaceutical preparations are prepared from the mixture in the usual manner. It is possible to prepare the drug in the form of a product obtained by freeze-drying, and injections can be dosed into a vein, subcutaneous layer and muscle. Preferred examples for the suspending agent include methyl cellulose, polysorbate 80, hydroxyethyl cellulose, gum arabic, tragacanth powder, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate and the like; preferred examples for the solvent additive include polyoxyethylene cured castor oil, polysorbate 80, nicotinic acid amide, polyoxyethylene sorbitan monolaurate and the like; preferred examples for the stabilizer include sodium sulfite, sodium metasulfite, ether, and the like; preferred examples for the preservative include methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, sorbic acid, phenol, cresol, chlorocresol and the like. In addition, (4) in the case of external use, there is no particular restriction on the method for producing the pharmaceutical preparation; nevertheless, the usual method is used for preparation. So, for example, with regard to the base substance used, various substances can be used that are used for pharmaceuticals, quasi-drugs, cosmetics, etc. Specific examples of the base material used are animal / vegetable oil, mineral oil, essential oil, waxes, higher alcohols, fatty acids, silicone oil, surfactant, phospholipids, alcohols, polyhydric alcohols, water soluble high molecular weight substances, clay minerals and pure water and, if necessary, the addition of a pH adjusting agent, antioxidant, chelating agent, antiseptic, antifungal agent, dye, perfume, etc. is possible. If necessary, in addition, it is possible to add other components to the compound, such as a component having a differentiation inducing effect, a blood flow promoter, a bactericide, an anti-inflammatory agent, a cell activator, vitamins, an amino acid, a moisturizer and a keratin solubilizing agent.

The dose of a pharmaceutical agent according to the invention varies depending on the severity of the symptom, age, gender, body weight, dosage form, type of salt, sensitivity to pharmaceutical preparations, specific type of disease, etc .; for adults, the daily dose for oral administration is usually about 30 mcg-10 g, preferably 100 mcg-5 g or more preferably 100 mcg-100 mg, while in the case of administration by injection it is usually about 30 mcg-1 g preferably 100 μg to 500 mg or more preferably 100 μg to 30 mg. The dose is administered once a day or in several parts per day.

In accordance with the present invention, a novel compound (I) is provided which exhibits a strong inhibitory effect on the AMPA receptor and / or the kainate receptor and is useful as a pharmaceutical. In addition, a useful technological method has been developed for preparing said compound or its salt and a useful intermediate for this method. According to this method, the inventive compound can be obtained in high yield and a compound meeting high safety requirements can be obtained. Compound (I) of the present invention inhibits the neurotoxicity of excitatory neurotransmitters and is capable of providing a high neuroprotective effect as a pharmaceutical. Accordingly, the compounds of the present invention are useful as therapeutic, prophylactic and condition enhancing agents for various nervous diseases and are used, for example, as therapeutic and prophylactic agents for the treatment of acute neurodegenerative diseases (such as acute cerebrovascular disorders, subarachnoid hemorrhage, head trauma, spinal cord injury, nervous system disease (neuropathy) due to hypoxia or hypoglycemia th, etc.), chronic neurodegenerative diseases (such as Alzheimer's disease, Parkinson’s disease, Huntington’s chorea, amyotrophic lateral sclerosis or a disorder associated with degeneration of the spinal cord and cerebellum), epilepsy, hepatic encephalopathy, peripheral neuropathy, Parkinson’s syndrome, ( muscle) spasticity, pain, neuralgia, schizophrenia, anxiety, substance abuse, nausea, vomiting, urination disorders; visual impairment caused by glaucoma; hearing impairment caused by antibiotics, food poisoning, infectious cerebrospinal meningitis (such as cerebrospinal meningitis caused by HIV), cerebrovascular senile dementia or dementia or nerve symptoms due to meningitis. In addition, the compound of the present invention is used as an agent for the treatment or prophylaxis of a demyelinating disorder (such as encephalitis, acute multiple disseminated encephalomyelitis, multiple (multiple) sclerosis, acute demyelinating polyneuropathy, Hyena-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, Markiapha disease, demyelination of nerve fibers related to the central Varolian bridge, optic neuromyelitis, Devic's syndrome, Balo's disease, myelopathy, obus caught HIV; myelopathy due to the human T-cell leukemia virus (HTLV); progressive multifocal leukoencephalopathy and secondary demyelinating disorder (such as dimyelinating disorder with lupus erythematosus, nodosa (nodular) polyarteritis, Sjogrenitis syndrome, sarcoidosis and isolated).

The following reference examples, examples, and test examples are illustrative and are intended to in no way limit the present invention. The person skilled in the art may make various changes to the reference examples, examples and test examples, as well as the claims, in order to make full use of this invention. The above changes should not go beyond the scope of the attached claims.

Reference Example 1

5-bromo-3-iodo-1,2-dihydropyridin-2-one

2-amino-5-bromopyridine (CAS No. 1072-97-5) (300 g) was dissolved in a mixed solvent consisting of 1000 ml of acetic acid and 200 ml of water, 30 ml of concentrated sulfuric acid was gradually added dropwise into the resulting solution, with stirring. . Then, 79.1 g of periodic acid hydrate and 179 g of iodine were added to the mixture, followed by stirring at 80 ° C. for 4 hours. Periodic acid hydrate (40 g) and iodine (22 g) were added to the reaction mixture, followed by further stirring at 80 ° C. for 2 hours. After cooling to room temperature, the reaction mixture was poured onto ice (3000 ml) and neutralized with 5N aqueous sodium hydroxide to a pH of 7.0. The resulting crystals were collected by filtration, dissolved in ethyl acetate / diethyl ether in a mixed solvent, washed successively with aqueous sodium thiosulfate, water, 1N aqueous sodium hydroxide and brine, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated, yielding 392 g of 2-amino-5-bromo-3-iodopyridine (76% yield). 2-amino-5-bromo-3-iodopyridine (100 g) was gradually added to 300 ml of concentrated sulfuric acid under ice-cooling. After the reaction mixture was stirred at room temperature for 2 hours, it was again cooled with ice. 35 g of sodium nitrite are gradually added thereto, followed by stirring at room temperature for 3 days and nights. The reaction solution was poured onto ice (3000 ml) and neutralized with sodium hydroxide to a pH of 4.0. The resulting crystals were collected by filtration, washed with water and dried with warm air at 60 ° C. for one day and night to obtain 102 g (quantitative yield) of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.60 (d, 1H), 8.14 (d, 1H).

Reference Example 2

5-bromo-1-phenyl-3-iodo-1,2-dihydropyridin-2-one

5-Bromo-3-iodo-1,2-dihydropyridin-2-one (10.0 g) obtained in Reference Example 1, 10.0 g of phenylboronic acid and 8.1 g of copper acetate are suspended in 500 ml of dichloromethane. 15 ml of triethylamine was added to the suspension, followed by stirring at room temperature for 5 days and nights. 200 ml of water and 50 ml of aqueous ammonia are added to the reaction solution, followed by vigorous stirring. Then the insoluble matter is filtered off through celite, the filtrate is extracted with dichloromethane, the extract is dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was recrystallized from ethyl acetate / hexane to give 6.54 g (52% yield) of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.34-7.38 (m, 2H), 7.44-7.52 (m, 3H), 7.53 (d, 1H), 8.10 (d, 1H).

Reference Example 3

5-bromo-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

5-Bromo-1-phenyl-3-iodo-1,2-dihydropyridin-2-one (11.69 g) obtained in Reference Example 2, 8.0 g of 2- (2-cyanophenyl) -1.3, 2-dioxaborinate and 16.0 g of cesium carbonate are suspended in 150 ml of dimethylformamide. 3.0 g of tetrakistriphenylphosphine palladium was added to the suspension, followed by stirring at 80 ° C. under nitrogen for 2 hours. The reaction solution was poured into water, the mixture was extracted with ethyl acetate, the extract was washed successively with water and brine, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate), followed by recrystallization from ethyl acetate / hexane, to give 5.67 g (52% yield) of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.42-7.54 (m, 6H), 7.61-7.65 (m, 4H), 7.66 (d , 1H); 7.74-7.77 (m, 1H).

Reference Example 4

5- (2-Pyridyl) -1,2-dihydropyridin-2-one

2,5-Dibromopyridine [CAS No. 624-28-2] (400 g) was added to 3500 ml of a 28% methanol solution of sodium methoxide, the mixture was stirred at 60 ° C for 3 hours and allowed to cool, the reaction solution was poured into 3 liter of water, the mixture was extracted with diethyl ether (9000 ml), the extract was washed with brine three times, dried over anhydrous magnesium sulfate and the solvent was evaporated in vacuo. The residue was dissolved in 2 liters of dimethylformamide, 900 g of tri-N-butyl- (2-pyridyl) tin [Cas # 59020-10-9] and 20 g of tetrakistriphenylphosphine palladium were added and the mixture was stirred at 120 ° C. under nitrogen for 3 hours. The reaction solution was allowed to cool and poured into 3 liters of water, the mixture was extracted with 10 liters of diethyl ether, the extract was washed successively with saturated sodium bicarbonate solution and saturated brine, and the solvent was evaporated in vacuo. A 48% aqueous solution (800 ml) of hydrogen bromide was added to the residue, and the mixture was stirred at 110 ° C. for 3 hours. After cooling the reaction solution, it is washed with 3 liters of diethyl ether, poured into 2 liters of ice, adjusted to pH 11.0 with 5N sodium hydroxide solution and washed again with 3 liters of diethyl ether. The aqueous layer was adjusted to pH 7.0 and extracted with dichloromethane. The crude crystals obtained by evaporating the solvent in vacuo were washed with a mixed solvent of diethyl ether and hexane to give 201.5 g (69% yield) of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.72 (d, 1H), 7.20 (ddd, 1H), 7.50-7.54 (m, 1H), 7.73 (dt, 1H), 8.12-8.15 (m, 1H), 8.19 (dd, 1H), 8.60-8.64 (m, 1H).

Reference Example 5

3-bromo-5- (2-pyridyl) -1,2-dihydropyridin-2-one

5- (2-Pyridyl) -1,2-dihydropyridin-2-one (201.5 g) obtained in Reference Example 4 was dissolved in 1300 ml of dimethylformamide, 208.3 g of N-bromosuccinimide was added thereto, and the mixture was stirred at room temperature. temperature for 2 hours. The reaction mixture was poured into 4 liters of ice water, the precipitate was filtered off and dried with heated air at 50 ° C. for two days and nights to obtain 230 g (79% yield) of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21-7.26 (m, 1H), 7.52 (d, 1H), 7.75 (dt, 1H), 8.21 (d, 1H), 8.61-8.64 (m, 1H), 8.67 (d, 1H).

Reference Example 6

3-Bromo-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

Dichloromethane (300 ml) was added to 18.75 g of 3-bromo-5- (2-pyridyl) -1,2-dihydropyridin-2-one obtained in Reference Example 5, and 18.36 g of 3-pyridineboronic acid, then 3.47 g of di-μ-hydroxybis [(N, N, N'N'-tetramethylethylenediamine) copper (II)] chloride are added and the mixture is stirred under an atmosphere of oxygen for 4 days and nights. The reaction solution was purified by means of a short column filled with NH-silica gel (eluting with ethyl acetate), the solvent was evaporated in vacuo, and the resulting crude crystals were washed with diethyl ether to obtain 24.26 g (99% yield) of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.26 (m, 1H), 7.47-7.51 (m, 1H), 7.52-7 56 (m, 1H), 7.77 (dt, 1H), 7.87-7.91 (m, 1H), 8.19 (d, 1H), 8.53 (d, 1H), 8, 59-8.62 (m, 1H), 8.71-8.75 (m, 2H).

Reference Example 7

1- (2-Pyridyl) -1,2-dihydropyridin-2-one

25 ml of a solution of dimethylformamide containing 4.00 g of 2 (1H) -pyridone and 8.00 g of 2-bromopyridine are mixed with 3.80 g of potassium carbonate and 0.51 g of copper (I) iodide, followed by stirring at 120 ° C. within 2 hours. After the mixture is returned to room temperature, water is added to it. The mixture was extracted with ethyl acetate, the ethyl acetate layer was washed with water and brine, and then dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane = 1: 1) to obtain 1.58 g of the title compound as a pale yellow wax.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.31 (dt, 1H), 6.67 (d, 1H), 7.33 (ddd, 1H), 7.40 ( ddd, 1H), 7.82-7.90 (m, 2H), 7.96 (dd, 1H), 8.57 (dd, 1H).

Reference Example 8

1- (2-Pyridyl) -5-bromo-1,2-dihydropyridin-2-one

Under ice cooling, 15 ml of a dimethylformamide solution containing 1.50 g of 1- (2-pyridyl) -1,2-dihydropyridin-2-one is mixed with 1.60 g of N-bromosuccinic acid imide. The mixture was stirred at room temperature for 2 hours and then diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane = 1: 3) to obtain 1.13 g of the title compound as a pale brown powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.57 (d, 1H), 7.34 (ddd, 1H), 7.42 (dd, 1H), 7.85 ( dt, 1H), 7.97 (dd, 1H), 8.10 (d, 1H), 8.57 (dd, 1H).

Reference Example 9

1- (2-Pyridyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

2.5 ml of a solution of dimethylformamide containing 0.10 g of 1- (2-pyridyl) -5-bromo-1,2-dihydropyridin-2-one and 0.30 g of 2-tributylstannylpyridine are mixed with 0.05 g of dichlorobistriphenylphosphine palladium with subsequent stirring at 130 ° C for 2 hours. The mixture was returned to room temperature, followed by dilution with water and extraction with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate) to obtain 0.076 g of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.77 (d, 1H), 7.22 (dd, 1H), 7.36 (dd, 1H), 7.61 ( d, 1H), 7.76 (dt, 1H), 7.87 (dt, 1H), 7.97 (d, 1H), 8.12 (dd, 1H), 8.60-8.65 (m , 2H); 8.67 (d, 1H).

Reference Example 10

1- (2-Pyridyl) -5- (2-pyridyl) -3-bromo-1,2-dihydropyridin-2-one

2 ml of dimethylformamide solution containing 0.07 g of 1- (2-pyridyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one is mixed with 0.07 g of N-bromosuccinic acid imide with stirring and ice cooling. After the mixture was stirred at room temperature for 2 hours, it was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane = 3: 1) to obtain 0.05 g of the title compound as a pale brown powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.33 (ddd, 1H), 7.58 (ddd, 1H), 7.83-7.88 (m, 2H), 7.97 (dd, 1H), 8.07 (dt, 1H), 8.59-8.62 (m, 1H), 8.68-8.80 (m, 1H), 8.72 (d, 1H), 8.81 (d, 1H).

Reference Example 11

3,5-dibromo-2-methoxypyridine

80 ml of a 28% sodium methoxide solution are mixed with 30.0 g of 2,3,5-tribromopyridine under ice-cooling, followed by stirring at 50 ° C. for 2 hours. The reaction solution was diluted with water and extracted with diethyl ether. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane = 1: 20) to obtain 18.5 g of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.99 (s, 3H), 7.93 (d, 1H), 8.14 (d, 1H).

Reference Example 12

3- (2-Pyridyl) -5-bromo-2-methoxypyridine

100 ml of dimethylformamide solution containing 6.3 g of 3,5-dibromo-2-methoxypyridine and 8.1 g of 2-tributylstannylpyridine was mixed with 1.0 g of tetrakistriphenylphosphine palladium, followed by stirring at 120 ° C. for 2 hours under nitrogen atmosphere. After the mixture was returned to room temperature, the solvent was evaporated and the residue was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane = 1: 3) to obtain 2.8 g of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.02 (s, 3H), 7.31 (dd, 1H), 7.80 (dt, 1H), 8.02 ( ddd, 1H), 8.25 (d, 1H), 8.40 (d, 1H), 8.71-8.74 (m, 1H).

Reference Example 13

3- (2-Pyridyl) -5-phenyl-2- (1H) -pyridone

A mixture of 1.0 g of 3- (2-pyridyl) -5-bromo-2-methoxypyridine, 0.9 g of phenylboronic acid, 0.3 g of dichlorobistriphenylphosphine palladium and 2 ml of triethylamine is stirred at 120 ° C. for 1.5 hours in 30 ml of xylene in a nitrogen atmosphere. The mixture was returned to room temperature, diluted with ethyl acetate, washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated and the residue was mixed with 47% hydrobromic acid and heated at 70 ° C. for 1 hour. The reaction solution was cooled with ice, diluted with water and neutralized with potassium carbonate. The resulting precipitate was collected by filtration, washed with water and ether, and then air dried to give 0.5 g of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.30-7.37 (m, 2H), 7.43 (dd, 2H), 7.62 (d, 2H) ), 7.82-7.90 (m, 1H), 7.87 (d, 1H), 8.64-8.69 (m, 2H), 8.57 (d, 1H), 12.30 ( bc, 1H).

Reference Example 14

1-Phenyl-3-nitro-5- (2-pyridyl) -1,2-dihydropyridin-2-one

(14a) 3-Nitro-1-phenyl-1,2-dihydropyridin-2-one

5 g of 2-hydroxy-3-nitropyridine, 7.14 g of phenylboronic acid, 2.6 g of copper (II) acetate, 9.9 ml of triethylamine and 5.8 ml of pyridine are added to 100 ml of tetrahydrofuran, followed by stirring overnight. The reaction mixture was poured into aqueous ammonia and extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue was suspended in ether and collected by filtration to obtain 4.71 g of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.39 (dd, 1H), 7.36-7.40 (m, 2H), 7.49-7.54 (m , 3H), 7.73 (dd, 1H), 8.38 (dd, 1H).

(14b) 5-Bromo-3-nitro-1-phenyl-1,2-dihydropyridin-2-one

10 ml of a solution of dimethylformamide containing 1 g of 3-nitro-1-phenyl-1,2-dihydropyridin-2-one is mixed with 988 mg of N-bromosuccinimide, followed by stirring at room temperature overnight. Then the reaction mixture was stirred at 50 ° C for 3 hours. The reaction mixture was poured into ice / water, and the resulting precipitate was collected by filtration to obtain 1.27 g of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.36-7.39 (m, 2H), 7.50-7.57 (m, 3H), 7.88 (d , 1H); 8.42 (d, 1H).

(14c) 3-Nitro-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

1.27 g of 5-bromo-3-nitro-1-phenyl-1,2-dihydropyridin-2-one, 2.38 g of 2-tri-n-butylstannylpyridine and 248 mg of tetrakistriphenylphosphine palladium are added to 20 ml of xylene, followed by stirring at 120 ° C. overnight under nitrogen. The reaction mixture was purified by silica gel chromatography (ethyl acetate / hexane) to give 638 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.28 (ddd, 1H), 7.45-7.63 (m, 6H), 7.80 (dt, 1H), 8.61 (ddd, 1H), 8.63 (d, 1H), 9.03 (d, 1H).

Reference Example 15

3-amino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

100 mg of 10% palladium-carbon is added to 20 ml of an ethanol solution containing 546 mg of 3-nitro-1-phenyl-5- (pyridin-2-yl) -1,2-dihydropyridin-2-one, followed by stirring overnight in a hydrogen atmosphere. The reaction mixture was filtered through silica gel and concentrated to give 411 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.36-4.42 (m, 1H), 7.18 (dd, 1H), 7.28 (d, 1H), 7.44-7.54 (m, 6H), 7.61 (d, 1H), 7.70 (dt, 1H), 8.57-8.60 (m, 1H).

Reference Example 16

3- (2-cyanophenyl) -5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one

6 g of methyl 5-bromo-6-hydroxynicotinate synthesized in a known manner from 6-hydroxynicotinic acid, and 6.3 g of phenylboronic acid are dissolved in 200 ml of tetrahydrofuran. 939 mg of copper acetate and 1 ml of pyridine were added to the mixture, followed by stirring at room temperature for 3 nights. Aqueous ammonia was added to the reaction solution, and the solution was extracted with chloroform. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue obtained as a solid was washed with diethyl ether to obtain 7.35 g of 3-bromo-5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one as white crystals. 5 g of the product are dissolved in 100 ml of dimethylformamide, followed by the addition of 4.6 g of 2- (2-cyanophenyl) -1,3,2-dioxaborinate, 7.9 g of cesium carbonate and 375 mg of tetrakistriphenylphosphine palladium and stirring at 140 ° C for 1 hours in an atmosphere of nitrogen. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. Then, the extract was washed successively with water and brine, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated, and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 3.23 g of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.89 (s, 3H), 7.42-7.55 (m, 6H), 7.61-7.66 (m , 2H), 7.75 (dd, 1H), 8.14 (d, 1H), 8.35 (d, 1H).

Reference Example 17

3- (2-Chlorophenyl) -5-hydroxymethyl-1-phenyl-1,2-dihydropyridin-2-one

36 mg of 3- (2-chlorophenyl) -5-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one synthesized by the method of Reference Example 3 from 3-bromo-5-methoxycarbonyl-1-phenyl-1,2- dihydropyridin-2-one and 2-chloroboronic acid, dissolved in 20 ml of toluene. After cooling to −78 ° C., 0.1 ml of diisobutylaluminum hydride (1.5 M solution in tetrahydrofuran) was added dropwise to the solution. When heated from -78 ° C to room temperature, the mixture was stirred overnight. Then, 1N hydrochloric acid was added thereto, followed by stirring. The mixture was neutralized with an aqueous solution of sodium bicarbonate and then extracted with ethyl acetate. Then, the extract was washed successively with water and brine, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated, and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 12 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.48 (s, 2H), 7.25-7.29 (m, 3H), 7.37-7.51 (m , 8H).

Erie-Mass (ESI-Mass, electrospray ionization-mass spectrometry): 312 [M ⁺ + H].

Reference Example 18

3-methoxycarbonyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

4.5 g of methyl 5-bromo-2-hydroxynicotinate synthesized in a known manner from 2-hydroxynicotinic acid and 4.7 g of phenylboronic acid are dissolved in 200 ml of tetrahydrofuran. To the mixture was added 705 mg of copper acetate and 1 ml of pyridine, followed by stirring at room temperature for 3 nights in a stream of air. Aqueous ammonia was added to the reaction solution, and the solution was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue obtained as a solid was washed with diethyl ether to obtain 3.59 g of 5-bromo-3-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one as white crystals. 3.2 g of the product are dissolved in 100 ml of dimethylformamide and 7.7 g of tri-N-butyl- (2-pyridyl) tin [CAS No. 59020-10-9] and 240 mg of tetrakistriphenylphosphine palladium are added to this solution, followed by stirring at 110 ° C for 3 hours in a nitrogen atmosphere. After cooling to room temperature, the reaction solution was poured into water, extracted with ethyl acetate. Then, the extract was washed successively with water and brine, dried over anhydrous magnesium sulfate, and then filtered through NH-silica gel and silica gel. Then the filtrate was evaporated and the resulting precipitate was washed with ether and hexane and dried, yielding 1.59 g of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.95 (s, 3H), 7.22 (ddd, 1H), 7.42-7.54 (m, 5H), 7.62 (dt, 1H), 7.76 (td, 1H), 8.52 (d, 1H), 8.58 (ddd, 1H), 8.85 (d, 1H).

Reference Example 19

3- (2-cyanophenyl) -5-nitro-1-phenyl-1,2-dihydropyridin-2-one

(19a) 5-Nitro-1-phenyl-1,2-dihydropyridin-2-one

5.93 g of the title compound was prepared according to the method used in Reference Example (14a) from 5 g of 2-hydroxy-5-nitropyridine.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.67 (d, 1H), 7.39-7.43 (m, 2H), 7.53-7.59 (m , 3H), 8.18 (dd, 1H), 8.68 (dd, 1H).

(19b) 3-Bromo-5-nitro-1-phenyl-1,2-dihydropyridin-2-one

4.72 g of the title compound was prepared according to the method used for Reference Example (14b), from 5.93 g of 5-nitro-1-phenyl-1,2-dihydropyridin-2-one.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.38-7.42 (m, 2H), 7.54-7.58 (m, 3H), 8.59-8 61 (m, 1H); 8.66-8.68 (m, 1H).

(19c) 5-Nitro-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

758 mg of the title compound was prepared according to the method used for Reference Example 3 from 3 g of 3-bromo-5-nitro-1-phenyl-1,2-dihydropyridin-2-one.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.47-7.63 (m, 7H), 7.68 (dt, 1H), 7.80 (ddd, 1H), 8.38 (d, 1H); 8.78 (d, 1H).

Reference Example 20

5-amino-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

414 mg of the title compound was prepared according to the method used for Reference Example 15, from 708 mg of 5-nitro-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.99 (d, 1H), 7.39-7.49 (m, 7H), 7.60 (dt, 1H), 7.73 (d, 1H); 7.75 (d, 1H).

Example 1

3- (2-cyanophenyl) -5- (2-nitrophenyl) -1-phenyl-1,2-dihydropyridin-2-one

5-Bromo-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one (100 mg), 60 mg of 2-nitrophenylboronic acid and 130 mg of cesium carbonate are suspended in 10 ml of dimethylformamide, then 20 mg tetrakistriphenylphosphine palladium and the mixture was stirred at 120 ° C. under nitrogen for 4 hours. After cooling was achieved, the reaction solution was poured into water, the mixture was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, the solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 35 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.40-7.80 (m, 14H), 7.97 (dd, 1H).

Example 2

5- (2-aminophenyl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

3- (2-Cyanophenyl) -5- (2-nitrophenyl) -1-phenyl-1,2-dihydropyridin-2-one (32 mg) is dissolved in 15 ml of ethyl acetate, 5 mg of 10% palladium-on-carbon are added ( substance containing water) and the mixture is stirred at room temperature in a hydrogen atmosphere for 15 minutes. The catalyst was filtered off and the solvent was evaporated in vacuo to give 20 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.95 (br s, 2H), 6.76 (dd, 1H), 6.80 (dt, 1H), 7.14 ( dd, 1H), 7.17 (dt, 1H), 7.41-7.55 (m, 6H), 7.59 (d, 1H), 7.62 (dt, 1H), 7.74-7 82 (m, 2H); 7.88 (d, 1H).

Example 3

3- (2-cyanophenyl) -5- (2-methylsulfonylaminophenyl) -1-phenyl-1,2-dihydropyridin-2-one

5- (2-aminophenyl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one (16 mg) is dissolved in 10 ml of dimethylformamide, then 0.05 ml of triethylamine and 3 drops of methanesulfonyl chloride are added. and the mixture was stirred at room temperature for one hour. Ethyl acetate was added to the reaction solution, the mixture was washed with water and brine, the solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 5 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.19 (s, 3H), 6.88-6.95 (m, 1H), 7.08-7.15 (m , 1H), 7.38-7.55 (m, 8H), 7.61 (dt, 1H), 7.69-7.76 (m, 3H), 7.91 (d, 1H), 7, 92-7.97 (m, 1H).

Example 4

3- (2-Chloro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

3-Iodo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one (200 mg) synthesized in the same manner as mentioned in Reference Example 6, 130 mg of 2-chloro-3 -pyridylboronic acid and 250 mg of cesium carbonate are suspended in 10 ml of dimethylformamide, 40 mg of tetrakistriphenylphosphine palladium are added and the mixture is stirred at 100 ° C. under nitrogen for 3 hours. After cooling was achieved, the reaction solution was poured into water, the mixture was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, the solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 143 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20-7.24 (m, 1H), 7.31 (dd, 1H), 7.44-7.59 (m 6H), 7.75 (dt, 1H), 7.91 (dd, 1H), 8.25 (d, 1H), 8.33 (d, 1H), 8.41 (dd, 1H), 8 59-9.62 (m, 1H).

Example 5

3- (2-cyanophenyl) -5- (2-pyridyl) -2-methoxypyridine

Tetrakistriphenylphosphine palladium (0.15 g) is added to a mixed solution of 0.50 g of 5- (2-pyridyl) -3-bromo-2-methoxypyridine, 0.42 g of 2- (2-cyanophenyl) -1,3,2-dioxaborinate , 0.82 g of cesium carbonate and 20 ml of dimethylformamide, and the mixture was stirred at 140 ° C. under nitrogen for 5 hours. After cooling to room temperature, ethyl acetate was added thereto, the mixture was washed with water and brine, and dried over magnesium sulfate. The solvent was concentrated in vacuo and the residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1: 3) to obtain 0.36 g of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.03 (3H, s), 7.24-7.28 (1H, m), 7.46-7.51 (1H , ddd), 7.57 (1H, dd), 7.65-7.69 (1H, ddd), 7.72-7.82 (3H, m), 8.31 (1H, d), 8, 66-8.69 (1H, m), 8.83 (1H, d).

Example 6

3- (2-cyanophenyl) -5- (2-pyridyl) -2 (1H) -pyridone

Chlorotrimethylsilane (0.1 ml) was added to a suspension of 0.20 g of 3- (2-cyanophenyl) -5- (2-pyridyl) -2-methoxypyridine and 0.12 g of sodium iodide in 10 ml of acetonitrile and the mixture was stirred at room temperature within 3 hours. A saturated sodium bicarbonate solution was added to the mixture, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water and brine and dried over magnesium sulfate. The solvent was concentrated in vacuo and the residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1: 1) to obtain 0.11 g of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26 -7.30 (1H, ddd), 7.55-7.60 (1H, ddd), 7.66 (1H dd), 7.74-7.79 (1H, ddd), 7.80-7.86 (1H, ddd), 7.89-7.94 (2H, m), 8.28 (1H, d ), 8.37 (1H, d), 8.56-8.59 (1H, m).

Example 7

3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

Suspension 0.11 g of 3- (2-cyanophenyl) -5- (2-pyridyl) -2 (1H) -pyridone, 0.12 g of phenylboronic acid, 0.1 g of copper acetate and 0.3 ml of triethylamine in 10 ml methylene chloride was stirred at room temperature overnight. To this was added 5 ml of concentrated aqueous ammonia, 10 ml of water and 40 ml of ethyl acetate, the organic layer was separated, washed with water and brine, and dried over magnesium sulfate. The solvent was concentrated in vacuo and the residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1: 2) to obtain 0.06 g of the title product as a pale yellow powder.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.29-7.33 (1H, m), 7.48-7.63 (6H, m), 7.71 -7.75 (1H, dd), 7.76-7.88 (2H, m), 7.92-7.95 (1H, m), 8.01 (1H, d), 8.48 (1H d) 8.54 (1H, d), 8.58-8.61 (1H, m).

Example 8

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitrophenyl) -1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.28 (m, 1H), 7.49 (dt, 1H), 7.63-7.81 (m 6H), 7.95-7.98 (m, 1H), 8.31-8.37 (m, 3H), 8.45 (t, 1H), 8.60-8.63 (m, 1H )

Example 9

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one

Iron powder (180 mg) and 342 mg of ammonium chloride are added to a solution of 317 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitrophenyl) -1,2-dihydropyridin-2-one a mixture of 10 ml of 2-propanol and 5 ml of water, followed by boiling under reflux for 4 hours. The reaction mixture was concentrated, partitioned into ethyl acetate / water, the organic layer was washed with water, dried and concentrated, the residue was purified by silica gel column chromatography (ethyl acetate / hexane) to obtain 235 mg of the title compound as a pale yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.84 (s, 2H), 6.75 (dd, 1H), 6.82-6.87 (m, 2H), 7.20 (dd, 1H), 7.26-7.30 (m, 1H), 7.45 (td, 1H), 7.59-7.65 (m, 2H), 7.72-7, 80 (m, 3H), 8.29 (s, 2H), 8.56-8.61 (m, 1H).

Example 10

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminophenyl) -1,2-dihydropyridin-2-one

Triethylamine (0.2 ml) is added to a solution of 31 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one in 2 ml of tetrahydrofuran, 0.1 ml of methanesulfonic acid chloride was added dropwise thereto under ice-cooling, and the mixture was stirred for 10 minutes. To this was added 2 ml of 2N sodium hydroxide, the mixture was stirred at room temperature for 5 minutes and partitioned into ethyl acetate / water, the organic layer was washed with water, dried and concentrated, the residue was purified by silica gel column chromatography (ethyl acetate / hexane), to give 38 mg of the title compound as a pale yellow amorphous substance.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.93 (s, 3H), 4.00-4.09 (m, 1H), 7.22-7.31 (m , 3H), 7.36 (t, 1H), 7.43 (t, 1H), 7.46 (dd, 1H), 7.61 (dt, 1H), 7.65 (td, 1H), 7 73-7.78 (m, 3H), 8.27 (d, 1H), 8.31 (d, 1H), 8.59-8.61 (m, 1H).

Example 11

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminophenyl) -1,2-dihydropyridin-2-one

Paraformaldehyde (41 mg) and 119 mg of sodium triacetoxyborohydride are added to a solution of 50 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one in 3 ml of acetic acid, followed by stirring at room temperature for one night. To this was added an aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic layer was washed with water, dried and concentrated, the residue was purified by silica gel column chromatography (ethyl acetate / hexane) to obtain 11 mg of the title compound as a pale yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.00 (s, 3H), 7.11-7.14 (m, 1H), 7.21 (ddd, 1H), 7.35 (t, 1H), 7.44-7.49 (m, 2H), 7.59 (d, 1H), 7.66 (td, 1H), 7.70-7.77 (m, 4H), 8.25 (d, 1H), 8.51 (s, 1H), 8.58-8.61 (m, 1H).

Example 12

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-dimethylaminophenyl) -1,2-dihydropyridin-2-one

Paraformaldehyde (41 mg) and 119 mg of sodium triacetoxyborohydride are added to a solution of 50 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one in 3 ml of acetic acid, followed by stirring at room temperature for 6 hours. To this was added another 41 mg of paraformaldehyde and 119 mg of sodium triacetoxyborohydride, the mixture was stirred for one night, an aqueous solution of sodium bicarbonate was added thereto, the mixture was extracted with ethyl acetate, the organic layer was washed with water, dried and concentrated, the residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give 38 mg of the title compound as a pale yellow amorphous substance.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.99 (s, 6H), 6.77-6.80 (m, 3H), 7.18-7.21 (m , 1H), 7.32-7.37 (m, 1H), 7.44 (t, 1H), 7.59-7.64 (m, 2H), 7.71-7.83 (m, 3H ), 8.32 (s, 2H), 8.58-8.60 (m, 1H).

Example 13

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- [3- (5-methoxymethyl-2-oxazolidinon-3-yl) phenyl] -1,2-dihydropyridin-2-one

Glycidyl methyl ether (0.01 ml) and 22 mg of magnesium periodate are added to a solution of 38 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2- it is in 6 ml of acetonitrile, followed by stirring at room temperature. After 2 hours, an additional 0.01 ml of glycidyl methyl ether and 22 mg of magnesium periodate were added thereto, the mixture was stirred at room temperature for 1 hour and then stirred at 50 ° C for another 1 hour. The reaction mixture was partitioned between ethyl acetate / water, the organic layer was washed with water, dried and concentrated, the residue was dissolved in 6 ml of tetrahydrofuran, 32 mg of carbonyldiimidazole was added thereto, and the mixture was heated under reflux for 2 hours. The mixture was partitioned between ethyl acetate / water, the organic layer was washed with water, dried and concentrated, the residue was purified by preparative thin layer chromatography (ethyl acetate / hexane) to give 21 mg of the title compound as a pale yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.43 (s, 3H), 3.64 (dd, 2H), 3.97 (dd, 1H), 4.09 ( t, 1H), 4.77 (ddd, 1H), 7.22 (ddd, 1H), 7.29 (ddd, 1H), 7.46 (td, 1H), 7.53 (t, 1H), 7.59-7.79 (m, 7H), 8.30 (d, 1H), 8.31 (d, 1H), 8.58-8.61 (m, 1H).

Example 14

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-methoxycarbonylphenyl) -1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.94 (s, 3H), 7.23 (ddd, 1H), 7.47 (td, 1H), 7.59- 7.68 (m, 4H), 7.73-7.80 (m, 3H), 7.88-7.91 (m, 2H), 8.31 (d, 1H), 8.32 (d, 1H), 8.59-8.61 (m, 1H).

Example 15

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminocarbonylphenyl) -1,2-dihydropyridin-2-one

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-methoxycarbonylphenyl) -1,2-dihydropyridin-2-one (10 mg) is added to 6 ml of a 40% methanol methanol solution, followed by stirring at room temperature for one night. The reaction solution was concentrated in vacuo to give 10 mg of the title compound as a pale yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.00 (d, 3H), 6.51 (br, 1H), 7.23 (ddd, 1H), 7.47 ( td, 1H), 7.58-7.68 (m, 4H), 7.73-7.80 (m, 3H), 7.88-7.91 (m, 2H), 8.31 (d, 1H), 8.32 (d, 1H), 8.59-8.61 (m, 1H).

Example 16

3- (2-cyano-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

Path 1

3- (2-Chloro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one (281 mg) is dissolved in 20 ml of dimethylformamide, 170 mg of copper cyanide are added and the mixture stirred at 130 ° C for 10 hours. The reaction solution was cooled to room temperature, aqueous ammonia and ethyl acetate were added, the organic layer was separated, washed with water and dried over anhydrous sodium sulfate, the drying agent was filtered off, the filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 120 mg the title compound as a colorless amorphous substance.

Way 2

3-Bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one (2.9 g), synthesized in the same manner as mentioned in Reference Example 6, was dissolved in 200 ml of xylene, 5 ml of bis (tributyltin) and 400 mg of tetrakistriphenylphosphine palladium are added and the mixture is stirred at 140 ° C. for 2 hours. 3-bromo-2-cyanopyridine (3.2 g) and 100 mg of tetrakistriphenylphosphine palladium were added thereto, and the mixture was stirred at 140 ° C. for 2 hours.

Tetrakistriphenylphosphine palladium (1.0 g) and 800 mg of copper iodide are divided into four portions and added every hour, then 2 g of 3-bromo-2-cyanopyridine is added thereto and the mixture is stirred at 140 ° C. for one night. The reaction solution was cooled to room temperature, water and ethyl acetate were added thereto, the organic layer was separated, washed with water and dried over anhydrous sodium sulfate, the drying agent was filtered off, the filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane / ethyl acetate), to give 1 8 g of the title compound as a colorless amorphous substance.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (ddd, 1H), 7.47-5.57 (m, 6H), 7.63 (d, 1H), 7.68 (td, 1H), 8.22 (dd, 1H), 8.37 (dd, 1H), 8.43 (d, 1H), 8.59-8.61 (m, 1H), 8 69 (dd, 1H).

ERI-Mass: 351 [M ⁺ + H].

Example 17

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-methoxyphenyl) -1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 4.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.84 (s, 3H), 6.98-7.03 (m, 2H), 7.19 (ddd, 1H), 7.28-7.33 (m, 2H), 7.40-7.46 (m, 2H), 7.46-7.51 (m, 2H), 7.53-7.57 (m, 1H ), 7.72 (ddd, 1H), 8.12 (d, 1H), 8.29 (d, 1H), 8.57-8.61 (m, 1H).

Example 18

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-hydroxyphenyl) -1,2-dihydropyridin-2-one

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-methoxyphenyl) -1,2-dihydropyridin-2-one (440 mg) is dissolved in 5 ml of 48% hydrobromic acid and heated to boiling with reflux for 1 hour. After the reaction solution was cooled to room temperature, it was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The desiccant was filtered off, the filtrate was concentrated in vacuo and purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 292 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.67-6.73 (m, 2H), 7.12-7.18 (m, 2H), 7.19-7 24 (m, 1H), 7.30-7.38 (m, 2H), 7.47-7.53 (m, 2H), 7.56 (d, 1H), 7.70 (s, 1H ), 7.73 (ddd, 1H), 8.18 (d, 1H), 8.26 (d, 1H), 8.57-8.62 (m, 1H).

Example 19

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-hydroxyphenyl) -1,2-dihydropyridin-2-one (82 mg) and 57 mg of N, N-dimethylaminoethyl chloride are dissolved in 2 ml of dimethylformamide 55 mg of potassium carbonate are added thereto at 60 ° C. and the mixture is stirred for one night. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The desiccant was filtered off, the filtrate was concentrated in vacuo and purified by NH silica gel column chromatography (hexane / ethyl acetate) to obtain 27 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.55 (s, 6H), 2.76 (t, 2H), 4.11 (t, 2H), 6.99- 7.05 (m, 2H), 7.19 (ddd, 1H), 7.26-7.34 (m, 2H), 7.39-7.45 (m, 2H), 7.45-7, 51 (m, 2H), 7.55 (d, 1H), 7.72 (ddd, 1H), 8.12 (d, 1H), 8.28 (d, 1H), 8.57-8.61 (m, 1H).

Example 20

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-formylphenyl) -1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (ddd, 1H), 7.84 (ddd, 1H), 7.63 (d, 1H), 7.66 ( ddd, 1H), 7.72 (dd, 1H), 7.75-7.82 (m, 3H), 7.84-7.88 (m, 1H), 8.00 (ddd, 1H), 8 05-8.08 (m, 1H), 8.32 (d, 1H), 8.35 (d, 1H), 8.59-8.62 (m, 1H), 10.08 (s, 1H) )

Example 21

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-hydroxymethylphenyl) -1,2-dihydropyridin-2-one

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-formylphenyl) -1,2-dihydropyridin-2-one (585 mg) was dissolved in 20 ml of methanol, 260 mg of sodium borohydride was added while cooling ice and the mixture was stirred at room temperature for one night. The reaction solution was diluted with ethyl acetate, washed with brine and dried over anhydrous magnesium sulfate. The desiccant is filtered off, the filtrate is concentrated in vacuo and purified by NH silica gel column chromatography (ethyl acetate). The resulting crude crystals were recrystallized from ethyl acetate / diethyl ether to give 320 mg of the title compound.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 4.60 (d, 2H), 5.37 (t, 1H), 7.29-7.33 (m, 1H ), 7.42-7.47 (m, 2H), 7.48-7.55 (m, 2H), 7.59 (ddd, 1H), 7.73 (dd, 1H), 7.78 ( dd, 1H), 7.83 (ddd, 1H), 7.94 (dd, 1H), 8.01 (d, 1H), 8.48 (d, 1H), 8.52 (d, 1H), 8.57-8.61 (m, 1H).

Example 22

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-cyanomethylphenyl) -1,2-dihydropyridin-2-one

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-hydroxyphenyl) -1,2-dihydropyridin-2-one (53 mg) is dissolved in 2 ml of tetrahydrofuran, then 60 are added thereto under ice cooling μl of triethylamine and 20 μl of methanesulfonyl chloride and the mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with an aqueous sodium bicarbonate solution, extracted with ethyl acetate and the extract was dried over anhydrous magnesium sulfate. The desiccant is filtered off, the filtrate is concentrated in vacuo, the resulting residue is dissolved in 1 ml of dimethyl sulfoxide, 3 mg of sodium cyanide are added and the mixture is stirred at room temperature for 1 hour. The reaction solution was diluted with ethyl acetate, washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, the filtrate was concentrated in vacuo, and the resulting crude crystals were recrystallized from ethyl acetate / diethyl ether / hexane to give 12 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.85 (s, 2H), 7.21-7.26 (m, 1H), 7.41-7.81 (m , 10H), 8.29-8.32 (m, 2H), 8.59-8.62 (m, 1H).

The following compounds are obtained in the same manner as in the above example 22.

Example 23

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetylaminomethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.04 (s, 3H) 4.47-4.52 (m, 2H), 7.22 (ddd, 1H), 7 37-7.53 (m, 5H), 7.61 (d, 1H), 7.65 (ddd, 1H), 7.72-7.81 (m, 3H), 8.28 (d, 1H) ), 8.31 (d, 1H), 8.59-8.62 (m, 1H).

Example 24

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminomethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.91 (s, 3H), 4.36 (d, 2H), 5.00-5.06 (m, 1H), 7.22 (ddd, 1H), 7.43-7.49 (m, 3H), 7.50-7.55 (m, 2H), 7.61 (ddd, 1H), 7.64 (ddd, 1H), 7.73-7.79 (m, 3H), 8.28-8.31 (m, 2H), 8.60 (ddd, 1H).

Example 25

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-acetoxymethylphenyl) -1,2-dihydropyridin-2-one

To 56 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-hydroxymethylphenyl) -1,2-dihydropyridin-2-one, 1 ml of acetic anhydride and 1 ml of pyridine are added and the mixture is stirred at room temperature. temperature for one night. The reaction solution was concentrated in vacuo and purified by NH silica gel chromatography (hexane / ethyl acetate) to obtain 30 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.13 (s, 3H), 5.18 (s, 2H), 7.23 (ddd, 1H), 7.44- 7.56 (m, 5H), 7.60-7.67 (m, 2H), 7.73-7.81 (m, 3H), 8.30-8.33 (m, 2H), 8, 59-8.62 (m, 1H).

Example 26

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylthiophenyl) -1,2-dihydropyridin-2-one

The title compound was obtained in the same manner as in Example 7.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.53 (s, 3H), 7.21-7.24 (m, 1H), 7.36-8.79 (m , 10H), 8.28-8.32 (m, 2H), 8.59-8.61 (m, 1H).

Example 27

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylsulfonylphenyl) -1,2-dihydropyridin-2-one

70% m-chloroperbenzoic acid (500 mg) is added gradually over 2 hours to a solution of 50 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylthiophenyl) -1,2-dihydropyridine- 2-one in 4 ml of methylene chloride, followed by stirring under ice cooling. A saturated aqueous sodium bicarbonate solution was added thereto, the mixture was partitioned between ethyl acetate / water, the organic layer was washed with water, dried and concentrated, the residue was purified by silica gel column chromatography (ethyl acetate / hexane) to obtain 5 mg of the title compound as a yellow solid .

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.11 (s, 3H), 7.24-7.28 (m, 1H), 7.50 (dt, 1H), 7.61-7.82 (m, 7H), 8.20 (d, 2H), 8.30-8.33 (m, 2H), 8.60-8.63 (m, 1H).

Example 28

3- (2-cyanophenyl) -5- (2-formylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one

The title compound was prepared according to Example 1.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.29 (d, 1H), 7.42-7.57 (m, 6H), 7.65 (dt, 1H), 7.71 (d, 1H), 7.77-7.82 (m, 3H), 7.85 (d, 1H), 10.10 (s, 1H).

Example 29

3- (2-cyanophenyl) -5- (2-diethylaminomethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one

A solution of 20 mg of 3- (2-cyanophenyl) -5- (2-formylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one, 0.1 ml of a 2 M solution of diethylamine in tetrahydrofuran and 0, 1 ml of acetic acid in 2 ml of tetrahydrofuran was stirred at room temperature for 15 minutes, 20 mg of sodium triacetoxyborohydride was added and the mixture was stirred for another 3 hours. A 2N aqueous sodium hydroxide solution was added to the mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was concentrated in vacuo and the residue was purified by NH silica gel column chromatography to obtain 15 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.38 (t, 6H), 2.99-3.20 (m, 4H), 4.57 (d, 2H), 7.07 (d, 1H), 7.40-7.58 (m, 8H), 7.60-7.67 (m, 2H), 7.77 (d, 1H), 7.87 (d, 1H).

Example 30

3- (2-cyanophenyl) -5- (2-hydroxymethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one

Sodium triacetoxyborohydride (10 mg) is added to a solution of 10 mg of 3- (2-cyanophenyl) -5- (2-formylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one in 2 ml of tetrahydrofuran and a mixture stirred for 1 hour. A 10% aqueous solution of sodium carbonate was added thereto, the mixture was extracted with ethyl acetate, the organic layer was washed with water and brine, and dried over magnesium sulfate. The solvent was concentrated in vacuo and the residue was purified by NH silica gel column chromatography to obtain 8 mg of the title compound as a white powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.86 (s, 2H), 7.11 (d, 1H), 7.33 (d, 1H), 7.42- 7.54 (m, 6H), 7.60-7.65 (m, 1H), 7.75 (d, 1H), 7.76-7.79 (m, 1H), 7.81-7, 84 (m, 1H); 7.91 (d, 1H).

MS (ERI): 385 (MH ⁺ ).

Example 31

3- (2-cyanophenyl) -5- (2-pyridyl) -1-benzyl-1,2-dihydropyridin-2-one

3- (2-Cyanophenyl) -5- (2-pyridyl) -2 (1H) -pyridone (46 mg), 36 mg of benzyl alcohol and 88 mg of triphenylphosphine are dissolved in 2 ml of tetrahydrofuran, 147 mg of a 40% solution are added under ice-cooling diethyl azodicarboxylate in toluene and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated in vacuo and purified by silica gel chromatography (hexane / ethyl acetate) to obtain 12 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 5.33 (s, 2H), 7.18 (ddd, 1H), 7.31-7.40 (m, 3H), 7.42-7.48 (m, 3H), 7.53 (dd, 1H), 7.64 (ddd, 1H), 7.68-7.79 (m, 3H), 8.18 (d, 1H), 8.30 (d, 1H), 8.56-8.60 (m, 1H).

Example 32

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

3-Bromo-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one (5.39 g) is dissolved in 200 ml of dimethylformamide, then 6.42 g of cesium carbonate is added thereto. 3.69 g of 2- (2'-cyanophenyl) -1,3,2-dioxaborinate and 949 mg of tetrakistriphenylphosphine palladium and the mixture was stirred at 120 ° C for 1 hour. The reaction solution was cooled to room temperature, water and ethyl acetate were added thereto, the organic layer was separated, washed with water and dried over anhydrous magnesium sulfate, the drying agent was filtered off, the filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane / ethyl acetate), so as to obtain 4 8 g of the title compound as a colorless amorphous substance.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.26 (m, 1H), 7.46-7.52 (m, 2H), 7.62 (dt , 1H), 7.66 (td, 1H), 7.74-7.81 (m, 3H), 7.97 (ddd, 1H), 8.32 (s, 2H), 8.61 (ddd, 1H), 8.72 (dd, 1H), 8.80-8.81 (m, 1H).

ERI-Mass: 351 [M ⁺ + H].

The following compounds are synthesized in the same manner as described in example 1.

Example 33

3- (2-Pyridyl) -5- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.35-7.40 (1H, m), 7.49-7.64 (5H, m), 7.77-7 81 (2H, m), 7.86 (1H, dt), 7.96 (1H, d), 8.22 (1H, d), 8.51 (1H, d), 8.66-8, 71 (2H, m).

Example 34

3- (2-cyanophenyl) -5- (3-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.38 (dd, 1H), 7.45-7.58 (m, 6H), 7.65 (ddd, 1H), 7.72 (d, 1H), 7.77-7.86 (m, 3H), 7.94 (d, 1H), 8.60 (dd, 1H), 8.79 (d, 1H).

Example 35

3- (2-cyanophenyl) -5- (4-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.44 (dd, 2H), 7.46-7.58 (m, 6H), 7.66 (ddd, 1H), 7.81 (dd, 2H), 7.84 (d, 1H), 8.01 (d, 1H), 8.66 (dd, 2H).

Example 36

3- (2-cyanophenyl) -5- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26-7.59 (m, 7H), 7.62-7.72 (m, 3H), 7.76-7 80 (m, 2H); 7.82-7.84 (m, 1H); 7.86-7.88 (m, 2H).

ERI-Mass: 374 [M ⁺ + H].

Example 37

3,5-diphenyl-1- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.36-7.40 (3H, m), 7.41-7.47 (4H, m), 7.52 -7.56 (2H, m), 7.74-7.78 (2H, m), 7.84-7.90 (2H, m), 7.98-8.01 (1H, m), 8 11 (1H, d), 8.61-8.63 (1H, m).

Example 38

3-phenyl-5- (2-cyanophenyl) -1- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.34-7.40 (2H, m), 7.40-7.50 (3H, m), 7.53 (2H, dd), 7.67 (1H, dt), 7.75-7.81 (2H, m), 7.83 (1H, d), 7.88 (1H, dt), 8.02 ( 1H, d), 8.15 (1H, d), 8.59-8.62 (1H, m).

Example 39

3- (2-cyanophenyl) -5-phenyl-1- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.33-7.40 (2H, m), 7.41-7.50 (3H, m), 7.54 -7.59 (2H, m), 7.65 (1H, dt), 7.75 (1H, dd), 7.80 (1H, dd), 7.88 (1H, dt), 7.96 ( 1H, d), 8.03 (1H, d), 8.23 (1H, d), 8.60-8.64 (1H, m).

Example 40

3- (2-cyanophenyl) -5- (2-cyanophenyl) -1- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.36-7.40 (1H, m), 7.45-7.51 (2H, m), 7.61 -7.66 (1H, m), 7.66-7.71 (2H, m), 7.75-7.80 (3H, m), 7.86-7.91 (2H, m), 8 05-8.09 (1H, m), 8.34 (1H, d), 8.59-8.62 (1H, m).

Example 41

3- (2-cyanophenyl) -1,5-diphenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.32-7.37 (m, 1H), 7.41-7.56 (m, 10H), 7.63 (td) , 1H), 7.69 (d, 1H), 7.77-7.82 (m, 2H), 7.98 (d, 1H).

ERI-Mass: 349 [M ⁺ + H].

Example 42

3- (2-cyanophenyl) -5- (2-methoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.88 (s, 3H), 6.95-7.04 (m, 3H), 7.29-7.54 (m 7H), 7.58-7.64 (m, 1H), 7.71 (d, 1H), 7.74-7.79 (m, 2H), 7.95 (d, 1H).

Example 43

3- (2-cyanophenyl) -5- (3,4-dimethoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.91 (s, 3H), 3.94 (s, 3H), 6.92 (d, 1H), 7.00- 7.02 (m, 1H), 7.04 (dd, 1H), 7.40-7.59 (m, 6H), 7.60-7.68 (m, 2H), 7.76-7, 79 (m, 1H), 7.82-7.86 (m, 1H), 7.97 (d, 1H).

Example 44

3- (2-cyanophenyl) -5- (thiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (dd, 1H), 7.35 (dd, 1H), 7.41 (dd, 1H), 7.43- 7.56 (m, 6H), 7.63 (dt, 1H), 7.70 (d, 1H), 7.76-7.81 (m, 2H), 7.96 (d, 1H).

Example 45

3- (2-cyanophenyl) -5- (2-fluorophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.16 (ddd, 1H), 7.23 (dt, 1H), 7.29-7.36 (m, 1H), 7.42-7.54 (m, 6H), 7.60-7.67 (m, 2H), 7.74-7.81 (m, 3H), 7.92 (dd, 1H).

Example 46

3- (2-cyanophenyl) -5- (thiophen-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.07 (dd, 1H), 7.17 (dd, 1H), 7.25-7.28 (m, 1H), 7.43-7.56 (m, 6H), 7.64 (dt, 1H), 7.72 (d, 1H), 7.74-7.80 (m, 2H), 7.93 (d, 1H).

Example 47

3- (2-cyanophenyl) -5-phenyl-1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.32-7.39 (1H, m), 7.41-7.47 (2H, m), 7.52 -7.65 (2H, m), 7.73-7.80 (4H, m), 7.94 (1H, d), 8.06-8.11 (1H, m), 8.20 (1H d) 8.25 (1H, d), 8.68 (1H, dd), 8.83 (1H, d).

Example 48

3- (2-cyanophenyl) -5- (3-furyl) -1- (phenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.55 (dd, 1H), 7.42-7.56 (m, 7H), 7.58 (d, 1H), 7.60-7.67 (m, 2H), 7.74-7.79 (m, 2H), 7.82 (d, 1H).

Example 49

3- (2-cyanophenyl) -5- (2-furyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.12-7.24 (m, 2H), 7.42-7.55 (m, 6H), 7.58-7 65 (m, 3H); 7.66 (d, 1H); 7.74-7.77 (m, 2H).

Example 50

3- (2-cyanophenyl) -5- (2,4-dimethoxypyrimidin-5-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.03 (s, 3H), 4.07 (s, 3H), 7.42-7.57 (m, 5H), 7.60-7.70 (m, 3H), 7.75-7.80 (m, 2H), 7.86 (d, 1H), 8.29 (s, 1H).

Example 51

3- (2-cyanophenyl) -5- (3-methoxypyridin-5-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.92 (s, 3H), 7.30-7.34 (m, 1H), 7.44-7.58 (m 6H), 7.65 (ddd, 1H), 7.72 (d, 1H), 7.77-7.84 (m, 2H), 7.95 (d, 1H), 8.28-8, 33 (m, 1H), 8.36-8.40 (m, 1H).

Example 52

3- (2-cyanophenyl) -5- (2-methoxyphenyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.89 (s, 3H), 7.00 (d, 1H), 7.03-7.08 (ddd, 1H), 7.35-7.40 (m, 2H), 7.46-7.51 (ddd, 1H), 7.63-7.72 (m, 2H), 7.72 (d, 1H), 7, 77-7.80 (dd, 1H), 7.82-7.88 (m, 1H), 7.95 (d, 1H), 8.47-8.52 (d, 1H), 8.75- 8.80 (m, 1H); 8.96 (br, 1H).

Example 53

3- (2-cyanophenyl) -5- [2-methoxy-5- (2-cyanophenyl) phenyl] -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.97 (s, 3H), 7.12 (d, 1H), 7.41-7.50 (m, 2H), 7.54-7.62 (m, 3H), 7.62-7.68 (ddd, 2H), 7.70-7.80 (m, 5H), 8.03 (d, 1H), 8, 32-8.38 (m, 1H), 8.71-8.76 (m, 1H), 8.93 (br s, 1H).

Example 54

3- (2-cyanophenyl) -5- (3-methyl-2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.56 (s, 3H), 7.42-7.70 (m, 10H), 7.71-7.78 (m , 2H), 7.89-7.93 (m, 1H), 8.46-8.54 (m, 1H).

The following compounds are synthesized by a method that is the same as, or in accordance with the method mentioned in example 4.

Example 55

3- (2-Methoxyphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 3.76 (3H, s), 7.00 (1H, dt), 7.09 (1H, d), 7, 25-7.40 (3H, m), 7.46-7.60 (4H, m), 7.76-7.84 (2H, m), 7.94 (1H, d), 8.23 ( 1H, d), 8.38 (1H, d), 8.55-8.58 (1H, m).

Example 56

3- (2-Methoxyphenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.82 (3H, s), 6.97-7.05 (2H, m), 7.16-7.23 (2H , m), 7.24-7.32 (1H, m), 7.36 (1H, dt), 7.44 (1H, dd), 7.50-7.66 (2H, m), 7, 74-7.90 (1H, m), 8.02-8.08 (1H, m), 8.18-8.45 (2H, m), 8.58-8.64 (1H, m).

Example 57

3- (2-Chlorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.76-6.81 (2H, m), 6.86-6.91 (1H, m), 7.17-7 22 (2H, m), 7.26-7.75 (5H, m), 7.61 (1H, d), 7.78-7.86 (1H, m), 8.11 (1H, d) ), 8.41 (1H, brs), 8.60-8.64 (1H, m).

Example 58

3- (2-Methoxycarbonylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 3.65 (3H, s), 7.28-7.32 (1H, m), 7.47-7.71 (8H, m), 7.78-7.86 (2H, m), 8.01-8.20 (1H, m), 8.33 (1H, d), 8.42 (1H, d), 8.58-8.60 (1H, m).

Example 59

3- (2-Methylaminocarbonylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 2.65 (3H, d), 7.26-7.31 (1H, m), 7.40-7.45 (1H, m), 7.46-7.53 (5H, m), 7.53-7.59 (2H, m), 7.80-7.86 (1H, m), 7.96 (1H d), 8.06-8.12 (1H, m), 8.22 (1H, d), 8.37 (1H, d), 8.57-8.60 (1H, m).

Example 60

3- (2-Tolyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 2.24 (3H, s), 7.22-7.34 (4H, m), 7.47-7.60 (6H, m), 7.78-7.84 (1H, m), 7.99 (1H, d), 8.21-8.24 (1H, m), 8.44-8.47 (1H , m), 8.55-8.59 (1H, m).

Example 61

3-phenyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.28-7.32 (1H, m), 7.35-7.40 (1H, m), 7.41 -7.47 (2H, m), 7.49-7.54 (2H, m), 7.56-7.60 (3H, m), 7.76-7.86 (3H, m), 8 02 (1H, dd), 8.42 (1H, d), 8.44 (1H, d), 8.58-8.61 (1H, m).

Example 62

3- (2-Pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.29-7.40 (2H, m), 7.50-7.63 (5H, m), 7.80 -7.88 (2H, m), 7.99 (1H, d), 8.50 (1H, d), 8.54 (1H, d), 8.62-8.66 (1H, m), 8.70-8.74 (1H, m), 9.31 (1H, d).

Example 63

3- (3-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.24 (ddd, 1H), 7.46-7.66 (m, 8H), 7.78 (td, 1H), 8.10 (dt, 1H), 8.16 (t, 1H), 8.25 (d, 1H), 8.31 (d, 1H), 8.61-8.63 (m, 1H).

Example 64

3- (4-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.22-7.26 (m, 1H), 7.47-7.60 (m, 6H), 7.70-7 78 (m, 3H), 7.95-7.98 (m, 2H), 8.26 (d, 1H), 8.33 (d, 1H), 8.61-8.63 (m, 1H )

Example 65

3- (3-Chlorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.21-7.36 (m, 3H), 7.47-7.76 (m, 5H), 7.58-7 60 (m, 1H), 7.71-7.75 (m, 2H), 7.84-7.87 (m, 1H), 8.23-8.26 (m, 2H), 8.60 -8.63 (m, 1H).

ERI-Mass: 359 [M ⁺ + H].

Example 66

3- (4-Chlorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.22 (ddd, 1H), 7.37-7.41 (m, 2H), 7.44-7.60 (m 5H), 7.72-7.80 (m, 3H), 8.12-8.16 (m, 1H), 8.21-8.25 (m, 2H), 8.62 (ddd, 1H )

ERI-Mass: 359 [M ⁺ + H].

Example 67

3- (3-Pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.22-7.52 (m, 1H), 7.33-7.37 (m, 1H), 7.45-7 57 (m, 5H), 7.59-7.61 (m, 1H), 7.56 (td, 1H), 8.24-8.27 (m, 2H), 8.30 (d, 1H) ), 8.59 (dd, 1H), 8.61-8.63 (m, 1H), 8.95-8.96 (m, 1H).

ERI-Mass: 326 [M ⁺ + H].

Example 68

3- (2-Aminocarbonyl-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 5.46 (br s, 1H), 7.19 (ddd, 1H), 7.39-7.53 (m, 6H), 7.55-7.58 (m, 1H), 7.58 (br, 1H), 7.71 (ddd, 1H), 7.82 (dd, 1H), 8.08 (d, 1H), 8 21 (d, 1H), 8.57 (dd, 1H), 8.59 (ddd, 1H).

Example 69

3- (3-Methoxyphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.84 (s, 3H), 6.92 (ddd, 1H), 7.20 (ddd, 1H), 7.31- 7.38 (m, 2H), 7.42-7.55 (m, 6H), 7.57-7.59 (m, 1H), 7.73 (td, 1H), 8.23 (d, 1H), 8.24 (d, 1H), 8.60 (ddd, 1H).

ERI-Mass: 355 [M ⁺ + H].

Example 70

3- (4-Methoxyphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.85 (s, 3H), 6.94-6.98 (m, 2H), 7.20 (ddd, 1H), 7.42-7.55 (m, 5H), 7.57-7.60 (m, 1H), 7.73 (td, 1H), 7.77-7.81 (m, 2H), 8, 18-8.20 (m, 2H); 8.20-8.59 (m, 1H).

ERI-Mass: 355 [M ⁺ + H].

Example 71

3- (2-Fluorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.13-7.22 (m, 3H), 7.31-7.59 (m, 7H), 7.66 (td) , 1H), 7.74 (td, 1H), 8.22 (dd, 1H), 8.29 (d, 1H), 8.58-8.60 (m, 1H).

Example 72

3- (3-Fluorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.03-7.08 (m, 1H), 7.21 (ddd, 1H), 7.35-7.63 (m 9H), 7.74 (td, 1H), 8.23 (d, 1H), 8.27 (d, 1H), 8.59-8.62 (m, 1H).

Example 73

3- (4-Fluorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.08-7.14 (m, 2H), 7.21 (ddd, 1H), 7.44-7.60 (m 6H), 7.74 (td, 1H), 7.78-7.83 (m, 2H), 8.21 (d, 1H), 8.22 (d, 1H), 8.60-8, 62 (m, 1H).

Example 74

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.84 (s, 3H), 6.96-7.01 (m, 1H), 7.04-7.11 (m , 2H), 7.17-7.23 (m, 1H), 7.26-7.34 (m, 2H), 7.40 (dd, 1H), 7.46-7.53 (m, 2H) ), 7.54-7.58 (m, 1H), 7.73 (ddd, 1H), 8.14 (d, 1H), 8.29 (d, 1H), 8.57-8.62 ( m, 1H).

Example 75

3- (2,4-Dimethoxyphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.93 (s, 6H), 6.93 (d, 1H), 7.19-7.23 (m, 1H), 7.33 (dd, 1H), 7.41-7.57 (m, 6H), 7.58-7.60 (m, 1H), 7.74 (td, 1H), 8.19 (d, 1H), 8.22 (d, 1H), 8.60-8.62 (m, 1H).

ERI-Mass: 385 [M ⁺ + H].

Example 76

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.20-7.28 (m, 2H), 7.44-7.56 (m, 5H), 7.56-7 60 (m, 1H), 7.75 (td, 1H), 8.19-8.21 (m, 1H), 8.26 (ddd, 1H), 8.30 (d, 1H), 8, 34 (t, 1H), 8.59-8.61 (m, 1H).

ERI-Mass: 344 [M ⁺ + H].

Example 77

3- (2-Methoxy-5-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.98 (s, 3H), 6.80 (d, 1H), 7.22 (ddd, 1H), 7.44- 7.59 (m, 6H), 7.72-7.77 (m, 1H), 8.15 (dd, 1H), 8.21 (s, 2H), 8.50-8.52 (m, 1H), 8.59-8.62 (m, 1H).

ERI-Mass: 356 [M ⁺ + H].

Example 78

3- (3-Cyano-2-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.30-7.34 (ddd, 1H), 7.49-7.57 (m, 1H), 7.57 -7.62 (m, 4H), 7.62-7.66 (dd, 1H), 7.82-7.87 (ddd, 1H), 8.02 (d, 1H), 8.39-8 43 (dd, 1H), 8.59-8.62 (m, 1H), 8.63 (d, 1H), 8.65 (d, 1H), 8.94-8.96 (dd, 1H) )

Example 79

3- (3-Cyano-2-pyridyl) -5-phenyl-1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.33-7.38 (m, 1H), 7.44 (d, 1H), 7.46 (d, 1H) ), 7.64 (d, 1H), 7.65 (d, 1H), 7.72-7.76 (m, 2H), 8.07-8.11 (m, 1H), 8.30 ( d, 1H), 8.34 (d, 1H), 8.42 (dd, 1H), 8.68-8.71 (m, 1H), 8.82-8.84 (m, 1H), 8 86-8.93 (m, 1H).

Example 80

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.85 (s, 3H), 6.99-7.10 (m, 3H), 7.20-7.31 (m , 2H), 7.40-7.47 (m, 1H), 7.58 (d, 1H), 7.76 (ddd, 1H), 8.18-8.23 (m, 1H), 8, 23-8.32 (m, 2H), 8.32-8.37 (m, 1H), 8.58-8.64 (m, 1H).

Example 81

3- (2-Methoxy-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 3.98 (s, 3H), 6.96 (dd, 1H), 7.18-7.22 (m, 1H), 7.44-7.59 (m, 6H), 7.74 (dt, 1H), 7.90 (dd, 1H), 8.17 (dd, 1H), 8.25-8.28 (m, 2H), 8.58-8.61 (m, 1H).

Example 82

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.18-7.30 (m, 4H), 7.46-7.52 (m, 2H), 7.58 (d , 1H), 7.76 (ddd, 1H), 8.20-8.27 (m, 2H), 8.29 (d, 1H), 8.31-8.35 (m, 1H), 8, 59-8.64 (m, 1H).

Example 83

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (pyrimidin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.25-7.32 (m, 2H), 7.61 (d, 1H), 7.79 (ddd, 1H), 8.16-8.22 (m, 1H), 8.24-8.27 (m, 1H), 8.29 (d, 1H), 8.34-8.37 (m, 1H), 8, 61-8.64 (m, 1H), 9.01 (s, 2H), 9.32 (s, 1H).

Example 84

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (4-methylthiophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 2.53 (s, 3H), 7.20-7.28 (m, 2H), 7.36-7.43 (m 4H), 7.57 (d, 1H), 7.75 (td, 1H), 8.19-8.27 (m, 2H), 8.28 (d, 1H), 8.33 (t, 1H), 8.59-8.61 (m, 1H).

ERI-Mass: 390 [M ⁺ + H].

Example 85

3- (2-Pyridon-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 6.67 (d, 1H), 7.21-7.26 (m, 1H), 7.45-7.59 (m 6H), 7.75 (td, 1H), 7.96 (dd, 1H), 8.14 (d, 1H), 8.26 (d, 1H), 8.32 (m, 1H), 8 62 (m, 1H).

ERI-Mass: 342 [M ⁺ + H].

Example 86

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (2-methoxy-5-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 4.00 (s, 3H), 6.88 (dd, 1H), 7.22-7.29 (m, 2H), 7.44-7.79 (m, 5H), 8.20-8.24 (m, 1H), 8.27-8.29 (m, 1H), 8.33-8.36 (m, 1H) ), 8.61 (ddd, 1H).

Example 87

3- (2-Fluoro-3-pyridyl) -5-phenyl-1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.31-7.37 (m, 1H), 7.41-7.48 (m, 2H), 7.52 -7.66 (m, 2H), 7.71-7.76 (m, 2H), 8.06-8.10 (m, 1H), 8.16-8.28 (m, 4H), 8 66-8.70 (m, 1H); 8.80-8.82 (m, 1H).

Example 88

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 7.17-7.33 (m, 5H), 7.48-7.55 (m, 1H), 7.56-7 61 (m, 1H), 7.76 (ddd, 1H), 8.20-8.27 (m, 2H), 8.29 (d, 1H), 8.32-8.35 (m, 1H) ), 8.59-8.63 (m, 1H).

Example 89

3- (2-Dimethylamino-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 1.70 (s, 6H), 7.19 (ddd, 1H), 7.41-7.60 (m, 7H), 7.71 (td, 1H), 7.82 (d, 1H), 8.08 (d, 1H), 8.21 (d, 1H), 8.57 (dd, 1H), 8.58-8 60 (m, 1H).

ERI-Mass: 369 [M ⁺ + H].

The following compounds are synthesized in the same manner as mentioned in example 7.

Example 90

3,5-diphenyl-1- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.33-7.40 (3H, m), 7.41-7.47 (4H, m), 7.54 (2H dd), 7.76 (2H, dd), 7.86-7.90 (2H, m), 7.99 (1H, ddd), 8.11 (1H, d), 8.61-8, 64 (1H, m).

Example 91

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.18-7.25 (m, 3H), 7.44-7.55 (m, 3H), 7.59-7 67 (m, 2H), 7.72-7.81 (m, 3H), 8.27-8.33 (m, 2H), 8.58-8.63 (m, 1H).

Example 92

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.15-7.25 (m, 2H), 7.28-7.36 (m, 2H), 7.44-7 54 (m, 2H), 7.58-7.68 (m, 2H), 7.72-7.82 (m, 3H), 8.28-8.33 (m, 2H), 8.57 -8.63 (m, 1H).

Example 93

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-cyanophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.26 (m, 1H), 7.49 (dt, 1H), 7.61-7.86 (m 9H), 7.28-8.30 (m, 2H), 8.60-8.62 (m, 1H).

Example 94

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-cyanophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.26 (m, 1H), 7.49 (dt, 1H), 7.61-7.89 (m 9H), 8.30 (s, 2H), 8.60-8.62 (m, 1H).

Example 95

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-methoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.86 (s, 3H), 7.02 (d, 2H), 7.21 (ddd, 1H), 7.42- 7.80 (m, 8H), 8.29 (d, 1H), 8.31 (d, 1H), 8.58-8.60 (m, 1H).

Example 96

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.85 (s, 3H), 6.95-7.03 (m, 1H), 7.06-7.10 (m , 2H), 7.20-7.22 (m, 1H), 7.41-7.81 (m, 7H), 8.31 (s, 2H), 8.59-8.61 (m, 1H )

Example 97

3-phenyl-5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.15-7.24 (m, 2H), 7.26-7.33 (m, 2H), 7.34-7 40 (m, 1H), 7.40-7.53 (m, 3H), 7.57-7.62 (m, 1H), 7.72-7.82 (m, 3H), 8.20 -8.23 (m, 2H); 8.59-8.63 (m, 1H).

Example 98

3-phenyl-5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.18-7.24 (m, 3H), 7.34-7.39 (m, 1H), 7.40-7 45 (m, 2H), 7.46-7.52 (m, 2H), 7.57-7.61 (m, 1H), 7.72-7.77 (m, 1H), 7.77 -7.82 (m, 2H), 8.19-8.23 (m, 2H), 8.59-8.62 (m, 1H).

Example 99

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.16-7.24 (m, 3H), 7.29-7.35 (m, 2H), 7.45-7 54 (m, 4H), 7.56 (d, 1H), 7.70-7.76 (m, 1H), 8.12 (d, 1H), 8.28 (d, 1H), 8, 58-8.62 (m, 1H).

Example 100

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.27 (m, 1H), 7.48 (ddd, 1H), 7.60-7.69 (m , 2H), 7.72-7.82 (m, 5H), 8.03-8.09 (m, 2H), 8.29 (d, 1H), 8.33 (d, 1H), 8, 58-8.62 (m, 1H), 10.10 (s, 1H).

Example 101

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-formylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20-7.25 (m, 1H), 7.44-7.52 (m, 2H), 7.61-7 70 (m, 3H), 7.73-7.83 (m, 4H), 8.06 (dd, 1H), 8.31 (d, 1H), 8.36 (d, 1H), 8, 57-8.60 (m, 1H), 10.05 (s, 1H).

Example 102

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-chlorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21-7.25 (m, 1H), 7.43-7.50 (m, 4H), 7.55-7 58 (m, 1H), 7.59-7.68 (m, 2H), 7.73-7.81 (m, 3H), 8.27-8.31 (m, 2H), 8.58 -8.62 (m, 1H).

Example 103

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-tolyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.43 (s, 3H), 7.20-7.23 (m, 1H), 7.26-7.35 (m , 3H), 7.39-7.48 (m, 2H), 7.60-7.66 (m, 2H), 7.72-7.81 (m, 3H), 8.31 (s, 2H) ), 8.58-8.61 (m, 1H).

Example 104

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-trifluoromethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.25 (m, 1H), 7.47 (t, 1H), 7.61-7.82 (m 9H), 8.31 (s, 2H), 8.59-8.62 (m, 1H).

Example 105

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (thiophen-3-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.25 (m, 1H), 7.37-7.49 (m, 3H), 7.59-7 67 (m, 3H), 7.74-7.80 (m, 3H), 8.27 (d, 1H), 8.40 (d, 1H), 8.60-8.62 (m, 1H) )

Example 106

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-furyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.83-6.86 (m, 1H), 7.19-7.26 (m, 1H), 7.48 (ddd , 1H), 7.52 (dd, 1H), 7.60-7.69 (m, 2H), 7.73-7.82 (m, 3H), 8.21 (d, 1H), 8, 27-8.30 (m, 1H), 8.47 (d, 1H), 8.61-8.65 (m, 1H).

Example 107

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-tolyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.41 (s, 3H), 7.18-7.22 (m, 1H), 7.30-7.46 (m 5H), 7.59-7.65 (m, 2H), 7.71-7.80 (m, 3H), 8.29 (d, 1H), 8.31 (d, 1H), 8, 58-8.60 (m, 1H).

Example 108

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-trifluoromethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.25 (m, 1H), 7.48 (td, 1H), 7.61-7.82 (m 9H), 8.30 (d, 1H), 8.32 (d, 1H), 8.59-8.61 (m, 1H).

Example 109

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.00 (s, 3H), 6.88 (d, 1H), 7.23 (ddd, 1H), 7.47 ( td, 1H), 7.59-7.62 (m, 1H), 7.65 (td, 1H), 7.73-7.82 (m, 4H), 8.28-8.31 (m, 3H), 8.60 (ddd, 1H).

ERI-Mass: 381 [M ⁺ + H].

Example 110

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-cyanophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26-7.35 (m, 2H), 7.52-7.58 (m, 2H), 7.64-7 71 (m, 2H), 7.72-7.85 (m, 5H), 8.51 (d, 1H), 8.68-8.72 (m, 1H), 8.77 (d, 1H) )

Example 111

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (pyrimidin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.32 (m, 1H), 7.48-7.54 (m, 1H), 7.61-7 72 (m, 2H), 7.73-7.85 (m, 3H), 8.31 (d, 1H), 8.33 (d, 1H), 8.60-8.65 (m, 1H ), 9.04 (s, 2H), 9.32 (s, 1H).

Example 112

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- [2- (pyrrolidin-1-yl) -pyridin-5-yl] -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.01-2.07 (m, 4H), 3.49-3.52 (m, 4H), 6.44 (dd , 1H), 7.21 (ddd, 1H), 7.45 (td, 1H), 7.58-7.67 (m, 3H), 7.72 (dd, 1H), 7.76-7, 88 (m, 2H), 8.23 (dd, 1H), 8.28 (dd, 2H), 8.59 (ddd, 1H).

ERI-Mass: 420 [M ⁺ + H].

Example 113

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- [2- (4-benzylpiperazin-1-yl) -pyridin-5-yl] -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.57 (t, 4H), 3.63 (t, 4H), 3.57 (s, 2H), 6.70 ( d, 1H), 7.21 (ddd, 1H), 7.25-7.38 (m, 5H), 7.45 (td, 1H), 7.58 (d, 1H), 7.63 (td) , 1H), 7.68 (dd, 1H), 7.73 (dd, 1H), 7.75-7.79 (m, 2H), 8.26-8.29 (m, 3H), 8, 58-8.60 (m, 1H).

Example 114

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-benzyloxyethoxypyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.84-3.87 (m, 2H), 4.55-4.58 (m, 2H), 4.64 (s , 2H), 6.93 (d, 1H), 7.23 (ddd, 1H), 7.25-7.40 (m, 5H), 7.47 (td, 1H), 7.60 (d, 1H), 7.65 (td, 1H), 7.74-7.82 (m, 4H), 8.27 (d, 1H), 8.28 (d, 1H), 8.30 (d, 1H) ), 8.59-8.61 (m, 1H).

ERI-Mass: 501 [M ⁺ + H].

Example 115

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-benzyloxymethylpyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.64 (s, 2H), 4.66 (s, 2H), 7.23-7.26 (m, 1H), 7.26-7.38 (m, 5H), 7.48 (td, 1H), 7.61 (d, 1H), 7.68 (td, 1H), 7.74-7.81 (m, 3H), 7.95-7.98 (m, 1H), 8.29 (d, 1H), 8.32 (d, 1H), 8.61 (d, 1H), 8.69 (d, 1H) ), 8.72 (d, 1H).

ERI-Mass: 471 [M ⁺ + H].

Example 116

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-ethylthiopyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.41 (t, 3H), 3.23 (q, 2H), 7.23 (ddd, 1H), 7.29 ( dd, 1H), 7.47 (td, 1H), 7.60 (dt, 1H), 7.65 (td, 1H), 7.72 (dd, 1H), 7.74-7.80 (m , 3H), 8.28 (d, 1H), 8.30 (d, 1H), 8.57 (dd, 1H), 8.60 (ddd, 1H).

Example 117

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.26 (m, 1H), 7.49 (td, 1H), 7.55-7.57 (m , 2H), 7.61 (d, 1H), 7.67 (td, 1H), 7.73-7.81 (m, 3H), 8.29 (d, 1H), 8.30 (d, 1H), 8.61 (ddd, 1H), 8.82 (d, 2H).

ERI-Mass: 351 [M ⁺ + H].

Example 118

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.91 (s, 3H), 7.22-7.27 (m, 1H), 7.46-7.51 (m , 2H), 7.60-7.64 (m, 1H), 7.66 (ddd, 1H), 7.74-7.82 (m, 3H), 8.30 (d, 1H), 8, 32 (d, 1H), 8.38 (d, 1H), 8.43 (d, 1H), 8.60-8.63 (m, 1H).

Example 119

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-hydroxyethoxypyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.04 (br, 1H), 3.97-4.03 (m, 2H), 4.51-4.54 (m , 2H), 6.93 (d, 1H), 7.23 (dd, 1H), 7.47 (td, 1H), 7.61 (dd, 1H), 7.65 (td, 1H), 7 74-7.80 (m, 3H); 7.84 (dd, 1H); 8.27-8.30 (m, 3H); 8.61 (ddd, 1H).

ERI-Mass: 411 [M ⁺ + H].

Example 120

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-chloropyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.28 (m, 1H), 7.47-7.52 (m, 2H), 7.61 (d , 1H), 7.67 (t, 1H), 7.72-7.81 (m, 3H), 7.95 (dd, 1H), 8.28 (d, 1H), 8.30 (d, 1H), 8.59 (d, 1H), 8.61 (dt, 1H).

ERI-Mass: 385 [M ⁺ + H].

Example 121

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- [2- (4-methylpiperazin-1-yl) pyridin-5-yl] -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.37 (s, 3H), 2.54 (t, 4H), 3.66 (t, 4H), 6.73 ( d, 1H), 7.21 (ddd, 1H), 7.46 (td, 1H), 7.59 (d, 1H), 7.64 (td, 1H), 7.70 (dd, 1H), 7.72-7.79 (m, 3H), 8.27-8.29 (m, 3H), 8.58-8.60 (m, 1H).

ERI-Mass: 449 [M ⁺ + H].

Example 122

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-tert-butyldimethylsilyloxymethylpyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 0.13 (s, 6H), 0.95 (s, 9H), 4.85 (s, 2H), 7.24 ( dd, 1H), 7.45-7.81 (m, 7H), 7.88 (s, 1H), 8.29 (d, 1H), 8.32 (d, 1H), 8.61 (dd , 1H); 8.68 (d, 1H).

Example 123

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-fluoropyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.11 (dd, 1H), 7.25 (ddd, 1H), 7.42-7.84 (m, 6H), 8.08 (ddd, 1H), 8.30 (t, 2H), 8.41 (dd, 1H), 8.61 (ddd, 1H).

ERI-Mass: 369 [M ⁺ + H].

Example 124

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-ethylpyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.36 (t, 3H), 2.91 (q, 2H), 7.23 (m, 1H), 7.33 ( d, 1H), 7.47 (td, 1H), 7.60 (d, 1H), 7.65 (td, 1H), 7.73-7.80 (m, 3H), 7.86 (dd , 1H), 8.30 (d, 1H), 8.31 (d, 1H), 8.60 (d, 1H), 8.68 (d, 1H).

ERI-Mass: 379 [M ⁺ + H].

Example 125

3-phenyl-5- (2-pyridyl) -1- (2-cyanophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.24-7.54 (6H, m), 7.62-7.81 (4H, m), 7.93 (1H, dt), 8.11 (1H, d), 8.57 (1H, d), 8.69-8.72 (1H, m), 8.89-8.94 (1H, m).

Example 126

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-methoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 3.80 (3H, s), 7.12 (1H, t), 7.24-7.33 (2H, m ), 7.44 (1H, dt), 7.49 (1H, dt), 7.59 (1H, dt), 7.71 (1H, d), 7.75-7.86 (2H, m) 7.90-8.00 (2H, m), 8.42 (1H, d), 8.47 (1H, d), 8.56-8.60 (1H, m).

The following compounds are synthesized in the same manner as mentioned in example 32.

Example 127

3-Phenyl-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23 (ddd, 1H), 7.36-7.50 (m, 4H), 7.60 (td, 1H), 7.75 (dd, 1H), 7.76-7.80 (m, 2H), 7.94 (ddd, 1H), 8.22 (d, 1H), 8.24 (d, 1H), 8 62 (ddd, 1H); 8.71 (dd, 1H); 8.75-8.79 (m, 1H).

ERI-Mass: 326 [M ⁺ + H].

Example 128

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23 (ddd, 1H), 7.31-7.36 (m, 2H), 7.41-7.51 (m , 3H), 7.56-7.59 (m, 1H), 7.75 (td, 1H), 7.95 (ddd, 1H), 8.15 (d, 1H), 8.30 (d, 1H), 8.60-8.62 (m, 1H), 8.69 (dd, 1H), 8.80 (d, 1H).

ERI-Mass: 360 [M ⁺ + H].

Example 129

3- (2-Methoxyphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.84 (s, 3H), 6.98-7.05 (m, 2H), 7.21 (ddd, 1H), 7.37 (td, 1H), 7.41-7.49 (m, 2H), 7.56 (d, 1H), 7.74 (td, 1H), 7.94-7.97 (m, 1H), 8.13 (d, 1H), 8.25 (d, 1H), 8.58-8.60 (m, 1H), 8.67 (dd, 1H), 8.79 (d, 1H) )

ERI-Mass: 356 [M ⁺ + H].

Example 130

3- (2-Formylthiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.28 (m, 1H), 7.46-7.52 (m, 2H), 7.57 (d , 1H), 7.50-7.79 (m, 2H), 7.92-7.96 (m, 1H), 8.24 (d, 1H), 8.30 (d, 1H), 8, 61-8.63 (m, 1H), 8.74 (dd, 1H), 8.79 (d, 1H), 9.99 (d, 1H).

Example 131

3- (2,4-Dichlorophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.25 (m, 1H), 7.32 (dd, 1H), 7.41-7.61 (m , 4H), 7.74-7.79 (m, 1H), 7.93-7.96 (m, 1H), 8.15 (d, 1H), 8.29 (d, 1H), 8, 59-8.63 (m, 1H), 8.69-8.72 (m, 1H), 8.79 (d, 1H).

ERI-Mass: 394 [M ⁺ + H].

Example 132

3- (2-Trifluoromethylphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22 (ddd, 1H), 7.44-7.56 (m, 4H), 7.59-7.63 (m , 2H), 7.72-7.78 (m, 1H), 7.94 (ddd, 1H), 8.04 (d, 1H), 8.30 (d, 1H), 8.59-8, 61 (m, 1H), 8.69 (dd, 1H), 8.78-8.79 (m, 1H).

ERI-Mass: 394 [M ⁺ + H].

Example 133

3- (Thiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (ddd, 1H), 7.39 (dd, 1H), 7.50 (dd, 1H), 7.60- 7.63 (m, 1H), 7.65 (dd, 1H), 7.77 (td, 1H), 7.93 (ddd, 1H), 8.15 (d, 1H), 8.32 (dd , 1H), 8.44 (d, 1H), 8.62-8.64 (m, 1H), 8.72-8.73 (m, 1H), 8.77 (d, 1H).

ERI-Mass: 332 [M ⁺ + H].

Example 134

3- (1-tert-Butoxycarbonylpyrrol-2-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.47 (s, 9H), 6.25 (t, 1H), 6.34-6.36 (m, 1H), 7.21 (dd, 1H), 7.37 (dd, 1H), 7.43-7.48 (m, 1H), 7.57 (d, 1H), 7.72-7.77 (m, 1H), 7.88-7.92 (m, 1H), 8.06 (d, 1H), 8.22 (d, 1H), 8.59-8.61 (m, 1H), 8.68 (dd, 1H); 8.76 (d, 1H).

ERI-Mass: 415 [M ⁺ + H].

Example 135

3- (2,6-Dimethylphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.23 (s, 6H), 7.11-7.27 (m, 3H), 7.45-7.55 (m , ZN), 7.65-8.02 (m, 2H), 8.20-8.33 (m, 1H), 8.59-8.61 (m, 1H), 8.68-8.81 (m, 3H).

ERI-Mass: 354 [M ⁺ + H].

Example 136

3- (3-Acetylaminophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.08 (s, 3H), 7.21-7.26 (m, 1H), 7.34 (d, 1H), 7.44-7.49 (m, 2H), 7.58-7.61 (m, 2H), 7.75 (td, 1H), 7.82 (br, 1H), 7.84-7, 88 (m, 1H), 7.89-7.92 (m, 1H), 8.20-8.23 (m, 2H), 8.59-8.61 (m, 1H), 8.69- 8.71 (m, 1H); 8.77-8.78 (m, 1H).

ERI-Mass: 383 [M ⁺ + H].

Example 137

3- (2-Cyanothiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.26 (m, 1H), 7.50 (dd, 1H), 7.61-7.74 (m , 3H), 7.79 (td, 1H), 7.91-7.94 (m, 1H), 8.36 (d, 1H), 8.57 (d, 1H), 8.60-8, 61 (m, 1H), 8.74 (dd, 1H), 8.79 (d, 1H).

ERI-Mass: 357 [M ⁺ + H].

Example 138

3- (2-cyano-6-methoxyphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.82 (s, 3H), 7.18-7.27 (m, 2H), 7.35-7.38 (dd , 1H), 7.43-7.50 (m, 2H), 7.60 (d, 1H), 7.74-7.80 (m, 1H), 7.98-8.02 (m, 1H ), 8.16 (d, 1H), 8.35 (d, 1H), 8.59-8.62 (m, 1H), 8.67-8.72 (m, 1H), 8.83 ( d, 1H).

Example 139

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21-7.29 (m, 2H), 7.45-7.52 (m, 1H), 7.59 (d , 1H), 7.78 (dt, 1H), 7.91-7.95 (m, 1H), 8.19-8.25 (m, 2H), 8.30 (d, 1H), 8, 35 (t, 1H), 8.60-8.63 (m, 1H), 8.70-8.73 (m, 1H), 8.79 (d, 1H).

The following compound is synthesized in the same manner as mentioned in example 15.

Example 140

3- (2-Aminocarbonylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.17 (1H, br), 7.26-7.31 (1H, m), 7.40-7.64 (10H, m), 7.82 (1H, dt), 7.96 (1H, d), 8.21 (1H, d), 8.36 (1H, d), 8.56-8.59 ( 1H, m).

The following compounds are synthesized in the same manner as mentioned in example 18.

Example 141

3- (2-Hydroxyphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 6.87-6.93 (2H, m), 7.22 (1H, dt), 7.30 (1H, ddd ), 7.38 (1H, dd), 7.48-7.60 (5H, m), 7.82 (1H, dt), 7.99 (1H, d), 8.41 (1H, d) 8.45 (1H, d); 8.57-8.60 (1H, m); 9.43 (1H, s).

Example 142

3- (2-Hydroxyphenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 6.86-6.93 (2H, m), 7.22 (1H, dt), 7.30 (1H, ddd ), 7.36-7.44 (3H, m), 7.62-7.68 (2H, m), 7.83 (1H, dt), 7.98 (1H, d), 8.40 ( 1H, d), 8.45 (1H, d), 8.57-8.60 (1H, m), 9.40 (1H, s).

Example 143

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (3-hydroxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.71-6.76 (m, 1H), 6.85-6.91 (m, 2H), 7.19-7 34 (m, 4H), 7.41-7.50 (m, 2H), 7.56 (d, 1H), 7.74 (ddd, 1H), 8.17 (d, 1H), 8, 23 (d, 1H), 8.58-8.62 (m, 1H).

The following compounds are synthesized in the same manner as mentioned in example 19.

Example 144

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.89 (s, 6H), 3.41 (t, 2H), 4.54 (t, 2H), 6.99- 7.04 (m, 1H), 7.13 (dd, 1H), 7.14-7.18 (m, 1H), 7.21 (ddd, 1H), 7.30-7.35 (m, 2H), 7.43-7.51 (m, 3H), 7.58 (d, 1H), 7.74 (ddd, 1H), 8.15 (d, 1H), 8.28 (d, 1H) ), 8.59-8.62 (m, 1H).

Example 145

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (4-dimethylaminopropoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.98 (tt, 2H), 2.26 (s, 6H), 2.46 (t, 2H), 4.06 ( t, 2H), 6.97-7.03 (m, 2H), 7.19 (ddd, 1H), 7.28-7.33 (m, 2H), 7.39-7.44 (m, 2H), 7.46-7.51 (m, 2H), 7.53-7.58 (m, 1H), 7.72 (ddd, 1H), 8.12 (d, 1H), 8.28 (d, 1H), 8.58-8.61 (m, 1H).

Example 146

3- (2-Chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminopropoxyphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.96 (tt, 2H), 2.25 (s, 6H), 2.44 (t, 2H), 4.05 ( t, 2H), 6.95-7.01 (m, 1H), 7.04-7.11 (m, 2H), 7.17-7.24 (m, 1H), 7.28-7, 35 (m, 2H), 7.36-7.43 (m, 1H), 7.45-7.53 (m, 2H), 7.56 (d, 1H), 7.73 (ddd, 1H) 8.14 (d, 1H); 8.29 (d, 1H); 8.58-8.63 (m, 1H).

The following compounds are synthesized in the same manner as mentioned in example 21.

Example 147

3- (2-Hydroxymethylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 4.46 (2H, d), 5.04 (1H, t), 7.24-7.60 (10H, m ), 7.78-7.84 (1H, m), 7.96-8.00 (1H, m), 8.25 (1H, d), 8.45 (1H, d), 8.55- 8.59 (1H, m).

Example 148

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-hydroxymethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.81 (t, 1H), 4.78 (d, 2H), 7.19-7.24 (m, 1H), 7.46 (ddd, 1H), 7.51-7.55 (m, 4H), 7.59-7.66 (m, 2H), 7.72-7.80 (m, 3H), 8, 28-8.32 (m, 2H); 8.58-8.61 (m, 1H).

Example 149

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-hydroxymethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.35 (dd, 1H), 4.52 (dd, 1H), 4.62 (dd, 1H), 7.21 - 7.24 (m, 1H), 7.35 (dd, 1H), 7.46-7.57 (m, 3H), 7.60-7.69 (m, 3H), 7.72-7, 81 (m, 3H), 8.26 (d, 1H), 8.36 (d, 1H), 8.58-8.62 (m, 1H).

The following compounds are synthesized in the same manner as mentioned in example 22.

Example 150

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-cyanomethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.84 (s, 2H), 7.23 (ddd, 1H), 7.47 (ddd, 1H), 7.49- 7.54 (m, 2H), 7.55-7.63 (m, 3H), 7.65 (ddd, 1H), 7.73-7.81 (m, 3H), 8.28-8, 32 (m, 2H), 8.58-8.62 (m, 1H).

Example 151

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-cyanomethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.81 (d, 1H), 3.91 (d, 1H), 7.24 (ddd, 1H), 7.39- 7.44 (m, 1H), 7.46-7.58 (m, 3H), 7.62 (d, 1H), 7.64-7.71 (m, 3H), 7.73-7, 81 (m, 2H), 8.22 (d, 1H), 8.34 (d, 1H), 8.59-8.63 (m, 1H).

The following compounds are synthesized in the same manner as mentioned in example 27.

Example 152

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-ethylsulfonylpyridin-5-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.36 (t, 3H), 3.47 (q, 2H), 7.26-7.29 (m, 1H), 7.51 (td, 1H), 7.63 (d, 1H), 7.68 (td, 1H), 7.71-7.82 (m, 3H), 8.23-8.29 (m, 2H), 8.31-8.33 (m, 2H), 8.61-8.63 (m, 1H), 8.97-8.98 (m, 1H).

ERI-Mass: 443 [M ⁺ + H].

Example 153

3- (2-Fluoro-3-pyridyl) -5- (2-pyridyl) -1- (4-methylsulfonylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.11 (s, 3H), 7.24-7.30 (m, 2H), 7.60 (d, 1H), 7.75-7.80 (m, 3H), 8.12 (t, 1H), 8.14 (t, 1H), 8.17-8.24 (m, 2H), 8.30 (d, 1H), 8.35 (t, 1H), 8.61-8, 63 (m, 1H).

ERI-Mass: 422 [M ⁺ + H].

The following compounds are synthesized in the same manner as mentioned in example 29.

Example 154

3- (2-Dimethylaminomethylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one dihydrochloride

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 2.06 (6H, s), 3.37 (2H, s), 7.25-7.39 (4H, m ), 7.44-7.61 (6H, m), 7.81 (1H, dt), 7.96 (1H, d), 8.24 (1H, d), 8.43 (1H, d) 8.55-8.58 (1H, m).

Example 155

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-dimethylaminomethylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.16 (s, 6H), 3.30 (d, 1H), 3.46 (d, 1H), 7.18- 7.23 (m, 1H), 7.34-7.38 (m, 1H), 7.40-7.49 (m, 3H), 7.55-7.66 (m, 3H), 7, 70-7.79 (m, 3H), 8.21 (d, 1H), 8.37 (d, 1H), 8.58-8.61 (m, 1H).

Example 156

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (4-dimethylaminomethylphenyl) -1, 2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.28 (s, 6H), 3.49 (s, 2H), 7.22 (ddd, 1H), 7.43- 7.49 (m, 5H), 7.59-7.66 (m, 2H), 7.72-7.81 (m, 3H), 8.30 (d, 1H), 8.33 (d, 1H), 8.58-8.61 (m, 1H).

Example 157

3- (2-cyanophenyl) -5- (6-diethylaminomethyl-2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.49 (6H, t), 3.10-3.33 (4H, m), 4.36 (2H, br), 7.46-7.60 (7H, m), 7.63-7.68 (2H, m), 7.79-7.89 (3H, m), 8.28 (1H, d), 8, 39 (1H, d).

The following compound is synthesized in the same manner as mentioned in example 31.

Example 158

3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenethyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.18 (t, 2H), 4.33 (t, 2H), 7.19 (ddd, 1H), 7.22- 7.34 (m, 3H), 7.39 (d, 1H), 7.43-7.50 (m, 3H), 7.62-7.74 (m, 4H), 7.96 (d, 1H), 8.18 (d, 1H), 8.56-8.60 (m, 1H).

Example 159

3- (2-cyanophenyl) -1- (2-pyridyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

A mixture of 0.05 g of 1- (2-pyridyl) -5- (2-pyridyl) -3-bromo-1,2-dihydropyridin-2-one, 0.04 g of 2- (2-cyanophenyl) -1.3 , 2-dioxaborinate, 0.02 g of tetrakistriphenylphosphine palladium and 0.1 g of cesium carbonate are stirred at 120 ° C. under nitrogen for 2 hours in dimethylformamide. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water, then with saturated aqueous saline and dried with anhydrous magnesium sulfate. The solvent was concentrated in vacuo and the residue was purified by silica gel chromatography (ethyl acetate / hexane = 3: 1) to obtain 0.04 g of the subject compound as a white powder.

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.33 (dd, 1H), 7.56-7.64 (m, 2H), 7.75 (d, 1H) ), 7.78-7.83 (m, 1H), 7.84-7.90 (m, 2H), 7.95 (d, 1H), 8.00 (d, 1H), 8.07 ( dt, 1H), 8.50 (d, 1H), 8.61 (d, 1H), 8.70 (d, 1H), 8.83 (d, 1H).

Example 160

1- (2-Cyanophenyl) -3- (2-pyridyl) -5-phenyl-1,2-dihydropyridin-2-one

5 ml of a solution of dimethylformamide containing 0.26 g of 3- (2-pyridyl) -5-phenyl-2 (1H) -pyridone is mixed with 0.04 g of sodium hydride. After 15 minutes, the solution was mixed with 0.15 g of 2-fluorobenzonitrile and 0.10 g of copper (I) iodide and stirred vigorously at 100 ° C. for 2 hours. The solution was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was washed with water and then with saturated aqueous saline and dried with anhydrous magnesium sulfate. The solvent is distilled off under vacuum. The residue was purified by silica gel chromatography (ethyl acetate / hexane = 1: 2), to give 0.03 g of the subject compound as a pale yellow powder.

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.34-7.42 (m, 2H), 7.45-7.50 (m, 2H), 7.70 -7.78 (m, 3H), 7.84-7.90 (m, 2H), 7.96 (dt, 1H), 8.11 (d, 1H), 8.31 (d, 1H), 8.47 (dd, 1H), 8.71-8.74 (m, 1H), 8.88 (d, 1H).

Example 161

1-Phenyl-3- (1-phenylacetylen-2-yl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

100 mg of 3-bromo-1-phenyl-5- (pyridin-2-yl) -1,2-dihydropyridin-2-one, 55 mg of phenylacetylene, 1 mg of copper (I) iodide and 4 mg of palladium dichlorobis (triphenylphosphine) palladium are added to a mixed solvent of 1.5 ml of triethylamine and 1 ml of dimethylformamide and the mixture was stirred at 50 ° C. under nitrogen overnight. The reaction mixture was partitioned between ethyl acetate and aqueous layers. The organic layer was washed with water, dried and concentrated, the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 7 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22 (dd, 1H), 7.33-7.35 (m, 3H), 7.46-7.60 (m 8H), 7.75 (dt, 1H), 8.26 (d, 1H), 8.34 (d, 1H), 8.60 (ddd, 1H).

Example 162

5- (5-Acetoxypyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

(162a) 3- (2-Cyanophenyl) -1-phenyl-5- (tri-n-butylstannyl) -1,2-dihydropyridin-2-one

5.50 g of 5-bromo-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one, 45.5 g of bistributyltin and 907 mg of tetrakistriphenylphosphine palladium are added to 60 ml of xylene and the mixture is stirred at 120 ° C under nitrogen for 40 minutes. The reaction mixture was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 3.42 g of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 0.90 (t, 9H), 1.07-1.11 (m, 6H), 1.30-1.39 (m 6H), 1.52-1.60 (m, 6H), 7.29 (d, 1H), 7.39-7.47 (m, 5H), 7.49-7.52 (m, 2H ), 7.60 (d, 1H), 7.71-7.75 (m, 2H).

(162b) 5- (5-Acetoxypyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

3.42 g of 3- (2-cyanophenyl) -1-phenyl-5- (tri-n-butylstannyl) -1,2-dihydropyridin-2-one, 1.57 g of 5-acetoxy-2-chloropyridine and 352 mg tetrakistriphenylphosphine palladium is added to 40 ml of xylene and the mixture is stirred at 120 ° C. under nitrogen for 8.5 hours. The reaction mixture was purified by silica gel chromatography (ethyl acetate / hexane) to give 953 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.36 (s, 3H), 7.44-7.56 (m, 6H), 7.62-7.68 (m , 3H), 7.77-7.80 (m, 2H), 8.27 (d, 1H), 8.28 (d, 1H), 8.40 (dd, 1H).

Example 163

3- (2-cyanophenyl) -5- (5-hydroxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

953 mg of 5- (5-acetoxypyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one and 192 mg of potassium carbonate are added to 50 ml of methanol and the mixture is stirred at room temperature. temperature for 30 minutes. The mixture was then combined with 50 ml of methanol and stirred at 40 ° C. for 15 minutes. The reaction mixture was diluted with ethyl acetate and filtered through silica gel. The filtrate was concentrated in vacuo and washed with a mixed solvent of ether / methanol to give 786 mg of the subject compound.

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 7.19 (dd, 1H), 7.49-7.52 (m, 1H), 7.55-7.61 (m, 5H), 7.71 (dd, 1H), 7.78 (dt, 1H), 7.82 (d, 1H), 7.93 (dd, 1H), 8.14 (d, 1H) 8.34 (d, 1H); 8.37 (d, 1H).

Example 164

3- (2-cyanophenyl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

63 mg of 2-tributyltin pyrimidine obtained in accordance with Tetrahedron 50 (1), 275 (1994), 50 mg of 5-bromo-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one and 5 mg tetrakistriphenylphosphine palladium is added to 2 ml of xylene and the mixture is stirred at 120 ° C. under nitrogen overnight. The reaction mixture was purified by silica gel chromatography (ethyl acetate / hexane) to give 10 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.15 (t, 1H), 7.44-7.54 (m, 6H), 7.64 (dt, 1H), 7.72-7.78 (m, 2H), 8.70 (s, 1H), 8.71 (s, 1H), 8.72 (d, 1H), 8.76 (d, 1H).

Example 165

3- (2-Hydroxypyridin-6-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

20 mg of 3- (2-methoxypyridin-6-yl) -1-phenyl-5- (pyridin-2-yl) -1,2-dihydropyridin-2-one is added to 3 ml of 5N hydrochloric acid. The mixture was heated under reflux for 3 hours, 0.5 ml of concentrated hydrochloric acid was added thereto, and then stirred for 1 hour. The reaction mixture was concentrated in vacuo and washed with ether to obtain the subject compound quantitatively.

¹ H-NMR (DMSO-d ₆ , 400 MHz): δ (ppm) 6.44 (d, 1H), 7.08 (brs, 1H), 7.47 (dd, 1H), 7, 52-7.62 (m, 6H), 8.02-8.06 (m, 1H), 8.18 (d, 1H), 8.62 (d, 1H), 8.68 (dd, 1H) 8.82 (dd, 1H).

Example 166

1- (2-Aminobenzothiazol-6-yl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

150 mg of 1- (3-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one and 63 mg of ammonium thiocyanate are added to 2 ml of acetic acid. The mixture was stirred at room temperature for 1 hour, 0.022 ml of bromine was added thereto, and then stirred for 1 hour. The reaction mixture was partitioned between layers of ethyl acetate and water and neutralized with a 20% aqueous potassium carbonate solution. The organic layer was washed with water, dried and concentrated, the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 58 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 5.37 (br s, 1H), 6.76 (d, 1H), 7.20-7.24 (m, 1H), 7.41-7.80 (m, 8H), 8.28-9.40 (m, 2H), 8.59-8.61 (m, 1H).

Example 167

1,3-diphenyl-4-methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

The subject compound was prepared in 27% yield according to the method for Reference Examples 4, 5 and 6 and Example 32 from 2,5-dibromo-4-methylpyridine.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.10 (s, 3H), 7.27 (ddd, 1H), 7.30-7.51 (m, 12H), 7.76 (ddd, 1H); 8.66-8.70 (m, 1H).

Example 168

1-Phenyl-3- [N- (N'-phenylureylenyl)] - 5- (2-pyridyl) -1,2-dihydropyridin-2-one

50 mg of 3-amino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one and 25 mg of phenylisocyanate are dissolved in 1 ml of tetrahydrofuran and the solution is stirred at room temperature for 2 hours and at 60 ° C for 2 hours. The reaction solution was allowed to cool to room temperature and diethyl ether was added to it. The resulting crystals were filtered off to obtain 30 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.03-7.14 (m, 3H), 7.17-7.33 (m, 4H), 7.38-7 44 (m, 2H), 7.45-7.50 (m, 2H), 7.59 (br, 1H), 7.68-7.76 (m, 2H), 8.02 (d, 1H) ), 8.54-8.57 (m, 1H), 8.58 (br, 1H), 9.00 (d, 1H).

Example 169

3-Benzoylamino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

30 mg of 3-amino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one is dissolved in a mixture of 1 ml of methylene chloride and 1 ml of pyridine, 19 mg of benzoyl chloride is added to the solution under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction mixture was concentrated, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried with magnesium sulfate and purified by NH silica gel chromatography (ethyl acetate). The solvent was concentrated and the resulting crude crystals were washed with ethyl acetate / hexane to give 35 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23 (ddd, 1H), 7.47-7.60 (m, 8H), 7.70-7.80 (m , 2H), 7.95-8.00 (m, 2H), 8.12 (d, 1H), 8.57-8.61 (m, 1H), 9.28 (d, 1H), 9, 35 (br, 1H).

Example 170

3-Benzylamino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

40 mg of 3-amino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one and 10 mg of sodium hydride are added to 1 ml of toluene and 30 mg of benzyl chloride are added dropwise thereto at 70 ° C. . The mixture was stirred for 30 minutes and heated for 1 hour at the boil under reflux. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate and washed with water and brine. The organic layer was dried with magnesium sulfate and purified by NH silica gel chromatography (ethyl acetate / hexane) to give 13 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.48 (d, 2H), 5, 60 (pcs, 1H), 6.86 (d, 1H), 7.15 ( ddd, 1H), 7.26-7.32 (m, 1H), 7.34-7.40 (m, 2H), 7.40-7.56 (m, 9H), 7.66 (ddd, 1H), 8.55-8.58 (m, 1H).

Example 171

3- (2-cyanophenyl) -1-cyclopentyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

2.00 g of 3-bromo-5- (2-pyridyl) -1,2-dihydropyridin-2-one as the starting material, N-alkylate in the usual manner 5.94 g of bromocyclopentane and 5.50 g of potassium carbonate to obtain 506 mg 3-bromo-1-cyclopentyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one, 150 mg of which is treated according to the method of example 32, to obtain 120 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.73-2.02 (m, 6H), 2.23-2.35 (m, 2H), 5.37 (quintet , 1H), 7.20 (ddd, 1H), 7.45 (ddd, 1H), 7.57 (d, 1H), 7.64 (ddd, 1H), 7.70-7.79 (m, 3H), 8.11 (d, 1H), 8.36 (d, 1H), 8.59-8.63 (m, 1H).

Example 172

1- {3- [1- (Benzyloxycarbonyl) piperidin-4-yl-hydroxy] phenyl} -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

0.99 g of 3-bromo-1- (3-hydroxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one is obtained by the method of example 18 from 1.02 g of 3-bromo-1- ( 3-methoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, synthesized by the method of Reference Example 6. It was dissolved in 30 ml of tetrahydrofuran and 10 ml of N, N-dimethylformamide, to this was added 1, 52 g of triphenylphosphine and 1.36 g of N-benzyloxycarbonyl-4-piperidinol, then 2.52 g of a 40% toluene diethyl azodicarboxylate solution are added dropwise under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction solution was concentrated in vacuo and purified by silica gel chromatography (ethyl acetate / hexane) to give 0.98 g of 1- {3- [N- (benzyloxycarbonyl) piperidin-4-yl-hydroxy] phenyl} -3-bromo-5- (2-Pyridyl) -1,2-dihydropyridin-2-one, from which 0.85 g of the subject compound are obtained according to the method of Example 32.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.73-1.87 (m, 2H), 1.88-2.02 (m, 2H), 3.43-3 52 (m, 2H), 3.70-3.80 (m, 2H), 4.50-4.58 (m, 1H), 5.14 (s, 2H), 6.98-7.02 (m, 1H), 7.06-7.11 (m, 2H), 7.22 (dd, 1H), 7.30-7.38 (m, 5H), 7.40-7.49 (m , 2H), 7.60 (ddd, 1H), 7.64 (ddd, 1H), 7.72-7.80 (m, 3H), 8.29 (d, 1H), 8.31 (4, 1H), 8.58-8.61 (m, 1H).

Example 173

3- (2-Cyanophenyl) -5- (2-pyridyl-1-oxide) -1-phenyl-1,2-dihydropyridin-2-one

1.00 g of 3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 30 ml of chloroform, 0.99 g of 60% m is added to this solution. -chloroperbenzoic acid and the mixture was stirred at room temperature for 2 hours. An additional 1.00 g of 60% m-chloroperbenzoic acid was added to the mixture, and the mixture was stirred for 3 hours. The reaction solution was mixed with 50 ml of a 1N aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with saturated aqueous brine, dried with anhydrous magnesium sulfate and the solvent was distilled off in vacuo. The residue was recrystallized from ethyl acetate / diethyl ether to give 0.46 g of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21-7.27 (m, 1H), 7.36 (dt, 1H), 7.43-7.48 (m , 2H), 7.50-7.54 (m, 4H), 7.61 (dd, 1H), 7.63 (dt, 1H), 7.78 (dd, 1H), 7.81-7, 85 (m, 1H), 8.10 (d, 1H), 8.21 (dd, 1H), 8.83 (d, 1H).

Example 174

3-Phenylamino-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

53 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one and 23 mg of aniline are dissolved in 10 ml of toluene, 2 mg of palladium acetate, 7 mg 1.1 'bis (diphenylphosphino) ferrocene and 23 mg sodium tert-butoxide and the mixture was stirred at 110 ° C. overnight. The reaction solution was cooled to room temperature, filtered through silica gel, washed with ether and the filtrate was subjected to vacuum distillation to remove the solvent. The residue was purified by silica gel chromatography (NH-silica gel) (hexane / ethyl acetate) to obtain 47 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.06 (tt, 1H), 7.15-7.19 (m, 2H), 7.29-7.31 (m , 2H), 7.38 (tt, 2H), 7.43-7.56 (m, 5H), 7.67 (d, 1H), 7.69 (td, 1H), 7.75 (d, 1H), 8.58 (ddd, 1H).

ERI-Mass: 340 [M ⁺ + H].

Example 175

3-Phenoxy-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

100 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one and 58 mg of phenol are dissolved in 10 ml of dimethylformamide, 84 mg of potassium carbonate and 6 mg of copper iodide are added to this solution and the mixture was stirred at 150 ° C for 5 hours. The reaction solution was cooled to room temperature, aqueous ammonia was added thereto, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous brine, dried with anhydrous magnesium sulfate and the solvent was distilled off in vacuo. The residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 66 mg of the subject compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.13-7.19 (m, 3H), 7.26-7.27 (m, 2H), 7.36-7 54 (m, 7H), 7.60-7.61 (m, 1H), 7.66-7.71 (m, 1H), 8.03-8.04 (m, 1H), 8.54 -8.57 (m, 1H).

ERI-Mass: 341 [M ⁺ + H].

Example 176

3- (1-Adamantylamino) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

27 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one and 130 mg of 1-adamantylamine are dissolved in 10 ml of dimethylformamide. 20 mg of sodium hydride was added to the mixture, followed by stirring at 130 ° C. under a nitrogen atmosphere. After the reaction solution was cooled to room temperature, a saturated aqueous solution of ammonium chloride and water were added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 3 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.19-2.29 (m, 16H), 7.06-7.33 (m, 3H), 7.34-7 61 (m, 5H); 7.66-7.69 (m, 1H); 8.08-8.11 (m, 2H).

ERI-Mass: 398 [M ⁺ + H].

Example 177

3- [4- (2-Cyanophenyl) piperadin-1-yl] -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

29 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 200 mg of 1- (2-cyanophenyl) piperazine, followed by heating at 130 ° C for 72 hours . After the reaction solution was cooled to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 8 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.20-3.22 (m, 4H), 3.50-3.56 (m, 4H), 7.00-7 13 (m, 3H); 7.32-7.61 (m, 10H); 7.79-7.84 (m, 2H).

ERI-Mass: 434 [M ⁺ + H].

Example 178

3- (1-Adamantyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

40 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 10 ml of tetrahydrofuran. To the mixture was added 5 mg of [1,1-bis (diphenylphosphino) ferrocene] dichloropalladium (II) and 1.2 mg of copper (I) iodide. While the mixture was stirred at room temperature in a nitrogen atmosphere overnight, 0.4 ml of 1-adamantylzinc bromide (0.5 M solution in tetrahydrofuran) was added dropwise to it. After stirring under nitrogen overnight, aqueous ammonia was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 12 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.44-2.19 (m, 15H), 7.13 (ddd, 1H), 7.31-7.55 (m 6H), 7.66 (td, 1H), 7.93 (d, 1H), 8.05 (d, 1H), 8.55-8.58 (m, 1H).

ERI-Mass: 383 [M ⁺ + H].

Example 179

3- (1,1-Dichlorohexyl-1-hydroxymethyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

13 mg of 3-methoxycarbonyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 20 ml of tetrahydrofuran, followed by the addition of 0.05 ml of cyclohexyl magnesium chloride (2.0 M solution, dropwise) in diethyl ether) under nitrogen with ice cooling and stirring. After stirring the mixture for 3 hours while warming to room temperature, a saturated aqueous solution of ammonium chloride was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 8 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 0.89-1.84 (m, 20H), 2.72-2.90 (m, 2H), 7.06-7 12 (m, 1H), 7.25-7.49 (m, 8H), 7.59-7.68 (m, 1H), 8.50-8.54 (m, 1H).

ERI-Mass: 443 [M ⁺ + H].

Example 180

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (1-benzyl-1,2,5,6-tetrahydropyridin-3-yl) -1,2-dihydropyridin-2-one

718 mg of 3-bromo-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 40 ml of acetonitrile. 383 mg of benzyl bromide was added to the solution, followed by stirring at 10 ° C. overnight. Then, 383 mg of benzyl bromide was added thereto, followed by stirring at 70 ° C. for 2 nights. After cooling to room temperature, the mixture was evaporated. The residue was dissolved in 30 ml of methanol, followed by cooling to 0 ° C. with stirring. 265 mg of sodium borohydride was added thereto, followed by stirring overnight while heating from 0 ° C to room temperature. Water was added, the solvent was evaporated, and then the residue was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 550 mg of 3-bromo-5- (2-pyridyl) -1- (1-benzyl-1,2,5,6-tetrahydropyridin-3-yl ) -1,2-dihydropyridin-2-one. 270 mg of the product are dissolved in 20 ml of dimethylformamide. To the solution were added 179 mg of 2- (2-cyanophenyl) -1,3,2-dioxaborinate, 313 mg of cesium carbonate and 15 mg of tetrakistriphenylphosphine palladium, followed by stirring at 120 ° C for 1 hour. After cooling to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 174 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.38-2.42 (m, 2H), 2.70 (t, 2H), 3.43 (d, 2H), 3.68 (s, 2H), 6.05 (t, 1H), 7.21 (dd, 1H), 7.22-7.26 (m, 1H), 7.30 (t, 2H), 7 36 (d, 2H), 7.44 (t, 1H), 7.54 (d, 1H), 7.63 (t, 1H), 7.70-7.77 (m, 3H), 8, 19 (d, 1H), 8.23 (d, 1H), 8.60 (dd, 1H).

Example 181

3- (2-cyanophenyl) -5-phenylaminocarbonyl-1-phenyl-1,2-dihydropyridin-2-one

41 mg of the carboxylate obtained by hydrolysis of the 3- (2-cyanophenyl) -5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one ester group is dissolved in 5 ml of dichloromethane. Under ice cooling, a solution of 25 mg of oxalyl chloride in dichloromethane was added dropwise to the resulting solution, and a catalytic amount of dimethylformamide was added thereto, followed by stirring at room temperature under nitrogen for 1 hour. The reaction solution was evaporated and the residue was dissolved in dichloromethane. The solution was added dropwise to a solution of 13 mg of aniline and 0.03 ml of triethylamine in dichloromethane under ice-cooling. After warming to room temperature, the reaction mixture was stirred under nitrogen for 3 hours. Under ice cooling, the mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 11 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.15 (tt, 1H), 7.33-7.39 (m, 2H), 7.42-7.55 (m 6H), 7.56-7.60 (m, 2H), 7.65 (td, 1H), 7.73-7.79 (m, 2H), 7.85 (br, 1H), 8, 06 (d, 1H), 8.25 (d, 1H).

Example 182

3- (2-cyanophenyl) -5- (1-phenylbenzimidazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

24 mg of the carboxylate obtained by hydrolysis of the 3- (2-cyanophenyl) -5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one ester group is dissolved in 20 ml of dichloromethane. Under ice cooling, a solution of 16 mg of oxalyl chloride in dichloromethane was added dropwise to the resulting solution. A catalytic amount of dimethylformamide is added thereto, followed by stirring at room temperature under a nitrogen atmosphere for 1 hour. The reaction solution was evaporated and the residue was dissolved in dichloromethane. The solution was added dropwise to a solution of 21 mg of N-phenyl-1,2-phenylenediamine in dichloromethane under ice-cooling. The mixture was warmed to room temperature, followed by stirring under nitrogen overnight. The dichloromethane was evaporated, 10 ml of acetic acid was added and the mixture was stirred at 100 ° C for 5 hours. After cooling to room temperature, acetic acid was evaporated. Under ice cooling, the residue was poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 18 mg of the title compound as white crystals.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.19-7.30 (m, 4H), 7.33-7.37 (m, 1H), 7.39-7 43 (m, 4H), 7.44-7.45 (m, 1H), 7.46-7.47 (m, 1H), 7.55-7.61 (m, 3H), 7.61 -7.66 (m, 2H), 7.68 (d, 1H), 7.71 (dd, 1H), 7.81-7.84 (m, 1H), 7.87 (d, 1H).

ERI-Mass: 465 [M ⁺ + H].

Example 183

3- (2-Chlorophenyl) -5- (benzothiazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

19 mg of the carboxylate obtained by hydrolysis of the 3- (2-chlorophenyl) -5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one ester group (synthesized from 3-bromo-5- (methoxycarbonyl) -1- phenyl-1,2-dihydropyridin-2-one and 2-chlorophenylboronic acid according to the method of Reference Example 3) are dissolved in 20 ml of dichloromethane. Under ice cooling, a solution of 11 mg of oxalyl chloride in dichloromethane was added dropwise to the resulting solution, and a catalytic amount of dimethylformamide was added thereto, followed by stirring at room temperature under a nitrogen atmosphere for 1 hour. The reaction solution was evaporated and the residue was dissolved in dichloromethane. The solution was added dropwise to a solution of 22 mg of 2-aminobenzothiol in dichloromethane under ice-cooling. After warming to room temperature, the dichloromethane was evaporated. 1 ml of polyphosphoric acid was added to the residue, followed by stirring at 180 ° C. overnight. After cooling to room temperature, the reaction mixture was neutralized with a 1N aqueous sodium hydroxide solution and a saturated aqueous sodium hydrogen carbonate solution under ice-cooling, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate), to give 4 mg of the title compound as white crystals.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.32-7.35 (m, 2H), 7.37-7.41 (m, 1H), 7.46-7 51 (m, 4H), 7.51-7.55 (m, 4H), 7.87-7.89 (m, 1H), 8.00 (d, 1H), 8.14 (d, 1H) ), 8.42 (d, 1H).

ERI-Mass: 415 [M ⁺ + H].

Example 184

3- (2-Chlorophenyl) -5- (benzoxazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

19 mg of the carboxylate obtained by hydrolysis of the 3- (2-chlorophenyl) -5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one ester group (synthesized from 3-bromo-5- (methoxycarbonyl) -1- phenyl-1,2-dihydropyridin-2-one and 2-chlorophenylboronic acid according to the method of Reference Example 3) are dissolved in 20 ml of dichloromethane. Under ice cooling, a solution of 11 mg of oxalyl chloride in dichloromethane was added dropwise to the resulting solution, and a catalytic amount of dimethylformamide was added thereto, followed by stirring at room temperature under a nitrogen atmosphere for 1 hour. The reaction solution was evaporated and the residue was dissolved in dichloromethane. The solution was added dropwise to a solution of 19 mg of 2-aminophenol in dichloromethane under ice-cooling. After warming to room temperature, the dichloromethane was evaporated. 1 ml of polyphosphoric acid was added to the residue, followed by stirring at 180 ° C. overnight. After cooling to room temperature, the reaction mixture was neutralized with a 1N aqueous sodium hydroxide solution and a saturated aqueous sodium hydrogen carbonate solution under ice cooling. The mixture was extracted with ethyl acetate, and the resulting organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 3 mg of the title compound as white crystals.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.31-7.38 (m, 4H), 7.45, 7.57 (m, 8H), 7.69-7 71 (m, 1H), 8.29 (d, 1H), 8.49 (d, 1H).

ERI-Mass: 399 [M ⁺ + H].

Example 185

3- (2-Chlorophenyl) -5-phenoxymethyl-1-phenyl-1,2-dihydropyridin-2-one

24 mg of 3- (2-chlorophenyl) -5-hydroxymethyl-1-phenyl-1,2-dihydropyridin-2-one is dissolved in 10 ml of tetrahydrofuran. 9.4 mg of phenol, 33 mg of triphenylphosphine polymer (3 mmol / g of polymer) and 17 mg of 1,1'-azobis (N, N-dimethylformamide) were added thereto, followed by stirring at 60 ° C. overnight. Then, 50 mg of triphenylphosphine polymer (3 mmol / g polymer) and 30 mg of 1,1'-azobis (N, N-dimethylformamide) were added, followed by stirring at 60 ° C. overnight. After cooling to room temperature, ethyl acetate was added thereto and the triphenylphosphine polymer was removed by filtration through celite. The filtrate was washed with water and a 1N aqueous sodium hydroxide solution. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 12 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.87 (s, 2H), 6.97 (dd, 2H), 7.01 (dd, 1H), 7.26- 7.34 (m, 4H), 7.40-7.51 (m, 7H), 7.54-7.56 (m, 1H), 7.60 (d, 1H).

ERI-Mass: 388 [M ⁺ + H].

Example 186

3- (2-Cyanophenyl) -5- (1-methyl-1,2,3,6-tetrahydropyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

99 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 10 ml of acetonitrile. 2 ml of methylbenzenesulfonate was added to the solution, followed by stirring at 100 ° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooling to 0 ° C. with stirring. Sodium borohydride is added 5 times at intervals of 5 hours, 1 g each time, followed by further stirring at 0 ° C. overnight. Then, the solvent was evaporated, and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 107 mg of 3-bromo-5- (1-methyl-1,2,3,6-tetrahydropyridin-2-yl) -1-phenyl-1, 2-dihydropyridin-2-one. The product is dissolved in 10 ml of dimethylformamide. To this solution 81 mg of 2- (2-cyanophenyl) -1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added, followed by stirring at 140 ° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 41 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.26 (s, 3H), 2.30-2.50 (m, 1H), 2.90-2.98 (m , 1H), 3.15 (dd, 1H), 3.31-3.40 (m, 1H), 3.85 (t, 1H), 5.72-5.78 (m, 1H), 5, 79-5.85 (m, 1H), 7.40 (d, 1H), 7.40-7.57 (m, 5H), 7.60 (td, 1H), 7.64-7.70 ( m, 1H), 7.72-7.73 (m, 1H), 7.74-7.75 (m, 1H), 7.76 (d, 1H).

Example 187

3- (2-Pyridylethenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

23 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 20 ml of acetonitrile. To the mixture was added 0.2 mg of palladium acetate, 4.3 mg of tri-o-tolylphosphine and 0.04 ml of triethylamine, followed by stirring at 110 ° C. under nitrogen overnight. 9.2 mg of 2-vinylpyridine was added to the mixture, followed by stirring at 110 ° C. under nitrogen for 5 hours. After cooling to room temperature, the reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 2 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.12-7.16 (m, 1H), 7.18-7.23 (m, 1H), 7.36 (d , 1H), 7.44-7.51 (m, 3H), 7.51-7.55 (m, 2H), 7.57-7.60 (m, 1H), 7.64 (dt, 1H ), 7.70-7.79 (m, 1H), 7.78-7.82 (m, 1H), 8.03-8.07 (m, 1H), 8.24 (d, 1H), 8.28 (d, 1H); 8.57-8.63 (m, 2H).

ERI-Mass: 352 [M ⁺ + H].

Example 188

3- (4-Chlorophenylthio) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

25 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 20 ml of dimethylformamide. To the mixture were added 17 mg of 4-chlorothiophenol, 3 mg of sodium hydroxide and 2 mg of copper iodide, followed by stirring at 150 ° C. under nitrogen overnight. After cooling to room temperature, the reaction mixture was poured into water. To this was added aqueous ammonia, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 8 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.17 (ddd, 1H), 7.30 (d, 1H), 7.39-7.56 (m, 9H), 7.61 (d, 1H), 7.67 (td, 1H), 8.08 (d, 1H), 8.52-8.54 (m, 1H).

ERI-Mass: 391 [M ⁺ + H].

Example 189

3- (2-Chlorophenyl) -5-cyclohexyl-1-phenyl-1,2-dihydropyridin-2-one

30 mg 5-bromo-3- (2-chlorophenyl) -1-phenyl-1,2-dihydropyridin-2-one, synthesized from 5-bromo-1-phenyl-3-iodo-1,2-dihydropyridin-2- she and 2-chlorophenylboronic acid, in accordance with the method of Reference Example 3, are dissolved in 20 ml of tetrahydrofuran, followed by the addition of 1 mg of [1,3-bis (diphenylphosphino) propane] nickel (II) chloride to the solution. While stirring under nitrogen, 0.1 ml of cyclohexyl magnesium chloride (2.0 M ether solution) was added dropwise to the mixture. After stirring at room temperature in a nitrogen atmosphere overnight, the mixture was heated at the boil under reflux for 1 hour. After cooling to room temperature, a saturated aqueous solution of ammonium chloride was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (chloroform / methanol mixture) to obtain 6 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.15-1.47 (m, 5H), 1.53-1.93 (m, 5H), 2.33-2 37 (m, 1H); 6.99-7.34 (m, 3H); 7.36-7.60 (m, 8H).

ERI-Mass: 364 [M ⁺ + H].

Example 190

3- (1H-Benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

25 mg of the carboxylate obtained by removing the protective ester group from 3-methoxycarbonyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one in the usual manner is dissolved in 20 ml of dichloromethane. Under ice-cooling, a solution of 16 mg of oxalyl chloride in dichloromethane was added dropwise to the resulting solution, and a catalytic amount of dimethylformamide was added thereto, followed by stirring at room temperature under a nitrogen atmosphere for 1 hour. The reaction solution was evaporated and dichloromethane was added to the residue. The solution was added dropwise to a solution of 17 mg of o-phenylenediamine in dichloromethane under ice-cooling. After warming to room temperature, the mixture was stirred under nitrogen overnight. The dichloromethane was evaporated, then methanol was added and the mixture was heated under reflux for 5 hours. After cooling to room temperature, the reaction mixture was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 1.3 mg of the title compound as white crystals.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.10-7.94 (m, 13H), 8.57 (d, 1H), 8.58-8.62 (m , 1H); 9.43 (d, 1H).

ERI-Mass: 365 [M ⁺ + H].

Example 191

3- (2-Pyridon-1-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

40 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one and 23 mg of 2-hydroxypyridine are dissolved in 10 ml of dimethylformamide. There are added 34 mg of potassium carbonate and 3 mg of copper iodide, followed by stirring at 140 ° C. overnight. After the reaction mixture was cooled to room temperature, aqueous ammonia was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (NH-silica gel) (chloroform / methanol mixture) to obtain 10 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.24 (td, 1H), 6.69 (dd, 1H), 7.22 (dd, 1H), 7.37- 7.42 (m, 2H), 7.45-7.57 (m, 6H), 7.73 (td, 1H), 8.33 (d, 1H), 8.36 (d, 1H), 8 58-8.60 (m, 1H).

Example 192

3-Cyclohexyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

34 mg of 3-bromo-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 10 ml of tetrahydrofuran followed by 1 mg of [1,3-bis (diphenylphosphino) propane] nickel ( Ii) chloride. While stirring under nitrogen, 0.1 ml of cyclohexyl magnesium chloride (2.0 M ether solution) was added dropwise to the mixture. The mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour, followed by heating under reflux for 72 hours. After cooling to room temperature, water was added, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (chloroform / methanol mixture) to obtain 5 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.22-1.52 (m, 5H), 1.73-1.80 (m, 1H), 1.81-1 89 (m, 2H), 1.97-2.04 (m, 2H), 2.90-2.99 (m, 1H), 7.18 (ddd, 1H), 7.53-7.55 (m, 6H), 7.71 (td, 1H), 7.78 (dd, 1H), 8.04 (d, 1H), 8.59 (ddd, 1H).

Example 193

3- [2- (5-Methyl-1,2,4-oxadiazol-3-yl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

53 mg of 3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 10 ml of ethanol containing 20% water. To the solution were added 19 mg of hydroxylamine hydrochloride and 17 mg of sodium acetate, followed by heating under reflux for 24 hours. Then, 19 mg of hydroxylamine hydrochloride and 17 mg of sodium acetate are added thereto, followed by heating under reflux for 36 hours. After cooling to room temperature, the mixture was evaporated and the resulting crystals were washed with water, dried and 50 mg of amidoxime compound was collected by filtration. 20 mg of the product is dissolved in 4 ml of toluene. 16 mg of acetic anhydride was added to the solution, followed by heating under reflux for 96 hours. After cooling to room temperature, the mixture was neutralized with potassium carbonate while cooling with ice. After extraction with ethyl acetate, the extract was washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 4 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.56 (s, 3H), 7.18 (ddd, 1H), 7.38-7.59 (m, 8H), 7.72 (ddd, 1H), 7.71 (ddd, 1H), 8.08 (ddd, 1H), 8.11 (d, 1H), 8.27 (d, 1H), 8.58 (ddd , 1H).

ERI-Mass: 410 [M ⁺ + H].

The following compounds are synthesized by methods analogous to the method, or in accordance with the method of example 1.

Example 194

3- (2-cyanophenyl) -5- (1-methylpyrazol-4-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.01 (s, 3H), 7.46-7.56 (m, 8H), 7.62-7.68 (m , 3H); 7.78-7.81 (m, 2H).

Example 195

3- (2-cyanophenyl) -5- (6-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2, 56 (s, 3H), 7.07 (d, 1H), 7.40-7.66 (m, 9H), 7.76-7.80 (m, 2H), 8.28 (d, 1H), 8.30 (d, 1H).

Example 196

3- (2-cyanophenyl) -5- (5-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.36 (s, 3H), 7.42-7.56 (m, 8H), 7.63 (dt, 1H), 7.76-7.80 (m, 2H), 8.26 (d, 1H), 8.28 (d, 1H), 8.41-8.42 (m, 1H).

Example 197

3- (2-cyanophenyl) -5- (4-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.36 (s, 1H), 7.43-7.57 (m, 8H), 7.63 (dt, 1H), 7.77-7.80 (m, 2H), 8.27 (d, 1H), 8.28 (d, 1H), 8.41-8.42 (m, 1H).

Example 198

3- (2-cyanophenyl) -5- (3-hydroxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20 (dd, 1H), 7.31 (dd, 1H), 7.51-7.60 (m, 6H), 7.68 (dd, 1H), 7.75 (dt, 1H), 7.83 (dd, 1H), 8.11 (dd, 1H), 8.51 (d, 1H), 8.55 (d , 1H).

Example 199

3- (2-cyanophenyl) -1-phenyl-5- (2-pyrazinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.57 (m, 6H), 7.66 (dt, 1H), 7.75-7.81 (m , 2H), 8.33 (d, 1H), 8.35 (d, 1H), 8.50 (d, 1H), 8.55 (dd, 1H), 8.93 (d, 1H).

Example 200

3- (2-cyanophenyl) -5- (2-methoxypyridin-5-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.69 (s, 3H), 6.67 (d, 1H), 7.18 (d, 1H), 7.44- 7.66 (m, 8H), 7.78-7.81 (m, 2H), 8.27 (d, 1H), 8.34 (d, 1H).

Example 201

3- (2-cyanophenyl) -1-phenyl-5- (2-triazolyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.31 (d, 1H), 7.45-7.56 (m, 6H), 7.65 (dt, 1H), 7.72 (dd, 1H), 7.77-7.80 (m, 2H), 8.18 (d, 1H), 8.25 (d, 1H).

Example 202

3- (2-cyanophenyl) -1-phenyl-5- (4-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.59 (m, 7H), 7.66 (dt, 1H), 7.76-7.81 (m , 2H), 8.31 (d, 1H), 8.56 (d, 1H), 8.74 (d, 1H), 9.16 (d, 1H).

Example 203

3- (2-cyanophenyl) -1-phenyl-5- (5-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.47-7.58 (m, 6H), 7.66 (dt, 1H), 7.75 (d, 1H), 7.78-7.81 (m, 2H), 7.92 (d, 1H), 8.92 (s, 2H), 9.22 (s, 1H).

Example 204

3- (2-cyanophenyl) -1-phenyl-5- (3-pyridazinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.56 (m, 7H), 7.66 (dt, 1H), 7.77-7.83 (m , 3H), 8.32 (d, 1H), 8.54 (d, 1H), 9.15 (dd, 1H).

Example 205

3- (2-cyanophenyl) -1-phenyl-5- (4-pyridazinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.48-7.61 (m, 7H), 7.67 (dt, 1H), 7.79-7.83 (m , 2H), 7.92 (d, 1H), 8.00 (d, 1H), 9.23 (dd, 1H), 9.40 (dd, 1H).

Example 206

3- (2-cyanophenyl) -5- (6-methoxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.96 (s, 3H), 6.67 (dd, 1H), 7.18 (dd, 1H), 7.44- 7.66 (m, 8H), 7.77-7.81 (m, 2H), 8.27 (d, 1H), 8.33 (d, 1H).

Example 207

3- (2-cyanophenyl) -1-phenyl-5- (thiazol-4-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.57 (m, 6H), 7.66 (ddd, 1H), 7.72-7.81 (m , 3H), 7.87 (d, 1H), 7.97 (s, 1H), 8.76 (s, 1H).

Example 208

3- (2-cyanophenyl) -5- (3-oxo-1-cyclohexen-1-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.12-2.19 (m, 2H), 2.46-2.50 (m, 2H), 2.65-2 69 (m, 2H), 6.36 (s, 1H), 7.45-7.57 (m, 6H), 7.62-7.70 (m, 2H), 7.76-7.79 (m, 2H); 7.88 (d, 1H).

Example 209

3- (2-cyanophenyl) -5- (5,6-dihydro-1,4-dioxin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.12-4.14 (m, 2H), 4.21-4.23 (m, 2H), 7.42-7 78 (m, 12H).

Example 210

3- (2-cyanophenyl) -5- (1-naphthyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.41-7.67 (m, 9H), 7.55-7.83 (m, 2H), 7.88-7 94 (m, 2H), 8.02 (ddd, 1H), 8.11 (d, 1H), 8.70 (d, 1H), 8.83 (d, 1H).

ERI-Mass: 400 [M ⁺ + H].

Example 211

3- (2-cyanophenyl) -5- (2-naphthyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.44-7.58 (m, 4H), 7.61-7.70 (m, 3H), 7.78-7 82 (m, 2H), 7.83-7.90 (m, 2H), 7.92 (d, 1H), 7.95-7.96 (m, 1H), 8.00 (ddd, 1H) ), 8.12 (d, 1H), 8.72 (dd, 1H), 8.83 (d, 1H).

ERI-Mass: 400 [M ⁺ + H].

Example 212

3- (2-cyanophenyl) -5- (8-quinolinyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.43-7.50 (m, 3H), 7.60-7.69 (m, 2H), 7.75-7 79 (m, 1H), 7.81-7.87 (m, 2H), 8.03-8.10 (m, 2H), 8.18 (d, 1H), 8.23 (dd, 1H) ), 8.68-8.72 (m, 2H), 8.87 (d, 1H), 8.98 (dd, 1H).

ERI-Mass: 401 [M ⁺ + H].

Example 213

3- (2-Cyanophenyl) -5- (3-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.45-7.51 (m, 1H), 7.59 (ddd, 1H), 7.64 (dd, 1H ), 7.75-7.82 (m, 2H), 7.94 (d, 1H), 8.10 (ddd, 1H), 8.15-8.20 (m, 1H), 8.28 ( d, 1H), 8.39-8.41 (m, 1H), 8.53-8.56 (m, 1H), 8.69 (dd, 1H), 8.84 (d, 1H), 8 90-8.98 (m, 1H).

ERI-Mass: 351 [M ⁺ + H].

Example 214

5 - [(1-Benzenesulfonyl) indol-2-yl] -3- (2-cyanophenyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.70 (d, 1H), 7.23-7.43 (m, 4H), 7.45-7.56 (m 5H), 7.65 (d, 1H), 7.68 (td, 2H), 7.78 (td, 2H), 7.83 (d, 1H), 8.02 (ddd, 1H), 8 30 (dd, 1H), 8.72 (dd, 1H), 8.79 (d, 1H).

ERI Mass: 529 [M ⁺ + H].

The following compounds are synthesized by methods analogous to the method, or in accordance with the method of example 2.

Example 215

1- (4-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.86 (br s, 2H), 6.76 (td, 2H), 7.20 (ddd, 1H), 7.28 ( td, 2H), 7.44 (dt, 1H), 7.60 (td, 1H), 7.64 (dd, 1H), 7.77-7.80 (m, 3H), 8.28 (d , 1H), 8.29 (d, 1H), 8.60 (ddd, 1H).

Example 216

5- (3-aminopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.05 (br, 2H), 7.07-7.08 (m, 2H), 7.42-7.47 (m , 2H), 7.51-7.53 (m, 4H), 7.62 (ddd, 1H), 7.75-7.78 (m, 1H), 7.79-7.82 (m, 1H ), 7.99 (dd, 1H), 8.06 (dd, 1H), 8.15 (dd, 1H).

Example 217

5- (5-aminopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.77 (br s, 2H), 7.04 (dd, 1H), 7.39-7.52 (m, 7H), 7.60-7.64 (m, 1H), 7.76-7.80 (m, 2H), 8.08 (dd, 1H), 8.13 (d, 1H), 8.22 (d, 1H).

Example 218

1- (3-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.85 (br, 2H), 6.76 (ddd, 1H), 6.84 (t, 1H), 6.86 ( ddd, 1H), 7.14 (t, 1H), 7.27-7.31 (m, 1H), 7.45 (dt, 1H), 7.63 (dt, 1H), 7.71-7 78 (m, 2H), 8.69-8.71 (m, 3H), 8.75 (d, 1H).

Example 219

3- (2-aminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.23-7.37 (m, 3H), 7.40-7.47 (m, 1H), 7.47 -7.56 (m, 2H), 7.56-7.66 (m, 5H), 7.88 (ddd, 1H), 8.08 (d, 1H), 8.46 (d, 1H), 8.58 (d, 1H); 8.59-8.64 (m, 1H).

Example 220

3- (3-aminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.70 (br, 2H), 6.68-6.72 (m, 1H), 7.13-7.26 (m , 3H), 7.42-7.56 (m, 5H), 7.56-7.60 (m, 1H), 7.64-7.76 (m, 2H), 8.22 (s, 2H) ), 8.58-8.61 (m, 1H).

Example 221

3- (4-aminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.77 (br s, 2H), 6.70-6.76 (m, 2H), 7.17-7.21 (m , 1H), 7.42-7.60 (m, 6H), 7.64-7.75 (m, 3H), 8.15 (s, 2H), 8.58-8.61 (m, 1H )

Example 222

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-amino-4-methylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.21 (s, 3H), 3.76 (s, 2H), 6.78-6.83 (m, 2H), 7.17 (d, 1H), 7.20 (ddd, 1H), 7.44 (td, 1H), 7.58 (d, 1H), 7.63 (td, 1H), 7.73 (td) , 1H), 7.78 (td, 2H), 8.29 (s, 2H), 8.59 (ddd, 1H).

ERI-Mass: 379 [M ⁺ + H].

The following compounds are synthesized by methods similar to or in accordance with the method of example 3.

Example 223

3-Benzenesulfonylamino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22 (ddd, 1H), 7.31-7.33 (m, 2H), 7.44-7.60 (m 7H), 7.76 (dt, 1H), 7.92-7.95 (m, 2H), 7.97 (d, 1H), 8.21 (d, 1H), 8.56-8, 58 (m, 1H).

Example 224

3- (2-cyanophenyl) -5-benzenesulfonylamino-1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26-7.27 (m, 1H), 7.30-7.33 (m, 2H), 7.41-7 65 (m, 10H); 7.70-7.73 (m, 1H); 7.83-7.86 (m, 2H).

Example 225

3- (2-Cyanophenyl) -5- (3-methylsulfonylaminopyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.40 (s, 3H), 7.43-7.48 (m, 4H), 7.50-7.54 (m , 4H), 7.64-7.66 (m, 2H), 7.74 (dd, 1H), 7.95 (d, 1H), 8.20 (d, 1H), 8.77 (dd, 1H).

Example 226

3- (2-Methylsulfonylamino) phenyl-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.96 (s, 3H), 7.25 (ddd, 1H), 7.30-7.35 (m, 1H), 7.43-7.63 (m, 9H), 7.76 (ddd, 1H), 8.30 (br, 1H), 8.33 (d, 1H), 8.39 (d, 1H), 8 60-8.64 (m, 1H).

Example 227

3- (4-Methylsulfonylamino) phenyl-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.01 (s, 3H), 6.57 (ss, 1H), 7.20-7.28 (m, 3H), 7.45-7.61 (m, 6H), 7.77 (ddd, 1H), 7.79-7.85 (m, 2H), 8.22 (d, 1H), 8.24 (d, 1H), 8.60-8.64 (m, 1H).

Example 228

3- (3-Methylsulfonylamino) phenyl-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.92 (s, 3H), 6.98 (ss, 1H), 7.20-7.32 (m, 2H), 7.36-7.61 (m, 8H), 7.69-7.78 (m, 2H), 8.22 (d, 1H), 8.26 (d, 1H), 8.59-8, 63 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 10.

Example 229

5- (6-Acetylaminopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.22 (s, 3H), 7.33 (dd, 1H), 7.44-7.80 (m, 10H), 7.85 (d, 1H), 8.08-8.12 (m, 1H), 8.24 (d, 1H), 8.28 (d, 1H).

Example 230

3- (2-Acetylaminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 1.96 (s, 3H), 7.19-7.26 (m, 1H), 7.30 (ddd, 1H) ), 7.34-7.40 (m, 1H), 7.40-7.46 (m, 1H), 7.48-7.56 (m, 1H), 7.56-7.64 (m 4H), 7.72 (d, 1H), 7.83 (ddd, 1H), 8.01 (d, 1H), 8.32 (d, 1H), 8.50 (d, 1H), 8 57-8.61 (m, 1H); 9.16 (br s, 1H).

Example 231

3- (2-Diacetylaminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.28 (s, 6H), 7.18 (ddd, 1H), 7.23-7.27 (m, 1H), 7.42-7.60 (m, 9H), 7.71 (ddd, 1H), 7.95 (d, 1H), 8.35 (d, 1H), 8.54-8.58 (m, 1H).

Example 232

3- (3-Acetylaminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.11 (s, 3H), 7.19-7.23 (m, 1H), 7.34-7.40 (m , 1H), 7.42-7.56 (m, 6H), 7.60 (d, 1H), 7.64-7.77 (m, 3H), 7.83-7.87 (m, 1H ), 8.24 (d, 1H), 8.26 (d, 1H), 8.58-8.62 (m, 1H).

Example 233

3- (4-Acetylaminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.15 (s, 3H), 7.21 (ddd, 1H), 7.34 (br, 1H), 7.44- 7.57 (m, 8H), 7.59 (ddd, 1H), 7.74 (ddd, 1H), 7.80 (d, 1H), 8.21 (8, 2H), 8.59-8 62 (m, 1H).

The following compound is synthesized by a method similar to or in accordance with the method of example 12.

Example 234

3- (4-Dimethylaminophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.00 (s, 6H), 6.75-6.80 (m, 2H), 7.19 (ddd, 1H), 7.41-7.54 (m, 5H), 7.57-7.60 (m, 1H), 7.73 (ddd, 1H), 7.76-7.81 (m, 2H), 8, 14-8.17 (m, 2H), 8.58-8, 61 (m, 1H).

The following compound is synthesized by a method similar to or in accordance with the method of example 15.

Example 235

5- (6-Aminocarbonylpyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.60 (m, 6H), 7.64 (dt, 1H), 7.74 (dd, 1H), 7.80-7.83 (m, 1H), 7.91-7.95 (m, 2H), 8.14-8.17 (m, 2H), 8.52 (d, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 16, path 1.

Example 236

3- (2-cyanophenyl) -5- (2-cyanopyridin-6-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.57 (m, 6H), 7.60 (dd, 1H), 7.66 (dt, 1H), 7.79-7.83 (m, 3H), 7.89 (dd, 1H), 8.29 (d, 1H), 8.41 (d, 1H).

The following compounds are synthesized by methods similar to or in accordance with the method of example 18.

Example 237

3- (3-Hydroxyphenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 6.74-6.78 (m, 1H), 7.15-7.26 (m, 3H), 7.27 -7.32 (m, 1H), 7.47-7.61 (m, 5H), 7.83 (ddd, 1H), 8.02 (d, 1H), 8.41 (s, 2H), 8.57-8.62 (m, 1H); 9.43 (br s, 1H).

Example 238

3- (4-Hydroxyphenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 6.79-6.84 (m, 2H), 7.28 (ddd, 1H), 7.47-7.59 (m, 5H), 7.61-7.66 (m, 2H), 7.82 (ddd, 1H), 8.00 (d, 1H), 8.33 (d, 1H), 8.35 ( d, 1H), 8.57-8.61 (m, 1H), 9.57 (br, 1H).

The following compounds are synthesized in the same manner as in example 19.

Example 239

3- (2-cyanophenyl) -1- (3-dimethylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.34 (s, 6H), 2.74 (t, 2H), 4.10 (t, 2H), 7.01- 7.05 (m, 1H), 7.07-7.11 (m, 2H), 7.21 (ddd, 1H), 7.42 (dd, 1H), 7.45 (ddd, 1H), 7 59-7.66 (m, 2H), 7.72-7.81 (m, 3H), 8.30 (s, 2H), 8.58-8.61 (m, 1H).

Example 240

3- (2-cyanophenyl) -1- (3-piperidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.39-1.48 (m, 2H), 1.56-1.64 (m, 4H), 2.46-2 56 (m, 4H), 2.78 (t, 2H), 4.14 (t, 2H), 6.99-7.03 (m, 1H), 7.06-7.11 (m, 2H) ), 7.21 (ddd, 1H), 7.41 (dd, 1H), 7.45 (ddd, 1H), 7.59-7.66 (m, 2H), 7.72-7.81 ( m, 3H), 8.30 (s, 2H), 8.58-8.61 (m, 1H).

Example 241

3- (2-cyanophenyl) -1- (3-pyrrolidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.76-1.86 (m, 4H), 2.57-2.70 (m, 4H), 2.92 (t , 2H), 4.16 (t, 2H), 7.03 (ddd, 1H), 7.06-7.11 (m, 2H), 7.21 (ddd, 1H), 7.41 (dd, 1H), 7.45 (ddd, 1H), 7.59-7.66 (m, 2H), 7.72-7.81 (m, 3H), 8.30 (s, 2H), 8.58 -8.61 (m, 1H).

Example 242

3- (2-cyanophenyl) -1- (3-diisopropylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.03 (d, 12H), 2.83 (t, 2H), 3.04 (heptet, 2H), 3.92 ( t, 2H), 6.97-7.01 (m, 1H), 7.04 (dd, 1H), 7.07 (ddd, 1H), 7.21 (ddd, 1H), 7.41 (dd , 1H), 7.45 (ddd, 1H), 7.59-7.66 (m, 2H), 7.72-7.82 (m, 3H), 8.29-8.32 (m, 2H) ), 8.58-8.61 (m, 1H).

Example 243

3- (2-cyanophenyl) -1- (3-dimethylaminopropoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.96 (tt, 2H), 2.24 (s, 6H), 2.44 (t, 2H), 4.05 ( t, 2H), 7.00 (ddd, 1H), 7.05-7.09 (m, 2H), 7.21 (ddd, 1H), 7.41 (dd, 1H), 7.45 (ddd , 1H), 7.59-7.66 (m, 2H), 7.72-7.81 (m, 3H), 8.30 (s, 2H), 8.58-8.61 (m, 1H )

Example 244

3- (2-cyanophenyl) -1- (3-piperidinopropoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.37-1.50 (m, 2H), 1.53-1.64 (m, 4H), 1.97 (tt) , 2H), 2.30-2.45 (m, 4H), 2.47 (t, 2H), 4.04 (t, 2H), 6.97-7.02 (m, 1H), 7, 04-7.09 (m, 2H), 7.21 (ddd, 1H), 7.41 (dd, 1H), 7.45 (ddd, 1H), 7.59-7.66 (m, 2H) 7.70-7.82 (m, 3H); 8.31 (s, 2H); 8.58-8.62 (m, 1H).

Example 245

3- (2-cyanophenyl) -1- (3-morpholinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.48-2.65 (m, 4H), 2.81 (t, 2H), 3.68-3.80 (m , 4H), 4.15 (t, 2H), 6.99-7.04 (m, 1H), 7.06-7.13 (m, 2H), 7.22 (ddd, 1H), 7, 42 (dd, 1H), 7.46 (ddd, 1H), 7.61 (dd, 1H), 7.64 (ddd, 1H), 7.74 (ddd, 1H), 7.78 (dd, 2H) ), 8.28-8.33 (m, 2H), 8.58-8.62 (m, 1H).

Example 246

3- (2-cyanophenyl) -1- (3-diethylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.07 (t, 6H), 2.64 (q, 4H), 2.89 (t, 2H), 4.08 ( t, 2H), 7.01 (ddd, 1H), 7.05-7.10 (m, 2H), 7.21 (ddd, 1H), 7.41 (dd, 1H), 7.45 (ddd , 1H), 7.59-7.66 (m, 2H), 7.72-7.81 (m, 3H), 8.31 (s, 2H), 8.58-8.61 (m, 1H )

Example 247

3- (3-Dimethylaminoethoxyphenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.34 (s, 6H), 2.74 (t, 2H), 4.13 (t, 2H), 6.92- 6.98 (m, 1H), 7.19-7.24 (m, 1H), 7.33 (dd, 1H), 7.37-7.42 (m, 1H), 7.44-7, 56 (m, 6H), 7.57-7.62 (m, 1H), 7.75 (ddd, 1H), 8.25 (s, 2H), 8.59-8.63 (m, 1H) .

Example 248

3- (4-Dimethylaminoethoxyphenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.35 (s, 6H), 2.76 (t, 2H), 4.12 (t, 2H), 6.95- 7.00 (m, 2H), 7.20 (ddd, 1H), 7.43-7.54 (m, 5H), 7.59 (ddd, 1H), 7.73 (ddd, 1H), 7 76-7.81 (m, 2H), 8.17-8.20 (m, 2H), 8.59-8.62 (m, 1H).

Example 249

3- (2-cyanophenyl) -1- [3- (4-piperidinobutoxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.38-1.46 (m, 2H), 1.54-1.61 (m, 4H), 1.62-1 71 (m, 2H), 1.75-1.83 (m, 2H), 2.30-2.43 (m, 6H), 4.01 (t, 2H), 6.97-7.01 (m, 1H), 7.03-7.08 (m, 2H), 7.21 (ddd, 1H), 7.40 (dd, 1H), 7.45 (ddd, 1H), 7.59- 7.66 (m, 2H), 7.72-7.82 (m, 3H), 8.30 (s, 2H), 8.58-8.61 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 29.

Example 250

3- (2-cyanophenyl) -1- (3-pyrrolidinomethylphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.74-1.84 (m, 4H), 2.48-2.58 (m, 4H), 3.69 (s , 2H), 7.14-7.25 (m, 2H), 7.38-7.51 (m, 4H), 7.61 (d, 1H), 7.63 (ddd, 1H), 7, 72-7.82 (m, 3H), 8.30 (d, 1H), 8.32 (d, 1H), 8.58-8.62 (m, 1H).

Example 251

1- [3- (4-Acetylpiperazinomethyl) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.07 (s, 3H), 2.45 (dd, 4H), 3.45 (dd, 2H), 3.58 ( s, 2H), 3.63 (dd, 2H), 7.22 (ddd, 1H), 7.40-7.54 (m, 5H), 7.60-7.67 (m, 2H), 7 73-7.80 (m, 3H), 8.29 (d, 1H), 8.33 (d, 1H), 8.58-8.62 (m, 1H).

The following compounds are synthesized by methods similar to or in accordance with the method of example 32.

Example 252

3- (2-cyanophenyl) -1- (4-nitrophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.30 (m, 1H), 7.47-7.52 (m, 1H), 7.61-7 82 (m, 7H), 8.31 (dd, 2H), 8.42 (d, 2H), 8.60-8.63 (m, 1H).

Example 253

1-Phenyl-3- (2-pyrazinyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21-7.25 (m, 1H), 7.49-7.59 (m, 5H), 7.72-7 79 (m, 2H), 8.46 (d, 1H), 8.54 (d, 1H), 8.61 (ddd, 1H), 8.65 (dd, 1H), 9.14 (d, 1H), 9.87 (d, 1H).

Example 254

1-Phenyl-3- (2-pyrimidinyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20 (ddd, 1H), 7.25 (t, 1H), 7.44-7.54 (m, 5H), 7.66 (d, 1H), 7.75 (dt, 1H), 8.45 (d, 1H), 8.58-8.60 (m, 1H), 8.82 (d, 1H), 8 88 (s, 1H); 8.89 (s, 1H).

Example 255

1-Phenyl-5- (2-pyridyl) -3- (2-thiazolyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.26 (m, 1H), 7.48-7.57 (m, 6H), 7.78-7 80 (m, 2H), 8.00 (dd, 1H), 8.52 (dd, 1H), 8.59-8.61 (m, 1H), 9.29 (d, 1H).

Example 256

1-Phenyl-3- (4-pyrimidinyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.26 (m, 1H), 7.48-7.59 (m, 5H), 7.77-7 82 (m, 2H), 8.53 (d, 1H), 8.60-8.62 (m, 1H), 8.73-8.77 (m, 2H), 9.27 (dd, 1H) ), 9.40 (d, 1H).

Example 257

1-Phenyl-3- (5-pyrimidinyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.27 (m, 1H), 7.48-7.61 (m, 7H), 7.77 (dt) , 1H), 8.28 (d, 1H), 8.37 (d, 1H), 8.63 (ddd, 1H), 9.21 (d, 1H), 9.22 (s, 1H).

Example 258

1-Phenyl-3- (3-pyridazinyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.25 (m, 1H), 7.48-7.58 (m, 6H), 7.78-7 80 (m, 2H), 8.55 (d, 1H), 8.60 (m, 1H), 8.78 (dd, 1H), 9.14 (dd, 1H), 9.34 (d, 1H).

Example 259

1-Phenyl-3- (4-pyridazinyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.28 (m, 1H), 7.47-7.62 (m, 6H), 7.78 (dt) , 1H), 8.16 (dd, 1H), 8.33 (d, 1H), 8.53 (d, 1H), 8.63-8.65 (m, 1H), 9.23 (dd, 1H), 9.62 (dd, 1H).

Example 260

3- (6-Methoxypyridin-2-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.07 (s, 3H), 6.73 (dd, 1H), 7.22 (ddd, 1H), 7.46- 7.56 (m, 5H), 7.62-7.70 (m, 2H), 7.78 (ddd, 1H), 8.35 (dd, 1H), 8.39 (d, 1H), 8 66 (ddd, 1H); 9.21 (d, 1H).

Example 261

3- (2-cyanophenyl) -1- (3-pyridyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.18 (t, 1H), 7.46-7.52 (m, 2H), 7.65 (dt, 1H), 7.71 (dd, 1H), 7.74-7.80 (m, 1H), 7.99 (ddd, 1H), 8.72-8.75 (m, 5H), 8.82 (dd, 1H).

Example 262

3- (2-Fluoropyridin-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.16 (t, 1H), 7.24-7.27 (m, 2H), 7.48-7.57 (m 5H), 8.19-8.23 (m, 2H), 8.69-8.76 (m, 3H).

Example 263

3- (2-Fluoropyridin-3-yl) -1- (3-pyridyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.19 (t, 1H), 7.26-7.30 (m, 1H), 7.47-7.52 (m , 1H), 7.94 (ddd, 1H), 8.17 (ddd, 1H), 8.70-8.80 (m, 7H).

Example 264

3- (2-cyanopyridin-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.17 (t, 1H), 7.47-7.56 (m, 6H), 8.14 (dd, 1H), 8.70 (dd, 1H), 8.72 (d, 2H), 8.80 (d, 1H), 8.85 (d, 1H).

Example 265

3- (2-cyanopyridin-3-yl) -1- (3-pyridyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20 (t, 1H), 7.52 (ddd, 1H), 7.58 (dd, 1H), 7.97 ( ddd, 1H), 8.11 (dd, 1H), 8.71-8.76 (m, 4H), 8.78 (d, 1H), 8.81 (dd, 1H), 8.66 (d , 1H).

Example 266

3- (2-cyanophenyl) -1- (3-nitrophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20 (t, 1H), 7.49 (ddd, 1H), 7.65-7.80 (m, 5H), 7.98 (ddd, 1H), 8.36 (ddd, 1H), 8.46 (t, 1H), 8.73-8.77 (m, 3H).

Example 267

1-Phenyl-5- (2-pyridyl) -3- (thiazol-4-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24-7.28 (m, 1H), 7.48-7.58 (m, 5H), 7.64 (td) , 1H), 7.79 (dt, 1H), 8.23 (d, 1H), 8.58 (d, 1H), 8.64-8.66 (m, 2H), 8.85 (d, 1H).

Example 268

3- (3-Oxo-1-cyclohexen-1-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.09-2.16 (m, 2H), 2.48-2.51 (m, 2H), 2.87-2 91 (m, 2H), 6.53 (t, 1H), 7.22 (ddd, 1H), 7.43-7.57 (m, 6H), 7.75 (dt, 1H), 8, 17 (d, 1H), 8.25 (d, 1H), 8.60 (ddd, 1H).

Example 269

3- (5,6-dihydro-1,4-dioxin-2-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.18-4.20 (m, 2H), 4.30-4.32 (m, 2H), 7.19 (ddd , 1H), 7.41-7.54 (m, 5H), 7.63 (td, 1H), 7.73 (dt, 1H), 8.02 (s, 1H), 8.10 (d, 1H), 8.28 (d, 1H), 8.58 (ddd, 1H).

Example 270

3- (2-Nitrophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22 (ddd, 1H), 7.40-7.61 (m, 9H), 7.68 (ddd, 1H), 7.74 (ddd, 1H), 8.06 (dd, 1H), 8.22-8.25 (m, 2H), 8.60-8.63 (m, 1H).

Example 271

3- (4-biphenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20-7.25 (m, 1H), 7.33-7.40 (m, 1H), 7.42-7 57 (m, 6H), 7.60-7.79 (m, 7H), 7.90-7.95 (m, 2H), 8.25 (d, 1H), 8.30 (d, 1H) ), 8.60-8.64 (m, 1H).

Example 272

3- (2-Acetylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.59 (s, 3H), 7.16-7.21 (m, 1H), 7.40-7.60 (m 8H), 7.63-7.67 (m, 1H), 7.68-7.75 (m, 1H), 8.16 (d, 1H), 8.22 (d, 1H), 8, 57-8.61 (m, 1H).

Example 273

3- (3-Nitrophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (ddd, 1H), 7.46-7.64 (m, 7H), 7.76 (ddd, 1H), 8.20-8.26 (m, 2H), 8.27 (d, 1H), 8.37 (d, 1H), 8.61-8.65 (m, 1H), 8.69 (dd, 1H).

Example 274

1-Phenyl-3- (4-pyridyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (ddd, 1H), 7.46-7.62 (m, 6H), 7.73-7.81 (m , 3H), 8.28 (d, 1H), 8.39 (d, 1H), 8.61-8.64 (m, 1H), 8.66 (dd, 2H).

Example 275

3- (4-Nitrophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.26 (m, 1H), 7.47-7.58 (m, 5H), 7.60 (ddd , 1H), 7.76 (ddd, 1H), 8.01-8.06 (m, 2H), 8.26-8.31 (m, 3H), 8.38 (d, 1H), 8, 61-8.65 (m, 1H).

Example 276

1- (3-Benzyloxyphenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 5.10 (s, 2H), 7.05-7.14 (m, 2H), 7.17 (dd, 1H), 7.21 (ddd, 1H), 7.30-7.48 (m, 7H), 7.60 (ddd, 1H), 7.64 (ddd, 1H), 7.71-7.81 (m, 3H), 8.29-8.32 (m, 2H), 8.58-8.61 (m, 1H).

Example 277

1- (3-Acetylphenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.66 (s, 3H), 7.24 (ddd, 1H), 7.48 (ddd, 1H), 7.61- 7.69 (m, 3H), 7.74-7.81 (m, 4H), 8.07 (ddd, 1H), 8.11 (ddd, 1H), 8.32 (d, 1H), 8 34 (d, 1H); 8.59-8.62 (m, 1H).

Example 278

3- [4- (tert-Butylaminosulfonyl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.26 (s, 9H), 4.46 (s, 1H), 7.24 (ddd, 1H), 7.46- 7.58 (m, 5H), 7.58-7.61 (m, 1H), 7.76 (ddd, 1H), 7.90-7.99 (m, 4H), 8.26 (d, 1H), 8.33 (d, 1H), 8.61-8.64 (m, 1H).

Example 279

3- (1-Naphthyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21 (dd, 1H), 7.42-7.50 (m, 3H), 7.51-7.61 (m , 3H), 7.71 (td, 1H), 7.81-7.85 (m, 1H), 7.87-7.90 (m, 2H), 7.96-7.99 (m, 1H ), 8.20 (d, 1H), 8.37 (d, 1H), 8.60 (d, 1H), 8.67 (d, 1H), 8.84 (d, 1H).

ERI-Mass: 376 [M ⁺ + H].

Example 280

3- (1-Naphthyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.19 (ddd, 1H), 7.38-7.59 (m, 9H), 7.71 (td, 2H), 7.84-7.89 (m, 3H), 8.18 (d, 1H), 8.39 (d, 1H), 8.59 (ddd, 1H).

ERI-Mass: 375 [M ⁺ + H].

Example 281

3- (8-Quinolinyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.18-7.23 (m, 1H), 7.38-7.56 (m, 3H), 7.58-7 84 (m, 3H), 7.86-8.01 (m, 3H), 8.19-8.23 (m, 1H), 8.30-8.36 (m, 2H), 8.56 -8.62 (m, 1H), 8.66-8.70 (m, 1H), 8.91-8.97 (m, 1H).

ERI-Mass: 377 [M ⁺ + H].

Example 282

3- (8-Quinolinyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.18 (dd, 1H), 7.39-7.54 (m, 4H), 7.55-7.65 (m , 3H), 7.66-7.73 (m, 2H), 7.85 (dd, 1H), 7.98 (dd, 1H), 8.2 (dd, 1H), 8.34 (d, 1H), 8.36 (d, 1H), 8.58 (d, 1H), 8.94 (dd, 1H).

ERI-Mass: 376 [M ⁺ + H].

Example 283

3- (2-Naphthyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.28 (m, 1H), 7.48-7.53 (m, 3H), 7.64 (dt) , 1H), 7.78 (td, 1H), 7.85-7.91 (m, 4H), 7.97 (ddd, 1H), 8.25 (d, 1H), 8.35 (s, 1H), 8.38 (d, 1H), 8.64 (ddd, 1H), 8.72 (d, 1H), 8.81 (d, 1H).

ERI-Mass: 376 [M ⁺ + H].

Example 284

3- (2-Naphthyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21 (dd, 1H), 7.44-7.50 (m, 4H), 7.53-7.56 (m , 3H), 7.62 (dd, 1H), 7.72-7.77 (m, 1H), 7.83-7.91 (m, 2H), 7.92 (td, 2H), 8, 25 (d, 1H), 8.37 (d, 1H), 8.39 (br, 1H), 8.61-8.64 (m, 1H).

Example 285

3- (2-Pyrrolidinopyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.00-2.04 (m, 4H), 3.50 (t, 4H), 7.74-7.78 (m 9H), 8.03 (d, 1H), 8.06 (d, 1H), 8.21 (d, 1H), 8.57-8.60 (m, 2H).

ERI-Mass: 396 [M ⁺ + H].

Example 286

3- (2-Formylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21-7.29 (m, 2H), 7.46-7.57 (m, 6H), 7.73 (d , 1H), 7.75 (td, 1H), 8.22 (d, 1H), 8.31 (d, 1H), 8.60-8.62 (m, 1H), 10.00 (s, 1H).

ERI-Mass: 359 [M ⁺ + H].

Example 287

3- (2-Chloropyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.24 (ddd, 1H), 7.37 (d, 1H), 7.44-7.51 (m, 3H), 7.53-7.60 (m, 2H), 7.64-7.70 (m, 1H), 7.76 (td, 1H), 8.24 (d, 1H), 8.26 (t, 1H), 8.31 (d, 1H), 8.62 (ddd, 1H), 8.75 (d, 1H).

ERI-Mass: 360 [M ⁺ + H].

Example 288

3- (2-Fluoropyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.99 (dd, 1H), 7.24 (dd, 1H), 7.47-7.57 (m, 5H), 7.59 (dd, 1H), 7.76 (tdd, 1H), 8.25 (dd, 1H), 8.30 (dd, 1H), 8.37 (td, 1H), 8.57-8 58 (m, 1H); 8.63 (dt, 1H).

Example 289

3- (2-Ethylthiopyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.39 (t, 3H), 3.20 (q, 2H), 7.20-7.24 (m, 2H), 7.44-7.59 (m, 6H), 7.75 (td, 1H), 8.08 (dd, 1H), 8.23 (d, 1H), 8.26 (d, 1H), 8 61 (ddd, 1H); 8.78 (d, 1H).

ERI-Mass: 386 [M ⁺ + H].

Example 290

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (2-naphthyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22 (ddd, 1H), 7.47 (td, 1H), 7.53-7.60 (m, 2H), 7.62-7.67 (m, 3H), 7.76 (td, 1H), 7.81 (td, 2H), 7.88-7.94 (m, 2H), 7.98 (d, 1H), 7.99 (s, 1H), 8.34 (d, 1H), 8.43 (d, 1H), 8.60 (ddd, 1H).

ERI-Mass: 400 [M ⁺ + H].

Example 291

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-naphthyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.21 (ddd, 1H), 7.45 (td, 1H), 7.54-7.65 (m, 6H), 7.65-7.83 (m, 4H), 7.93-8.02 (m, 2H), 8.30 (d, 1H), 8.46 (d, 1H), 8.57 (ddd, 1H).

ERI-Mass: 400 [M ⁺ + H].

Example 292

3- (2-cyanophenyl) -5- (2-pyridyl) -1- (8-quinolinyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.18 (ddd, 1H), 7.43 (td, 1H), 7.48 (dd, 1H), 7.61 ( td, 1H), 7.63 (d, 1H), 7.69 (dd, 1H), 7.72 (td, 1H), 7.78 (dd, 1H), 7.86 (dd, 1H), 7.92 (dd, 1H), 7.98 (dd, 1H), 8.26 (dd, 1H), 8.36 (d, 1H), 8.43 (d, 1H), 8.55-8 57 (m, 1H); 8.95 (dd, 1H).

Example 293

3- (1-Benzenesulfonylindol-2-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.95 (d, 1H), 7.21 (ddd, 1H), 7.22 (ddd, 1H), 7.26- 7.33 (m, 3H), 7.42 (dt, 1H), 7.44-7.49 (m, 2H), 7.50-7.56 (m, 4H), 7.60 (dt, 1H), 7.71-7.77 (m, 3H), 8.07 (dd, 1H), 8.20 (d, 1H), 8.34 (d, 1H), 8.60 (ddd, 1H )

Example 294

3- (2-Cyanopyridin-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.20-7.28 (m, 1H), 7.51 (dd, 1H), 7.58 (dd, 1H), 7.64 (d, 1H), 7.79 (td, 1H), 7.94-7.97 (m, 1H), 8.18 (dd, 1H), 8.35 (d, 1H), 8 44 (d, 1H), 8.60-8.63 (m, 1H), 8.72 (dd, 1H), 8.74 (dd, 1H), 8.81 (d, 1H).

ERI-Mass: 352 [M ⁺ + H].

Example 295

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (pyrrol-3-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.46-6.50 (m, 1H), 6.79 (dd, 1H), 7.21 (dd, 1H), 7.29-7.32 (m, 1H), 7.45 (t, 1H), 7.60-7.66 (m, 2H), 7.72-7.80 (m, 3H), 8, 23 (d, 1H), 8.47 (d, 1H), 8.61 (d, 1H), 8.72 (br s, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 162.

Example 296

3- (2-cyanophenyl) -5- (3-nitropyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.43-7.54 (m, 7H), 7.62-7.67 (m, 2H), 7.73-7 76 (m, 2H), 8.03 (d, 1H), 8.24 (dd, 1H), 8.82 (dd, 1H).

Example 297

3- (2-Cyanophenyl) -5- [2- (2,6-dimethylpyrrol-1-yl) pyridin-6-yl] -1-phenyl-1, 2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.17 (s, 6H), 5.91 (s, 2H), 7.12 (dd, 1H), 7.45- 7.56 (m, 6H), 7.61 (dd, 1H), 7.65 (dd, 1H), 7.78-7.80 (m, 2H), 7.88 (t, 1H), 8 35 (d, 1H); 8.40 (d, 1H).

Example 298

5- (2-aminopyridin-6-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.44 (br s, 2H), 6.43 (dd, 1H), 6.96 (d, 1H), 7.42- 7.54 (m, 7H), 7.63 (dt, 1H), 7.76-7.78 (m, 2H), 8.24 (d, 1H), 8.26 (d, 1H).

Example 299

3- (2-cyanophenyl) -5- (5-nitropyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.47-7.59 (m, 6H), 7.67 (dt, 1H), 7.75-7.82 (m , 3H), 8.35 (d, 1H), 8.52 (dd, 1H), 8.55 (d, 1H), 9.39 (dd, 1H).

Example 300

5- (6-Bromopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.39 (dd, 1H), 7.45-7.67 (m, 9H), 7.78-7.80 (m , 2H), 8.23 (d, 1H), 8.34 (d, 1H).

Example 301

3- (2-Cyanophenyl) -1-phenyl-5- (5-trifluoromethylpyridin-2-yl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.46-7.58 (m, 6H), 7.63-7.68 (m, 1H), 7.72 (d , 1H), 7.78-7.81 (m, 2H), 7.97 (ddd, 1H), 8.33 (d, 1H), 8.44 (d, 1H), 8.83-8, 84 (m, 1H).

Example 302

3- (2-cyanophenyl) -5- (2-morpholinopyridin-6-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.55 (t, 4H), 3.83 (t, 4H), 6.57 (d, 1H), 6.97 ( d, 1H), 7.43-7.66 (m, 8H), 7.77-7.80 (m, 2H), 8.18 (d, 1H), 8.31 (d, 1H).

Example 303

3- (2-Cyanophenyl) -5- (2-methoxycarbonylpyridin-6-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.99 (s, 3H), 7.44-7.57 (m, 6H), 7.65 (dt, 1H), 7.78-7.81 (m, 3H), 7.91 (t, 1H), 8.04 (dd, 1H), 8.30 (d, 1H), 8.37 (d, 1H).

The following compound is synthesized by a method similar to or in accordance with the method of example 164.

Example 304

5- [4- (tert-Butylaminosulfonyl) phenyl] -3- (2-cyanophenyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.25 (s, 9H), 4.72 (s, 1H), 7.47-7.54 (m, 2H), 7.60-7.71 (m, 4H), 7.73-7.83 (m, 2H), 7.93-8.02 (m, 4H), 8.73 (dd, 1H), 8, 79 (d, 1H).

The following compound is synthesized by a method similar to or in accordance with the method of example 167.

Example 305

3- (2-cyanophenyl) -4-methyl-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.12 (s, 3H), 7.28 (ddd, 1H), 7.38-7.52 (m, 8H), 7.59 (s, 1H), 7.66 (ddd, 1H), 7.75-7.80 (m, 2H), 8.66-8.70 (m, 1H).

The following compounds are synthesized by methods similar to or in accordance with the method of example 168.

Example 306

1-Phenyl-3- [N- (N'-phenylthiourehenyl)] - 5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.19-7.24 (m, 1H), 7.26-7.36 (m, 3H), 7.37-7 54 (m, 7H), 7.70 (d, 1H), 7.78 (ddd, 1H), 7.92 (br, 1H), 8.09 (d, 1H), 8.55-8, 59 (m, 1H), 9.33 (br, 1H), 10.03 (d, 1H).

Example 307

3- (2-cyanophenyl) -1-phenyl-5- [N- (N'-phenylureylenyl)] -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 6.95 (dd, 1H), 7.25 (dd, 1H), 7.41-7.61 (m, 8H) ), 7.65 (d, 1H), 7.71 (d, 1H), 7.77 (dd, 1H), 7.92 (d, 1H), 8.03 (d, 1H), 8.56 -8.66 (m, 1H); 9.02-9.10 (m, 1H).

Example 308

3- {4- [N- (N'-butylureylenyl) phenyl]} - 1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 0.90 (t, 3H), 1.32 (tt, 2H), 1.42 (tt, 2H), 3, 09 (dt, 2H), 6.16 (pcs, 1H), 7.29 (dd, 1H), 7.44 (d, 2H), 7.47-7.54 (m, 1H), 7.54 -7.60 (m, 4H), 7.69 (d, 2H), 7.82 (ddd, 1H), 8.02 (d, 1H), 8.35 (d, 1H), 8.39 ( d, 1H), 8.53 (br, 1H), 8.58-8.61 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 169.

Example 309

3- (2-cyanophenyl) -1-phenyl-5- (2-pyridinecarbonyl) amino-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.42-7.54 (m, 7H), 7.63 (ddd, 1H), 7.74-7.79 (m , 3H), 7.92 (ddd, 1H), 8.20 (d, 1H), 8.58 (d, 1H), 8.59-8.62 (m, 1H), 9.80 (br, 1H).

Example 310

1-Phenyl-3- [2- (1-pyrrolidino) acetylamino] -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.78-1.86 (m, 4H), 2.66-2.74 (m, 4H), 3.36 (s , 2H), 7.20 (ddd, 1H), 7.44-7.56 (m, 5H), 7.66 (d, 1H), 7.75 (ddd, 1H), 8.07 (d, 1H), 8.54-8.58 (m, 1H), 9.12 (d, 1H), 10.15 (br, 1H).

Example 311

1-Phenyl-3- {3- [1- (4-phenylpiperadino)] propionylamino} -5 (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.66 (t, 2H), 2.69-2.76 (m, 4H), 2.80 (t, 2H), 3.30-3.36 (m, 4H), 6.81-6.86 (m, 1H), 6.90-6.97 (m, 2H), 7.18 (ddd, 1H), 7, 22-7.29 (m, 2H), 7.40-7.53 (m, 5H), 7.62-7.67 (m, 1H), 7.73 (ddd, 1H), 8.03 ( d, 1H), 8.53-8.57 (m, 1H), 9.11 (d, 1H), 10.56 (br, 1H).

Example 312

3- (3-Pyrrolidinopropionyl) amino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.80-1.88 (m, 4H), 2.58-2.67 (m, 6H), 2.86 (t , 2H), 7.17 (ddd, 1H), 7.42-7.54 (m, 5H), 7.65 (d, 1H), 7.73 (ddd, 1H), 8.03 (d, 1H), 8.53-8.57 (m, 1H), 9.11 (d, 1H), 10.91 (br, 1H).

The following compounds are synthesized by methods similar to or in accordance with the method of example 170.

Example 313

5-benzylamino-3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.15 (s, 2H), 6.70 (d, 1H), 7.30-7.36 (m, 1H), 7.36-7.43 (m, 8H), 7.43-7.49 (m, 3H), 7.59 (ddd, 1H), 7.72-7.77 (m, 2H).

Example 314

3-Dibenzylamino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.52 (s, 4H), 7.12 (ddd, 1H), 7.16-7.33 (m, 10H), 7.37-7.54 (m, 7H), 7.63 (ddd, 1H), 7.80 (d, 1H), 8.50-8.54 (m, 1H).

Example 315

3- (2-cyanophenyl) -1- (3-hydroxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

52 mg of 1- (3-benzyloxyphenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one and 20 mg of 5% palladium-carbon are added to 3 ml of methanol followed by stirring at room temperature in a hydrogen atmosphere overnight. After filtering off the resulting insoluble matter, the filtrate was evaporated. The residue was purified by silica gel chromatography (ethyl acetate / hexane) to give 26 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.76 (dd, 1H), 6.87-6.92 (m, 1H), 6.93 (dd, 1H), 7.22-7.30 (m, 2H), 7.44 (ddd, 1H), 7.60-7.67 (m, 2H), 7.73-7.80 (m, 3H), 8, 25 (d, 1H), 8.32 (d, 1H), 8.33 (br s, 1H), 8.59-8.63 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 171.

Example 316

1-Benzyloxymethyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.76 (s, 2H), 5.63 (s, 2H), 7.22 (ddd, 1H), 7.26- 7.42 (m, 5H), 7.47 (ddd, 1H), 7.57 (d, 1H), 7.64-7.80 (m, 4H), 8.23 (d, 1H), 8 34 (d, 1H); 8.60-8.64 (m, 1H).

Example 317

3- (2-cyanophenyl) -1-cyclopentylmethyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.32-1.42 (m, 2H), 1.55-1.64 (m, 2H), 1.65-1 75 (m, 2H), 1.76-1.86 (m, 2H), 2.53 (ddd, 1H), 4.10 (d, 2H), 7.21 (ddd, 1H), 7, 45 (ddd, 1H), 7.58 (dd, 1H), 7.64 (ddd, 1H), 7.71-7.79 (m, 3H), 8.16 (d, 1H), 8.28 (d, 1H), 8.59-8.63 (m, 1H).

Example 318

1- [1- (tert-Butoxycarbonyl) piperidin-4-yl] methyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.22-1.35 (m, 2H), 1.45 (s, 9H), 1.68-1.78 (m , 2H), 2.14-2.27 (m, 1H), 2.61-2.76 (m, 2H), 3.90-4.25 (m, 4H), 7.22 (ddd, 1H ), 7.46 (ddd, 1H), 7.58 (ddd, 1H), 7.65 (ddd, 1H), 7.73 (ddd, 2H), 7.78 (dd, 1H), 8.17 (d, 1H), 8.21 (d, 1H), 8.59-8.63 (m, 1H).

Example 319

1- (1-Benzyloxycarbonylpiperidin-4-yl) methyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.25-1.38 (m, 2H), 1.68-1.81 (m, 2H), 2.17-2 30 (m, 1H), 2.70-2.86 (m, 2H), 3.92-4.08 (m, 2H), 4.15-4.32 (m, 2H), 5.12 (s, 2H), 7.22 (ddd, 1H), 7.28-7.38 (m, 5H), 7.46 (ddd, 1H), 7.57 (d, 1H), 7.65 ( ddd, 1H), 7.69-7.79 (m, 3H), 8.17 (d, 1H), 8.20 (d, 1H), 8.59-8.62 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 174.

Example 320

3- (pyrrol-1-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.33 (t, 2H), 7.22 (ddd, 1H), 7.36 (t, 2H), 7.45- 7.57 (m, 6H), 7.74 (td, 1H), 8.10 (d, 1H), 8.12 (d, 1H), 8.61 (ddd, 1H).

ERI-Mass: 314 [M ⁺ + H].

Example 321

3- (2-cyanophenylamino) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.06 (ddd, 1H), 7.21 (ddd, 1H), 7.41-7.65 (m, 9H), 7.71 (td, 1H), 7.76 (d, 1H), 7.88 (d, 1H), 8.60 (ddd, 1H).

ERI-Mass: 365 [M ⁺ + H].

Example 322

3- (2-Pyridylamino) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.80-6.86 (m, 2H), 7.20 (dd, 1H), 7.44-7.58 (m 6H), 7.70 (d, 1H), 7.77 (td, 1H), 7.87 (d, 1H), 7.96 (s, 1H), 8.37 (d, 1H), 8 59 (d, 1H); 9.29 (d, 1H).

ERI-Mass: 341 [M ⁺ + H].

Example 323

3- (1-Isoquinolylamino) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.15-7.24 (m, 3H), 7.46-7.59 (m, 5H), 7.66 (t , 1H), 7.77 (d, 2H), 7.80 (td, 1H), 7.97 (d, 1H), 8.10 (d, 1H), 8.25 (d, 1H), 8 61 (d, 1H); 9.11 (s, 1H); 9.60 (d, 1H).

ERI-Mass: 391 [M ⁺ + H].

Example 324

3- (1-Indazolyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.52 (dt, 1H), 7.06 (ddd, 1H), 7.22 (ddd, 1H), 7.31 ( td, 1H), 7.36 (ddd, 1H), 7.43-7.57 (m, 7H), 7.75 (dt, 1H), 8.03 (s, 1H), 8.09 (d , 1H); 8.50 (dd, 1H).

ERI-Mass: 365 [M ⁺ + H].

Example 325

3- (9-Carbazolyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.29 (m, 4H), 7.35-7.63 (m, 9H), 7.52-7 57 (m, 1H), 8.12 (dd, 2H), 8.43 (dd, 1H), 8.46 (dd, 1H), 8.61 (ddd, 1H).

Example 326

3- (Indol-1-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.68 (d, 1H), 7.17 (td, 1H), 7.20-7.26 (m, 2H), 7.47-7.55 (m, 7H), 7.62 (d, 1H), 7.66 (d, 1H), 7.74 (td, 1H), 8.27 (d, 1H), 8 34 (d, 1H); 8.61 (ddd, 1H).

ERI-Mass: 364 [M ⁺ + H].

Example 327

3- (2-Methyl-5-phenylpyrrol-1-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

25 mg of 3-amino-1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 10 ml of toluene. To the mixture were added 20 mg of 1-phenyl-1,4-pentanedione and 0.2 mg of p-toluenesulfonate (hydrate), followed by heating under reflux for 1 hour. After cooling to room temperature, the reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 12 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.26 (s, 3H), 6.10 (d, 1H), 6.34 (d, 1H), 7.21 ( tt, 1H), 7.17 (ddd, 1H), 7.21-7.27 (m, 2H), 7.28-7.32 (m, 3H), 7.39-7.54 (m, 5H), 7.66 (td, 1H), 7.83 (d, 1H), 8.31 (d, 1H), 8.53 (ddd, 1H).

The following compounds are synthesized by a method similar to or in accordance with the method of example 327.

Example 328

3- (2,5-Dimethylpyrrol-1-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.16 (s, 6H), 5.92 (s, 2H), 7.22 (ddd, 1H), 7.43- 7.56 (m, 6H), 7.75 (td, 1H), 8.07 (d, 1H), 8.37 (d, 1H), 8.60 (ddd, 1H).

Example 329

3- (2-cyanophenyl) -1- (piperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

The title compound (382 mg) was obtained by catalytic hydrogenation of 590 mg of 1- [1- (benzyloxycarbonyl) piperidin-4-yl] methyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridine -2-she, using a conventional method using 10% palladium-on-carbon.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.22-1.34 (m, 2H), 1.62-1.77 (m, 2H), 2.08-2 20 (m, 1H), 2.55-2.63 (m, 2H), 3.05-3.13 (m, 2H), 4.00 (d, 2H), 7.21 (ddd, 1H ), 7.45 (ddd, 1H), 7.58 (ddd, 1H), 7.64 (ddd, 1H), 7.70-7.79 (m, 3H), 8.17 (d, 1H) 8.21 (d, 1H); 8.59-8.63 (m, 1H).

The following compounds are synthesized by a method similar to or in accordance with the method of example 329.

Example 330

3- (2-Cyanophenyl) -1- [3- (4-piperidyloxy)] phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.60-1.73 (m, 2H), 1.98-2.07 (m, 2H), 2.69-2 77 (m, 2H), 3.08-3.17 (m, 2H), 4.39-4.46 (m, 1H), 6.98-7.02 (m, 1H), 7.04 -7.09 (m, 2H), 7.21 (ddd, 1H), 7.38-7.48 (m, 2H), 7.58-7.67 (m, 2H), 7.72-7 81 (m, 3H), 8.29-8.32 (m, 2H), 8.58-8.61 (m, 1H).

Example 331

1- (1-Benzoylpiperidin-4-yl) methyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

30 mg of 3- (2-cyanophenyl) -1- (piperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 2 ml of chloroform. Under ice cooling, 0.04 ml of triethylamine and 19 mg of benzoyl chloride were added to the resulting solution, followed by stirring at room temperature for 2 hours. The reaction solution was diluted with chloroform and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate, then evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 25 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.22-1.52 (m, 2H), 1.65-1.78 (m, 1H), 1.80-1 98 (m, 1H), 2.28-2.41 (m, 1H), 2.70-2.86 (m, 1H), 2.88-3.06 (m, 1H), 3.70 -3.88 (m, 1H), 3.90-4.23 (m, 2H), 4.65-4.87 (m, 1H), 7.22 (dd, 1H), 7.36-7 42 (m, 5H), 7.46 (dd, 1H), 7.55-7.60 (m, 1H), 7.62-7.72 (m, 2H), 7.72-7.79 (m, 2H), 8.16 (d, 1H), 8.22 (d, 1H), 8.59-8.63 (m, 1H).

The following compounds are synthesized by methods similar to or in accordance with the method of example 331.

Example 332

1- (1-Acetylpiperidin-4-yl) methyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.22-1.38 (m, 2H), 1.75-1.86 (m, 2H), 2.08 (s , 3H), 2.20-2.35 (m, 1H), 2.50-2.60 (m, 1H), 2.98-3.08 (m, 1H), 3.79-3.87 (m, 1H), 3.95 (dd, 1H), 4.05-4.15 (m, 1H), 4.61-4.70 (m, 1H), 7.23 (ddd, 1H), 7.47 (ddd, 1H), 7.58 (d, 1H), 7.63-7.71 (m, 2H), 7.72-7.80 (m, 2H), 8.17 (d, 1H), 8.21 (d, 1H), 8.59-8.63 (m, 1H).

Example 333

1- [3- (N-Acetylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.77-2.02 (m, 4H), 2.12 (s, 3H), 3.37-3.45 (m , 1H), 3.59-3.72 (m, 2H), 3.75-3.83 (m, 1H), 4.57-4.62 (m, 1H), 7.01 (ddd, 1H) ), 7.07-7.12 (m, 2H), 7.22 (ddd, 1H), 7.43 (dd, 1H), 7.46 (ddd, 1H), 7.61 (ddd, 1H) 7.64 (ddd, 1H), 7.72-7.80 (m, 3H), 8.29 (d, 1H), 8.31 (d, 1H), 8.58-8.62 (m , 1H).

Example 334

1- [3- (N-Benzoylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.75-2.13 (m, 4H), 3.30-3.47 (m, 1H), 3.58-3 72 (m, 1H), 3.75-3.87 (m, 1H), 3.88-4.03 (m, 1H), 4.56-4.68 (m, 1H), 6.99 -7.03 (m, 1H), 7.07-7.13 (m, 2H), 7.20-7.25 (m, 1H), 7.38-7.49 (m, 7H), 7 59-7.67 (m, 2H), 7.72-7.80 (m, 3H), 8.28 (d, 1H), 8.31 (d, 1H), 8.58-8.62 (m, 1H).

Example 335

1- (1- (Benzenesulfonylpiperidin-4-yl) methyl-3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

30 mg of 3- (2-cyanophenyl) -1- (piperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 2 ml of chloroform. Under ice-cooling, 0.04 ml of triethylamine and 23 mg of benzenesulfonyl chloride were added to the resulting solution, followed by stirring at room temperature for 2 hours. The reaction solution was diluted with chloroform and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate, then evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 30 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.41-1.60 (m, 2H), 1.77-1.85 (m, 2H), 1.95-2 06 (m, 1H), 2.20-2.31 (m, 2H), 3.80-3.88 (m, 2H), 3.98 (d, 2H), 7.22 (dd, 1H) ), 7.45 (ddd, 1H), 7.48-7.68 (m, 6H), 7.70-7.79 (m, 4H), 8.15 (d, 1H), 8.17 ( d, 1H), 8.59-8.63 (m, 1H).

The following compounds are synthesized by methods similar to or in accordance with the method of example 335.

Example 336

3- (2-cyanophenyl) -1- (1-methylsulfonylpiperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.43-1.56 (m, 2H), 1.83-1.92 (m, 2H), 2.17-2 30 (m, 1H), 2.63-2.72 (m, 2H), 2.77 (s, 3H), 3.80-3.88 (m, 2H), 4.03 (d, 2H) ), 7.20-7.26 (m, 1H), 7.44-7.51 (m, 1H), 7.55-7.61 (m, 1H), 7.63-7.72 (m , 2H), 7.73-7.82 (m, 2H), 8.17 (d, 1H), 8.21 (d, 1H), 8.59-8.64 (m, 1H).

Example 337

1- [3- (1- (Benzenesulfonylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.90-2.10 (m, 4H), 3.10-3.23 (m, 4H), 4.38-4 45 (m, 1H), 6.87-6.92 (m, 1H), 6.98 (dd, 1H), 7.05 (ddd, 1H), 7.22 (ddd, 1H), 7, 38 (dd, 1H), 7.46 (ddd, 1H), 7.52-7.66 (m, 5H), 7.72-7.80 (m, 5H), 8.25-8.28 ( m, 2H), 8.57-8.60 (m, 1H).

Example 338

3- (2-Cyanophenyl) -1- [3- (1-methylsulfonylpiperidin-4-yl-hydroxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.98-2.10 (m, 4H), 2.81 (s, 3H), 3.30-3.41 (m , 4H), 4.56-4.62 (m, 1H), 6.98-7.02 (m, 1H), 7.08-7.13 (m, 2H), 7.23 (ddd, 1H) ), 7.44 (ddd, 1H), 7.47 (ddd, 1H), 7.61 (ddd, 1H), 7.65 (ddd, 1H), 7.73-7.80 (m, 3H) 8.28 (d, 1H); 8.32 (d, 1H); 8.59-8.62 (m, 1H).

Example 339

3- (2-Cyanophenyl) -1- (1-benzylpiperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

80 mg of 3- (2-cyanophenyl) -1- (piperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 2 ml of chloroform. 73 mg of benzaldehyde, 97 mg of sodium triacetoxyborohydride and 41 mg of acetic acid were added to the mixture, followed by stirring at room temperature for 4 hours. The reaction solution was diluted with chloroform and washed with saturated aqueous sodium bicarbonate and brine. The organic layer is dried over magnesium sulfate. The mixture was then evaporated and the residue was purified by NH silica gel chromatography (hexane / ethyl acetate) to obtain 80 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.44 (ddd, 2H), 1.68-1.76 (m, 2H), 1.92-2.06 (m , 3H), 2.37-2.93 (m, 2H), 3.48 (s, 2H), 4.01 (d, 2H), 7.18-7.25 (m, 2H), 7, 27-7.32 (m, 4H), 7.45 (ddd, 1H), 7.56 (d, 1H), 7.64 (ddd, 1H), 7.70-7.78 (m, 3H) 8.16 (d, 1H); 8.19 (d, 1H); 8.58-8.61 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 339.

Example 340

3- (2-cyanophenyl) -1- (1-methylpiperidin-4-yl) methyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.38-1.50 (m, 2H), 1.65-1.80 (m, 2H), 1.88-2 05 (m, 3H), 2.25 (s, 3H), 2.82-2.92 (m, 2H), 4.01 (d, 2H), 7.19-7.24 (m, 1H ), 7.43-7.49 (m, 1H), 7.56-7.60 (m, 1H), 7.62-7.68 (m, 1H), 7.70-7.80 (m , 3H), 8.17 (d, 1H), 8.20 (d, 1H), 8.59-8.63 (m, 1H).

Example 341

1- [3- (N-Methylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.80-1.93 (m, 2H), 1.97-2.08 (m, 2H), 2.23-2 37 (m, 5H), 2.60-2.73 (m, 2H), 4.33-4.42 (m, 1H), 6.97-7.02 (m, 1H), 7.04 -7.10 (m, 2H), 7.19-7.24 (m, 1H), 7.38-7.49 (m, 2H), 7.58-7.68 (m, 2H), 7 72-7.82 (m, 3H), 8.28-8.33 (m, 2H), 8.58-8.62 (m, 1H).

Example 342

1- [3- (N-Benzylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.78-1.88 (m, 2H), 1.97-2.06 (m, 2H), 2.26-2 35 (m, 2H), 2.58-2.76 (m, 2H), 3.52 (s, 2H), 4.33-4.41 (m, 1H), 6.97-7.01 (m, 1H), 7.04-7.08 (m, 2H), 7.21 (ddd, 1H), 7.24-7.28 (m, 1H), 7.30-7.34 (m , 4H), 7.40 (dd, 1H), 7.46 (ddd, 1H), 7.60 (ddd, 1H), 7.64 (ddd, 1H), 7.72-7.80 (m, 3H), 8.30 (s, 2H), 8.58-8.61 (m, 1H).

Example 343

3- (4-Sulfamoylphenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

80 mg of 3- [4- (tert-butylaminosulfonyl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 3 ml of trifluoroacetic acid, followed by heating under reflux within 1 hour. The reaction mixture was allowed to cool to room temperature, then it was diluted with ethyl acetate / tetrahydrofuran and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and then evaporated. The resulting crude crystals were washed with ethyl acetate to give 60 mg of the title compound.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 5 (ppm) 7.31 (ddd, 1H), 7.49-7.61 (m, 5H), 7.82-7, 90 (m, 3H), 7.97-8.02 (m, 2H), 8.03-8.07 (m, 1H), 8.48 (d, 1H), 8.54 (d, 1H) 8.59-8.62 (m, 1H).

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 181.

Example 344

3-Cyclohexylaminocarbonyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.12-2.10 (m, 10H), 3.97-4.04 (m, 1H), 7.23 (ddd , 1H), 7.43-7.58 (m, 1H), 7.49-7.59 (m, 4H), 7.74-7.77 (m, 1H), 7.79 (td, 1H ), 8.55-8.56 (m, 1H), 8.57 (d, 1H), 9.18 (d, 1H), 9.64 (d, 1H).

ERI-Mass: 374 [M ⁺ + H].

Example 345

3- (2-cyanophenyl) -5- (1-adamantylaminocarbonyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.56-1.77 (m, 7H), 1.97-2.15 (m, 8H), 5, 63 (s , 1H), 7.42-7.54 (m, 6H), 7.63 (td, 1H), 7.74-7.78 (m, 2H), 7.88 (d, 1H), 8, 12 (d, 1H).

Example 346

3- (1-Adamantylaminocarbonyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.50-1.72 (m, 12H), 1.99-2.15 (m, 3H), 7.21-7 29 (m, 1H), 7.43-7.49 (m, 2H), 7.48-7.60 (m, 4H), 7.75-7.80 (m, 1H), 8.47 (d, 1H), 8.55 (d, 1H), 8.60 (ddd, 1H).

Example 347

3- {1- [4- (2-Cyanophenyl) piperadino] carbonyl} -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.12-3.31 (m, 4H), 3.59-3.79 (m, 4H), 6.99-7 06 (m, 2H), 7.22 (dd, 1H), 7.27-7.62 (m, 8H), 7.75 (td, 1H), 8.29 (d, 1H), 8, 37 (d, 1H); 8.58 (ddd, 1H).

ERI-Mass: 462 [M ⁺ + H].

Example 348

3 - [(2-Phenylhydrazino) carbonyl] -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.53 (d, 1H), 6.89 (t, 1H), 6.94 (d, 2H), 7.20- 7.30 (m, 3H), 7.62-7.47 (m, 5H), 7.71-7.77 (m, 1H), 7.80 (dd, 1H), 8.56-8, 57 (m, 1H), 8.64 (d, 1H), 9.16 (d, 1H), 11.23 (d, 1H).

ERI-Mass: 383 [M ⁺ + H].

Example 349

3-Phenylaminocarbonyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.06-7.17 (m, 1H), 7.23-7.28 (m, 1H), 7.31-7 37 (m, 2H), 7.46-7.62 (m, 5H), 7.73-7.83 (m, 4H), 8.58 (ddd, 1H), 8.63 (d, 1H) ), 9.29 (d, 1H), 11.86 (br s, 1H).

Example 350

(350A) 3- (2-Chlorophenyl) -5- (4-chlorobenzenesulfinyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

(350B) 3- (2-Chlorophenyl) -5- (4-chlorobenzenesulfonyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

38 mg of 3- (2-chlorophenyl) -5- (4-chlorophenylthio) -1- (3-pyridyl) -1,2-dihydropyridin-2-one is dissolved in 10 ml of dichloromethane. Under ice cooling, 15.4 mg of m-chloroperbenzoic acid was added to the resulting solution, followed by stirring at the same temperature for 1 hour. Then, 10 mg of m-chlorobenzoic acid was added thereto, followed by stirring for 2 hours under ice-cooling. The mixture was then diluted with 30 ml of ethyl acetate and washed with a 1N aqueous sodium hydroxide solution. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 9 mg of 3- (2-chlorophenyl) -5- (4-chlorobenzenesulfinyl) -1- (3-pyridyl) -1,2-dihydropyridin-2- she and 6 mg of 3- (2-chlorophenyl) -5- (4-chlorobenzenesulfonyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one as the title compounds.

(350A)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.27-7.33 (m, 3H), 7.36 (d, 1H), 7.40-7.44 (m , 1H), 7.48-7.57 (m, 3H), 7.63-7.67 (m, 2H), 7.87-7.92 (m, 1H), 7.97 (d, 1H) ), 8.70-8.76 (m, 2H).

ERI-Mass: 441 [M ⁺ + H].

(350V)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.30-7.37 (m, 2H), 7.44-7.52 (m, 3H), 7.56 (t , 1H), 7.58 (t, 1H), 7.34 (d, 1H), 7.84-7.88 (m, 1H), 7.89 (t, 1H), 7.92 (t, 1H), 8.24 (d, 1H), 8.71 (dd, 1H), 8.75 (dd, 1H).

ERI-Mass: 457 [M ⁺ + H].

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 182.

Example 351

3- (2-Cyanophenyl) -5- (5-methyl-1H-benzimidazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.45 (s, 3H), 7.05 (d, 1H), 7.34-7.43 (m, 7H), 7.57 (td, 2H), 7.62 (ddd, 1H), 7.68 (ddd, 1H), 8.18 (d, 1H), 8.27 (d, 1H).

ERI-Mass: 403 [M ⁺ + H].

Example 352

3- (2-Cyanophenyl) -5- (4-methyl-1H-benzimidazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.50 (br, 1.5H), 2.63 (br, 1.5H), 7.02 (d, 1H), 7.14 (t, 1H), 7.30-7.40 (m, 7H), 7.52-7.58 (m, 2H), 7.65 (d, 1H), 8.18-8, 23 (m, 1H), 8.24 (d, 1H).

ERI-Mass: 403 [M ⁺ + H].

Example 353

3- (2-Cyanophenyl) -5- (5,6-dichloro-1H-benzimidazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.39-7.49 (m, 6H), 7.52-7.54 (m, 1H), 7.60-7 66 (m, 2H), 7.70-7.72 (m, 1H), 7.72-7.74 (m, 1H), 8.21 (d, 1H), 8.37 (d, 1H) )

ERI-Mass: 457 [M ⁺ + H].

Example 354

3- (5,6-Dichloro-1H-benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.27 (ddd, 1H), 7.48-7.63 (m, 6H), 7.82 (td, 1H), 7.83-7.89 (m, 2H), 8.59 (d, 1H), 8.60 (dt, 1H), 9.38 (d, 1H), 12.15 (s, 1H).

ERI-Mass: 433 [M ⁺ + H].

Example 355

3- (6-Chloro-1H-benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.28 (m, 2H), 7.50-7.63 (m, 6H), 7.78-7 88 (m, 3H), 8.58 (dd, 1H), 8.61 (ddd, 1H), 9.40 (d, 1H).

ERI-Mass: 399 [M ⁺ + H].

Example 356

3- [1- (Pyridin-4-yl) benzimidazol-2-yl] -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.10-7.13 (m, 2H), 7.22-7.28 (m, 2H), 7.31-7 46 (m, 8H), 7.69 (dt, 1H), 7.77 (td, 1H), 7.91 (dt, 1H), 8.43 (d, 1H), 8.59 (ddd, 1H), 8.73-8.75 (m, 2H).

ERI-Mass: 442 [M ⁺ + H].

Example 357

3- [1- (1-Benzylpiperidin-4-yl) benzimidazol-2-yl] -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.01-2.20 (m, 4H), 2.56-2.66 (m, 2H), 3.02-3 07 (m, 2H), 3.58 (s, 2H), 4.09-4.18 (m, 1H), 7.21 (ddd, 1H), 7.24-7.30 (m, 3H) ), 7.31-7.36 (m, 2H), 7.45-7.50 (m, 4H), 7.52-7.60 (m, 3H), 7.64 (d, 1H), 7.74 (td, 1H), 7.77-7.84 (m, 2H), 8.48 (d, 1H), 8.49 (d, 1H), 8.58 (ddd, 1H).

ERI-Mass: 538 [M ⁺ + H].

Example 358

3- (2-Cyanophenyl) -5- (5,6-dihydro-4H-imidazo [4,5,1-i, j)] quinolin-2-yl) -1-phenyl-1,2-dihydropyridin-2 -he

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.30 (q, 2H), 3.02 (t, 2H), 4.47 (t, 2H), 7.04 ( dd, 1H), 7.20 (dd, 1H), 7.45-7.57 (m, 7H), 7.65 (td, 1H), 7.79 (dd, 1H), 7.81 (dd , 1H), 8.10 (d, 1H), 8.22 (d, 1H).

ERI-Mass: 429 [M ⁺ + H].

Example 359

3- (5,6-dihydro-4H-imidazo [4,5,1-i, j] quinolin-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2- he

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.20 (q, 2H), 2.98 (t, 2H), 4.35 (t, 2H), 7.03 ( d, 1H), 7.18-7.23 (m, 2H), 7.44-7.58 (m, 5H), 7.62 (d, 1H), 7.70 (d, 1H), 7 75 (dt, 1H), 8.52 (d, 1H), 8.57 (ddd, 1H), 8.70 (d, 1H).

ERI-Mass: 405 [M ⁺ + H].

Example 360

3- (1-Phenylbenzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.05-7.21 (m, 3H), 7.25-7.45 (m, 6H), 7.47-7 65 (m, 7H), 8.10 (d, 1H), 8.54-8.59 (m, 1H), 8.85-8.95 (m, 1H), 9.22 (d, 1H) )

ERI-Mass: 441 [M ⁺ + H].

Example 361

3- (2-Chlorophenyl) -5- (6-chloro-1H-benzimidazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.92 (td, 1H), 6.97-7.07 (m, 4H), 7.11-7.14 (m , 2H), 7.18-7.24 (m, 3H), 7.25-7.29 (m, 2H), 7.94 (d, 1H), 8.24 (d, 1H).

ERI-Mass: 432 [M ⁺ + H].

Example 362

3- (2-Cyanophenyl) -5- (1H-imidazo [4,5-c] pyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.04-7.09 (m, 1H), 7.28-7.31 (m, 1H), 7.44-7 60 (m, 5H), 7.66-7.70 (m, 2H), 7.74-7.78 (m, 1H), 7.80 (d, 1H), 7.93-7.96 (m, 1H), 8.01 (d, 1H), 8.40 (d, 1H), 8.51 (d, 1H).

ERI-Mass: 390 [M ⁺ + H].

Example 363

3- (6-Methyl-1H-benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.50 (s, 3H), 7.08-7.15 (m, 1H), 7.23-7.26 (m , 1H), 7.45-7.69 (m, 7H), 7.81 (td, 1H), 7.88 (d, 1H), 8.56 (d, 1H), 8.59 (ddd, 1H), 9.40 (d, 1H), 11.95-12.07 (m, 1H).

ERI-Mass: 379 [M ⁺ + H].

Example 364

3- (5-Methyl-1H-benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.49 (s, 3H), 7.12 (t, 1H), 7.24-7.27 (m, 1H), 7.31-7.72 (m, 7H), 7.80 (td, 1H), 7.87 (d, 1H), 8.56 (d, 1H), 8.59 (ddd, 1H), 9 40 (d, 1H); 11.94-12.07 (m, 1H).

ERI-Mass: 379 [M ⁺ + H].

Example 365

3- (2-Cyanophenyl) -5- [1- (1-benzylpiperidin-4-yl) benzimidazol-2-yl] -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.92 (dd, 2H), 2.36 (t, 2H), 2.75 (ddd, 2H), 3.05 ( d, 2H), 3.62 (s, 2H), 4.58 (tt, 1H), 7.26-7.41 (m, 7H), 7.44-7.51 (m, 2H), 7 52-7.56 (m, 4H), 7.65 (td, 1H), 7.70 (dd, 1H), 7.72 (d, 1H), 7.73-7.81 (m, 3H) ), 8.01 (d, 1H).

ERI-Mass: 562 [M ⁺ + H].

Example 366

3- (2-Cyanophenyl) -5- (5-methoxy-1H-benzimidazol-2-yl] -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.83 (s, 3H), 6.85 (dd, 1H), 7.24-7.47 (m, 8H), 7.50 (d, 2H), 7.60 (dt, 1H), 8.15 (s, 1H), 8.16 (s, 1H).

ERI-Mass: 419 [M ⁺ + H].

Example 367

3- (1H-Imidazo [4,5-s] pyridin-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.19-7.28 (m, 1H), 7.48-7.63 (m, 4H), 7.69-7 90 (m, 2H), 8.08 (d, 1H), 8.12 (d, 1H), 8.16-8.22 (m, 1H), 8.34 (d, 1H), 8, 59 (d, 1H), 8.58-8.62 (m, 1H), 9.44 (d, 1H), 12.20 (br, 1H).

ERI-Mass: 366 [M ⁺ + H].

Example 368

3- (2-cyanophenyl) -5- [1- (pyridin-4-yl) benzimidazol-2-yl] -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.29-7.34 (m, 4H), 7.35-7.51 (m, 8H), 7.59 (td) , 1H), 7.69 (d, 1H), 7.73 (dd, 1H), 7.82 (d, 1H), 7.84 (dt, 1H), 8.91 (dd, 2H).

ERI-Mass: 466 [M ⁺ + H].

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 183.

Example 369

3- (2-Chlorophenyl) -5- (5-trifluoromethylbenzothiazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.32-7.37 (m, 2H), 7.47-7.58 (m, 7H), 7.61 (ddd , 1H), 7.99 (d, 1H), 8.14 (d, 1H), 8.21-8.23 (m, 1H), 8.39 (d, 1H).

ERI-Mass: 483 [M ⁺ + H].

Example 370

3- (5-Trifluoromethylbenzothiazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26-7.30 (m, 1H), 7.51-7.64 (m, 6H), 7.81-7 87 (m, 2H), 8.08 (d, 1H), 8.39 (s, 1H), 8.63 (d, 1H), 8.64 (t, 1H), 9.50 (d, 1H).

ERI-Mass: 450 [M ⁺ + H].

Example 371

3- (2-Benzothiazolyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26-7.30 (m, 1H), 7.41 (t, 1H), 7.50-7.60 (m 6H), 7.84 (t, 1H), 7.88-7.94 (m, 1H), 7.98 (d, 1H), 8.12 (d, 1H), 8.60-8, 63 (m, 2H); 9.48-9.52 (m, 1H).

ERI-Mass: 382 [M ⁺ + H].

Example 372

5- (2-Benzothiazolyl) -3- [2- (2-benzothiazolyl) phenyl] -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.09-7.14 (m, 2H), 7.25-7.33 (m, 4H), 7.37 (td) , 1H), 7.42 (td, 1H), 7.46-7.52 (m, 4H), 7.80 (ddt, 2H), 7.90 (ddt, 2H), 7.95 (d, 1H), 8.12 (d, 1H), 8.30 (d, 1H).

ERI-Mass: 514 [M ⁺ + H].

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 184.

Example 373

5- (2-Benzoxazolyl) -3- [2- (2-benzoxazolyl) phenyl] -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.42 (m, 7H), 7.44-7.73 (m, 9H), 8.26 (d , 1H), 8.34 (d, 1H), 8.48 (d, 1H).

ERI-Mass: 482 [M ⁺ + H].

Example 374

3- (2-Benzoxazolyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.28 (m, 1H), 7.29-7.32 (m, 2H), 7.42-7 46 (m, 2H), 7.48-7.50 (m, 3H), 7.54-7.58 (m, 1H), 7.70-7.80 (m, 3H), 8.55 -8.60 (m, 2H); 9.03 (d, 1H).

ERI-Mass: 366 [M ⁺ + H].

Example 375

3- (2-Chlorophenyl) -5- (5-chlorobenzoxazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.27-7.35 (m, 3H), 7.41-7.51 (m, 4H), 7.52-7 57 (m, 4H), 7.67 (d, 1H), 8.25 (d, 1H), 8.49 (d, 1H).

ERI-Mass: 433 [M ⁺ + H].

Example 376

3- (5-Chlorobenzoxazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.26 (ddd, 1H), 7.33 (dd, 1H), 7.47-7.58 (m, 6H), 7.72 (dt, 1H), 7.79 (d, 1H), 7.79 (td, 1H), 8.55 (d, 1H), 8.62 (ddd, 1H), 9.12 (d , 1H).

ERI-Mass: 340 [M ⁺ + H].

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 315.

Example 377

3- [1- (piperidin-4-yl) benzimidazol-2-yl] -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.01-2.15 (m, 2H), 2.42-2.52 (m, 2H), 2.66-2 84 (m, 2H), 3.20-3.30 (m, 2H), 4.21-4.40 (m, 1H), 7.19-7.83 (m, 12H), 8.49 (d, 1H), 8.52 (d, 1H), 8.56-8.59 (m, 1H).

ERI-Mass: 448 [M ⁺ + H].

Example 378

(378A) 3- (2-Cyanophenyl) -5- [1- (piperidin-4-yl) benzimidazol-2-yl] -1-phenyl-1,2-dihydropyridin-2-one

(378B) 3- (2-Cyanophenyl) -5- [1- (1-methylpiperidin-4-yl) benzimidazol-2-yl] -1-phenyl-1,2-dihydropyridin-2-one

(378A)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.90-2.02 (m, 2H), 2.65 (ddd, 2H), 3.01 (t, 2H), 3.28 (d, 2H), 4.69 (tt, 1H), 7.27-7.29 (m, 2H), 7.47-7.55 (m, 6H), 7.67 (td, 1H), 7.71 (d, 1H), 7.67-7.83 (m, 4H), 8.05 (d, 1H).

ERI-Mass: 472 [M ⁺ + H].

(378V)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.90-2.00 (m, 2H), 2.35-2.40 (m, 2H), 2.41 (s , 3H), 2.73-2.87 (m, 2H), 3.00-3.10 (m, 2H), 4.51-4.62 (m, 1H), 7.26-7.30 (m, 2H), 7.44-7.54 (m, 6H), 7.65 (td, 1H), 7.70-7.83 (m, 5H), 8.03 (d, 1H).

ERI-Mass: 486 [M ⁺ + H].

Example 379

(379A) 3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (piperidin-3-yl) -1,2-dihydropyridin-2-one

(379B) 3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (N-benzylpiperidin-3-yl) -1,2-dihydropyridin-2-one

(379A)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.90-2.05 (m, 2H), 2.13-2.22 (m, 1H), 2.35-2 44 (m, 1H), 2.70 (td, 1H), 3.05-3.12 (m, 1H), 3.37 (d, 1H), 3.60-3.72 (m, 1H) ), 4.97-5.05 (m, 1H), 7.21 (ddd, 1H), 7.45 (td, 1H), 7.57 (d, 1H), 7.64 (td, 1H) 7.68-7.78 (m, 3H), 8.13 (d, 1H), 8.48 (d, 1H), 8.62 (ddd, 1H).

ERI-Mass: 357 [M ⁺ + H].

(379V)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.65-1.75 (m, 2H), 1.92-2.05 (m, 2H), 2.45-2 60 (m, 2H), 2.70-2.80 (m, 1H), 2.97 (dd, 1H), 3.55 (s, 2H), 5.15-5.20 (m, 1H) ), 7.22 (ddd, 1H), 7.27-7.32 (m, 1H), 7.40-7.49 (m, 4H), 7.52-7.58 (m, 2H), 7.61-7.77 (m, 5H), 8.15 (d, 1H), 8.65 (ddd, 1H).

ERI-Mass: 447 [M ⁺ + H].

Example 380

3- (2-cyanophenyl) -5- (N-methylpiperidin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.24-1.39 (m, 2H), 1.73-1.85 (m, 2H), 2.04-2 14 (m, 3H), 2.16 (s, 3H), 2.63 (dd, 1H), 3.00 (d, 1H), 7.37-7.56 (m, 5H), 7, 59 (td, 1H), 7.64-7.70 (m, 2H), 7.72-7.74 (m, 1H), 7.74-7.76 (m, 2H).

ERI-Mass: 370 [M ⁺ + H].

The following compound is synthesized in a manner analogous to the method of example 7.

Example 381

3- (2-Cyanophenyl) -5- (2-pyridyl) -1- (3-nitro-4-methylphenyl) -1,2-dihydropyridin-2-one

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.69 (s, 3H), 7.23-7.28 (m, 1H), 7.48 (td, 1H), 7.51-7.56 (m, 1H), 7.62 (d, 1H), 7.66 (t, 1H), 7.74-7.81 (m, 4H), 8.21 (d, 1H), 8.30 (d, 1H), 8.32 (d, 1H), 8.61 (d, 1H).

Example 382

(382A) 3- (4-Chlorobenzenesulfinyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

(382B) 3- (4-Chlorobenzenesulfonyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

6 mg of 3- (4-chlorophenylthio) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 3 ml of dichloromethane. Under ice cooling, 3 mg of m-chloroperbenzoic acid was added thereto, followed by stirring at the same temperature for 30 minutes. After stirring at room temperature for 5 hours, the mixture was diluted with 10 ml of ethyl acetate and washed with a 1N aqueous sodium hydroxide solution. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 1.2 mg of 3- (4-chlorobenzenesulfinyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one and 1.5 mg of 3- (4-chlorobenzenesulfonyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one as the title compounds.

(382A)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.29 (m, 2H), 7.37-7.54 (m, 6H), 7.72 (dt) , 1H), 7.79 (td, 1H), 7.87 (t, 1H), 7.89 (t, 1H), 8.44 (d, 1H), 8.57-8.60 (m, 1H), 8.69 (d, 1H).

ERI-Mass: 407 [M ⁺ + H].

(382V)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.30 (m, 2H), 7.37-7.40 (m, 2H), 7.42-7 52 (m, 4H), 7.67 (dt, 1H), 7.80 (td, 1H), 8.09 (t, 1H), 8.11 (t, 1H), 8.58 (d, 1H), 8.60 (ddd, 1H), 9.06 (d, 1H).

ERI-Mass: 423 [M ⁺ + H].

The following compounds are synthesized by methods analogous to, or in accordance with the method of example 382.

Example 383

(383A) 3- (2-Ethylsulfinylpyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

(383B) 3- (2-Ethylsulfonylpyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

(383A)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.24 (t, 3H), 2.96 (dt, 1H), 3.21 (dt, 1H), 7.23- 7.27 (m, 1H), 7.48-7.58 (m, 5H), 7.60 (d, 1H), 7.77 (td, 1H), 8.03 (d, 1H), 8 28 (d, 1H), 8.38 (d, 1H), 8.44 (dd, 1H), 8.64 (ddd, 1H), 9.04 (d, 1H).

ERI-Mass: 402 [M ⁺ + H].

(383V)

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.33 (t, 3H), 3.44 (q, 2H), 7.25-7.28 (m, 1H), 7.49-7.62 (m, 6H), 7.78 (dd, 1H), 8.14 (d, 1H), 8.31 (d, 1H), 8.41 (d, 1H), 8 51 (dd, 1H), 8.64 (ddd, 1H), 9.13 (d, 1H).

ERI-Mass: 418 [M ⁺ + H].

Example 384

3- (2-Ethylpyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

13 mg of 3- (2-chloropyridin-5-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 20 ml of dimethylformamide followed by 10 mg of potassium carbonate and 2 mg tetrakistriphenylphosphine palladium. While stirring at room temperature in a nitrogen atmosphere, triethylborane (1.0 M solution in tetrahydrofuran) is added dropwise thereto, followed by heating with stirring at 100 ° C. for 1 hour in a nitrogen atmosphere. After the reaction mixture was cooled to room temperature, water was added thereto and extracted with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 4 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.33 (t, 3H), 2.87 (q, 2H), 7.20-7.24 (m, 2H), 7.44-7.60 (m, 5H), 7.64-7.70 (m, 1H), 7.75 (td, 1H), 8.18 (dd, 1H), 8.25 (d, 1H), 8.26 (d, 1H), 8.60-8.62 (m, 1H), 8.84 (d, 1H).

Example 385

3- (2-Chlorophenyl) -5- (4-chlorophenylthio) -1- (3-pyridyl) -1,2-dihydropyridin-2-one

The title compound was synthesized in a manner analogous to the method of Example 188.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23-7.50 (m, 8H), 7.52 (d, 1H), 7.55-7.58 (m , 1H), 7.72 (d, 1H), 7.86-7.93 (m, 1H), 8.66-8.76 (m, 2H).

Example 386

3- (2-cyanophenyl) -5- (1H-benzimidazol-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

The above compound is synthesized in a manner analogous to the method of example 190.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.22-7.28 (m, 2H), 7.32-7.50 (m, 7H), 7.54-7 76 (m, 4H), 8.20-8.21 (m, 1H), 8.28-8.34 (m, 1H).

ERI-Mass: 389 [M ⁺ + H].

Example 387

3- (2-Adamantyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

The above compound is synthesized in a manner analogous to the method of example 178.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.21-2.06 (m, 12H), 2.48 (s, 2H), 3.25 (s, 1H), 7.18 (ddd, 1H), 7.33-7.52 (m, 5H), 7.54 (d, 1H), 7.72 (td, 1H), 8.09 (d, 1H), 8 11-8.13 (m, 1H); 8.60 (ddd, 1H).

Example 388

3- (2-Cyanophenyl) -5- (4-methylimidazo [4,5-b] pyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one

3 mg of 3- (2-cyanophenyl) -5- (1H-imidazo [4,5-c] pyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 3 ml of acetone. To the mixture was added 2 ml of methyl iodide, followed by stirring at room temperature overnight. The mixture was evaporated and the residue was diluted with 1 ml of water. 20 mg of sodium hydroxide was added to the mixture, followed by stirring at room temperature for 4 hours. The reaction solution was extracted with ethyl acetate, the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and the residue was purified by silica gel chromatography (NH-silica gel) (hexane / ethyl acetate) to obtain 2 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.31 (s, 3H), 7.07 (dd, 1H), 7.43-7.61 (m, 7H), 7.64 (td, 1H), 7.72 (dd, 1H), 7.76 (dd, 1H), 8.09 (d, 1H), 8.71 (d, 1H), 8.73 (d , 1H).

ERI-Mass: 404 [M ⁺ + H].

Example 389

3- (2-cyanophenyl) -1-phenyl-5- (3-phenyl-1,2,4-oxadiazol-5-yl) -1,2-dihydropyridin-2-one

31 mg of a carboxylic acid obtained by hydrolysis of 3- (cyanophenyl) -5- (methoxycarbonyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 20 ml of dichloromethane, followed by the dropwise addition of a solution of 20 mg of oxalyl chloride in dichloromethane at ice cooling. A catalytic amount of dimethylformamide was added to the mixture, followed by stirring at room temperature for 1 hour under a nitrogen atmosphere. The reaction solution was evaporated and the residue was dissolved in dichloromethane. The mixture was added dropwise to a solution of 16 mg of benzamidoxime and 0.05 ml of triethylamine in toluene under ice cooling. After warming to room temperature, the mixture was stirred under nitrogen overnight. The reaction mixture was heated to 100 ° C for 1 hour, cooled to room temperature and then washed with water. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and 28 mg of the residue was dissolved in 10 ml of toluene, followed by heating under reflux for 5 hours. After cooling to room temperature, the solvent was evaporated, yielding 24 mg of the title compound as white crystals.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.40-7.66 (m, 9H), 7.68 (dd, 2H), 7.80 (dd, 1H), 8.12 (dd, 2H), 8.32 (dd, 1H), 8.52 (dd, 1H).

Example 390

3- (3-Phenyl-1,2,4-oxadiazol-5-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

The above compound is synthesized in a manner analogous to the method of example 389.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.25-7.29 (m, 2H), 7.46-7.59 (m, 7H), 7.70 (d , 1H), 7.81 (td, 1H), 8.20-8.23 (m, 2H), 8.59 (d, 1H), 8.63 (ddd, 1H), 9.14 (d, 1H).

Example 391

3- (2-Cyanothiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

22 mg of 3- (2-formylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 20 ml of ethanol. To the mixture were added 6.4 mg of hydroxylamine hydrochloride and 10.1 mg of sodium acetate, followed by heating at 80 ° C for 3 hours. After the reaction mixture was cooled to room temperature, it was poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue (25 mg) obtained as an oxime compound was dissolved in 10 ml of dimethylformamide followed by the addition of 0.02 ml of triethylamine. Under ice cooling, 43 mg of 1,1'-carbonyldiimidazole was added thereto, followed by stirring at 60 ° C. for 1 hour. The mixture was then cooled to room temperature, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 15 mg of the title compound as white crystals.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.23 (ddd, 1H), 7.46-7.58 (m, 5H), 7.59 (d, 1H), 7.65 (d, 1H), 7.77 (td, 1H), 7.78 (d, 1H), 8.38 (d, 1H), 8.57 (d, 1H), 8.59 (ddd , 1H).

ERI-Mass: 356 [M ⁺ + H].

Example 392

3- [2- (5-Oxazolyl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

13 mg of 3- (2-formylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one is dissolved in 10 ml of methanol. 11 mg of tosylmethyl isocyanide and 8 mg of potassium carbonate were added to the mixture, followed by heating under reflux overnight. After the reaction mixture was cooled to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate, filtered through NH-silica gel and silica gel, and the filtrate was evaporated. The resulting precipitate was washed with ether and dried, yielding 9 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.98 (s, 1H), 7.20 (ddd, 1H), 7.36-7.51 (m, 7H), 7.54 (dt, 2H), 7.72 (ddd, 2H), 7.84 (s, 1H), 8.11 (d, 1H), 8.30 (d, 1H), 8.59 (ddd , 1H).

Example 393

3- [2- (5-Oxazolyl) thiophen-3-yl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one

The title compound was synthesized in a manner analogous to the method of Example 392.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.14 (s, 1H), 7.16-7.76 (m, 10H), 7.82 (s, 1H), 8.16 (d, 1H), 8.29 (d, 1H), 8.58 (d, 1H).

Example 394

3- (2-cyanophenyl) -5- (2-pyridinecarbonyl) -1-phenyl-1,2-dihydropyridin-2-one

(394a) α- (2-Methoxypyridin-5-yl) -2-pyridinomethanol

50 ml of a tetrahydrofuran solution containing 3.00 g of 2-methoxy-5-bromopyridine are cooled to -78 ° C, followed by dropwise addition of 10 ml of n-butyllithium (1.6 M solution in hexane). After completion of the dropwise addition of n-butyllithium, 1.70 g of picoline aldehyde was immediately added thereto, followed by stirring at -78 ° C for 1 hour, after which the mixture was slowly returned to room temperature. A saturated aqueous solution of ammonium chloride was added to the mixture, and then it was extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, and then dried over magnesium sulfate. The solvent was evaporated and the resulting residue was purified by silica gel chromatography (ethyl acetate) to obtain 1.53 g of the title compound as a pale yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.93 (s, 3H), 5.87 (ss, 1H), 6.72 (d, 1H), 7.24 ( d, 1H), 7.31-7.36 (m, 1H), 7.55-7.59 (m, 1H), 7.74-7.80 (m, 1H), 8.21 (d, 1H), 8.62 (d, 1H).

(394b) 5- (2-Pyridinecarbonyl) -2-methoxypyridine

To a solution of 0.83 g of α- (2-methoxypyridin-5-yl) -2-pyridinomethanol in 20 ml of acetone was added 1.70 g of activated manganese dioxide, followed by vigorous stirring at room temperature for 30 minutes. The precipitate obtained is filtered off and washed with acetone. The filtrate was then concentrated, yielding 0.80 g of the title compound as a white solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.04 (s, 3H), 6.84 (dd, 1H), 7.48-7.54 (m, 1H), 7.89-7.95 (m, 1H), 8.09 (d, 1H), 8.36-8.40 (m, 1H), 8.70-8.74 (m, 1H), 9, 09 (d, 1H).

(394s) 5- (2-Pyridinecarbonyl) -1,2-dihydropyridin-2 (1H) -one

0.79 g of 5- (2-pyridinecarbonyl) -2-methoxypyridine is dissolved in 5.0 ml of 48% hydrobromic acid and the mixture is stirred at 70 ° C. for 30 minutes. The mixture is cooled with ice, diluted with water and neutralized with potassium carbonate. The resulting precipitate was collected by filtration, washed with water and hexane, and dried, yielding 0.51 g of the title compound as a white powder.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 6.45 (d, 1H), 7.65-7.70 (m, 1H), 7.95-8.00 (m, 1H), 8.05-8.20 (m, 2H), 8.68-8.75 (m, 2H), 12.17 (br, 1H).

(394d) 5- (2-Pyridinecarbonyl) -3-bromo-1,2-dihydropyridin-2 (1H) -one

To a solution of 0.23 g of 5- (2-pyridinecarbonyl) -1,2-dihydropyridin-2 (1H) -one in 2.0 ml of dimethylformamide, 0.21 g of N-bromosuccinimide was added at room temperature, followed by stirring for 1 hour . The mixture was diluted with water and the resulting precipitate was collected by filtration, washed with water and dried, yielding 0.26 g of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.67-7.71 (m, 1H), 7.99-8.03 (m, 1H), 8.04 -8.08 (m, 1H), 8.47 (d, 1H), 8.73-8.75 (m, 1H), 8.79 (br, 1H), 12.72 (br, 1H).

(394e) 5- (2-Pyridinecarbonyl) -1-phenyl-3-bromo-1,2-dihydropyridin-2-one

A suspension of 0.24 g of 5- (2-pyridinecarbonyl) -3-bromo-1,2-dihydropyridin-2 (1H) -one, 0.23 g of phenylboronic acid, 0.30 g of copper acetate and 1 ml of triethylamine in 10 ml tetrahydrofuran was stirred at room temperature overnight. Concentrated aqueous ammonium (3 ml), water (30 ml) and ethyl acetate (100 ml) were added to the mixture to separate an organic layer. It is washed with water and brine, and then dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 0.21 g of the title compound as a white powder.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.50-7.60 (m, 5H), 7.64-7.68 (m, 1H), 8.02 -8.09 (m, 1H), 8.57 (d, 1H), 8.66-8.70 (m, 1H), 9.00 (d, 1H).

(394f) 3- (2-Cyanophenyl) -5- (2-pyridinecarbonyl) -1-phenyl-1,2-dihydropyridin-2-one

To the stirred liquid 200 mg of 5- (2-pyridinecarbonyl) -1-phenyl-3-bromo-1,2-dihydropyridin-2-one, 130 mg of 2- (2-cyanophenyl) -1,3,2-dioxaborinate, 400 mg of cesium carbonate and 6 ml of dimethylformamide add 60 mg of tetrakistriphenylphosphine palladium, followed by stirring at 130 ° C for 5 hours in a nitrogen atmosphere. After cooling to room temperature, ethyl acetate was added thereto. The extract was washed with water and brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 45 mg of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.40-7.58 (m, 8H), 7.62-7.68 (m, 1H), 7.75-7 78 (m, 1H), 7.89-7.94 (m, 1H), 8.11-8.25 (m, 1H), 8.47 (d, 1H), 8.65-8.68 (m, 1H), 9.16 (d, 1H).

Example 395

5- (2-Pyridinecarbonyl) -1-phenyl-3-phenyl-1,2-dihydropyridin-2-one

A mixed liquid of 10 mg of 5- (2-pyridinecarbonyl) -1-phenyl-3-bromo-1,2-dihydropyridin-2-one, 10 mg of phenylboronic acid, 40 mg of cesium carbonate, 6 mg of tetrakistriphenylphosphine palladium and 1 ml of dimethylformamide is stirred at 130 ° C for 2 hours in a nitrogen atmosphere. After cooling to room temperature, ethyl acetate was added thereto. The extract was washed with water and brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 6 mg of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.32-7.58 (m, 8H), 7.75-7.79 (m, 2H), 7.88-7 94 (m, 1H), 8.09-8.13 (m, 1H), 8.42 (d, 1H), 8.63-8.66 (m, 1H), 9.01 (d, 1H) )

Example 396

3- (2-cyanophenyl) -5- (α-hydroxy-2-picolyl) -1-phenyl-1,2-dihydropyridin-2-one

To a solution of 25 mg of 3- (2-cyanophenyl) -5- (2-pyridinecarbonyl) -1-phenyl-1,2-dihydropyridin-2-one in 5 ml of methanol was added 2 mg of sodium borohydride under ice-cooling. After 30 minutes, the mixture was diluted with saturated aqueous sodium hydrogen carbonate, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water and brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate) to obtain 15 mg of the title compound as a pale yellow powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 5.72 (br s, 1H), 7.32-7.72 (m, 13H), 7.80-7.92 (m , 1H); 8.57-8.65 (m, 1H).

Example 397

3- (2-Cyanophenyl) -5- (2-pyridin-2-yl-vinyl) -1-phenyl-1,2-dihydropyridin-2-one

Mixed liquid 100 mg 3- (2-cyanophenyl) -1-phenyl-5-bromo-1,2-dihydropyridin-2-one, 100 mg 2-vinylpyridine, 6 mg palladium acetate, 17 mg tri- (o-tolyl) phosphine and 3 ml of triethylamine are stirred at 130 ° C for 2 hours in a nitrogen atmosphere. After cooling to room temperature, ethyl acetate was added thereto. The extract was washed with water and brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (ethyl acetate / hexane) to obtain 16 mg of the title compound as a white powder.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 6.95-7.00 (m, 1H), 7.16-7.21, (m, 1H), 7.26- 7.35 (m, 1H), 7.44-7.60 (m, 7H), 7.62-7.81 (m, 5H), 8.03 (d, 1H), 8.57-8, 61 (m, 1H).

Example 398

3- (2-Ethoxycarbonylvinylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one

To a solution of 7.5 mg of ethyl diethylphosphonoacetate in tetrahydrofuran was added 1.3 mg of sodium hydride in a nitrogen atmosphere under ice-cooling, followed by the dropwise addition of a solution of 10 mg of 3- (2-formylthiophen-3-yl) -5- (2-pyridyl) - 1-phenyl-1,2-dihydropyridin-2-one in tetrahydrofuran. After the mixture was stirred at room temperature for 1 hour under nitrogen, water was added thereto. Then it is extracted with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel chromatography (hexane / ethyl acetate) to obtain 4 mg of the title compound.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 1.28 (t, 3H), 4.21 (q, 2H), 6.34 (d, 1H), 7.19 - 7.23 (m, 2H), 7.34-7.41 (m, 2H), 7.43-7.56 (m, 5H), 7.74 (td, 1H), 7.88 (d, 1H), 8.00 (d, 1H), 8.30 (d, 1H), 8.58-8.60 (m, 1H).

ERI-Mass: 429 [M ⁺ + H].

Example 399

5-bromo-2-methoxypyridine

2,5-Dibromopyridine (200 g) and a 28% methanol solution of sodium methoxide (1535 g) are heated at the boil under reflux for 30 minutes, followed by cooling to room temperature. The mixture was partitioned between water (1.6 L) and tert-butyl methyl ether (1.6 L). The resulting organic layer was washed with brine (1 L) 3 times and then dried over anhydrous magnesium sulfate overnight. The dried organic layer was evaporated at 65 ° C to give 160 g (96%) of the title compound as a brown oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.91 (3H, s), 6.66 (1H, d), 7.64 (1H, dd), 8.20 ( 1H, d).

MS: MH ⁺ 188, 190.

Example 400

6-methoxy-3-pyridylboronic acid

5-Bromo-2-methoxypyridine (152 g) was dissolved in anhydrous tetrahydrofuran (1520 ml) with stirring in a nitrogen atmosphere, followed by cooling to -75.1 ° C as the average mass temperature. While cooling and stirring, 380 ml of a 2.46 mol / L butyl lithium solution are added dropwise to this mass, followed by dropwise adding 192 ml of trimethoxyborane. The cooling bath was removed 30 minutes after completion of the dropwise addition of trimethoxyborane and the mixture was stirred at room temperature overnight. The next day, 1.5 L of a 2 mol / L aqueous solution of hydrochloric acid was added to the mixture, followed by stirring for 1.5 hours. Then it is neutralized with 460 ml of an aqueous solution of sodium hydroxide with a concentration of 5 mol / L. The mixture was then extracted with 1 L of ethyl acetate and the resulting aqueous layer was again extracted with 1 L of ethyl acetate. The combined organic layer was washed twice with 1 L of 10% salt water, dried over anhydrous magnesium sulfate and then evaporated to give 105 g (88%) of the title compound as a slightly yellowish white solid.

¹ H-NMR (CDCl ₃ , 400 MHz): 3.83 (3H, s), 6.74 (1H, d), 7.98 (1H, dd), 8.10 (2H, s), 8, 50 (1H, s).

Example 401

2-Methoxy-5- (pyridin-2-yl) -pyridine

6-Methoxy-3-pyridylboronic acid (105 g), 2-bromopyridine (90 g), palladium acetate (3.21 g), triphenylphosphine (15 g), potassium carbonate (237 g), 1,2-dimethoxyethane (900 ml) and water (900 ml) are heated at the boil under reflux for 5 hours and 40 minutes with stirring. After cooling the reaction solution, ethyl acetate (1 L) was added thereto to extract. The organic layer was washed with 1 L of a 10% aqueous solution of ammonium chloride, 1 L of 10% aqueous ammonia and 1 L of 10% saline and then evaporated, to give 126 g (87%) of the title compound.

¹ H-NMR (CDCl ₃ , 400 MHz): 4.00 (3H, s), 6.85 (1H, d), 7.21-7.26 (1H, m), 7.67 (1H, d ), 7.75 (1H, dt), 8.25 (1H, dd), 8.66-8.70 (1H, m), 8.74 (1H, d).

MS: MH ⁺ 187.

Example 402

5- (Pyridin-2-yl) -2 (1H) -pyridone

A mixture of 2-methoxy-5- (pyridin-2-yl) -pyridine (550 g) and 4 mol / L aqueous hydrochloric acid (2.4 L) was heated under reflux for 3 hours. After the reaction solution was cooled, it was washed with tert-butyl methyl ether (2.2 L). An 8 mol / L sodium hydroxide aqueous solution (1.1 L) was added to the aqueous layer while cooling with ice / water, and then the mixture was washed twice with tert-butyl methyl ether (2.2 L). The mixture was then adjusted to pH 8 with concentrated hydrochloric acid (310 ml) and 8 mol / L aqueous sodium hydroxide (100 ml), followed by partitioning the mixture between 1-butanol (4.5 L) and brine (1.8 L) . The aqueous layer was extracted again with 1-butanol (4.5 L) and the combined organic layer was evaporated at 45-50 ° C. Tert-butyl methyl ether (2.2 L) was added to the resulting residue to give crystals. The resulting crystals were collected by filtration under reduced pressure and air dried at 60 ° C. Then water (1.6 L) is added thereto to dissolve when heated. Then the mixture is cooled with water and recrystallized. The resulting crystals were collected by filtration under reduced pressure and air dried at 60 ° C to obtain 188 g (66%) of the title compound as grayish-white crystals.

¹ H-NMR (DMSO-d ₆ , 400 MHz): 6.42 (1H, d), 7.19-7.26 (1H, m), 7.74-7.81 (2H, m), 8 11 (1H, d), 8.17 (1H, dd), 8.52-8.55 (1H, m).

MS: MH ⁺ 173.

Example 403

1-Phenyl-5- (pyridin-2-yl) -2 (1H) -pyridone

Mixing a mixture of 5- (pyridin-2-yl) -2 (1H) -pyridone (185 g), phenylboronic acid (261 g), copper acetate (19.4 g), pyridine (173 ml) and dimethylformamide (1480 ml) at room temperature, air is blown through it at a speed of 2.0 L per minute to initiate reactions. Since 7% after the initiation of the reaction, 26% of the reagent remains unreacted, the air flow is stopped to suspend the reaction. The next day, to resume the reaction, air was again passed into the solution and after 5.5 hours the reagent was consumed to 0.57% of the initial mass. The reaction solution was poured into ice-cooled 10% aqueous ammonia (7.5 L) to obtain a precipitate. The resulting precipitate was collected by filtration under reduced pressure and washed with water (3 L). The resulting crystals were suspended in 10% aqueous ammonia (3.6 L) with stirring at room temperature for 1 hour. Then, the crystals were collected by filtration under reduced pressure and washed with water (2 L). The resulting crystals were dried in air overnight to obtain 187 g (68%) of the title compound as brown crystals.

¹ H-NMR (CDCl ₃ , 400 MHz): 6.77 (1H, d), 7.19 (1H, dd), 7.42-7.48 (3H, m), 7.49-7.55 (3H, m), 7.72 (1H, dt), 8.04 (1H, dd), 8.21 (1H, d), 8.57-8.59 (1H, m).

MS: MH ⁺ 249.

Example 404

3-Bromo-1-phenyl-5- (pyridin-2-yl) -2 (1H) -pyridone

1-Phenyl-5- (pyridin-2-yl) -2 (1H) -pyridone (186 g), N-bromosuccinimide (141.7 g) and N, N-dimethylformamide (900 ml) were stirred at room temperature. After 2.5 hours, 6.45 g of N-bromosuccinimide was added thereto. After confirming the complete consumption of the reagent, the reaction solution was poured into water (4.5 L) under ice cooling, followed by stirring in a cold room (approximately 4 ° C) overnight. The resulting crystals were collected by filtration under reduced pressure, followed by dissolution in isopropanol (3.25 L) and water (650 ml) under heating. After confirming the completion of dissolution, the solution was allowed to cool gradually and then cooled with ice. The mixture was then stirred in a cold room overnight. The resulting crystals were collected by filtration under reduced pressure and air dried at 60 ° C to give 191 g (81%) of the title compound.

¹ H-NMR (CDCl ₃ , 400 MHz): 7.19-7.24 (1H, m), 7.42-5.56 (6H, m), 7.74 (1H, dt), 8.19 (1H, d), 8.51 (1H, d), 8.58-8.61 (1H, m).

MS: MH ⁺ 327, 329.

Among the above examples, particularly preferred compounds include 3- (2-cyanophenyl) -5- (2-methylsulfonylaminophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chloro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitrophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-dimethylaminophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- [3- (5-methoxymethyl-2-oxazolidinon-3-yl) phenyl] -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxycarbonylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminocarbonylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyano-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-hydroxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-formylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-hydroxymethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-cyanomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetylaminomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetoxymethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylthiophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylsulfonylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-formylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-diethylaminomethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-hydroxymethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1-benzyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5-phenyl- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1,5-diphenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-methoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (3,4-dimethoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (thiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-fluorophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (thiophen-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (3-furyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-furyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-methoxycarbonylphenyl) -5- (2-pyridyl) -1-phenyl- 1,2-dihydropyridin-2-one; 3-phenyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-fluorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-methoxy-5-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one; 3-phenyl-5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1, 2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-formylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-formylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-chlorophenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-tolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-trifluoromethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (thiophen-3-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-furyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-tolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-trifluoromethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (pyrimidin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-benzyloxymethylpyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-ethylthiopyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-chloropyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-fluoropyridin-5-yl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-methoxyphenyl) -1,2-dihydropyridin-2-one; 3-phenyl-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (thiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2,6-dimethylphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanothiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-hydroxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminopropoxyphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-hydroxymethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-cyanomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-cyanomethylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (6-diethylaminomethyl-2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-hydroxypyridin-6-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- (2-aminobenzothiazol-6-yl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-benzyl-1,2,5,6-tetrahydropyridin-5-yl) -1,2-dihydropyridin-2-one; 3- [2- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (6-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (5-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (3-hydroxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1-phenyl-5- (2-thiazolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (6-methoxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one; 1- (4-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- (3-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-amino-4-methylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-dimethylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-piperidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-pyrrolidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-diisopropylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- [3- (4-piperidinobutoxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (4-nitrophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1-phenyl-5- (2-pyridyl) -3- (2-thiazolyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-pyridyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-fluoropyridin-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-cyanopyridin-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-nitrophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one; 3- (2-nitrophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-formylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-naphthyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-naphthyl) -1,2-dihydropyridin-2-one; 5- (2-aminopyridin-6-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 5- (6-bromopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-morphorinopyridin-6-yl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- (3-hydroxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- [3- (4-piperidyloxy)] phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- [3- (N-acetylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -1- [3- (1- (methylsulfonylpiperidin-4-yl-hydroxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 1- [3 - (N-methylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- (6-chloro-1H- benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one; 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3- nitro-4-methylphenyl) -1,2-dihydropyridin-2-one; 3- (2-cyanothiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one ; 3- [2- (5-oxazolyl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one; 3- [2- (5-oxazolyl) thiophen-3- yl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one and 3- (2-ethoxycarbonylvinylthiophen-3-yl) -5- (2 -pyridyl) -1-phenyl-1,2-dihydropyridin-2-one.

Test Example 1

The inhibitory effect of the compounds of the present invention on calcium intake into nerve cells induced by AMPA was investigated using the primary culture system of nerve cells of the cerebral cortex of a rat embryo.

Cultivation conditions

The cerebral cortex was dissected from a rat brain with a gestational age of 18 days and treated with trypsin and DNase to disperse the cells. Cells were collected using MPS (MEM) containing 10% serum, seeded in a culture vial, in which the propagation of astrocytes was carried out. Astrocytes are redispersed with trypsin and plated in a 96-well plate. After incubation for one week, having received confirmation that the astrocytes covered the entire bottom, then the nerve cells of the cerebral cortex, which were dispersed in the aforementioned manner, were seeded. After incubation for 24 hours, the medium is replaced, the incubation is carried out for one week, and then the medium is replaced with a medium containing 1 μM MK-801. Use nerve cells that have been incubated for at least 8-10 days.

AMPA-inhibitory effect on calcium intake into nerve cells

Calcium uptake into nerve cells was measured using Fura2-AM, which was a calcium sensitive fluorescent dye. The dye was treated in a medium containing Fura2-AM for 1 hour, included in the cells, replaced with a Tyrode solution containing 1 μM MK-801, and stimulation was performed using 2 μM AMPA. The change in the amount of calcium entering the cells was determined by the change in fluorescence intensity at an excitation wavelength of 340/380 nm. The effect of the test compound was evaluated using, as a control, the reaction caused by the addition of AMPA to the Tyrode solution containing no compound. The results are presented in table 2.

GYKI 52446 (Le Peillet, et al., Brain Res., 571, 115, 1992) was used as a control compound. IR ₅₀ (IC ₅₀ ) For GYKI 52466 was 9.02 μM.

Test Example 2

AMPA anticonvulsant effect

The test compound was suspended in a 0.5% methylcellulose solution or in sesame oil and was administered orally (25 mg / kg) to mice of the male ddy strain. 30 minutes or 1 hour after oral administration, AMPA was continuously injected (2 nmol / 5 μl / minute / mouse) into the lateral ventricle to induce convulsions. The effect was evaluated by the time period of action, during which convulsions did not stop with continuous injection of AMPA.

results

The compound represented by the above formula (I) in accordance with the invention exhibits a strong anticonvulsant effect. For example, the compounds of examples 4, 7, 9, 12, 16, 32, 41, 47, 57, 61, 76, 78, 91, 126, 128, 137, 139, 164, 199, 261, 262, 264, 270 and 298 demonstrate a significant significant anticonvulsant effect.

Test Example 3

Midbrain Artery Occlusion Model

The usefulness of the compound related to the invention for the treatment of the acute stage of cerebral vascular disorder has been confirmed by the test described below. Namely, the cerebral (cerebral) blood flow of the arteries of the midbrain was blocked by inserting a 4-0 specification nylon suture, the edge of which was flame treated, 17 mm from the branch of the internal carotid artery, through the internal carotid artery to the external carotid artery of the male rat strain Sprange Dawley, and a cerebral infarction was simulated (Zea Longa et al., Storke 20: 84-91, 1989). The size of the necrosis zone of the brain tissue was evaluated by obtaining sections of the brain tissue having a thickness of 2 mm and measuring the area of the area that was not stained when stained with TTC. The effect of the test substance was evaluated using this model by comparing the size of the necrosis zone in the group treated with the solvent and the group treated with the test substance.

As a result, it was found that the claimed compound exhibits excellent action as a therapeutic agent in the acute stage of cerebral vascular disorder.

Test Example 4

Antisympathomimetic effect

(S) - (+) - N, α-dimethylphenethylamine (hereinafter referred to as "methamphetamine") is administered by intraperitoneal injection of a rat or mouse that have been subjected to the test compound, and the amount of active movement is evaluated using an apparatus for measuring active movement ( SCANET SV-10; manufactured by TOYO Sangyo Co., Ltd.). The activity of the compound as a therapeutic agent for schizophrenia was evaluated using methamphetamine-induced regulation of active movement in the direction of its hyperdynamic manifestation (K.E. Vanover, Psychopharmacology 136; 123-131, 1998). It was found that the test substance has a regulatory effect on the amount of active movement shown in comparison with the control group receiving the solvent.

As a result, the claimed compound showed an excellent antisympathomimetic effect.

Test Example 5

Muscle Stiffness Model Due to External Exposure

On the animal model, myotonia of the muscles of the anteroposterior extremities of the rat was obtained by electro-freezing. The effect of muscle relaxation was assessed by the controlling effect of increasing muscle contraction, which is generated when the mobility of the hind limbs of the rat returns back and forth. The action of the test substance is confirmed by changes in the number of muscle contractions manifested before the administration of the test compound and after its administration.

The compound of the present invention has an excellent muscle relaxation effect.

Test Example 6

Light darkness test

The mouse is placed in a dark boxing unit, which consists of two lighted and dark blocks connected by a tunnel, and after that, the mouse behavior is recorded for 5 minutes according to the points below.

1. Time spent in lighted and dark blocks.

2. The time during which the mouse moved between the lighted and dark blocks.

3. The time during which the mouse moved before entering the light block.

An alarming effect of the test compound was found, manifested in prolongation of the time spent in the light and dark blocks, an increase in the time during which the mouse cruised between the light and dark blocks, and in an increase in the time during which the mouse moved before entering the light block, comparison with the control group receiving the solvent (Hascoet M., Bourin M., Pharm. Biochem. Behav. 60: 645-653, 1998).

According to the present test, confirmation has been obtained that the compound related to the present invention has an excellent sedative effect.

Test Example 7

The destruction model of 6-hydroxidopamine-inductive nigrosis

10 mg / kg L-dihydroxyphenylalanine (L-DOPA) (twice daily) is administered intraperitoneally to a rat every day, one side of which neurocyte nigra was destroyed by injection of 6-hydroxydopamine (6-OHDA) in nigra, resulting in an increase in rotational movement in the opposite direction of encephalopathy (C. Marin et al., Synapse 36 (4): 267-274, 2000). After administration of a dose of a solvent or test compound to a rat, the effect of this treatment on the induced rotational movement is examined. The test compound slowed down the time until the primitive rotation movement began to show the maximum value after dosing L-DOPA, and increased the time of manifestation of rotation, which is half or more of the maximum rotation number.

Test Example 8

Acetic Acid Twisting Method

In rats, a state of torment (flour) is provoked, in which the lower half of the rat body was twisted, their abdominal cavity (abdomen) was pressed and their hind legs extended, injecting a 0.6% physiological solution of acetic acid into the abdominal cavity of rats. After dosing the test compound and the solvent, physiological solution of acetic acid is injected into the abdominal cavity and the analgesic effect is evaluated by comparing the times of the above abnormal manifestations of behavior within the observation period (5 to 15 minutes after the dose of acetic acid), which occur after the dose of acetic acid acids (Basic Pharmacology Experiment, edited by Kazuhiko Kubota, pages 45-47, Nankoh-do).

As a result of this, it can be argued that the compound of the present invention substantially regulates the times of abnormal (pathological) manifestations of behavior and has an excellent analgesic effect.

Test Example 9

Cisplatin-induced vomiting model

An intravenous catheter is inserted into a ferret and restored after surgery. A vomiting reaction is then induced by injecting 10 mg / kg of cisdiamindichloroplatin (cisplatin) (A. Fink-Jensen et al., Neuroscience Letters 137: 173-177, 1992). Cisplatin (10 mg / kg) is injected with a ferret, which is pre-treated with a test compound or solvent, then the ferret is placed in a cage for observation, and during the observation period of 240 minutes, the latent period (incubation period of time) and the times are measured until the rhythmic stops contraction of the abdominal cavity (defined as vomiting).

As a result, the compound of the present invention prolongs the latent period and substantially reduces the period of time during which vomiting occurs.

Test Example 10

An experimental model of autoimmune encephalomyelitis

Female rats of the Lewis strain (weight 205 ± 10 g) obtained from Charles River, Kent UK, were placed in pairs in controlled environmental conditions (light / dark cycle 6:00 a.m. to noon - 6:00 p.m.; 22-24 ° C; humidity 45-55%) and provided them with free access to food and water. The experimental groups consisted of 9-12 animals. Rats were immunized in each hind paw with 20-50 μl of inoculum containing 50 μg of guinea pig myelin basic protein (MBP); final concentration 2 mg / ml) emulsified in Freund's complete adjuvant (CFA; Sigma, UK) containing Mycobacterium tuberculosis H37Ra (final concentration 5.5 mg / ml Difco Laboratories, UK). Animals were weighed and monitored daily and the clinical disease was rated as (0) no clinical symptoms; (1) flaccid tail and weight loss; (2) hind limb hypotension with further weight loss; (3) complete hind limb paralysis; (4) paraplegia; and (5) death. In addition, intermediate estimates are established for animals that demonstrate loss of tone in the distal half of the tail (score = 0.5), paralysis of one hind limb (score = 2.5) or complete paralysis of the hind limbs with weakness of the forelimbs (score = 3, 5). During administration of the compound (10-16 days after immunization; dpi), animals were evaluated 15 hours after injection of vehicle or compound in order to avoid any drastic effect of the treatment on disease assessment. Compounds were dissolved / suspended in 0.5% methyl cellulose using a hand held Polytron homogenizer (PT1200; 2 min). Rats were dosed per os with either methyl cellulose excipient (2.5 ml / kg) or compound at a dose of 5.10 and 20 mg / kg.

Results: from the point of view of experimental autoimmune encephalomyelitis, the compound of the invention is improved. For example, the compounds of Examples 7, 32, 76, 139, 164, 261, 262, and 264 provide an effect that is superior to the bulking group.

table 2 Example IR ₅₀ (μm) Example IR ₅₀ (μm) Example IK ₅₀ (MKM) 1 0.8 29th 0.1 63 1,1 2 1.8 thirty 0.04 64 2,8 3 0.3 31 0.1 65 0.6 4 0.1 32 0.1 66 2,4 5 0.6 33 0.7 67 6.5 6 9.3 34 3,7 69 0.9 7 0.1 35 3,1 70 3,1 8 0.1 36 1,1 71 0.05 nine 0,03 37 0.7 72 0.7 10 0.05 38 6.3 73 1,2 eleven 0.06 39 0.3 74 0.2 12 0.1 41 0.08 76 0.1 thirteen 0.2 42 0.2 77 0.02 14 0.1 43 0.5 78 1.4 fifteen 0.05 44 0.3 79 2.6 16 0.1 45 0.2 80 0.3 17 0.7 46 0.4 81 2.7 eighteen 0.02 47 0.6 82 0.8 19 0.08 48 0.04 84 0.9 twenty 0.04 49 0.2 86 1.9 21 0,03 52 1,1 87 1,2 22 0.06 55 0.8 88 0.3 23 0.2 56 3.2 90 0.7 24 0.2 57 0.2 91 0.05 25 0,03 58 0.1 92 0.05 26 0.02 60 1.7 93 1.9 27 0.05 61 0.2 94 1,5 28 0.2 62 3,1 95 0.3

Example IR ₅₀ (μm) Example IR ₅₀ (μm) Example IR ₅₀ (μm) 96 0.06 152 4.0 235 4.4 97 0.4 154 5,0 236 0.6 98 0.6 157 0.5 237 1,5 99 0.1 159 1,6 238 0.6 100 0.4 163 8.2 239 0.3 101 0.2 164 0.08 240 0.1 102 0.02 165 0.4 241 0.4 103 0,03 166 0.3 242 0.5 104 0.2 171 2,3 243 1,2 105 0,03 173 4.2 244 1.8 106 0,07 174 3.3 245 1,2 107 0,07 176 5,4 246 1,1 108 0,03 178 2.0 247 3.6 109 0.01 180 0.5 248 3.4 110 2.0 182 6.0 249 0.3 111 0.4 184 2,3 250 0.9 112 0.6 185 1.7 251 0.9 113 1,2 187 6.1 252 0.3 114 0.6 188 8.5 253 4.7 115 0.06 190 0.6 255 0.5 116 0.2 192 1,1 256 1,2 117 0.4 193 0.4 257 3,7 118 0.1 195 0.2 259 2.0 119 1.7 196 0.3 260 2.7 120 0.2 197 2.9 261 0.08 121 0.6 198 0.3 262 0.3 123 0.2 199 0.7 263 1,0 124 0.7 200 2.0 264 0.05 126 0.3 201 0.2 265 0.7 127 0.4 202 0.7 266 0.1 128 0,07 204 1,6 267 1,0 129 2.6 206 0.5 268 4.2 130 0.9 209 7.0 269 1.9 131 3,7 210 5.2 270 0.14 132 3,1 211 3.6 272 3.3 133 0.3 215 0.1 275 6.1 135 0.04 216 2,4 276 1.9 137 0.05 217 1.3 277 0.6 139 0.3 218 0.1 278 2,8 140 6.6 219 3,7 279 3,7 141 0.7 220 0.6 280 1.3 142 2.2 221 7.1 282 9.0 143 0.1 222 0.2 284 2,8 144 0.01 226 9.5 285 7.2 146 0.2 227 1.8 286 0.3 147 1,6 228 2.7 287 5,6 148 0.8 229 4.2 288 1,2 149 0.1 230 4.0 290 0.2 150 0.3 232 4.3 291 0.14 151 0.3 234 0.9 292 3.3

Example IR ₅₀ (μm) Example IR ₅₀ (μm) Example IR ₅₀ (μm) 293 3.3 326 0.9 362 3,7 294 0.6 327 8.0 365 2.7 297 4.2 330 0.4 367 0.6 298 0.3 333 0.3 371 0.6 299 4.4 334 0.6 379-B 6.4 300 0.3 337 0.7 381 0.4 302 0.3 338 0.4 382-B 2,3 303 0.9 341 0.2 385 1,1 307 2.0 342 1.3 386 3,5 308 1,6 343 3.2 387 7.0 309 4.1 344 4.7 388 2.9 313 5.9 346 3,7 390 1,0 314 4.6 351 3.3 391 0.1 315 0.08 352 1,6 392 0.1 316 2.1 354 1,5 393 0.3 317 0.6 355 0.2 394 1.4 318 3,1 356 2.1 395 0.9 319 2.0 358 1.4 398 0.2 320 2,3 359 2,3 321 4.0 360 3,1

Claims (97)

1. The compound represented by the following formula, its salt or its hydrates

where Q is O; R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different from each other and each means a hydrogen atom, a halogen atom, a C _1-6 alkyl group or a group represented by the formula —X — A, where X is simple bond, C _1-6 alkylene group, C _2-6 alkenylene group, C _2-6 alkynylene group, -O-, -S-, -SO-, -SO ₂ -, -N (R ⁶ ) -, -N (R ⁷ ) —CO—, —CO — N (R ⁸ ) -, —N (R ⁹ ) —CH ₂ -, —N (R ¹¹ ) —S (O) _m -, —N (R ¹³ ) - CO-N (R ¹⁴ ) -, where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ represent a hydrogen atom, a C _1-6 alkyl group and m means the whole numbers independently selected from 0, 1 or 2 and A represents a C _5-8 cycloalkyl group, a 5-14 membered nearoma matic heterocyclic group, C _6-14 aromatic gidrokarbotsiklicheskuyu group or a 5-14-membered aromatic heterocyclic group which may be substituted respectively, provided that 3 groups of R ^1, R ^2, R ^3, R ⁴ and R ⁵ are always the same or different from each other and each means -X-A, and the remaining 2 groups always mean a hydrogen atom, a halogen atom or a C _1-6 alkyl group, provided that in the above definition the cases are excluded when (1) Q represents O , R ¹ and R ⁵ represent hydrogen atoms and R ² , R ³ and R ⁴ represent phenyl groups, (2) Q represents O, R ¹ and R ⁴ represent hydrogen atoms and R ² , R ³ and R ⁵ represent phenyl groups, and (3) Q represents O, R ¹ and R ² represent hydrogen atoms and R ³ , R ⁴ and R ⁵ represent phenyl groups. 2. The compound according to claim 1, its salt or its hydrates, which is represented by the formula

where Q is O; X ¹ , X ² and X ³ are the same or different from each other and each denotes a single bond, a C _1-6 alkylene group, a C _2-6 alkenylene group, a C _2-6 alkynylene group, -O-, -S-, -SO-, -SO ₂ -, -N (R ⁶ ) -, -N (R ⁷ ) -CO-, -CO-N (R ⁸ ) -, -N (R ⁹ ) -CH ₂ -, -N (R ¹¹ ) S (O) _m -, -N (R ¹³ ) -CO-N (R ¹⁴ ), where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ^{14 is} a hydrogen atom, a C _1-6 alkyl group, and m is an integer, 0, 1, or 2; A ¹ , A ² and A ³ are the same or different from each other and each means an optionally substituted C _5-8 cycloalkyl group, a 5-14 membered non-aromatic heterocyclic group, a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic a heterocyclic group; R ¹⁷ and R ¹⁸ are the same or different from each other and each means a hydrogen atom, a halogen atom or a C _1-6 alkyl group. 3. The compound according to claim 2, its salt or its hydrates, where X ¹ , X ² and X ³ represent (1) a single bond, (2) a C _1-6 alkylene group, a C _2-6 alkenylene group or C _{2- 6} alkynylene group, (3) -O-, (4) -S-, (6) -SO-, (7) -SO ₂ -, (8) -N (R ⁶ ) -, (9) -N ( R ⁷ ) —CO—, (10) —CO — N (R ⁸ ) -, (11) —N (R ⁹ ) —CH ₂ -, (15) —N (R ¹¹ ) —S (O) _m , (21) -N (R ¹³ ) -CO-N (R ¹⁴ ) - (where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , m has such the same values as defined in the above paragraph 1), and A ¹ , A ² and A ³ represent a C _5-8 cycloalkyl group, a 5-14 membered non-aromatic heterocyclic group, a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromas a heterocyclic group which may optionally be substituted with one or more groups selected from the following substituent group b: Deputy b: a group consisting of (1) a hydroxy group, (2) a halogen atom, (3) a nitrile group, (4) a nitro group, (5) a C _1-6 alkyl group, a C _2-6 alkenyl group, or a C _2-6 alkynyl group, which may optionally be substituted, respectively, by one or more groups selected from the group consisting of a hydroxy group, a nitrile group, a halogen atom, a C _1-6 alkylamino group, a di- (C _1-6 alkyl) amino group, a C _2-6 alkenylamino group di (C _2-6 alkenylamino) groups, C _2-6 alkynylamino groups, di (C _2-6 alkynylamino) groups, NC _1-6 alkyl-NC _2-6 alkenylamino groups py, N-C _1-6 alkyl-N-C _2-6 alkynylamino groups, NC _2-6 alkenyl-N-C _2-6 alkynylamino groups, aralkyloxy groups, TBDMS oxy groups, C _1-6 alkylsulfonylamino groups, C _1-6 alkylcarbonyloxy groups, C _2-6 alkenylcarbonyloxy groups, C _2-6 alkynylcarbonyloxy groups, NC _1-6 alkylcarbamoyl groups, NC _2-6 alkenylcarbamoyl groups and N-C _2-6 alkynylcarbamoyl groups, (6) C _1-6 alkoxy groups, C _2-6 alkenyloxy groups or C _2-6 alkynyloxy group which may be optionally substituted respectively with one or more groups selected from the group consisting of C _1-6 alkylamino, and alkyloxy and a hydroxy group, (7) C _1-6 alkylthio, C _2-6 alkenylthio or C _2-6 alkynylthio group which may be optionally substituted respectively with one or more groups selected from the group consisting of hydroxy group, nitrile group, a halogen atom, C _1-6 alkylamino group, aralkyloxy group, TBDMS oxy group, C _1-6 alkylsulfonylamino, C _1-6 alkylcarbonyloxy and C _1-6 alkilkarbamoilgruppy, (8) a carbonyl group substituted by a group selected from the group consisting of C _1-6 alkoxy, amino groups, C _1-6 alkyl lamino groups, di (C _1-6 alkyl) amino groups, C _2-6 alkenylamino groups, di (C _2-6 alkenyl) amino groups, C _2-6 alkynylamino groups, di (C _2-6 alkynyl) amino groups, N-C _1-6 alkyl-N — C _2-6 alkenylamino groups, N — C _1-6 alkyl-N — C _2-6 alkynylamino groups and N — C _2-6 alkenyl-N — C _2-6 alkynylamino groups, (9) an amino group, which may be optionally substituted with one or more groups selected from the group consisting of a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylsulfonyl group, a C _2-6 alkenylsulfonyl group, C _{2 -6} alkynylsulfonyl g groups, C _1-6 alkylcarbonyl group, C _2-6 alkenylcarbonyl group and C _2-6 alkynylcarbonyl group, (10) C _1-6 alkylsulfonyl group, (11) C _2-6 alkenylsulfonyl group, (12) C _2-6 alkynylsulfonyl group, (13) C _1-6 alkylsulfinyl group, (14) C _2-6 alkenylsulfinyl group, (15) C _2-6 alkynylsulfinyl group, (16) formyl group, (17) C _3-8 cycloalkyl group or C _3-8 cycloalkenyl group, which may be optionally substituted, respectively, by one or more groups selected from the group consisting of hydroxy-group, a halogen atom, a nitrile group, a C _1-6 alkyl group, a C _1-6 alkyloxy group, a C _1-6 alkyloxy C _1-6 alkyl group and an aralkyl group, (18) a 5-14 membered non-aromatic heterocyclic group, which may optionally be substituted with one or more groups selected from the group consisting of hydroxy, halogen atom, nitrile group, C _1-6 alkyl group, C _1-6 alkyloxy, C _1-6 alkyloxyC _1-6 alkyl group and aralkyl group, (19) With a _6-14 aromatic hydrocarbocyclic group, which may be optionally substituted and one or more groups selected from the group consisting of hydroxy, halogen atom, nitrile group, C _1-6 alkyl group, C _1-6 alkyloxy, C _1-6 alkyloxyC _1-6 alkyl group and aralkyl group, and (20) A 5-14 membered aromatic heterocyclic group which may optionally be substituted with one or more groups selected from the group consisting of a hydroxy group, a halogen atom, a nitrile group, a C _1-6 alkyl group, a C _1-6 alkyloxy group, a C _1-6 alkyloxyC _1-6 alkyl group and aralkyl group. 4. The compound according to claim 2, its salt or its hydrates, where A ¹ , A ² and / or A ³ are the same and / or different from each other and each represents an optionally substituted C _5-8 cycloalkyl or 5-14 membered non-aromatic hetero ring. 5. The compound according to claim 2, its salt or its hydrates, where A ¹ , A ² and / or A ³ are the same or different from each other and each represents an optionally substituted C _6-14 aromatic hydrocarbon ring or 5-14 membered aromatic hetero ring. 6. The compound according to claim 2, its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents a phenyl group, a pyrrolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group, carbazolyl group, cyclopent an alkyl group, a cyclohexyl group, a cyclohexenyl group, a dioxinyl group, an adamantyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group or a morpholyl group, which may optionally have a substituent, respectively. 7. The compound according to claim 2, its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents a group represented by the formula

or

which may be substituted. 8. The compound according to claim 2, its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each is optionally substituted by a hydroxyl group, a halogen atom, an amino group or a nitrile group. 9. The compound according to claim 7, its salt or its hydrates, where the substituents A ¹ , A ² and A ³ are the same or different from each other and each represents a hydroxyl group, a halogen atom or an amino group, a nitrile group or a nitro group. 10. The compound according to claim 1 or 2, its salt or its hydrates, where X ¹ , X ² and X ³ are the same or different from each other and each represents a simple bond, -CH ₂ -, -CH ₂ -CH ₂ - , -CH = CH -, - C≡C-, -O-. 11. The compound according to claim 2, its salt or its hydrates, where X ¹ , X ² and X ³ represent simple bonds. 12. The compound according to claim 2, its salt or its hydrates, where R ¹⁷ and R ¹⁸ are the same or different from each other and each represents a hydrogen atom, fluorine, chlorine, bromine, iodine, methyl group, ethyl group, n-propyl a group or an isopropyl group. 13. The compound according to claim 2, its salt or its hydrates, where R ¹⁷ and R ¹⁸ represent a hydrogen atom. 14. The compound according to claim 1, its salt or its hydrates, which is represented by the formula

where X ¹ , X ² and X ³ , A ¹ , A ² , A ³ , R ¹⁷ and R ¹⁸ are as specified in claim 2. 15. The compound according to 14, its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents an optionally substituted C _6-14 aromatic hydrocarbon ring or a 5-14 membered aromatic hetero ring . 16. The compound according to 14, its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents an optionally substituted phenyl group, pyrrolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group, carba olilnuyu group, cyclopentyl group, cyclohexyl group, cyclohexenyl group, dioxinyl group, adamantyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group or morfolilnuyu group. 17. The compound according to 14, its salt or its hydrates, where A ¹ , A ² and A ³ are the same or different from each other and each represents a group represented by the following formula:

or

which may be substituted. 18. The compound according to 14, its salt or its hydrates, where the place of attachment of the substituent on A ¹ , A ² and / or A ³ is the α-position of the carbon atom, which is associated with the group X ¹ , X ² and X ³ , respectively . 19. The compound according to 14, its salt or its hydrates, where X ¹ , X ² and X ³ represent simple bonds. 20. The compound according to 14, its salt or its hydrates, where R ¹⁷ and R ¹⁸ represent hydrogen atoms. 21. The compound according to claim 1, its salt or its hydrates, which is any one of the compounds selected from: 3- (2-cyanophenyl) -5- (2-methylsulfonylaminophenyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-chloro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitrophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-aminophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonylaminophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-dimethylaminophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- [3- (5-methoxymethyl-2-oxazolidinon-3-yl) phenyl] -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxycarbonylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylaminocarbonylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyano-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-hydroxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-dimethylaminoethoxy-phenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-formylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-hydroxymethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-cyanomethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetylaminomethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methylsulfonyl-aminomethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-acetoxymethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylthiophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methylsulfonylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-formylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-diethylaminomethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-hydroxymethylthiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1-benzyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5-phenyl- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1,5-diphenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-methoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (3,4-dimethoxyphenyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (thiophen-3-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-fluorophenyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (thiophen-2-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (3-furyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-furyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-methoxycarbonylphenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3-phenyl-5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-fluorophenyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-methoxy-5-pyridyl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-methoxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxyphenyl) -1,2-dihydropyridin-2-one, 3-phenyl-5- (2-pyridyl) -1- (3-fluorophenyl) -1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (4-fluorophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-formylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-formylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-chlorophenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-tolyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-trifluoromethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (thiophen-3-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-furyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-tolyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-trifluoromethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (pyrimidin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-benzyloxymethylpyridin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-ethylthiopyridin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-methoxypyridin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-chloropyridin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-fluoropyridin-5-yl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-methoxyphenyl) -1,2-dihydropyridin-2-one, 3-phenyl-5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (thiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (2,6-dimethylphenyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanothiophen-3-yl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-fluoro-3-pyridyl) -5- (2-pyridyl) -1- (3-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-hydroxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminoethoxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-chlorophenyl) -5- (2-pyridyl) -1- (3-dimethylaminopropoxyphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-hydroxymethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (4-cyanomethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-cyanomethylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (6-diethylaminomethyl-2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one, 3- (2-hydroxypyridin-6-yl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one, 1- (2-aminobenzothiazol-6-yl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-benzyl-1,2,5,6-tetrahydropyridin-5-yl) -1,2-dihydropyridin-2-one, 3- [2- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (6-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (5-methylpyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (3-hydroxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1-phenyl-5- (2-thiazolyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (6-methoxypyridin-2-yl) -1-phenyl-1,2-dihydropyridin-2-one, 1- (4-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 1- (3-aminophenyl) -3- (2-cyanophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-amino-4-methylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-dimethylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-piperidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-pyrrolidinoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-diisopropylaminoethoxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- [3- (4-piperidinobutoxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (4-nitrophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 1-phenyl-5- (2-pyridyl) -3- (2-thiazolyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-pyridyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one, 3- (2-fluoropyridin-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl-3-yl) -1-phenyl-5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-nitrophenyl) -5- (2-pyrimidinyl) -1,2-dihydropyridin-2-one, 3- (2-nitrophenyl) -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-formylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (2-naphthyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (1-naphthyl) -1,2-dihydropyridin-2-one, 5- (2-aminopyridin-6-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one, 5- (6-bromopyridin-2-yl) -3- (2-cyanophenyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-morphorinopyridin-6-yl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- (3-hydroxyphenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- [3- (4-piperidyloxy)] phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one, 1- [3- (N-acetylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -1- [3- (1-methylsulfonylpiperidin-4-yl-hydroxy) phenyl] -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 1- [3- (N-methylpiperidin-4-yl-hydroxy) phenyl] -3- (2-cyanophenyl) -5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- (6-chloro-1H-benzimidazol-2-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- (2-cyanophenyl) -5- (2-pyridyl) -1- (3-nitro-4-methylphenyl) -1,2-dihydropyridin-2-one, 3- (2-cyanothiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one, 3- [2- (5-oxazolyl) phenyl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one, 3- [2- (5-oxazolyl) thiophen-3-yl] -1-phenyl-5- (2-pyridyl) -1,2-dihydropyridin-2-one and 3- (2-ethoxycarbonylvinylthiophen-3-yl) -5- (2-pyridyl) -1-phenyl-1,2-dihydropyridin-2-one. 22. A method of obtaining a compound represented by the formula

where each A ^1a and A ^3a are the same or different and each means an optionally substituted C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group; W ″ ″ represents a halogen atom, or its salt, consisting in the fact that the compound represented by the formula

where A ^1a and A ^3a have the same meanings as defined above, or its salt is subjected to a halogenation reaction. 23. A method of obtaining a compound represented by the formula

where a ^1a and a ^3a have the same meanings as defined above, or its salt, namely, that the compound represented by the formula

where A ^3a has the same meaning as defined above, or a salt thereof and a boronic acid derivative represented by the formula A ^1a B (OH) ₂ , where A ^1a is an optionally substituted C _6-14 aromatic hydrocarbon ring or a 5-14 membered aromatic hetero ring, subjected to a coupling reaction in the presence of a copper compound. 24. The method according to item 23, wherein the compound represented by the above formula (VIII), or a salt thereof, obtained by deprotecting a compound represented by the formula

where A ^3a has the same meaning as defined above; Z ³ means a protective group of an alcohol hydroxy group, and the boronic acid derivative represented by the formula A ^1a B (OH) ₂ , where A ^1a has the same meaning as defined above, is subjected to a coupling reaction in the presence of a copper compound. 25. The method according to item 23, which includes obtaining a compound represented by the aforementioned formula (VIII), or its salt by deprotecting a compound represented by the aforementioned formula (IX), or a salt thereof, obtained by a combination reaction of a boronic acid derivative represented by the formula

where Z ³ has the same meaning as defined above, or its salts and compounds represented by the formula A ^3a -Z ¹ , where A ^3a has the same meaning as defined above; Z ¹ represents a halogen atom or a salt thereof in the presence of a palladium catalyst; and then the step that the compound (VIII) or its salt and a boronic acid derivative represented by the formula A ^1a B (OH) ₂ , where A ^1a has the same meaning as defined above, is subjected to a coupling reaction in the presence of a copper compound . 26. The method according to item 23, which includes obtaining a compound represented by the above formula (X), or its salt by reacting a compound represented by the formula

where Z ³ has the same meaning as defined above; W 'represents a halogen atom, or its salt and trimethoxyborane in the presence of a base; obtaining a compound represented by the aforementioned formula (IX), or a salt thereof by subjecting a compound (X) or a salt thereof and a compound represented by the formula A ^3a -Z ¹ wherein A ^3a and Z ¹ have the same meanings as defined above, or a salt thereof coupling reactions in the presence of a palladium catalyst; obtaining a compound represented by the above formula (VIII) or a salt thereof by subjecting a compound (IX) or a salt thereof to a deprotection reaction; and then the step that the compound (VIII) and the boronic acid derivative represented by the formula A ^1a B (OH) ₂ , where A ^1a has the same meaning as defined above, are subjected to a coupling reaction in the presence of a copper compound. 27. The method according to item 23, which includes obtaining a compound represented by the aforementioned formula (X), or its salt by reacting a compound represented by the aforementioned formula (XI), or its salt, obtained by reacting a compound represented by a formula

where W 'and W''are the same or different from each other and each represents a halogen atom, or its salt and a compound represented by the formula Z ³ OM, where Z ³ has the same meaning as defined above; M represents an alkali metal atom, and trimethoxyborane in the presence of a base; obtaining a compound represented by the aforementioned formula (IX), or a salt thereof by subjecting a compound (X) or a salt thereof and a compound represented by the formula A ^3a -Z ¹ wherein A ^3a and Z ¹ have the same meanings as defined above, or its a coupling reaction salt in the presence of a palladium catalyst; obtaining a compound represented by the above formula (VIII) or a salt thereof by subjecting a compound (IX) or a salt thereof to a deprotection reaction; and then the step that the compound (VIII) and the boronic acid derivative represented by the formula A ^1a B (OH) ₂ , where A ^1a has the same meaning as defined above, are subjected to a coupling reaction in the presence of a copper compound. 28. The production method according to claim 22, which comprises halogenating the compound represented by the above formula (VI) and obtained by the method according to any one of claims 23-27, or a salt thereof. 29. The method according to item 22 or 28, where W represents bromine or iodine. 30. The method according to item 22 or 28, where the halogenation reaction to obtain compound (VII) or its salt is (1) a bromination reaction using N-bromosuccinimide or a mixture of acetic acid-bromine or (2) an iodination reaction using N-iodosuccinimide or iodine. 31. The method according to item 22 or 28, where the halogenation reaction to obtain compound (VII) or its salt is carried out using N, N-dimethylformamide as a solvent. 32. The method according to item 22 or 28, where A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl a group, a naphthyl group, a quinolyl group, an isoquinolyl group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, an imidazopyridyl group or a carbazolyl group. 33. The method according to any one of paragraphs.23-27, where A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group , a furyl group, a naphthyl group, a quinolyl group, an isoquinolyl group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, an imidazopyridyl group or a carbazolyl group. 34. The method according to any one of claims 23 to 28, wherein the copper compound used for the coupling reaction using compound (VIII) or a salt thereof is copper acetate or di-μ-hydroxy bis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride. 35. The method according to any one of claims 23 to 28, wherein the coupling reaction using the compound (VIII) or a salt thereof is carried out in the presence of a base. 36. The method according to clause 35, where the base is triethylamine, pyridine or tetramethylenediamine. 37. The method according to any one of claims 23 to 28, wherein the coupling reaction using compound (VIII) or a salt thereof is carried out using N, N-dimethylformamide as a solvent. 38. The method according to any one of paragraphs.24-28, where Z ³ represents a C _1-6 alkyl group or a C _1-6 aralkyl group. 39. The method according to claims 24-28, wherein the deprotection reaction of compound (IX) or its salt is carried out in the presence of an acid. 40. The method according to § 39, where the acid is hydrochloric acid. 41. The method according to claims 25-28, wherein the catalyst for the coupling reaction using compound (X) or a salt thereof is palladium acetate and triphenylphosphine. 42. The method according to claims 25-28, wherein the coupling reaction using compound (X) or a salt thereof is carried out in the presence of a base. 43. The method according to § 42, where the base is cesium carbonate, sodium carbonate or potassium carbonate. 44. The method according to any one of paragraphs.26-28, where W represents bromine. 45. The method according to claims 26-28, wherein the base used for the reaction of compound (XI) or its salt with trimethoxyborane is n-butyllithium. 46. The method according to item 27 or 28, where W 'and W "represent bromine. 47. The method according to item 27 or 28, where the compound represented by formula Z ³ OM is sodium methoxide or sodium ethoxide. 48. A method of obtaining a compound represented by the formula where ring D represents an optionally substituted pyridine ring; ring E represents an optionally substituted benzene ring; W "" has the same meaning as defined above, or its salt, namely, that the compound represented by the formula

where the ring D and E have the same meanings as defined above, or its salt is subjected to a halogenation reaction. 49. A method of obtaining a compound represented by the formula

where ring D and ring E have the same meanings as defined above, or its salt, namely, that the compound represented by the formula

where ring D has the same meaning as defined above, or a salt thereof and a boronic acid derivative represented by the formula PhB (OH) ₂ , where Ph is an optionally substituted phenyl group, are subjected to coupling reactions in the presence of a copper compound. 50. The method according to § 49, wherein the compound represented by formula (VIII) ', or a salt thereof, obtained by deprotecting a compound represented by formula

where the ring D and Z ³ have the same meanings as defined above, or its salts, and the boronic acid derivative represented by the formula PhB (OH) ₂ , where Ph has the same meaning as defined above, undergo a coupling reaction in the presence of a copper compound . 51. The method according to § 49, which comprises preparing a compound represented by the aforementioned formula (VII) 'or a salt thereof by deprotecting a compound represented by the aforementioned formula (IX)' or a salt thereof obtained by subjecting a boronic acid derivative, represented by the formula

where Z ³ has the same meaning as defined above, or its salt and optionally substituted 2-halogen pyridine or its salt of the coupling reaction in the presence of a palladium catalyst; and then the step that compound (VIII) 'or a salt thereof and a boronic acid derivative represented by the formula PhB (OH) ₂ , where Ph has the same meaning as defined above, is subjected to a coupling reaction in the presence of a copper compound. 52. The method according to § 49, which comprises obtaining a compound represented by formula (X), or a salt thereof, by reacting a compound represented by formula

where Z ³ has the same meaning as defined above; W 'represents a halogen atom, or its salt and trimethoxyborane in the presence of a base; preparing a compound represented by the aforementioned formula (IX) 'or a salt thereof by subjecting a compound (X) or a salt thereof and optionally substituted 2-halogen pyridine or a salt thereof to a coupling reaction in the presence of a palladium catalyst; the preparation of a compound represented by the aforementioned formula (VIII) 'or a salt thereof by a deprotection reaction of a compound (IX)' or a salt thereof; and then the step that the compound (VIII) 'and the boronic acid derivative represented by the formula PhB (OH) ₂ , where Ph has the same meaning as defined above, is subjected to a coupling reaction in the presence of a copper compound. 53. The method according to § 49, which comprises obtaining a compound represented by the aforementioned formula (X) or a salt thereof by reacting a compound represented by the aforementioned formula (XI) or a salt thereof obtained by reacting a compound represented by a formula

where W 'and W''are the same or different from each other and each represents a halogen atom, or its salt and a compound represented by the formula Z ³ OM, where Z ³ and M have the same meanings as defined above, and trimethoxyborane in the presence of grounds; preparing a compound represented by the aforementioned formula (IX) 'or a salt thereof by subjecting a compound (X) or a salt thereof and optionally substituted 2-halogen pyridine or a salt thereof to a coupling reaction in the presence of a palladium catalyst; preparing a compound represented by the above formula (VIII) or a salt thereof by subjecting a compound (IX) ′ or a salt thereof to a deprotection reaction; and then the step that compound (VIII) 'and a boronic acid derivative represented by the formula PhB (OH) ₂ , where Ph has the same meaning as defined above, are subjected to a coupling reaction in the presence of a copper compound. 54. The method according to paragraph 24, which includes a stage of a halogenation reaction of the compound represented by the above formula (VI) 'and obtained by the method according to any one of paragraphs 28-31, or its salt. 55. The method according to p. 48 or 54, where W "" represents bromine or iodine. 56. The method of claim 48 or 54, wherein the halogenation reaction to produce compound (VII) or a salt thereof is (1) a bromination reaction using N-bromosuccinimide or an acetic acid-bromine mixture, or (2) an iodination reaction using N- iodosuccinimide or iodine. 57. The method according to p. 48 or 54, where the halogenation reaction to obtain compound (VII) or its salt is carried out using N, N-dimethylformamide as a solvent. 58. The method of claim 48 or 54, wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl a group, a naphthyl group, a quinolyl group, an isoquinolyl group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, an imidazopyridyl group or a carbazolyl group. 59. The method according to any one of claims 49-53, wherein A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a thienyl group, a thiazolyl group , a furyl group, a naphthyl group, a quinolyl group, an isoquinolyl group, an indolyl group, a benzimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, an imidazopyridyl group or a carbazolyl group. 60. The method according to any one of claims 49-54, wherein the copper compound used for the coupling reaction using compound (VIII) or a salt thereof is copper acetate or di-μ-hydroxy bis [(N, N, N ', N'-tetramethylethylenediamine) copper (II)] chloride. 61. The method according to any one of claims 49-54, wherein the coupling reaction using compound (VIII) or a salt thereof is carried out in the presence of a base. 62. The method of claim 61, wherein the base is triethylamine, pyridine, or tetramethylethylenediamine. 63. The method according to any one of claims 49-54, wherein the coupling reaction using compound (VIII) or a salt thereof is carried out using N, N-dimethylformamide as a solvent. 64. The method according to any one of claims 50-54, wherein Z ³ is a C _1-6 alkyl group or an aralkyl group. 65. The method according to claims 50-54, wherein the deprotection reaction of compound (IX) or its salt is carried out in the presence of an acid. 66. The method of claim 65, wherein the acid is hydrochloric acid. 67. The method according to claims 51-54, wherein the catalyst in the coupling reaction using compound (X) or a salt thereof is palladium acetate and triphenylphosphine. 68. The method according to claims 51-54, wherein the coupling reaction using the compound (X) or a salt thereof is carried out in the presence of a base. 69. The method according to p, where the base is cesium carbonate, sodium carbonate or potassium carbonate. 70. The method according to any one of paragraphs.52-54, where W 'represents bromine. 71. The method according to paragraphs 52-54, wherein the base used for the reaction of the compound (XI) or its salt with trimethoxyborane is n-butyllithium. 72. The method according to paragraphs 53, 54, where W 'and W "represent bromine. 73. The method of claim 53 or 54, wherein the compound represented by formula Z ³ OM is sodium methoxide or sodium ethoxide. 74. The method according to any one of claims 51-54, wherein the optionally substituted 2-halo-pyridine is optionally substituted 2-bromopyridine. 75. The compound represented by the following formula, its salt or its hydrates

where A ^1a and A ^3a are the same or different from each other and each means an optionally substituted C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group; R is a hydrogen atom or a halogen atom. 76. The compound according to item 75, its salt or its hydrates, where A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, thienyl group, thiazolyl group, furyl group, naphthyl group, quinolyl group, isoquinolyl group, indolyl group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridyl group or carbazolyl group. 77. The compound according to item 75, its salt or its hydrates, where A ^1a and A ^3a are the same or different from each other and each represents an optionally substituted phenyl group, pyridyl group, pyrimidinyl group, thienyl or furyl group. 78. The compound according to item 75, its salt or its hydrates, where R represents a hydrogen atom or bromine. 79. A pharmaceutical composition having inhibitory activity against AMPA or kainate receptors, comprising a compound represented by the following formula, a salt thereof or hydrates thereof:

where Q is O; and R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different from each other and each means a hydrogen atom, a halogen atom, a C _1-6 alkyl group or a group represented by the formula —X — A, where X is single bond, C _1-6 alkylene group, C _2-6 alkenylene group, C _2-6 alkynylene group, —O—, —S—, —SO—, —SO ₂ -, —N (R ⁶ ) -, - N (R ⁷ ) -CO-, -CO-N (R ⁸ ) -, -N (R ⁹ ) -CH ₂ -, - N (R ¹¹ ) S (O) _m -, -N (R ¹³ ) - CO-N (R ¹⁴ ) -, where R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ represent a hydrogen atom, a C _1-6 alkyl group and m means the whole a number independently selected from 0, 1 or 2; A means a C _5-8 cycloalkyl group, a 5-14 membered non-aromatic heterocyclic group, a C _6-14 aromatic hydrocarbocyclic group or a 5-14 membered aromatic heterocyclic group, which may be substituted, respectively, provided that 3 groups of R ¹ , R ² , R ³ , R ⁴ and R ⁵ are always the same or different from each other and each means —X — A, and the remaining 2 groups always mean a hydrogen atom, a halogen atom or a C _1-6 alkyl group. 80. The pharmaceutical composition according p, where it is an inhibitor for the receptor of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. 81. The pharmaceutical composition according p, where it is an inhibitor for the AMPA receptor. 82. The pharmaceutical composition according p, where it is an inhibitor for kainate receptor. 83. The pharmaceutical composition according to p, which is a therapeutic or prophylactic agent for the treatment of diseases in which the AMPA receptor or kainate receptor is involved. 84. The pharmaceutical composition according to p, which is a therapeutic or prophylactic agent for the treatment of diseases in which the kainate receptor is involved. 85. The pharmaceutical composition according to p, which is a therapeutic or prophylactic agent for the treatment of acute neurodegenerative disease. 86. The pharmaceutical composition according to p, which is a therapeutic or prophylactic agent for the treatment of acute cerebrovascular disorders, head injury, spinal cord injury, diseases of the nervous system (neuropathy) caused by hypoxia or hypoglycemia. 87. The pharmaceutical composition according to p, which is a therapeutic or prophylactic agent for the treatment of chronic neurodegenerative disease. 88. The pharmaceutical composition according to p, which is a therapeutic or prophylactic agent for the treatment of Alzheimer's disease, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis or disorders associated with degeneration of the spinal cord and cerebellum. 89. The pharmaceutical composition according to p. 79, which is a tool for the treatment or prevention of epilepsy, hepatic encephalopathy, peripheral neuropathy, Parkinson's syndrome, spasticity, pain, neuralgia, schizophrenia, anxiety, substance abuse, nausea, vomiting, dysuria; visual impairment caused by glaucoma; hearing impairment caused by antibiotics or food poisoning. 90. The pharmaceutical composition according to p. 79, for the treatment or prevention of Parkinson's disease, epilepsy, peripheral neuropathy, Parkinson's syndrome, pain, neuralgia, anxiety or multiple sclerosis. 91. The pharmaceutical composition according to p, which is a tool for the treatment or prevention of infectious encephalomyelitis, cerebrovascular senile dementia or dementia or neurosis caused by cerebrospinal meningitis. 92. The pharmaceutical composition of claim 91, wherein the infectious encephalomyelitis is HIV-induced encephalomyelitis. 93. The pharmaceutical composition according to p, which is a tool for the treatment or prevention of demyelinating disease. 94. The pharmaceutical composition according to p. 93, where the demyelinating disease is encephalitis, acute disseminated encephalomyelitis, multiple (multiple) sclerosis, acute demyelinating polyneuropathy, Hyena-Barre syndrome; chronic inflammatory demyelinating polyneuropathy, Markiafava-Binyami disease; demyelination of nerve fibers related to the central Varolian bridge, optic neuromyelitis, Devic's disease, Balo's disease; HIV myelopathy; myelopathy due to HTLV (human T-cell leukemia virus); progressive multifocal leukoencephalopathy or secondary demyelinating disease. 95. The pharmaceutical composition according to paragraph 94, where the secondary demyelinating disease is a demyelinating disorder with lupus erythematosus, polyarteritis nodosa, Sjogren's syndrome, sarcoidosis or isolated cerebral vasculitis. 96. A method for the prevention or treatment of diseases in which the AMPA receptor or the kainate receptor is involved by administering to a patient a pharmacologically effective dose of a compound represented by formula (I), a salt thereof or its hydrates. 97. The method according to p, where the disease is an acute neurodegenerative disease, cerebrovascular disorders in the acute stage, head injury, spinal cord injury; diseases of the nervous system (neuropathy) caused by hypoxia or hypoglycemia; chronic neurodegenerative disease, Alzheimer's disease, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis; a disorder associated with degeneration of the spinal cord and cerebellum; epilepsy, hepatic encephalopathy, peripheral neuropathy, Parkinson's syndrome, (muscle) spasticity, pain, neuralgia, schizophrenia, anxiety, substance abuse, nausea, vomiting, dysuria; visual impairment caused by glaucoma; hearing impairment caused by antibiotics; food poisoning, infectious encephalomyelitis, including HIV-related encephalomyelitis; cerebrovascular senile dementia, dementia or neurosis caused by cerebrospinal meningitis; or demyelinating diseases, such as encephalitis; acute disseminated encephalomyelitis; multiple (multiple) sclerosis; acute demyelinating polyneuropathy; Hyena-Barre Syndrome; chronic inflammatory demyelinating polyneuropathy, Markiafava-Binyami disease; demyelination of nerve fibers related to the central Varolian bridge, optic neuromyelitis, Devic's disease; Balo's disease; HIV myelopathy HTLV myelopathy (human T-cell leukemia virus); progressive multifocal leukoencephalopathy; and secondary demyelinating diseases, such as demyelinating disorder with lupus erythematosus; nodose polyarteritis; Sjogren's syndrome; sarcoidosis and isolated cerebral vasculitis.