Derivatives of pyridazinone and triazinone and their using as pharmaceutical preparations

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to derivatives of pyridazinone or triazinone represented by the following formula, their salts or their hydrates: wherein each among A1, A2 and A3 represents independently of one another phenyl group that can be optionally substituted with one or some groups chosen from the group including (1) hydroxy-group, (2) halogen atom, (3) nitrile group, (4) nitro-group, (5) (C1-C6)-alkyl group that can be substituted with at least one hydroxy-group, (6) (C1-C6)-alkoxy-group that can be substituted with at least one group chosen from the group including di-(C1-C6-alkyl)-alkylamino-group, hydroxy-group and pyridyl group, (7) (C1-C6)-alkylthio-group, (8) amino-group, (9) (C1-C6)-alkylsulfonyl group, (10) formyl group, (11) phenyl group, (12) trifluoromethylsulfonyloxy-group; pyridyl group that can be substituted with nitrile group or halogen atom or it can be N-oxidized; pyrimidyl group; pyrazinyl group; thienyl group; thiazolyl group; naphthyl group; benzodioxolyl group; Q represents oxygen atom (O); Z represents carbon atom (C) or nitrogen atom (N); each among X1, X2 and X3 represents independently of one another a simple bond or (C1-C6)-alkylene group optionally substituted with hydroxyl group; R1 represents hydrogen atom or (C1-C6)-alkyl group; R2 represents hydrogen atom; or R1 and R2 can be bound so that the group CR2-ZR1 forms a double carbon-carbon bond represented as C=C (under condition that when Z represents nitrogen atom (N) then R1 represents the unshared electron pair); R3 represents hydrogen atom or can be bound with any atom in A1 or A3 to form 5-6-membered heterocyclic ring comprising oxygen atom that is optionally substituted with hydroxyl group (under condition that (1) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; and each among A1, A2 and A3 represents phenyl group, (2) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o,p-dimethylphenyl group; A2 represents o-methylphenyl group, and A3 represents phenyl group, or (3) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o-methylphenyl group; A2 represents p-methoxyphenyl group, and A3 represents phenyl group, and at least one among R2 and R means the group distinct from hydrogen atom) with exception of some compounds determined in definite cases (1), (3)-(8), (10)-(16) and (19) given in claim 1 of the invention. Compounds of the formula (I) elicit inhibitory activity with respect to AMPA receptors and/or kainate receptors. Also, invention relates to a pharmaceutical composition used in treatment or prophylaxis of disease, such as epilepsy or demyelinization disease, such as cerebrospinal sclerosis wherein AMPA receptors take part, a method for treatment or prophylaxis of abovementioned diseases and using compound of the formula (I) for preparing a medicinal agent used in treatment or prophylaxis of abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

32 cl, 10 tbl, 129 ex

 

The scope of the invention

The present invention relates to a new compound, its salts and their hydrates, to methods for their preparation and use as pharmaceuticals. More specifically, the present invention relates to a derivative of pyridazinone and triazinone used as inhibitors of receptors, non-NMDA, in particular as inhibitors of AMPA receptors.

The level of technology

Glutamate and aspartate are important aminosilane that participate in neural functions, such as recognition, memory, movement, respiration, regulation of cardiovascular activity and sensitivity, and are also exciting neutrotransmitters. In the exercise of their physiological activity is an important factor in their interaction with the specific receptor, and the well-known two types of receptors: receptor-type ion channel and receptor associated G-protein. First, in addition, are classified into the receptor N-methyl-D-aspartate (NMDA)receptor α-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA), kainite-induced receptor and the like. On the other hand, it is known that the amino acid as an excitatory neurotransmitter causes neurotoxicity, for example, an abnormal excitation of the nerves of the Central nervous system. It was noted that the specified toxi is ness is so significant, accompanied by the death of nerve cells, which leads to various nervous diseases. The main known nervous diseases are cerebral ischemia, traumatic brain injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington Hantington, nervous disorders, AIDS, epilepsy, neurodegeneration observed after hypoxic condition, mental disorders, mobility, pain, spasticity, nervous disorders caused by food poisoning, various neurodegenerative diseases, various mental illnesses, chronic pain, migraine pain and cancer pain and pain caused by the breakdown in diabetes. They represent a serious disease, most of the mechanisms of formation and so forth, still not clear, and pharmaceutical agents effective to treat them, still not found, but I think that they are directly related to excessive release/accumulation of excitatory neurotransmitters, with changes expressed by the set of receptors, and the like. For example, it was reported that in stroke, cerebral ischemia, traumatic brain and spinal cord, the concentration of glutamate in the cerebrospinal fluid and plasma increased (Castillo, J., Dazalos, A. and Noya, M., Lancet, 1997 346:79-83; and the like). There is a message stating that if excessive exposure to nerve cells, glutamate, NMDA, AMPA, kainate and the like, occurs neuropathy (Meldrum, B., Brain Res. Reviews, 18, 293, 1993). There are reports that in Alzheimer's disease β-amyloid protein enhances the neurotoxicity of glutamate and promotes the release of glutamate (Arias, C., Arrieta, I. and Tapia, R., J. Neurosci. Res., 1995, 41:561-566; and the like). In the case of Parkinson's disease, there are reports of a hydroxide of L-DOPA activates the AMPA receptor (Cha, J. J., et. al., Neurosci. Lett., 1991, 132:55-58) and enhances neurotoxicity (Olney, J. W., et. al., 1990, 108:269-272; Rosenberg, P. A., et. al., Proc. Natl. Acad. Sci. USA, 1991, 88:4865-4869). There are other reports that L-DOPA helps the formation of free radicals, which leads to increased oxidative stress (Smith, T. S., et. al., Neuroreport, 1994, 5:1009-1011). If horei of Hantington, there are reports that a substance that inhibits the release of glutamate, is effective for improving symptoms. In the case of ALS, there is a lot of data pointing to the involvement of glutamate in its pathology. There are several cases where AIDS patients are deficient nerve detection, and even if such a nervous disease implies the involvement of glutamate. For example, it was reported that gp 120, which is a glycoprotein membrane of the HIV virus, the hearth is employed, the uptake of glutamate 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 the release of glutamate suppresses neurodegeneration caused by gp 120 (Sindou, P., et. al., J. Neurosci. 1994, 126:133-137; Muller, W. E. G., et. al., Eur. J. Pharmacol. Molec. Pharmacol., 1992, 226:209-214; Lipton, S. A., Neurology, 1992, 42:1403-1405). With regard to allergic encephalomyelitis, a message indicating that mice that have the above inflammation, an enzyme that cleaves glutamate included on the outside of the cells is defective (Hardin-Pouzet, H., Glia., 1997, 20:79-85). Olivopontocerebellar atrophy is a disease that is sometimes associated with Parkinson's disease. It was found antibody to GluR2, which is a subunit, component of the AMPA receptor, (Gahring, L. C., Neurology, 1997, 48:494-500) and confirmed the relationship between olivopontocerebellar atrophy and AMPA receptor. As for the message about epilepsy, there is evidence that in mice that are incapable of producing in the receptor GluR2 AMPA, increases the permeability of the AMPA receptor in relation to the CA2+, which is why it can cause a sudden attack leading to death (Brusà, R., Science, 1995, 270:1677-1680). In addition, it is reported that NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzoic[f]cinoxacin; Sheardown, at al., Science, 247, 571, 1990) and other compounds that inhibit AMPA receptors, have a calming and against the convulsive action (J. Pharmacol. Exp. Ther., 260, 742, 1992; Pharmacol. Biochem. Behavior, 1998, 60:119-124), and so reported on the relationship of receptor AMPA/kainite-induced receptor with urinary disorders, drug addiction, pain and the like (J. Pharmacol. Exp. Ther., 280, 894-904, 1997; Neuroscience Letters, 268:127-130, 1999).

It can be expected that the substance showing an antagonistic effect on the excitatory neurotransmitter receptors, are useful in the treatment of the above conditions affecting the nervous system.

Now most probable usefulness of the substances having antagonistically effect on non-NMDA receptors, such as receptor AMPA and kainite-induced receptor. For example, it was reported that inhibitors of the interaction of glutamate and AMPA and/or kainite-induced receptor complex useful in the treatment of demyelinating disorders such as encephalitis, acute disseminated encephalomyelitis, acute demyelinizing polyneuropathy (Guillain-Barre syndrome), chronic inflammatory demyelinizing polyneuropathy, multiple sclerosis, a disease of Marchiafava-Bignami, Central Pontigny myelinosis syndrome), Balo disease, HIV or HTLV-myelopathy, progressive mnogofotonnaya leucoencephalopathy, secondary demyelinizing disorder; WO 00/01376 as a secondary demyelinating disorders, and the like described, for example, CNS lupus erythematosus, polyarteritis polyarteritis, with ngram Sjogren, sarcoidosis, localized cerebral vasculitis, and the like. As for compounds with inhibitory activity against receptor AMPA and kainite-induced receptor is, for example, messages about the following compounds.

(1) Competitive inhibiting AMPA receptor compounds represented by the following formula.

(2) Noncompetitive inhibiting AMPA receptor compounds represented by the following formula.

(3) in Addition to the above, in WO 94/25469, WO 96/10023, in U.S. patent 5356902 and so on, are reported competitive inhibiting AMPA receptor compounds having hinoksalinovym skeleton, and in WO 95/01357, WO 97/28135, WO 97/28163, WO 97/43276, WO 97/34878, WO 98/38173, EP 802195, DE 19643037 and so on are reported noncompetitive inhibiting AMPA receptor compounds.

In WO 97/17970 reported derived peridotites possessing inhibitory activity against neurocytotoxicity of kainate, which is based on non-competitive antagonism against AMPA receptor response. In WO 00/27851 reported condensed derived pyridazinone with action, improves memory, which is based on increased activity of NMDA receptors and inhibiting AMPA activity. In WO 00/47567 reports the connection as a function gets is of radiation, with antagonism against non-NMDA receptor, which is represented by the formula:

where A represents O, S or NR3(where R3represents a hydrogen atom or a group of the lower alkyl); R1and R2do not depend on each other and each represents optionally substituted (hetero)aryl group; and R4and R5independently represent hydrogen, hydroxyl group, halogen, cyano, nitro, lower alkyl, (hetero)aryl group and the like.

In WO 99/10331, WO 99/10332 and WO 00/24719 reported pyridazinone the compound as an inhibitor of cyclooxygenase-2 and the like, which is represented by the following formula or its salt, or ester, or prodrug:

where X represents O, S, and so on; R represents an aryl group and so forth; and at least one R1, R2and R3represents a phenyl group substituted by a specific group, and so on, while the other two groups represent an aryl group, and so on. In WO 99/25697, 99/44995 and WO 00/50408 reported derived pyridazinone as an inhibitor of the synthesis of interleukin-1β. In WO 00/09488 reported derived pyridazinone possessing inhibitory activity against adhesion of cells. In WO 97/07104, EP0860435, EP 0963978, WO 00/34249, U.S. patent 6107250, JP-A 5-25164, DE 4423934 and so on, also reported derived pyridazinone having antimicrobial activity and herbicide activity for use in Agrochemistry, but not described and not known for its relationship with the receptor AMPA/kainite-induced receptor. There are also several reports on the use of triazinone compounds as pesticides, but not described and not known for their interaction with the receptor AMPA/kainite-induced receptor. Also not aware of the relationship derived pyridazin-3-one having a cyclic replacement group at the 2-, 4 - and 6-positions, and derived 1,2,4-triazine-3-one with receptor AMPA/kainite-induced receptor.

It is desirable to have a compound that exhibits excellent inhibitory activity against AMPA receptor and/or kainite-induced receptor and is highly effective as a pharmaceutical drug in clinical practice. Thus, the aim of the present invention is to research and discover a compound that inhibits AMPA receptor and/or kainite-induced receptor that inhibits the neurotoxicity of excitatory neurotransmitters and achieves excellent neuroprotective actions in the form of pharmaceuticals to be used as funds for the treatment, prevention or improvement of various nervous C the problems.

Description of the invention

In such conditions, the authors of the present invention conducted a thorough investigation. As a result, they was first successfully performed the synthesis of compounds (compound (I)represented by the following formula, its salt or its hydrate, and was found a great way of obtaining this compound, its salts and their hydrates. In addition, unexpectedly, they discovered that the above-mentioned compound (I), its salt, or a hydrate, demonstrates excellent antagonism against AMPA receptor and/or kainite-induced receptor, in consequence of which was completed this invention.

In the formula, A1, A2and A3do not depend on each other and each represents a C3-8cycloalkyl group, C3-8cycloalkenyl group, 5 to 14-membered non-aromatic heterocyclic group, a C6-14aromatic hydrocarbon cyclic group or a 5 to 14-membered aromatic heterocyclic group, each of which may be substituted; Q represents O, S or NH; Z represents C or N; X1X2and X3do not depend on each other and each represents a simple bond, optionally substituted C2-6alkylenes group, optionally substituted C2-6alkynylamino group, optionally substituted C2-6alkynylamino groups who, -NH-, -O-, -N (R4)CO-, -CON (R5)-, -N (R6)CH2-, -CH2N (R7)-, -CH2CO-, -COCH2-, -N (R8)SO0-2-, -SO0-2N (R9)-, -CH2SO0-2-, -SO0-2CH2-, -CH2O-, -OCH2-, -N (R10)CON (R11)-, -N (R12)CS-N (R13)- or-SO0-2- (where R4, R5, R6, R7, R8, R9, R10, R11, R12and R13do not depend on each other and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup; R1and R2do not depend on each other, and each represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C2-6alkenylphenol group or optionally substituted C2-6alkylamino group, or R1and R2can be connected to each other so that CR2-ZR1forms a double carbon-carbon bond, represented as C=C (provided that, when Z represents N, R1is a lone pair); R3represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C2-6alkenylphenol group or optionally substituted C2-6alkylamino group, or may be bonded to any atom in A1or A3with education, together with the atom, the long is correctly substituted C 5-8hydrocarbon ring or an optionally substituted 5-8-membered heterocyclic ring, provided that (1)when Z represents N; each of X1X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group, (2) when Z represents N; each of X1X2and X3represents a simple bond; A1represents o,p-dimethylphenyl group; A2is an on-methylphenylene group; and A3represents a phenyl group, or (3) when Z represents N; each of X1X2and X3represents a simple bond; A1is an on-methylphenylene group; A2represents the p-metoksifenilny group; and A3represents a phenyl group, at least one of R2and R3is a group other than hydrogen), provided that, in the above definitions, no connections are allowed in the following, with (1) through (20), where:

(1) the case when part of the structure ZR1-CR2is a C=C; R3represents a hydrogen atom; X1represents-CH2CH2-; A1represents the p-chloraniline group; A2represents the p-bromperidol group; and A3isone phenyl group, group p-tolil or p-metoksifenilny group, (2) the case when part of the structure ZR1-CR2is a C=C; R3represents a hydrogen atom; X2represents-CH2CH2CH2-; A2is a group of [4-(m-chlorophenyl)]piperazinil; and each of the A1and A3represents a phenyl group, (3) the case when part of the structure ZR1-CR2is a C=C; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group, (4) the case when part of the structure ZR1-CR2is a C=C; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each of the A1and A2represents a phenyl group; and A3represents the p-taillow group or p-metoksifenilny group, (5) the case when part of the structure ZR1-CR2is a C=C; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each of the A2and A3represents a phenyl group; and A1represents the p-metoksifenilny group, N-piperazinilnom group, N-piperidinyl the group or N-morpholinyl group, (6) the case when part of the structure ZR1-CR2is a C=C; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1represents a 2,4,6-trimethylphenyl group; A2represents a phenyl group; and A3represents a 3,4-dichloraniline group, (7) the case when Z represents C, each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group, (8) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each of the A1and A2represents a phenyl group; and A3represents the p-taillow group, p-chloraniline group, p-metoksifenilny group, 3-methoxy-4-iodophenyl group, 3-chloro-4-metoksifenilny group, 9-antarctilyne group, 3-bromo-4-metoksifenilny group or 4-methyl-3-iodophenyl group, (9) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1p is ecstasy a 3,5-dimethyl-1H-pyrazole-1-ilen group; A2represents a phenyl group; and A3represents a phenyl group, p-bromperidol group, p-chloraniline group, p-metoksifenilny group, p-taillow group, 3,4-dichloraniline group, 2,4-dimethylphenyl group or 3-methyl-4-chloraniline group, (10) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1represents a 2,4-dimethylphenyl group; A2represents a phenyl group; and A3represents a phenyl group, p-taillow group, 3,4-dichloraniline group, 2,4-dimethylphenyl group or 4-methyl-3-bromperidol group, (11) for the case when Z represents C; each of R1, R2and R2represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1represents a 2,4,6-trimethylphenyl group; A2represents a phenyl group; and A3represents a phenyl group or a 3,4-dichloraniline group, (12) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1represents a 2,4,6-trimeth fanilow group; A3represents a 3,4-dinitrophenyl group; and A2is a 4-nitrophenyl group or 2,4-dinitrophenyl group, (13) the case where Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1is a 2.5 dimethylphenyl group; A2represents a phenyl group; and A3represents the p-diphenylene group, 3,4-dichloraniline group or 3-methyl-4-chloraniline group, (14) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A2represents a phenyl group; A3represents the p-bromperidol group; and A1represents the p-taillow group, p-ethylphenyl group or p-isopropylphenyl group, (15) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A2represents a phenyl group; and each of the A1and A3represents the p-metoksifenilny group or 3,4-dimethylphenyl group, (16) for the case when Z is a C; b the th of R 1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; A1represents the p-taillow group; A2represents a phenyl group; and A3represents the p-chloraniline group, (17) the case where Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each of the A1and A3represents a phenyl group; and A2is a group 1 methylpiperidin-4-yl, (18) the case where Z represents C; each of R1, R2and R3represents a hydrogen atom, each of X1X2and X3represents a simple bond; A1represents a 2,4,6(1H,3H,5H)-pyrimidinetrione-5-ilen group; A2represents a phenyl group; and A3represents a 3-methyl-4-chloraniline group, (19) the case when Z represents C; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each of the A1and A3represents a 2,4-dimethylphenyl group; and A2represents a 2,4-dinitrophenyl group, and (20) for the case when Z represents N; X12and R3represents a hydrogen atom; each of X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group.

That is, the present invention relates (1) to the compound represented by the above formula (I), its salt or hydrate; (2) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where A1, A2and/or A3do not depend on each other, and each represents a C3-8cycloalkyl group, C3-8cycloalkenyl group or 5 to 14-membered non-aromatic heterocyclic group, each of which may be substituted; (3) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where A1, A2and A3do not depend on each other, and each represents a C6-14aromatic hydrocarbon cyclic group or a 5 to 14-membered aromatic heterocyclic group, each of which may be substituted; (4) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where A1, A2and A3do not depend on each other, and each represents a phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group which, thiazolidine group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexenyl group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidinyl group, piperazinilnom group or morpholinyl group, each of which may be substituted; (5) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where A1, A2and A3do not depend on each other, and each represents a group represented by the formula:

each of which may be substituted; (6) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where X1X2and X3do not depend on each other and each represents (a) a simple link, (b) C2-6alkylenes group, C2-6alkenylamine group or a C2-6alkynylamino group, each of which may be substituted by one or more groups selected from the group below substituents, (c) -NH-, (d) -O-, (e) -N (R4)CO-, (f),- CON (R5)- (g) -N(R6)CH2-, (h) -CH2N (R7)- (i) -CH2CO-, (j) -COCH 2-, (k) -N(R8)SO0-2-, (l) -SO0-2N (R9)-, (m) -CH2SO0-2-, (n) -SO0-2CH2-, (o) -CH2O - (p) -OCH2-, (q) -N (R10)CON (R11)-, (r) -N(R12)CS-N (R13)- or (s) -SO0-2- (where R4, R5, R6, R7, R8, R9, R10, R11, R12and R13have the same meaning as defined in the above item (1), respectively); and A1, A2and A3do not depend on each other, and each represents a C3-8cycloalkyl group, C3-8cycloalkenyl group, 5 to 14-membered non-aromatic heterocyclic group, a C6-14aromatic hydrocarbon cyclic group or a 5 to 14-membered aromatic heterocyclic group, each of which may be substituted by one or more groups selected from the group of substituents b below:

<group Vice a>: group consisting of hydroxyl group, halogen atom and cyanopropyl;

<a group of substituents b>: group (a) hydroxyl group, (b) halogen atom, (c) nitrile group, (d) nitro, (e) from C1-6alkyl group, a C2-6alkenylphenol group or a C2-6alkenylphenol groups, each of which may be substituted by at least one group selected from the group consisting of a hydroxyl group, a nitrile group, a halo atom is s, C1-6alkylamino, di (C1-6alkyl)amino, C2-6alkynylamino, di (C2-6alkenyl)amino, C2-6alkynylamino, di (C2-6quinil)amino, N-C1-6alkyl-N-C2-6alkynylamino, N-C1-6alkyl-N-C2-6alkynylamino, N-C2-6alkenyl-N-C2-6alkynylamino, aralkylated, TBDMS (tert-butyldimethylsilyl) actigraphy, C1-6alkylsulfonamides, C1-6alkylcarboxylic, C2-6alkenylboronic, C2-6alkylcarboxylic, N-C1-6alkylcarboxylic group, N-C2-6alkenylamine group and N-C2-6alkylcarboxylic group, (f) from C1-6alkoxygroup, C2-6alkenylacyl or C2-6alkyloxy, each of which may be substituted by at least one group selected from the group consisting of C1-6alkylamino, aralkylated and hydroxyl group, (g) from C1-6allylthiourea, C2-6altertekhnogrupp or C2-6alinytjara, each of which may be substituted by at least one group selected from the group consisting of a hydroxyl group, a nitrile group, a halogen atom, a C1-6alkylamino, aralkylated, TBDMS actigraphy, C1-6alkylsulfonamides,1-6alkyls is boilershop and C 1-6alkylcarboxylic group, (h) a carbonyl group substituted by a group selected from the group consisting of C1-6alkoxygroup, amino, C1-6alkylamino, di(C1-6alkyl)amino, C2-6alkynylamino, di(C2-6alkenyl)amino, C2-6alkynylamino, di (C2-6quinil)amino, N-C1-6alkyl-N-C2-6alkynylamino, N-C1-6alkyl-N-C2-6alkynylamino and N-C2-6alkenyl-N-C2-6alkynylamino, (i) an amino group which may be substituted by one or two groups selected from the group consisting of C1-6alkyl group, a C2-6alkenylphenol group, C2-6alkenylphenol group, C1-6alkylsulfonyl group, C2-6alkanesulfonyl group, C2-6alkylsulfonyl group, C1-6alkylcarboxylic group, C2-6alkenylamine group and C2-6alkylcarboxylic group, (j) from C1-6alkylsulfonyl group, (k) from C2-6alkanesulfonyl group, (l) from C2-6alkylsulfonyl group, (m) from C1-6alkylsulfonyl group (n) from C2-6alkanesulfonyl group, (o) from C2-6alkylsulfonyl group, (p) formyl group, (q) from C3-8cycloalkyl group or a C3-8cycloalkenyl groups, each of which shall be substituted, at least one group selected from the group consisting of hydroxyl group, halogen atom, nitrile group, With1-6alkyl group, a C1-6alkoxygroup,1-6alkoxy-C1-6alkyl groups and aranceles group (r) of 5 to 14-membered non-aromatic heterocyclic group which may be substituted by at least one group selected from the group consisting of hydroxyl group, halogen atom, nitrile group, With1-6alkyl group, a C1-6alkoxygroup, C1-6alkoxy-C1-6alkyl groups and aranceles group (s) of C6-14aromatic hydrocarbon cyclic group which may be substituted by at least one group selected from the group consisting of hydroxyl group, halogen atom, nitrile group, a C1-6alkyl group, a C1-6alkoxygroup, C1-6alkoxy-C1-6alkyl groups and aranceles group, and (t) of 5 to 14-membered aromatic heterocyclic group which may be substituted by at least one group selected from the group consisting of hydroxyl group, halogen atom, nitrile group, a C1-6alkyl group, a C1-6alkoxygroup, C1-6alkoxy-C1-6alkyl groups and aranceles group, and (u) of Tilney group; (7) to the connection in accordance with Visayas is authorized by paragraph (1), salts thereof or their hydrate, where the group of substituents in the A1, A2and/or A3do not depend on each other, and each represents a hydroxyl group, halogen atom, nitrile group, or a nitro-group; (8) to the connection in accordance with the above compound (1), salts thereof or their hydrate, where Q represents O; (9) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where X1X2and X3do not depend on each other, and each represents a simple bond, -CH2-, -CH (OH)-, -CH2CH2-, -CH=CH - or-C=C-; (10) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where X1X2and X3each represents a simple bond; (11) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where R1, R2and/or R3represents an optionally substituted C1-6alkyl group; (12) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where R1, R2and/or R3each represents a hydrogen atom; (13) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where R1and R2connected to each other so that part of the structure ZR1-CR2forms a carbon-carbon double bond represented by the formula C=C; (14) to which the Association in accordance with the above paragraph (1), salts thereof or their hydrate, where R3attached to the atom in A1with the formation of a ring with the atom and X1; (15) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where R3attached to the atom in A3with the formation of a ring with the atom and X3; (16) to the connection in accordance with the above paragraphs (14) or (15), its salt or hydrate, where the ring formed by R3represents (a) optionally substituted C5-8hydrocarbon ring or (b) a 5-8-membered heterocyclic ring which contains an oxygen atom and is optionally substituted; (17) the compound according to any one of items (14)to(16), salts thereof or their hydrate, where X3represents a simple bond; (18) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, where the provisions of the accession of substitution groups in A1, A2and/or A3are α-the provisions of the carbon atoms in A1, A2and/or A3, each of which is associated with X1X2and X3respectively; (19) to the compound represented by the following formula, its salt or hydrate:

where A1a, A2aand A3ado not depend on each other, and each represents a C6-14aromatic hydrocarbon cyclic group and the and 5 to 14-membered aromatic heterocyclic group, each of which may be substituted; X1X2and X3are the same values that are defined in the above item (1), respectively; and part of the structure:

represents a single or double bond, provided that, in the above definitions, no connections are allowed in the following, (1) and (2), cases:

(1) the case when part of the structure:

is a double carbon-carbon bond; R3represents a hydrogen atom; and have the following from (1A) to (1f), cases:

(1a) the case when X1represents-CH2CH2-; A1is a group of p-chlorphenyl; A2represents the p-bromperidol group; and A3represents a phenyl group, p-taillow group or p-metoksifenilny group, (1b) the case when X2represents-CH2CH2CH2-; A2represents [4-(m-chlorophenyl)]piperazinilnom group; and each of the A1and A2represents a phenyl group, (1C) case where each of X1X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group, (1d) case, when each of X1X2and X3represents a simple bond; each is output from the A 1and A2represents a phenyl group; and A3represents the p-taillow group or p-metoksifenilny group, (1e) case where each of X1X2and X3represents a simple bond; each of the A2and A3represents a phenyl group; and A1represents the p-metoksifenilny group, N-piperazinilnom group, N-piperidinyloxy group or N-morpholinyl group, and (1f) case where each of X1X2and X3represents a simple bond; A1represents a 2,4,6-trimethylphenyl group; A2represents a phenyl group; and A3represents a 3,4-dichloraniline group, and

(2) the case when part of the structure:

represents a simple bond; each of X1X2and X3represents a simple bond; and the following, with (2A) to (2m), cases:

(2a) the case when each of the A1, A2and A3represents a phenyl group, (2b) case, when each of the A1and A2represents a phenyl group; and A3represents the p-taillow group, p-chloraniline group, p-metoksifenilny group, 3-methoxy-4-iodophenyl group, 3-chloro-4-metoksifenilny group, 9-antarctilyne group, 3-bromo-4-metoksifenilny group and the 4-methyl-3-iodophenyl group, (2c) the case when A1represents 3,5-dimethyl-1H-pyrazole-1-ilen group; A2represents a phenyl group; and A3represents a phenyl group, p-bromperidol group, p-chloraniline group, p-metoksifenilny group, p-taillow group, 3,4-dichloraniline group, 2,4-dimethylphenyl group or 3-methyl-4-chloraniline group, (2d) case when A1represents a 2,4-dimethylphenyl group; A2represents a phenyl group; and A3represents a phenyl group, p-taillow group, 3,4-dichloraniline group, 2,4-dimethylphenyl group or 4-methyl-3-bromperidol group, (2e) case when A1represents a 2,4,6-trimethylphenyl group; A2represents a phenyl group; and A3represents a phenyl group or a 3,4-dichloraniline group, (2f) case when A1represents a 2,4,6-trimethylphenyl group; A3represents a 3,4-dichloraniline group; and A2is a 4-nitrophenyl group or 2,4-dinitrophenyl group, (2g) case when A1is a 2.5 dimethylphenyl group; A2represents a phenyl group; and A3represents the p-diphenylene group, 3,4-dichloraniline group or 3-methyl-4-chloraniline group, (2h) case when A2before the hat is phenyl group; A3represents the p-bromperidol group; and A1represents the p-taillow group, p-ethylphenyl group or p-isopropylphenyl group, (2i) case when A2represents a phenyl group; and A1and A3do not depend on each other, and each represents a p-metoksifenilny group or 3,4-dimethylphenyl group, (2j) case when A1represents the p-taillow group; A2represents a phenyl group; and A3represents the p-chloraniline group (2k) case, when each of the A1and A3represent a phenyl group; and A2is a 1-methylpiperidin-4-ilen group (2l) case when A1represents a 2,4,6 (1H,3H,5H)-pyrimidinetrione-5-ilen group; A2represents a phenyl group; and A3represents a 3-methyl-4-chloraniline group, and (2m) case, when each of the A1and A3represent 2,4-dimethylphenyl group; and A2represents a 2,4-dinitrophenyl group; (20) the compound according to the above item (19), its salt or hydrate, where A1a, A2aand A3aindependently represent a phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group, t is asailing group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexenyl group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidinyl group, piperazinilnom group or morpholinyl group, each of which may be substituted; (21) the compound according to the above item (19), its salt or hydrate, where each of X1X2and X3represents a simple bond; (22) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the formula:

where, A1a, A2aand part of the structure:

has the same values that are defined in the above item (19), respectively; X1X2and X3are the same values that are defined in the above item (1), respectively; the ring A3brepresents a C6-8aromatic hydrocarbon ring or a 5-8-membered aromatic heterocyclic ring, each of which may be substituted; and ring B represents (a) is not necessarily alseny C 5-9cycloalkane or C5-9cycloalken or (b) 5-9-membered non-aromatic heterocyclic ring which contains a heteroatom selected from the group consisting of N, O and S and may be substituted; (23) the compound according to the above item (22), its salt or hydrate, where A1a, A2aand A3bdo not depend on each other, and each represents a phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group, thiazolidine group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexenyl group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidinyl group, piperazinilnom group or morpholinyl group, each of which may be substituted; (24) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the formula:

where A2a, A3aand part of the structure:

are the same values that you defined in EUcasino paragraph (19), respectively; X1X2and X3are the same values that are defined in the above item (1), respectively; the ring A1brepresents a C6-8aromatic hydrocarbon ring or a 5-8-membered aromatic heterocyclic ring, each of which may be substituted; and ring represents (a) optionally substituted C5-9cycloalkane or C5-9cycloalken or (b) 5-9-membered non-aromatic heterocyclic ring which contains a heteroatom selected from the group consisting of N, O and S and may be substituted; (25) the compound according to the above item (24), its salt or hydrate, where A1a, A2aand A3aindependently represents a phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group, thiazolidine group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexenyl group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidinyl group, piperazinilnom groups is or morpholinyl group, each of which may be substituted; (26) the compound according to the above item (22), its salt or its hydrate, which is represented by the formula:

where A1a, A2a, A3band part of the structure:

are the same values that are defined in the above item (22); and D represents a group-CH2-, -(CH2)2-, -C=C-, -C≡C-, -O-, -OCH2-, -CH2O-, -SO0-2-, -SCH2-, -CH2S-, -SOCH2-, -CH2SO-, -SO2CH2-, -CH2SO2-, -NR14-, -NR14CH2- or-CH2NR14- (where R14represents a hydrogen atom, a C1-6alkyl group, optionally substituted C3-8cycloalkyl group, optionally substituted 5 to 14-membered non-aromatic heterocyclic group, optionally substituted C6-14aromatic hydrocarbon cyclic group or optionally substituted 5 to 14-membered aromatic heterocyclic group), and those provisions in D, which may be substituted, may be substituted; (27) the compound according to the above item (24), its salt or its hydrate, which is represented by the formula:

where A1b, A2a, A3aand part of the structure:

are those the e values, defined in the above (24), respectively; and E represents-CH2-, -(CH2)2-, -C=C-, -C≡C-, -O-, -OCH2-, -CH2O-, -SO0-2-, -SCH2-, -CH2S-, -SOCH2-, -CH2SO-, -SO2CH2-, -CH2SO2-, -NR14-, -NR14CH2- or-CH2NR14- (where R14has the same meaning as defined in the above item (26)), and related provisions in E can be substituted; (28) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the formula:

where A1, A2, A3and part of the structure:

have the same values as those defined above, respectively; (29) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the formula:

where A1, A3and part of the structure:

have the same values as those defined above, respectively; the ring A2brepresents a C6-14aromatic hydrocarbon ring or a 5 to 14-membered aromatic heterocyclic ring, each of which may be optionally substituted; and R15represents a hydroxyl group, halogen atom, nitrile group, the 1-6alkyl group, a C1-6alkoxygroup, the nitro-group, amino group, With1-6alkylamino, formyl group, C1-6alkylcarboxylic group or triptorelin group; (30) to the connection in accordance with the above paragraph (29), its salt or hydrate, where A1, A2band A3do not depend on each other, and each represents a phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group, thiazolidine group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexenyl group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidinyl group, piperazinilnom group or morpholinyl group, each of which may be substituted; (31) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the formula:

where A1, A2, A3X1X2and X3have the same values as those defined above, respectively, when the condition is and, that excluded the following compounds (a)-(d) cases:

(a) the case when X1represents-NHCO-; each of X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group, (b) case where each of X1X2and X3represents a simple bond; and each of the A1, A2and A3represents a phenyl group, (c) case where each of X1X2and X3represents a simple bond; A1represents o,p-dimethylphenyl group; A2is an on-methylphenylene group; and A3represents a phenyl group, and (d) case where each of X1X2and X3represents a simple bond; A1is an on-methylphenylene group; A2represents the p-metoksifenilny group; and A3represents a phenyl group; (32) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the formula:

where A1, A2and A3are the same values that are defined in the above item (1), respectively, provided that excluded the following compounds (a)-(C) cases:

(a) the case when each of the A1, A2and A3is the Wallpaper phenyl group, (b) a case when A1represents o,p-dimethylphenyl group; A2is an on-methylphenylene group; and A3represents a phenyl group, and (c) the case when A1is an on-methylphenylene group; A2represents the p-metoksifenilny group; and A3represents a phenyl group; (33) the compound according to the above item (32), salts thereof or their hydrate, where A1, A2and A3do not depend on each other, and each represents a C6-14aromatic hydrocarbon cyclic group or a 5 to 14-membered aromatic heterocyclic group, each of which may be substituted; (34) the compound according to the above item (32), salts thereof or their hydrate, where A1, A2and A3do not depend on each other, and each represents a phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group, thiazolidine group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexene is inuu group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidinyl group, piperazinilnom group or morpholinyl group, each of which may be substituted; (35) the compound according to the above item (32), salts thereof or their hydrate, where A1, A2and A3do not depend on each other, and each is selected from the group represented by the formula:

each of which may be substituted; (36) the compound according to the above item (32), salts thereof or their hydrate, where each of the A1, A2and A3may be substituted by at least one group selected independently from the group consisting of a halogen atom, ceanography, hydroxyl group, amino group, formyl group and nitro group; (37) the compound according to the above item (32), salts thereof or their hydrate, where the provisions of joining groups of substituents in the A1, A2and/or A3are α-the provisions of the carbon atoms in A1, A2and/or A3, each of which is attached directly to triazinone ring; (38) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is represented by the following formula:

where, A1, A2, A3, A1b, A3bX 1X2X3, D, E, and R2have the same values as those defined above, respectively; (39) to the connection in accordance with the above paragraph (1), salts thereof or their hydrate, which is any compound selected from 2-(2-bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-[3-(2-hydroxyethoxy)-phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-(2-cyanophenyl)-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-(2-itfeel)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-cyanophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 4-(4-methoxybenzyl)-6-phenyl-2-(2-tolyl)-3(2H)-pyridazinone, 2,6-diphenyl-4-(α-hydroxy-2-picolyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(4-morpholinosydnonimine)-6-phenyl-3(2H)-pyridazinone, 2-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-2H-pyridazino[4,5-b]benzofuran-3-one, 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(4-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-feast of the deal)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-itfeel)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-methoxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-phenyl-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4,6-diphenyl-2-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-methoxyphenyl)-2-(2-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-bromophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-methoxyphenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-phenyl-2-(2-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-forfinal)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(4-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-6-(2-hydroxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-dimethylaminoethoxy)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-6-(2-dimethylaminoethoxy)-4-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-[3-(2-picolylamine)]-6-(2-who iridis)-3(2H)-pyridazinone, 2-phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-bromophenyl)-2-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-9-fluoro-4-phenyl-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-cyanophenyl)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano-[4,3-C]pyridazin-3-one, 2-(2-bromophenyl)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-9-fluoro-5-hydroxy-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-cyanophenyl)-9-fluoro-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-phenyl-6-(2-pyridyl)-4-(2-trifluoromethyl-sulfonyloxy)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-itfeel)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-phenyl-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-bromophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-chlorophenyl)-4-(4-morpholinosydnonimine)-6-phenyl-3(2H)-pyridazinone, 2-(2-nitrophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3-tolyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(4-methanesulfonyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(4-biphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-naphthyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3,4-methylenedioxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3,4-dichlorophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-pyridyl)-4-(2-pyridyl)-6-(2-methoxyphenyl)-3(2H)-pyridazinone, 2-(3-formylphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(thiophene-3-yl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3-pyridyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3-pyridyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-methoxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-methyl-2,4,6-triphenyl-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone, 2-(3-pyridine-1-oxide)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyano-5-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyano-3-the l)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyano-5-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-cyano-3-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyrazinyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(triazole-2-yl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-dimethylaminoethoxy)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she 4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she 4-(2-cyanophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-6-(2-m is toxigenic)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she 4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-phenyl-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-she 4-(2,4-acid)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-phenyl-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she 4-(2-bromophenyl)-2,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(2-bromophenyl)-6-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she 4-(2-bromophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(2,5-acid)-6-(2-methoxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H- , 4-(2,5-acid)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-phenyl-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she 2-(2-bromophenyl)-4-(4-biphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(4-forfinal)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(3-formylphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(3-tolyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(4-dimethoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-bromophenyl)-4-(2-chloropyridin-5-yl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-(2-cyanophenyl)-4-(3-AMINOPHENYL)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she and 2-(2-chlorophenyl)-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it; (40) to pharmaceutical compositions containing as active ingredient a compound represented by the formula (I) in the above item (1), its salt or hydrate; (41) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an inhibitor of receptor α-amino-3-hydroxy-5-methyl-4-isoxazolidinone acid (hereinafter called "AMPA") and/or inhibitor of kainite-induced receptor; (42) the pharmaceutical composition according to the above item (40), which is an inhibitor of AMPA receptor; (43) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an inhibitor of kainite-induced receptor; (44) to be supplied with the tion of the arrangement in accordance with the above paragraph (40), which is a tool for the treatment or prevention of disease, in which participates the AMPA receptor or kainite-induced receptor; (45) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an agent for the treatment or prevention of disease, which can participate "AMR"; (46) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an agent for the treatment or prevention of acute neurodegenerative diseases; (47) to the pharmaceutical compositions in accordance with the above paragraph (40), which is a tool for the treatment or prevention of cerebrovascular diseases in the acute stage, head injury, spinal cord injury, neuropathy caused by hypoxia, or neuropathy caused by hypoglycemia; (48) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an agent for the treatment or prevention of chronic neurodegenerative disease; (49) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an agent for the treatment or prevention of Alzheimer's disease, Parkinson's disease, horei of Hantington, amyotrophic lateral sclerosis or spinal cerebellar degeneracy is; (50) the pharmaceutical composition according to the above item (40), which is an agent for the treatment or prevention of epilepsy, hepatic encephalopathy, peripheral neuropathy, Parkinson's disease, spasticity, pain, neuralgia, schizophrenia, anxiety, drug abuse, nausea, vomiting, dysuria, impairment of vision caused by glaucoma, paracasei caused by antibiotics or food poisoning; (51) to the pharmaceutical compositions in accordance with the above paragraph (40), which is an agent for the treatment or prevention of infectious encephalomyelitis, cerebrovascular dementia, or dementia, or neurosis caused by cerebrospinal meningitis; (52) the pharmaceutical composition according to the above item (51), where infectious encephalomyelitis encephalomyelitis is HIV; (53) to the pharmaceutical compositions in accordance with the above paragraph (40), which is a failure for the treatment or prevention of demyelinating disease; (54) pharmaceutical compositions in accordance with the above paragraph (53)where demyelinizing disease is encephalitis, acute disseminated encephalomyelitis, multiple sclerosis, acute demyelinizing polyneuropathy, Guillain-Barre syndrome, chronic inflammatory de is ilinishna polyneuropathy, disease Marchiafava-Bignami, Central Pontigny myelinosis, neuroptimal syndrome), Balo disease, myelopathy HIV or myelopathy with HTLV, progressive mnogofotonnaya leucoencephalopathy or secondary demyelinizing disease; (55) to the pharmaceutical compositions in accordance with the above paragraph (54), where the second demyelinizing disease is CNS lupus erythematosus, polyarteritis polyarteritis, Sjogren syndrome, sarcoidosis or localized cerebral vasculitis, and the like.

The compound of the present invention can be a pharmaceutically acceptable salt or a pharmacologically acceptable hydrate.

The pharmaceutical composition according to this invention can comprise a pharmaceutically acceptable carrier.

The present invention relates to a method of treatment or prevention of disease, in which participates the AMPA receptor or kainite-induced receptor by introducing the patient a pharmacologically effective dose of the compounds represented by the above formula (I), its salt or its hydrate.

The present invention relates to the use of compounds represented by the above formula (I), its salt or hydrate to obtain funds for the treatment or prevention of disease involving the AMPA receptor or Cain fair receptor.

Here and further explains the meaning of symbols, terms, and so on, which are used in this description, and describes in detail the invention.

As acute neurodegenerative diseases" according to this invention are, for example, cerebrovascular diseases in the acute stage of subarachnoid hemorrhage, ischemic stroke, and the like), head injury, spinal cord injury and neuropathy due to hypoxia or hypoglycemia; and the like. As a chronic neurodegenerative diseases are, for example, Alzheimer's disease, Parkinson's disease, Huntington Hantington, amyotrophic lateral sclerosis, spinal cerebellar degeneration and the like. As "infectious encephalomyelitis" is, for example, encephalomyelitis with HIV, and as a "demyelinating disease" are encephalitis, acute disseminated encephalomyelitis, multiple sclerosis, acute demyelinizing polyneuropathy, Guillain-Barre syndrome, chronic inflammatory demyelinizing neuropathy, a disease of Marchiafava-Bignami, Central Pontigny myelinosis, neuroptimal syndrome), Balo disease, myelopathy in HIV myelopathy with HTLV, progressive mnogofotonnaya leucoencephalopathy, secondary demyelinizing disease is s, and the like. As a secondary demyelinating disease", mentioned above, are, for example, CNS lupus erythematosus, polyarteritis polyarteritis, Sjogren syndrome, sarcoidosis, localized cerebral vasculitis, and the like.

In this regard, in this specification of the present application, despite the fact that the structure of the formula of compound may for convenience to represent a specific isomer, the present invention includes all isomers such as geometrical isomers, due to the structure of the compound, optical isomers due to asymmetric carbon, rotamer, stereoisomers and tautomers as well as mixtures of isomers, and the present invention is not limited to the description of the formula, shown for convenience, and may be another isomer, or may be a mixture. Accordingly, although it is possible the presence in the molecule of the asymmetric carbon atom and, therefore, the presence of optically active compounds and racemic mixtures, the present invention is not restricted by them, but encompasses any of them. In addition, there may be crystalline polymorphism, and again, there is no restriction, and will receive any form of a crystal or a mixture. The compound (I) or its salt, having regard to the present invention may be an anhydride or a hydrate, and any of them is part of the claims in the present invention. Metabolite which is produced by decomposition of the compound (I) of the present invention in vivo, and the prodrug of compound (I) or its salt, which are relevant to the present invention, are also included in the scope of the claims of the present invention.

Used in this description of "halogen atom" includes fluorine atom, chlorine atom, bromine atom and iodine atom, and preferred atom is a fluorine atom, a chlorine atom or a bromine atom.

Used in this description, "C1-6alkyl group" refers to an alkyl group containing from 1 to 6 carbon atoms, and preferred examples include linear or branched alkyl groups such as methyl group, ethyl group, n-sawn group, isopropyl group, n-bucilina group, isobutylene group, sec-bucilina group, tert-bucilina group, n-pencilina group, 1,1-dimethylpropylene group, 1,2-dimethylpropylene group, 2,2-dimethylpropylene group, 1-ethylpropyl group, 2-ethylpropyl group, n-exilda group, 1-methyl-2-ethylpropyl group, 1-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group, 1-popypropylene 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 the Naya group, 2-ethylbutyl group, 2-methylpentyl group or 3-methylpentyl group.

Used in this description, "C2-6Alchemilla group" refers to alkenylphenol group containing from 2 to 6 carbon atoms, and preferred examples include vinyl group, allyl group, 1-propenyloxy group, 2-propenyloxy group, Isopropenyl group, 2-methyl-1-propenyloxy group, 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-pentanediol group, 1-hexenyl group, 1,3-hexadienyl group, 1,6-hexadienyl group and so on.

Used in this description, "C2-6Alchemilla group" refers to alkenylphenol group containing from 2 to 6 carbon atoms, and preferred examples include etinilnoy group, 1-propenyloxy group, 2-propenyloxy group, 1-butenyloxy group, 2-butenyloxy group, 3-butenyloxy group, 3-methyl-1-propenyloxy group, 1-ethinyl-2-propenyloxy group, 2-methyl-3-propenyloxy group, 1-pantanillo group, 1-hexylamino group, 1,3-hexadienyl group, 1,6-hexadienyl group and so forth.

Used in this description, "C1-6alkoxygroup" refers to alkoxygroup containing from 1 to 6 carbon atoms, and preferred the reamers include a methoxy group, ethoxypropan, n-propoxylate, isopropoxy, sec-propoxylate, n-butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, n-pentyloxy, isopentylamine, sec-pentyloxy, n-hexachrome, isohexadecane, 1,1-DIMETHYLPROPANE, 1,2-DIMETHYLPROPANE, 2,2-DIMETHYLPROPANE, 2-ethylpropoxy, 1-methyl-2-ethylpropoxy, 1-ethyl-2-methylpropoxy, 1,1,2-trimethylpropyl, 1,1-Dimethylbutane, 1,2-Dimethylbutane, 2,2-Dimethylbutane, 2,3-Dimethylbutane, 1,3-Dimethylbutane, 2-ethylbutane, 1,3-Dimethylbutane, 2-methylphenoxy, 3-methylphenoxy, hexyloxy and so on.

Used in this description, "C2-6alkenylacyl" refers to alkanolamine containing from 2 to 6 carbon atoms, and preferred examples include vinyloxy, alloctype, 1-propenyloxy, 2-propenyloxy, isopropenylacetate, 2-methyl-1-propenyloxy, 3-methyl-1-propenyloxy, 2-methyl-2-propenyloxy, 3-methyl-2-propenyloxy, 1-butenyloxy, 2-butenyloxy, 3-butenyloxy, 1-pentyloxy, 1-hexaniacinate, 1,3-hexadienoic, 1,6-hexadienoic and so on.

Used in this description, "C3-8cycloalkyl the group" refers to cycloalkyl group, containing from 3 to 8 carbon atoms, and preferred examples include cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group, cyclooctyl group and so on. "C3-8cycloalkyl" refers to a cyclic structure corresponding to the above C3-8cycloalkyl group", and its preferred examples are also consistent with the examples above, "C3-8cycloalkyl group".

Used in this description, "C3-8cycloalkenyl group" refers to C3-8cycloalkenyl group containing from 3 to 8 carbon atoms, and preferred examples include cyclopropene-1-yl, cyclopropene-3-yl, cyclobuta-1-yl, cyclobuta-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-cyclopentadiene-5-yl, cyclohexen-1-yl, cyclohexen-3-silt, cyclohexen-4-yl, 1,3-cyclohexadiene-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-cycloheptadiene-5-yl, 1,3-cycloheptadiene-6-yl, 1,4-cycloheptadiene-3-yl, 1,4-cycloheptadiene-2-yl, 1,4-cycloheptadiene-1-yl, 1,4-cycloheptadiene-6-yl, 1,3,5-cycloheptatrien-3-yl, 1,3,5-cyclohepta the EN-2-yl, 1,3,5-cycloheptatrien-1-yl, 1,3,5-cycloheptatrien-7-yl, cycloocten-1-yl, cycloocta-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-cyclooctadiene-6-yl, 1,4-cyclooctadiene-7-yl, 1, 5cyclooctadiene-3-yl, 1, 5cyclooctadiene-2-yl, 1,3,5-cyclooctadiene-3-yl, 1,3,5-cyclooctadiene-2-yl, 1,3,5-cyclooctadiene-1-yl, 1,3,5-cyclooctadiene-7-yl, 1,3,6-cyclooctadiene-2-yl, 1,3,6-cyclooctadiene-1-yl, 1,3,6-cyclooctadiene-5-yl, 1,3,6-cyclooctadiene-6-ilen group and so on. "C3-8cycloalkyl" refers to a cyclic structure corresponding to the above-mentioned "C3-8cycloalkenyl group, and preferred examples are also consistent with the examples above, "C3-8cycloalkenyl group".

Used in this invention "5 to 14-membered non-aromatic heterocyclic group" means a monocyclic type, bicyclic type or tricyclic type 5-14-membered nonaromatic heterocyclic group that contains one or more heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom. Preferred examples of this group include, for example, pyrrolidinyl group, pyrrolidino group, piperidino group, piperazinilnom group, imide is solidarily group, pyrazolidinone group, morpholinyl group, tetrahydrofuryl group, tetrahydropyranyl group, dihydropyridine group, dihydropyrazolo group, imidazolidinyl group, oxazolidinyl group and so on. In addition, the group obtained from Spiridonovka rings and non-aromatic condensed ring (for example, a group derived from phthalimide rings, operations of the rings, and the like) are also included in non-aromatic heterocyclic group.

Used in the present invention, "C6-14aromatic hydrocarbonaceous group" and "aryl group" means an aromatic hydrocarbonaceous group comprising 6-14 carbon atoms, and monocyclic group, and it also includes condensed group dziklicska group, tricyclic group, and the like. Specific examples of this group include phenyl group, indenolol group, 1-naftalina group, 2-naftalina group, azulinebloo group, heptylaniline group, biphenylene group, indenolol group, acenaphthylene group, fluorenyl group, phenalenyl group, phenanthroline group, antarctilyne group, Cyclopentasiloxane group, benzocyclobutene group and so on. In addition, under "C6-14aromatic hydrocarbon ring" means what I cyclic structure, corresponding to the above-mentioned "C6-14aromatic hydrocarbon cyclic group, and preferred examples are also consistent with the examples above, "C6-14aromatic hydrocarbon cyclic group".

Under used in the present invention "5 to 14-membered aromatic heterocyclic group" and "heteroaryl group" refers to monocyclic type, bicyclic type or tricyclic type 5-14-membered aromatic heterocyclic group that contains one or more heteroatoms selected from the group comprising a nitrogen atom, a sulfur atom and an oxygen atom. Preferred examples of this group include aromatic heterocyclic groups containing nitrogen, such as pyrrolidine group, Peregrina group, pyridazinyl group, pyrimidinyl group, piratininga group, thiazolidine group, tetrataenia group, benzotriazolyl group, pyrazolidine group, imidazolidinyl group, benzimidazolyl group, indayla group, isoindolyl group, indolizinyl group, prisilna group, indazolinone group, kinolinna group, izochinolina group, finalserena group, talasila group, naphthylidine group, khinoksalinona group, chinadaily group, indolenine group, pteridinyl the group, imidazolidinyl group, pirazinamida group, accidenily group, phenanthridinone group, carbazolyl group, carbazolyl group, pyrimidinyl group, phenanthroline group, ventimilia group, imidazopyridine group, imidazolidinyl group, pyrazolopyrimidine group and so forth; aromatic heterocyclic groups containing sulfur, such as thienyl group or benzothiazoline group; an aromatic heterocyclic group containing oxygen, such as furilla group, Pernilla group, cyclopentadienyl group, benzoperylene group or isobenzofuranone group; and aromatic heterocyclic groups containing 2 or more different heteroatoms, such as thiazolidine group, isothiazolinone group, benzothiazolyl group, benzothiadiazole group, phenothiazinyl group, isoxazolyl group, furazolidine group, phenoxypyridine group, oxazoline group, isoxazoline group, benzoxazolyl group, oxadiazolyl group, pyrazoloquinoline group, imidazothiazole group, thienopyridine group, properally group or piridostigmina group and so on. Under the "5 to 14-membered aromatic heterocyclic ring" means a cyclic structure (s) is appropriate above "5 to 14-membered aromatic heterocyclic group", and preferred examples are also consistent with the examples of the above "5 to 14-membered aromatic heterocyclic group".

In this description, "C5-8hydrocarbon ring" refers to a ring selected from C5-8cycloalkane, C5-8cycloalkene and C6-8aromatic hydrocarbon ring. Preferred ring in particular is not limited and includes preferred examples of C5-8cycloalkane, C5-8cycloalkene and C6-8aromatic hydrocarbon ring, as defined above.

In this description, "5-8-membered heterocyclic ring" refers to a ring selected from a 5-8-membered non-aromatic heterocyclic ring and an aromatic heterocyclic ring, and the preferred ring, in particular, is not limited and includes preferred examples 5-8-membered non-aromatic heterocyclic ring and an aromatic heterocyclic ring, as defined above.

The group denoted by A1, A2and A3in compound (I) of the present invention independently represent optionally substituted C3-8cycloalkyl group, optionally substituted C3-8cycloalkenyl group, optionally substituted 5 to 14-membered non-aromatic heterocyclic group, optionally substituted C6-14aromaticas hydrocarbonaceous group or optionally substituted 5 to 14-membered aromatic heterocyclic group, and each group has the same values as in the above definitions, respectively. The preferred group in A1, A2and A3not specifically limited, but preferred group includes phenyl group, pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, thienyl group, thiazolidine group, follow group, naftalina group, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, imidazopyridine group, carbazolyl group, cyclopentyl group, tsiklogeksilnogo group, cyclohexenyl group, dioxinlike group, adamantly group, pyrrolidinyl group, piperidino group, piperazinilnom group and morpholinyl group which may be substituted, respectively, and so on. A more preferred group includes a group represented by the formula:

which may be optionally substituted, respectively, and so on, and the most preferred group includes a group represented by the formula:

which may be optionally substituted, respectively, and so on.

Examples of preferred groups "Zam is stitely" groups, designated A1, A2and A3in compound (I)include a group such as a hydroxy-group, halogen atom, nitrile group, a nitrogroup, C1-6alkyl group, a C2-6Alchemilla group, C2-6Alchemilla group1-6alkoxygroup, C2-6alkenylacyl, C2-6alkyloxy,1-6allylthiourea, C2-6alchemistjoshua, C2-6alinytjara, amino group, substituted carbonyl group, a C1-6alkylsulfonyl group, C2-6alkanesulfonyl group, C2-6alkylsulfonyl group1-6alkylsulfonyl group, C2-6alkanesulfonyl group, C2-6alkylsulfonyl group, formyl group, kalkilya group, heteroallyl group, oralchroma, heteroarylboronic, C3-8cycloalkyl group, C3-8cycloalkenyl group, 5 to 14-membered non-aromatic heterocyclic group, a C6-14aromatic hydrocarbon group, a 5-14-membered aromatic heterocyclic group and so forth, which may be substituted, respectively.

Examples of preferred group of the above-mentioned "substituents" of the groups denoted by A1, A2and A3include fluorine atom, chlorine atom, bromine atom, iodine atom and so forth, and more preferable example includes a fluorine atom, the chlorine atom and a bromine atom. Examples of preferred groups "C1-6alkyl group which may optionally have substituents"include methyl group, ethyl group, n-sawn group, isopropyl group, n-boutelou group, isobutylene group, tert-boutelou group, n-pentelow group, isopentyl group, neopentyl group, n-hexoloy 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 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 and so forth, each of which may be substituted. Examples of preferred groups "C2-6alkenylphenol group which may optionally have substituents" include a vinyl group, allyl group, 1-propenyloxy group, Isopropenyl group, 1-butene-1-ilen group, 1-butene-2-ilen group, 1-butene-3-ilen group, 2-butene-1-ilen group, 2-butene-2-ilen group and so forth, each of which may be substituted. Examples of preferred groups "C2-6alkenylphenol group which may optionally have substituents, respectively, what about the" include etinilnoy group, 1-propenyloxy group, 2-propenyloxy group, butenyloxy group, pantanillo group, hexylamino group and so forth, each of which may be substituted. Moreover, preferred examples of the "substituents" in the case of groups, which may optionally have substituents"include 1 or more groups selected from a hydroxy-group, nitrile group, halogen atom, N-C1-6alkylamino, N,N-di-C1-6alkylamino, N-C2-6alkynylamino, N,N-di-C2-6alkynylamino, N-C2-6alkynylamino, N,N-di-C2-6alkynylamino, C6-14aromatic hydrocarbonaceous group (for example, phenyl group and so forth), 5-14-membered aromatic heterocyclic groups (e.g. thienyl group, shriley group, peredelnoj group, pyridazinyl group, pyrimidinyl group, personalni group and so on), aralkylated, heterokaryosis, TBDMS-oxypropyl,1-6alkylsulfonamides, C2-6alkanesulfonyl, C2-6alkylsulfonamides, C1-6alkylcarboxylic, C2-6alkenylboronic, C2-6alkylcarboxylic,1-6alkylcarboxylic group, C2-6alkenylamine group, C2-6alkylcarboxylic group and so on.

Predpochtitel the examples of "C 1-6alkoxygroup, which may optionally have substituents" include metaxylene group, ethoxyline group, n-propoxylate, isopropoxy, sec-propoxylate, n-butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, n-phenoxypropan, isobutoxy, sec-phenoxypropan, tert-phenoxypropan, n-hexachrome, isohexadecane, 1,2-DIMETHYLPROPANE, 2-ethylpropoxy, 1-methyl-2-ethylpropoxy, 1-ethyl-2-methylpropoxy, 1,1,2-trimethylpropyl, 1,1-Dimethylbutane, 2,2-Dimethylbutane, 2-ethylbutane, 1,3-Dimethylbutane, 2-methylphenoxy, 3-methylphenoxy, hexyloxy and so on. Preferred examples of "C2-6alkenylacyl, which may optionally have substituents" include vinyloxy, alloctype, 1-propenyloxy, isopropenylacetate, 1-butene-1-lexigraphy, 1-butene-2-lexigraphy, 1-butene-3-lexigraphy, 2-butene-1-lexigraphy, 2-butene-2-lexigraphy and so on. Preferred examples of "C2-6alkenylacyl, which may optionally have substituents" include atenololviagrawp, 1-propenyloxy, 2-propenyloxy, butenyloxy, pentyloxy, hexyloxy and so on. Moreover, preferred examples cover the oil" in the case of groups, "that may not necessarily have substituents" include 1 or more groups selected from C1-6alkylamino, aralkylated, hydroxy-group, and so on.

Accordingly, preferred examples of the "C1-6allylthiourea, which may optionally have substituents", "C2-6altertekhnogrupp, which may optionally have substituents" and "C2-6alinytjara, which may optionally have substituents" include1-6allylthiourea (for example, methylthiourea, ethylthiourea, n-PropertyGroup, isopropylthio, n-butylthiourea, isobutylthiazole, tert-butylthiourea, n-intelligroup, isopentype, pointertype, n-vexillographer and so on), C2-6altertekhnogrupp (for example, visiteurope, lilleoru, 1-PropertyGroup, isopropylthio, 1-butene-1-itigroup, 1-butene-2-itigroup, 1-butene-3-itigroup, 2-butene-1-itigroup, 2-butene-2-itigroup and so forth) and C2-6alinytjara (for example, tinytip, 1-propylthiourea, 2-propylthiourea, BUSINESSEUROPE, Penicillium, hexeditor and so forth), which may be optionally substituted by 1 or more groups selected from the group containing, hydroxy-group, halogen atom, nitrile group and a nitro-group.

Preferred is entrusted examples of the carbonyl group, which substituted" include a group represented by the formula-CO-W (examples of W in the formula include1-6alkyl group, a C2-6alkenylphenol group, C2-6alkylamino group1-6alkoxygroup, amino, N-C1-6alkylamino, N,N-di (C1-6alkyl)amino group, N-C2-6alkynylamino, N,N-di (C2-6alkenyl)amino group, N-C2-6alkynylamino, N,N-di (C2-6quinil)amino group, N-C1-6alkyl-N-C2-6alkynylamino, N-C1-6alkyl-N-C2-6alkynylamino, N-C2-6alkenyl-N-C2-6alkynylamino and so on).

Examples of "substituents" of the "amino group which may optionally have substituents" include 1 or 2 groups selected from C1-6alkyl group, a C2-6alkenylphenol group, C2-6alkenylphenol group1-6alkylsulfonyl group, C2-6alkanesulfonyl group, C2-6alkylsulfonyl group1-6alkylcarboxylic group, C2-6alkenylamine group, C2-6alkylcarboxylic group and so forth, which may be respectively substituted. Preferred examples of the "substituents" C1-6alkyl group, a C2-6alkenylphenol group, C2-6alkenylphenol group, C1-6alkylsulfonyl group, C2-6alkanesulfonyl group is s, C2-6alkylsulfonyl group1-6alkylcarboxylic group, C2-6alkenylamine group and C2-6alkylcarboxylic group include a hydroxy-group, halogen atom, nitrile group, With1-6alkoxygroup,1-6allylthiourea and so on. Particularly preferred examples of the "amino group which may optionally have substituents" include methylaminopropyl, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, tert-butylamino, n-pentylamine, isopentylamine, neopentylene, n-hexylamine, 1-methylpropylamine, 1,2-dimethylpropylene, 2-ethylpropylamine, 1-methyl-2-ethylpropylamine, 1-ethyl-2-methylpropylamine, 1,1,2-trimethylpropyl, 1-methylbutylamine, 2-methylbutylamine, 1,1-dimethylbutylamino, 2,2-dimethylbutylamino, 2-ethylbutylamine, 1,3-dimethylbutylamino, 2-methylpentylamino, 3-methylpentylamino, N,N-dimethylaminopropyl, N,N-diethylaminopropyl, 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-is exil) amino group, N,N-di (1-methylpropyl)amino group, N,N-di (1,2-dimethylpropyl)-amino, N-methyl-N-ethylamino, N-ethyl-N-(n-propyl)amino group, N-methyl-N-(isopropyl)amino group, minilaparoscopy, allmenalp, amino group, isopropylamino (1-propenyl), (1-butene-1-yl) amino group, (1-butene-2-yl)-amino group, (1-butene-3-yl)amino group, (2-butene-1-yl)-amino group, (2-butene-2-yl)amino group, N,N-diphenylamino, N,N-diallylamine, N,N-di (propenyl)amino group, N,N-di (isopropyl)amino group, N-vinyl-N-allmenalp, itinerating, 1-propanaminium, 2-propylamino, butylamino, pentylamine, hexylamine, N,N-diethylaminopropyl, N,N-di(1-PROPYNYL)the amino group, N,N-di (2-PROPYNYL)amino group, N,N-dibutylamino, N,N-diphenhydramine, N,N-dijksynagogue, hydroxymethylamino, 1-hydroxyethylamino, 2-hydroxyethylamino, 3-hydroxy-n-propylamino, methylsulfonylamino, ethylsulfonylimidazo, n-propylsulfonyl, isopropylaniline, n-butylsulfonyl, tert-butylsulfonyl, vinylsulfonylacetamido, arylsulfonamides, isopropylacetanilide, isopentenyladenine, etinilestradiolo, medicalbilling, ethylcarbodiimide, n-propylmalonate is Gruppo, isopropylcarbodiimide, n-BUTYLCARBAMATE, tert-BUTYLCARBAMATE, vinylnorbornene, arylcarboxamide, isopropylcarbodiimide, isopentenyladenosine, atenololviagrawp and so on.

Accordingly, preferred examples of the "C1-6alkylsulfonyl group which may optionally have substituents", "C2-6alkanesulfonyl group which may optionally have substituents", "C2-6alkylsulfonyl group which may optionally have substituents", "C1-6alkylsulfonyl group which may optionally have substituents", "C2-6alkanesulfonyl group which may optionally have substituents" and "C2-6alkylsulfonyl group which may optionally have substituents" include methylsulfonyl group, ethylsulfonyl group, n-propylsulfonyl group, isopropylphenyl group, n-butylsulfonyl group, tert-butylsulfonyl group, vinylsulphonyl group, arylsulfonyl group, isopropylacetanilide group, isopentenyladenosine group, etinilestradiolo group, methylsulfinyl group, ethylsulfinyl group, n-propylsulfonyl group, isopropylphenyl group, n-butylsulfide the ilen group, tert-butylsulfonyl group, vinylsulphonyl group, arylsulfenyl group, isopropylacetanilide group, isopentenyladenine group, etinilestradiolo group and so on.

Preferred examples of "Uralkaliy group" and "heteroallyl group" include benzyl group, fenetylline group, naphthylmethyl group, naphthylethylene group, pyridylmethyl group, pyridylamino group, thienylmethyl group, titilating group and so forth, the preferred examples of "aralkylated" include benzyloxy, penetrometry, phenylpropoxy, naphthalenyloxy, naphthylisocyanate, afterpropertiesset and so forth, and the preferred examples of "heteroarylboronic" include pyridylmethylamine, personalityyou, pyrimidinediamine, pyrrolidinyloxy, imidazolylalkyl, personalmessage.php, chinainteractivecorp, ethanolammonium, furfurylamine, titillations, thiazolinediones and so on.

Preferred examples of "C3-8cycloalkyl group which may optionally have substituents" and "C3-8cycloalkenyl group which may optionally have substituents" include C3-8cycloalkyl is the Rupp (for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group, and so forth) and C3-8cycloalkenyl group (for example, cyclopropyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, and so forth), which may not necessarily be respectively substituted by 1 or more groups selected from a hydroxy-group, halogen atom, nitrile group, a C1-6alkyl group (e.g. methyl group, ethyl group, n-sawn group, isopropyl group, n-butilkoi group, isobutylene group, tert-butilkoi group, n-Pintilei group, isopentyl group, neopentyl group, n-hexylene group, and so forth), C1-6alkoxygroup (for example, metaxylene group, ethoxyline group, n-propoxylate, isopropoxy, sec-propoxylate, n-butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, n-phenoxypropan, isobutoxy, sec-pentoxide, tert-pentoxide, n-hexachrome and so on), With1-6alkoxyl1-6alkyl group, aranceles group (e.g. benzyl group, fenetylline group, naphthylmethyl group, naphthylethylene group and so on), and the like.

Preferred examples of the "5 to 14-membered ring is non-aromatic heterocyclic group", "C6-14aromatic hydrocarbonaceous group" and "5 to 14-membered aromatic heterocyclic group" in the case of "optionally substituted 5 to 14-membered non-aromatic heterocyclic group", "optionally substituted C6-14aromatic hydrocarbonaceous group" and "optionally substituted 5 to 14-membered aromatic heterocyclic group" is not specifically limited, but preferred "5 to 14-membered non-aromatic heterocyclic group" includes pyrrolidinyloxy group, pyrrolidino group, piperidinyl group, piperazinilnom group, imidazolidinyl group, pyrazolidine group, imidazolidinyl group, morpholinyl group, telemedicine group, Succinimidyl group and so forth; the preferred "C6-14aromatic hydrocarbonaceous group" includes phenyl group, indenolol group, naftalina group, azulinebloo group, heptylaniline group, biphenylene group and so forth; the preferred "5 to 14-membered aromatic heterocyclic group" includes pyrrolidino group, pyridyloxy group, pyridazinyl group, pyrimidinyl group, personilnya group, pyrazolidine group, imidazolidinyl group, thienyl group, follow group, thiazolidine group, isothiazolinone gr the PPU, pinolillo group, izohinolinove group, indolenine group, benzimidazolyl group, benzothiazolyl group, benzoxazolyl group, carbazolyl group, dioxinlike group and so forth, respectively. Moreover, preferred examples of the "substituents" in the case of groups, which may optionally have substituents" include 1 or more groups selected from a hydroxy-group, halogen atom (e.g. fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), nitrile groups, With1-6alkyl group (e.g. methyl group, ethyl group, n-sawn group, isopropyl group, n-bucilina group, isobutylene group, tert-bucilina group, n-pencilina group, isopentyl group, neopentyl group, n-exilda group, and so forth), C1-6alkoxygroup (metaxylene group, amoxilina group, n-propoxylate, isopropoxide, second-propoxylate, n-butoxypropyl, isobutoxy, second-butoxypropan, tert-butoxypropan, n-phenoxypropan, isobutoxide, second-phenoxypropan, tert-phenoxypropan, n-hexachrome and so on), With1-6alkoxy With1-6alkyl groups (for example, methoxymethyl group, ethoxyethylene group, ethoxymethylene group, amoxicilina group and so on), aranceles group (e.g. benzyl group, Ekaterina group, naphthylmethyl group, naphthylethylene group and so on), and the like. In addition, as preferred substituents of the amino group, cyclic amino group, and the group alkoxyamino, which may optionally have substituents.

In compound (I) Q represents O (oxygen atom), S (sulfur atom or NH. About is the preferred atom.

In compound (I), Z represents a carbon atom) or N (nitrogen atom).

In compound (I), when Z represents N, R1as a substitution group is absent. In this case, R1represents a single pair n

X1X2and X3do not depend on each other, and each represents a simple bond, optionally substituted C1-6alkylenes group, optionally substituted C2-6alkynylamino group, optionally substituted C2-6alkynylamino group, -NH-, -O-, -N (R4)CO-, -CON (R5)-, -N (R6)CH2-, -CH2N (R7)-, -CH2CO-, -COCH2-, -N (R8)SO0-2-, -SO0-2N (R9)-, -CH2SO0-2-, -SO0-2CH2-, -CH2O-, -OCH2-, -N (R10)CON (R11)-, -N (R12)CS-N (R13)- or-SO0-2-. In these formulas, R4, R5, R6, R8, R8, R9, R10, R11, R12and R13do not depend on each other, and each represents sobo is a hydrogen atom, With1-6alkyl group or a C1-6alkoxygroup, and "C1-6the alkyl group is preferably methyl group, ethyl group, n-sawn group, isopropyl group, n-butilkoi group or tert-butilkoi group, and "C1-6alkoxygroup" preferably is metaxylene group, ethoxyline group, n-propoxyphene, isopropoxycarbonyl, n-butoxypropyl, tert-butyloxycarbonyl or so forth.

In the above formulas, -SO0-2means that S as connecting circuit is 0, 1 or 2 oxygen atom, and especially SO0-2- represents-S-, -SO - or-SO2-.

The above "C1-6Allenova group", "C2-6alkenylamine group" and "C2-6akinlana group" respectively refer to connecting circuits corresponding to the above C1-6alkyl group", "C2-6alkenylphenol group" and "C2-6alkenylphenol group, and preferred examples include-CH2-, -(CH2)2-, -CH (CH3)-, -(CH2)3-, -CH (CH3)-CH2-, -CH2CH (CH3)-, -CH=CH-, -CH=CHCH2-, -CH2CH=CH-, -C (CH3)=CH-, -CH=C (CH3)-, -C≡C-,-C≡CCH2-, -CH2CC and so forth, and more preferable examples include-CH2-, -(CH2)2-, -(CH2)3-, -CH=CH-, -CH=CHCH2-, -CH2CH=CH-, -C≡C-, -CCCH 2-, -CH2C≡C - and so on. Preferred examples of the "group of deputies" in cases of "optionally substituted C1-3alkalinous group", "optionally substituted C2-3alkenylamine group" and "optionally substituted C2-3alkynylamino group" include halogen atom (e.g. fluorine atom, chlorine atom, bromine atom, etc.), hydroxyl group, nitrile group, a nitrogroup, and so forth. Preferred examples of the "optionally substituted C1-3alkalinous group", "optionally substituted C2-3alkenylamine group" and "optionally substituted C2-3alkynylamino groups include-CH2-, -CH (OH)-, -CH (CN)-, -CH2CH2-, -CH (OH)CH2-, -CH (CN)CH2-, -CH2CH (OH)-, -CH2CH (CN)-, -CH=CH-, -CH=CHCH2-, -CH=CHCH (OH)-, -CH=CHCH (CN)-, -CH (OH)CH=CH-, -CH (CN)CH=CH-, -C≡C - and so on.

Preferred examples X1X2and X3include a simple link, -CH2-, -CH (OH)-, -CH (CN)-, -CH2CH2-, -CH (OH)CH2-, -CH (CN)CH2-, -CH2CH (OH)-, -CH2CH (CN)-, -CH=CH-, -CH=CHCH2-, -CH=CHCH (OH)-, -CH=CHCH (CN)-, -CH (OH)CH=CH-, -CH (CN)CH=CH-, -C≡C - or-NHCONH-. More preferred examples include a simple link, -CH2-, -CH (OH)-, -CH (CN)-, -CH2CH2-, -CH (OH)CH2-, -CH (CN)CH2-, -CH2CH (OH)-, -CH2CH (CN)-, -CH=CH - and-C≡C is, moreover, preferable examples include a simple link,-CH2 - , and-CH (OH)-, and the most preferable example is a simple link.

In compound (I), (1) where Z represents C, R1and R2independently represent a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C2-6alkenylphenol group or optionally substituted C2-6alkylamino group, or R1and R2can be connected to each other, so that a partial structure of CR1-CR2forms a carbon-carbon double bond, that is, the structure represents a C=C. moreover, (2) when Z represents N, R1represents a single pair; and R2represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C2-6alkenylphenol group or optionally substituted C2-6alkylamino group.

The phrase "optionally substituted" of "optionally substituted C1-6alkyl group", "optionally substituted C2-6alkenylphenol group" and "optionally substituted C2-6alkenylphenol group means that this group may be substituted by at least one group selected from a hydroxyl group, Tilney group, nitrile group, halogen atom (e.g. fluorine atom, chlorine atom, bromine atom, iodine atom and so on is), nitro, amino, C1-6alkylamino, di-C1-6alkylamino, C2-6alkynylamino, di-C2-6alkenylamine, C2-6alkynylamino, di-C2-6alkynylamino, C6-14aromatic hydrocarbon group (for example, phenyl group and so forth), 5-14-membered aromatic heterocyclic groups (e.g. thienyl group, furilla group, Peregrina group, pyridazinyl group, pyrimidinyl group, piratininga group and so on), aralkylated, heterokaryosis, TBDMS actigraphy, C1-6alkylsulfonamides, C2-6alkanesulfonyl, C2-6alkylsulfonamides,1-6alkylcarboxylic, C2-6alkenylboronic, C2-6alkylcarboxylic,1-6alkylcarboxylic group, C2-6alkenylamine group and C2-6alkylcarboxylic group, more preferably a group of substituents, such as hydroxyl group, nitrile group, a halogen atom, a nitro-group and amino group. "C1-6alkyl group", "C2-6Alchemilla group" and "C2-6Alchemilla group" shall have the same meaning defined above.

In compound (I) R3represents a hydrogen atom, optionally substituted C1-6alkyl g is the SCP, optionally substituted C2-6alkenylphenol group or optionally substituted C2-6alkylamino group, or may be bonded to any atom A1or A3with education together with the atom optionally substituted C5-8hydrocarbon ring or a 5-8-membered heterocyclic ring. However, when Z represents N, each of X1X2and X3represents a simple bond, and each of the A1, A2and A3represents a phenyl group, when Z represents N, each of X1X2and X3represents a simple bond, A1represents o,p-dimethylphenyl group, A2is an o-methylphenyl group and A3represents a phenyl group, or when Z represents N, each of X1X2and X3represents a simple bond, A1is an on-methylphenylene group, A2represents the p-metoksifenilny group and A3represents a phenyl group, at least one of R2and R3is a group that is not a hydrogen atom.

"Optionally substituted C1-6alkyl group", "optionally substituted C2-6Alchemilla group" and "optionally substituted C2-6Alchemilla group" have t the same values defined for R1and R2. In the case of the "optionally substituted C5-8hydrocarbon ring" and "optionally substituted 5-8-membered heterocyclic ring", "C5-8hydrocarbon ring" and "5-8-membered heterocyclic ring" have the same meanings defined above, and values of the groups of substituents in the "C5-8hydrocarbon ring" and "5-8-membered heterocyclic ring" are identical to the values of the groups of substituents (A1, A2and A3.

In the case of the "optionally substituted C5-8hydrocarbon ring or optionally substituted 5-8-membered heterocyclic ring, which is formed of R3together with any atom A1or A3, with which R3attached, the preferred form is a ring or compounds represented by the formula:

,

where each symbol has the same meaning as defined above. A more preferred embodiment of the invention is a ring or compounds represented by the formula:

,

where D and E each represents-CH2-, -(CH2)2-, -C=C-, -C≡C-, -O-, -OCH2-, -CH2O-, -SO0-2-, -SCH2-, -CH2S-, -SOCH2-, -CH2S-, -SO2CH2-, -CH2SO2-, -NR14-, -NR14CH2- or-CH2NR14- (where R14represents a hydrogen atom, a C1-6alkyl group, optionally substituted C3-8cycloalkyl group, optionally substituted 5 to 14-membered non-aromatic heterocyclic group, optionally substituted C6-14aromatic cyclic hydrocarbon group or optionally substituted 5 to 14-membered aromatic heterocyclic group), and regulation D and E, which may be substituted; and other symbols have the same meanings defined above. Moreover, the preferred embodiment of the invention represents the case when D or E is-CH2-, -(CH2)2-, -O-, -S-, -SO-, -SO2-, -NR14-, -O-CH2-, -CH2-O-, -S-CH2-, -CH2-S-, -SO-CH2-, -CH2-SO-, -SO2-CH2- or-CH2-SO2-and the most preferred embodiment of the invention represents the case when D or E is-CH2-, -O-, -S-, -SO - or-SO2-where R14has the same meaning as defined above.

In compound (I), when R3bonded to any atom in A1or A3with the formation of the ring with the atom, the ring may optionally have one or more substituents. Preferred examples of the same, the groups of the substituents include a hydroxyl group, halogen atom, cyano and nitro-group, optionally substituted C1-6alkyl group, a C2-6alkenylphenol group, C2-6alkylamino group, C1-6alkoxygroup,2-6alkenylacyl,1-6allylthiourea,2-6altertekhnogrupp, an amino group and so on.

The type of the compound (I) in this invention is not specifically limited, and the corresponding groups can easily be arbitrarily combined by the person skilled in the art, the compound (I) in the preferred embodiment of the invention is a compound where A1, A2and A3independently represents a C6-14aromatic hydrocarbon group or a 5-14-membered aromatic heterocyclic group, each of which may be substituted, and more preferred embodiment of the invention it is a connection, where Q represents O, that is, the compound represented by the formula:

where ring A1a, A2aand A3ado not depend on each other, and each represents a C6-14aromatic cyclic hydrocarbon group or a 5-14-membered aromatic heterocyclic group, each of which may be substituted; and X1X2X3, Z, R1, R2and R3are the same values that are defined is use. In addition, the preferred embodiment of the invention is a compound where A1, A2and A3do not depend on each other, and each represents a C6-14aromatic cyclic hydrocarbon group or a 5-14-membered aromatic heterocyclic group, each of which may be substituted; Q represents O; and each X1X2and X3represents a simple bond, i.e. a compound represented by the formula:

In this description, the "salt" is not specifically limited, if it forms a salt with the connection on this and the salt is pharmaceutically acceptable. Preferably, the salt with a hydrogen halide (such as, hydroptere, hydrochloride, hydrobromide and hydroiodide), salt with inorganic acid (such as sulfate, nitrate, perchlorate, phosphate, carbonate or bicarbonate), salt with an organic carboxylic acid such as acetate, triptorelin, oxalate, maleate, tartrate, fumarate or citrate), salt with organic acid (such as methanesulfonate, triftorbyenzola, aconsultant, bansilalpet, toluensulfonate or camphor sulfonate), salt with amino acid such as aspartate or glutamate), salt with the Quaternary-amine, a salt with an alkaline metal (such as sodium salt or potassium salt) and salt with the alkaline is Zemelny metal (such as, salt of magnesium or calcium salt). More preferred examples of the pharmacologically acceptable salts are the hydrochloride, oxalate and the like.

The compound (I) in accordance with the present invention can be obtained in a known manner or way, it is similar. Typical methods of obtaining described below. "Room temperature"in the following typical methods of obtaining, in the reference examples and examples, refers to a temperature of from 0 to about 40°C.

As a compound in accordance with the present invention, which is represented by the above formula (I), or a derivative ketocarboxylic acid (i) or a derivative of metacarbonate (iii) with a derivative of the substituted hydrazine (ii) or (ii)', as shown in the reaction scheme, can be obtained from compounds represented by the following formula (I-1) or (III)where Z is a carbon atom:

A method of obtaining a 1-a

or

A method of obtaining a 1-b

where X1X2X3, A1, A2, A3, A1a, A2aAnd3b, B, R1, R2and R3have the same meanings defined above; and Y represents a carboxylic acid or group of ester. From the point of view of efficiency, this reactions is preferably carried out in the presence of a solvent and under stirring. Depending on the source of the product, reagents and the like, the solvent is changed and is not specifically limited if it is inert to the reaction, and to a certain extent dilutes the original product, and preferred examples include ethanol, toluene, xylene, acetic acid and so on. Used substituted derivative of hydrazine varies depending on the source of the product, the used solvent, the reaction temperature and the like, and is not specifically limited if it is inert to the reaction. From the viewpoint of the stability and suitability of the hydrazine derivative is preferably a hydrochloride. The reaction is usually carried out at room temperature or at boiling under reflux, preferably at 50-120°C. However, the reaction temperature varies depending on the source of the product, reagents and the like, and is not specifically limited. As an additive to improve outcomes, such as reducing the time of passage of the reaction, the increase of yield and the like, the reaction can be added acidic catalyst such as p-toluensulfonate acid or camphorsulfonic acid.

From among the compounds of the present invention, which are represented by the above formula (I), compounds (decree is authorized following formula (I-2) or (III-1)), where Z represents C; X2represents a simple bond; and A2represents an optionally substituted aromatic ring or an optionally substituted heterocyclic ring, can be obtained by introducing the substitution group in the 2 position pyridazinone derivative (iv) or (v), synthesized by the reaction of condensation derived ketocarboxylic acid (i) or a derivative of metacarbonate (iii) with hydrazine, as shown in reaction scheme:

The method of obtaining 2-and

or

The method of obtaining 2-b

where X1X3, A1, A3, A1a, A3b, B, R1, R2and R3have the same meaning as defined above; Y represents a carboxylic acid or group of ester; Ar represents an aromatic hydrocarbon ring or an aromatic heterocyclic group, each of which may be substituted; and L represents a bromine atom or an iodine atom.

From the point of view of efficiency, the condensation reaction preferably is carried out in the presence of a solvent and under stirring. Depending on the source of the product, reagents and the like, the solvent is changed and is not specifically limited if it is inert to the reaction, and to a certain extent and dissolves the original product, and preferred examples include ethanol, toluene, xylene, and so forth. Preferred examples of hydrazine include the anhydride of hydrazine, hydrazine hydrate, hydrazine hydrochloride and so on, and hydrazine varies depending on the solvent and so forth, and is not specifically limited. The reaction temperature varies depending on the source of the product, the used solvent and so forth, and contrino is not limited, however, the reaction is usually carried out at room temperature or at boiling under reflux, preferably at 40-120°C.

The method of introduction of the substitution group in the 2 position derived pyridazinone (iv) or (v) includes, for example, the Ullman reaction with a halogen derivative of the aryl (Ar-L in the reaction scheme above) for the introduction of aryl groups. The reaction conditions are not specifically limited, however, the reaction is normally and preferably carried out in the presence of copper, copper bromide, copper iodide, and so forth, with a base such as potassium carbonate, sodium carbonate, potassium acetate, sodium acetate, and so forth, in a solvent, with stirring. The solvent used in the above reaction Ullman, varies depending on the source of the product, reagent, and so forth, and is not specifically limited if it is a reaction-a trade the grave and to a certain extent dilutes the original product. Preferred examples of such solvent include dimethylformamide, dichlorobenzene, nitrobenzene, amyl alcohol, and so forth. The reaction temperature varies depending on the source of the product, the used solvent and so forth, and is not specifically limited. Preferably, the reaction is carried out by boiling under reflux. At this temperature, the reaction can be completed in a short period of time and has a good result.

An alternative way of introducing a group of substituents in the 2 position derived pyridazinone (iv) or (v) is a method of joining a derivative of pyridazinone (iv) or (v) to the derived arylboronic acid (Ar-B (OH)2in the reaction scheme shown above) in the presence of a base with a compound of copper. As used derived arylboronic acid, preferred are, for example, optionally substituted derived phenylboronic acid, and optionally substituted heterocyclic derivative Bronevoy acid. Used the base varies depending on the source of the product, the used solvent and so forth, and is not specifically limited, if it is a reaction-inert. Preferred examples include triethylamine, pyridine, tetramethylethylenediamine and so on. In addition, p is impactfully examples of copper compounds include, for example, copper acetate, chloride, di-μ-hydroxo-bis[ (N,N,N',N'-tetramethylethylenediamine)copper (II)] and so on. This reaction accession preferably carried out in the presence of a solvent, and the solvent varies depending on the source of the product, reagent, and so forth, and is not specifically limited if it is a reaction-inert and to a certain extent dilutes the original product. Preferred examples include dichloromethane, tetrahydrofuran, ethyl acetate, dimethylformamide and so on. Moreover, to improve results, such as reducing the time of reaction, increase product yield and so on, this reaction can be conducted in an atmosphere of oxygen or in the air stream.

The method of obtaining 3

where X2X3, A2, A3, R2and R3have the same meanings defined above; and Ar' is an optionally substituted aromatic ring or optionally substituted heterocyclic group. Connection in accordance with the present invention, which is represented by the above formula (1-3)can be obtained by introducing a group of the substituent in the 4 position pyridazinones rings derived pyridazinone represented by the formula (vi). The preferred method of introducing the group to cover the El is for example, the way in which strong acid acts on (vi) with the formation of the anion in the 4 position and interacts with arilaldegidov. Used strong base varies depending on the source of the product, the used solvent and the like, and is not specifically limited if it is inert to the reaction. Preferred examples include diisopropylamide lithium, bestremembered lithium and so on. From the point of view of the efficiency of this reaction is preferably carried out in the presence of a solvent, under stirring and temperature control. The solvent varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include tetrahydrofuran, diethyl ether, and so forth. The reaction temperature varies depending on the starting material, the solvent used and the like, and is not specifically limited. Usually the temperature is 0°C or less, preferably -78°s or lower, and under these temperature conditions, the product yield can be significantly improved.

As a compound in accordance with the present invention, which is represented by the above formula (I)may be the Holocene connection, represented by the following formula (1-4), where Z represents N, derived by converting α-halogenation (vii) the azide derivative α-ketone (viii), followed by condensation of (viii) with a derivative of hydrazine (ii) to obtain the hydrazide derivative α-azide (ix), followed by recovery (ix) converting it into a derived α-aminoglikozida (x) and then triazinone ring (xi), and by introducing the substituent group 4 position of the ring, as shown in reaction scheme:

The method of obtaining 4

where X1X2X3, A1, A2, A3, R2and R3have the same meaning as defined above; L' represents a halogen atom such as chlorine atom, bromine atom or iodine atom; and Ar represents an optionally substituted aromatic ring or an optionally substituted heterocycle.

Agent sideropenia used in the reaction of sideropenia when receiving (viii)varies depending on the source of the product, the used solvent and the like, and is not specifically limited if it is inert to the reaction. Preferred examples include sodium azide, lithium azide, and so forth. From the point of view of efficiency of reaction sideropenia preferably in the presence of Rast is orites, under stirring, security and so on. Solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert towards the reaction, and to a certain extent dilutes the original product. Preferred examples include dimethylformamide, chloroform, dichloromethane, and so forth. The reaction temperature varies depending on the reagent, solvent and so forth, but usually, from a security point of view, the reaction is carried out at temperatures below room or bedroom, preferably while cooling on ice.

Used in obtaining (ix) hydrazine derivative (ii) may be a salt, and is not specifically limited unless it inhibits the reaction. From the point of view of safety and applicability, the most preferred is the hydrochloride. Solvent used varies depending on the source of the product, reagents, and so is more similar, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include ethanol, toluene, chloroform, and so on. The reaction temperature varies depending on the reagent, solvent and the like, but usually the reaction is carried out at room tempera is ur or by boiling under reflux. In addition, to improve outcomes, such as reducing the time of reaction, the increase of yield and the like, as an additive in the reaction can be added acidic catalyst such as p-toluensulfonate or camphorsulfonic acid.

Conditions for restoration of azide group to obtain (x) is not specifically limited if the condition is mild, and to restore preferably using triphenylphosphine. Solvent used varies depending on the source of the product, reagents and the like, and is not specifically limited if it is inert at the reaction and to a certain extent dissolves the starting material. Preferred examples include tetrahydrofuran, chloroform, toluene, and so forth. The reaction temperature varies depending on the reagent, solvent and so forth, but usually the reaction is carried out at room temperature or at boiling under reflux, preferably at a temperature of from 60°C to 120°C.

For cyclization triazinone ring when receiving (xi), preferably, (x) interacted with carbonyliron reagent, such as triphosgene, 1,1'-carbonyldiimidazole or diethylcarbamyl, preferably, triphosgene, in the presence of a base, such as, triethylenephosphoramide solvent varies depending on the source of the product, reagents and so on, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include tetrahydrofuran, acetonitrile and so on. The reaction temperature varies depending on the reagent, solvent and so forth, but usually the reaction is carried out while cooling on ice or boiling under reflux.

In the introduction phase group of the substituent in the 4 position derived triazinone (xi)" as the final stage of obtaining the compound (I-4) in accordance with the present invention, a typical way of introducing the aryl group is, for example, the Ullman reaction with a derivative of halogenfree. Reaction conditions are not specifically limited and, for example, the reaction is carried out in the presence of copper, copper bromide, copper iodide, and so forth, with a base such as potassium carbonate, sodium carbonate, potassium acetate, sodium acetate, and so forth, in the system of solvent under stirring. Solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dissolves the starting material. Preferred examples include dimethylformamide, dichlorobenzene, nitrobenzene, amyl is Peart and so on. The reaction temperature varies depending on the reagent, solvent and so forth, but usually the reaction can be completed in a short period of time while boiling under reflux. An alternative way of introducing a group of the substituent in the 4 position derived triazinone (xi) is a way of communication (xi) and derived arylboronic acid (Ar-B (OH)2in the reaction scheme above) in the reactions proceed in the presence of a base with a compound of copper. Preferably used is a derivative of arylboronic acid is, for example, optionally substituted derived phenylboronic acid or optionally substituted heterocyclic derivative Bronevoy acid. Used the base varies depending on other used reagents used solvent and so forth, and is not specifically limited unless it inhibits the reaction. Preferred examples include triethylamine, pyridine, tetramethylethylenediamine and so on. Preferably, the connection of copper is, for example, copper acetate, chloride, di-μ-hydroxo-bis[ (N,N,N',N'-tetramethylethylenediamine)copper (II)] or the like. This reaction is preferably carried out in the presence of a solvent. Solvent used varies depending on the source product is the one reagents and so on, and is not specifically limited if it is inert towards the reaction, and to a certain extent dilutes the original product. Preferred examples include dichloromethane, tetrahydrofuran, ethyl acetate, dimethylformamide and so on. In addition, to improve results, such as reducing the time of reaction, increase product yield and so on, this reaction can be carried out in oxygen atmosphere or in air flow. To further improve the output can be added to the base, such as sodium hydride, tert-butoxy potassium, etc.

The method of obtaining 5

where X1X2X3, A1, A2, A3, R2, R3and L' have the same meanings defined above. The connection represented by the above formula (1-4), in accordance with the present invention may also be obtained in accordance with the method of obtaining 5 shown in the above reaction scheme.

That is, the intermediate derived α-aminoketone (xiii) is obtained by reaction of condensation derivative α-halogenation (vii) with an amine derivative (xii). From the point of view of efficiency, this stage is preferably carried out in a solvent in the presence of organic bases such as triethylamine, and inorganic bases, t is anyone as potassium carbonate, or with an excess of amine derivative (xii) and under stirring. Solvent used varies depending on the starting material, reagent, etc. and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include ethanol, acetone, tetrahydrofuran, and so forth. Improved the outcome, such as reducing the time of reaction, increase product yield, and so forth, can be obtained by adding potassium iodide, sodium iodide, and so forth.

Derived α-aminoglikozida (xiv) are obtained by the condensation reaction derived α-aminoketone (xiii) with a derivative of hydrazine (ii). Used a derivative of the substituted hydrazine may be Sol, and it is not specifically limited unless it inhibits the reaction. From the point of view of stability and applicability, preferred is the hydrochloride. Solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include ethanol, toluene, chloroform, and so on. The reaction temperature varies depending on, for example, used reagent, solvent, catalysis is the Torah, and so forth, but usually the reaction is carried out at room temperature or by boiling under reflux. As an additive to improve results, such as reducing the time of reaction, increase product yield and so on, can be added acidic catalyst such as p-toluensulfonate or camphorsulfonic acid.

"Cyclization triazinone ring", which is the final stage (i.e. stage between the intermediate compound (xiv) and (I-4)) to obtain the compound (1-4) of the present invention, is carried out by interaction (xiv), preferably carbonyliron reagent, such as triphosgene, or Carboniferous reagent such as 1,1'-carbonyldiimidazole or diethylcarbamyl, in the presence of a base such as triethylamine. More preferably, the reaction is carried out using triphosgene. Solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include tetrahydrofuran, acetonitrile and so on. The reaction temperature varies depending on the reagent, solvent and so forth, but usually the reaction is carried out while cooling on ice or at Kip the treatment under reflux.

The method of obtaining 6

where X1X2X3, A1, A2, A3, R2, R3, L' and Ar have the same meanings defined above; and R' represents a C1-6alkyl or benzyl group.

Connection in accordance with the present invention, which is represented by the compound (1-4)can also be obtained by the condensation reaction of hydrazinecarboxamide (NH2NHCO2R' in the reaction scheme) with a derivative of aminoketone (xiii)obtained in the above production method of 5, to obtain the triazine derivative (xv), followed by the introduction of group substituent in the 2-position of the compound (xv).

From the point of view of efficiency, the reaction of condensation (xiii) of hydrazinecarboxamide (NH2NHCO2R' in the scheme of the reaction) is preferably carried out in the presence of a solvent and under stirring. Solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include ethanol, toluene, xylene, and so forth. The reaction temperature varies depending on the reagent, solvent, catalyst and so on, and is not specifically limited, but usually the reaction is carried out at to matnog temperature or boiling under reflux, preferably at 40-120°C.

In the introduction phase of the group of substituents in the 2-nd position derived triazinone (xv)"as the final stage of obtaining the compound (I-4) in accordance with the present invention, the usual way of introducing aryl group is, for example, the reaction Ullman with halogenosilanes derived. Reaction conditions are not specifically limited and, for example, the reaction is carried out in the presence of copper, copper bromide, copper iodide, and so forth, with a base such as potassium carbonate, sodium carbonate, potassium acetate, sodium acetate, and so forth, in a solvent under stirring. Solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited, if it is inerti against reaction and to a certain extent dilutes the original product. Preferred examples include dimethylformamide, dichlorobenzene, nitrobenzene, amyl alcohol, and so forth. The reaction temperature varies depending on the reagent, solvent and so forth, but usually the reaction can be completed in a short period of time by boiling under reflux. An alternative way of introducing a group substituent in the 2-nd position derived triazinone (xv) is a way of interacting compounds (xv) and derived arylboronic acid is (Ar-B (OH) 2in the reaction scheme shown above) in the reactions proceed in the presence of a base with a compound of copper. Preferred examples of the derived arylboronic acids include optionally substituted derived phenylboronic acid or optionally substituted heterocyclic derivative Bronevoy acid. Used the base varies depending on the source of the product, the used solvent and so forth, and is not specifically limited if it is inert at the reaction. Preferred examples include triethylamine, pyridine, tetramethylethylenediamine and so on. Preferred examples of copper compounds include copper acetate, chloride, di-μ-hydroxo-bis[ (N,N,N',N'-tetramethylethylenediamine)copper (II)] and so on. This reaction is conducted preferably in the presence of a solvent, and the solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. Preferred examples include dichloromethane, tetrahydrofuran, ethyl acetate, dimethylformamide and so on. In addition, to improve outcomes, such as reducing the time of reaction, the increase in output is a product, and so forth, this reaction can be carried out in oxygen atmosphere or in air flow.

When A1, A2and/or A3in compound (I) in this invention have a group substituent, the substituent can be easily converted in a known manner or way, it is similar. For example, (1) when the substituent is a nitro-group and, although there is no particular limitation for a method and resulting product, as an example can be given of the method of conversion into amino by reduction reactions. Although usually there are no special restrictions conditions for a redox reaction, the preferred conditions are the conditions the way in which iron, zinc or tin are used in acidic conditions, method of hydrogenation, in which palladium, rhodium, ruthenium, platinum or complex is used as catalyst. When using derivatives, obtained by the above reduction reactions, it can easily additionally be converted to aminosidine, the connection carbamate, compound sulfonamida, a halogen compound, a compound substituted amine and so forth. (2) When the substituent is alkoxygroup, the example of conversion to the functional group of alkoxygroup is the way of transformation in about svodnoe alcohol removal methods of protection. The derived alcohol, which was obtained above, can be easily transformed into a complex compound of ether by dehydration condensation with a carboxylic acid derivative, or by reaction with acid chloride acid or easily converted into a simple connection of an ether by reaction Mitsunobu (Mitsunobu) or by the condensation reaction with the compound of halogen. (3) When the Deputy is an aldehyde group, various known reactions convert the aldehyde group to the functional group, and although there is no particular limitation for the method of conversion and the resulting product, an example is the conversion to carboxylic acid derivative by reaction of oxidation. Carboxylic acid derivative obtained above, can easily be optionally converted to the compound of ester, compound ketone, and so forth. In addition, on the basis of the specified carboxylic acid derivative, it can easily be derived alcohol using a redox reaction, the amine derivative using the reaction of reductive amination, secondary alcohol with additional reactions with organic metallomesogenes and various alkyl derivatives by the reaction of Wittig (Wittig). (4) When the substituent is an ATO is halogen, an example of converting a functional group of halogen atom as a substituent is a method of conversion to nitrile derived by substitution reactions. In addition to the above, can be easily converted into various kinds of connections with, for example, organolithium compounds, magyarkanizsa compounds, ORGANOTIN compounds or derived organoboronic acid and so on.

The above represents the typical examples of the production method of compound (I) in accordance with the present invention, and source products and various reagents for obtaining compounds of this invention can be in the form of salts or hydrates, to vary from the original product, the used solvent and so forth, and is not specifically limited if it is inert to the reaction. Of course, the solvent used varies depending on the source of the product, reagents, and so forth, and is not specifically limited if it is inert at the reaction and to a certain extent dilutes the original product. When the compound (I) of the present invention obtained as free agents, it can be converted into the salt by conventional means. In addition, various isomers (for example, a geometric isomer, enantiomer, based on the symmetric carbon rotamer, stereoisomer, tautomer and so on), which were obtained instead of the compound (I) of the present invention, purified by conventional separation methods, such as recrystallization, the way diastereomeric salt, animals, various chromatographic methods (for example, thin layer chromatography, column chromatography, gas chromatography, and so forth), and can be separated.

Connection in accordance with the present invention, which is represented by the above formula (I), its salt or hydrate, can be used in its original form or in a mixture with essentially known pharmacologically acceptable carriers to form pharmaceutical preparations using a conventional method. As the preferred dosage form may be given tablets, diluted powder, fine granules, granules, coated tablets, capsules, syrup, trosha, preparations for inhalation, suppositories, injections, ointments, eye ointments, eye drops, medicines for nose, ear drops, poultices, lotions, and so forth. Upon receipt of the pharmaceutical preparations can be used commonly used excipients, binders, disintegrating agents, lubricating agents, dyes, corrigentov, if necessary, stabilizers, emulsifiers, emulsifying agents, substances that increase the POG is osenia, surfactant, a substance that regulates the pH level, antiseptics, antioxidants, and so forth, and, after receiving a mixture of ingredients that are commonly used as materials for pharmaceutical preparations from it are pharmaceutical drugs using a conventional method.

Examples of such ingredients are animal and vegetable oils such as soybean oil, beef tallow or synthetic glycerides; hydrocarbons such as liquid paraffin, squalane or solid paraffin; ester oil such as octyldodecanol or isopropylmyristate; higher alcohol such as cetosteatil alcohol or beganovic alcohol; silicone polymer; silicone oil; a surfactant, such as ester polyoxyethylene fatty acid ester sorbinovoj fatty acid, an ester of glycerin fatty acid ester serviceprincipalnames fatty acids, polyoxyethylene gidrirovannoe castor oil or polyoxyethylene block copolymers of polyoxypropylene; water-soluble high-molecular substance, such as hydroxyethylcellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinylpyrrolidone or methyl cellulose; lower alcohol, such as ethanol or isopropanol; polyhydric alcohol such as glycerin, propelling the Col, dipropyleneglycol or sorbitol; a saccharide such as glucose or sucrose; inorganic powder such as silicic acid anhydride, magnesium aluminum silicate or aluminum silicate; clean water and so on. Relevant examples of the filler include lactose, corn starch, sugar, glucose, mannitol, sorbitol, crystalline cellulose, silicon dioxide, and so forth; examples of the binder is polyvinyl alcohol, polyvinyl ether, methylcellulose, ethylcellulose, gum Arabic, tragakant, gelatin, shellac, methylcellulose of hydroxypropyl, hydroxypropylcellulose, polyvinylpyrrolidone, a block copolymer of polyoxyethylene polypropyleneglycol, meglumine, calcium citrate, dextrin, pectin and the like; examples of disintegrating agents include starch, agar-agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, calcium citrate, dextrin, pectin, calcium carboxylmethylcellulose and so forth; examples of lubricants are magnesium stearate, talc, polyethylene glycol, silica, gidrirovannoe vegetable oil and so forth; examples of the dye is such dyes that can be added to pharmaceutical preparations; examples corrigentov include cocoa powder, menthol, aromatic powder, pepper-mint oil, borneol and max is the first powder; examples of the developer are oxidants, which are allowed to be added to pharmaceutical preparations, such as ascorbic acid, α-tocopherol and so on.

When getting drugs for oral administration, the compound of the present invention or pharmacologically acceptable salt mixed with a filler and, if necessary, optionally with a binder, baking powder, lubricant, dye, Corrigendum so forth, and the mixture is prepared in the form of reconstituted powder, particles, granules, tablets, coated tablets, capsules, and so forth, using a conventional method.

In the case of tablets and coated tablets, of course, is not a hindrance that, if necessary, such pills and granules, coated with sugar, gelatin or covered accordingly.

In the case of liquid preparations such as syrup, injection and eye drops can be added to the agent regulating the pH, a solubilizer, an agent for isotonicity so forth, and if necessary, an auxiliary solubilizer, stabilizer, buffer, suspendisse substance, an antioxidant and so forth, with the subsequent formation of pharmaceuticals in the usual way. The drug can be obtained as a product, freeze dried, and injection can be dosed for vnutrivennogo is, subcutaneous and intramuscular injection. Preferred examples of the suspending agent include methylcellulose, Polysorbate 80, hydroxyethyl cellulose, Arabic gum, powder tragakant, carboxymethylcellulose sodium, sorbitanoleat of polyoxyethylene and the like; preferable examples of the auxiliary dissolving agent include polyoxyethylene cured castor oil, Polysorbate 80, nicotinic acidemia, polyoxyethylene sorbitanoleat and so on; preferable examples of the stabilizer include sodium sulfite, meta, sodium sulfite, ether and the like; preferable examples of the preservative include methyl p-oxybenzoic, ethyl p-oxybenzoic, sorbic acid, phenol, cresol, chlorocresol and so on.

In the case of outdoor use, there are no special restrictions for the method of producing a pharmaceutical product, but when getting used conventional method. Thus, as for the main material used, it is possible to use various substances that are typically used for pharmaceuticals, quasilocal, cosmetic products and so forth. Typical examples of the basic material used are animal/vegetable oil, mineral oil, essential oil, waxes, you the high alcohols, fatty acid, silicone oil, surfactants, phospholipids, alcohols, polyhydric alcohols, water-soluble high-molecular substances, clay minerals, and clean water and, if necessary, it is possible to add substances that regulate the pH, antioxidant, chelating substances, antiseptic, antifungal agent, colorant, flavouring agent, and so forth. If you want, you can also add other connections such as component, activating differentiation, increasing blood flow, bactericide, anti-inflammatory agent, cell activators, vitamins, amino acid, humectant and keratin-solubilizers agent.

The pharmaceutical preparation containing the compound (I) in accordance with the present invention, its salt, or a hydrate, as the active ingredient, is used for the treatment and prevention of diseases in mammals (e.g. humans, mice, rats, Guinea pigs, rabbits, dogs, horses, monkeys and the like), especially for the treatment and prevention of diseases in humans. Dose of a pharmaceutical preparation in accordance with the present invention varies depending on the characteristics of the symptoms, age, sex, body weight, dosage form, type of salt, sensitivity to pharmaceuticals, specifically the th type of disease and the like. In the case of man, the pharmaceutical preparation is administered to an adult one daily intake, or divided into several, with the dose for oral administration, usually equal to about 30 μg to 10 g, preferably 100 μg to 10 g, more preferably 100 μg to 5 g, for administration by injection is equal to approximately 30 μg - 10,

In accordance with the present invention it is possible to obtain a new compound (I), which exhibits excellent inhibitory activity against AMPA receptor and/or kainite-induced receptor and that can be used as pharmaceuticals. Moreover, it presents a useful method for obtaining compounds or salts thereof and receiving the intermediate compounds. In accordance with this method, the compound of the present invention, can be obtained with high yield, and can be obtained high-security connection. The compound (I) of the present invention suppresses the neurotoxicity of excitatory neurotransmitters and as pharmaceutical agents has excellent neuroprotective activity. Accordingly, the compounds of the present invention is useful as a therapeutic, preventive, and improve funds regarding various nervous disorders and may be useful as a therapeutic and preventive agent for acute neurodegen is exploring diseases (such as cerebrovascular disease in the acute stage, subarachnoid hemorrhage, head injury, spinal cord injury, neuropathy caused by hypoxia or hypoglycaemia, and the like), chronic neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease, horei of Hantington, amyotrophic lateral sclerosis or spinocerebellar degeneration, epilepsy, hepatic encefalopatia, peripheral neuropathy, Parkinson's disease, spasticity, pain, neuralgia, schizophrenia, anxiety condition, drug abuse, nausea, vomiting, urination, visual disturbance caused by glaucoma, hearing loss caused by antibiotics, food poisoning, infection of cerebrospinal meningitis (cerebrospinal meningitis caused by HIV), cerebrovascular dementia or dementia or nervous symptoms caused by meningitis. Moreover, the connection according to the present invention is useful as a drug for treatment or prevention of demyelinating diseases such as encephalitis, acute disseminated encephalomyelitis, multiple sclerosis, acute demyelinizing polyneuropathy, Guillain-Barre syndrome, chronic inflammatory demyelinizing neuropathy, a disease of Marchiafava-Bignami, Central Pontigny myelinosis, neuroptimal syndrome), Balo disease, myelopathy the HIV, myelopathy with HTLV, progressive mnogofotonnaya leucoencephalopathy and secondary demyelinizing disease (such as CNS lupus erythematosus, polyarteritis polyarteritis, Sjogren syndrome, sarcoidosis, localized cerebral vasculitis).

Examples

Reference examples, examples (in addition, their pharmacologically acceptable salts, hydrates and pharmaceuticals or containing pharmaceutical compositions) and a case study, shown below, is described only for the purpose of illustration, and compounds in this invention, in any case, not limited to the following further examples. The present invention can best be carried out by a person skilled in the art by introducing various changes not only in the examples following hereinafter, but also in the claims of this specification, and such modifications are included in the scope of the claims of this application.

Reference example 1

1-(2-Pyridyl)-3-(3-methoxyphenyl)-2-propen-1-he

Tert-piperonyl potassium (2.4 g) was added to a solution of 2-acetylpyridine (25 g) and 3-methoxybenzaldehyde (28 g) in tetrahydrofuran (150 ml), then was stirred for 5 hours. The reaction mixture was separated between ethyl acetate and water, and the organic layer was washed with water, dried and concentrated. The residue was purified on a column of silica gel (system ethyl acetate/hexane)to obtain compound (17,2 g), specified in the header, in the form of a yellow solid product.1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.87 (s, 3H), of 6.96-6,99 (m, 1H), 7.24 to 7,26 (m, 1H), 7,32-7,34 (m, 2H), 7,50 (DDD, 1H), 7,88 (dt, 1H), to $ 7.91 (d, 1H), 8,19 (TD, 1H), 8,28 (d, 1H), 8,75 (DDD, 1H).

Reference example 2

2-(3-Methoxyphenyl)-4-(2-pyridyl)-4-oxobutanoic

According To J. Chem. Soc. (1958) 4193, compound (16.7 g), specified in the header was received in the form of a brown oil of 1-(2-pyridyl)-3-(3-methoxyphenyl)-2-propen-1-it (17,2 g).1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.80 (DD, 1H), 3,82 (s, 3H), of 4.00 (DD, 1H), 4,50 (DD, 1H), 6,86 (DD, 1H), 6,97 (t, 1H), 7,00-7,03 (m, 1H), 7,29 (m, 1H), 7,50 (DDD, 1H), 7,86 (TD, 1H), 8,07 (TD, 1H), 8,65 (DDD, 1H).

Reference example 3

2-(3-Methoxyphenyl)-4-(2-pyridyl)-4-oxomalonate acid

According To J. Heterocyclic. Chem., 25, 799 (1988), the compound (12.3 g), specified in the header was received in the form of a brown solid from 2-(3-methoxyphenyl)-4-(2-pyridyl)-4-oxobutanamide (16.7 g).1H-NMR (400 MHz, CDCl3); δ (ppm) 3,52-to 3.58 (m, 1H), of 3.77 (DD, 1H), 3,79 (8, 1H), 8,55 (DD, 1H), PC 6.82 (DDD, 1H), 6,85-6,89 (m, 1H), 6,94 (t, 1H), 6,98 (d, 1H), 7,47 (DDD, 1H), 7,83 (dt, 1H), 8,02 (d, 1H), 8,67 (DDD, 1H).

Reference example 4

Ethyl 4-(2-Methoxyphenyl)-2-(2-pyridyl)-4-oxobutyl

Under ice cooling to a solution of ethyl 2-pyridylacetate (5.5 g) in dimethylformamide (50 ml) was added 60% sodium hydride (1.5 g), then stirred. After 1 hour, was added 2-methoxybenzylamine (7.7 g)and the mixture was stirred for 1 hour under cooling in which IDU, and then was stirred overnight at room temperature. The reaction mixture was evaporated and distributed between ethyl acetate and water. The organic layer was washed with water, dried and concentrated. The residue was purified on a column of silica gel (system ethyl acetate-hexane) to obtain compound (6.6 g)as specified in the header, in the form of a reddish-brown solid product.1H-NMR (400 MHz, CDCl3); δ (ppm) of 1.20 (t, 3H)and 3.59 (DD, 1H), 3,88 (s, 3H), of 3.95 (DD, 1H), 4,11-4,20 (m, 2H), 4,51 (DD, 1H), 6,94-7,00 (m, 2H), 7,15-to 7.18 (m, 1H), was 7.36 (dt, 1H), 7,43-7,47 (m, 1H), 7,65 (TD, 1H), 7,73 (DD, 1H), 8,54-8,56 (m, 1H).

Reference example 5

4-Phenyl-2,3,4,4a-tetrahydro-5H-((1)benzopyrano[4,3-C]pyridazin-3-one

Synthesized according to the method described in example 1, 4-oxo-4H-2,3-dihydro-1-benzofuran-3-acetic acid (4,00 g) was dissolved in ethanol (60 ml) was added hydrazine monohydrate (0.68 g), then heated under reflux for 3 hours. After cooling to room temperature, the resulting crystals were separated by filtration to obtain compound (1,95 g, 49%)as specified in the header.1H-NMR (400 MHz, DMSO-d6); δ (ppm) 3,65-a-3.84 (m, 3H), of 4.00 (DD, 1H), 6,91 (DD, 1H),? 7.04 baby mortality (DDD, 1H), 7,27-7,41 (m, 6H), of 7.90 (DD, 1H), 11,18 (s, 1H).

Reference example 6

3-Chloro-6-methoxy-5-tributylammonium

To a solution of Diisopropylamine (6,7 ml) in tetrahydrofuran (60 ml) was added 2.5 M utility (19,4 ml) at -40°C the nitrogen atmosphere. After stirring for 20 minutes under ice cooling was added dropwise a solution of 3-chloro-6-methoxypyridazine (5,76 g) and tributyltinchloride (15,56 g) in tetrahydrofuran (30 ml) at -72°C and was stirred for 1 hour. Added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. Then the residue was purified through column chromatography with silica gel (system ethyl acetate/hexane) to obtain compound (12,77 g)specified in the header, in the form of a pale yellow oil.1H-NMR (400 MHz, CDCl3); δ (ppm) to 0.89 (t, 9H), 1,10-1,15 (m, 6H), 1,27-of 1.36 (m, 6H), 1,48-of 1.53 (m, 6H), 4,06 (s, 3H), 7,38 (s, 1H).

Reference example 7

3-Chloro-6-methoxy-5-phenylpyridazin

3-Chloro-6-methoxy-5-tributylammonium (3,20 g), brobinson (11,57 g), tetrakis (triphenylphosphine)palladium (428 mg) and copper iodide (I) (70 mg) were added to xylene (130 ml), then stirred at 120°C for 2 hours in nitrogen atmosphere. The reaction mixture was purified through column chromatography with silica gel (system ethyl acetate/hexane) to obtain compound (1.10 g)as specified in the header, in the form of a colorless oil.1H-NMR (400 MHz, CDCl3); δ (ppm) to 4.16 (s, 3H), 7,40 (s, 1H), 7,47-to 7.50 (m, 3H), 7,60-7,63 (m, 2H).

Reference example 8

6-Chloro-4-phenyl-3(2H)-pyridazinone

The reaction mixture of 3-chloro-6-methoxy-5-phenylpyridazin (267 mg) and conc. hydrochloric acid (2 ml) was boiled under reflux for 2 hours. After concentration the residue was purified through column chromatography with silica gel (ethyl acetate) to obtain compound (159 mg)as specified in the header, in the form of a colorless solid.1H-NMR (400 MHz, CDCl3); δ (ppm) 7,38 (s, 1H), 7,47-7,49 (m, 3H), 7,81-to 7.84 (m, 2H), 11,34 (Ushs, 1H).

Reference example 9

6-Chloro-2-(2-cyanophenyl)-4-phenyl-3(2H)-pyridazinone

A suspension of 6-chloro-4-phenyl-3(2H)-pyridazinone (80 mg), 2-(2-cyanophenyl)-1,3,2-dioxaborinane (144 mg), copper acetate (II) (35 mg), triethylamine (107 μl) and pyridine (62 μl) in methylene chloride (5 ml) was stirred for 4 days under oxygen atmosphere. The reaction mixture was distributed between aqueous ammonia and ethyl acetate, and the organic layer was washed with water, dried and concentrated. The residue was then purified through column chromatography with silica gel (system ethyl acetate/hexane) to give the compound indicated in heading (83 mg)as a colourless solid.1H-NMR (400 MHz, CDCl3); δ (ppm) the 7.43 (s, 1H), 7,46 is 7.50 (m, 3H), 7,56 (dt, 1H), 7,68 (DDD, 1H), 7,76 (DDD, 1H), 7,81-to 7.84 (m, 3H).

Reference example 10

3-Methoxy-4-phenyl-6-(2-pyrimidinyl)pyridazin

2-Tributyltinchloride (2.10 g), obtained in accordance with Tetrahydron 50, 275-284 (1994), 3-chloro-6-methoxy-5-phenylpyridazin (800 mg) and tetrakis (triphenylphosphine)palladium (208 mg) was added to xylene (10 ml), then stirred at 120°C for 2 hours in ATM is the field of nitrogen. The reaction mixture was purified through column chromatography with NH-silica gel (system ethyl acetate/hexane) to give the compound indicated in heading (403 mg)as a brown solid.1H-NMR (400 MHz, CDCl3); δ (ppm) to 4.28 (s, 3H), 7,37 (t, 1H), 7,46-7,53 (m, 3H), 7,73-7,76 (m, 2H), charged 8.52 (s, 1H), to 8.94 (d, 2H).

Reference example 11

4-Phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone

A solution of 3-methoxy-4-phenyl-6-(2-pyrimidinyl)pyridine (1.07 g) in 5 G. hydrochloric acid (15 ml) was boiled under reflux for 2 hours. After neutralization with 5 N. aqueous solution of sodium hydroxide obtained residue was collected by filtration and washed with ethyl acetate to obtain the connection specified in the header (609 mg), as a colourless solid.1H-NMR (400 MHz, CDCl3); δ (ppm) 7,38 (m, 1H), 7,47-7,53 (m, 3H), 7,95-7,98 (m, 2H), at 8.60 (s, 1H), 8,95 (d, 2H).

Reference example 12

2-(Asiacell)pyridine

Acetylpyridine (2,46 g) was dissolved in acetic acid (4 ml) and gradually dropwise added bromine (1.1 ml) at a temperature of 70°C. After cooling the reaction solution to room temperature, the resulting crystals were collected by filtration. An aqueous solution of sodium bicarbonate was added to the crude crystals (4.8 g), then was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant who was b filtered, the filtrate was evaporated. The residue (4,06 g) was dissolved in dimethylformamide (50 ml)was added sodium azide (1.5 g) and the mixture was stirred at room temperature for 2 hours. Then added water and was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated to obtain the connection specified in the header, in the form of a brown oil (2,74 g, 83%).1H-NMR (400 MHz, CDCl3); δ (ppm) to 4.87 (s, 2H), 7,51-of 7.55 (m, 1H), 7,87-to $ 7.91 (m, 1H), of 8.09 (d, J=8.0 Hz, 1H), 8,66 (dt, J=4,8 Hz, 0.8 Hz, 1H).

Reference example 13

2-Pyridyl-aminomethyl-2'-bromophenylacetate

2-(Asiacell)pyridine (2.7 g) was dissolved in ethanol (50 ml) was added 2-bromophenylacetate (3.4 g), then stirred overnight at room temperature. The reaction mixture was evaporated, and the residue was dissolved in tetrahydrofuran (40 ml). Then was added triphenylphosphine (4.94 g) and stirred at room temperature for 3 hours. Was added water (1 ml), the mixture was stirred for 1 hour and then was heated over night at 80°C. After cooling to room temperature the mixture was evaporated. The residue was purified through column chromatography with silica gel (system hexane/ethyl acetate) to obtain the compound indicated in heading (2,69 g, 53%)as a brown oil.1H-NMR (400 MHz, CDCl3); δ (ppm) of 1.84 (Ushs, 2H), to 4.41 (s, 2H), 6,74 (TD, J=8,4 Hz, 1.2 Hz, 1H), 7,16-7,17 (m, 1H), 7,25-7,30 (m, 1H), 7,45 (DD, J=8.0 Hz, 1.2 Hz, 1H), 7.62mm (DD, J=8,4 Hz, 1.6 Hz, 1H), to 7.67 (TD, J=8.0 Hz, 0.8 Hz, 1H), 8,14 (d, J=8.0 Hz, 1H), 8,50-8,51 (m, 1H), is 11.39 (Ushs, 1H).

Reference example 14

2-(2-Bromophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3-(2H)-he

2-Pyridyl-aminomethyl-2'-bromophenylacetate (2,69 g) was dissolved in anhydrous tetrahydrofuran (100 ml), then added triphosgene (1.31 g) and triethylamine (2.7 ml) under cooling on ice. While the temperature of the mixture was gradually raised from 0°C to room temperature, the mixture was stirred over night. Insoluble matter was filtered, and the filtrate was evaporated. The residue was purified through column chromatography with NH-silica gel (system hexane/ethyl acetate) to obtain the compound indicated in heading (1,00 g, 31%)as brown powder.1H-NMR (400 MHz, CDCl3); δ (ppm) rate 4.79 (s, 2H), 5,50 (s, 1H), 7.23 percent-7,30 (m, 2H), 7,39-of 7.48 (m, 1H), 7,53 (DD, J=7.8 Hz, 1.8 Hz, 1H), to 7.67-7,72 (m, 2H), 8,04 (d, J=8.0 Hz, 1H), 8,57 (DDD, J=4,8 Hz, 1.8 Hz, 1.0 Hz, 1H).

ECI-Mass; 331 [M++H].

Example 1

2-(2-Bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

In accordance with Indian J. Chem., Sect. B30 (1991) 6, 589, the connection specified in the header (1.1 g)was obtained as a brown solid from 2-(3-methoxyphenyl)-4-(2-pyridyl)-4-oxomalonate acid (3 g) and 2-brompheniramine (2 g).1H-NMR (400 MHz, CDCl3); δ (ppm) 3,44-3,86 (m, 2H), of 3.73 (s, 3H), 394-4,15 (m, 1H), for 6.81 (DD, 1H), 6,97-7,01 (m, 2H), 7,21-7,29 (m, 3H), 7,37-7,41 (m, 2H), 7,65-of 7.69 (m, 2H), with 8.05 (d, 1H), 8,61-8,63 (m, 1H).

Example 2

2-(2-Bromophenyl)-4-(3-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

A solution of 1 M tribromide boron in methylene chloride (7 ml) was added to a solution of 2-(2-bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone (1.1 g) in dichloromethane (20 ml) while cooling on ice, and then stirred for 1 hour. In the reaction mixture were added ice and distributed between aqueous ammonia and ethyl acetate. The organic layer was dried and concentrated, and the product is then suspended in ether, collected by filtration to obtain the connection specified in the header (0.8 g)as a pale brown solid product.1H-NMR (400 MHz, CDCl3); δ (ppm) 4,00 (Ushs, 2H), 4,12 (Ushs, 1H), of 6.68 (DD, 1H), 6,84-6,89 (m, 2H), 7,13 (t, 1H), 7.23 percent-7,31 (m, 2H), was 7.36-7,46 (m, 2H), 7,65-7,71 (m, 2H), of 8.04 (d, 1H), 8,60-to 8.62 (m, 1H).

Example 3

2-(2-Bromophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone

To a solution of 2-(2-bromophenyl)-4-(3-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone (173 mg) in dimethylformamide (5 ml) was added 60%sodium hydride (40 mg) under cooling on ice. After stirred for 30 minutes was added (2-bromoethoxy)-tert-butyldimethylsilyl (300 mg) and was stirred over night at room temperature. To the mixture was added ethyl acetate and washed with water, dried, concentrated and then purified on a column of silica gel (system ethyl acetate/hexane). The obtained brown oil was dissolved in tetrahydrofuran (5 ml) was added 5 N. hydrochloric acid (1 ml). After stirring for 10 minutes, the mixture was neutralized 5 N. sodium hydroxide and was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue was purified on a column of silica gel (system ethyl acetate/hexane) to obtain the specified title compound (111 mg) as a pale red amorphous substance.1H-NMR (400 MHz, CDCl3); δ (ppm) 3,94-to 3.99 (m, 2H), 4.16 the (t, 2H), 7,02 (DD, 1H), 7,32-7,41 (m, 3H), 7,49-7,58 (m, 3H), 7.68 per-7,79 (m, 3H), 8,14 (dt, 1H), 8,67-8,68 (m, 2H).

Example 4

2-(2-Cyanophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone

The copper cyanide (I) (20 mg) was added to a solution of 2-(2-bromophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone (70 mg) in dimethylformamide (3 ml), then stirred at 120°C for 1 hour. The reaction solution was distributed between ethyl acetate and ammonia water, and the organic layer was washed with water, dried and concentrated. Then the residue was purified on a column of silica gel (system ethyl acetate-hexane) to obtain the specified title compound (50 mg) as a colorless solid.1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.96-4.00 points (m, 2H), 4.16 the (t, 2H),? 7.04 baby mortality (DDD, 1H), 7,35 (DDD, 1H), 7,40 (t, 1H), 7,52-to 7.61 (m, 3H), 7,74-7,89 (m, 4H), by 8.22 (dt, 1H), 8,64 (s, 1H), 8,67-8,69 (m, 1H).

Example 5

2-(2-B is Amphenol)-6-(2-methoxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone

2-Bromophenylacetate (681 mg) was added to a solution of ethyl 4-(2-methoxyphenyl)-2-(2-pyridyl)-4-oxybutyrate (1,14 g) in ethanol (16 ml), then stirred at 80°C for 3 hours. The reaction mixture was concentrated, and then added nitrobenzene (20 mg) and stirred overnight at 180°C. the Reaction mixture was distributed between ethyl acetate and water, and the organic layer was washed with water, dried and concentrated. The residue was purified on a column of silica gel (system ethyl acetate-hexane) to obtain the specified title compound (294 mg) as a brown solid.1H-NMR (400 MHz, CDCl3); δ (ppm) 3,91 (s, 3H), 6,99-7,05 (m, 2H), 7,31-7,42 (m, 3H), of 7.48 (TD, 1H), 7,55 (DD, 1H), 7.62mm (DD, 1H), 7,75-7,80 (m, 2H), 8,70-8,72 (m, 1H), total of 8.74 (dt, 1H), 8,78 (s, 1H).

Example 6

2-(2-Cyanophenyl)-4-phenyl-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-e]pyridazin-3-one

4-Phenyl-2,3,4,4a-tetrahydro-5H-((1)benzopyrano[4,3-c]pyridazin-3-one (974 mg) was dissolved in methylene chloride (20 ml) and to it was added 2-(2-cyanophenyl)-1,3,2-dioxaborinane (1,96 g), copper acetate (1.27 g) and triethylamine (1.06 g), then stirred overnight at room temperature. The reaction solution was diluted with ethyl acetate, washed with aqueous ammonia, 1 N. hydrochloric acid and brine, and dried over anhydrous magnesium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified on a column of silica the LEM system (hexane-ethyl acetate). The crude crystals are recrystallized from ethyl acetate-hexane to obtain specified in the title compound (140 mg, 11%).1H-NMR (400 MHz, CDCl3); δ (ppm) 3,66-with 3.79 (m, 2H), 3,93-4,01 (m, 1H), 4.04 the is 4.13 (m, 1H), 6.89 in-6,94 (m, 1H), 6,99-7,05 (m, 1H), 7,29-7,40 (m, 4H), 7,41-of 7.48 (m, 3H), to 7.61-7,72 (m, 2H), 7,72-to 7.77 (m, 1H), 8,03 (DD, 1H).

Example 7

2-(2-Cyanophenyl)-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-e]pyridazin-3-one

2-(2-Cyanophenyl)-4-phenyl-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-e]pyridazin-3-one (91 mg) was dissolved in acetic acid (4 ml) at 60°C, thereto was added bromine (42 mg)and the mixture was stirred at 70°C for 30 minutes. The reaction solution was diluted with diethyl ether, washed with water and aqueous saturated solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. The desiccant was filtered, the filtrate was evaporated and purified on a column of NH silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (14 mg, 15%).1H-NMR (400 MHz, CDCl3); δ (ppm) of 5.06 (s, 2H), 6,98-7,02 (m, 1H), 7,07-7,13 (m, 1H), 7,33-7,38 (m, 1H), 7,38-the 7.43 (m, 2H), 7,46-7,58 (m, 4H), 7,71-7,80 (m, 2H), 7,82-7,87 (t, 1H), 8,03-8,08 (m, 1H).

Example 8

2-(2-Itfinal)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one

The connection specified in the header, synthesized in accordance with the method described in example 6.1H-NMR (400 MHz, CDCl3); δ (ppm) 3,65-a 3.83 (m, 2H), 3.95 to 4,10 (m, 2H), 6,93 (d, 1H), 6,97-,05 (m, 1H), 7,10-7,17 (m, 1H), 7,29-7,37 (m, 1H), 7,37-7,44 (m, 1H), 7,44-7,56 (m, 2H), of 7.64-to 7.77 (m, 1H), of 7.90-8,03 (m, 2H), 8,54 (d, 1H), 8,64 (DD, 1H).

Example 9

2-(2-Cyanophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one

2-(2-Itfinal)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one (75 mg) was dissolved in 1-methyl-2-pyrrolidone (2 ml), was added cyanide zinc (55 mg) and tetrakis (triphenylphosphine)palladium (5 mg), then stirred at 100°C for 1 hour. The reaction solution was diluted with ethyl acetate, washed with an aqueous solution of saturated sodium bicarbonate and dried over anhydrous magnesium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified on a column of silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (34 mg, 57%).1H-NMR (400 MHz, DMSO-d6); δ (ppm) to 5.21 (s, 2H), 7,10 (d, 1H), 7,12-7,20 (m, 1H), 7,42-of 7.48 (m, 1H), 7,56-to 7.61 (m, 1H), 7,70-to 7.77 (m, 1H), 7,88-of 8.00 (m, 4H), 8.07-a to 8.12 (m, 1H), 8,64 is 8.75 (m, 2H).

Example 10

4-(4-Methoxybenzyl)-6-phenyl-2-(2-tolyl)-3(2H)-pyridazinone

6-Phenyl-2-(2-tolyl)-2,3,4,5-tetrahydropyridine-3(2H)-he (0.54 g)was obtained from 3-benzoylpropionic acid (CAS No. 2051-95-8), and 2-tolylhydrazine (CAS No. 635-26-7) was dissolved in tetrahydrofuran (20 ml). After cooling to -78°C was gradually added 1.5 M diisopropylamide lithium (1.2 ml). Then the mixture was gradually added a solution of 4-anisic aldehyde (0.27 g) in Tetra is hydrofuran (10 ml), then was stirred overnight to ensure that the temperature became room temperature. In the reaction solution was added ethyl acetate, and the mixture was washed with salt solution and water. Then the solvent was evaporated, and the residue was purified on a column of silica gel (system of hexane-ethyl acetate) to obtain 0.10 g specified in the connection header.1H-NMR (400 MHz, CDCl3); δ (ppm) 2,19 (s, 3H), 3,83 (s, 3H), of 3.95 (s, 2H), 6,88-6,94 (m, 2H), 7.24 to 7,28 (m, 2H), 7.29 trend was 7.36 (m, 4H), 7,37-7,40 (m, 2H), 7,45-of 7.48 (m, 1H), 7,66-of 7.70 (m, 2H), 7,82-a 7.85 (m, 1H).

Example 11

2,6-Diphenyl-4-(α-hydroxy-2-picolyl)-4,5-dihydro-3(2H)-pyridazinone

2,6-Diphenyl-2,3,4,5-tetrahydropyridine-3(2H)-he (0.10 g), synthesized from 3-benzoylpropionic acid (CAS No. 2051-95-8) and phenylhydrazine (CAS No. 100-63-0), and 2-pyridinecarboxamide (0.05 g) was dissolved in tetrahydrofuran (10 ml). After cooling to -78°C was gradually added 1.5 M diisopropylamide lithium (0.2 ml). The reaction mixture was leaking within 1 hour, and then it was added 2-pyridinecarboxamide (0.05 g) and 1.5 M lithium diisopropylamide (0.2 ml). After stirring for 2 hours the temperature was gradually raised to room. To the reaction solution was added ethyl acetate, and the mixture was washed with saturated saline solution and water. Then the solvent was evaporated, and the residue was purified on a column of silica gel (system of hexane-ethyl acetate) to obtain the specified reception in the e compound (23 mg). 1H-NMR (400 MHz, CDCl3); δ (ppm) of 2.75 (DD, 1H), 3,13 (DD, 1H), 3,23 (DDD, 1H), 4,25 (Ushs, 1H), 5,68 (Ushs, 1H), 7.24 to 7,31 (m, 2H), 7,33-7,39 (m, 3H), 7,40-7,46 (m, 2H), 7,51 (DD, 1H), to 7.59-7,63 (m, 2H), 7,66-7,71 (m, 2H), 7,76 (dt, 1H), 8,55-8,58 (m, 1H).

Example 12

2-(2-Cyanophenyl)-4-(4-morpholinylcarbonyl)-6-phenyl-3(2H)-pyridazinone

Ethyl 2-etoxycarbonyl-4-phenyl-4-oxybutyrate was obtained from 2-bromoacetophenone and diethylmalonate, and then he was subjected to interaction with hydrazine monohydrate with the formation of 6-phenyl-4-etoxycarbonyl-4,5-dihydro-3(2H)-pyridazinone. Then he interacted with bromine in acetic acid to obtain 6-phenyl-4-etoxycarbonyl-3(2H)-pyridazinone. 6-Phenyl-4-etoxycarbonyl-3(2H)-pyridazinone (2.00 g) was dissolved in dichloromethane (50 ml), then were added 4-(2-amino-ethyl)morpholine (1.60 g). After boiling under reflux for 2 days it was purified on a column of silica gel (system dichloromethane-methanol) and was converted in the usual way using methanol/hydrochloric acid to obtain 4-(4-morpholinylcarbonyl)-6-phenyl-3(2H)-pyridinemethanol (1,83 g). The hydrochloride of 4-(4-morpholinylcarbonyl)-6-phenyl-3(2H)-pyridazinone (0.36 g) and 2-bromobenzonitrile (0.50 g) was dissolved in 1,2-dichlorobenzene (15 ml) was added copper acetate (0.2 g) and potassium (1.0 g), then stirred at 190°C for 1 hour. In the reaction solution were added ethyl acetate and the mixture washed with water. Dissolve Italy was evaporated, and the residue was purified on a column of silica gel (system of hexane-ethyl acetate) to obtain 13 mg specified in the connection header.1H-NMR (400 MHz, CDCl3); δ (ppm) 2,48-of 2.66 (m, 6H), to 3.58 is 3.76 (m, 6H), 7,45-7,51 (m, 3H), a 7.62 (dt, 1H), of 7.70 (DD, 1H), 7,80 (dt, 1H), 7,86-7,94 (m, 3H), 8,84 (s, 1H), 9,58 (Ushs, 1H).

Example 13

2-(2-Cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-2H-pyridazino[4,5-b]benzofuran-3-one

To a solution of 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone (200 mg) in dimethylformamide (6 ml) was added copper cyanide (I) (85 mg), then stirred at 120°C for 50 minutes. The mixture was distributed between ethyl acetate and aqueous ammonia, and the organic layer was washed with water, dried and concentrated. Then the residue was purified on a column of silica gel (system ethyl acetate-hexane) to obtain the compound indicated in heading (31 mg)as a pale brown solid.1H-NMR (400 MHz, CDCl3); δ (ppm) 7,46 (DDD, 1H), 7,54 (TD, 1H), 7,60 (TD, 1H), 7,65 (DDD, 1H), to 7.77-a 7.85 (m, 3H), 7,88-to 7.93 (m, 2H), compared to 8.26 (dt, 1H), 8,33-8,35 (m, 1H), 8,88-of 8.90 (m, 1H).

Specified in the title compounds of examples 14-28 synthesized in accordance with the method described in above example 1.

Example 14

2-(2-Bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,47 (Ushs, 1H), 3,80 (Ushs, 1H), 3,84 (s, 3H), 4,29 (Ushs, 1H), 6.90 to-to 6.95 (m, 2H), of 6.96-7,29 (m, 3H), 7,43 (TD, 1H), 7,51-rate of 7.54 (m, 1H),7,65-7,71 (m, 2H), 8,07 (dt, 1H), 8,58 (d, 1H).

Example 15

2-(2-Bromophenyl)-4-(4-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.78 (s, 3H), 3,79 (Ushs, 2H), 4.04 the (Ushs, 1H), 6,86 (d, 2H), 7.24 to 7,34 (m, 4H), 7,37-7,44 (m, 2H), to 7.67-7,71 (m, 2H), 8,04-8,08 (m, 1H), 8,62-8,64 (m, 1H).

Example 16

2-(2-Bromophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,36-of 3.46 (m, 1H), 3,82 (s, 3H), 3,82-3,90 (m, 1H), 4,14-4.26 deaths (m, 1H), 6,78 (d, 1H), 7,25-7,29 (m, 2H), 7,35-7,52 (m, 4H), 7,66-7,71 (m, 2H), 8,07 (d, 2H), 8,58 (d, 1H).

Example 17

2-(2-Itfinal)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.85 (s, 3H), 3,86 (Ushs, 1H), 4,30 (Ushs, 1H), 6.90 to-6,97 (m, 2H), 7,08-7,13 (m, 1H), 7.24 to 7,79 (m, 3H), 7,44-7,51 (m, 2H), 7,66-7,71 (m, 1H), 7,95 (DD, 1H), of 8.09 (d, 1H), 8,56-8,59 (m, 1H).

Example 18

4-(2-Methoxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,47 (DD, 1H, in), 3.75 (DD, 1H), 3,85 (s, 3H), 4,28 (DD, 1H), 6,91-to 6.95 (m, 2H), 7,21 (DD, 1H), 7.24 to 7,30 (m, 3H), 7,41 was 7.45 (m, 2H), 7,65-7,73 (m, 3H), of 8.15 (dt, 1H), 8,56-8,58 (m, 1H).

Example 19

2-(2-Bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,50-3,70 (m, 1H), 4,00-4,20 (m, 2H), 7.24 to 7,35 (14, 5H), 7,39-7,44 (m, 4H), 7,66-7,72 (m, 2H), of 8.06 (d, 1H), 8,62-8,64 (m, 1H).

Example 20

2-(2-Bromophenyl)-4-phenyl-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,40-to 3.49 (m, 2H), 4,01-to 4.14 (m, 1H), 7.23 percent-7,47 (m, 9H) to 7.67 (d, 1H), 8,07 (d, 1H), to 8.62 (DD, 1H), of 8.95 (s, 1H).

Example 21

4,6-Diphenyl-2-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.42 (DD, 2H), of 4.05 (DD, 1H), 7,22-7,40 (m, 9H), 7,56 (dt, 1H), 7,76-7,80 (m, 1H), 8,59-8,61 (m, 1H).

Example 22

4-(2-Methoxyphenyl)-2-(2-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,51 (DD, 1H), 3,79 (DD, 1H), 3,81 (s, 3H), 4,32 (DD, 1H), 6,88-to 6.95 (m, 2H), 7,21-7,28 (m, 4H), 7,60-of 7.69 (m, 2H), 7,75-7,79 (m, 1H), 8,15 (dt, 1H), 8,54-8,55 (m, 1H), 8,61-to 8.62 (m, 1H).

Example 23

4-(2-Cyanophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 7.35 (DDD, 1H), 7,42-7,46 (m, 1H), 7,51-EUR 7.57 (m, 3H), of 7.70 (dt, 1H), 7,75-7,83 (m, 5H), 8,21 (dt, 1H), 8,65 (s, 1H), 8,65-8,67 (m, 1H).

Example 24

2-(2-Bromophenyl)-4-(2-methoxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.35 (DD, 1H), of 3.45 (DD, 1H), a 3.87 (s, 3H), 4,33 (Ushs, 1H), 6,93-of 6.99 (m, 2H), 7.23 percent-to 7.32 (m, 4H), 7,44 (TD, 1H), of 7.70 (DD, 1H), 8,05-8,10 (m, 1H), at 8.60 (DD, 1H), 8,89-8,93 (m, 1H).

Example 25

4-(2-Bromophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.41 (DD, 1H), a 3.87 (DD, 1H), 4,49 (DD, 1H), 7,13-7,17 (m, 1H), 7,25-7,34 (m, 4H), 7,42-7,47 (m, 2H), 7,60-7,74 (m, 4H), of 8.15 (dt, 1H), 8,57-8,59 (m, 1H).

Example 26

2-(2-Methoxyphenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.58 (DD, 1H), of 3.77 (s, 3H), 3,78-a 3.87 (m, 1H), 4,08 (t, 1H), 7,00 (d, 1H), 7.03 is (TD, 1H), 7.23 percent-the 7.43 (m, 8H), to 7.64 (DDD, 1H), 8,03 (dt, 1H), 8,58 at 8.60 (m, H).

Example 27

4-Phenyl-2-(2-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,70 (DD, 1H), 3,78 (DD, 1H), 4,06 (DD, 1H), 7,26-7,39 (m, 6H), 7,46-7,52 (m, 1H), to 7.67-7,74 (m, 3H), 7,97-8,02 (m, 2H), 8,61-8,64 (m, 1H).

Example 28

2-(2-Forfinal)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.64 (DD, 1H), 3,83 (DD, 1H), 4,10 (DD, 1H), 7,15-7,40 (m, 9H), 7,46 (DD, 1H), of 7.70 (DDD, 1H), 8,07 (dt, 1H), 8,61-8,63 (m, 1H).

Specified in the title compounds of examples 29-34 synthesized in accordance with the method described in the above example 2.

Example 29

2-(2-Bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,47 (Ushs, 1H), 4,25 (Ushs, 1H), 4,43 (Ushs, 1H), for 6.81 (TD, 1H), 6,97 (d, 1H), 7,10 (d, 1H), 7,18 (TD, 1H), 7,25-7,44 (m, 4H), 7,68 (Ushs, 1H), 7,74 (TD, 1H), 8,10 (dt, 1H), 8,72 (d, 1H).

Example 30

2-(2-Bromophenyl)-4-(4-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,60 (Ushs, 2H), was 4.02 (Ushs, 1H), 5,20 (s, 1H), 6,74 (d, 2H), 7.23 percent-to 7.32 (m, 4H), 7,38-7,44 (m, 2H), to 7.67-7,72 (m, 2H), of 8.06 (d, 1H), 8,62-8,64 (m, 1H).

Example 31

2-(2-Bromophenyl)-6-(2-hydroxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,01-7,05 (m, 2H), 7,34-the 7.43 (m, 3H), 7,50-7,56 (m, 2H), 7,89 (d, 1H), 8,76-8,79 (m, 2H), remaining 9.08 (s, 1H), 10,50 (s, 1H).

Example 32

4-(2-Hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ(ppm) 7,05-7,10 (m, 2H), of 7.36 was 7.45 (m, 2H), 7,56 (DD, 1H), to 7.64 (DDD, 1H), to 7.77-to 7.84 (m, 3H), of 7.90 (DD, 1H), 8,23 (d, 1H), 8,78 (s, 1H), 8,88-of 8.92 (m, 1H), 9,05 (Ushs, 1H).

Example 33

4-(2-Hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.43 (DD, 1H), 4,30 (DD, 1H), at 6.84 (TD, 1H), 7,01-to 7.09 (m, 2H), 7,32-7,37 (m, 1H), 7,41-of 7.48 (m, 3H), 7,55-7,58 (m, 2H), 7,82 (TD, 1H), 8,20 is 8.22 (m, 1H), 8,58 (s, 1H), 8,76-8,77 (m, 1H).

Example 34

2-(2-Bromophenyl)-4-(2-hydroxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.43 (DD, 1H), 3,54-3,63 (m, 1H), 4,35-of 4.44 (m, 1H), 6,82-to 6.88 (m, 2H), 7,05 (Ushs, 1H), 7,14 (TD, 1H), 7,26 (TD, 1H), of 7.36 was 7.45 (m, 3H), 7,66 (d, 1H), 8,18 (dt, 1H), 8,66 (DD, 1H), 9,00 (s, 1H).

Specified in the title compounds of examples 35-38 synthesized in accordance with the method described in the above example 3.

Example 35

2-(2-Bromophenyl)-4-(2-dimethylaminoethoxy)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 2.25 (s, 6H), of 2.72 (t, 2H), 4,10-4,16 (m, 2H), 7,00 (d, 1H), 7.03 is (TD, 1H), 7,29-7,39 (m, 3H), of 7.48 (TD, 1H), 7,54 (DD, 1H), 7,60 (DD, 1H), 7,72-to 7.77 (m, 2H), 8,13 (dt, 1H), to 8.62 (s, 1H), 8,63-8,65 (m, 1H).

Example 36

2-(2-Bromophenyl)-6-(2-dimethylaminoethoxy)-4-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 2,24 (s, 6H), 2.77-to and 2.83 (m, 2H), 4,20 (t, 2H), 6,99-7,05 (m, 2H), 7,30-7,41 (m, 3H), of 7.48 (TD, 1H), 7,56 (DD, 1H), 7,66 (DD,1H), 8,69-8,71 (m, 1H), total of 8.74-8,77 (m, 1H), of 8.95 (s, 1H).

Example 37

2-(2-Bromophenyl)-4-[3-(2-picolylamine)]-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400MHz, CDCl3); δ (ppm) of 5.2 (s, 2H), 7,07 (DD, 1H), 7,21-7,24 (m, 1H), 7,32-7,40 (m, 3H), 7,49-7,63 (m, 4H), 7,70-7,79 (m, 4H), to 8.14 (d, 1H), 8,59-8,61 (m, 1H), 8,65 (s, 1H), 8,67-8,69 (m, 1H).

Example 38

2-Phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.34 (DD, 1H), 4,01 (DD, 1H), or 4.31 (DD, 1H), 7,28-7,33 (m, 2H), was 7.36-of 7.48 (m, 6H), 7,63 (DD, 2H), 7,74 (dt, 1H), 8,17 (TD, 1H), at 8.60 (DDD, 1H).

Specified in the title compounds of examples 39-47 synthesized in accordance with the method described in the above example 4.

Example 39

2-(2-Cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.50 (DD, 1H), 3,86 (s, 3H), 3,88 (DD, 1H), 4,29 (DD, 1H), 6,92-6,98 (m, 2H), 7,26-7,31 (m, 3H), 7,43 (DDD, 1H), 7,65 for 7.78 (m, 4H), 8,17 (dt, 1H), 8,57-8,59 (m, 1H).

Example 40

2-(2-Cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.87 (s, 1H), 7,01 (d, 1H),? 7.04 baby mortality (TD, 1H), 7,33 (DDD, 1H), 7,41 (DDD, 1H), 7,50-7,56 (m, 2H), 7,73 (TD, 1H), 7,76-7,81 (m, 2H), a 7.85 (DD, 1H), 8,23 (TD, 1H), 8,54 (s, 1H), 8,62-8,66 (m, 1H).

Example 41

2-(2-Cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.56 (DD, 1H), 4,14 (DD, 1H), 4,42 (DD, 1H), 6,85 (TD, 1H), of 6.96 (DD, 1H), 7,14 (DD, 1H), 7,20 (TD, 1H), 7,38 (DDD, 1H), 7,46 (TD, 1H), 7,58 (DD, 1H), of 7.70 (dt, 1H), 7,74 for 7.78 (m, 2H), 8,17 (dt, 1H), 8,70 (dt, 1H).

Example 42

2-(2-Cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1 H-NMR (400 MHz, CDCl3); δ (ppm) 7,05-7,11 (m, 2H), 7,38 (DDD, 1H), 7,43 (DDD, 1H), 7,56 (DD, 1H), to 7.64 (DDD, 1H), 7,78-to 7.84 (m, 3H), 7,89-a 7.92 (m, 1H), 8,23 (TD, 1H), 8,24-8,71 (m, 1H), 8,78 (s, 1H), 9,04 (s, 1H).

Example 43

2-(2-Cyanophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 7.35 (DDD, 1H), 7,46 is 7.50 (m, 3H), EUR 7.57 (DDD, 1H), 7,74-of 7.82 (m, 3H), 7,88 (DD, 1H), 7.95 is-of 7.97 (m, 2H), 8,23 (TD, 1H), 8,63 (s, 1H), 8,67-8,69 (m, 1H).

Example 44

2-(2-Cyanophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,85 (8, 3H), to 6.88 (d, 1H), 7,34 (DDD, 1H), 7,50 (DD, 1H), 7,55 (TD, 1H), 7,63 (d, 1H), 7,72-7,81 (m, 3H), 7,86 (DD, 1H), they were 8.22 (dt, 1H), 8,53 (s, 1H), 8,64-8,66 (m, 1H).

Example 45

2-(2-Cyanophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,37 (DDD, 1H), 7,42 (DDD, 1H), 7,44 to 7.62 (m, 1H), 7,78-7,83 (m, 3H), 7,88 (dt, 1H), they were 8.22 (dt, 1H), 8,35 (DDD, 1H), 8,67-8,71 (m, 3H), 9,12 (DD, 1H).

Example 46

2-(2-Cyanophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 7.35 (DDD, 1H), 7,54-of 7.60 (m, 2H), 7,70-7,89 (m, 7H), 8,24 (d, 1H), 8,65-8,67 (m, 1H), 8,71 (s, 1H).

Example 47

4-(2-Bromophenyl)-2-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,32-7,39 (m, 2H), 7,49-to 7.59 (m, 3H), 7,68 (TD, 1H), 7,74-of 7.82 (m, 4H), 8,14 (dt, 1H), 8,65-8,67 (m, 1H), 8,71 (s, 1H).

Specified in the title compounds of examples 48-50 synthesized in accordance with the method described in the above example 6.

Example 48

2-(2-Cyanophenyl)-9-fluoro-4-phenyl-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,66-3,74 (m, 2H), 3,90-3,98 (m, 1H), a 4.03-4.09 to (m, 1H), to 6.88 (DD, 1H),? 7.04 baby mortality (DDD, 1H), 7,28-7,33 (m, 2H), 7,35-7,49 (m, 4H), to 7.64-to 7.77 (m, 4H).

Example 49

2-(2-Cyanophenyl)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-((1) benzopyrano[4,3-c]pyridazin-3-one

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,66-of 3.80 (m, 2H), 3,97-4,10 (m, 2H), 6,91-to 6.95 (m, 1H), 7,00-7,06 (m, 1H), 7,32-7,37 (m, 1H), 7,41-7,51 (m, 2H), 7,66-7,79 (m, 4H), 8,01-of 8.06 (m, 1H), 8,50 are 8.53 (m, 1H), 8,64-8,68 (m, 1H).

Example 50

2-(2-Bromophenyl)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.64-of 3.77 (m, 1H), 3,93 (d, 1H), 4,01-4,12 (m, 2H), 6,94 (d, 1H), 6,98? 7.04 baby mortality (m, 1H), 7,28-7,38 (m, 2H), 7,42-7,58 (m, 2H), 7,66-7,74 (m, 2H), 7,98 (DD, 1H), 8,01-8,07 (m, 1H), 8,67-a total of 8.74 (m, 2H,).

Specified in the title compounds of examples 51-61 synthesized in accordance with the method described in the above example 7.

Example 51

2-(2-Bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm)? 7.04 baby mortality-to 7.09 (m, 2H), 7,35-7,45 (m, 3H), 7,54-to 7.59 (m, 3H), 7,76-7,81 (m, 2H), 8,17 (dt, 1H), 8,67-8,71 (m, 1H), 8,79 (s, 1H), 9,36 (s, 1H).

Example 52

2-(2-Bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,86 (s, 3H), 6,98 (d, 2H), 7,31-7,38 (m, 2H), of 7.48-7,56 (m, 2H), 7,73 for 7.78 (m, 2H), 8,04 (d, 2H), 8,14 (dt, 1H), at 8.60 (s, 1H), 8,67-8,68 (m, 1H).

Example 53

2-(2-Cyanophenyl)-9-fluoro-5-hydroxy-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one

1H-NMR (400 MHz, CDCl3); B4; (ppm) 3,61 (d, 1H), 6,10 (d, 1H), 7,01 (DD, 1H), 7,07-7,14 (m, 1H), 7,47-rate of 7.54 (m, 3H), 7,54-7,66 (m, 3H), 7,72-7,80 (m, 3H), 7,83-7,88 (m, 1H).

Example 54

2-(2-Cyanophenyl)-9-fluoro-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,09 (s, 2H), of 6.96 (DD, 1H), 7,02-to 7.09 (m, 1H), 7,37-the 7.43 (m, 2H), 7,45-of 7.60 (m, 4H), 7,72 (DD, 1H), 7,74-7,79 (m, 2H), 7,86 (d, 1H).

Example 55

2-Phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,33 (DDD, 1H), 7,41 was 7.45 (m, 2H), 7,49-of 7.55 (m, 4H), of 7.65 (DD, 1H), 7,73-of 7.55 (m, 1H), 7,79 (dt, 1H), 8,21 (TD, 1H), to 8.57 (s, 1H), 8,65 (DDD, 1H).

Example 56

2-(2-Bromophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 7.32 (DDD, 1H), was 7.36 (DDD, 1H), 7,44 is 7.50 (m, 4H), 7,54 (TD, 1H), 7,73 for 7.78 (m, 2H), 7,99 shed 8.01 (m, 2H), 8,14 (dt, 1H), 8,65 (s, 1H), 8,66-8,68 (m, 1H).

Example 57

2-(2-Bromophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one

1H-NMR (400 MHz, DMSO-d6); δ (ppm) 5,12 is 5.28 (m, 2H), 7,06-to 7.15 (m, 2H), 7,43 (DDD, 1H), 7,49 (DDD, 1H), 7,55-to 7.64 (m, 2H), 7,71 (DD, 1H), 7,84-to 7.93 (m, 3H), 8,64 (d, 1H), 8,68 (DD, 1H).

Example 58

2-(2-Itfinal)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one

1H-NMR (400 MHz, DMSO-d6); δ (ppm) 5,15 is 5.28 (m, 2H), 7,06-7,16 (m, 2H), 7,27-7,33 (m, 1H), 7,40-7,46 (m, 1H), 7,55-to 7.67 (m, 3H), 7,86 (DD, 1H), of 7.90 (DDD, 1H), of 8.06 (DD, 1H), 8,64 (d, 1H), 8,69 (DD, 1H).

Example 59

2-Phenyl-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 7.35 (DDD,1H), 7,40-of 7.48 (m, 1H), 7,52-7,56 (m, 2H), 7,71 to 7.75 (m, 2H), 7,80 (TD, 1H), to 8.20 (dt, 1H), of 8.37 (dt, 1H), 8,67-8,69 (m, 3H), 9,12 (d, 1H).

Example 60

4-(2-Bromophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,27-7,53 (m, 7H), of 7.69 (DD, 1H), to 7.77-7,81 (m, 3H), by 8.22 (dt, 1H), of 8.47 (s, 1H), 8,63-8,65 (m, 1H).

Example 61

2-(2-Bromophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,33-7,42 (m, 3H), 7,52 (TD, 1H), 7,55 (DD, 1H), to 7.77 (TD, 2H), 8,15 (dt, 1H), 8,18 (dt, 1H), 8,67-8,69 (m, 2H), 8,72 (s, 1H), 9,15 (DD, 1H).

Example 62

2-(2-Chlorophenyl)-4-(4-morpholinosydnonimine)-6-phenyl-3(2H)-pyridazinone

Specified in the title compound was synthesized according to the method described in the above example 12.

1H-NMR (400 MHz, CDCl3); δ (ppm) 2,45-of 2.64 (m, 6H), to 3.58 is 3.76 (m, 6N), 7,46-7,53 (m, 6H), to 7.59-7,63 (m, 1H), 7,86-to $ 7.91 (m, 2H), 8,84 (s, 1H), for 9.64 (Ushs, 1H).

Example 63

2-(2-Nitrophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

2-(3-Pyridyl)-4-(2-pyridyl)-4-oxomethane acid (100 mg) was dissolved in 1-butanol (5 ml), was added 2-nitrophenylhydrazine (60 mg)and the mixture is boiled under reflux for 3 hours. After cooling to room temperature the mixture was evaporated. The residue was dissolved in acetic acid (5 ml) and boiled under reflux during the night. After cooling to room temperature the mixture was evaporated. The residue was diluted with ethyl acetate and washed with podnimetsia saturated sodium bicarbonate and saturated saline solution. The organic layer was dried over magnesium sulfate, evaporated and purified on a chromatographic column with silica gel (ethyl acetate) to obtain the specified title compound (20 mg).

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,34-7,42 (t, 2H), 7,66 (DDD, 1H), 7,74-a 7.85 (m, 3H), 8,10 (DDD, 1H), 8,17 (DD, 1H), 8,32 (DDD, 1H), 8,67-8,71 (m, 2H), 8,72 (s, 1H), 9,10 (DD, 1H).

Example 64

2-(3-Tolyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone 64-1) 4-(3-Pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

2-(3-Pyridyl)-4-(2-pyridyl)-4-oxomethane acid (1.88 g) was dissolved in ethanol (40 ml) was added hydrazinoacetate (0,37 g), then boiled under reflux during the night. After cooling to room temperature the mixture was evaporated. The residue was diluted with methylene chloride, washed with water and saturated salt solution. The organic layer was dried over magnesium sulfate, then evaporated and purified on a chromatographic column with silica gel (methanol-chloroform) to obtain the specified title compound (1.77 g).

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.45 (DD, 1H), 3,71 (DD, 1H), 3,88 (DD, 1H), 7,27-7,34 (m, 2H), 7,66 (DDD, 1H), 7,76 (DDD, 1H), with 8.05 (DDD, 1H), 8,55 (DD, 1H), 8,57-to 8.62 (m, 2H), 8,78 (Ushs, 1H).

64-2) 2-(3-Tolyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

4-(3-Pyridyl)-4-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone (50 mg) was dissolved in N,N-dimethylformamide (2 ml), was added m-tolylboronic acid (54 mg), triethylamine (0,0 ml) and copper acetate (7 mg), then was stirred at room temperature for 1 day. The reaction solution was diluted with ethyl acetate and washed with aqueous ammonia and saturated salt solution. The organic layer was dried over magnesium sulfate, then evaporated and purified on a chromatographic column with NH silica gel (ethyl acetate-hexane) to obtain the specified title compound (10 mg).

1H-NMR (400 MHz, CDCl3); δ (ppm) to 2.46 (s, 3H), 7,26-7,30 (m, 1H), 7,35 (DDD, 1H), 7,38 was 7.45 (m, 2H), 7,47-rate of 7.54 (m, 2H), 7,80 (DDD, 1H), to 8.20 (DDD, 1H), at 8.36 (DDD, 1H), 8,66 (s, 1H), 8,67-to 8.70 (m, 2H), 9,10-9,12 (m, 1H).

Specified in the title compounds of examples 65-69 synthesized in accordance with the method described in the above example, 64.

Example 65

2-(4-Methanesulfonyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.12 (s, 3H), 7,40 (DDD, 1H), 7,43 (DD, 1H), to 7.84 (DDD, 1H), 8,02-8,07 (m, 2H), 8,10-of 8.15 (m, 2H), to 8.20 (d, 1H), 8,32 (DDD, 1H), 8,69-8,73 (m, 3H), 9,11 (d, 1H).

Example 66

2-(4-Biphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,34-7,44 (m, 3H), 7,46-7,51 (m, 2H), 7,63-to 7.68 (m, 2H), 7,73-to 7.77 (m, 2H), 7,79-to 7.84 (m, 3H), 8,24 (DD, 1H), of 8.37 (DDD, 1H), 8,68-8,71 (m, 3H), 9,13 (d, 1H).

Example 67

2-(2-Naphthyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 7.36 (DDD, 1H), 7,42 (DD, 1H), 7,53-of 7.60 (m, 2H), 7,78-7,86 (m, 2H), of 7.90-of 7.96 (m, 2H), 8,00 (d, 1H), they were 8.22-of 8.27 (m, 2H), scored 8.38 (DDD, 1H), 8,68-8,73 (m, 3H), 9,14 (d, 1H).

Prima is 68

2-(3,4-Methylenedioxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 6,07 (s, 2H), 6,93-of 6.96 (m, 1H), 7,17-7,21 (m, 2H), was 7.36 (DD, 1H), 7,41 (DD, 1H), 7,80 (DDD, 1H), 8,18 (d, 1H), 8.34 per (DDD, 1H), 8,65 (s, 1H), 8,67-8,71 (m, 2H), 9,11 (d, 1H).

Example 69

2-(3,4-Dichlorophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,38 (DDD, 1H), 7,42 (DDD, 1H), 7,60 (d, 1H), 7,68 (DD, 1H), 7,83 (DDD, 1H), to 7.93 (d, 1H), 8,19 (DDD, 1H), 8,32 (DDD, 1H), 8,67 (s, 1H), 8,68-8,72 (m, 2H), remaining 9.08 (d, 1H).

Example 70

2-(2-Cyanophenyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone

4-Phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone (100 mg) was dissolved in methylene chloride (5 ml), was added 2-(2-cyanophenyl)-1,3,2-dioxaborinane (0,22 g), pyridine (0.10 g) and copper acetate (0.15 g), then stirred at room temperature for 1 day. The reaction solution was diluted with methylene chloride and washed with aqueous ammonia, water and saturated salt solution. The organic layer was dried over magnesium sulfate and then evaporated. The residue was purified through column chromatography with NH silica gel (ethyl acetate-hexane) to obtain the specified title compound (29 mg).

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,37 (DD, 1H), 7,46-7,53 (m, 3H), EUR 7.57 (DDD, 1H), 7,72-7,80 (m, 2H), to 7.84 (DD, 1H), 7.95 is-8,00 (m, 2H), to 8.70 (s, 1H), 8,92 (d, 2H).

Example 71

2-(2-Pyridyl)-4-(2-pyridyl)-6-(2-methoxyphenyl)-3(2H)-pyridazinone

The connection specified in the header, sintezirovan and in accordance with the method, described in the above example 5.

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.89 (s, 3H), 6,98? 7.04 baby mortality (m, 2H), 7,31-7,42 (m, 4H), a 7.62 (DD, 1H), 7,68 (dt, 1H), 7,78 (DDD, 1H), to $ 7.91 (DDD, 1H), 8,70-8,73 (m, 3H).

Specified in the title compounds of examples 72-75 synthesized in accordance with the method described in the above example 6.

Example 72

2-(3-Formylphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,37-7,44 (m, 2H), 7,72 (t, 1H), 7,83 (dt, 1H), 7,98 (TD, 1H), 8,08 (DDD, 1H), 8,21 (TD, 1H), 8.30 to-at 8.36 (m, 2H), 8,69-8,72 (m, 3H), 9,10-9,12 (m, 1H), 10,11 (s, 1H).

Example 73

2-(Thiophene-3-yl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 7.36-7,44 (m, 3H), to 7.77 (DD, 1H), 7,82 (DDD, 1H), to 8.20 (DD, 1H), compared to 8.26 (dt, 1H), 8,32 (DDD, 1H), 8,61 (s, 1H), 8,68-8,71 (m, 2H), remaining 9.08 (DD, 1H).

Example 74

2-(3-Pyridyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 7.36 (DDD, 1H), 7,44-7,52 (m, 4H), of 7.82 (dt, 1H), 7,92-to 7.95 (m, 2H), 8,18 is 8.22 (m, 2H), 8,63 (s, 1H), 8,66 (DD, 1H), 8,69 (DDD, 1H), 9,06 (d, 1H).

Example 75

2-(3-Pyridyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,38 (m, 1H), 7,44-7,52 (m, 4H), 7,94-of 7.96 (m, 2H), 8,11 (DDD, 1H), 8,64 (s, 1H), 8,67 (DD, 1H), 8,93 (d, 2H), 9,02 (DD, 1H).

Specified in the title compounds of examples 76-78 synthesized in accordance with the method described in above example 1.

Example 76

2-(2-Methoxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-PI is icasino

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.56-3,88 (m, 5H), 4,10 (t, 1H), 7,00-7,07 (m, 2H), 7,25-7,29 (m, 2H), 7,34-7,40 (m, 2H), to 7.67 (dt, 1H), 7,75-7,80 (m, 1H), with 8.05 (dt, 1H), charged 8.52 (DD, 1H), at 8.60 (DDD, 1H), 8,65-8,69 (m, 1H).

Example 77

4-Methyl-2,4,6-triphenyl-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) to 1.70 (s, 3H), 3,11 (d, 1H), and 3.72 (d, 1H), 7,22-7,30 (m, 4H), 7,33 and 7.36 (m, 2H), 7,38-7,42 (m, 5H), 7,53-EUR 7.57 (m, 2H), 7,75 for 7.78 (m, 2H).

Example 78

2-(2-Bromophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone

1H-NMR (400 MHz, CDCl3); δ (ppm) of 1.73 (s, 3H), 3,17 (d, 1H, in), 3.75 (d, 1H), 7,22-7,25 (m, 2H), 7,28-to 7.32 (m, 2H), was 7.36-7,42 (m, 7H), to 7.64-to 7.68 (m, 2H), 7,72 for 7.78 (m, 2H).

Example 79

2-(3-Pyridine-1-oxide)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

To a solution of 2-(3-pyridyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone (224 mg) in dichloromethane (5 ml) was slowly added 70% m-chloroperbenzoic acid (1.27 g) under ice cooling, followed by stirring for 1 hour. The reaction mixture was distributed between 2 N. aqueous sodium hydroxide and ethyl acetate, and the organic layer was washed with water, dried and concentrated. The residue was purified through column chromatography with NH-silica gel (ethyl acetate) to obtain the specified title compound (117 mg) as a pale yellow solid.

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,38-7,42 (m, 2H), of 7.48-7,52 (m, 3H), to 7.84 (dt, 1H), 7,89-to $ 7.91 (m, 2H), 7,99 (DDD, 1H), 8,21 (TD, 1H), 8,25 (DDD, 1H), to 8.62 (s, 1H), 8,69 (DDD, 1H), 8,84 (t, 1H).

Example 80

80A) 2-(2-Cyano-5-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

80B) 2-(2-Cyano-3-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone

Centripetally (0,12 ml) and triethylamine (84 ml) was added to a solution of 2-(3-pyridine-1-oxide)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone (52 mg) in a mixture solvent of acetonitrile (2 ml) and chloroform (2 ml), and then boiled under reflux during the night. After concentrating the reaction mixture, the residue was purified through column chromatography with NH-silica gel system (chloroform/hexane) to give 2-(2-cyano-5-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone (24 mg) as colorless solids and 2-(2-cyano-3-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone (12 mg) as a yellow solid.

80 A;

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,40 (DDD, 1H), 7,49-7,52 (m, 3H), 7,83-7,92 (14, 4H), 8,19 (TD, 1H), 8,64 (s, 1H), 8,70 (DDD, 1H), 9,27 (DD, 1H).

80B;

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,38 (DDD, 1H), of 7.48-7,52 (m, 3H), of 7.70 (DD, 1H), 7,82 (dt, 1H), 7,93-to 7.95 (m, 2H), by 8.22 (DD, 1H), compared to 8.26 (dt, 1H), 8,66 (s, 1H), 8,69 (DDD, 1H), 8,79 (DD, 1H).

Example 81

81A) 2-(2-Cyano-5-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone

81B) 2-(2-Cyano-3-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone

2-(2-Cyano-5-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone and 2-(2-cyano-3-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone was obtained similarly to the method described above in which the Rimera 80.

81A;

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,42 (t, 1H), 7,50-rate of 7.54 (m, 3H), a 7.85 (DD, 1H), to $ 7.91-to 7.93 (m, 2H), of 8.37 (DD, 1H), 8,63 (s, 1H), to 8.94 (d, 2H), 9,23 (DD, 1H).

V;

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,40 (t, 1H), 7,49-7,52 (m, 3H), 7,71 (DD, 1H), 7.95 is-of 7.97 (m, 2H), 8,12 (DD, 1H), 8,71 (s, 1H), 8,79 (DD, 1H), 8,93 (d, 2H).

Example 82

2-(2-Cyanophenyl)-4-phenyl-6-(2-pyrazinyl)-3(2H)-pyridazinone

6-Chloro-2-(2-cyanophenyl)-4-phenyl-3(2H)-pyridazinone (16 mg), 2-tributylstannyl (25 mg) and tetrakis (triphenylphosphine)-palladium (3 mg) were added to xylene (1 ml) followed by stirring at 120°C for 2 hours in nitrogen atmosphere. The reaction mixture was purified through column chromatography with NH-silica gel (system ethyl acetate/hexane) to give the compounds specified in the header (14 mg)as a pale yellow solid.

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,45 to 7.62 (m, 4H), 7,78-7,80 (m, 2H), 7,88-of 7.96 (m, 3H), 8,54 (s, 1H), 8,62-8,64 (m, 2H), 9,45 (d,2H).

Example 83

2-(2-Cyanophenyl)-4-phenyl-6-(triazole-2-yl)-3(2H)-pyridazinone

Specified in the title compound was synthesized according to the above example 82.

1H-NMR (400 MHz, CDCl3); δ (ppm) 7,47 is 7.50 (m, 4H), to 7.59 (DDD, 1H), 7,75-7,81 (m, 2H), 7,87 (DDD, 1H), 7,92-to 7.95 (m, 3H), 8,40 (s, 1H).

Example 84

2-(2-Cyanophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone

Specified in the title compound was synthesized according to the above example 4.

1H-NMR (400 MHz,CDCl 3); δ (ppm) of 1.75 (s, 3H), 3,21 (d, 1H), 3,74 (d, 1H), 7,25-7,27 (m, 1H), 7,29-7,34 (m, 2H), 7,37 was 7.45 (m, 6H), EUR 7.57 (DDD, 1H), 7,66 (DDD, 1H), 7,73 (DDD, 1H), 7,75 for 7.78 (m, 2H).

Example 85

2-(2-Bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

2-(2-Bromophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he (70 mg) was dissolved in anhydrous tetrahydrofurane (10 ml), was added copper acetate (77 mg), sodium hydride (25 mg) and 2-methoxyphenylalanine acid (77 mg), then stirred at room temperature for 1 hour. Next was added sodium hydride (25 mg) and 2-methoxyphenylalanine acid (50 mg), and stirred at room temperature for 6 hours. Then the organic layer was distributed by adding ethyl acetate and aqueous ammonia. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the compound indicated in heading (55 mg, 60%)as a colorless powder.

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.85 (s, 3H), 5,02 (s, 2H), 6,94-of 6.99 (m, 2H), 7,20-7,31 (m, 3H), 7,35-7,42 (m, 2H), 7.62mm (DD, J=7,6 Hz, 1.6 Hz, 1H), 7,66-7,73 (m, 2H), 8,09-8,11 (m, 1H), 8,54 (DDD, J=5.0 Hz, 1.8 Hz, 1.6 Hz, 1H).

Example 86

2-(2-Bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

To a solution of 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-di is Idro-1,2,4-triazine-3(2H)-it (48 mg) in dichloromethane (10 ml) was added 1 M tribromide boron in methylene chloride (0.3 ml) under cooling on ice, and was stirred for 5 hours. The organic layer was distributed, adding to the reaction mixture an aqueous solution of saturated sodium bicarbonate and dichloromethane, washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (36 mg, 78%) as a colorless amorphous substance.

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,23 (Ushs, 2H), 7,02-7,10 (m, 2H), 7,20 was 7.36 (m, 4H), 7,46 (TD, J=8.0 Hz, 1.2 Hz, 1H), 7.62mm (DD, J=8.0 Hz, 1.8 Hz, 1H), 7,71-7,76 (m, 2H), of 8.09 (d, J=8.0 Hz, 1H), 8,59 (d, J=5,2 Hz, 1H).

ESI-Mass; 423 [M++N].

Example 87

2-(2-Cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

2-(2-Bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he (99 mg) was dissolved in dimethylformamide (20 ml), was added copper cyanide (51 mg), then stirred at 150°C for 3 hours. After cooling the reaction solution to room temperature, the organic layer was distributed by adding aqueous ammonia (20 ml) and ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After drying, the substance was filtered, the residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified header is compound (72 mg, 83%) as a colorless amorphous substance.

1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.87 (s, 3H), 5,04 (s, 2H), 6,97-7,01 (m, 2H), 7,25-7,39 (m, 4H), to 7.61-7,66 (m, 1H), 7,72 for 7.78 (m, 3H), by 8.22 (d, J=8.0 Hz, 1H), 8,54 (DDD, J=4,8 Hz, 1.6 Hz, 1.2 Hz, 1H).

ESI-Mass; 384 [M++H].

Example 88

2-(2-Bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

2-(2-Bromophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he (12 mg) was dissolved in anhydrous dichloromethane (30 ml), was added triethylamine (0.1 ml), copper acetate (13.2 mg) and phenylboronic acid (13.3 mg), then stirred at room temperature for 48 hours. Then was added sodium hydride (3 mg) and phenylboronic acid (10 mg) and stirred at room temperature for 5 hours. Then the organic layer was distributed by adding aqueous ammonia and ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After drying, the substance was filtered, the residue was purified through column chromatography with NH silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (11 mg, 75%) as a colorless powder.

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,15 (Ushs, 2H), 7,21-7,31 (m, 3H), of 7.36-7,46 (m, 3H), 7,47-7,52 (m, 2H), 7.62mm (DD, J=8.0 Hz, 1.8 Hz, 1H), 7.68 per-7,74 (m, 2H), 8,10 (dt, J=8.0 Hz, 1.4 Hz, 1H), 8,57 (DDD, J=5.0 Hz, 1.8 Hz, 0.8 Hz, 1H).

ESI-Mass; 407 [M++H].

Example 89

2-(2-Bromophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-it

The synthesis was carried out according to the method Horst Gnichtel, Widah I. Salem and Lothar Waretschek; Liebigs Ann. Chem. (1978) 2033-2043 in the following way. 2-Bromo-2'-methoxyacetophenone (1,33 g) and aniline (1.06 g) was dissolved in ethanol (20 ml) and stirred at room temperature for 72 hours. Then insoluble substances were filtered off, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate). The obtained colorless oily derivative of acetophenone (1.12 g) was dissolved in ethanol (20 ml) was added 2-bromophenyl hydrazine (930 mg), followed by stirring at room temperature over night. The reaction solution was evaporated, and the residue (1.84 g) was dissolved in tetrahydrofuran (20 ml). Added triphosgene (459 mg) and triethylamine (1.4 ml) under cooling on ice, and the mixture was stirred for 3 hours while the temperature of the mixture gradually rose to room temperature. The reaction solution was evaporated, and the residue was purified through column chromatography with silica gel (hexane-ethyl acetate) to obtain the specified title compound (438 mg, 17%) as a colorless amorphous substance.

1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.87 (s, 3H), around 4.85 (s, 2H), 6,92 (d, J=8,4 Hz, 1H), 7,01 (t, J=7,4 Hz, 1H), 7.18 in-7,25 (m, 2H), 7,27-7,46 (m, 6H), to 7.64-7.68 per (t, 2H), 7,71 (dt, J=7,6 Hz, 1.6 Hz, 1H).

ESI-Mass; 436 [M++H].

Example 90

2-(2-Bromophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dig the DRO-1,2,4-triazine-3(2H)-he

In accordance with the method described in example 86, indicated in the title compound (135 mg, 95%) was obtained from 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she (147 mg).

1H-NMR (400 MHz, CDCl3); δ (ppm) to 4.98 (s, 2H), 6,91 (t, J=8.0 Hz, 1H), 7,00 (DD, J=8.0 Hz, 0.8 Hz, 1H), 7,25-7,35 (m, 4H), 7,40-of 7.48 (m, 5H), 7,58 (DD, J=8.0 Hz, 1.6 Hz, 1H), 7,69 (DD, J=7,8 Hz and 1.4 Hz, 1H), 10,96 (s, 1H).

ESI-Mass; 424 [M++H].

Example 91

2-(2-Bromophenyl)-6-(2-dimethylaminoethoxy)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

2-(2-Bromophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he (100 mg) was dissolved in dimethylformamide (20 ml) was added potassium carbonate (66 mg). Was added dropwise excess dimethylaminoethoxide and stirred at 120°C during the night. Then the reaction solution was cooled to room temperature, the organic layer was distributed, adding water and ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (65 mg, 55%) as colorless crystals.

1H-NMR (400 MHz, CDCl3); δ (ppm) and 2.26 (s, 6H), to 2.65 (t, J=5.8 Hz, 2H), 4,11 (t, J=5.8 Hz, 2H), is 4.93 (s, 2H), 6,91 (d, J=8.0 Hz, 1H), 6,98 (TD, J=7,6 Hz, 0.8 Hz, 1H), 7,16-7,25 (m, 2H), 7,33-7,39 (m, 3), 7,40-7,46 (m, 3H), 7,66 (TD, J=8.0 Hz, 1.6 Hz, 2H), 7,72 (DD, J=7.8 Hz, 1.8 Hz, 1H).

ESI-Mass; 495 [M++H].

Example 92

2-(2-Bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

2-(2-Bromophenyl)-6-(2-methoxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he (193 mg)synthesized in accordance with the method described in examples 85-87, was dissolved in dimethylformamide (20 ml), was added 2-bromopyridine (300 mg), potassium carbonate (185 mg) and copper iodide (20.4 mg), then was heated at 130°C for 5 hours. After cooling to room temperature, the organic layer was distributed by adding aqueous ammonia (20 ml) and ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with NH silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (126 mg, 54%) as a colorless powder.

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.84 (s, 3H), 5,10 (Ushs, 2H), 6,86-6,97 (m, 3H), 7,14-to 7.18 (m, 1H), 7,29-7,38 (m, 2H), 7,54-7,63 (m, 4H), 7,92-to 7.95 (m, 1H), 8,29-8,31 (m, 1H).

ESI-Mass; 437 [M++H].

Specified in the title compounds of examples 93-96 synthesized in accordance with the method described in the above example 86.

Example 93

2-(2-Cyanophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) to 5.0 (s, 2H), 6,91-of 6.96 (m, 1H), 7,02 (DD, J=8,4 Hz, 0.8 Hz, 1H), 7,27-7,49 (m, 8H), 7,70-7,73 (m, 2H), 7,73-to 7.77 (m, 1H), 10,83 (s, 1H).

ESI-Mass; 369 [M++H].

Example 94

2-(2-Bromophenyl)-4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, DMSO-d6); δ (ppm) rate 4.79 (s, 2H), 6,59 (DD, J=8,8 Hz, 2.8 Hz, 1H), 6,70-6,74 (m, 2H), 6.89 in (DD, J=13,2 Hz, 0.8 Hz, 2H), 7,28-7,37 (m, 2H), 7,49-EUR 7.57 (m, 2H), 7,66 (DD, J=7,8 Hz, 1.0 Hz, 1H), 7,76 (d, J=8,2 Hz, 1H), of 8.92 (s, 1H), which is 9.09 (Ushs, 1H), 10,52 (Ushs, 1H).

ESI-Mass; 454 [M++H].

Example 95

4-(2,5-Dihydroxyphenyl)-6-(2-hydroxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, DMSO-d6); δ (ppm) 4,78 (s, 2H), 6,60 (DD, J=8,8 Hz, 2.8 Hz, 1H), 6,70 to 6.75 (m, 2H), 6,91 (DD, J=12,8 Hz and 7.6 Hz, 2H), 7.23 percent-7,34 (m, 2H), 7,39 was 7.45 (m, 2H), 7,54-to 7.61 (m, 3H), of 8.92 (s, 1H), 9,04 (s, 1H), a 10.74 (s, 1H).

Example 96

2-(2-Cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.87 (s, 2H), 6,69-PC 6.82 (m, 1H), 6,94-7,10 (m, 2H), 7,22-7,52 (m, 5H), 7,62-7,66 (m, 1H), 7,72-7,76 (m, 1H), 7,98-with 8.05 (m, 1H), 8,54-8,67 (m, 1H).

ESI-Mass; 370 [M++H]

Specified in the title compounds of examples 97-103 synthesized in accordance with the method described in the above example 87.

Example 97

2-(2-Cyanophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) a 3.87 (s, 3H), a 4.86 (s, 2H), 6,93 (d, J=8,4 Hz, 1H),? 7.04 baby mortality (TD, J=7,2 Hz, 0.8 Hz, 1H), 7,20-7,27 (m, 1H), 7,34 was 7.45 (m, 6H), the 7.65 (TD, J=7.8 Hz, 1.6 Hz, 1H), 7,71 (DD, J=7,6 Hz, 1.6 Hz, 1H), to 7.77-and 7.1 (m, 2H).

ESI-Mass; 383 [M++H].

Example 98

4-(2-Cyanophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.85 (s, 3H), around 4.85 (s, 2H), 6.90 to-6,94 (m, 1H), 6,99-7,06 (m, 1H), 7,20-7,26 (m, 1H), 7,33-the 7.43 (m, 4H), 7,49-7,52 (m, 1H), 7,62-to 7.77 (m, 5H).

ESI-Mass; 383 [M++H].

Example 99

2-(2-Cyanophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,91 (s, 3H), to 5.21 (s, 2H), 6,95 (d, J=8,4 Hz, 1H), 7,00-was 7.08 (m, 2H), 7,39-7,44 (m, 2H), of 7.64-7,80 (m, 5H), 7,98 shed 8.01 (m, 1H), 8,39 (DDD, J=4,8 Hz, 1.8 Hz, 0.8 Hz, 1H).

ESI-Mass; 384 [M++H].

Example 100

2-(2-Cyanophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) to 5.17 (s, 2H), 7.24 to 7,33 (m, 2H), 7,38-7,44 (m, 3H), 7,46 is 7.50 (m, 2H), 7,65-of 7.69 (m, 1H), 7,74-7,79 (m, 3H), 8,19 is 8.22 (m, 1H), 8,57 (DDD, J=4,8 Hz, 1.6 Hz, 0.8 Hz, 1H).

ESI-Mass; 354 [M++H].

Example 101

2-(2-Cyanophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,19 (s, 2H), 7,28-7,35 (m, 3H), 7,43 (TD, J=7,6 Hz, 1.2 Hz, 1H), 7,47 (DD, J=5,2 Hz, 1.6 Hz, 1H), 7,66-7,79 (m, 4H), 8,19 (dt, J=8.0 Hz, 1.0 Hz, 1H), 8,59-8,61 (m, 1H).

Example 102

2-(2-Cyanophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) vs. 5.47 (s, 2H), 7,10 (DDD, J=7,0 Hz, 4.6 Hz, 1.0 Hz, 1H), 7,30-7,34 (m, 1H), 7,38-7,52 (m, 2H), of 7.64-7,79 (m, 4H), 7,99 shed 8.01 (m, 1H), 8,18 (DD, J=8.0 Hz, 0.8 Hz, 1H), of 8.47-8,49 (m, 1H), 8,64-8,66 (m, 1H).

ESI-Mass; 355 [M++H].

Example 103

2-(2-C is anafanil)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,22 (s, 2H), 7,32-7,38 (m, 2H), 7,44 (TD, J=7,6 Hz, 1.2 Hz, 1H), of 7.70 (TD, J=7,4 Hz, 1.6 Hz, 1H), 7,74-7,80 (m, 3H), 7,88 (DDD, J=8,4 Hz, 2.8 Hz, 1.2 Hz, 1H), 8,19 (d, J=8.0 Hz, 1H), 8,50 are 8.53 (m, 1H), 8,59 (DDD, J=4,8 Hz, 1.6 Hz, 0.8 Hz, 1H), 8,78-8,82 (m, 1H).

ESI-Mass; 355 [M++H].

Specified in the title compounds of examples 104 to 111 was synthesized according to the method described in the above example 88.

Example 104

4-(2-Cyanophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) of 5.15 (s, 2H), 7,21-7,33 (m, 2H), was 7.36-7,46 (m, 3H), 7,52-EUR 7.57 (m, 1H), 7,65-7,79 (m, 5H), 8,18 (d, J=8,4 Hz, 1H), 8,54-8,56 (m, 1H).

ESI-Mass; 354 [M++H].

Example 105

2-Phenyl-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,14 (s, 2H), 7.24 to 7,28 (m, 1H), 7,28-7,34 (m, 3H), 7,42-7,47 (m, 2H), 7,50 (DD, J=5,2 Hz, 1.2 Hz, 1H), 7,52-the 7.65 (m, 2H), 7,76 (TD, J=7,8 Hz, 2.0 Hz, 1H), 8,16 (d, J=8.0 Hz, 1H), 8,59-8,61 (m, 1H).

ESI-Mass; 335[M++H].

Example 106

2-(2-Bromophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,18 (Ushs, 2H), 7.24 to 7,32 (m, 4H), 7,45 (t, J=7,6 Hz, 1H), 7,52-rate of 7.54 (m, 1H), to 7.59-to 7.61 (m, 1H), 7,69-7,74 (m, 2H), 8,08 (DD, J=7,8 Hz, 1.0 Hz, 1H), 8,59-8,61 (m, 1H).

ESI-Mass; 415 [M++H]

Example 107

4-(2,4-Acid)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) is 3.82 (s, 3H), 3,83 (s, 3H), 4,96 (s, 2H), of 6.49 (DD, J=8,4 Hz, 2.8 Hz, 1H), 6,53 (d, J=2,8 Hz, 1H), 7,20-of 7.23(m, 3H), of 7.36-7,42 (m, 2H), 7,66-to 7.67 (m, 2H), of 7.75 (TD, J=8.0 Hz, 1.6 Hz, 1H), 8,18 (d, J=8,4 Hz, 1H), 8,54 (d, J=4,8 Hz, 1H).

ESI-Mass; 389 [M++H].

Example 108

2-(2-Bromophenyl)-6-(2-methoxyphenyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) to 3.92 (s, 3H), 4,89 (s, 2H), 6,95 (d, J=8,4 Hz, 1H), 7,10 (t, J=7,6 Hz, 1H), 7,14-7,16 (m, 1H), 7,21-7,29 (m, 3H), 7,38 to 7.62 (m, 3H), 7,62-to 7.64 (m, 1H), to 7.67-of 7.70 (m, 1H).

Example 109

2-Phenyl-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,16 (s, 2H), 7,27 was 7.36 (m, 3H), 7,45 (t, J=7.8 Hz, 2H), 7,63-7,66 (m, 2H), to 7.77 (TD, J=8.0 Hz, 1.8 Hz, 1H), 7,86 (DDD, J=8,2 Hz, 2.8 Hz, 1.6 Hz, 1H), 8,19 (dt, J=8.0 Hz, 1.0 Hz, 1H), 8,48 (DD, J=4,8 Hz, 1.6 Hz, 1H), 8,58 (DDD, J=4,8 Hz, 1.8 Hz, 0.8 Hz, 1H), 8,78 (d, J=2.0 Hz, 1H).

ESI-Mass; 330 [M++H].

Example 110

2-(2-Bromophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,20 (Ushs, 2H), 7,26-7,35 (m, 2H), 7,43-of 7.48 (m, 2H), 7,60-7,76 (m, 3H), 7,89 (DDD, J=7.8 Hz, 2.8 Hz, 1.4 Hz, 1H), 8,10 (d, J=8.0 Hz, 1H), 8,48 (DD, J=4,8 Hz, 1.6 Hz, 1H), 8,59 (d, J=4,8 Hz, 1H), 8,80 (d, J=2.4 Hz, 1H).

ESI-Mass; 410 [M++H].

Example 111

2-(2-Bromophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,19 (s, 2H), 7.24 to 7,32 (m, 2H), 7,41 (DD, J=7,6 Hz, 1.2 Hz, 1H), 7,45 (DD, J=7,6 Hz, 1.2 Hz, 1H), EUR 7.57 (DD, J=8.0 Hz, 0.8 Hz, 1H), of 7.64 to 7.75 (m, 5H), 8,11 (d, J=8.0 Hz, 1H), 8,55 (DDD, J=5.0 Hz, 1,8 Hz, 0.8 Hz, 1H).

Specified in the title compounds of examples 112-117 synthesized in accordance with the way the m described in the above example 89.

Example 112

2-(2-Bromophenyl)-4,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) to 4.92 (s, 2H), 7,22-7,27 (m, 2H), 7,39-7,47 (m, 8H), 7,62-the 7.65 (m, 1H), to 7.67-of 7.70 (m, 1H), 7,72 to 7.75 (m, 2H).

Example 113

4-(2-Bromophenyl)-2,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) of 4.67 (d, J=to 15.4 Hz, 1H), 4,94 (d, J=to 15.4 Hz, 1H), 7,21-7,31 (m, 3H), of 7.36-7,46 (m, 6H), 7,49 (DD, J=8.0 Hz, 1.6 Hz, 1H), to 7.67-7,71 (m, 2H), 7,73-to 7.77 (m, 2H).

ESI-Mass; 406 [M++H].

Example 114

2-(2-Bromophenyl)-4-(2-bromophenyl)-6-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 4,74 (d, J=15.6 Hz, 1H), 5,44 (d, J=15.6 Hz, 1H), 6,78-PC 6.82 (m, 1H), 6,95-6,98 (m, 1H), 7,12-7,30 (m, 3H), 7,38-7,53 (m, 4H), to 7.59-7,74 (m, 3H), 8,54-8,58 (m, 1H).

ESI-Mass; 486 [M++H].

Example 115

4-(2-Bromophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) is 3.82 (s, 3H), 4,55-4,82 (m, 2H), 6,88-6,98 (m, 1H),? 7.04 baby mortality (t, J=7,6 Hz, 1H), 7,13-7,27 (m, 3H), 7,32-7,41 (m, 3H), 7,45 (TD, J=7.8 Hz, 1.6 Hz, 1H), to 7.61-7,71 (m, 3H), 7,76 (DD, J=7,6 Hz, 1.6 Hz, 1H).

ESI-Mass; 436[M++H].

Example 116

2-(2-Bromophenyl)-4-(2,5-acid)-6-(2-methoxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.75 (s, 6H), 3,82 (s, 3H), 4,70 (s, 2H), 6,80 (DD, J=9,0 Hz, 3.0 Hz, 1H), 6.87 in (d, J=8,8 Hz, 1H), 6.89 in (d, J=8,4 Hz, 1H), of 6.96 (d, J=2,8 Hz, 1H), 7,00 (TD, J=7,4 Hz, 0.4 Hz, 1H), 7,17-7,20 (m, 1H), 7,35-7,40 (m, 2H), to 7.64 (DD, J=4,8 Hz, 1.6 Hz, 1H), 7,66 (DD, J=4,8 Hz, 1.6 Hz, 1H), 7,73 (DD, J=7,6 Hz, 1.6 Hz,1H).

Example 117

4-(2,5-Acid)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,74 (s, 3H), 3,76 (s, 3H), 3,81 (s, 3H), of 4.66 (s, 2H), 6,83 (DD, J=9,0 Hz, 3.0 Hz, 1H), 6,86-6,94 (m, 3H), 7,03 (t, J=7,6 Hz, 1H), 7,17 (t, J=7,4 Hz, 1H), 7,32-7,41 (m, 3H), to 7.67-7,71 (m, 2H), of 7.75 (DD, J=7,6 Hz, 1.6 Hz, 1H).

ESI-Mass; 418 [M++H].

Example 118

2-(2-Bromophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

Specified in the title compound was synthesized according to the method described in example 92 above.

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,16 (m, 1H), 5.25 to the 5.51 (m, 1H), 7,06-to 7.09 (m, 1H), 7,27-7,32 (m, 1H), 7,37-7,52 (m, 2H), to 7.59-7,74 (m, 4H), 8,03 (d, J=8,4 Hz, 1H), 8,08-8,11 (m, 1H), 8,46-8,49 (m, 1H), 8,63-8,66 (m, 1H).

ESI-Mass; 408 [M++H].

Example 119

2-Phenyl-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

119-1) N-Methoxycarbonyl-N-phenylglycine

N-Phenylglycine (7.2 g) was dissolved in tert-butylmethylether ether (120 ml) was added 1 N. aqueous sodium hydroxide (105 ml). The mixture was cooled to 0°C and was added dropwise methylcarbonate (6 ml) under vigorous stirring, then stirred at room temperature overnight. The organic layer was removed, and the aqueous layer was added an aqueous solution of sodium dihydrophosphate, then was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered out is, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (9.1 g, 92%) as colorless crystals.

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,27 (Ushs, 3H), 4,39 (m, 2H), 7.24 to 7,39 (m, 5H).

119-2) N-Methoxycarbonyl-N-phenylamino-2-ethanol

N-Methoxycarbonyl-N-phenylglycine (395 mg) was dissolved in anhydrous tetrahydrofuran (50 ml), cooled to 0°C and added dropwise complex of 1.0 M borane-tetrahydrofuran in tetrahydrofuran (2.4 ml) in nitrogen atmosphere. After stirring at 0°C for 2 hours, then was added dropwise a 1.0 M complex, borane-tetrahydrofuran in tetrahydrofuran (2.4 ml). This procedure was repeated twice. Then was stirred at 0°C for 4 hours, was added dropwise methanol (40 ml) and after stirring at the same temperature for 2 minutes, the mixture was evaporated. Added ethyl acetate, the reaction solution was washed with saturated aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated to obtain specified in the title compound as a colourless oil (420 mg, quantitative yield).

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,68 (Ushs, 3H), 3,76 (t, 2H), 3,83 (dt, 2H), 7,15-7,39 (m, 5H).

119-3) N-Methoxycarbonyl-N-phenyl-aminoacetaldehyde

N-is ethoxycarbonyl-N-phenylamino-2-ethanol (420 mg) was dissolved in dimethyl sulfoxide (13 ml) was added triethylamine (5 ml), then was cooled to 0°C. was Gradually added sulfur trioxide (500 mg) under vigorous stirring at the same temperature, then stirred at room temperature overnight. Added water and the reaction solution was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium hydroxide and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound as a brown oil (191 mg, 46%).

1H-NMR (400 MHz, CDCl3); δ (ppm) and 3.72 (s, 3H), and 4.40 (s, 2H), 7.24 to 7,39 (m, 5H), to 9.70 (s, 1H).

119-4) N-Phenyl-2-(N"-phenyl-N"-methoxycarbonylamino)-atariwriter bromide

N-Methoxycarbonyl-N-phenylimidazole (500 mg) was dissolved in ethanol (20 ml)was added phenylhydrazine (280 mg) and the mixture was stirred overnight under nitrogen atmosphere. The reaction solution was evaporated and N-methoxycarbonyl-N-phenylimidazole of phenylhydrazone obtained as a residue was obtained is listed in the title compound (158 mg) as a reddish brown oil, in accordance with the method described in Tetrahedron, volume 52, pages 661-668, 1996.

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.75 (s, 3H), 4,79 (C, H), 6,85 (d, 2H), 7,22-7,38 (m, 8H), 7,68 (s, 1H).

119-5) (Z)-2'-(N-Phenyl-N-methoxycarbonylamino)-2-acetylpyridine phenylhydrazone

N-Phenyl-2-(N"-phenyl-N"-methoxycarbonylamino)-etanidazole (158 mg) was dissolved in xylene (10 ml) was added 2-renormalisability (241 mg), tetrakis (triphenylphosphine)palladium (25 mg) and copper iodide (5 mg), then stirred at 110°C for 4 hours in nitrogen atmosphere. After cooling to room temperature, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (37 mg, 23%) as brown crystals.

1H-NMR (400 MHz, CDCl3); δ (ppm) of 3.73 (s, 3H), 5,10 (s, 2H), 7,01-7,11 (m, 2H), 7,15-7,20 (m, 2H), 7,25-7,30 (m, 3H), 7,35-7,39 (m, 4H), 8,81 (d, 2H), 13,30 (s, 1H).

119-6) (E)-2'-(N-phenyl-N-methoxycarbonylamino)-2-acetylpyridine phenylhydrazone

(Z)-2'-(N-Phenyl-N-methoxycarbonylamino)-2-acetylpyridine phenylhydrazone (5 mg) was dissolved in 4 N. hydrochloric acid-ethyl acetate (0.5 ml) at 0°C. After stirring at room temperature for 2 minutes, the reaction solution was neutralized by adding saturated aqueous sodium bicarbonate solution. The reaction process which was extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous sodium sulfate. After the desiccant was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (5 mg) as brown crystals.

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,74 (s, 3H), 5,28 (s, 2H), 6,95 (t, 1H), 7,06-was 7.08 (m, 2H), 7,16-7,21 (m, 3H), 7,26-7,30 (m, 3H), 7,41-7,44 (m, 2H), 8,49 (d, 2H), 10,45 (s, 1H).

119-7) 2-Phenyl-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

(E)-2'-(N-Phenyl-N-methoxycarbonylamino)-2-acetylpyridine phenylhydrazone (5 mg) was dissolved in ethanol (3 ml) was added sodium ethylate (1.1 mg) at 0°C, then stirred at room temperature for 1 hour. After heating at 110°C for 1 minute and the mixture was cooled to room temperature. In the reaction solution was added saturated aqueous solution of ammonium chloride and water and was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After drying, the substance was filtered, the filtrate was evaporated. The residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (2 mg) as colorless crystals.

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,12 (s, 2H), 7,25-7,30 (m, 2H), 7,32 (m, 1H), 7,40-7,47 (m, 4), 7,51-EUR 7.57 (m, 4H), cent to 8.85 (d, 2H).

Specified in the title compounds of examples 120-126 synthesized in accordance with the above example 85.

Example 120

2-(2-Bromophenyl)-4-(4-biphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,20 (Ushs, 2H), 7,19 to 7.75 (m, 15H), 8,11 (d, 1H), 8,57-8,59 (m, 1H).

Example 121

2-(2-Bromophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,23 (Ushs, 2H), 7,22-7,35 (m,2H), 7,47 (TD, 1H), 7,55 (t, 1H), 7,60 (DD, 1H), 7,70 for 7.78 (m, 2H), to $ 7.91 (DD, 1H), 8,08-to 8.12 (m, 2H), scored 8.38 (t, 1H), at 8.60 (m, 1H).

ESI-Mass; 452[M++H].

Example 122

2-(2-Bromophenyl)-4-(4-forfinal)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,12 (Ushs, 2H), 7,06-7,11 (m, 2H), 7.24 to 7,29 (m, 1H), 7,30 (DDD, 1H), 7,41-7,49 (m, 3H), 7,60 (DD, 1H), 7.68 per to 7.75 (m, 2H), 8,10 (d, 1H), 8,56-8,58 (m, 1H).

Example 123

2-(2-Bromophenyl)-4-(3-formylphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,20 (Ushs, 2H), 7.18 in-7,34 (m, 2H), 7,46 (TD, 1H), EUR 7.57 (t, 1H), 7,63 (DD, 1H), 7,56-of 7.70 (m, 3H), 7,83 (DDD, 1H), 8,02 (t, 1H), 8,11 (dt, 1H), 8,58-8,59 (m, 1H), there is a 10.03 (s, 1H).

Example 124

2-(2-Bromophenyl)-4-(3-tolyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) is 2.37 (s, 3H), 5,13 (Ushs, 2H),? 7.04 baby mortality (t, 1H), 7.23 percent-7,33 (m, 5H), 7,44 (TD, 1H), 7.62mm (DD, 1H), 7.68 per-of 7.70 (m, 1H), 7,73 (DD, 1H), 8,10 (d, 1H), 8,56-8,58 (m, 1H).

Example 125

2-(2-Bromophenyl)-4-(4-dimethoxyphenyl)-6-(2-pyridyl)-4,5-dihydro,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) of 2.50 (s, 3H), 5,13 (Ushs, 2H), 7,26-to 7.32 (m, 3H), 7,42-7,47 (m, 2H), 7,53-EUR 7.57 (m, 1H), 7,63 (DD, 1H), 7,70-7,76 (m, 3H), 8,11 (d, 1H), 8,57 at 8.60 (m, 1H).

Example 126

2-(2-Bromophenyl)-4-(2-chloropyridin-5-yl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,18 (Ushs, 2H), 6,99-8,11 (m, 10H), 8,56 at 8.60 (m, 1H).

Example 127

2-(2-Cyanophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

In accordance with the above example 87 specified in the title compound was synthesized from 2-(2-bromophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it.

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,24 (Ushs, 2H), was 7.36 (DDD, 1H), 7,46 (TD, 1H), to 7.59 (t, 1H), 7,69-7,81 (m, 4H), of 7.90 (DDD, 1H), 8,12 (DDD, 1H), to 8.20 (dt, 1H), scored 8.38 (t, 1H), at 8.60 (DDD, 1H).

ESI-Mass; 399[M++H].

Example 128

2-(2-Cyanophenyl)-4-(3-AMINOPHENYL)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he

2-(2-Cyanophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he (15 mg) was dissolved in methanol (3 ml), was added 10% palladium powder coal (hydrate) (21 mg)and the mixture was stirred for 4 hours at room temperature in a hydrogen atmosphere. Powder of palladium on coal was filtered, and the filtrate was evaporated. The resulting residue was purified through column chromatography with silica gel (system of hexane-ethyl acetate) to obtain the specified title compound (13 mg) as colorless crystals.

1H-NMR (400 MHz, CDCl3); δ (ppm) 3,72 (Ushs, 2H), 5,13 (s, 2H), return of 6.58 (DDD, 1H), 6,82-6,85 (m, 2H), 7,19 (t, 1H), 7,32 (DDD, 1H), 7,40 (TD, 1H), to 7.67 (dt, 1H), 7,73 for 7.78 (m, 3H), to 8.20 (dt, 1H), 8,58 (DDD, 1H).

ESI-Mass; 369 [M++H].

Example 129

2-(2-Chlorophenyl)-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he.

Specified in the title compound was synthesized in accordance with the above example 119.

1H-NMR (400 MHz, CDCl3); δ (ppm) 5,18 (Ushs, 2H), 7,25 (TT, 1H), 7,28-7,44 (m, 5H), 7,47-7,51 (m, 3H), of 7.65 (DD, 1H), 8,84 (d, 2H).

ESI-Mass; 364 [M++H].

Below is the chemical structure of the compounds of the above examples. Each symbol in table 1-9 corresponds to the character of each group of the substituent in the structural formula shown in the header table 1-9. Each substituent directly linked via a simple link, having a free end for substitution, as shown in the structural formula in the table. "Me" in the table denotes a methyl group.

Table 1
Exampleandb
1
2
14
15
16
17
18
19
20
21
22
24

Table 1
Exampleandb
25
26
27
28
29
30
33
34
38
39
41
76

tr>
Table 2
Exampleandb
3
4
5
23
31
32
35
36
37
40
42
43
44

Table 2
Exampleandb
45
46/td>
47
51
52
55
56
59
60
61
63
64
65
66

Table 2
Exampleandb
67
68
69
70
71
72
73
74
75
79
80A
80V

Table 2
Exampleandb
81A
W
82
83
Table 3
Exampleandbdef
60HH
8 0HH
480FH
490HH
500HH

Table 4
Exampleandbdef
70HH
90HH
53 0FOH
540FH
570HH
680HH

Table 5
Exampleandbcx
10
12
62
Table 6
Exampleandbx
11

Table 7
Examplead
13O
Table 8
Exampleandbr
77Me
78Me
84Me

Table 9
Exampleandb
85
86
87
88
89
90
91
92
93
94
95
96

Table 9
ExampleAndbc
97
98
99
100
101
102
103
104
105
106
107
108
109
110

Table 9
Exampleabc
111
112
113
114
115
116
117
118
119
120
121
122
123

126
Table 9
Exampleab
124
125
127
128
129

Particularly preferred compounds in the above example, include 2-(2-bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-e]pyridazin-3-one, 2-(2-cyanophenyl)-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-e]pyridazin-3-one, 2-(2-itfinal)-4-(3-pyridyl)-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-cyanophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano-[4,3-pyridazin-3-one, 4-(4-methoxybenzyl)-6-phenyl-2-(2-tolyl)-3(2H)-pyridazinone, 2,6-diphenyl-4-(α-hydroxy-2-picolyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(4-morpholinylcarbonyl)-6-phenyl-3(2H)-pyridazinone, 2-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-2H-pyridazino[4,5-b]benzofuran-3-one, 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(4-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-itfinal)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-methoxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-phenyl-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4,6-diphenyl-2-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-methoxyphenyl)-2-(2-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-(2-bromophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-methoxyphenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-phenyl-2-(2-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-forfinal)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(4-hydroxyphenyl)-6-(2-pyridyl)-45-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-6-(2-hydroxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-dimethylaminoethoxy)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-6-(2-dimethylaminoethoxy)-4-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-[3-(2-picolylamine)]-6-(2-pyridyl)-3(2H)-pyridazinone, 2-phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-bromophenyl)-2-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-9-fluoro-4-phenyl-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-(2-cyanophenyl)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-bromophenyl)-4-(3-pyridyl)-2,3,4,4a-tetrahydro-5H-(I)benzopyrano[4,3-c]peridas the n-3-one, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-9-fluoro-5-hydroxy-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-(2-cyanophenyl)-9-fluoro-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-one, 2-phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-one, 2-(2-itfinal)-4-(3-pyridyl)-2,3-dihydro-5H-( (1)benzopyrano[4,3-c]pyridazin-3-one, 2-phenyl-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 4-(2-bromophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-chlorophenyl)-4-(4-morpholinosydnonimine)-6-phenyl-3(2H)-pyridazinone, 2-(2-nitrophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazine, 2-(3-tolyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(4-methanesulfonyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(4-biphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-naphthyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3,4-methylenedioxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3,4-dichlorophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-pyridyl)-4-(2-pyridyl)-6-(2-methoxyphenyl)-3(2H)-pyridazinone, 2-(3-formylphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,2-(thiophene-3-yl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3-pyridyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(3-pyridyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-methoxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone, 4-methyl-2,4,6-triphenyl-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone, 2-(3-pyridine-1-oxide)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyano-5-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyano-3-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone, 2-(2-cyano-5-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-cyano-3-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyrazinyl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-phenyl-6-(triazole-2-yl)-3(2H)-pyridazinone, 2-(2-cyanophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone, 2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he, 2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-dimethylaminoethoxy)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-6-(2-hydroxy who enyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-he 2-(2-bromophenyl)-4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2-cyanophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it, 2-phenyl-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2,4-acid)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-phenyl-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2-bromophenyl)-2,6-diphenyl-4,5-dihyd the on-1,2,4-triazine-3(2H)-he 2-(2-bromophenyl)-4-(2-bromophenyl)-6-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2-bromophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(2,5-acid)-6-(2-methoxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 4-(2,5-acid)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-phenyl-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(4-biphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(4-forfinal)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(3-formylphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(3-tolyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he, 2-(2-bromophenyl)-4-(4-dimethoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-bromophenyl)-4-(2-chloropyridin-5-yl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, 2-(2-cyanophenyl)-4-(3-AMINOPHENYL)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H) -, and 2-(2-chlorophenyl)-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-he.

Experimental example 1

Suppressively activity on the reuptake of calcium nerve cells induced AMPA

Suppressors activity of the compounds of the present invention to reverse the Wat calcium nerve cells, induced AMPA, was investigated using primary cultures of nerve cells of the cerebral cortex of embryos of rats.

The cultivation conditions:

The cerebral cortex was separated from the brain of rats on day 18 embryonic development and were treated with trypsin and Dnazol for dispersing cells. Cells were washed with MEM containing 10% serum, were sown in the flask cultivation and astrocytes proliferated. Astrocytes resuspendable trypsin and inoculated in 96-well plate. After a week of incubation was found that astrocytes cover the bottom and then there were sown nerve cells of the cerebral cortex, dispersed as described previously. After 24 hours incubation the medium was replaced and incubation was carried out for one week, after which the medium was changed to medium containing 1 μm MK-801. Used nerve cells, which are incubated for at least 8-10 days.

Method of study.

Reverse flow of calcium into the cells was measured using Fura2-AM, which is a calcium-sensitive fluorescent dye. Cells were treated for 1 h with medium containing Fura2-AM, which was absorbed by the cells, the medium was replaced by a Tyrode solution containing 1 μm MK-801 and stimulated with 2 μm AMPA. Changes the amount of reverse flow of calcium into the cells was measured as the change in intensity f is waitetoko exciting light at a wavelength of 340/380 nm. The effect of the compounds was evaluated, using as control the effects of Tyrode solution with added AMPA without a connection. The control connection is used GYKI52466 (Le Peillet, et al., Brain Res., 571, 115, 1992).

Results.

The compound (I) of the present invention significantly inhibited the reverse flow of calcium into the nerve cells, induced AMPA (table 10). IC50GYKI52466 was 9,02 microns.

1.2
Table 10
Number exampleIC50(μ M)Number exampleIC50(μ M)Number exampleIC50(μ M)
10.1420.1910.3
20.1430.1920.1
30.2440.2930.03
40.06450.2940.9
56.7460.3950.05
60.1470.2960.6
7 0.2480.1970.7
80.1490.07980.4
90.02500.1990.07
119.9510.81000.05
123.9520.21010.1
130.3530.51020.1
140.2540.11030.1
150.2550.81040.5
160.7560.21050.2
170.2570.21060.1
180.1580.41070.3
190.06590.61084.0
200.1600.21090.3
210.5 610.31100.1
222.7624.01110.4
230.1630.31120.3
240.06640.71137.1
250.2700.81157.2
260.3731.11180.03
270.04740.91194.3
280.1750.71210.4
290.1766.21225.2
300.2797.21230.3
310.980A7.11240.2
320.180V0.21250.6
330.07W0.71270.4
340.3821280.1
363.0830.61293.0
364.5850.2
370.1860.1
380.4870.05
390.05880.1
400.1895.0
410.03900.9

Experimental example 2

Anticonvulsant effect caused by AMPA

Analyzed the connection suspensively 0.5% solution of methylcellulose or sesame oil and oral was administered (25 mg/kg) to male mice of ddy strain. After 30 minutes or 1 hour after oral administration was continuously introduced AMPA in the form of injections (2 nmol/5 μl/min/mouse) into the lateral ventricle to cause seizures. The effect of the compounds was assessed by the duration of the action before convulsing with the constant introduction of AMPA.

Results.

The compound (I) of the present is briteney shows excellent anticonvulsant activity. For example, the compounds of examples 9, 29, 45, 59, 88, 97, 100, 102 and 103 significantly inhibited convulsions caused by AMPA.

Experimental example 3

Model occlusion of the middle cerebral artery

The usefulness of the compounds of the present invention in medicinal drug for the treatment of hemorrhagic stroke acute phase was confirmed by the study described below. That is, the blood flow in male rats Sprange Dawley blocked in the middle cerebral artery, placing seam nylon thread specifications 4-0, the edges of which burned through 17 mm from the bifurcation of the internal carotid artery to the internal carotid artery from the external carotid artery and had a cerebral infarction (Zea Longa et al., Stroke 20:84-91, 1989). The size of cerebral infarction was evaluated by obtaining cross-slice of the brain of a thickness of 2 mm and a dimension of the area, some of which were not stained by the dye TTC. The effect of the compounds on this model was evaluated by comparing the size of infarction between the groups treated with solvent, and groups treated with the investigational compound.

As a result, the compound (I) of the present invention showed excellent effect as a therapeutic agent in the treatment of hemorrhagic stroke in the acute stage.

Experimental example 4

Anti-meth effect

(S)-(+)-N,α-dimethylphenethylamine (here and onwards is marked as "methamphetamine") dosage was administered intraperitoneally to the rat or mouse, which dosage was administered an investigational compound and measured the number of active movements, using the device for measurement of active movements (SCANET SV-10; manufacture of TOYO Sangyo Co., Ltd.). Evaluated the potency of the compound as a therapeutic agent in schizophrenia, using as control giperdinamicheskim effective control of the movements caused by methamphetamine (K.E.Vanover, Psychopharmacology 136: 123-131, 1998). The effect of the compounds was evaluated using the control effect of the number of distinct movements compared with the group injected with a solvent.

As a result, the compound (I) of the present invention showed excellent anti-meth effect.

Experimental example 5

Model intermolecularly decerebration rigidity

Animal model, which was provoked by myotonia limbs, received electric partitioning between the upper gallicolumba and bottom gallicolumba rats. The effect of muscle relaxation was evaluated based on the effect of controlled muscle relaxation, which appears when the hindquarters of the animal in this model, moving forward and back. The effect of the compounds was assessed by changes in the extent of muscle relaxation before the introduction of the compounds and the degree of muscle relaxation after E. what about the injection.

The compound (I) of the present invention showed excellent effect of relaxation of the muscles.

Experimental example 6

Test light-darkness

The mouse was placed in a dark box, consisting of two boxes - light and dark, connected by a tunnel, and within 5 minutes after this was recorded the behavior of the mouse, using the following indicators:

1. The time spent in the light and dark box.

2. The time during which the mouse was running from a dark drawer in the light, and back.

3. The time during which ran the mouse to log in to the light box.

Anti-anxiety effect of the investigated compounds were defined as an increase in time spent in light box as increasing the time during which the mouse was running from a dark drawer in the light and back and as the increase of time during which ran the mouse to log in to the light box, relative to the group that was injected solvent (Hascoet m, Bourin M., Pharm. Biochem. Behav. 60: 645-653, 1998).

The compound (I) of the present invention showed excellent anti-anxiety effect.

Experimental example 7

6-OHDA-induced Hemi-Parkinsonian rats as a model of Parkinson's disease

10 mg/kg L-dihydroxyphenylalanine (L-DOPA) (twice a day) was administered vnutribryushinno doses every day of the rat, in which one half of the black substance destroyed by injection of 6-hydroxy who apamin (6-OHDA) into the medial nodes forebrain. Was due to the increase in contralateral rotation on the intact side (C.Marin et al, Synapse 36 (4):267-274, 2000). After the introduction of the rat solvent or the compounds studied the effect caused by the rotation.

The compound (I) according to the present invention as a sample delayed time to maximum rotational response after administration of L-DOPA and increased the time of occurrence of rotation by half or more from the value of maximum rotation.

Experimental example 8

Model curvature with the introduction of acetic acid

A painful condition in which the lower half of the body of the mouse is bent, her belly pressed and the hind limbs are stretched, was caused by the injection of 0.6% acetic acid in a saturated salt solution in the stomach mouse. After administration of the compounds and solvent acetic acid in a saturated salt solution was injected into the stomach and analgesic effect was evaluated in comparison with the time of abnormal actions during the observed time (5-15 minutes after injection of acetic acid)that occur after the introduction (Basic Pharmacology Experiment, edited by Kazuhiko Kubota, pages 45-47, Nankoh-do).

As a result, it should be noted that the compound (I) according to the present invention substantially controls the time of abnormal actions and has an excellent analgesic effect.

<> Experimental example 9

Model of vomiting induced by cisplatin

An intravenous catheter was introduced to the ferret and the animal was given time to postoperative recovery. Then injection of 10 mg/kg CIS-diaminedichloroplatinum (cisplatin) (A.Fink-Jensen et al., Neuroscience Letters 137:173-177, 1992) caused a gag reaction. Cisplatin (10 mg/kg) was administered to ferrets, which has been treated with an investigational compound or solvent, then the ferret was placed in a cage for observation and measured the rhythmic contractions of the stomach (called vomiting) and time until vomiting during the observation period of 240 minutes.

As a result, the compound (I) of the present invention significantly increased the latency time and reduced time status of vomiting.

Experimental example 10

Experimental model of autoimmune encephalomyelitis

Female Lewis rats (205 ± 10 g)obtained from Charles River, Kent, UK, was placed in pairs in conditions of controlled environment (6:00-18:00 cycle light-dark; 22-24°C; humidity 45-55%) and were given free access to food and drink. The experimental group consisted of 9-12 animals. Rats were immunized 20-50 µl inoculation containing 50 μg myelin basic protein Guinea pigs (MBP; final concentration 2 mg/ml)emulsified in complete Freund's adjuvant (CFA; Sigma, UK)containing Mycobacterium tuberculosis H37Ra (the end to which the concentrations of 5.5 mg/ml; Difco Laboratories, UK). Animals were weighed and watched them on a daily basis and clinical manifestations of the disease were recorded as (0) no clinical signs; (1) soft tail and weight loss; (2) hypotension hind limbs along with additional weight reduction; (3) a complete hind limb paralysis; (4) paraplegia and (5) death. In addition, animals were evaluated using intermediate points, which showed a decrease in tone of the distal tail (0.5 points), paralysis of one hind limb (2.5 points) or complete paralysis of hind limbs and their weakness (3.5 points). In the period of introduction of the compound (10-16 days after immunization; dpi) animals were evaluated after 15 hours after the injection of the carrier or connection, to avoid the influence of any effect of the acute phase treatment at the points of evaluation of the disease. Compounds were dissolved/suspended in 0.5% methylcellulose using a hand-held homogenizer transmitter station (PT1200; 2 minutes). Rats orally, injected or methylcellulose media (2.5 ml/kg), or compound in an amount of 5, 10 and 20 mg/kg

Results.

The connection according to this invention is the best tool in terms of experimental autoimmune encephalomyelitis. The compound (I) of the present invention shows an excellent effect compared with the group that was administered the media.

1. Derivatives of pyridazinone Il is triazinone, represented by the following formula, their salts or their hydrates:

where a1And2and3each, independently of one another, represent a phenyl group which may be optionally substituted by one or more groups selected from the group comprising (1) a hydroxy-group, (2) halogen atom, (3) nitrile group, (4) a nitro-group, (5)1-6alkyl group which may be substituted by at least one hydroxy-group, (6) With1-6alkoxygroup, which may be substituted by at least one group selected from the group comprising di(C1-6alkyl)alkylamino, the hydroxy-group and pyridyloxy group, (7)1-6allylthiourea, (8) amino, (9)1-6alkylsulfonyl group, (10) formyl group, (11) phenyl group, (12) triftormetilfullerenov; pyridyloxy group which may be substituted by a nitrile group or a halogen atom, or may be N-oxidized; pyramidalnou group; personilnya group; thienyl group; thiazolidine group; naftalina group; benzodioxolyl group;

Q represents O;

Z represents C or N;

X1X2and X3each, independently of one another, represent a simple bond or a C1-6alkylenes group, obazatelno substituted hydroxyl group;

R1represents a hydrogen atom or a C1-6alkyl group;

R2represents a hydrogen atom;

or R1and R2can be connected to each other so that CR2-ZR1forms a double carbon-carbon bond, represented as C=C (provided that, when Z represents N, R1is a lone pair);

R3represents a hydrogen atom or may be bonded to any atom in the a1or And3with the formation of a 5-6-membered heterocyclic ring containing an oxygen atom, which is optionally substituted hydroxyl group

(provided that (1) when Z represents N; each of X1X2and X3represents a simple bond; each And1And2and3represents a phenyl group, (2) when Z represents N; each of X1X2and X3represents a simple bond; And1represents o,p-dimethylphenyl group; And2is an on-methylphenylene group; And3represents a phenyl group, or (3) when Z represents N; each of X1X2and X3represents a simple bond; And1is an on-methylphenylene group; And2represents the p-label is iverilog group; And3represents a phenyl group, at least one of R2and R3is a group other than hydrogen atom), provided that the above definitions are not allowed connection in the following cases: (1), (3)-(8), (10)-(16) and (19)

(1) the case when part of the structure ZR1-CR2represents the C=S; R3represents a hydrogen atom; X1represents-CH2CH2-; A1represents the p-chloraniline group; And2represents the p-bromperidol group; And3represents a phenyl group, p-taillow group or p-metoksifenilny group, (3) the case when part of the structure ZR1-CR2represents the C=S; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each And1And2and3represents a phenyl group, (4) the case when part of the structure ZR1-CR2represents the C=S; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each And1and2represents a phenyl group; And3represents the p-taillow group or p-metoksifenilny group, (5) the case when part of the structure ZR1-CR2represents the C=S; R3 represents a hydrogen atom; each of X1X2and X3represents a simple bond; each And2and3represents a phenyl group; and1represents the p-metoksifenilny group, (6) the case when part of the structure ZR1-CR2represents the C=S; R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And1represents a 2,4,6-trimethylphenyl group; And2represents a phenyl group; and3represents a 3,4-dichloraniline group, (7) the case when Z represents S, each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; and each And1And2and3represents a phenyl group, (8) the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each And1and2represents a phenyl group; and3represents the p-taillow group, p-chloraniline group, p-metoksifenilny group, 3-methoxy-4-itfinally group, 3-chloro-4-metoksifenilny group, 3-bromo-4-metoksifenilny group or 4-meta the-3-itfinally group, (10) the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And1represents a 2,4-dimethylphenyl group; And2represents a phenyl group; And3represents a phenyl group, p-taillow group, 3,4-dichloraniline group, 2,4-dimethylphenyl group or 4-methyl-3-bromperidol group, (11) for the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And1represents a 2,4,6-trimethylphenyl group; And2represents a phenyl group; And3represents a phenyl group or a 3,4-dichloraniline group, (12) the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And1represents a 2,4,6-trimethylphenyl group; And3represents a 3,4-dinitrophenyl group; And2is a 4-nitrophenyl group or 2,4-dinitrophenyl group, (13) the case where Z represents S; each of R1, R2and R3represents a hydrogen atom; each is of X 1X2and X3represents a simple bond; And1is a 2.5 dimethylphenyl group; And2represents a phenyl group; and3represents the p-diphenylene group, 3,4-dichloraniline group or 3-methyl-4-chloraniline group, (14) the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And2represents a phenyl group; And3represents the p-bromperidol group; And1represents the p-taillow group, p-ethylphenyl group or p-isopropylphenyl group, (15) the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And2represents a phenyl group; each of And1and3represents the p-metoksifenilny group or 3,4-dimethylphenyl group, (16) for the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; And1represents the p-taillow group; And2represents a phenyl group; and3the submitted is a p-chloraniline group, (19) the case when Z represents S; each of R1, R2and R3represents a hydrogen atom; each of X1X2and X3represents a simple bond; each And1and3represents a 2,4-dimethylphenyl group; And2represents a 2,4-dinitrophenyl group.

2. Compounds according to claim 1, and their salts or their hydrates, where a1And2and3each, independently of one another represent a group represented by the formula:

3. Compounds according to claim 1, and their salts or their hydrates, where the group of substituents, And when1And2and/or And3represent substituted phenyl, independent from each other, and each represents a hydroxyl group, halogen atom, nitrile group, or a nitro-group.

4. Compounds according to claim 1, and their salts or their hydrates, where X1X2and X3independent from each other and each represents a simple bond, -CH2-, -CH(OH)- or-CH2CH2-.

5. Compounds according to claim 1, and their salts or their hydrates, where X1X2and X3each represents a simple bond.

6. Compounds according to claim 1, and their salts or their hydrates, where R1represents a C1-6alkyl group.

7. Compounds according to claim 1, and their salts or their hydrates, where R1, R2and/or R3, each is th, represent a hydrogen atom.

8. Compounds according to claim 1, and their salts or their hydrates, where R1and R2connected to each other so that part of the structure ZR1-CR2forms a double carbon-carbon bond represented by the formula C=C.

9. Compounds according to claim 1, and their salts or their hydrates, where R3associated with an atom in A1.

10. Compounds according to claim 1, and their salts or their hydrates, where R3associated with an atom in A3.

11. Compounds according to claim 9 or 10, their salts or their hydrates, where X3is a simple link.

12. Compounds according to claim 1, and their salts or their hydrates, where the provisions of the accession of substitution groups And1And2and/or And3are α-the provisions of the carbon atoms in the a1And2and/or And3, each of which is associated with X1X2and X3respectively.

13. Compounds according to claim 1, and their salts or their hydrates, represented by the following formula:

where values And1aAnd2aand3ahave the same meaning As1And2and3in claim 1; X1X2and X3are the same values that are defined in the above claim 1, respectively; the part of the structure:

represents a single or double bond, provided that the above definitions are not the DOP who repent connection in the following, (1) and (2), cases:

(1) the case when part of the structure:

is a double carbon-carbon bond; R3represents a hydrogen atom; and the following, with (1a), (1c)-(1f), cases:

(1A) the case when X1represents-CH2CH2-; And1arepresents the p-chloraniline group; And2arepresents the p-bromperidol group; and3arepresents a phenyl group, p-taillow group or p-metoksifenilny group,

(1C) case where each of X1X2and X3represents a simple bond and each And1aAnd2aand3arepresents a phenyl group,

(1d) case, when each of X1X2and X3represents a simple bond; each And1aand2arepresents a phenyl group and a3arepresents the p-taillow group or p-metoksifenilny group,

(1E) case where each of X1X2and X3represents a simple bond; each And2aand3arepresents a phenyl group; And1arepresents the p-metoksifenilny group, and

(1f) the case when each of X1X2and X3represents a simple bond; And1arepresents the t of a 2,4,6-trimethylphenyl group; And2arepresents a phenyl group; And3arepresents a 3,4-dichloraniline group, and

(2) the case when part of the structure:

represents a simple bond; each of X1X2and X3represents a simple bond; and the following, with (2A), (2b), (2d)-(2j) and (2m), cases:

(2A) the case that each And1aAnd2aand3arepresents a phenyl group, (2b) the case that each And1aand2arepresents a phenyl group; and3arepresents the p-taillow group, p-chloraniline group, p-metoksifenilny group, 3-methoxy-4-itfinally group, 3-chloro-4-metoksifenilny group, 3-bromo-4-metoksifenilny group or 4-methyl-3-itfinally group,

(2d) case, when And1arepresents a 2,4-dimethylphenyl group; And2arepresents a phenyl group; and3arepresents a phenyl group, p-taillow group, 3,4-dichloraniline group, 2,4-dimethylphenyl group or 4-methyl-3-bromperidol group,

(2) the case when A1arepresents a 2,4,6-trimethylphenyl group; And2arepresents a phenyl group; and3Arepresents a phenyl group or a 3,4-dichloraniline group,

(2f) the case when A 1arepresents a 2,4,6-trimethylphenyl group; And3arepresents a 3,4-dichloraniline group; and2ais a 4-nitrophenyl group or 2,4-dinitrophenyl group,

(2g) the case when A1ais a 2.5 dimethylphenyl group; And2arepresents a phenyl group; and3arepresents the p-diphenylene group, 3,4-dichloraniline group or 3-methyl-4-chloraniline group,

(2h) the case when A2arepresents a phenyl group; And3arepresents the p-bromperidol group; and1arepresents the p-taillow group, p-ethylphenyl group or p-isopropylphenyl group,

(2i) a case when A2arepresents a phenyl group; and1aand3aindependent, and each represents a p-metoksifenilny group or 3,4-dimethylphenyl group,

(2j) the case when A1arepresents the p-taillow group; And2arepresents a phenyl group; And3arepresents the p-chloraniline group, and

(2m) be the case that each And1aand3arepresent 2,4-dimethylphenyl group; And2arepresents a 2,4-dinitrophenyl group.

14. Connection 13, their salts or their hydrates, where each of X1X2and X3presented yet a simple link.

15. Compounds according to claim 1, and their salts or their hydrates, which is represented by the formula:

where And1aAnd2aand part of the structure

are the same values that are defined in the above item 13, respectively; X1X2and X3are the same values that are defined in the above claim 1, respectively; the ring And3bcorresponds to A3in claim 1; and ring b is a 5-6-membered non-aromatic heterocyclic ring which contains an oxygen atom and may be substituted by a hydroxyl group.

16. Compounds according to claim 1, and their salts or their hydrates, which are represented by the formula:

where a2aAnd3aand part of the structure

are the same values that are defined in item 13, respectively; X1X2and X3are the same values that are defined in claim 1, respectively; the ring And1bcorresponds to A1in claim 1; the ring is a 5-6-membered non-aromatic heterocyclic ring which contains an oxygen atom and may be substituted by a hydroxyl group.

17. Connections § 15, their salts or their hydrates, which are represented by the formula:

where a1aAnd2aAnd3band part of the structure

are the same values that are defined in the above item 15; and D represents-O-.

18. Connection P16, their salts or their hydrates, which are represented by the formula:

where a1bAnd2aAnd3aand part of the structure

are the same values that are defined in claim 1, respectively; E represents-O-.

19. Compounds according to claim 1, and their salts or their hydrates, which are represented by the formula:

where a1And2And3and part of the structure

are the same values that are defined in claim 1, respectively.

20. Compounds according to claim 1, and their salts or their hydrates, which are represented by the formula:

where a1And3and part of the structure

are the same values that are defined in claim 1, respectively; the ring And2brepresents a phenyl group; and R15represents a hydroxyl group, halogen atom, nitrile group, a C1-6alkyl group, a C1-6alkoxy group, nitro group, Eminoglu the PU or formyl group.

21. Compounds according to claim 1, and their salts or their hydrates, which are represented by the formula:

where a1And2And3X1X2and X3are the same values that are defined in claim 1, respectively, provided that excluded the following compounds (2)-(4) cases:

(2) the case where each of X1X2and X3represents a simple bond; and each And1And2and3represents a phenyl group,

(3) the case where each of X1X2and X3represents a simple bond; And1represents o,p-dimethylphenyl group; And2is an on-methylphenylene group; and3represents a phenyl group,

(4) the case where each of X1X2and X3represents a simple bond; And1is an on-methylphenylene group; And2represents the p-metoksifenilny group; and3represents a phenyl group.

22. Compounds according to claim 1, and their salts or their hydrates, which are represented by the formula;

where a1And2and3are the same values that are defined in claim 1, respectively, provided that excluded the compounds in the following cases from (1) to (3):

(1) with the learn where each And1And2and3represents a phenyl group,

(2) the case where a1represents o,p-dimethylphenyl group; And2is an on-methylphenylene group; and3represents a phenyl group, and

(3) the case where a1is an on-methylphenylene group; And2represents the p-metoksifenilny group; and3represents a phenyl group.

23. Connection p.22, their salts or their hydrates, where a1And2and3independent, and each represents a group represented by the formula:

24. Connection p.22, their salts or their hydrates, where the phenyl group may be substituted by at least one group selected independently from the group consisting of a halogen atom, ceanography, hydroxyl group, amino group, formyl group and nitro group.

25. Connection p.22, their salts or their hydrates, where the provisions of joining groups of substituents in the A1And2and3are α-the provisions of the carbon atoms in the a1And2and3, each of which is associated directly with the ring of triazinone.

26. Compounds according to claim 1, and their salts or their hydrates, which are represented by the following formula:

where And1And2And3And1bAnd3bX1X2X3, D, E, and R2have the same values as those defined above, respectively.

27. Compounds according to claim 1, and their salts or their hydrates, which are any of the compounds chosen from:

2-(2-bromophenyl)-4-(3-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(3-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-[3-(2-hydroxyethoxy)phenyl]-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-phenyl-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-cyanophenyl)-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-itfeel)-4-(3-pyridyl)-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-cyanophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

4-(4-methoxybenzyl)-6-phenyl-2-(2-tolyl)-3(2H)-pyridazinone,

2,6-diphenyl-4-(a-hydroxy-2-picolyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-2H-pyridazino[4,5-b]benzofuran-3-it,

2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(4-methoxyphenyl)-6-(2-PI is ideal)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-itfeel)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-(2-methoxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-phenyl-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4,6-diphenyl-2-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-(2-methoxyphenyl)-2-(2-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone

4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-(2-bromophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-methoxyphenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-phenyl-2-(2-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-forfinal)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(4-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-6-(2-hydroxyphenyl)-4-(2-pyridyl)-3(2H)-pyridazinone,

4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(3-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(2-dimethylaminoethoxy)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-6-(2-dimethylaminoethoxy)-4-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-[3-(2-picolylamine)]-6-(2-pyridyl)-3(2H)-pyridazinone,

2-phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(3-bromo-6-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

4-(2-bromophenyl)-2-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-9-fluoro-4-phenyl-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-cyanophenyl)-4-(3-pyridyl)-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-bromophenyl)-4-(3-pyridyl)-2,3,4,4A-tetrahydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(4-methoxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-9-fluoro-5-hydroxy-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-c]pyridazin-3-it,

2-(2-cyanophenyl)-9-fluoro-4-phenyl-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-phenyl-6-(2-pyridyl)-4-(2-triftormetilfullerenov)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-(2-itfeel)-4-(3-pyridyl)-2,3-dihydro-5H-(1)benzopyrano[4,3-C]pyridazin-3-it,

2-phenyl-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

4-(2-bromophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-nitrophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(3-tolyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(4-methanesulfonyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(4-biphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-naphthyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(3,4-methylenedioxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(3,4-dichlorophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-phenyl-6-(2-pyrimidinyl)-3(H)-pyridazinone,

2-(2-pyridyl)-4-(2-pyridyl)-6-(2-methoxyphenyl)-3(2H)-pyridazinone,

2-(3-formylphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(thiophene-3-yl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(3-pyridyl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(3-pyridyl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone,

2-(2-methoxyphenyl)-4-(3-pyridyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-methyl-2,4,6-triphenyl-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone,

2-(3-pyridine-1-oxide)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyano-5-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyano-3-yl)-4-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyano-5-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone,

2-(2-cyano-3-yl)-4-phenyl-6-(2-pyrimidinyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-phenyl-6-(2-pyrazinyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-phenyl-6-(thiazol-2-yl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-methyl-4,6-diphenyl-4,5-dihydro-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(bromophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-dimethylaminoethoxy)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-6-(2-hydroxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2,5-dihydroxyphenyl)-6-(2-hydroxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-6-(2-methoxyphenyl)-4-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2-cyanophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-6-(2-methoxyphenyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-4-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-phenyl-6-(2-pyridyl)-4-thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-pyridyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2,4-acid)-2-phenyl-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-methoxyphenyl)-4-(thiophene-3-yl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-phenyl-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-pyridyl)-4-(3-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2-bromophenyl)-2,6-diphenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(2-bromophenyl)-6-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2-bromophenyl)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(2,5-acid)-6-(2-methoxyphenyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

4-(2,5-acid)-6-(2-methoxyphenyl)-2-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-6-(2-pyridyl)-4-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-phenyl-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(4-biphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(4-forfinal)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-what Ravenel)-4-(3-formylphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(3-tolyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(4-dimethoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-bromophenyl)-4-(2-chloropyridin-5-yl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-4-(3-nitrophenyl)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-cyanophenyl)-4-(3-AMINOPHENYL)-6-(2-pyridyl)-4,5-dihydro-1,2,4-triazine-3(2H)-she

2-(2-chlorophenyl)-4-phenyl-6-(2-pyrimidinyl)-4,5-dihydro-1,2,4-triazine-3(2H)-it.

28. Compounds according to item 27, their salts or their hydrates, which are any of the compounds chosen from:

2-(2-bromophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-(2-cyanophenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-bromophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

4-(2-hydroxyphenyl)-2-phenyl-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-methoxyphenyl)-6-(2-pyridyl)-4,5-dihydro-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-hydroxyphenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-(2-cyanophenyl)-4-(2-cyanophenyl)-6-(2-pyridyl)-3(2H)-pyridazinone,

2-phenyl-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone and

2-(2-bromophenyl)-4-(3-pyridyl)-6-(2-pyridyl)-3(2H)-pyridazinone.

29. Pharmaceutical companies who stand, which is the inhibitor of receptor α-amino-3-hydroxy-5-methyl-4-isoxazolidinone acid (hereinafter referred to as "AMR"), containing the compound of formula (I) according to claim 1, its salt or hydrates as an active ingredient.

30. The pharmaceutical composition according to clause 29 for the treatment or prevention of disease, such as epilepsy, or demyelinating diseases such as multiple sclerosis, involving AMPA receptor.

31. Method for the treatment or prevention of disease, such as epilepsy, or demyelinating diseases such as multiple sclerosis, involving AMPA receptor by the introduction of patient a pharmacologically effective dose of a compound according to claim 1 represented by the above formula (I), its salts or their hydrates.

32. The use of compounds represented by formula (I) according to claim 1, their salts or their hydrates to obtain funds for the treatment or prevention of disease, such as epilepsy, or demyelinating diseases such as multiple sclerosis, involving AMPA receptor.

Priority points and features:

18.09.2000 - claims 1 to 20, 29-32 for all these values of the radicals A1, A2, A3, Q, X1X2X3, R1, R2, R3and Z =C; p, 28 for derivatives of pyridazinone with variations in the definitions of the radicals A1, A2, A3, Q, X1X2X3, R1, R2, R3;

22.09.2000 - claims 1 to 12, 21-26, 29-32 for all these values radicals And1And2And3, Q, X1X2X3, R1, R2, R3and Z=N, p, 28 for derivatives of triazinone with variations in the definitions of radicals And1And2And3, Q, X1X2X3, R1, R2, R3;

09.11.2000 - PP, 28 for derivatives of pyridazinone with variations in the definitions of radicals And1And2And3, Q, X1X2X3, R1, R2, R3;

05.02.2001 - PP, 28 for derivatives of pyridazinone with variations in the definitions of the radicals A1, A2, A3, Q, X1X2X3, R1, R2, R3;

05.02.2001 - PP, 28 for derivatives of triazinone with variations in the definitions of radicals And1And2And3, Q, X1X2X3, R1, R2, R3.



 

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FIELD: organic chemistry, medicine, ophthalmology, pharmacy.

SUBSTANCE: invention relates to new pyranoindazoles of the formula (1): wherein R1 and R2 are chosen independently from hydrogen atom or alkyl group; R3 and R4 represent independently hydrogen atom or alkyl group; R5, R6 and R7 mean hydrogen atom; R8 and R9 mean hydrogen atom, hydroxyl, alkoxy-group, -NR10R11, -OC(=O)NR1R2, -OC(=O)-(C1-C4)-alkyl or alkylthiol; R10 and R11 mean hydrogen atom; A means -(CH2)n, C=O; B means a simple or double bond; n = 0-2; Y means nitrogen atom (N); X means carbon atom C; dotted line means the corresponding simple or double bond. Also, invention relates to a pharmaceutical composition based on compounds of the formula (1), to a method for regulating normal or enhanced intraocular pressure, method for treatment of glaucoma and method for blocking or binding serotonine receptors. Invention provides preparing new pyranoindazoles possessing the valuable pharmaceutical effect.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 4 tbl, 22 ex

FIELD: organic chemistry, pharmacy, biochemistry.

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EFFECT: valuable medicinal properties of compounds.

8 cl, 2 tbl, 6 ex

FIELD: organic chemistry, biochemistry, medicine.

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EFFECT: valuable medicinal and biochemical properties of compounds.

3 cl, 2 tbl, 9 ex

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EFFECT: improved and valuable properties of compounds.

6 cl, 5 tbl, 19 ex

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< / BR>
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EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and composition.

14 cl, 11 sch, 7 tbl, 13 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:

wherein Ag represents (1) group of the formula:

; (2) group represented by the formula:

or ; (3) group represented by the formula:

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EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.

40 cl, 51 tbl, 741 ex

FIELD: organic chemistry, peptides, medicine, pharmacy.

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EFFECT: improved preparing method, valuable medicinal properties of compounds.

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

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EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

The invention relates to derivatives of 6-sulfamoylbenzoic-4-carboxylic acid of formula (1), where R1, R2, R3and R4such as defined in the claims

3-piperidine, methods for their preparation and pharmaceutical composition based on them" target="_blank">

The invention relates to tricyclic3-piperidinol General formula (1), where X is O or S, R1means hydrogen, halogen, C1-6alkyl or C1-4alkyloxy, Alk means C1-6alcander, a D such as defined in the claims

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FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula: or wherein x means 1, 2, 3 or 4; m means 1 or 2; n means 1 or 2; Q represents carbon atom (C) or nitrogen atom (N); A represents oxygen atom (O) or sulfur atom (S); R1 represents lower alkyl; X represents -CH; R2 represents hydrogen (H) or halogen atom; R2a, R2b and R2c can be similar or different and they are chosen from hydrogen atom (H), alkyl, alkoxy-group or halogen atom; R3 represents aryloxycarbonyl or alkoxyaryloxycarbonyl; Y represents -CO2R4 wherein R4 represents hydrogen atom (H) or alkyl, and including all their stereoisomers, their prodrugs as esters and their pharmaceutically acceptable salts. These compounds are useful antidiabetic and hypolipidemic agents and agents used against obesity also.

EFFECT: valuable medicinal properties of compounds.

29 cl, 12 tbl, 587 ex

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