MXPA00002417A - Phthalazine derivatives and remedies for erectile dysfunction - Google Patents

Abstract

Novel compounds which are compounds represented by general formula (I) or salts thereof having a steroid C17-20 lyase inhibitory activity and being useful as preventives or remedies for tumors such as prostatism and mammary cancer. In said formula, A1 represents a five- or six-membered ring optionally having substituent(s) excluding cyclic ones;A2 represents an optionally substituted aromatic ring;X represents a divalent group;Y represents nitrogen or methine;Z represents optionally substituted ethenylene or ethynylene;and R represents an optionally substituted heterocyclic group, provided that 3,4-dihydro-6-[3-(1H-imidazol-1-yl) -1-propenyl]-2(1H)-quinolone and 2-[3-[5-ethyl-6-methyl-2-(benzyloxy) -3-pyridyl]-1-propenyl-benzoxazole]are excluded therefrom.

Description

Ftalazine Compounds and Therapeutic Agents for Erectile Dysfunction Field of the Invention The present invention relates to phthalazine compounds. More specifically, it is related to prophylactic and therapeutic agents for male erectile dysfunction and to prophylactic and therapeutic agents for female sexual dysfunction or dysmenorrhea.

Previous Technique It is said that the number of latent patients with erectile dysfunction amounts to approximately 3,000,000 in Japan. In the US, it has been reported that the number of patients with erectile dysfunction reaches 20,000,000 and 15% of men of fifty years and approximately 1/3 of those of sixty suffer from this disease. In this society that ages more and more, sexual relations are considered as pleasant and emotional behavior. With the existing needs in terms of a better quality of life, it is anticipated that erectile dysfunction will not only constitute a medical problem, but also a social problem in the future. This disease is classified within the organic impotence, caused by disorders in the nerves, in the blood vessels or in the muscles of the penis per se or in the sexual hormones, and of the functional (psychic) impotence, caused by mental or psychological problems . There are three factors necessary for erection, that is, an increase in the arterial blood flow of the penis, the regulation of the exit of the blood from the veins of the penis and the relaxation of the cavernous tissue. Erectile dysfunction arises when at least one of these conditions is inhibited. The urological treatments for erectile dysfunction performed today involve drug therapy and surgical penile prosthesis using prosthetic devices for the penis. As drug therapy, it is possible to inject papaverine hydrochloride or prostaglandin El into the cavernous tissue of the penis. However, this treatment is hardly performed today, since it is not allowed in Japan for a patient to self-treat an injection and it is impossible in practice to see a doctor every time he performs intercourse. In addition, the injection of papaverine hydrochloride pro-duciria, although exceptionally, a painful symptom called priapism. Thus, treatments with existing drugs are not usable in practice. Consequently, there has been an urgent desire to develop drug therapy for this purpose that is clinically effective in practice. In 1984, Bowman and Drummond described that a selective cyclic phosphodiesterase GMP inhibitor, M & B22948 (zaprinast), increased cyclic GMP in the tissue and relaxed the penile retractor muscle in bovine (cyclic GMP mediates muscle neurogenic relaxation penile retractor, Br. J. Pharmacol., 81, 665-674 (1984) Subsequently, other researchers have described one after another the relaxation of the corpora cavernosa of the penis increasing the cyclic GMP in the tissue (Int. J. Impotence Res., 85-93, 1992, J. Urol., 147, 1650-1655, 1992, and N. Engl. J. Med., 326, 90-94, 1992.) However, none of the compounds used in these studies can be successfully used in the clinic due to poor efficacy, etc. An inhibitor of type V phosphodiesterase is also effective against female sexual dysfunction.Fthalazine compounds are described that have an inhibitory action on phosphodiesterase type V in WO9605176 (JP-A 8-2255 41), but neither spiro compounds containing nitrogen atoms or 6-membered heterocyclic and bicyclic compounds are described, nor is the prevention and therapy for erectile dysfunction described. Description of the Invention The present inventors have conducted various studies and have thus seen that the phthalazine compounds represented by the formula (I) show a high selectivity for type V iophosphodiesterase, which is an enzyme which degrades cyclic GMP, and a potent inhibitory effect on it, and exhibits a strong relaxation action on the corpora cavernosa of the penis, with an increase in bioavailability, and which possess a high security, thus completing the present invention. The present invention relates to phthalazine compounds not specifically described in JA-A 8-225541, with phthalazine compounds not suggested there and, further, with a process for producing some of the compounds. It relates to a phthalazine compound represented by formula (I), a pharmacologically acceptable salt thereof or a hydrate thereof: where R1 and R2 are the same or different from each other and represent a halogen atom, a Cl to C4 alkyl group which may be substituted with a halogen atom, a hydroxyl group, a Cl to C4 alkoxy group which may be substituted with an atom of halogen, or a cyano group; X represents a cyano group, a nitro group, a halogen atom, a thiocarbamoyl group, a hydroxyimino group which may be substituted with a Cl to C4 alkyl group, an arylalkyl group (Cl to C4) or a carboxyalkyl group (Cl to C4) ), or a heteroaryl group which may be substituted with 1 to 3 substituent groups selected from the following substituent groups A; Y represents: i) a group represented by the formula (II): where ring A represents a 4 to 8 membered amine ring, which may be substituted with a methyl group and may have a double bond; D represents a single bond or an oxygen atom; R3 represents a hydrogen atom, a Cl to C4 alkyl group or a halogen atom; m represents an integer from 0 to 3; represents an amino group, a hydroxyl group, a cyano group, a carboxyl group which may be protected, or a Cl to C4 alkoxy group; ii) a group represented by the formula (III): wherein ring B represents a 4- to 8-membered amine ring which may have a double bond and n and p are the same or different from each other and represent an integer from 0 to 3; iii) a group represented by the formula (IV): where the ring G represents a 4 to 8 membered amine ring which may have a double bond, E represents a hydroxyl group, a halogen atom, a Cl to C4 alkyl group or a Cl to C4 alkoxy group; J is the formula - (CHR4) qQ (where R4 represents a hydrogen atom or a Cl to C4 alkyl group, Q represents a hydroxyl group, a halogen atom, a carboxyl group which may have a protective group, a carbamoyl group or an azolyl group that does not contain a heteroatom other than a nitrogen atom, q is an integer of 0 or 4), or E and J can form a 3 to 6-membered ring together with the carbon atom to which they are attached joined, the ring optionally having a heteroatom and optionally having a substituent group; iv) a group represented by the formula (V): where M represents a bond or a Cl to C4 alkylene group which may be substituted with a hydroxyl group, a carboxyl group, a Cl to C4 alkyl group or a Cl to C4 alkoxy group; the ring K represents a 5- to 8-membered amine ring formed together with M, and the ring L represents a 5- to 8-membered alkyl ring which "may have a substituent group and may have an oxygen atom; a group represented by the formula (VI): wherein the ring P represents a 5-7 membered amine ring and R5 represents a hydrogen atom or a Cl to C4 alkyl group which may be substituted with a halogen atom, a hydroxyl group or a carboxyl group; vi) an alkynyl group, an alkenyl group or an alkyl group, all of which may have a substitutent group; vii) a phenyl group which may be substituted with 1 to 3 substituent groups selected from the following substituent groups A; or viii) a pyridyl group, a pyrimidyl group, a thienyl group, a thiazolyl group or a furyl group, all of which may be substituted with 1 to 3 substituent groups selected from the following substituent groups A; (substituent group A) a Cl to C4 alkyl group which may be substituted with a halogen atom, a cyano group, a nitro group or a hydroxyl group; a Cl to C4 alkoxy group which may be substituted with a halogen atom, a cyano group, a nitro group or a carboxyl group which may have a protecting group; a hydroxyl group which may have a protecting group; a carbamoyl group which may be substituted with a lower alkyl group; a halogen atom, and an amino group which may be substituted with an acyl group Cl to C4, an alkylsulfonyl group Cl to C4 or an arylsulfonyl group which may have a substituent group; 1 is an integer from 1 to 3; with the proviso that the following cases are excluded: the case where 1 is 1 or 2, X is a cyano group, a nitro group or a chlorine atom, R1 is a chlorine atom, R2 is a methoxy group , ring A is a 5- or 6-membered amine ring, D is a single bond, m is 0 and W is a carboxyl group which may have a protecting group or a C1 to C4 alkoxy group; the case where 1 is 1, R1 is a chlorine atom, R2 is a methoxy group, ring A is a saturated amine ring of 5 or 6 members, D is a single bond and W is a hydroxyl group; the case where 1 is 1, ring B is an amine ring of 5 or 6 members and both n and p are 0; the case where 1 is 1, E and Q are hydroxyl groups and q is 0, and the case where 1 is 1, X is a chlorine atom and Y is a phenyl group substituted with a methoxy group. In addition, the present inventors have seen that the compounds of the following formula (VII) also exhibit a strong relaxing action on the corpora cavernosa of the penis, with an increase in bioavailability, and that they have a high safety. In this way, they have completed the present invention. A therapeutic agent for erectile dysfunction, consisting of a phthalazine compound represented by the formula (VII), a pharmacologically acceptable salt or a hydrate thereof as an active component: where 1 'is an integer from 1 to 3; R6 represents a halogen atom, a Cl to C4 alkyl group which may be substituted with a halogen atom or a cyano group; X1 represents a cyano group, a nitro group or a halogen atom; Y1 represents: i) a group represented by the formula (VIII): -N * AA.1l - (CH2) ml- (V? D where the ring Al represents a 5- or 6-membered amine ring, ml is an integer of 0 or 3 and Z represents an amino group, a hydroxyl group which may have a protective group, a carboxyl group which may have a protecting group, a Cl to C4 alkoxy group or a cyano group; ii) a group represented by the formula (IX): where the ring Bl represents an amine ring of 5 or 6 members and ni and pl are integers of 0 or 1 to 3; iii) a thiomorpholino group, where its morpholino group or its sulfur atom may be oxidized; iv) a phenyl group which may be substituted with 1 to 3 substituent groups selected from the following substituent groups Al; v) a heteroaryl group which is a pyridyl group, a pyrimidyl group, a thienyl group or a furyl group, all of which may be substituted with 1 to 3 substituent groups selected from the following substituent groups Al; or vi) a group of formula -N (R7) - (CH2) S-Het, wherein R7 represents a lower alkyl group, Het represents a pyridyl group or a pyrimidyl group, all of which may be substituted with 1 to 3 substituent groups selected from the following substituent groups Al, and s is an integer of 0 or 1 to 3; (substituent group Al) a lower alkyl group substituted with a halogen atom, a cyano group, a nitro group or a hydroxyl group; a lower alkoxy group which may be substituted with a halogen atom, a cyano group, a nitro group or a hydroxyl group; a cyano group; a nitro group; a carboxyl group which may have a protecting group; a hydroxyl group which may have a protecting group; a carbamoyl group which may be substituted with a lower alkyl group; a halogen atom, and a phenyl group which may be substituted with an alkyl group, an alkoxy group, a halogen atom or an amino group. The present invention provides a process for producing a compound represented by the formula (XI): (where X, Y3, R1, R2 and 1 have the same meanings as defined above), which consists in the step of reacting a compound represented by the formula (X): (where Hal represents a halogen atom and R1, R2, 1 and X have the same meanings as defined above) with a compound of formula Y3-B (OH) (where Y3 represents a phenyl group, a pyridyl group, a group pyrimidyl, a thienyl group - or a furyl group, all of which may have a substituent group selected from the above substituent groups Al). The present invention provides a prophylactic and therapeutic agent for erectile dysfunction, which consists of the phthalazine compound represented by the above formula (I), a pharmacologically acceptable salt thereof or a hydrate thereof as the active component. In addition, it provides a prophylactic and therapeutic agent for female sexual dysmenorrhea or dysmenorrhea, which consists of the phthalazine compound represented by the above formula (I) or (VII), a pharmacologically acceptable salt thereof or a hydrate thereof. active component. The present invention provides a pharmaceutical composition comprising a pharmacologically or clinically effective amount of the phthalazine compound represented by the above formula (I) or (XI), or a pharmacologically acceptable salt thereof or a hydrate thereof, and pharmacologically carriers. acceptable The present invention provides a method or use for preventing or treating erectile dysfunction, female sexual dysfunction or dysmenorrhea, which consists in the step of administering a pharmacologically or clinically effective amount of the phthalazine compound represented by the above formula (I) or (VII), a pharmacologically acceptable salt thereof or a hydrate thereof to a patient suffering from erectile dysfunction, female sexual dysfunction or dysmenorrhea. In the definitions established in the present invention, the halogen atoms defined in X, R 1, R 2, R 3, R 4, R 5, E, Q and substituent groups A and Al, mean a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The Cl to C4 alkyl groups defined in R1, R2, R3, R4, R5, R6, R7 and substituent groups A and Al mean linear or branched alkyl groups having from 1 to 4 carbon atoms, such as methyl, ethyl, n -propyl, isopropyl, n-butyl, isobutyl, 1-methylpropyl and tere-butyl. The C1 to C4 alkoxy groups defined in R1, R2 and substituent groups A and Al signify groups derived from the aforementioned Cl to C4 alkyl groups and such groups include, for example, a methoxy group, an ethoxy group, a group propoxy, etc. Protective groups of the carboxyl group which may have a protecting group defined in Q, W and substituent groups A and Al mean, for example, lower alkyl groups, such as a methyl group, an ethyl group and a tere-butyl group; lower alkyl groups substituted with a phenyl group which may have a substituent group, such as p-methoxybenzyl, p-nitrobenzyl, 3,4-dimethoxybenzyl, diphenylmethyl, triflyl and phenethyl; lower alkyl groups halogenated, such as 2,2,2-trichloroethyl and 2-iodoethyl; alkanoyloxy (lower) alkyl groups (lower), such as pivaloyloxymethyl, acetoxymethyl, propionyloxymethyl, butyloxymethyl, valeryloxymethyl, 1-acetoxyethyl, 2-acetoxyethyl, 1- pivaloyloxyethyl and 2-pivaloyloxyethyl; alkanoyloxy groups (upper) alkyl (lower), such as palmitoyloxyethyl, heptadecanoyloxymethyl and 1-palmitoyloxyethyl; lower alkoxycarbonyloxyalkyl groups, such as methoxycarbonyloxymethyl, 1-butoxycarbonyloxyethyl and 1- (isopropoxycarbonyloxy) ethyl; carboxyalkyl groups (lower), such as carboxymethyl and 2-carboxyethyl; heteroaryl groups, such as 3-phthalidyl; benzoyloxyalkyl (lower) groups optionally having a substituent group, such as 4-glycyloxybenzoyloxymethyl; groups (substituted dioxolene) alkyl (lower), such as (5-methyl-2-oxo-l, 3-dioxolen-4-yl) methyl; cycloalkylalkanoyloxy (substituted lower) alkyl groups (lower), such as 1-cyclohexylacetyloxyethyl, and cycloalkyloxycarbonyloxyalkyl (lower) groups, such as 1-cyclohexyloxycarbonyloxyethyl. In summary, any group that can be degraded by any means in vivo to form a carboxylic acid can serve as a protecting group for the carboxyl group. The protecting groups of the hydroxyl group which may have a protecting group defined in the substituent groups A and Al signify, for example, acyl groups such as a formyl group, an acetyl group and a benzoyl group, and lower alkoxymethyl groups such as a 2-methoxyethoxymethyl group. In summary, any group that can be degraded by any means in vivo to form a hydroxyl group can serve as a protecting group for the hydroxyl group. The azolyl group not containing a heteroatom other than a nitrogen atom defined in Q means groups derived from pyrrole, pyrazole, imidazole, triazole, tetrazole, indazole, benzimidazole and benzotriazole. In the formula (IV), a compound produced from a ring formed by E and J together with the carbon atom to which they are attached and a ring G is a spiro compound. The ring formed by E and J together with the carbon atom to which they are attached includes cyclobutane, cyclopentane, cyclohexane, oxirane, tetrahydrofuran, tetrahydropyran, bu-thyrolactone and butyrolactam. In addition, a substituent group in these rings includes a hydroxyl group, the carboxyl group which may have the above protecting group, a Cl to C4 alkyl group which may be substituted with a hydroxyl group such as a hydroxymethyl group and a hydroxyethyl group, a group carbonyl and a halogen atom such as a fluorine atom and a chlorine atom.

In the formula (V), a bicyclo ring which, when M is an alkylene group Cl to C4, is formed of the rings K and L, is intended to be a criss-cross ring. A substituent group on the L ring includes a hydroxyl group, a carboxy group which may have the above protecting group, a Cl to C4 alkyl group which may be substituted with a hydroxyl group such as a hydroxymethyl group and a hydroxyethyl group, a Cl to C4 alkyl group which may be substituted with a carboxyl group such as a carboxymethyl group and a carboxyethyl group, a halogen atom such as a fluorine atom and a chlorine atom, a vinyl group, etc. Substituent groups of the alkynyl group, the alkenyl group or the alkyl group where Y may have a substituent group include Cl to C4 alkyl groups, such as a methyl group, an ethyl group, a propyl group, a 'isopropyl group, a butyl group, an isobutyl group, a sec-butyl group and a tere-butyl group; groups derived from cycloalkanes, such as cyclopropane, cyclobutane, cyclopentane and cyclohexane; Cl to C4 alkoxy groups derived from the above Cl to C4 alkyl groups, such as a methoxy group, an ethoxy group and a propoxy group, etc .; a hydroxyl group; an amino group which may be substituted with a Cl to C4 alkyl group; cyclic amines which may be substituted with a hydroxy group, for example aziridine, azetidine, pyrrolidine and piperidine; hydroxyalkyl groups Cl a C4; hydroxyalkoxy Cl to C4 groups; carboxyalkoxy groups, and halogen atoms, such as fluorine atom and chlorine atom. In X, the heteroaryl group includes groups derived from pyrrole, pyrazole, imidazole, triazole, tetrazole, indazole, benzimidazole, benzotriazole, thiazole, isothiazole, thiadiazole, benzothiadiazole, pyridine, pyrimidine, triazine, quinoline, isoquipoline, naphthylidine, phthalazine, etc. In the present invention, the pharmacologically acceptable salt includes, for example, salts of inorganic acids, such as hydrochloride, sulfate, hydrobromide and phosphate, and salts of organic acids, such as formate, acetate, maleate, fumarate, tartrate, methanesulfonate. , benzenesulfonate and toluenesulfonate. It goes without saying that, in the case of compounds having an asymmetric carbon atom in the present invention, their optically active compounds are included within the scope of the present invention. In addition, compounds that are metabolized in vi-TO to form the compounds of the present invention and compounds formed by metabolism of compounds of the present invention are also included within the scope of the present invention. Because they are excellent in terms of oral absorption and long-term action, these phthalazine compounds, their pharmacologically acceptable salts or their hydrates can be administered percutaneously, intravenously or orally for treatment without having to resort to injection directly into the corpus cavernosum of the penis. or in the pudendas, which makes them favorable as prophylactic and therapeutic agents for erectile dysfunction and as prophylactic and therapeutic agents for female sexual dysfunction or dysmenorrhea. Although the administration dose of the compounds of the present invention is not particularly limited, they are generally administered to an adult in a dose of 5 μg to 100 mg, preferably 10 to 1,000 μg, in the case of intravenous administration, or in a dose of 1 to 1,000 mg, preferably 5 to 100 mg, in the case of oral administration. Production Process 1 Production methods for producing analogous compounds of the phthalazine compounds of the present invention or their pharmacologically acceptable salts are described in WO9605176 (JP-A 8-225541) and the phthalazine compounds of the present invention are produced therefrom. way as follows: where Y is where the ring A, D, R, m and have the same meanings as defined above; where the ring B, n and p have the same meanings as defined above; where the ring G, E and J have the same meanings as defined above; iv) -QT) where the ring K, the ring L and M have the same meanings as defined above, and where the ring P and R have the same meanings as defined above; Hal is a halogen atom and R1, R2, 1 and X have the same meanings as defined above. It is the reaction, in which the compound represented by the formula (X) reacts with HY 2 in a solvent to give the compound represented by the formula (XII) - As the solvent of the reaction, the N-methyl-2-pyrrolidine is preferable , but any solvent can be used, provided that it is inert to the reaction. Preferable results can be obtained by using HY in an excessive amount with respect to the compound (X), or by using an organic base, such as diisopropylethylamine, or a salt, such as potassium carbonate, sodium carbonate or sodium hydrogen carbonate. The temperature of the reaction is in the range of from room temperature to the boiling point of the solvent, preferably 100 ° C or more. The synthesis of HY2, necessary for the production of the compound in which W is a cyano group, which is not described in WO 9605176 (JP-A 8-225541), is carried out as follows: dehydration )? tr- CN And, in the case where W defined above is an amino group, which is not specifically described in the aforementioned publication, HY2, where an amino group is protected, it is synthesized and then deprotected as follows: In the formula (I), HY2, where Y is represented by the formulas (IV) and (V), can be produced using a compound described in WO9806720 or using a procedure described therein. 1) For example, some of the compounds represented by the formula (IV) are produced in the following procedure. (a) Wittig reaction Cyclization epoxidation n where Gl represents a ring of 4 to 8 members; Q 1 represents a pyrrolyl, pyrazolyl, imidazolyl, triazoyl, tetrazolyl, indazolyl, benzimidazolyl or benzotria-zolyl group or a fluorine atom and Pro represents a protecting group for the nitrogen atom. In a solvent such as toluene, xylene or tetrahydrofuran, methyltrifenylsulfonium bromide is treated with a base, such as tert-butoxide potassium or butyllithium, and is added. it reacts with the ketone compound represented by the formula (a), whereby the compound represented by the formula (b) can be obtained. the reaction temperature is preferably -78 ° C at room temperature. Compound (b) reacts with trichloroacetyl chloride in a solvent such as diethyl ether, dimethoxyethane or tetrahydrofuran to give the dichlorocyclobuta-none compound (f) (alternatively, when reacted with diacetyl chloride, a monochloro compound is obtained. The monochloro compound can also be obtained by reaction with trichloroacetyl chloride, followed by treatment with acetic acid) and the product is then treated with a reducing agent, such as zinc powder, whereby the cyclobutanone compound represented by the formula (g). The temperature of the reaction is preferably 10 to 50 ° C. When the compound (g) is treated with a peroxide, such as 3-chloroperbenzoic acid, in the presence of sodium hydrogen carbonate in a solvent such as dichlo-romethane, the lactone compound represented by the formula (h) can be obtained. The temperature of the reaction is preferably in the range of from room temperature to 40 ° C. When the compound (b) is treated with dichlorocetene and diazomethane, a cyclopentane compound of formula (f) is obtained and, when the compound (g) is treated with diazomethane, a cyclopentanone compound of formula (g) is obtained . When the cyclopentanone compound is re-treated with diazomethane, a cyclohexane compound is obtained. When the compound (b) is treated with a permeate, such as magnesium phthalate monoperacid, the epoxide compound represented by the formula (c) is obtained. When the epoxide compound (c) reacts with a sodium salt of azole containing nitrogen atoms only as heteroatoms, in a solvent such as dimethylformamide, the corresponding compound represented by the formula (d) is obtained (Q1 is a group 1 -imidazolyl, a 1-triazolyl group, etc.). By treatment with hydrogen potassium fluoride at 100 to 150 ° C in the presence of BuN "H 2 F 3, a fluoromethyl compound is obtained as a compound represented by the formula (d), where Q 1 is a fluorine atom. Fluoro represented by formula (e) is obtained by treating compound (c) with hydrogen fluoride pyridine, in a solvent such as methylene chloride at -10 to 10 ° C. 2) Among the compounds represented by formula (V) , those in which M is methylene substituted with a hydroxyl group are produced by, for example, the following procedure.

Demethylation and deprotection of NH des-O-acylation N deprotection The compound in which the L ring contains an oxygen atom can also be produced in the same way.

Production Process 2 Compounds of formula (I) wherein Y is an alkynyl group, an alkenyl group or an alkyl group, all of which may have a substituent group, may be produced by the following procedure. reduce where Hal is a halogen atom, R8 is an optionally substituted Cl to C4 alkyl group or an optionally substituted cycloalkyl or cycloalkylalkyl group and R1, R2, 1 and X have the meanings defined above. The reaction of the compound of formula (X) with the alkyne compound is carried out in the presence of a catalytic amount of dichlorobistriphenylphosphine palladium (II), cuprous iodide and a tertiary amine, at room temperature or with heating. The solvent used includes dimethylformamide or 1-methylpyrrolidinone. The tertiary amine used includes triethylamine, diisopropylethyl-aa, DBU and dimethylaniline. The reaction temperature is preferably 0 to 150 ° C. The conversion of the alkyne compound represented by the formula (XIII) to the alkene compound represented by the formula (XIV) or the alkane compound represented by the formula (XV) is carried out by catalytic reduction, etc., in the presence of a catalyst of Lindlar or a Pd-C catalyst. Production process 3 In addition, the phthalazine compounds in which Y is Y3, which is an optionally substituted aryl group or a heteroaryl group, are produced as follows: where Y is a phenyl group, a pyridyl group, a pyrimidyl group, a thienyl group or a furyl group, all of which may have from 1 to 3 substituent groups, selected from the above groups A; Hal is a halogen atom, and R1, R2, 1 and X have the same meanings as defined above. The reaction is carried out by coupling the 1-halogenoquinazoline compound represented by the formula (X) by a zero valent or palladium complex divalent to a boric acid, dialkoxyborane or trialkyltin compound having an aryl group or corresponding heteroaryl group. . The boric acid, dialkoxyborane or trialkyltin compound having an aryl group or a heteroaryl group and the palladium complex are dissolved or suspended in a 2-phase solvent consisting of an organic solvent and an aqueous solution of sodium carbonate. And the mixture reacts at a temperature in the range of from room temperature to the boiling point of the solvent for about 1 to 24 h, in a stream of nitrogen gas. As a palladium complex, any palladium complex allowing the reaction to proceed may be used and tetrakis (triphenylphosphine) palladium, etc. are preferable. As the organic solvent, any solvent which is inert to the reaction can be used and xylene, toluene, tetrahydrofuran or a mixed solvent thereof are preferable. Production Process 4 In the formula (I), the compounds shown in the following reaction scheme can be produced by combining known reactions using the compound (XVII), wherein X is a cyano group. where R9 is a hydrogen atom, a Cl to C4 alkyl group which may be substituted with a halogen atom, an arylalkyl group (Cl to C4) or a carboxyalkyl group (Cl a 04 'R 10 is a Cl to C 4 alkyl group, and R 1, R 2, 1 and Y have the same meanings as defined above. Production procedure 5 Some of the compounds of formula (I) in which X is a heteroaryl group can be produced in the same way as in Production Method 3. (k) where Hal is a halogen atom, Het is a heteroaryl group and R1, R2, 1 and Y have the same meanings as defined above. The halogen atom is preferably a bromine atom or an iodine atom. further, the compounds of formula (I) with an azolyl group which do not have a heteroatom other than a nitrogen atom, are produced according to the aforementioned Production Procedure 1, after previously producing the corresponding compound represented by the formula (X ). The corresponding compound of formula (X) is produced, for example, according to a method described in WO9605176, after treating dimethyl 4-fluorophthalate with azole which does not contain a heteroatom other than a nitrogen atom, to give dimethyl 4-azolylphthalate , and then treating it with hydrazine to obtain 6-azolyl-2,3-dihydro-1,4-phthalazinedione. Production process 6 The compound of formula (I) can be produced in which Y is represented by formula (VI) by converting the compound represented by the following formula (XXIV) into the oxime by a known method: where R1, R2, R5, 1 and X have the same meanings as defined above. The effect of the compounds of the present invention will now be described with reference to Experimental Examples. 1) Inhibitory action on the cGMP-PDE enzyme obtained from porcine platelets The inhibitory activity of a test compound on the cGMP-PDE enzyme prepared from porcine platelets was determined by adding a solution of the test compound dissolved in DMSO to a solution of reaction, where 1 μM cGMP was used as a substrate in the presence of 1 mM EGTA, according to a method of Tompson et al. The final concentration of DMSO in the reaction solution was 1% or less. The preparation of cGMP-PDE was carried out as follows. Porcine platelets were added to buffer A (20 mM Tris / HCl, 2 mM magnesium acetate, 10 mM 2-mercaptoethanol, 0.1 mg IMTA, pH 7.4) and then sonicated. The resulting suspension was centrifuged at 10000 xg for 60 minutes and the resulting supernatant was subjected to a column (DEAE-Toyopearl 650S, produced by Tosoh, Tokyo, Japan). After washing the column with buffer A, the enzyme was eluted with a gradient of 0.075 to 0.25 M NaCl in buffer A to obtain a cGMP-PDE fraction. The resulting fraction was dialyzed, concentrated and stored. Table 1. Inhibitory action on PDE5 2) Increase action of the PDE5 inhibitor on the relaxing action of nitroprusside in a cavernous body preparation of the penis extracted from a rabbit The penis was extracted from a white NZ rabbit (approximately 3 kg) sacrificed by intravenous administration of pentobarbital (50 mg / kg). After extraction, the cavernous body was exposed by removing the surrounding tissues, such as the tunica albuginea, to obtain a preparation (approximately 10x1.5x1.5 mm). This preparation was suspended in a Magnus tube that had been filled with 10 ml of Krebs-Henseleit nutrient solution (118.4 mM NaCl, 4.7 mM KC1, 2.5 mM CaCl2, 1.3 mM MgSO4, KH2P04 1 , 2 mM, 25.0 mM NaHC03, 11.0 mM glucose, 0.026 mM EDTA and 0.001 mM indomethacin) at 37 ° C and a gaseous mixture was bubbled into it (95% oxygen + 5% carbon dioxide) . The isometric tension was then recorded under a load of 2 g. To stabilize the contraction, the contraction was provoked by adding a solution of potassium chloride (final concentration: 100 mM) and a wash was performed, repeating both times twice, and, in addition, the contraction was also caused by adding phenylephrine (final concentration: 10 μM) and washing was performed. It was refilled with 10 ml of Krebs-Henseleit solution and L-NG-nitroarginine methyl ester was added. (final concentration: 100 μM) to inhibit the formation of endogenous nitrogen monoxide. Contraction was caused by adding phenylephrine (final concentration: 10 μM) and a chemical solution was added at a final concentration of 3, 30 or 300 nM. Dimethyl sulfoxide was used as a medium in this reaction. 15 minutes after adding the chemical agent, nitroprusside (final concentration: 300 μM) was added to relax the preparation. Papaverine was also added (final concentration: 100 μM) to determine maximum relaxation. After the experiment, the tension generated by adding papaverine as a baseline was used and the relaxation of the preparation was recorded by adding nitroprusside on a graph using a DEGIMATIC CALIBRATOR to determine the degree of relaxation.

Table 2. Action of increase of the PDE5 inhibitor on the relaxation produced by nitroprusside of the preparation of the cavernous body of the penis extracted from a rabbit The values in the table indicate the relaxation ratio (%) after adding nitroprusside to the preparation pretreated with 3, 30 and 300 nM of compound and the average was recorded in a duplicate experiment. In addition, the EC50 value indicates the concentration of the compound at which the contraction caused by phenylephrine relaxes by 50% and this value was calculated by regression analysis of a relaxation curve in a duplicate experiment. Nitrogen monoxide formed by nitroprusside activated guanylate cyclase to promote the formation of cGMP from GTP, thus relaxing the cavernous body of the penis. The PDE5 inhibitor increased this relaxation action by inhibiting the degradation of cGMP. As described above, it was demonstrated that the compounds of the present invention have an inhibitory action on PDE5 and increase the relaxation action of nitroprusside on the cavernous body sample of the rabbit penis in a dose-dependent manner. That is, that the present invention is useful as a prophylactic and therapeutic agent for erectile dysfunction. Examples of production and Examples are given to facilitate the understanding of the present invention, but, in fact, the present invention is not limited to these compounds. Production Example 1 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-l- [(3R) -3-hydroxypiperidino] phthalazine hydrochloride A mixture of 1.0 g of l-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine, 1.92 g of (R) - (+) - 3-hydroxypiperidine hydrochloride was stirred, 1.80 g of diisopropylethylamine and 12 ml of l-methyl-2-pyrrolidone at 170 ° C for 1 h and 15 min. After cooling, ethyl acetate was added to the reaction solution, which was then washed with water and brine. It was dried over anhydrous sodium sulfate, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography. The resulting free compound was suspended in acetic acid / ethanol / water, 1N aqueous hydrochloric acid was added and dissolved by heating. After cooling, the resulting crystals were collected by filtration to obtain 860 mg of the title compound as a yellow powder. MASS (ESI): 424, 1 (MH +). XH-NMR (Nuclear Magnetic Resonance) (400MHz, DMSO-d6) d: 1.39-1.50 (HH, m), 1.65-1.78 (HH, m), 1.75-1.98 (2H, m), 2.82-2.91 (HH, m), 2.93-3.02 (HH, m), 3.33-3.48 (2H, m), 3.79-3.88 (HH, m), 3.85 (3H, s), 4.72 (2H, broad), 7.16 (1H, d, J = 8.4Hz), 7.47. (ÍH, dd, J = 8.4, 1.6Hz), 7.62 (1H, d, J = 1, 6Hz), 8,31 (1H, d, J = 8,4Hz), 8,48 (1H, d, J = 8,4Hz), 9.38-9.46 (1H, m), 10.27 (1H, broad). Production Example 2 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-l- [(3S) -3-hydroxypyrrolidino] phthalazine hydrochloride The title compound was obtained using (S) -3-hydroxypyrrolidine in place of (R) - (+) - 3-hydroxypiperidine hydrochloride in Production Example 1. MASS (ESI): 410.0 (MH +). XH-NMR (400MHz, DMSO-dg) d: 1.94-2.10 (2H, m), 3.50-3.62 (1H, m), 3.42-3.68 (HH, m), 3.83 (3H, s), 3.93-4.10 (2H, m), 4.43-4.50 (HH) , m), 4.50-4.64 (2H, m), 5.30 (ÍH, broad), 7.13 (HH, d, J = 8.4Hz), 7.34-7.44 (1H) , m), 7.48-7.56 (HH, m), 8.38-8.46 (HH, m), 8.62-8.74 (1H, m), 9.10-9.32 (ÍH, m).

Production Example 3 4- (3-Chloro-4-methoxybenzyl) amino-β-cyano-1- [(2S) -2-hydroxymethylpyrrolidino] phthalazine hydrochloride The title compound was obtained using (S) -2-hydroxymethylpyrrolidine in place of (R) - (+) - 3-hydroxypiperidine hydrochloride in Production Example 1. MASS (ESI): 424.1 (MH +). XH-NMR (400MHz, DMSO-d6) d: 1.60-2.39 (4H, m), 3.44-3.53 (1H, m), 3.83 (3H, s), 3.89 -3.99 (HH, m), 4.34-4.70 (3H, m), 7.12-7.16 (HH, m), 7.38-7.46 (HH, m), 7 , 52-7.59 (HH, m), 8.40-8.43 (HH, m), 8.43-8.60 (HH, m), 9.23-9.30 (HH, m) . Production Example 4 4- (3-Chloro-4-methoxybenzyl) amino-β-cyano-1- (3-hydroxymethylpiperidino) phthalazine hydrochloride The title compound was obtained using 3-hydroxymethylpiperidine in place of (R) - (+) - 3-hydroxypiperidine hydrochloride in Production Example 1. MASS (ESI): 438.2 (MH +). ^ -NMR (400MHz, DMSO-d6) d: 1.13-1.28 (lH, m), 1.70-1.86 (3H, m), 1.87-1.99 (lH, m) , 2.67-2.75 (1H, m), 2.86-2.95 ; iH, m), 3.33-3.50 (3H, m 3.51-3.60 (HH, m), 3.16 (3H, s), 3.85 (3H, s), 4, 71 (2H, broad s), 7.16 (ÍH, d, J = 8.4Hz), 7.44 (HH, dd, J = 8.4, 0.8Hz), 7.59 (HH, d, J = 0.8Hz), 8.23 (HH, d, J = 8.8Hz), 8.45 (ÍH, dd, J = 8.8, 0.4Hz), 9.28-9.35 (HH, m), 9.95 (HH, broad), 14.00 (HH, broad). Production Example 5 4- (3-Chloro-4-methoxyphenethyl) amino-6-cyano-1- (3-hydroxymethylpiperidino) phthalazine hydrochloride The title compound was obtained using l-chloro-4- (3-chloro-4-methoxyphenethyl) amino-6-cyanophthalazine in place of 1-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine in Production Example 4. MASS (ESI): 452.3 (MH +). XH-NMR (400MHz, DMSO-d6) d: 1.70-1.90 (2H, m), 1.90-2.05 (2H, m), 2.70 (1H, broad t), 2, 88 (ÍH, broad t), 2.95-3.08 (2H, m), 3.25-3.63 (2H, m), 3.78 (2H, m), 3.83 (3H, s) ), 7.09 (HH, d, J = 8.6Hz), 7.29 (HH, d, J = 8.6Hz), 7.47 (HH, s), 8.25 (HH, d, J = 8.6Hz), 8.49 (HH, d, J = 8.6Hz), 9.48 (HH, s).

Production Example 6 4- (3-Chloro-4-methoxyphenethyl) amino-6-cyano-1- (4-hydroxymethylpiperidino) phthalazine The title compound was obtained using 4-hydroxymethylpiperidine in place of 3-hydroxymethylpiperi-dine in Production Example 5. MASS (ESI): 452.3 (MH +). lt-IN R (400MHz, CDC13) d: 1.51-1.65 (2H, m), 1.79-1.85 (HI, m), 1.93 (2H, m), 2.99- 3.09 (4H, m), 3.56-3.68 (4H, m), 3.90 (3H, s), 3.85-3.99 (2H, m), 4.94 (1H, broad t), 6.88 (HH, d, J = 8.4Hz), 7.13 (HH, dd, J = 2.2, 8.4Hz), 7.28 (HH, d, J = 2.2Hz), 7.94 (1H, d, J = 8.4Hz), 7.98 (1H, s), 8.13 (1H, d, J = 8.4Hz). Production Example 7 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-l- [methyl (2-pyridylmethyl) amino] phthalazine dihydrochloride The title compound was obtained by the same treatment as in Production Example 1, except for the use of N-methyl- [(2-pyridyl) methyl] amine instead of (R) - (+) - 3 hydrochloride -hydroxypiperidine. MASS (ESI): 445.3 (MH +). 1 H-NMR (400MHz, DMSO-d 6) d: 2.95 (3H, s), 3.85 (3H, s), 4.73-4.79 (4H, m), 7.16 (1H, d) , J = 8.4Hz), 7.49 (HH, dd, J = 8.4, 2.0Hz), 7.64 (HH, d, J = 2.0Hz), 7.65-7.72 ( HH, m), 7.83-7.87 (1H, m), 8.18-8.26 (HH, m), 8.52 (HH, dd, J = 8.4, 1.2Hz), 8.60 (HH, d, J = 8.4Hz), 8.74 (HH, d, J = 4.8Hz), 9.53-9.55 (HH, m), 10.64 (HH, broad ). Production Example 8 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-1-dihydrochloride. { N-methyl- [2- (2-pyridyl) ethyl] amino} phthalazine The title compound was obtained by the same treatment as in Production Example 7, except for the use of N-methyl- [2- (2-pyridyl) -ethyl] amine instead of N-methyl- [(2- pyridyl) methyl] amine.

MASS (ESI): 459.2 (MH +). XH-NMR (400MHz, DMSO-d6) d: 3.00 (3H, s), 3.35 (2H, t, J = 6.4Hz), 3.76 (2H, t, J = 6.4Hz) , 3.85 (3H, s), 4.73-4.77 (2H, m), 7.18 (HH, d, J = 8.4Hz), 7.50 (HH, d, J = 8, 4Hz), 7.53-7.64 (HH, m), 7.65 (HH, s), 7.68-7.77 (HH, m), 8.10-8.30 (HH, m) , 8.16 (HH, d, J = 8.6Hz), 8.44 (HH, d, J = 8.6Hz), 8.55-8.61 (HH, m), 9.45-9, 51 (ÍH, m), 10.53 (ÍH, broad).

Production Example 9 4- (3-Chloro-4-methoxyphenethyl) amino-6-cyano-1- (4-methoxypiperidino) phthalazine hydrochloride The title compound was obtained by the same treatment as in Production Example 5, except for the use of 4-methoxypiperidine hydrochloride in place of 3-hydroxymethylpiperidine. MASS (ESI): 452.2 (MH +). 1 H-NMR (400MHz, DMSO-d 6) d: 1.66-1.76 (2H, m), 2.00-2.08 (2H, m), 2.91-2.97 (2H, m) , 2.99-3.07 (2H, m), 3.29 (3H, s), 3.37-3.49 (3H, m), 3.70-3.77 (2H, m), 3 , 81 (3H, s), 7.07 (HH, d, J = 8.6Hz), 7.26 (HH, dd, J = 8.6, 2.0Hz), 7.43 (1H, d, J = 2.0Hz), 8.24 (HH, d, J = 8.3Hz), 8.45 (HH, dd, J = 8.3, 1.6Hz), 9.22 (HH, d, J = l, 6Hz).

Production Example 10 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-1- (4-methoxyphenyl) phthalazine hydrochloride 423 mg of tetrakis (triphenylphosphine) palladium (0) was added to a mixture of 1.0 g of 1-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine, 423 mg of 4-methoxyphenylboronic acid 30 ml of toluene, 30 ml of tetrahydrofuran and 30 ml of 2 M aqueous sodium carbonate in a nitrogen atmosphere. The mixture was stirred at 80 ° C for 2 h and then at 10 ° C for 15.5 h. The reaction solution was returned to room temperature and extracted with aqueous ammonium chloride and ethyl acetate. The organic layer was washed with aqueous ammonia, water and brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the resulting residue was purified by silica gel column chromatography. The resulting coupled compound was dissolved in ethyl acetate / ethanol, a solution of 4 N hydrochloric acid / ethyl acetate was added and the resulting crystals were collected by filtration to obtain 460 mg of the title compound as a yellow powder. MASS (ESI): 431.2 (MH +). lt-I-NMR (400MHz, DMSO-d6) d: 3.85 (3H, s), 3.87 (3H, s), 4.82-4.85 (2H, m), 7.16-7 , 21 (3H, m), 7.49 (ΔI, dd, J = 8.6, 2.2Hz), 7.60-7.63 (3H, m), 8.08 (ΔI, d, J = 8.4Hz), 8.45 (1H, dd, J = 8.4, 1.4Hz), 9.45-9.49 (HI, m), 10.39 (1H, broad). Production Example 11 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxy-3-methylpiperidino) -6-phthalazinecarbonitrile hydrochloride The title compound was obtained by the same treatment as in Production Example 1, except for the use of 4-hydroxy-3-methylpiperidine in place of (R) - (+) - 3-hydroxypiperidine hydrochloride. XH-NMR (400MHz, DMSO-d6) d: 0.94 (3H, t, J = 8.0Hz), 1.59-2.03 (3H, m), 2.74-3.96 (5H, m), 3, 83 (3H, s), 4.68 (2H, d, J = 5.2Hz), 7.15 (HH, d, J = 8.4Hz), 7.43 (HH, d, J = 8.0Hz) ), 7.58 (HH, s), 8.23 (HH, t, J = 8.0Hz), 8.45 (HH, d, J = 8.4Hz), 9.29 (HH, s). Production Example 12 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxy-3, 3,5,5,5-tetramethylpiperidino) -6-phthalazinecarbonyltryl hydrochloride The title compound was obtained by the same treatment as in Production Example 1, except for the use of 4-hydroxy-3, 3, 5, 5-tetramethylpiperidine in place of (R) - (+) - 3-hydroxypiperidine hydrochloride. 1H-NMR (400MHz, DMSO-d6) d: 0.91 (6H, s), 1.15 (6H, s), 2.57 (1H, d, J = 12.4Hz), 2.95 (1H) , s), 3.21 (2H, d, J = 12.0Hz), 3.83 (3H, s), 4.47 (2H, d, J = 5.6Hz), 7.14 (1H, d) , J = 8.4Hz), 7.47 (HH, d, J = 8.8Hz), 7.63 (HH, s), 8.29 (HH, d, J = 8.4Hz), 8.55 (1H, d, J = 8.4Hz), 9.52 (HH, s), 10.63 (HH, broad).

Example of production of intermediate 1 l-Chloro-4- [[(4-methoxy-3-trifluoromethyl) benzyl] amino] -6-phthalazinecarbonitrile A mixture of 10 g of 2-trifluoromethylphenol, 17 g of potassium carbonate, 150 ml of acetone and 7.7 ml of iodomethane at reflux was heated for 2 h. After cooling, the insolubles were removed by filtration and the filtrate was evaporated. The resulting residue was dissolved in ethyl acetate and washed with water and brine. It was dried over anhydrous magnesium sulfate, filtered and evaporated to obtain 12.15 g of 2-triflu-ethylamnisol. A mixture of 8.5 g of 2-trifluoromethylanisole and 7.0 g of hexamethylenetetramine was stirred at 90 ° C for 1.5 h in 80 ml of trifluoroacetic acid. The reaction solution was evaporated. The resulting residue was dissolved in ethyl acetate and added dropwise to ice-cold saturated aqueous sodium bicarbonate. The ethyl acetate layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate, filtered and evaporated. The resulting residue was purified by silica gel column chromatography to obtain 5.8 g of 3-trifluoromethyl-p-anisaldehyde. A mixture of 5.8 g of 3-trifluoromethyl-p-anisaldehyde, 8.6 ml of formamide and 13.6 ml of formic acid was stirred at 130 ° C for 9 h. After cooling, water and ethyl acetate were added. The ethyl acetate layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate, filtered and evaporated. The resulting residue was purified by chromatography on a silica gel column to obtain 3.8 g of N- [4-methoxy-3- (trifluoromethyl) benzyl] formamide 3.8 g of N- [ 4-methoxy-3- (trifluoromethyl) benzyl] formamide in 20 ml of ethanol, 2 ml of concentrated hydrochloric acid were added and the mixture was heated at reflux for 3 h After cooling, diethyl ether was added and the crystals were collected. were obtained by filtration to obtain 2.5 g of 4-methoxy-3- (trifluoromethyl) benzylamine hydrochloride, 3.7 g of DBU were added to a mixture of 2.2 g of 1,4-dichlorophthalazine-6-carbonitrile, 2.5 g of 4-methoxy-3- (trifluoromethyl) benzylamine hydrochloride and 25 ml of 1-methyl-2-pyrrolidinone were added and the mixture was stirred at room temperature for 1.25 h. Ethyl acetate was added to the solution of the reaction, which was then washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated. This is followed by column chromatography on silica gel to obtain 1.66 g of the title compound as a less polar compound. XH-NMR (400MHz, DMS0-d6) d: 3.86 (3H, s), 4.74 (2H, d, J = 5.2Hz), 7.22 (ΔH, d, J = 9.6Hz) , 7.67-7.71 (2H, m), 8.20 (HH, d, J = 8.4Hz), 8.35 (HH, dd, J = 8.4, 1.4Hz), 8, 50 (ÍH, t, J = 5.2Hz), 8.99 (ÍH, d, J = 1, 4Hz). In the same way, l-chloro-4- [(3-iodo-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile was obtained from commercial 2-iodoanisole; 4- [(3-bromo-4-methoxybenzyl) ami-no] -1-chloro-6-phthalazinecarbonitrile from 3-bromo-p-anisaldehyde; l-chloro-4- [(3-fluoro-4-methoxybenzyl) ami-no] -6-phthalazinecarbonitrile from 3-fluoro-p-anisaldehyde, and l-chloro-4- [(4-methoxy-3- methylbenzyl) ami-no] -6-phthalazinecarbonitrile from 3-methyl-p-anisaldehyde. Example of production of intermediate 2 l-Chloro-4- [(3-iodo-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMS0-d6) d: 3.80 (3H, s), 4 , 67 (2H, d, J = 5.2Hz), 6.96 (HH, d, J = 8.4Hz), 7.42 (HH, dd, J = 8.4, 2.0Hz), 7, 83 (HH, d, J = 2.0Hz), 8.18 (HH, d, J = 8.4Hz), 8.34 (HH, dd, J = 8.4, 1.2Hz), 8.45 (ÍH, t, J = 5.2Hz), 8.99 (ÍH, d, J = 1, 2Hz). Example of intermediate production 3 4- [(3-Bromo-4-methoxybenzyl) amino] -l-chloro-6-phthalazinecar- • bonitrile 1H-NMR (400MHz, DMS0-d6) d: 3.82 (3H, s ), 4.70 (2H, d, J = 5.2Hz), 7.07 (IH, d, J = 8.4Hz), 7.41 (IH, dd, J = 8.4, 2.0Hz) , 7.63 (HH, d, J = 2.0Hz), 8.20 (HH, d, J = 8.4Hz), 8.34 (HH, dd, J = 8.4, 1.2Hz), 8,47 (ÍH, t, J = 5,2Hz), 8,99 (ÍH, d, J = 1, 2Hz). Example of production of intermediate 4 l-Chloro-4- [(3-fluoro-4-methoxybenzyl) amino] -6-phthalazine-carbonitrile 1H-NMR (400MHz, DMSO-d6) d: 3.81 (3H, s), 4.70 (2H, d, J = 5.4Hz), 7.11 (H, t, J = 8.8Hz), 7.19 ( HH, d, J = 8.8Hz), 7.26 (HH, dd, J = 12.8, 2.0Hz), 8.20 (HH, d, J = 8.4Hz), 8.35 (HH) , dd, J = 8.4, 0.8 Hz), 8.46 (ΔI, t, J = 5.4 Hz), 9.01 (ΔI, d, J = 0.8 Hz). Example of production of 5-l-Chloro-4- [(3-cyano-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile intermediate A mixture of 20 g of 4-methoxybenzyl chloride, 26 g of potassium phthalimide and 100 g of ethyl acetate was stirred. ml of dimethylformamide at 50 ° C for 5 h. After cooling, the reaction solution was poured into ice water and the resulting precipitates were collected by filtration. These were washed with water and dried to obtain 31 g of N- (4-methoxybenzyl) phthalimide. 18 g of hexamethylenetetramine were added little by little to a mixture of 31 g of N- (4-methoxybenzyl) phthalimide and 100 ml of trifluoroacetic acid, stirred at room temperature for 1 h and then heated to reflux for 4 h. The reaction solution was cooled to 0 ° C and water was added thereto. Potassium carbonate was added and the resulting crystals were collected by filtration. The crystals were dried to obtain 20 g of N- (3-formyl-4-methoxybenzyl) phthalimide. 5.2 g of hydroxylamine hydrochloride, 12.2 g of sodium acetate and 50 ml of water were added to a mixture of 20 g N- (3-formyl-4-methoxybenzyl) phthalimide and 200 ml of tetrahydrofuran and stirred at room temperature for 1 h. It was stirred at 60 ° C for 1 h and then evaporated. Water was added to the resulting residue and the insolubles were collected by filtration. These were washed with diethyl ether to obtain 20 g of N- (3-hydroxyimino-4-methoxybenzyl) phthalimide. 6.7 ml of acetic anhydride was added to a mixture of 20 g of N- (3-hydroxyimino-4-methoxybenzyl) phthalimide and 200 ml of xylene and the mixture was heated at reflux for 10 h. It was returned to room temperature and the resulting crystals were collected by filtration and washed with xylene to obtain 15 g of N- (3-cyano-4-methoxybenzyl) phthalimide. 3.9 g of hydrazine monohydrate was added to a mixture of 15 g of N- (3-cyano-4-methoxybenzyl) phthalimide and 200 ml of ethanol and the mixture was heated under reflux for 3 h. After cooling, insolubles were removed by filtration. The filtrate was evaporated and 1N aqueous sodium hydroxide was added to the resulting residue, which was extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to obtain 8.0 g of 3-cyano-4-methoxybenzylamine. 1,4-Dichlorophthalazine-6-carbonitrile and 3-cyano-4-methoxybenzylamine were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, thus obtaining l-clear-4- [(3-cyano-4 -methoxybenzyl) ami-no] -6-phthalazinecarbonitrile as a less polar product. 1H-NMR (400MHz, DMSO-d6) d: 3.87 (3H, s), 4.70 (2H, d, J = 5.6Hz), 7.20 (1H, d, J = 8.4Hz) , 7.70 (HH, dd, J = 2.4, 8.4Hz), 7.75 (1H, d, J = 2.4Hz), 8.19 (HH, d, J = 8.4Hz), 8.34 (1H, dd, J = 1, 2, 8,4Hz), 8,48 (1H, t, J = 5,6Hz), 8,97 (1H, s) - Example of intermediary production 6 l -Chloro-4- [(3-ethyl-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile 3.99 g of potassium t-butoxide was added to 80 ml of a solution of 12.7 g of methyltriphenylphosphine bromide -3N in tetrahydrofuran at 0 ° C, 7 g of N- (3-formyl-4-methoxybenzyl) phthalimide was added and the mixture was stirred at room temperature for 1 h. The reaction solution was filtered through Celite and then evaporated. The resulting residue was purified by silica gel column chromatography to obtain 2.75 g of N- (4-methoxy-3-vinylbenzyl) phthalimide. 2.75 g of N- (4-methoxy-3-vinylbenzyl) phthalimide was dissolved in 50 ml of tetrahydrofuran, 0.1 g of 10% Pd-C was added and the mixture was stirred for 40 minutes in an atmosphere. of hydrogen. The reaction solution was filtered through Celite and the filtrate was evaporated. The resulting residue was purified by silica gel column chromatography to obtain 2.55 g of N- (3-ethyl-4-methoxybenzyl) phthalimide. 0 were added, 84 ml of hydrazine monohydrate to a mixture of 2.55 g of N- (3-ethyl-4-methoxybenzyl) phthalimide and 60 ml of ethanol and the mixture was heated under reflux for 1 h. After cooling, it was evaporated and 2N aqueous sodium hydroxide was added to the resulting residue, which was then extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated, ethyl acetate was added and the insoluble matters were filtered. 4 N Hydrochloric acid (solution in ethyl acetate) was added and the resulting crystals were collected by filtration to obtain 1.75 g of 3-ethyl-4-methoxybenzylamine hydrochloride. 1,4-Dichlorophthalazine-6-carbonyl trile and 3-ethyl-4-methoxybenzylamine hydrochloride were stirred at room temperature in l-methyl-2-pyrrolidinone in the presence of DBU, thus obtaining l-chloro-4- [( 3-ethyl-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile as a less polar compound. XH-NMR (400MHz, CDC13) d: 1.14 (3H, t, J = 7.5Hz), 2.60 (2H, c, J = 7.5Hz), 3.81 (3H, s), 4 , 84 (2H, s), 6.80 (HH, d, J = 8.2Hz), 7.25 (HH, d, J = 2.0Hz), 7.30 (HH, dd, J = 2, 0, 8.2Hz), 8.06 (ÍH, d, J = 9.0Hz), 8.27 (ÍH, d, J = 9.0Hz), 8.42 (ÍH, m). Example of production of intermediate 7 l-Chloro-4- [(3-chloro-4-methylbenzyl) amino] -6-phthalazinecarbonitrile 15 ml of a solution of 2.0 g of 3-chloro-4-methylbenzonitrile were added dropwise in tetrahydrofuran to 40 ml of a solution of 453 mg of lithium aluminum hydride in tetrahydrofuran under a nitrogen atmosphere. The mixture was heated at reflux for 2 h and 10 min. The mixture was cooled with ice and 0.45 ml of water, 0.45 ml of 15% aqueous sodium hydroxide and 1.35 ml of water were added dropwise, so that the solution was maintained at 10 ° C. ° C or less. The solution was filtered through Celite and the resulting filtrate was dried by adding anhydrous sodium sulfate. It was filtered through a NH-form silica gel and the filtrate was evaporated to obtain 1.74 g of 3-chloro-4-methylbenzylamine. 1,4-Dichlorophthalazine-6-carbonitrile and 3-chloro-4-methylbenzylamine were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, thereby obtaining the title compound as a less polar compound. XH-NMR (400MHz, DMSO-d6) d: 2.29 (3H, s), 4.73 (2H, d, J = 5.2Hz), 7.28-7.32 (2H, m), 7 , 45 (HH, d, J = 0.8Hz), 8.20 (HH, dd, J = 8.4, 0.4Hz), 8.34 (HH, d, J = 8.4, 1.6Hz ), 8.52 (1H, t, J = 5.2Hz), 9.00 (1H, m). Example of production of intermediate 8 l-Chloro-4- [(4-chloro-3-methoxybenzyl) amino] -6-phthalazinecarbonitrile 4-Chloro-3-methoxybenzylaminebenzylamine hydrochloride synthesized according to the method described in O9518097 and 1, 4 were stirred. -dichlorophthalazine-6-carbonitrile at room temperature in l-methyl-2-pyrrolidinone in the presence of DBU, thereby obtaining l-chloro-4- [(4-chloro-3-methoxybenzyl) amino] -6-phthalazinecarbo-nitrile as a less polar product. ^ -NMR (400MHz, DMS0-d6) d: 3.86 (3H, s), 4.76 (2H, d, J = 5.5Hz), 4.74 (ÍH, d, J = 4.2Hz) , 6.99 (ÍH, dd, J = l, 8, 8,1Hz), 7,22 (ÍH, d, J = 1, 8Hz), 7,35 (ÍH, d, J = 8, lHz), 8.21 (ÍH, d, J = 8.6Hz), 8.36 (1H, d, J = 8.6Hz), 8.52 (1H, t, J = 5.5 Hz), 9.03 (ÍH, s). Example of production of intermediate 9 l-Chloro-4- [(3-dichlorobenzyl) amino] -6-phthalazinecarbonitri-lo XH-NMR (400MHz, DMSO-d6) d: 4.76 (2H, d, J = 5.4Hz), 7.40 (1H, dd, J = 8.4, 1.8Hz), 7.58 ( 1H, d, J = 8.4Hz), 7.68 (H, d, J = l, 8Hz), 8.21 (1H, dd, J = 8.4, 0.4Hz), 8.36 (1H, dd, J = 8.4, 1,6Hz), 8,57 (ÍH, t, J = 5,4Hz), 8,99 (ÍH, d, J = 1, 6Hz).

Example of production of 10-benzyl 4-fluoro-4-hydroxymethyl-1-piperidinecarboxylate intermediate 51.1 g of methyl tolyl phospho-nium bromide were added to a mixture of 16.1 g of tert-butoxy-potassium and 500 ml of tetrahydrofuran and then stirred for 1 h and 20 min at room temperature. 16.1 g of benzyl 4-oxo-l-piperidinecarboxylate were added and the mixture was stirred for 2 h and 40 min at room temperature. The reaction solution was evaporated, diethyl ether was added and then filtered through Celite. The filtrate was washed with water and brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the resulting residue was subjected to silica gel column chromatography to obtain 25.5 g of benzyl 4-methylene-1-piperidinecarboxylate. 14.7 g of benzyl 4-methylene-1-piperidinecarboxylate were dissolved in 300 ml of methanol, 20.4 g of monopeptide phthalic acid magnesium salt and 13.3 g of sodium bicarbonate were added and the mixture was stirred. mixed at room temperature for 7.5 h. The reaction solution was evaporated. Ethyl acetate was added to the resulting residue, which was then washed with water and brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and then chromatographed on a silica gel column to obtain 11.3 g of l-oxa-6-azaspiro [2.5] octane-6-carboxylic acid benzyl ester. A mixture of 5 ml of pyridine hydrogen fluoride and 20 ml of methylene chloride was cooled and 10 ml of a solution of 4.95 g of l-oxa-6-azaspiro [2.5] octane-6-carboxylate were added dropwise. of benzyl in methylene chloride over 25 minutes, such that the overall temperature was 0 ° C or less. The mixture was stirred for 35 minutes under ice cooling. The reaction solution was poured into a mixture of saturated sodium bicarbonate and ice. The organic layer was recovered, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and then subjected to silica gel column chromatography to obtain 2.84 g of the title compound. Example of production of tert-butyl 11 • 4-hydroxy-4- (lH-1-imidazolylmethyl) -1-piperidinecarboxylate 13.5 g of tert-butyl 4-methylene-l-piperidinecarboxylate were dissolved in 300 ml of methanol and 28.3 g of mono-peracid phthalic acid magnesium salt and 8.62 g of sodium bicarbonate were added and stirred the mixture at room temperature for 1 day. The reaction solution was filtered through Celite and the resulting filtrate was evaporated. Ethyl acetate was added to the resulting residue, which was then washed with water and brine, dried over magnesium sulfate and then filtered. The filtrate was evaporated and subjected to silica gel column chromatography to obtain 12.2 g of l-oxa-6-azaspiro [2.5] octane-6-carboxylic acid tert-butyl ester. 4.25 g of l-oxa-6-azaspiro- [2.5] octane-6-carboxylic acid tert-butyl ester were dissolved in 30 ml of dimethylformamide, 5.38 g of imidazole sodium were added and the mixture was stirred at 60 ° C. C for 3 h and 40 min. After cooling, ethyl acetate was added to the reaction solution and washed with water 3 times and then with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and subjected to silica gel column chromatography to obtain 4.93 g of tert-butyl 4-hydroxy-4- (1H-1-imidazolylmethyl) -1-piperidinecarboxylate. Example of Production of Intermediate 12 4-Hydroxy-4- (1H-1,2,4-triazol-1-ylmethyl) -1-piperidinecarboxylate of tert-butyl The title compound was obtained using 1, 2, 4- sodium triazole in place of imidazole sodium in the Example of production of intermediate 11. Example of production of intermediary 13 4-Fluoromethyl-4-hydroxy-1-piperidinecarboxylate benzyl 3.2 g of potassium hydrogen fluoride and 610 mg of tetra-n-butylammonium dihydrogen trifluoride were added to 5 g of l-oxa-6-azaspiro [2.5] octane-6-carboxylic acid benzyl ester and stirred at room temperature. 120 ° C for 7 h. After cooling, methylene chloride was added and filtered through Celite. The filtrate was evaporated and the resulting residue was subjected to silica gel column chromatography to obtain 4.7 g of the title compound. Example of production of intermediate 14 4-Hydroxy-4-piperidinecarboxamide hydrochloride A mixed solution of 18 ml of concentrated sulfuric acid and 1.8 ml of water at 0 ° C was cooled and 5 g of l-benzyl hydrochloride were added. 4-hydroxy-4-piperidinecarbonitrile little by little. A mixed solution of 25 ml of concentrated sulfuric acid and 2.5 ml of water was added and stirred at room temperature for 2 h. It was left overnight in a refrigerator. The reaction solution was poured onto ice and 47 g of sodium hydroxide were added little by little. It was extracted 3 times with a mixed solvent of tetrahydrofuran and ethyl acetate (1: 1). The extract was washed with brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and subjected to silica gel column chromatography to obtain 3.19 g of l-benzyl-4-hydroxy-4-piperidinecarboxamide. 3.19 g of l-benzyl-4-hydroxy-4-piperidinecarboxamide was dissolved in 150 ml of methanol and 1.5 g of 20% aqueous palladium hydroxide was added. The mixture was stirred for 4 h in a hydrogen atmosphere at a pressure of 4 atmospheres. The reaction solution was filtered through Celite and 5 ml of 4 N-dioxane HCl was added to the filtrate, which was then evaporated. The resulting crystalline residue was washed with diisopropyl ether and collected by filtration to give 1.96 g of the title compound. Example of production of intermediate 15 N- (3-Chloro-4-methoxybenzyl) -N- [4-chloro-7- (lH-1-pyrazolyl) -1-phthaladinyl] amine - 110 ml of thionyl chloride were added dropwise over 30 minutes to a mixture of 100 g of 4-fluorophthalic anhydride and 1,500 ml of methanol. The mixture was heated at reflux for 8 h and evaporated. Ice water was added to the resulting residue, which was then extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and filtered, the filtrate was evaporated to obtain 125 g of dimethyl 4-fluorophthalate, 26 g of oily sodium hydride were added in the course of 40 minutes. minutes at 200 ml of a solution of 44 g of pyrazole in 1-methyl-2-pyrrolidinone, 125 g of dimethyl 4-fluorophthalate were added over 30 minutes and the mixture was stirred at room temperature for 2 h. The reaction solution was added at 0 ° C and added to ice water, extracted with ethyl acetate and washed with saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and filtered, the filtrate was evaporated and the filtrate was evaporated. Diethyl ether was added to the resulting crystalline residue, which was then collected by filtration to obtain 77 g of dimethyl 4- (lH-1-pyrazolyl) phthalate 22. 22 ml of hydrazine monohydrate was added to a mixture of 77 g of 4- ( lH-1-pyrazolyl) dimethyl phthalate and 500 ml of ethanol and warmed efflux for 6 h After cooling, the resulting precipitates were collected by filtration to obtain 36 g of 6- (lH-1-pyrazolyl) -1,4-phthalazinedione. 15 ml of diisopropylethylamine was added to a mixture of 5.0 g of 6- (lH-1-pyrazolyl) -1,4-phthalazinedione and 20 ml of phosphorus oxychloride and the mixture was stirred at 110 ° C for 0.5. h. The reaction solution was cooled to 0 ° C, ethyl acetate was added and ice and water were added again little by little. The reaction solution was stirred at 0 ° C for 0.5 h and the insolubles were removed by filtration. The ethyl acetate layer was recovered, washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and ethyl acetate was added to the resulting crystalline residue, which was then collected by filtration to obtain 3.8 g of 1,4-dichloro-6- (lH-1-pyrazolyl) phthalazine. 14 ml of DBU was added to a mixture of 8 g of 1,4-dichloro-6- (lH-1-pyrazolyl) phthalazine, 9.5 g of 3-chloro-4-methoxybenzylamine hydrochloride and 30 ml of l-1 methyl-2-pyrrolidinone and the mixture was stirred at room temperature for 1 h. It was again stirred at 60 ° C for 3 h. The solution was cooled to 0 ° C and ethyl acetate was added, followed by washing with water and brine. It was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated. The resulting residue was purified by silica gel column chromatography, whereby 2.6 g of the title compound was obtained as a less polar compound. XH-NMR (400MHz, DMSO-d6) d: 3.80 (3H, s), 4.68 (2H, d, J = 6.0Hz), 6.70 (H, t, J = 2.0Hz) , 7.09 (HH, d, J = 8.8Hz), 7.35 (1H, dd, J = 2.0, 8.4Hz), 7.47 (HH, d, J = 2.0Hz), 7.91 (HH, d, J = 2.0Hz), 8.18 (HH, d, J = 9.2Hz), 8.32 (HH, t, J = 5.6Hz), 8.50 (HH) , dd, J = 2.0, 8.8Hz), 8.68 (ΔI, d, J = 2.4Hz), 8.78 (ΔI, d, J = 2.0Hz). Example of production of intermediate 16 N- (3-Chloro-4-methoxybenzyl) -N- [4-chloro-7- (1H-1,2,3-tria-zol-1-11) -1-phthalazinyl] amine The title compound was obtained in the same manner as in Example 15, except for the use of 1,2,3-triazole instead of pyrazole. ^ -NMR (400MHz, CD30D) d: 3.82 (3H, s), 4.72 (2H, s), 6.97 (1H, d, J = 8.4Hz), 7.34 (1H, dd) , J = 1, 6, 8,4Hz), 7,44 (HH, d, J = 1, 6Hz), 7,99 (HH, d, J = 1, 2Hz), 8,34 (HH, d, J = 8.8Hz), 8.52 (1H, dd, J = 1, 6, 8.8Hz), 8.72 (1H, d, J = 1, 2Hz), 8.81 (1H, d, J = 2Hz).

Example of intermediate production 17 6-Bromo-l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] phthalazine 96.9 ml of hydrazine monohydrate was added to a mixture of 20 g of 4-bromophthalic anhydride and 400 ml of ethanol and the mixture was heated under reflux for 8 h. After cooling, the resulting precipitates were collected by filtration to obtain 28 g of 6-bromo-1,4-phthalazinedione. ml of diisopropylethylamine was added to a mixture of 6.8 g of 6-bromo-1,4-phthalazinedione and 15 ml of phosphorus oxychloride and the mixture was heated at reflux for 1.5 h. After cooling, the reaction solution was poured into ice water, stirred well and extracted with methylene chloride. The aqueous layer was extracted with ethyl acetate. The combined extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and the resulting residue was subjected to silica gel column chromatography to obtain 4.3 g of 6-bromo-l, 4-dichlorophthalazine. 5.2 ml of DBU was added to a mixture of 3.8 g of 6-bromo-1,4-dichlorophthalazine, 3.5 g of 3-chloro-4-methoxybenzylamine hydrochloride and 30 ml of l-methyl-2 pyrrolidinone and the mixture was stirred at 100 ° C for 3 h. After cooling, water was added to the reaction solution, which was then extracted with ethyl acetate. The extract was washed with brine. It was dried over anhydrous magnesium sulfate and filtered and the filtrate was evaporated. The resulting residue was purified by silica gel column chromatography to obtain 1.8 g of the title compound as a less polar compound. Production Example of Intermediate 18 1- (1, 1-Dimethyl-2-propynyl) -4-piperidinol 24 mg of cuprous chloride and 15 mg of copper powder were added to a mixed solution of 5 ml of a solution of 7, 3 g of 4-hydroxypiperidine in diethyl ether (5 ml) and water (2.5 ml) under a nitrogen atmosphere. The mixture was cooled with ice and 2.5 ml of a solution of 2.7 ml of 3-chloro-3-methyl-1-butyne in diethyl ether was added dropwise at an overall temperature of 17 to 22 ° C. It was then stirred at room temperature overnight. Water was added and the resulting mixture was extracted with diethyl ether 5 times. The organic layers were combined and dried over potassium carbonate and then over potassium hydroxide and filtered. The filtrate was concentrated at normal pressure. The resulting crystalline residues were collected by filtration by adding ethyl acetate / hexane to obtain 2.54 g of the title compound. Production Example of Intermediate 19 1- (1,1-Dimethyl-2-propynyl) pyrrolidine The title compound was obtained from pyrrolidine and 3-chloro-3-methyl-1-butyne in the same manner as in Example intermediary production 18. Example of intermediate production 20 (2R) -l-Oxa-8-azaspiro [4.5] deca-2-ylmethanol 105.5 g of (5S) -5- (hydroxymethyl) tetrahydro-2- was dissolved furanone in 1.2 L of pyridine and 380 g of triflyl chloride were added at room temperature and the mixture was stirred at 80 ° C overnight. After completion of the reaction, the mixture was cooled, water was added, extracted with ethyl acetate and then washed with brine. The solvent was removed and the resulting residue was dissolved in 300 ml of chloroform and, after adding 600 ml of silica gel, the solvent was removed. The resulting residue was purified by silica gel column chromatography to obtain 149.3 g of (5S) -5 - [(trityloxy) methyl] tetrahydro-2-furanone. 26.9 g of (5S) -5- [(trityloxy) methyl] tetrahydro-2-furanone were dissolved in 200 ml of THF, 300 ml of a solution of 1 M vinylmagnesium bromide in THF were added at room temperature and was stirred for 1.5 h with heating at reflux. After completion of the reaction, saturated aqueous ammonium chloride was added under ice cooling, extracted with ethyl acetate and then washed twice with brine. The solvent was removed and the resulting residue was purified by silica gel column chromatography to obtain, 0 g of (2S) -1- (trityloxy) -5-vinyl-6-heptene-2,5-diol. 13.0 g of (2S) -1- (trityloxy) -5-vinyl-6-heptene-2,5-diol and 57.2 g of toluenesulfonyl chloride were dissolved in 200 ml of pyridine and stirred at 80 °. C during the night. After completion of the reaction, water was added and stirred at room temperature for 10 minutes. After extracting twice with ethyl acetate, it was washed with brine and dried over magnesium sulfate. The solvent was removed and the resulting residue was dissolved in toluene. After the solvent was removed again, the resulting residue was purified by chromatography on silica gel to obtain 5.88 g of (5R) -5 - [(trityloxy) methyl] -2,2-divinyltetrahydrofuran. 4.68 g of (5R) -5 - [(trityloxy) methyl] -2,2-divinyltetrahydrofuran, 100 ml of 0.5 M 9-BBN and 6.1 g of 9-BBN dimer in 100 ml were suspended. of THF and stirred for 30 h under heating at reflux. After cooling, 50 ml of 30% hydrogen peroxide and 50 ml of 3 N sodium hydroxide were added under cooling with ice and stirred at 50 ° C for 20 h. After completion of the reaction, the reaction solution was returned to room temperature, extracted with ethyl acetate, washed with brine and dried over magnesium sulfate. The solvent was removed and the resulting residue was purified by silica gel chromatography to obtain 2.68 g of 2- (5R) -2- (2-hydroxyethyl) -5- [(trityloxy) methyl] tetrahi-dro-2 -furanyl-l-ethanol. 2.68 g of 2- (5R) -2- (2-hydroxyethyl) -5 - [(trityloxy) methyl] tetrahydro-2-furanyl-l-ethanol and 12 ml of pyridine were dissolved in 30 ml of dichloromethane and they added 11.82 g of toluenesulfonyl chloride under cooling with ice and stirred for 2.5 h. After completion of the reaction, 30 ml of pyridine was added and then concentrated. After adding pyridine again and water cooling with ice, the mixture was stirred for 15 minutes. It was extracted with ethyl acetate, washed with brine and then dried over magnesium sulfate. The solvent was distilled off, toluene was added, the solvent was distilled again and the resulting residue was further purified by silica gel column chromatography to obtain 4-methyl-1-benzenesulfonate of 4.17 g of 2- (5R). -2- [2- [(4-Methylphenyl) sulfonyl] oxyethyl] -5- [(trityloxy) methyl] -tetrahydro-2-furanylethyl. 4.17 g of 2- (5R) -2- [2- [(4-methylphenyl) sulfonyl] oxy-ethyl] -5- [(trityloxy) methyl] tetrahydro 4-methyl-l-benzenesulfonate were dissolved. -2-furanylethyl and 5.36 g of benzylamine in 80 ml of DMF and stirred at 110 ° C for 11.5 h. After completion of the reaction, water was added and extracted with ethyl acetate and washed twice with brine and saturated aqueous sodium bicarbonate. After drying over magnesium sulfate, the solvent was removed and the resulting residue was purified by silica gel column chromatography to give 2.1 g of (2R) -8-benzyl-2- [(trityloxy) methyl] -l -oxa-8-azaspiro [4.5] decane. 2.10 g of (2R) -8-benzyl-2- [(trityloxy) methyl] -l-oxa-8-azaspiro [4.5] decane was dissolved in 20 ml of THF, 8 ml of 4 N hydrochloric acid was added. in 1,4-dioxane under cooling with ice and then stirred for 1 h. After completion of the reaction, water and saturated aqueous sodium bicarbonate were added, extracted twice with ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine and then dried over magnesium sulfate. The solvent was removed and the resulting residue was purified by silica gel column chromatography to obtain 1.03 g of [(2R) -8-benzyl-l-oxa-8-azaspiro [4.5] deca-2-yl] methanol 1.03 g of [(2R) -8-benzyl-l-oxa-8-azaspiro [4.5] deca-2-yl] methanol and 0.45 g of 10% palladium on carbon in 30 ml of ethanol were suspended and it was stirred at room temperature for 18 h in an atmosphere of hydrogen at a pressure of 1 atmosphere. The insoluble matters were removed by filtration, the solvent was removed and dried to give 0.76 g of the title compound. Intermediate example 21 800 ml of a solution of 25 was cooled, 0 g of tert-butyl 4-oxo-1-piperidinecarboxylate in diethyl ether in water / methanol and 138 ml of a solution of allylmagnesium bromide (1 M in diethyl ether) were added dropwise. The reaction mixture was stirred for 3 h and 10 min. The reaction solution was poured into a mixture of saturated aqueous ammonium chloride and ice. The diethyl ether layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the resulting residue was purified by silica gel column chromatography to obtain 15.9 g of tert-butyl 4-allyl-4-hydroxy-1-piperidinecarboxylate. 9.83 g of tert-butyl 4-allyl-4-hydroxy-l-piperidinecarboxylate were dissolved in 60 ml of tetrahydrofuran / water (9: 1), a solution (2.5% by weight, 2 ml) was added. of osmium tetraoxide in tert-butyl alcohol and 6.68 g of N-methylmorpholine N-oxide and the mixture was stirred at room temperature overnight. The reaction solution was evaporated and the resulting residue was partitioned between ethyl acetate and water, washed with brine and dried over magnesium sulfate. After filtration, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain 9.11 g of 4- (2,3-dihydroxypropyl) -4-hydroxy tert-butyl-piperidinecarboxylate. 9.11 g of 4- (2,3-dihydroxypropyl) -4-hydroxy-1-piperidinecarboxylic acid tert -butyl ester were dissolved in 40 ml of pyridine, 10.0 g of chlorotriphenylmethane were added and the mixture was stirred at room temperature. overnight. The reaction solution was partitioned between ethyl acetate and water, washed with 2N hydrochloric acid, water, saturated aqueous sodium bicarbonate and brine and dried over magnesium sulfate. After filtration, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give 10.3 g of 4- [3- (tert-butoxy) - 2-hydroxypropyl] -4-hydroxy-1-piperidinecarboxylic acid tert -butyl ester. 2.59 g of 4- [3- (tert-butoxy) -2-hydroxypropyl] -4-hydroxy-1-piperidinecarboxylic acid tert-butyl ester were dissolved in 10 ml of dimethylformamide, 400 mg of sodium hydride and 823 were added. mg of benzyl chloride and the mixture was stirred at room temperature for 20 minutes. The reaction solution was poured into ice water, extracted with ethyl acetate, washed with water and brine and dried over magnesium sulfate. After filtration, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 2.66 g of 4- [2- (benzyloxy) -3- (tert. tert-butyl-butoxy) propyl] -4-hydroxy-l-piperidinecarboxylate. 2.36 g of 4- [2- (benzyloxy) -3- (tere-butoxy) propyl] -4-hydroxy-1-piperidinecarboxylic acid tert-butyl ester were dissolved in 40 ml of acetonitrile, 426 mg of nitrate were added. cerium and ammonium and the mixture was stirred at room temperature overnight. Silica gel was added to the reaction solution and then evaporated. It was purified by adsorptive silica gel loaded on a non-adsorptive silica gel column with hexane-ethyl acetate to obtain 547 mg of 4- [2- (benzyloxy) -3-hydroxypropyl] -4-hydroxy-1- tert-butyl piperidinecarboxylate. 4.81 g of 4- [2- (benzyloxy) -3-hydroxypropyl] -4-hydroxy-1-piperidinecarboxylic acid tert-butyl ester were dissolved in 20 ml of pyridine, 2.76 g of tosyl chloride were added and The mixture was stirred at room temperature for 2 h. In addition, 1.00 g of tosyl chloride was added and the mixture was stirred at room temperature for 30 minutes and at 50 ° C for 35 minutes. The reaction mixture was partitioned between ethyl acetate and water, washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine and dried over magnesium sulfate. After filtration, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain, 72 g of 3- (benzyloxy) -l-oxa-8-azaspiro [4.5] decane-8-carboxylic acid tert-butyl ester. 6.47 g of 3- (benzyloxy) -l-oxa-8-azaspiro [4.5] decane-8-carboxylic acid tert-butyl ester were dissolved in 100 ml of tetrahydrofuran, 1.3 g of palladium on carbon were added and The mixture was stirred overnight under a hydrogen atmosphere. The catalyst was filtered from the reaction solution, 1.3 g of palladium on carbon was added and the solution was stirred overnight under a hydrogen atmosphere. The catalyst was filtered from the reaction solution, 2.6 g of palladium on carbon was added and the solution was stirred overnight under a hydrogen atmosphere at a pressure of 4.2 atmospheres. The catalyst was filtered from the reaction mixture, the solvent was evaporated and the resulting residue was purified by silica gel chromatography (ethyl acetate / methanol) to obtain 4.27 g of 3-hydroxy-1-oxa-8- azapiro [4.5] decane-8-carboxylic acid tert-butyl ester. Example of intermediary production 22 (Anti) -3-oxa-9-azabicyclo [3.3.1] nonan-7-ol hydrochloride 2.0 g of lithium aluminum hydride was suspended in 200 ml of tetrahydrofuran and a solution of 14.17 g of 9-methyl-3-oxa-9-azabicyclo [3.3.1] -nonan-7-one dissolved in 20 ml of tetrahydrofuran by dropwise cooling with ice. After stirring for 35 minutes, 2.0 ml of water, 2.0 ml of 15% aqueous sodium hydroxide and 6.0 ml of water were added to the reaction solution sequentially and the mixture was stirred at room temperature. The reaction solution was filtered and the solvent was evaporated. The resulting residue was dissolved in ethyl acetate and filtered through alumina. The solvent was evaporated to obtain 10.00 g of (anti) -9-methyl-3-oxa-9-azabicyclo [3.3.1] nonan-7-ol as yellow wax. 10.0 g of (anti) -9-methyl-3-oxa-9-azabicyclo [3.3.1] nonan-7-ol were dissolved in 100 ml of tetrahydrofuran, 10.7 ml of triethylamine, 7.2 were added. ml of acetic anhydride and 0.77 g of 4-dimethylaminopyridine and the mixture was stirred at 50 ° C overnight. The reaction solution was evaporated and the resulting residue was dissolved in ethyl acetate and filtered through alumina. The filtrate was concentrated and purified by alumina column chromatography (solvent: n-hexane / ethyl acetate) to obtain 8.68 g of (anti) -3-oxa-9-azabicyclo [3.3.1] acetate. nonan-7-yl as light yellow oil. 8.68 g of (anti) -3-oxa-9-azabicyclo [3.3.1] nonan-7-yl acetate were dissolved in 40 ml of 1,2-dichloroethane and 7.0 ml of vinyl chloroformate were added. . The mixture was stirred at room temperature for 30 minutes and then heated to reflux for 2 h and 35 minutes. The reaction solution was evaporated and purified by silica gel column chromatography (solvent: n-hexane / ethyl acetate) to obtain 8.96 g of (anti) -3-oxa-9-vinyloxycarbonyl-9 acetate. -azabicyclo- [3.3.1] nonan-7-yl as light yellow oil. 8.96 g of (anti) -3-oxa-9-vinyloxycarbonyl-9-azabicyclo [3.3.1] nonan-7-yl acetate were dissolved in 45 ml of methanol and 30 ml of water and 7.3 ml of water were added. g of potassium carbonate. The mixture was stirred at room temperature for 1 h and 30 minutes and stirred again at 50 ° C for 30 minutes. The reaction solution was evaporated, then brine was added and extracted with ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was evaporated, whereby 7.37 g of (anti) -3-oxa-9-vinyloxycarbonyl-9-azabicyclo [3.3.1] nonan-7-ol was obtained as light yellow oil. 17 ml of 4 N hydrogen chloride in dioxane were added to 7.37 g of (anti) -3-oxa-9-vinyloxycarbonyl-9-azabicyclo [3.3.1] nonan-7-ol and the mixture was stirred at room temperature. environment for 30 minutes. 40 ml of ethanol was added to the reaction solution and the mixture was heated at reflux for 1 h. The solvent was evaporated, ethyl acetate was added to the resulting residue and the resulting precipitates were collected by filtration, thereby obtaining, 55 g of the title compound in the form of white needles.

Example of intermediary production 23 (sin) -3-azabicyclo [3.2.1] octan-8-ol hydrochloride The title compound was obtained from 3-methyl-3-azabicyclo [3.2.1] octan-8- ona in the same way as in the Example of intermediary production 22. Example of production of intermediate 24 (anti) -3-oxa-7-azabicyclo [3.3.1] nonan-9-ol hydrochloride The title compound was obtained from 7-methyl-3-oxa-7-azabicyclo [3.3.1] nonan-9-one in the same manner as in Production example of intermediate 22. Example of production of intermediate 25 (anti) -9 Hydrochloride α-azabicyclo [3.3.1] nonan-3-ol The title compound was obtained from 9-methyl-9-azabicyclo [3.3.1] nonan-3-one in the same way as in Example of production of intermediate 22 Example of production of intermediate 26 (Exo) -8-azabicyclo [3.2.1] octan-3-ol hydrochloride The title compound was obtained after acetylation from (exo) -8-methyl-8- azabicyclo- [3.2.1] octan-3 - 'ol in the same manner as in Example of intermediate production 22. Example of intermediate production 27 (endo) -8-azabicyclo [3.2.1] octan-3-ol hydrochloride The title compound was obtained after acetyl - tion from. (endo) -8-methyl-8-azabicyclo- [3.2.1] octan-3-ol in the same manner as in Production example of intermediate 22. Example of intermediary production 28 (anti) -3-azabicyclohydrochloride [3.3.1] nonan-9-ol 1.0 g of lithium aluminum hydride was suspended in 100 ml of tetrahydrofuran and a solution of 7.00 g of 3-methyl-3-azabicyclo [3.3.1] nonan-9-one dissolved in 20 ml of tetrahydrofuran was added dropwise under cooling with ice. After stirring for 50 minutes, 1.0 ml of water, 1.0 ml of 15% aqueous sodium hydroxide and 3.0 ml of water were added to the reaction solution sequentially and stirred at room temperature. After filtering the reaction solution, the solvent was evaporated, whereby 7.08 g of a light yellow oil was obtained. The oil was dissolved in 90 ml of tetrahydrofuran, 9.55 ml of triethylamine was added and the mixture was then stirred under ice-cooling. 6.46 ml of acetic anhydride and 0.56 g of 4-dimethylaminopyridine were added and the mixture was stirred at room temperature for 14 h. Approximately 20 ml of methanol was added and the reaction solution was then evaporated. Aqueous potassium carbonate was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous sodium sulfate. The solvent was evaporated and the resulting residue was purified by silica gel column chromatography (solvent: n-hexane / ethyl acetate) to give 3.33 g of (anti) -3-methyl-3-azabicyclo [ 3.3.1] nonan-9-yl (a colorless oil) as a less polar compound. In addition, 2.06 g of (sin) -3-methyl-3-azabicyclo [3.3.1] nonan-9-yl acetate (a light orange oil) was obtained as a more polar compound. 2.06 g of (anti) -3-methyl-3-azabicyclo [3.3.1] nonan-9-yl acetate were dissolved in 10 ml of 1,2-dichloroethane, 2.07 ml of vinyl chloroformate was added. and the mixture was stirred at room temperature for 50 minutes. It was then heated to reflux for 5 hours and 25 minutes. The reaction solution was evaporated and water was added to the residue, which was then extracted with ethyl acetate. He washed the. organic layer with 1 N hydrochloric acid, saturated sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to obtain 2.51 g of (anti) -3-vinyloxycarbonyl-3-azabicyclo [3.3.1] nonan-9-yl acetate as a light orange oil. 4.02 g of (anti) -3-vinyloxycarbonyl-3-azabicyclo [3.3.1] nonan-9-yl acetate was dissolved in 36 ml of ethanol, 18 ml of 1 N aqueous sodium hydroxide was added and then stirred the mixture at room temperature for 1 h and 50 minutes. The reaction solution was evaporated and water was added to the resulting residue, which was then extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and then the resulting residue was purified by silica gel column chromatography (solvent: n-hexane / ethyl acetate) to obtain 3.09 g of (anti) -3-vinyloxycarbonyl-3-azabicyclo [3.3.1] nonan-9-ol as a fine yellow oil. 7 ml of a 4 N hydrogen chloride / dioxane solution was added to 3.09 g of (anti) -3-vinyloxycarbonyl-3-azabicicl [3.3.1] nonan-9-ol and the mixture was stirred at room temperature for 50 minutes. The reaction solution was evaporated and 30 ml of ethanol was added to the resulting residue, which was then heated to reflux for 50 minutes. The solvent was evaporated and then ethyl acetate was added to the resulting residue. The resulting precipitates were collected by filtration to obtain 2.41 g of the title compound as a milky white fine powder. Example of intermediate production 29 Acid salt of (sin) -3-azabicyclo [3.3.1] nonan-9-ol The title compound was obtained from (sin) -3-methyl-3-azabicyclo [3.3] .1] nonan-9-yl in the same manner as in the Example of production of intermediate 28.

Example of intermediary production 30 (anti) -2- (3-azabicyclo [3.3.1] non-9-yl) -1-ethanol hydrochloride 1.0 g of lithium aluminum hydride in 30 ml of tetrahydrofuran was suspended and 25 ml of a suspension of 3.24 g of (anti) -methyl- (3-azabicyclo [3.3.1] non-9-yl) acetate in tetrahydrofuran was added dropwise under cooling with ice. After stirring for 35 minutes, 1.0 ml of water, 1.0 ml of 15% aqueous hydroxide and 3.0 ml of water were added to the reaction solution sequentially and stirred at room temperature. The reaction solution was filtered by adding Celite and anhydrous sodium sulfate and the solvent was evaporated. The residue was dissolved in ethyl acetate, 5 ml of 4 N hydrogen chloride / ethyl acetate was added and the resulting precipitates were collected by filtration to obtain 2.29 g of the title compound as a white powder. Example of intermediate production 31 l-Chloro-4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecar-bonitrile XH-NMR (400MHz, DMSO-d6) d: 2.10 (3H, s) 3.73 (3H, s), 4.64 (2H, d, J = 5.4Hz), 6.85 (IH, d, J = 8.0Hz), 7.17-7.21 (2H, m), 8.15 (IH, d, J = 8.6Hz), 8.31 (ÍH, dd, J = 8.6, 1.2Hz), 8.35 (ÍH, t, J = 5,4Hz), 9,00 (ÍH, d, J = 1, 2Hz). Example 1 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-1- (3-pyridyl) phthalazine dihydrochloride ml of a solution (1.6 M) of n-butyllithium in hexane were added dropwise to 50 ml of a solution of 2.53 g of 3-bromopyridine in anhydrous diethyl ether at -70 ° C or less. us and stirred for 30 minutes. 10 ml of a solution of 5.21 g of tri-n-butyltin chloride in anhydrous diethyl ether was added to the resulting mixture. The reaction solution was returned to room temperature over 1 h. The reaction solution was poured into brine and the organic layer was washed with brine. It was dried over anhydrous magnesium sulfate and then evaporated to obtain 3- (1,1,1-tri-n-butylstannyl) pyridine as a yellow oil. A mixture of 1.80 g of 1-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine, 579 mg of tetrakis (triphenylphosphine) palladium, 25 ml of xylene and 3 ml of liter was stirred vigorously. methyl-2-pyrrolidone and heated to reflux and 25 ml of a solution of the 3- (1,1,1-tri-n-butylstannyl) pyridine obtained above in xylene were added dropwise over 1 h. The reaction solution was re-heated to reflux for 15 minutes. The reaction solution was returned to room temperature, washed 3 times with water and once with brine. It was purified by silica gel column chromatography to obtain a coupled product. It was suspended in a mixed solvent of tetrahydrofuran and methanol, then a solution of 4 N hydrochloric acid / ethyl acetate was added and the mixture was evaporated. The resulting product was recrystallized with ethyl acetate / methanol to obtain 1.80 g of the title compound as a colorless powder. MASS (ESI): 402.0 (MH +). 1H-NR (400MHz, DMSO-d6) d: 3.85 (3H, s), 4.06 (2H, broad), 4.89 (2H, broad), 7.18 (ÍH, d, J = 8 , 0Hz), 7.53 (HH, dd, J = 8.0, 1.2Hz), 7.67 (HH, d, J = 1, 2Hz), 7.81-7.90 (HH, m) , 8.07 (HH, dd, J = 8.8, 0.4Hz), 8.38-8.45 (HH, m), 8.46 (1H, dd, J = 8.8, 1.4Hz ), 8.90-9.00 (2H, m), 9.57 (1H, dd, J = 1, 4, 0.4Hz), 10.76 (1H, broad). Example 2 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-1- (2-pyridyl) phthalazine dihydrochloride The title compound was obtained in the same manner as in Example 1, except for the use of 2-bromopyridine instead of 3-bromopyridine. MASS (ESI): 402.0 (MH +). XH-NMR (400MHz, DMSO-d6) d: 3.83 (3H, s), 4.86-4.90 (2H, m), 7.16 (1H, d, J = 8.6Hz), 7 , 52 (ÍH, dd, J = 8.6, 2.1Hz), 7.63-7.69 (2H, m 7.97 (HH, d, J = 8.5Hz, 08-8.13 (HH) , m 8.47 (HH, dd, J = 8.5, 1.4Hz), 8.72-8.83 (2H, m), 9.56 (HH, d, J = 1, 4Hz), 10.82 -10.92 (ÍH, m). Example 3 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-1- (4-cyanopiperidino) phthalazine hydrochloride A mixture of 15 g of 4-piperidinecarboxamide, 16.3 g of benzyl chloride, was stirred., 3 g of potassium carbonate and 200 ml of N, N-dimethylformamide at 80 ° C for 4 h. The reaction solution was returned to room temperature and aqueous sodium hydroxide was added and then extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and then evaporated. The resulting crystalline residue was washed with hexane / ethyl acetate and collected by filtration. 12.7 g of l-benzyl-4-piperidinecarboxamide were obtained in the form of white scaly crystals. 5 ml of N, N-dimethylformamide was added to a mixture of 12.7 g of l-benzyl-4-piperidinecarboxamide and 60 ml of phosphorus oxychloride under cooling with ice and stirred at room temperature for 1.5 h. Evaporated and the resulting residue was dissolved in ethyl acetate and washed with aqueous sodium hydroxide and brine. After drying over anhydrous sodium sulfate, it was evaporated and the resulting residue was purified by silica gel column chromatography to obtain 11.0 g of l-benzyl-4-piperidinecarbonitrile. 11.0 g of l-benzyl-4-piperidinecarbonitrile were dissolved in 100 ml of 1,2-dichloroethane and 7.1 ml of 1-chloroethyl chloroformate were added under ice-cooling. The mixture was stirred at room temperature for 15 minutes and then heated to reflux for 1 h and 20 minutes. After evaporation, 50 ml of methanol was added and heated to reflux for 1 h. The reaction solution was evaporated and the crystalline residue was washed with ethyl acetate and collected by filtration to obtain 8.0 g of 4-piperidinecarbonitrile hydrochloride as white crystals. A mixture of 1.2 g of the resulting 4-piperidinecarbonitrile hydrochloride, 1.0 g of l-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine, 1.8 g of diol was stirred. sopropylethylamine and 10 ml of l-methyl-2-pyrrolidone at 170 ° C for 2 h and 30 minutes. After cooling, ethyl acetate was added to the reaction solution, which was then washed with water and brine. After drying over anhydrous sodium sulfate, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography. The resulting free compound was dissolved in ethyl acetate, then a solution of 4 N hydrochloric acid / ethyl acetate was added and the resulting crystals were collected by filtration to obtain 880 mg of the title compound as a yellow powder. MASS (ESI): 433.2 (MH +). ^ -NMR (400MHz, DMS0-d6) d: 1.98-2.17 (4H, m), 3.10-3.33 (5H, m), 3.86 (3H, s), 4.70 -4.74 (2H, m), 7.17 (HH, d, J = 8.4Hz), 7.45 (HH, dd, J = 8.4, 2.0Hz), 7.61 (HH, d, J = 2.0Hz), 8.27 (HH, d, J = 8.4Hz), 8.47 (HH, dd, J = 8.4, 0.8Hz), 9.34-9.38 (ÍH, m), 10.28 (1H, broad).

Example 4 4- (3-Chloro-4-methoxyphenethyl) amino-6-cyano-1- (4-cyanopiperidino) phthalazine hydrochloride The title compound was obtained using l-chloro-4- (3-chloro-4-methoxyphenethyl) amino-6-cyanophthalazine in place of 1-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine in Example 3. MASS (ESI): 447.1 (MH +). XH-NMR (400MHz, DMSO-d6) d 1.97-2.18 (4H, m), 2.94-3.00 (2H, m), 3.11-3.23 (3H, m) 3 , 33-3.40 (2H, m), 3.72-3.80 (2H, m), 3.82 (3H, s), 7.09 ÜH, d, J = 8.4Hz), 7, 27 (HH, dd, J = 8.4, 2.0Hz), 7.44 (HH, d, J = 2.0Hz), 8.28 (HH, d, J = 8.4Hz), 8.47 (HH, dd, J = 8.4, 0.8Hz), 9.23-9.28 (HH, m), 9.85 (HH, broad).

Example 5 1- (4-aminopiperidino) -4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine dihydrochloride .0 g of l-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine were dissolved in 50 ml of l-methyl-2-pyrrolidone, then 43.32 g of 4-hydroxypiperidine were added. and 10 ml of diisopropylethylamine and the mixture was heated at 170 ° C for 8 h. After cooling, ethyl acetate was added and the mixture was washed 3 times with water and once with brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated. The resulting residue was purified by silica gel column chromatography to obtain 10.1 g of 1- (4-hydroxypiperidino) -4- (3-chloro-4-methoxybenzyl) amino-6-cyano-n-phthalazine as yellow crystals. 30 ml of a solution of 3.48 g of diethyl azodicarboxylate in tetrahydrofuran was then added to 100 ml of a solution of 4.2 g of 1- (4-hydroxypiperidino) -4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine, 2.94 g of phthalimide and 5.24 g of triphenylphosphine in tetrahydrofuran over 30 minutes under ice-cooling and then stirred at 4 ° C for 24 h. The reaction solution was evaporated, water and ethyl acetate were added and insolubles were removed by filtration. The organic layer was concentrated and the resulting residue was purified by silica gel column chromatography to obtain 4.85 g of 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (4-phthalimidopiperidino) phthalazine A mixture of 4.85 g of the resulting 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (4-phthalimidopiperi-dione) phthalazine, 4 ml of hydrazine monohydrate and 40 ml of ethanol was heated. reflux for 1 h. The reaction solution was evaporated, dissolved in ethyl acetate and 1N hydrochloric acid was added thereto to adjust its pH to 3 and insolubles were removed by filtration. The aqueous layer of the filtrate was adjusted to pH 11 with 1 N sodium hydroxide and then extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, evaporated and then purified by silica gel column chromatography. The resulting product was suspended in ethanol / water, then 1N aqueous hydrochloric acid was added and dissolved by heating. After cooling, the resulting crystals were collected by filtration to obtain 440 mg of the title compound as a yellow powder. MASS ("FAB"): 423 (MH +). ^ -NMR (400MHz, DMSO-d6) d: 1.78-1.92 (2H, m), 2.03-2.11 (2H, m), 2.90-3.0 (2H, m) , 3.20-3.34 (HH, m), 3.54-3.63 (2H, m), 3.82 (3H, s), 4.70 (2H, d, J = 5.6Hz) , 7.13 (HH, d, J = 8.4Hz), 7.47 (HH, dd, J = 8.4, 2.0Hz), 7.62 (HH, d, J = 2.0Hz), 8.17 (HH, d, J = 8.4Hz), 8.35-8.45 (2H, m), 8.47 (HH, dd, J = 8.4, 1.0Hz), 9.54 (ÍH, d, J = l, 0Hz), 10.63 (ÍH, broad).

Example 6 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-l- [4-hydroxy-4- (hydroxymethyl) piperidino] phthalazine hydrochloride 7.9 g of 60% sodium hydride was washed with hexane, followed by drying under reduced pressure. 100 ml of dimethyl sulfoxide was added and stirred at 80 to 100 ° C for 30 minutes in a nitrogen atmosphere. It was cooled with ice and 180 ml of tetrahydrofuran was added. 150 ml of a solution of 4.37 g of trimethyl sulfonium iodide in dimethyl sulfoxide was added dropwise. After stirring the mixture for 30 minutes cooling with ice, 15 g of l-benzyl-4-piperidone was added, stirred for 30 minutes under ice cooling and then stirred at room temperature for 6 h. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. It was purified by chromatography on silica gel to obtain 6.8 g of 6-benzyl-l-oxo-6-azaspiro [2.5] octane. 100 ml of water and 10 ml of perchloric acid were added to 100 ml of a solution of 6.8 g of this 6-benzyl-l-oxo-6-azaspiro [2.5] octane in tetrahydrofuran and the mixture was stirred at room temperature for 7 h. The mixture was cooled with ice and aqueous sodium carbonate was added to adjust the pH thereof to 7 and the mixture was then evaporated. Ethyl acetate was added to the residue and the insolubles were removed by filtration. The filtrate was evaporated and then purified by silica gel column chromatography to give 4 g of l-benzyl: -4- (hydroxymethyl) -4-piperidinol. Then 1.46 g of l-benzyl-4- (hydroxymethyl) -4-piperidinol were dissolved in 30 ml of methanol, 10 ml of acetic acid and Pd 10% -C were added and then hydrogenated at a pressure of 4 atmospheres . The reaction solution was filtered through Celite and the filtrate was evaporated and dissolved in methanol. 4N Hydrochloric acid / ethyl acetate was added and then concentrated. The resulting crystals were crystallized with methanol / ethyl acetate by filtration to give 880 mg of 4- (hydroxymethyl) -4-piperidinol hydrochloride. The resulting 4- (hydroxymethyl) -4-piperidinol hydrochloride was reacted with l-chloro-4- (3-chloro-4-methoxybenzyl) amino-6-cyanophthalazine in the same manner as in Example 4 to obtain the Title. MASS (FAB): 454.2 (MH +). XH-NMR (400MHz, DMSO-d6) d: 1.46-1.54 (2H, m), 1.82-1.94 (2H, m), 3.16-3.30 (6H, m), 3.84 (3H, s), 4.68-4.72 (2H, m), 7.15 (H, d, J) = 8.6Hz), 7.44 (IH, dd, J = 8.6, 2.0Hz), 7.59 (1H, d, J = 2.0Hz), 8.22 (IH, d, J = 8.6Hz), 8.45 (HH, dd, J = 8.6, 1.0Hz), 9.36 (HH, d, J = 1, 0Hz).

Example 7 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-l- [(2S) -2- (methoxymethyl) pyrrolidino] phthalazine hydrochloride The title compound was obtained using (S) -2-methoxymethylpyrrolidine in place of (R) - (+) - 3-hydroxypiperidine hydrochloride in Production Example 1. MASS (ESI): 438.1 (MH +). 1 H-NMR (400MHz, DMSO-d 6) d: 1.81-1.89 (2H, m), 1.95-2.03 (1H, m), 2.15-2.24 (HH, m), 3.16 (3H, 3.28-3.37 (HH, m), 3.46-3.58 (2H, m) , 3.84 (3H, s), 3.87-3.98 (ÍH, m), 4.44-4.57 (HH, m), 4.62-4.78 (2H, m), 7.15 (HH, d, J = 8.6Hz), 7.47 (HH, dd, J = 8.6, 0.4Hz), 7.61 (IH, d, J = 0.4Hz), 8.41-8.51 (2H, m), 9.42-9.60 (HH, m), 10.50 (1H, broad), 13.79 (HH, broad) . Example 8 4- (3-Chloro-4-methoxybenzyl) amino-6-cyano-l-phenylphthalazine hydrochloride The title compound was obtained in the same manner as in Production Example 10, except for the use of phenylboronic acid instead of methoxyphenylboronic acid. MASS (ESI): 401.1 (MH +). XH-NMR (400MHz, DMSO-d6) d: 3.84 (3H, s), 4.81-4.85 (2H, m), 7.15 (1H, d, J = 8.6Hz), 7 , 48 (ÍH, dd, J = 8.6, 2.1Hz), 7.60-7.66 (6H, m) 00 (ÍH, d, J = 8.6Hz] 41 (ÍH, dd, J = 8.6 0.9Hz), 9.42 (ÍH, d, J = 0.9Hz). Example 9 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (2-hydroxy-7-azaspiro [3.5] non-7-yl) -6-phthalazinecarbonitrile hydrochloride 47.2 g of methyl toluene phospho-nium bromide and 21.9 g of tert-butyl 4-oxo-l-piperidinecarboxylate were added to a mixture of 14.8 g of tert-butoxy-potassium and 300 ml of tetrahydrofuran and stirred for 40 minutes at room temperature. The reaction solution was evaporated, diethyl ether was added and then filtered through Celite. The filtrate was washed with water and brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the resulting residue was subjected to silica gel column chromatography to obtain 20.8 g of tert-butyl 4-methylene-1-piperidinecarboxylate. 49.3 g of tert-butyl 4-methylene-l-piperidinecarboxylate were added to a mixture of 157.2 g of zinc-copper alloy and 500 ml of diethyl ether and 900 ml of a solution of 181.8 was added. g of trichloroacetyl chloride in dimethoxyethane by dripping over 5.5 hours. After stirring for 30 minutes, the reaction solution was cooled and saturated aqueous sodium bicarbonate was added at 0 ° C or less. The mixture was filtered through Celite and evaporated. The resulting residue was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and the resulting residue was subjected to silica gel column chromatography to obtain 62.5 g of 1,1-dichloro-2-oxo-7-azaspiro [3.5] nonane-7-carboxylate of tert. -butyl. 106.1 g of zinc powder were added to a mixture of 62.5 g of 1,1-dichloro-2-oxo-7-azaspiro [3.5] nonane-7-carboxylic acid tert-butyl ester and 500 ml of sodium chloride. ammonium saturated in methanol. The mixture was stirred for 1 h and 20 minutes at room temperature and filtered through Ce-lite. The filtrate was evaporated, 1N hydrochloric acid / ethyl acetate was added and the organic layer was recovered. The extract was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and the resulting residue was subjected to silica gel column chromatography to obtain 38.9 g of tert-butyl 2-oxo-7-azaspiro [3.5] nonane-7-carboxylate. 300 ml of ethanol were cooled with ice and 6.13 g of sodium borohydride were dissolved in it. 100 ml of a solution of 38.9 g of 2-oxo-7-azaspiro [3.5] nonane-7-carboxylic acid tert-butyl ester in ethanol was added dropwise over 25 minutes. The reaction solution was treated with saturated aqueous ammonium chloride and evaporated. The resulting residue was partitioned between ethyl acetate and water and the ethyl acetate layer was washed with brine and dried over magnesium sulfate. After the filtrationThe solvent was evaporated and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 36.6 g of 2-hydroxy-7-azaspiro [3.5] nonane-7-carboxylate of tert. -butyl. ^ • H-NMR (400MHz, CDCl3) d: 1.45 (9H, s), 1.43-1.57 (4H, m), 1.65-1.72 (2H, m), 3.27 -3.35 (4H, m), 4.32 (HH, quint., J = 7.2Hz). 6.22 g of tert-butyl 2-hydroxy-7-azaspiro [3.5] nonane-7-carboxylate were dissolved in 20 ml of tetrahydrofuran and 80 ml of a 4 N hydrogen chloride / dioxane solution was added to the solution resulting and was then stirred at room temperature for 1 h. The reaction solution was evaporated and the resulting residue was dissolved in 20 ml of l-methyl-2-pyrrolidinone, 4.67 g of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] - were added. 6-phthalazinecarbonitrile and 6.72 g of diisopropylethylamine and then stirred at 160 ° C for 9 hours. The reaction solution was returned to room temperature and partitioned between ethyl acetate and water and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layers were combined and washed with water (5 times) and with brine sequentially and dried over magnesium sulfate. After filtration, the solvent was evaporated and the resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) and the (ethyl acetate / methanol) were triturated and the resulting crude crystals were triturated and washed with diethyl ether to obtain 4.86 g of yellow crystals. The resulting product was dissolved in 150 ml of ethanol, 15 ml of a 4 N hydrogen chloride / dioxane solution was added and the solvent was evaporated. The resulting residue was dissolved in 150 ml of ethanol, heated to 80 ° C and seeded with separately synthesized crystals in aqueous ethanol and, when crystallization started, the heating stopped. After cooling to room temperature at room temperature, collection was carried out by filtration and washing with ethanol to obtain 4.35 g of the title compound. XH-NMR (400MHz, DMSO-d6) d: 1.58-1.66 (2H, m), 1.68-1.76 (4H, m), 2.14-2.22 (2H, m 3.05-3.16 (4H, m), 3.83 (3H, s), 4.12 (1H, t, J = 7 , 2Hz), 4.72 (2H, d, J = 5.6Hz), 7.14 (IH, d, J = 8.8Hz), 7.45 (IH, dd, J = 8.8, 2, 0Hz), 7.60 (ÍH, d, J = 2.0Hz), 8.20 (HH, d, J = 8.4Hz), 8.44 (HH, dd, J = 8.4, 1.2Hz), 9.46 (ÍH, s). Example 10 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-pyridyl) -6-phthalazinecarbonitrile The title compound was obtained in the same manner as in Example 1.

XH-NMR (400MHz, DMSO-d6) d: 3.80 (3H, s), 4.76 (2H, d, J = 5.5Hz), 7.10 (HI, d, J = 8.8Hz) , 7.38 (HH, dd, J = 8.8, 2.4Hz), 7.50 (HH, d, J = 2.4Hz), 7.64 (2H, d, J = 5.6Hz), 7.94 (1H, d, J = 8.8Hz), 8.20 (IH, d, J = 8.8Hz), 8.52 (IH, dd, J = 5.5, 5.5Hz), 8 , 73 (2H, d, J = 5.6Hz), 9.02 (ÍH, s).

EXAMPLE 11 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (3-oxo-2-oxa-8-azas-pyro [4.5] decen-8-yl) -6-phthalazinecarbonitrile 567 ml of a solution of 37.8 g of tert-butyl 2-oxo-7-azaspiro [3.5] nonane-7-carboxylate in chilled methanol in ice water were cooled and 43 g of 30% aqueous hydrogen peroxide were added. by drip 63 ml of 1 N aqueous sodium hydroxide were added dropwise and the mixture was stirred at room temperature for 2 h. 1000 ml of ethyl acetate, 600 ml of water and 100 ml of sodium thiosulfate were added saturated aqueous pentahydrate and the organic layer was recovered. The extracted solution was washed with brine, dried over anhydrous magnesium sulfate and filtered off. The filtrate was evaporated to obtain 28.4 g of 3-oxo-2-oxa-8-azaspiro [4.5] decane-8-carboxylic acid tert-butyl ester. 1.16 g of 3-oxo-2-oxa-8-azaspiro [4.5] decane-8-carboxylic acid tert-butyl ester were dissolved in 2.3 ml of methanol, 4.6 ml of 4 N hydrochloric acid / ethyl acetate and the mixture was stirred at room temperature for 1 h. 5 ml of ethyl acetate were added and the resulting crystals were collected by filtration to obtain 700 mg of 3-oxo-2-oxa-8-azaspiro [4.5] decane hydrochloride. A mixture of 657 mg of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile, 700 mg of 3-oxo-2-oxa-8-azaspiro hydrochloride [4.5] was stirred. de-Can, 0.44 ml of diethylaniline, 137 mg of sodium iodide and 1.7 ml of 1-methyl-2-pyrrolidinone at 130 ° C for 15 h and 40 minutes. After cooling, the reaction solution was diluted with 40 ml of tetrahydrofuran, 100 ml of ethyl acetate and 15 ml of 1-methyl-2-pyrrolidinone and then washed with saturated aqueous sodium bicarbonate and brine. It was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the resulting residue was purified by silica gel column chromatography to obtain 713 mg of 4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-oxo-2-oxa-8). -azaspiro- [4.5] de-cen-8-yl) -6-phthalazinecarbonitrile. XH-NMR (400MHz, CDC13) d: 1.88-2.01 (4H, m), 2.53 (2H, s), 3.22-3.40 (4H, m), 3.90 (3H , s), 4.20 (2H, s), 4.77 (2H, d, J = 5.2Hz), 5.20 (IH, t, J = 5.2Hz), 6.92 (IH, d , J = 8.4Hz), 7.32 (HH, dd, J = 8.4, 2.0Hz), 7.46 (HH, d, J = 2.0Hz), 7.96 (1H, dd, J = 8.4, 2.0Hz), 8.11 (HH, d, J = 8.4Hz), 8.14 (HH, d, J = 0.8Hz). Example 12 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (2-oxo-7-azaspiro- [3.5] non-7-yl) -6-phthalazinecarbonitrile 500 mg of 4- [(3-chloro-4-methoxybenzyl) amino] -1- (2-hydroxy-7-azaspiro [3.5] non-7-yl) -6-phthalazinecarbonitrile in 20 ml of dichloromethane was suspended and ml of tetrahydrofuran, then 690 mg of 1,1,1-triacetoxy-1,1-dihydro-1,2-benzyodoxsool-3 (1H) -one was added and the mixture was stirred at room temperature for 15 minutes. Ethyl acetate, 30 ml of saturated aqueous sodium bicarbonate and 2 ml of saturated aqueous sodium thiosulfate • 5H20 were added. The organic layer was recovered and the aqueous layer was extracted with ethyl acetate. The extracted solutions were combined, washed with brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the resulting residue was purified by silica gel column chromatography, crystallized from ethanol and the resulting crystals were collected by filtration by adding hexane, to obtain 420 mg of 4 - [(3-chloro-4-methoxybenzyl. ) amino] -1- (2-oxo-7-azaspiro [3.5] non-7-yl) -6-phthalazinecarbonitri-lo. XH-NMR (400MHz, DMS0-d6) d: 1.90 (4H, m), 2.86 (4H, m), 3.09 (4H, s), 3.80 (3H, s), 4, 62 (2H, d, J = 5,6Hz), 7,07 (ÍH, d, J = 8,5Hz), 7,33 (ÍH, d, J = 8,5Hz), 7,44 (ÍH, s ), 7.89 (HH, t, J = 5.6Hz), 8.09 (HH, d, J = 8.0Hz), 8.19 (1H, d, J = 8.0Hz), 8.88 (1H, s).

Example 13 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4-hydroxy-4- (lH-1-imidazolylmethyl) piperidino] -6-phthalazinecarbonitrile dihydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.49 (2H, d, J = 12.4Hz), 1.82-1.93 (2H, m), 3.13 (2H, t, J = 10.8Hz), 3.37 (2H, d, J = 12.4Hz), 3.82 (3H, s), 4.30 (2H, s), 4.74 (2H, d, J = 5, 6Hz), 7.13 (1H, d, J = 8.8Hz), 7.48 (IH, dd, J = 2.0, 8.4Hz), 7.63 (1H, d, J = 2.0Hz ), 7.66-7.71 (2H, m), 8.18 (HH, d, J = 8.4Hz), 8.48 (HH, d, J = 8.4Hz), 9.10 (HH) , s), 9.60 (ÍH, s).

Example 14 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4-hydroxy-4- (1H-1,2,4-triazol-1-ylmethyl) piperidino] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMS0-d6) d: 1.54 (2H, d, J = 12.8Hz), 1.82-1.92 (2H, m), 3.15 (2H, t, J = ll, 2Hz), 3.35 (2H, d, J = 12.8Hz), 3.82 (3H, s), 4.29 (2H, s), 4.73 (2H, d, J = 6, 0Hz), 7.13 (HH, d, J = 8.4Hz), 7.48 (HH, dd, J = 2.0, 8.4Hz), 7.62 (HH, d, J = 2.0Hz ), 8.20 (HH, d, J = 8.4Hz), 8.21 (1H, s), 8.45 (HH, dd, J = 1, 2, 8.4Hz), 8.79 (HH) , s), 9.56 (H, s), 10.75 (H, broad).

Example 15 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (1 H-1,2,3,4-tetrazol-5-yl) -1-phthalazinyl] -4-piperidinol 0.55 g of sodium azide was added to a mixture of 1.0 g of 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazinecarbonitrile, 1.2 g of triethylamine hydrochloride and 20 ml of l-methyl-2-pyrrolidinone and stirred at 100 ° C for 8 h. The reaction solution was returned to room temperature, water was added and the resulting crystals were collected by filtration to obtain 1.0 g of the title compound. 1H-NMR (400MHz, DMS0-d6) d: 1.58-1.7 (2H, m), 1.8-1.97 (2H, m), 2.8-2.98 (2H, m) , 3.3-3.43 (2H, m), 3.6-3.7 (HH, m), 3.79 (3H, s), 4.6 (2H, s), 7.06 (HH) , d, J = 8Hz), 7.34 (IH, d, J = 8Hz), 7.45 (IH, s), 7.95 (IH, d, J = 8Hz), 8.45 (1H, d , J = 8Hz), 8, 89 (ÍH, s). Example 16 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (1-methyl-1 H-1, 2, 3, 4-tetrazol-5-yl) -1-phthalazinyl] -4 -piperidinol 0.037 ml of methyl iodide was added to a mixture of 0.25 g of 1- [4- [(3-chloro-4-methoxybenzyl) -amino] -6- (1 H-1,2,3,4-tetrazole) -5-yl) -1-phthalazinyl] -4-pipe-ridinol, 1.2 g of potassium carbonate and 5 ml of dimethylformamide and was stirred at room temperature for 3 h. Water was added to the reaction solution and the precipitated insoluble matters were collected by filtration. It was then purified by silica gel column chromatography to obtain 50 mg of the title compound. XH-NMR (400MHz, DMS0-d6) d: 1.6-1.7 (2H, m), 1.85-1.95 (2H, m), 2.85-2.95 (2H, m) , 3.25-3.45 (2H, m), 3.6-3.7 (HH, m), 3.80 (3H, s), 4.48 (3H, s), 4.61 (2H , d, J = 5.6Hz), 4.73 (ΔI, d, J = 4.0Hz), 7.07 (ΔI, d, J = 8.4Hz), 7.34 (ΔI, dd, J = 2.0, 8.4Hz), 7.44 (IH, d, J = 2.0Hz), 8.07 (IH, t, J = 5.6Hz), 8.10 (IH, d, J = 8 , 4Hz), 8.47 (1H, d, J = 8.8Hz), 9.00 (ÍH, s). Example 17 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidi-no) -6-phthalazinecarbomethyl 3.7 ml of diethyl dithiophosphate was added to a mixture of 2.0 g of 4- [(3-chloro-4-methoxybenzyl) amino] -1- (hydroxypiperidino) -6-phthalazinecarbonitrile, 1 ml of water and 2 ml of isopropanol and the mixture was heated at reflux for 1 h. After cooling, water was added to the reaction solution and the resulting crystals were collected by filtration. The filtrate was extracted with ethyl acetate and washed with brine. It was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated and the resulting crystalline residue was combined with the crystals collected above by filtration, thereby obtaining 1.5 g of the title compound. XH-NMR (400MHz, DMS0-d6) 5: 1.6-1.7 (2H, m), 1.85-2.00 (2H, m), 2.90-3.1 (2H, m) , 3.3-3.5 (2H, m), 3.6-3.8 (HH, m), 3.81 (3H, s), 4.68 (2H, d, J = 4Hz), 7 , 13 (ÍH, d, J = 8Hz), 7.40 (1H, d, J = 8Hz), 7.54 (ÍH, s), 8.08 (1H, d, J = 8Hz), 8.3 -8.4 (HH, m), 8.9-9.1 (HH, m), 9.88 (HH, s), 10.33 (HH, s). Example 18 1- [4- [(3-Bromo-4-methoxybenzyl) amino] -6- (4-methyl-1,3-thia-zol-2-yl) -1-phthalazinyl] -4-piperidinol 1.5 g of 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazine-carbodii were dissolved in 50 ml of dimethylformamide, 1.1 ml of chloroacetone was added. and the mixture was stirred at 100 ° C for 4 h. After cooling, the reaction solution was added to water and the aqueous layer was separated by decantation. The residue was dried under reduced pressure and then purified by chromatography on silica gel to obtain 200 mg of the title compound. XH-NMR (400MHz, DMS0-d6) d: 1.6-1.7 (2H, m), 1.85-1.95 (2H, m), 2.47 (3H, s), 2.83 -2.94 (2H, m), 3.3-3.4 (2H, m), 3.6-3.7 (ÍH, m), 3.80 (3H, s), 4.63 (2H , d, J = 5.6Hz), 4.72 (ΔI, d, J = 4.0Hz), 7.07 (ΔI, d, J = 8.4Hz), 7.34 (ΔI, dd, J = 2.0, 8.4Hz), 7.44 (IH, d, J = 2.0Hz), 7.48 (IH, s), 7.96-8.04 (IH,), 8.01 (1H) , d, J = 8.4Hz), 8.36 (HH, dd, J = 1, 6, 8.4Hz), 8.76 (HH, d, J = 1, 6Hz).

Example 19 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (2-thienyl) -1-phthalazinyl] -4-piperidinol hydrochloride 24 mg of tetrakis (triphenylphosphine) palladium (0) and 1.4 ml of 2- (tributylstannyl) thiophene were added to a mixture of 200 mg of 1- [6-bromo-4- [(3-bromo-4-methoxybenzyl) ) amino] -1-phthalazinyl] -4-piperidinol and 2 ml of toluene. The mixture was heated at reflux for 2 h. After cooling, the reaction solution was poured into ice water and extracted with ethyl acetate. The extracted solution was dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the residue was purified by chromatography on silica gel. The resulting product was converted by means of 4 N hydrochloric acid / ethyl acetate in the hydrochloride, to obtain 73 mg of the title compound. XH-NMR (400MHz, DMSO-d6) d: 1.67 (2H, m), 1.92 (2H, m), 3.00 (2H, m), 3.45 (2H, m), 3, 74 (HH, m), 3.82 (3H, s), 4.73 (2H, m), 7.13 (HH, d, J = 7.2Hz), 7.27 (HH, s), 7 , 46 (HH, d, J = 7.2Hz), 7.61 (HH, s), 7.79 (HH, d, J = 5.6Hz), 8.03 (HH, d, J = 5, 6Hz), 8.09 (ÍH, d, J = 8.8Hz), 8.34 (1H, d, J = 8.8Hz), 9.20 (1H, broad s).

Example 20 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hi-droxipiperidino) -6-phthalazinecarbaldehyde oxime hydrochloride .0 g of 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazine-carbonitrile and 5.3 g of t-butyldimethylchlorosilane were dissolved in 80 ml of dimethylformamide and 4.8 g of imidazole were added. The mixture was stirred at room temperature overnight. Ethyl acetate was added to the reaction solution, which was then washed once with water and twice with brine. The mixture was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to obtain 11.7 g of 1- [4- [[1- (tert-butyl) -1,1-dimethylsilyl] oxy] piperidino] -4- [(3-chloro-4-methoxybenzyl) ) aiaino] -6-phthalazinecarbonitrile. 11.7 g of 1- [4- [[1- (tert-butyl) -1,1-dimethylsilyl] oxy] piperidino] -4- [(3-chloro-4-methoxybenzyl) amino] -6- were dissolved. phthalazinecarbonitrile in 150 ml of methylene chloride and cooled. 44 ml of a 1 M hydrogenated diisobutylaluminum solution in toluene was added at -78 ° C. After returning it to room temperature, the mixture was stirred overnight. 100 ml of saturated aqueous ammonium chloride were added and the mixture was stirred at room temperature for 0.5 h. After adding 40 ml of 10% sulfuric acid, it was extracted with ethyl acetate. The extracted solution was washed with brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the residue was purified by silica gel column chromatography to obtain 5.3 g of 1- [4- [titere-butyl) -1,1-dimethylsilyl] oxy] piperidino] -4 - [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbaldehyde. 1.5 g of 1- [4- [[1- (tert-butyl) -1,1-di-ethylsilyl] oxy] piperidino] -4- [(3-chloro-4-methoxybenzyl) amino] -6 was dissolved -ftalazinecarbaldehyde and 0.35 g of hydroxylamine hydrochloride in 50 ml of methanol and the mixture was heated at reflux for 2 h. After cooling, water was added, which was extracted with ethyl acetate. The extracted solution was washed with brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the residue was purified by silica gel column chromatography, to obtain 1.18 g of l- [4 - [[1- (tert -butyl) -1,1-dimethylsilyl] oxy] phenyl. peridino] -4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazine-carbaldehyde oxime. A 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran was added to 30 ml of a solution of 1.18 g of 1- [4- [[1- (tert-butyl) -1,1-dimethylsilyl] oxy] piperidino ] -4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbaldehyde oxime in tetrahydrofuran. The mixture was stirred at room temperature overnight. Water was added to the reaction solution, which was then extracted with ethyl acetate. The extracted solution was washed with brine, dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated and the resulting crystalline residue was washed with ethyl acetate and collected by filtration to obtain 0.34 g of the title compound. This product was converted in a usual way to the hydrochloride.

XH-NMR (400MHz, DMSO-d6) d: 1.58-1.70 (2H, m 1.86-1.95 (2H, m), 2.92-3.02 (2H, m), 3.08-3.22 (2H, m), 3.64-3.73 (HI, m), 3.82 (3H , s), 4.61-4.68 (2H, m), 4.77-4.79 (HH, m), 7.10 (HH, d, J = 8Hz), 7.38 (HH, d , J = 8Hz), 7.51 (ÍH, s), 8.06 (1H, d, J = 8Hz), 8.23 (HH, d, J = 8Hz), 8.28 (HH, s), 8, 69-8.76 (1H, m). Example 21 4- [(3-Chloro-4-methoxybenzyl) amino] -1 - [(2R) -2- (hydroxymethyl) -l-oxa-8-azaspiro [4.5] decan-8-yl] -6 hydrochloride -f talazinecarbonitrile 1.08 g of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile and 0.76 g of (2R) -l-oxa-8-azaspiro [4.5] decan were dissolved -2-ylmethanol in 20 ml of N-methyl-2-pyrrolidone and stirred at 160 ° C for 5 h. After completion of the reaction, the reaction solution was returned to room temperature, water and saturated aqueous sodium bicarbonate were added, extracted with ethyl acetate and washed with brine three times. After drying over magnesium sulfate, the solvent was removed and the residue was purified by silica gel column chromatography to obtain 0.60 g of a crystalline compound.

The resulting compound was dissolved in 20 ml of ethanol, 1.40 ml of 1N hydrochloric acid / ethanol was added at room temperature and the mixture was stirred for 10 minutes. After removing the solvent, the residue was treated with diisopropyl ether and then dried to obtain 555 mg of the title compound. XH-NMR (400MHz, DMSO-d6) d: 1.67-1.98 (8H, m), 3.15-3.40 (6H, m), 3.82 (3H, s), 3.90 -3.98 (HH, m), 4.68-4.77 (2H, m), 7.14 (1H, d, J = 9Hz), 7.46 (HH, dd, J = 2.9Hz) , 7.62 (HH, d, J = 2Hz), 8.23 (HH, d, J = 9Hz), 8.45 (HH, d, J = 9Hz), 9.50 (HH, s). Example 22 (Antí) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (7-hydroxy-3-oxa-9-azabicyclo [3.3.1] non-9-yl) -6 hydrochloride -ftala-zinacarbonitrile 1.5 g of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile, 1.13 g of (anti) -3-oxa-9-azabicyclohydrochloride [3.3 .1] nonan-7-ol and 2.16 ml of diisopropylethylamine to 8 ml of N-methyl-2-pyrrolidone and the mixture was stirred at 170 ° C for 9 h and 15 minutes. Water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic layer was washed with water and brine. After drying the mixture over anhydrous magnesium sulfate, the solvent was evaporated. The residue was purified by silica gel column chromatography (solvent: dichloromethane / methanol) to obtain 0.085 g of a yellow oil. The resulting oil was dissolved in ethyl acetate, then 0.05 ml of 4 N hydrogen chloride / ethyl acetate was added and the mixture was stirred at room temperature. The resulting precipitates were collected by filtration to obtain 0.075 g of the title compound. XH-NMR (400MHz, DMSO-d6) d: 1.69-1.78 (2H, m), 2.46-2.56 (2H, m), 3.77-3.84 (2H, m), 3.86 (3H, s), 3.86-3.95 (3H, m), 4.04-4.12 (2H) , m), 4.74 (2H, s), 7.17 (HH, d, J = 8.4Hz), 7.46 (HH, dd, J = 2.2, 8.4Hz), 7.61 (ÍH, d, J = 2.2Hz), 8.13 (1H, d, J = 8.4Hz), 8.45 (HH, d, J = 8.4Hz), 9.39 (HH, m). EXAMPLE 23 (Anti) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (9-hydroxy-3-azabicyclo [3.3.1] non-3-yl) -6-phthalazinecarbonitrile hydrochloride 1.5 g of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile, 1.12 g of (anti) -3-azabicyclo [3.3.1] nonan hydrochloride were added. -9-ol and 2.18 ml of diisopropylethylamine were added to 8 ml of N-methyl-2-pyrrolidone and the mixture was stirred at 170 ° C for 9 h. Water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic layer was washed with water and brine. It was dried over anhydrous magnesium sulfate and then the solvent was evaporated. Dichloromethane was added and the insolubles were collected by filtration to obtain 1.23 g of a light yellow powder. The resulting powder was suspended in ethyl acetate, 0.7 ml of 4 N hydrogen chloride / ethyl acetate was added and the mixture was stirred at room temperature. The resulting precipitates were collected by filtration to obtain 1, 28 g of the title compound as a light colored powder. XH-NMR (400MHz, DMSO-d6) d: 1.54 (1H, m), 1.66-1.75 (2H, m), 1.86-1.93 (2H, m), 2.11 -2.23 (2H, m), 2.38 (HH, m), 3.15-3.24 (2H, m), 3.62-3.70 (2H, m), 3.75 (HH) , m), 3.85 (3H, s), 4.74 (2H, s), 7.16 (1H, d, J = 8.4Hz), 7.47 (1H, dd, J = l, 8 , 8.4Hz), 7.62 (1, d, J = 1, 8Hz), 8.23 (1H, d, J = 8.4Hz), 8.56 (1H, dd, J = 1, 3, 8.4Hz), 9.49 (ÍH, m). Example 24 (Anti) -4- [(3-chloro-4-methoxybenzyl) amino] -1- [9- (2-hydroxyethyl) -3-azabicyclo [3.3.1] non-3-yl] -6 hydrochloride -ftalazinecarbonitrile 1.5 g of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile, 1.29 g of (anti) -2- (3-azabicyclo [3.3. 1] non-9-yl) -1-ethanol and 2.18 ml of diisopropylethylamine to 8 ml of N-methyl-2-pyrrolidone and the mixture was stirred at 170 ° C for 8 h and 40 minutes. Water was added to the reaction solution, which was then extracted with ethyl acetate, and the organic layer was washed with water and brine. The reaction solution was dried over anhydrous magnesium sulfate and the solvent was then evaporated. The residue was purified by silica gel column chromatography (solvent: dichloromethane / methanol) and crystallized with dichloromethane-ethyl acetate-ether to obtain 1.12 g of a light yellow powder. The resulting powder was suspended in acetone, 2 ml of 4 N hydrogen chloride / ethyl acetate and ethyl acetate were added and the mixture was stirred at room temperature. The resulting precipitates were collected by filtration to obtain 0.98 g of the title compound as light yellow powder. 1 H-NMR (400MHz, DMSO-d 6) d: 1.61 (1H, m), 1.66-1.73 (2H, m), 1.73-1.87 (5H, m), 1.88. -2.00 (2H, m), 2.42 (HH, m), 3.14-3.23 (2H, m), 3.49 (2H, t, J = 6.4Hz), 3.67 -3.76 (2H, m), 3.85 (3H, s), 4.73 (2H, s), 7.16 (HH, d, J = 8.6Hz), 7.47 (HH, dd) , J = 1, 6, 8.6Hz), 7.62 (1H, d, J = 1, 6Hz), 8.24 (1H, d, J = 8.4Hz), 8.55 (1H, dd, J = 1, 3, 8.4Hz), 9.46 (1H, m).

Example 25 1- (3-Amino-3-methyl-1-butynyl) -4- [(3-chloro-ro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile hydrochloride 0.39 ml of triethylamine was added to a mixture of 500 mg of l-chloro-4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile, 53 mg of cuprous iodide, 98 mg of dichlorobis (triphenylphosphine) ) palladium (II), 347 mg of 3-amino-3-methyl-1-butyne and 10 ml of dimethylformamide and the mixture was stirred at 80 ° C for 3 h in a nitrogen atmosphere. After cooling, ethyl acetate was added to the reaction solution, water and concentrated aqueous ammonia were then added and the organic layer was recovered. The organic layer was washed with dilute aqueous ammonia and brine and dried over anhydrous sodium sulfate. The filtrate was filtered and evaporated. The resulting residue was purified by NH-form silica gel column chromatography to obtain 446 mg of the title compound. The product was converted in the usual way to the hydrochloride. XH-NMR (400MHz, DMSO-d6) d: 1.75 (6H, s), 3.82 (3H, s), 4.76 (2H, d, J = 5.6Hz), 7.10 (1H) , d, J = 8.4Hz), 7.37 (HH, dd, J = 8.4, 2.2Hz), 7.50 (1H, d, J = 2.2Hz), 8.31 (HH, dd, J = 8.4, 1.4Hz), 8.35 (HI, d, J = 8.4Hz), 8.83 (1H, t, J = 5.6Hz), 8.92-9.05 (3H, m), 9.07 (ÍH, broad). Example 26 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (methoxyimino) piperidino] -6-phthalazinecarbonitrile hydrochloride A mixture of 1.19 g of 4 - [(3-chloro-4-methoxybenzyl) amino] -1- [4-oxopiperidino] -6-phthalazinecarbonitrile, 354 mg of ethoxy-amine hydrochloride, 1 was heated to reflux. 2 g of sodium carbonate and 10 ml of ethanol for 2 h. After cooling, saline was added to the reaction solution, which was then extracted with ethyl acetate. It was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated and the resulting residue was purified by silica gel column chromatography to obtain 620 mg of 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (methoxyimino) piperidino] -6 -fta-lazinecarbonitrile. This product was dissolved in a mixed solvent of methanol and ethanol and recrystallized by adding 0.35 ml of 4 N hydrochloric acid / ethyl acetate to obtain 388 mg of 4- [(3-chloro-4-methoxybenzyl) hydrochloride. ) amino] -1- [4- (methoxyimino) piperidino] -6-phthalazinecarbonitrile. XH-NMR (400MHz, DMSO-d6) d: 2.50-2.55 (2H, m), 2.74-2.80 (2H, m), 3.29-3.35 (4H, m) , 3.77 (3H, s), 3.85 (3H, s), 4.72 (2H, broad), 7.16 (ÍH, d, J = 8.4Hz), 7.45 (ÍH, dd , J = 8.4, 2.0Hz), 7.60 (ΔH, d, J = 2.0Hz), 8.33 (1H, d, J = 8.8Hz), 8.48 (ΔI, dd, J = 8.8, 0.8Hz), 9.35 (1H, d, J = 0.8Hz), 10.19 (1H, broad). The following compounds were synthesized using their corresponding starting materials in the same manner as in Production Examples s in the Examples. Example 27 4- [(3-Chloro-4-methylbenzyl) amino] -1- (4-hi-droxipiperidino) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.62-1.73 (2H, m), 1.90-1.99 (2H, m), 2.32 (3H, s), 2.98 -3.08 (2H, m), 3.42-3.50 (2H, m), 3.72-3.80 (1H,), 4.76 (2H, d, J = 5.6Hz), 7.36 (2H, s), 7.57 (HH, s), 8.23 (HH, d, J = 8.4Hz), 8.47 (HH, dd, J = 8.4, 1.2Hz ), 9.37 (1H, d, J = 1, 2Hz), 10.21 (1H, broad). Example 28 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (5-hydroxyperhydrocyclopenta [c] pyrrol-2-yl) -6-phthalazinecarbonitrile 1H-NMR (400MHz, DMSO-d6) d: 1.40-1.49 (2H, m), 2.02-2.12 (2H, m), 2.55-2.64 (2H, m), 3.24 (4H, d, J = 4.0Hz), 3.80 (3H, s), 3.94-4.04 (ÍH, m), 4.61 (2H, d, J = 5.2Hz), 4.72 (HH, d, J = 5.6Hz), 7.07 (HH, d, J = 8.4Hz), 7.32 (HH, dd, J = 2.0, 8.4Hz), 7.77-7.83 (HH, m), 8.14-8.23 (2H, m), 8.66 (HH, d, J = 0.8Hz ).

EXAMPLE 29 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (2-hydroxyethyl) -1,2,3,6-tetrahydro-l-pyridinyl] -6-phthalazinecarbonitrile 2H-NMR (400MHz, DMSO-d6) d: 2.15-2.22 (2H, m), 2.27-2.39 (2H, m), 3.20 (2H, t, J = 5, 6Hz), 3.48-3.60 (2H, m), 3.69 (2H, s), 3.80 (3H, s), 4.47 (HH, t, J = 5.6Hz), 4 , 61 (2H, d, J = 5,6Hz), 5,55 (ÍH, d, J = 0,4Hz), 7,08 (ÍH, d, J = 8,4Hz), 7,33 (ÍH, dd, J = 2.0, 8.4Hz), 7.44 (IH, d, J = 2.0Hz), 7.83-7.89 (IH, m), 8.04 (IH, d, J = 8.4Hz), 8.08 (HH, dd, J = 1, 2, 8.4Hz), 8.87 (HH, t, J = 0.4Hz). EXAMPLE 30 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3- (hydroxymethyl) te-trahydro-lH-1-pyrrolyl] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMSO-d6) d: 1.59-1.70 (HH, m), 1.83-2.02 (2H, m), 2.31-2.41 (HH, m) , 3.34-3.60 (5H, m), 4.58 (2H, J = 5.6Hz), 4.67 (HH, t, J = 5.6Hz), 7.07 (HH, d, J = 8.4Hz), 7.32 (IH, dd, J = 2.0, 8.4Hz), 7.43 (IH, d, J = 2.0Hz), 7.56-7.62 (IH) , m), 8,14 (ÍH, dd, J = 1, 6, 8,8Hz), 8,23 (ÍH, d, J = 8,8Hz), 8,820 (1H, d, J = 1, 2Hz) . EXAMPLE 31 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (hydroxymethyl) -1,2,3,6-tetrahydro-l-pyridinyl] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMSO-d6) d: 2.28 (2H, broad s), 3.19-3.26 (2H, m), 3.73 (2H, broad s), 3.80 (3H , s), 3.89 (2H, d, J = 4.4Hz), 4.62 (2H, d, J = 5.6Hz), 4.78 (H, t, J = 5.6Hz), 5 , 72 (ÍH, broad), 7,08 (ÍH, d, J = 8,4Hz), 7,33 (ÍH, dd, J = 2,0, 8,4Hz), 7,44 (ÍH, d , J = 2.0Hz), 7.87 (1H, t, J = 5.6Hz), 8.05 (ΔH, d, J = 8.4Hz), 8.18 (1H, dd, J = 1, 2, 8.4Hz), 8.87 (ÍH, d, J = 1, 2Hz).

Example 32 2- [1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6-cyano-l-phthalazinyl] -4-piperidinyl] propionic acid hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.08 (3H, d, J = 6.8Hz), 1.46-1.64 (2H, m), 1.66-1.83 (3H, m), 2.22-2.32 (HH, m), 2.78-2.90 (2H, m 3.54-3.64 (2H, m 3.83 (3H, s), 4.72 (2H, d, J = 6.0Hz), 7.14 (HH, d, J = 8.4Hz), 7.46 (HH, dd, J = 2.0, 8.4Hz), 7.61 (HH, d, J = 2.0Hz), 8.22 (1H, d, J = 8.4Hz), 8.45 (ÍH, dd, J = l, 6, 8.4Hz), 9.49 (ÍH, s). EXAMPLE 33 2- [1- [4- [(3-Chloro-4-methoxybenzyl) -amino] -6-cyano-1-phthalazinyl] -1,2,3,6-tetrahydro-4-pyridinium hydrochloride nil] acetic XH-NMR (400MHz, DMSO-d6) d: 2.38-2.44 (2H, m), 3.04 (2H, s), 3.79-3.83 (2H, m), 3.83 (3H, s), 4.72 (2H, t, J = 2.8Hz), 5.63-5.68 (HH, m), 7.15 (HH, d, J = 8.8Hz), 7 , 46 (HH, dd, J = 2.4, 8.4Hz), 7.61 (HH, d, J = 2.4Hz) ,. 8.21 (HH, d, J = 8.8Hz), 8.46 (1H, dd, J = 1, 2, 8.4Hz), 9.45 (HH, s). EXAMPLE 34 2- [1- [4- [(3-Chloro-4-methoxybenzyl) -amino] -6-cyano-l-phthalazinyl] -4-piperidinyl] -2-fluoroacetic acid hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.60-1.90 (4H, m), 2.03-2.20 (1H, m), 2.83-2.98 (2H, m) , 3.58-3.65 (2H, m), 3.83 (3H, s), 4.73 (2H, t, J = 2.8Hz), 4.98 (ΔH, dd, J = 4, 0, 48.4Hz), 7.14 (ÍH, d, J = 8.4Hz), 7.46 (ÍH, dd, J = 2.0, 8.4Hz), 7.61 (ÍH, d, J = 2.4Hz), 8.23 (ÍH, d, J = 8.4Hz), 8.44 (ÍH, dd, J = 1, 2, 8.4Hz), 8.46 (1H, s). Example 35 2- [1- [4- [(3-Chloro-4-methoxybenzyl) -amino] -6-cyano-l-phthalazinyl] -4-piperizyl] acetic acid hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.44-1.57 (2H, m), 1.79-1.84 (2H, m), 1.85-1.96 (1H, m) , 2.25 (2H, d, J = 6.8Hz), 2.89 (2H, t, J = 12.0Hz), 3.55 (2H, d, J = 12.0Hz), 3.84 ( 3H, s), 4.70 (2H, d, J = 6.0Hz), 7.15 (IH, d, J = 8.8Hz), 7.44 (IH, dd, J = 2.0, 8 , 4Hz), 7.94 (HH, d, J = 2.0Hz), 8.21 (HH, d, J = 8.4Hz), 8.46 (HH, dd, J = 1, 6, 8, 8Hz), 9.37 (ÍH, s).

Example 36 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (1-fluoro-2-hydroxyethyl) piperidino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.56-1.78 (3H, m), 1.83-1.99 (2H, m), 2.80-2.91 (2H, m) , 3.51-3.69 (4H, m), 3.83 (3H, s), 4.25-4.31 (1 / 2H, m), 4.37-4.43 (1 / 2H, m), 4.73 (2H, d, J = 5.6Hz), 7.14 (IH, d, J = 8.4Hz), 7.47 (IH, dd, J = 2.0, 8.4Hz) ), 7.62 (HH, d, J = 2.0Hz), 8.22 (HH, d, J = 8.4Hz), 8.45 (HH, dd, J = 1, 2, 8.4Hz) , 9.52 (HH, s), 10.58 (HH, s). Example 37 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (2-hydroxyethoxy) piperidino] -6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.68-1.77 (4H, m), 1.98-2.07 (2H, m), 2.98-3.07 (2H, m) , 3.44-3.52 (2H, m), 3.56-3.62 (3H, m), 3.83 (3H, s), 4.74 (2H, d, J = 5.6Hz) , 7.13 (HH, d, J = 8.4Hz), 7.48 (HH, dd, J = 2.0, 8.4Hz), 7.627 (HH, d, J = 2.0Hz), 8, 23 (HH, d, J = 8.4Hz), 8.45 (HH, dd, J = 1, 6, 8.4Hz), 9.57 (1H, s), 10.68 (HH, broad) . Example 38 2- [[1- [4- [(3-Chloro-4-methoxybenzyl) -amino] -6-cyano-l-phthalazinyl] -4-piperizyl] oxy] acetic acid hydrochloride ^ -NMR (400MHz, DMSO-d6) d: 1.69-1.82 (2H, m), 1.99-2.10 (2H, m), 2.98-3.09 (2H, m), 3.60-3.68 (HH, m), 3.83 (3H, s), 4.08 (2H, s), 4.72 (2H, d, J = 5.6Hz), 7.14 (1H, d, J = 8.4Hz), 7.46 (HH, dd, J = 2.4, 8.4Hz), 7.61 (HH, d, J = 2.0Hz), 8.24 (1H, d, J = 8.4Hz), 8.46 (IH, dd, J = 1, 2, 8.4Hz), 9.46 (ÍH, s), 10.46 (ÍH, s broad). Example 39 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (2-hydroxy-l-methylethyl) piperidino] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMSO-d6) d: 0.85 (3H, d, J = 6.4Hz), 1.40-1.59 (4H, m), 1.64-1.73 (2H, m), 2.68-2.79 (2H, m), 3.33-3.47 (4H, m), 3.78 (3H, m), 4.40 (H, t, J = 5, 2Hz), 4.60 (2H, d, J = 5.6Hz), 7.06 (HH, d, J = 8.4Hz), 7.31 (HH, dd, J = 2.0, 8.4Hz) ), 7.42 (HH, d, J = 2.0Hz), 7.85 (HH, t, J = 6.0Hz), 8.03 (HH, d, J = 8.4Hz), 8.16 (ÍH, dd, J = 1, 6, 8,4Hz), 8,85 (ÍH, d, J = 0, 8Hz). Example 40 2- [7- [4- [(3-Chloro-4-methoxybenzyl) -amino] -6-cyano-l-phthalazinyl] -7-azaspiro [3.5] non-2-yl] -acetic acid hydrochloride lll XH-NMR (400MHz, DMSO-d6) d: 1.45-1.53 (2H, m), 1.66-1.73 (2H, m), 1.77-1.84 (2H, m) , 1.96-2.04 (2H, m), 2.34 (2H, d, J = 7.6Hz), 3.02 (2H, broad s), 3.11 (2H, broad s), 3 , 82 (3H, s), 4.67 (2H, s), 7.11 (HH, d, J = 8.4Hz), 7.40 (HH, dd, J = 2.0, 8.4Hz) , 7.54 (HH, d, J = 2.0Hz), 8.15 (HH, d, J = 8.8Hz), 8.34 (HH, d, J = 8.8Hz), 9.24 ( ÍH, s). Example 41 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [2- (hydroxymethyl) perhydro [1.3] dioxolo [4,5-c] pyrrol-5-yl] -6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 3.54-3.67 (2H, m), 3.80-3.92 (2H, m), 4.16 (2 / 3H, broad s), 4.29 (4 / 3H, broad s), 4.54 (HH, t, J = 5.2Hz), 4.54-4.62 (HH, m), 5.16-5.32 (2H, m), 7,11 (ÍH, d, J = 8,4Hz), 7,34-7,40 (ÍH, m), 7,50 (ÍH, s), 8.37 (HH, d, J = 8.4Hz), 8.48-8.58 (HH, m), 9.12-9.21 (HH, m). Example 42 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (1-hydroxyethyl) piperidino-6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.07 (3H, d, J = 6.0Hz), 1.34-1.60 (3H, m), 1.65-1.76 (2H, m), 1.86-1.94 (2H, m), 2.75-2.86 (2H, m), 3.55-3.63 (2H, m), 3.82 (3H, s) , 4.73 (2H, d, J = 5.6Hz), 7.13 (ΔI, d, J = 8.8Hz), 7.48 (ΔI, dd, J = 2.0, 8.8Hz), 7.63 (1H, d, J = 2.0Hz), 8.20 (1H, d, J = 8.4Hz), 8.45 (1H, dd, J = 1, 2, 8.4Hz), 9 , 56 (ÍH, s), 10.69 (ÍH, s broad). E n emp lo 43 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4-f luoro-4- (hydroxymethyl) piperidino] -6-phthalazinecarbonitri-lo hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.69-1.77 (2H, m), 1.83-2.08 (2H, m), 3.05-3.16 (2H, m) , 3.48 (2H, d, J = 20.0Hz), 3.82 (3H, s), 4.74 (2H, d, J = 5.6Hz), 7.14 (IH, d, J = 8.8Hz), 7.48 (HH, dd, J = 2.0, 8.8Hz), 7.63 (HH, d, J = 2.0Hz), 8.26 (HH, d, J = 8 , 4Hz), 8.46 (ÍH, dd, J = 1, 2, 8.4Hz), 9.57 (1H, s), 10.73 (1H, broad). Example 44 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (hydroxymethyl) -4-methoxypiperidino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMS0-d6) d: 1.71-1.86 (4H, m), 3.04-3.16 (2H, m), 3.16 (3H, s), 3.41 (2H, s), 3.83 (3H, s), 4.72 (2H, d, J = 5.6Hz), 7.14 (HH, d, J = 8.4Hz), 7.46 (HH) , dd, J = 2.0, 8.4Hz), 7.61 (HH, d, J = 2.0Hz), 8.23 (HH, d, J = 8.8Hz), 8.44 (HH, dd, J = 1, 2, 8.8Hz), 9.48 (1H, s), 10.46 (1H, broad). Example 45 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (2-hydroxy-6-azaes? Iro [3.4] oct-6-yl) -6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.00-1.08 (2H, m), 1.82-2.04 (4H, m), 2.19-2.35 (2H, m) , 3.32-3.45 (2H, m), 3.55-3.60 (2H, m), 3.80 (3H, s), 4.04-4.19 (1H, m), 4 , 56 (2H, broad s), 7.10 (HH, d, J = 8.4Hz), 7.37 (1H, broad), 7.50 (HH, broad), 8.38 (HH, d, J = 8.4 Hz), 8.45-8.73 (1H, m). Example 46 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3- (hydroxymethyl) -2,5-dihydro-lH-l-pyrrolyl] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 3.82 (3H, s), 4.12 (2H, s), 4.45-4.83 (6H, m), 5.84 (1H, s) broad), 7.11 (HH, d, J = 9Hz), 7.33-7.56 (2H, m), 8.45 (HH, d, J = 9Hz), 8.66-9.14 ( 2H, m).

Example 47 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [(3R, 4S) -3,4-di (hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -6-phthalazinecarbonitrile hydrochloride 1H-NMR (400MHz, DMSO-d6) d: 2.50-2.57 (2H, m), 3.38-3.49 (2H, m), 3.56-3.60 (2H, m), 3.76-3.87 (4H, m), 3.81 (3H, s), 4.55 (2H, broad s) , 7.10 (HH, d, J = 8.4Hz), 7.36 (HH, d, J = 7.6Hz), 7.49 (HH, s), 8.41 (HH, d, J = 8.4Hz), 8.68 (HH, d, J = 8.4Hz), 9.13 (HH, s). Example 48 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6-cyano-1-phthalazinyl] -4-hydroxy-4-piperidinecarboxamide hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.56-1.64 (2H, m), 2.16-2.28 (2H, m), 3.12-3.24 (2H, m) , 3.32-3.48 (2H, m), 3.54 (1H, broad), 3.83 (3H, s), 4.10-4.30 (1H, m), 4.74 ( 2H, s), 7.13 (HH, d, J = 8.4Hz), 7.15 (HH, broad), 7.31 (HH, broad), 7.48 (1H, d, J = 8.4Hz), 7.64 (IH, s), 8.26 (IH, d, J = 8.4Hz), 8.44 (IH, d, J = 8.4Hz), 9.52-9, 60 (ÍH, m). Example 49 [4- (3-Chloro-4-methoxybenzyl) amino] -1- [4- (fluoromethyl) -4-hydroxypiperidino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMS0-d6) d: 1.54-1.64 (2H, m), 1.80-1.92 (2H, m), 3.18-3.26 (2H, m), 3.32-3.44 (4H, m), 3.83 (3H, s), 4.22 (2H, d, J = 7.6Hz), 4.72 (HH, d, J = 6.0Hz), 7.14 (HH, d, J = 8.4Hz), 7.48 (HH, dd, J = 8.4, 1,6Hz), 7,62 (ÍH, d, J = l, 6Hz), 8.23 (1H, d, J = 8.4Hz), 8.45 (1H, d, J = 8.4Hz), 9, 45 (ÍH, s broad). Example 50 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxyiminopiperidino) -6-phthalazinecarbonitrile hydrochloride ^ • H-NMR (400MHz, DMS0-d6) d: 2.50-2.52 (2H, m), 2.74-2.80 (2H, m), 3.26-3.35 (4H, m), 3.85 (3H, s), 4.71 (2H, broad), 7.17 (ÍH, d, J = 8.8Hz), 7.45 (1H, dd, J = 8.8, 2.0Hz), 7.60 (HH, d, J = 2.0Hz), 8.34 (HH, d, J = 8.4Hz), 8.49 (HH, dd, J = 8.4, 0 , 4Hz), 9.34 (1H, d, J = 0.4Hz), 10.53 (1H, broad). Example 51 (Anti) -2- [3- [4- [(3-Chloro-4-methoxy-benzyl) amino] -6-cyano-l-phthalazinyl] -3-azabicyclo [3.3.1] - hydrochloride non-9-yl] acetic XH-NMR (400MHz, DMSO-d6) d: 1.62 (HH, m), 1.75-2.00 (4H, m) 2.12 (HH, m), 2.52 (2H, d, J = 8, lHz), 3.16-3.24 (2H, m), 3.68-3.76 (2H, m), 3.85 (3H, s), 4.74 (2H, s) , 7.16 (HH, d, J = 8.6Hz), 7.48 (HH, dd, J = 1, 8, 8.6Hz), 7.62 (HH, d, J = 1, 8Hz), 8.23 (1H, d, J = 8.4Hz), 8.55 (1H, dd, J = 1, 3, 8, 4Hz), 9.48 (1H, m). Example 52 (Endo) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMS0-d6) d: 1.81-1.88 (2H, m), 1.90-1.98 (2H, m), 2.19-2.30 (4H, m) , 3.85 (3H, s), 4.04 (HH,), 4.16-4.26 (2H, m), 4.71 (2H, s), 7.16 (1H, d, J = 8.6Hz), 7. 46 (HH, d, J = 8.6Hz), 7.61 (HH, s), 8.29 (HH, d, J = 8.4Hz), 8. 47 (ÍH, dd, J = l, 3, 8.4Hz), 9.44 (ÍH, m).

Example 53 (sin) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (9-hydroxy-3-azabicyclo [3.3.1] non-3-i1) -6-phthalazinecarbo-nitrile hydrochloride ^ -H-NMR (400MHz, DMSO-d6) d: 1.53 (1H, m), 1.74-1.86 (2H, m), 1.87-1.93 (2H, m), 2.05-2.14 (2H, m), 2.37 (HH, m), 3.28-3.44 (2H, m), 3, 41-3.61 (2H, m), 3.68 (HH, m), 3.85 (3H, s), 4.73 (2H, s), 7.15 (HH, d, J = 8, 6Hz), 7.47 (ÍH, d, J = 8.6Hz), 7.62 (IH, s), 8.22 (1H, d, J = 8.6Hz), 8.54 (IH, d, J = 8, 6Hz), 9, 48 (ÍH, m). Example 54 (sin) -4- [(3-chloro-4-) amino] -1- (8-hydroxy-3-azabicyclo [3.2.1] oct-3-yl) -6-phthalazinecarbonitrile hydrochloride LH-NMR (400MHz, DMSO-de) d: 1.75-1.96 (4H, m), 2.02-2.09 (2H, m), 3.06-3.18 (2H, m) , 3.50-3.60 (2H, m), 3.86 (3H, s), 3.91 (HH, t, J = 4.8Hz), 4.73 (2H, s), 7.16 (HH, d, J = 8.6Hz), 7.47 (HH, d, J = 8.6Hz), 7.61 (HH, s), 8.36 (1H, d, J = 8.6Hz) , 8.48 (1H, dd, J = 1, 5, 8.6Hz), 9.43 (1H, m). Example 55 (Exo) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.68-1.83 (2H, m), 1.90-2.02 (4H, m), 3.85 (3H, s), 3.97 (HH, m), 4.18-4.28 (2H, m), 4.70 (2H, s), 7.15 (HH, d, J = 8.6Hz), 7.44 (HH, d) , J = 8.6Hz), 7.59 (HH, s), 8.29 (1H, d, J = 8.6Hz), 8.45 (HH, d, J = 8.6Hz), 9, 36 (1H, m). Example 56 (Anti) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (9-hydroxy-3-oxa-7-azabicyclo [3.3.1] non-7-yl) -6 hydrochloride -f talazinecarbonitrile 1 H-NMR (DMSO-de) d: 1.69-1.76 (2H, m), 3.24-3.38 (2H, m), 3.73-3.83 (2H, m), 3 , 85 (3H, s), 3.85-3.93 (2H, m), 4.11-4.20 (2H, m), 4.73 (2H, s), 7.16 (1H, d) , J = 8.6Hz), 7.47 (IH, d, J = 8.6Hz), 7.62 (IH, s), 8.36 (IH, d, J = 8.4Hz), 8.52 (ÍH, d, J = 8.4Hz), 9.43 (ÍH, m). 57 Ex emplo hydrochloride (anti) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-9-azabicyclo [3.3.1] non-9-yl) -6-ftalazinacarbonitrilo XH-NMR (400MHz, DMSO-d6) d: 1.38-1.54 (4H, m), 1.59 (1H, m), 1.90-2.02 (2H, m), 2.22 -2.45 (3H, m), 3.86 (3H, s), 3.87 (HH, m), 4.08-4.17 (2H, m), 4.69 (2H, s), 7.16 (HH, d, J = 8.6Hz), 7.44 (HH, d, J = 8.6Hz), 7.58 (HH, s), 8.07 (HH, d, J = 8 , 6Hz), 8.44 (HH, d, J = 8.6Hz), 9.29 (HH, m). Example 58 N1- [3- [4- [(3-Chloro-4-methoxybenzyl) amino] -6-cyano-l-phthala-zinyl] phenyl] acetamide XH-NMR (400MHz, DMSO-d6) d: 2.05 (3H, s), 3.81 (3H, s), 4.76 (2H, d, J = 6.0Hz), 7.09 (H) , d, J = 8.4Hz), 7.24 (ΔI, d, J = 8.0Hz), 7.38 (ΔI, dd, J = 8.0, 1.6Hz), 7.45 (ΔI, dd, J = 8.4, 8.0 Hz), 7.50 (HH, d, J = 1, 6Hz), 7.67 (HH, d, J = 8.0Hz), 7.86 (HH, m ), 7.92 (HH, d, J = 8.4Hz), 8.17 (HH, dd, J = 8.4, 1.6Hz), 8.35 (HH, dd, J = 6.0, 6.0Hz), 9.00 (ÍH, s), 10.09 (ÍH, s). Example 59 1- (3-aminophenyl) -4- [(3-chloro-4-methoxy-benzyl) amino] -6-phthalazinecarbonitrile dihydrochloride XH-NMR (400MHz, DMSO-d6) d: 3.83 (3H, s), 4.89 (2H, s am-püo), 7.16 (HH, d, J = 8.6Hz), 7, 38-7.44 (3H, m), 7.53 (HH, dd, J = 8.6, 2.0Hz), 7.58-7.62 (2H, m), 7.68 (HH, d , J = 2.0Hz), 8.02 (HH, d, J = 8.4Hz), 8.45 (HH, d, J = 8.4Hz), 9.65 (HH, s).

Example 60 N- [3- [4- [(3-Chloro-4-methoxybenzyl) amino] -6-cyano-1-phthalazinyl] phenyl] methanesulfonamide hydrochloride XH-NMR (400MHz, DMSO-d6) d: 3.06 (3H, s), 3.84 (3H, s), 4.86 (2H, d, J = 5.6Hz), 7.15 (H) , d, J = 8.4Hz), 7.35 (H, d, J = 7.6Hz), 7.43 (H, d, J = 7.6Hz), 7.50 (H, broad), 7.53 (1H, dd, J = 8.4, 2.0Hz), 7.55 (1H, dd, J = 7.6, 7.6Hz), 7.66 (HH, d, J = 2.0Hz), 8.03 (HH, d, J = 8.8Hz), 8.44 (HH, d, J = 8.8Hz), 9.60 (1H, broad) ), 10,14 (ÍH, s broad). Example 61 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (methylsulfinyl) phenyl] -6-f-talazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 2.84 (3H, s), 3.83 (3H, s), 4.87 (2H, broad s), 7.16 (1H, d, J = 8.4Hz), 7.51 (ÍH, d, J = 8.4Hz), 7.66 (ÍH, broad), 7.83 (2H, d, J = 8.4Hz), 7.92 (2H , d, J = 8.4Hz), 8.00 (HH, d, J = 8.4Hz), 8.43 (1H, d, J = 8.4Hz), 9.52-9.60 (HH, m). Example 62 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [4- (methylsulfonyl) phenyl] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 3.31 (3H, s), 3.82 (3H, s), 4.80 (2H, broad s), 7.12 (IH, d, J = 8.8Hz), 7.43 (1H, dd, J = 8.8, 2.0Hz), 7.56 (IH, d, J = 2.0Hz), 7.90 (2H, d, J = 8 , 0Hz), 7.93 (1H, d, J = 8.4Hz), 8.11 (2H, d, J = 8.0Hz), 8.28 (IH, d, J = 8.4Hz), 9 , 19-9.22 (ÍH, m). Example 63 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-formylphenyl) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 3.84 (3H, s), 4.86 (2H, broad s), 7.16 (ÍH, d, J = 8.4Hz), 7.51 ( ÍH, d, J = 8.4Hz), 7.66 (ÍH, broad), 7.86 (2H, d, J = 8.0Hz), 7.99 (1H, d, J = 8.8Hz) , 8.13 (2H, d, J = 8.0Hz), 8.42 (1H, d, J = 8.8Hz), 9.48-9.53 (1H, m), 10.15 (1H, s). Example 64 4- [(3-Chloro-4-methoxybenzyl) amino] -1 - [(4-hydroxymethyl) phenyl] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-de) d: 3.84 (3H, s), 4.62 (2H, s), 4.84 (2H, broad s), 7.16 (ÍH, d, J = 8.4Hz), 7.49 (HH, dd, J = 8.4, 2.0Hz), 7.55 (2H, d, J = 8.0Hz), 7.60 (2H, d, J = 8 , 0Hz), 7.65 (HH, d, J = 2.0Hz), 8.02 (HH, d, J = 8.4Hz), 8.43 (HH, d, J = 8.4Hz), 9 50-9.58 (1H, m).

Example 65 4- [4- [(3-Chloro-4-methoxybenzyl) amino] -6-cyano-l-phthalazinyl] benzoic acid ^ -NMR (400MHz, DMS0-d6) d: 3.84 (3H, s), 4.76 (2H, d, J = 6.0Hz), 7.10 (HI, d, J = 8.8Hz) , 7.38 (HH, dd, J = 8.8, 2.0Hz), 7.50 (HH, d, J = 2.0Hz), 7.72 (2H, d, J = 8.4Hz), 7.91 (1H, d, J = 8.8Hz), 8.08 (2H, d, J = 8.4Hz), 8.19 (HI, dd, J = 8.4, 1.6Hz), 8 , 44 (1H, dd, J = 6.0, 6.0Hz), 9.01 (ÍH, d, J = 1, 6Hz). Example 66 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (1,3-thiazol-2-yl) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMS0-d6) d: 3.80 (3H, s), 4.82 (2H, s), 7.13 (1H, d, J = 8.4Hz), 7.42 (%) , d, J = 8.4Hz), 7.57 (1H, s), 7.94 (1H, d, J = 3.6Hz), 8.11 (IH, d, J = 3.6Hz), 8 , 46 (HH, d, J = 8.4Hz), 9.20-9.26 (HH, m), 9.70 (HH, d, J = 8.4Hz). Example 67 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-3-methyl-1-butynyl) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.57 (6H, s), 3.84 (3H, s), 4.84 (2H, s), 7.15 (1H, d, J = 8 , 8Hz), 7.46 (1H, dd, J = 8.8, 2.0Hz), 7.61 (1H, d, J = 2.0Hz), 8.34 (ÍH, d, J = 8.4Hz), 8.52 (HH, dd, J = 8.4, 0.4Hz), 9.04 (HH, d, J = 0.4Hz), 10.36 (HH, broad). Example 68 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-1-propynyl) -6-phthalazinecarbonitrile hydrochloride H-NMR (400MHz, DMS0-d6) d: 3.84 (3H, s), 4.49 (2H, s), 4.81 (2H, d, J = 4.0Hz), 7.14 (H) , d, J = 8.4Hz), 7.43 (HH, dd, J = 8.4, 2.4Hz), 7.58 (HH, d, J = 2.4Hz), 8.35 (1H, d, J = 8.8 Hz), 8.48 (H, d, J = 8.8, 0.8 Hz), 9.28 (H, d, J = 0.8 Hz), 9.92 (H, broad) ). Example 69 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3,4-dihydroxy-3- (hydroxymethyl) -1-butynyl] -6-phthalazinecarbonitrile 1 H-NMR (400MHz, DMSO-d 6) d: 3.54-3.66 (4H, m), 3.82 (3H, s), 4.76 (2H, d, J = 5.2Hz), 4 , 98 (2H, t, J = 5.2Hz), 5.62 (IH, s), 7.10 (IH, d, J = 8.8Hz), 7.36 (IH, dd, J = 8, 8, 2.0Hz), 7.49 (ÍH, d, J = 2.0Hz), 8.29-8.34 (1H, m), 8.51 (1H, t, J = 5.2Hz), 8, 96 (ÍH, s). Example 70 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3- (dimethylamino) -1-propynyl] -6-phthalazinecarbonitrile dihydrochloride 1 H-NMR (400MHz, DMSO-de) d: 2.91 (6H, s), 3.83 (3H, s), 4.52 (2H, s), 4.83 (2H, d, J = 4 , 8Hz), 7,13 (ÍH, d, J = 8,8Hz), 7,42 (ÍH, dd, J = 8,8, 2,0Hz), 7,56 (ÍH, d, J = 2, 0Hz), 8.40 (HH, dd, J = 8.4, 1.4Hz), 8.46 (1H, d, J = 8.4Hz), 9.27 (HH, d, J = 1, 4Hz ), 9.76 (1H, broad), 11.39 (1H, broad). EXAMPLE 71 2- [[3- [4- [(3-Chloro-4-methoxybenzyl) -amino] -6-cyano-l-f-talazinyl] -1, 1-dimethyl-2-propynyl] oxy] -acetic acid hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.62 (6H, s), 3.84 (3H, s), 4,21-4,24 (2H, m), 4,77-4,82 (2H, broad), 7,11-7,15 (ÍH, m), 7,38-7,42 (ÍH, m ), 7.51-7.55 (HH, m), 8.19-8.24 (HH, m), 8.38-8.42 (HH, m), 9.12-9.16 (HH) , m).

Example 72 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3- (2-hydroxyethoxy) -3-methyl-l-butynyl] -6-phthalazinecarbonitrile hydrochloride ^ - MR (400MHz, DMSO-d6) d: 1.61 (6H, s), 3.55 (2H, t, J = 5.6Hz), 3.65 (2H, t, J = 5.6Hz), 3.84 (3H, s), 4.85 (2H, d, J = 4.8 Hz), 7.14 (ΔI, d, J = 8.6 Hz), 7.46 (ΔI, dd, J = 8.6, 2.2 Hz), 7.61 (ΔI, d, J = 2.2Hz), 8.30 (1H, d, J = 8.4Hz), 8.48 (1H, dd, J = 8.4, 1.6Hz), 9.42 (HH, d, J = 1, 6Hz), 10.41 (ÍH, broad). Example 73 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3- (4-hydroxypiperidino) -3-methyl-l-butynyl] -6-phthalazinecarbonitrile LH-NMR (400MHz, DMSO-d6) d: 1.79-2.04 (10H, m), 2.12-2.23 (HH, m) 3.04-3.19 (HH, m), 3.26-3.37 (2H, m), 3.54-3.77 (1H, m), 3.82 (3H, s), 4.83 (2H, d, J = 5.6Hz), 7.12 (IH, d, J = 8.4Hz), 7.43 (IH) , dd, J = 8.4, 1.2 Hz), 7.56 (ΔI, d, J = 1, 2 Hz), 8.38 (ΔI, dd, J = 8.4, 0.8 Hz), 8, 43 (HH, d, J = 8.4Hz), 9.30 (HH, d, J = 0.8Hz), 9.91 (HH, broad), 11.40-11, 66 (HH, m). Example 74 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (3-methyl-3-tetrahydro-lH-l-pyrrolyl-l-butynyl) -6-phthalazine-carbonitrile dichloride.

^ • H-NMR (400MHz, DMSO-d6) d: 1.85 (6H, s), 1.90-2.08 (4H, m), 3.30-3.42 (2H, m), 3 , 60-3.72 (2H, m), 3.83 (3H, s), 4.80 (2H, d, J = 5.2Hz), 7.11 (1H, d, J = 8.4Hz), 7.39 (IH, dd, J = 8.4, 2.0Hz), 7.52 ( HH, d, J = 2.0Hz), 8.28 (HH, d, J = 8.4Hz), 8.36 (1H, dd, J = 8.4, 0.8Hz), 9.14 (HH) , d, J = 0.8 Hz), 9.33 (1H, broad), 11.89 (1H, m). Example 75 1- (4-Hydroxypiperidino) -4- [[4-methoxy-3 (trifluoromethyl) benzyl] amino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.62-1.73 (2H, m), 1.90-1.99 (2H, m), 2.97-3.07 (2H, m) , 3.40-3.52 (2H, m), 3.72-3.80 (ÍH, m), 3.89 (3H, s), 4.80 (2H, d, J = 5.6Hz) , 7.28 (HH, d, J = 8.4Hz), 7.81-7.85 (2H, m), 8.24 (HH, d, J = 8.4Hz), 8.47 (HH, dd, J = 8.4, 1.2Hz), 9.53 (1H, d, J = 1, 2Hz), 10.29 (1H, broad), 14.02 (1H, broad). Example 76 1- (4-Hydroxypiperidino) -4- [(3-iodo-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.62-1.73 (2H, m), 1.90-2.00 (2H, m), 2.98-3.08 (2H, m) , 3.40-3.50 (2H, m), 3.72-3.80 (HH, m), 3.82 (3H, s), 4.68 (2H, d, J = 4.8Hz), 7.02 (HH, d, J = 8.8Hz), 7.50 (HH) , dd, J = 8.8, 2.2Hz), 7.93 (HH, d, J = 2.2Hz), 8.24 (HH, d, J = 8.6Hz), 8.46 (HH, dd, J = 8.6, 0.8 Hz), 9.32 (H, d, J = 0.8 Hz), 10.05 (H, broad). Example 77 4- [(3-Bromo-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.62-1.73 (2H, m), 1.90-1.99 (2H, m), 2.98-3.07 (2H, m) , 3.39-3.50 (2H, m), 3.72-3.80 (1H, m), 3.84 (3H, s), 4.71 (2H, d, J = 4.8Hz) , 7.13 (HH, d, J = 8.6Hz), 7.49 (HH, dd, J = 8.6, 2.2Hz), 7.75 (HH, d, J = 2.2Hz), 8.24 (1H, d, J = 8.4Hz), 8.46 (1H, dd, J = 8.4, 0.8Hz), 9.34 (1H, d, J = 0.8Hz), 10 , 11 (ÍH, broad). Example 78 4- [(3-Bromo-4-methoxybenzyl) amino] -1- [3- (hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -6-phthalazinecarbo-nitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.72-1.86 (HH, m), 1.99-2.12 (HH, m), 2.39-2.51 (HH, m) , 3.42 (HH, dd, J = 7.2, 10.8Hz), 3.48 (HH, dd, J = 6.0, 10.8Hz), 3.60-3.90 (4H, m ), 3.80 (3H, s), 7.06 (HH, d, J = 8.4Hz), 7.38-7.46 (HH, m), 7.64 (HH, s), 8, 40 (1H, dd, J = 1, 6, 8.8Hz), 8.65 (1H, d, J = 8.0Hz), 9.18 (1H, s). Example 79 4- [(3-Bromo-4-methoxybenzyl) amino] -1- [(3S) -3- (hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.58-1.76 (3H, m), 1.92-2.02 (2H, m), 2.29-2.42 (2H, m) , 3.42-3.60 (2H, m), 3.78 (3H, s), 4.58 (2H, J = 6.0Hz), 4.69 (IH, t, J = 5.6Hz) , 7.03 (HH, d, J = 8.4Hz), 7.36 (HH, dd, J = 2.0, 8.4Hz), 7.57 (HH, d, J = 2.0Hz), 7.59 (HH, d, J = 6.0Hz), 8.13 (HH, dd, J = 1, 2, 8.8Hz), 8.22 (HH, d, J = 8.8Hz), 8 , 81 (ÍH, d, J = 0.8Hz). Example 80 4- [(3-Bromo-4-methoxybenzyl) amino] -1- [(3R) -3- (hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -6-phthalazinecarbonitrile hydrochloride ^ -NMR (400MHz, DMSO-de) d: 1.72-1.86 (HH, m), 1.99-2.12 (HH, m), 2.39-2.51 (HH, m) , 3.42 (HH, dd, J = 7.2, 10.8Hz), 3.48 (HH, dd, J = 6.0, 10.8Hz), 3.60-3.90 (4H, m ), 3.80 (3H, s), 7.06 (HH, d, J = 8.8Hz), 7.38-7.46 (HH, m), 7.65 (HH, s), 8, 40 (ΔH, d, J = 8.8Hz), 8.59-8.68 (≤H, m), 9.26 (≤H, s). Example 81 4- [(3-Bromo-4-methoxybenzyl) amino] -1- [4- (2-hydroxyethyl) piperidino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.68-1.77 (2H,), 1.96-2.07 (2H, m), 3.02 (2H, t, J = 12.0Hz ), 3.38-3.59 (6H, m), 3.80 (3H, s), 3.81-3.99 (3H, m), 4.72 (2H, d, J = 6.0Hz) ), 7.10 (HH, d, J = 8.6Hz), 7.49 (HH, d, J = 8.6Hz), 7.76 (HH, s), 8.22 (1H, d, J) = 8.6Hz), 8.45 (ÍH, d, J = 8.6Hz), 9.50 (ÍH, s).

Example 82 4- [(3-Bromo-4-methoxybenzyl) amino] -1- (2-hydroxy-7-azaspiro [3.5] non-7-yl) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.58-1.66 (2H, m), 1.68-1.76 (4H, m), 2.14-2.23 (2H, m) , 3.08 (2H, broad s), 3.13 (2H, broad s), 4.08-4.17 (HH, m), 4.73 (HH, d, J = 5, 6Hz), 7 , 10 (HH, d, J = 8.4Hz), 7.52 (HH, dd, J = 2.0, 8.4Hz), 7.70 (HH, d, J = 2.0Hz), 8, 20 (HH, d, J = 8.4Hz), 8.44 (HH, dd, J = 1, 6, 8, 4Hz), 9.55 (HH, s). Example 83 4- [(3-Bromo-4-methoxybenzyl) amino] -1- [4-fluoro-4- (hydroxymethyl) piperidino] -6-phthalazinecarbonitrile hydrochloride Example 84 4- [(3-Bromo-4-methoxybenzyl) amino] -1- [4- [hydroxymethyl) piperidino] -6-f-talazinecarbonitrile hydrochloride ^ - MR (400MHz, DMSO-d6) d: 1.41-1.52 (2H, m), 1.58-1.69 (1H, m), 1.79-1.86 (2H, m) , 2.85-2.94 (2H, m), 3.35-3.40 (2H, m), 3.59 (2H, d, J = 12.8Hz), 3.84 (3H, s) , 4.71 (2H, d, J = 5.2Hz), 7.13 (HH, d, J = 8.4Hz), 7.50 (HH, dd, J = 8.4, 2.0Hz), 7.76 (HH, d, J = 2.0Hz), 8.22 (HH, d, J = 8.4Hz), 8.47 (HH, dd, J = 8.4, 0.8Hz), 9 , 38 (ÍH, broad), 10.21 (ÍH, broad). Example 85 (endo) -4- [(3-Bromo-4-methoxybenzyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl) -6-phthalazinecarbonitrile 1H-NMR (400MHz, DMSO-d6) 'd: 1.70-1.95 (4H, m), 2.14-2.28 (4H, m), 3.82 (3H, s), 4, 15 (HH, m), 4.09 (2H, m), 4.49 (HH, d, J = 2.2Hz), 4.62 (2H, d, J = 5.5Hz), 7.05 ( HH, d, J = 8.6Hz), 7.38 (HH, dd, J = 2.2, 8.6Hz), 7.60 (HH, d, J = 2.2Hz), 7.72 (1H , t, J = 5.5 Hz), 8.11 (1H, d, J = 8.6Hz), 8.18 (1H, dd, J = 1, 5, 8.6Hz), 8.87 (1H, d, J = 1, 5 Hz). Example 86 1- (4-Hydroxypiperidino) -4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.62-1.73 (2H, m), 1.90-1.99 (2H, m), 2.15 (3H, s), 2.98-3.07 (2H, m), 3.42-3.50 (2H, m), 3.72-3.80 (1H) , m), 3.78 (3H, s), 4.67-4.70 (2H, m), 6.94 (HH, d, J = 8.2Hz), 7.28 (HH, d, J = 2.0Hz), 7.31 (HH, dd, J = 8.2, 2.0 Hz), 8.23 (H, d, J = 8.4 Hz), 8.47 (H, d, J = 8.4, 1.2 Hz), 9.45 (H) , d, J = 1, 2Hz), 10.39 (1H, broad). Example 87 1- (2-Hydroxy-7-azaspiro [3.5] non-7-yl) -4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecarbonitrile hydrochloride ^ -NMR (400MHz, DMSO-d6) d: 1.57-1.66 (2H, m), 1.67-1.8 (4H, m), 2.11 (3H, s), 2.14 -2.23 (2H, m), 3.07 (2H, broad s), 3.12 (2H, broad s), 3.55-3.61 (1H, m), 4.07-4.17 (HH, m), 4.69 (HH, d, J = 5.2Hz), 6.91 (HH, d, J = 8.4Hz), 7.29 (HH, s), 7.31 (HH) , dd, J = 2.0, 8.4Hz), 8.19 (ΔI, d, J = 8.4Hz), 8.44 (ÍH, dd, J = 1, 2, 8,4Hz), 9,56 (ÍH, s), 10,59 (ÍH, s broad).

Example 88 1- [4-Fluoro-4- (hydroxymethyl) piperidino] -4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecarbonitrile hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.88-2.10 (4H, m), 2.15 (3H, s) 3.08-3.17 (2H, 3.40-3.50 (2H, m), 3.51 (2H, d, J = 19.6Hz), 3.78 (3H, s), 4.68 (2H, d, J = 5.2Hz), 6.94 (IH, d, J = 8.0Hz), 7.28-7.33 (2H, m), 8.28 (IH, d, J = 8.4Hz), 8.47 (ÍH, dd, J = 8.4, 1.4Hz), 9.42 (ÍH, dd, J = l, 4Hz), 10.26 (ÍH, broad), 13, 96 (1H, broad) Example 89 1- [4- (Hydroxymethyl) piperidino-4- [(3-methoxy-4-methylbenzyl) amino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.41-1.52 (2H, m), 1.58-1.68 (1H, m), 1.79-1.87 (2H, m) , 3.15 (3H, s), 2.82-2.93 (2H, m), 3.30-3.40 (2H, m), 3.58 (2H, d, J = 12.8Hz) , 3.78 (3H, s), 4.67 (2H, d, J = 5.2Hz), 6.94 (IH, d, J = 8.8Hz), 7.26-7.32 (2H, m), 8.22 (HH, d, J = 8.4Hz), 8.47 (HH, dd, J = 8.4, 0.8 Hz), 9.36 (1 H, broad), 10.09 (H, broad). Example 90 (endo) -1- (3-Hydroxy-8-azabicyclo [3.2.1] oct-8-yl) -4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMSO-d6) d: 1.79-1.93 (4H, m), 2.13 (3H, s), 2.13-2.27 (4H, m), 3.75 (3H, s), 4.03 (HH, m), 4.08 (2H, m), 4.49 (HH, d, J = 2.2Hz), 4.59 (2H, d, J = 5 , 3Hz), 6.87 (HH, d, J = 7.9Hz), 7.16-7.22 (2H, m), 7.61 (HH, t, J = 5.3Hz), 8.11 (HH, d, J = 8.4Hz), 8.17 (HH, dd, J = 1, 5, 8.4Hz), 8.90 (HH, d, J = l, 5Hz). EXAMPLE 91 1- [3- (Hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMSO-d6) d: 1.67 (HH, m), 2.00 (HH, m), 2.16 (3H, s), 2.38 (HH, m), 3.36-3.61 (6H, m), 3.75 (3H, s), 4.58 (2H, d, J = 5.5Hz ), 4.68 (HH, t, J = 5.5Hz), 6.86 (HH, d, J = 8, lHz), 7.16-7.22 (2H, m), 7.50 (IH, t, J = 5.3Hz), 8.15 (1H, dd, J = 1, 5, 8.6Hz), 8.24 (1H, dd, J = 8.6Hz), 8.88 (1H, d, J = 1, 5Hz). EXAMPLE 92 4- [(3-Fluoro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidi-no) -6-phthalazinecarbonitrile ^ • H-NMR (400MHZ, DMSO-d6) d: 1.60-1-73 (2H, m), 1.88-1.97 (2H, m), 2.86-2.94 (2H, m), 3.42-3.50 (2H, m), 3.64-3.71 (IH, m), 3.80 (3H, s), 4.62 (2H, d, J = 5, 4Hz), 4.77 (HH, d, J = 2.0Hz), 7.09 (HH, t, J = 8.2Hz), 7.18 (HH, d, J = 8.2Hz), 7, 23 (1H, dd, J = 12.0, 2.0Hz), 7.84 (IH, t, J = 5.4Hz), 8.04 (IH, d, J = 8.4Hz), 8.20 (ÍH, dd, J = 8.4, 1.2Hz), 8.89 (1H, d, J = 1, 2Hz). Example 93 4- [(4-Chloro-3-methoxybenzyl) amino] -1- (4-hydroxypiperidin-none) -6-phthalazinecarbonitrile 1H-NR (400MHz, DMSO-d6) d: 1.60-1.72 (2H, m), 1.87-1.96 (2H, m), 2.86-2.95 (2H, m) , 3.31-3.39 (2H, m), 3.68 (HH, m), 3.84 (3H, s), 4.72 (2H, d, J = 5.5Hz), 4.74 (1H, d, J = 4.2Hz), 6.98 (1H, dd, J = 1, 8, 8,1Hz), 7,20 (ÍH, d, J = 1, 8Hz), 7,34 ( 1H, d, J = 8, lHz), 7.92 (HH, t, J = 5.5Hz), 8.07 (HH, d, J = 8.6Hz), 8.21 (HH, dd, J = 1, 5, 8.6Hz), 8.92 (1H, d, J = 1, 5Hz).

Example 94 4- [(3-Cyano-4-methoxybenzyl) amino] -1- (4-hi-droxipiperidino) -6-phthalazinecarbonitrile hydrochloride H-NMR (400MHz, DMSO-d6) d: 1.6-1.73 (2H, m), 1.88-2.0 (2H,), 2.95-3.08 (2H, m), 3.4-3.7 (2H, m), 3.7-3.8 (ÍH, m), 3.90 (3H, s), 4.74 (2H, d, J = 5.6Hz), 7.27 (HH, d, J = 9.2Hz), 7.79 (HH, dd, J = 2.0, 8.8Hz), 7.87 (1H, d, J = 2.0Hz), 8 , 24 (1H, d, J = 8.4Hz), 8.47 (HH, dd, J = 1, 2, 8.4Hz), 9.38 (HH, s). Example 95 (Endo) -4- [(3-cyano-4-methoxybenzyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2.1] oct-8-11) -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.9-1.96 (4H, m), 2.17-2.29 (4H, m), 3.91 (3H, s), 4.04 (HH, m), 4.15 (2H, m), 4.68 (2H, s), 7.25 (HH, d, J = 8.6Hz), 7.74 (HH, d, J = 8 , 6Hz), 7.80 (HH, s), 8.21 (HH, d, J = 8.6Hz), 8.34 (HH, m), 9.07 (1H, m). Example 96 4- [(3-Cyano-4-methoxybenzyl) amino] -1- [3- (hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.84 (HH, m), 2.09 (HH, m), 2.48 (HH, m), 3.40-3.55 (2H, m ), 3.64-3.90 (4H, m), 3.91 (3H, s), 4.59 (2H, m), 7.24 (IH, d, J = 8.8Hz), 7, 74 (HH, d, J = 8.8Hz), 7.79 (HH, s), 8.42 (HH, d, J = 9.3Hz), 8.70 (HH, m), 9.15 ( ÍH, m). Example 97 4- [(3-Ethyl-4-methoxybenzyl) amino] -1- (4-hi-droxipiperidino) -6-phthalazinecarbonitrile hydrochloride 1H-NMR (400MHz, DMSO-d6) d: 1.14 (3H, t, J = 7.5Hz), 1.63-1.74 (2H, m), 1.90-2.01 (2H, m), 2.57 (2H, c, J = 7.5Hz), 2.97-3.08 (2H, m), 3.40-3.54 (2H, m), 3.75 (ÍH, m), 3.79 (3H, s), 4.69 (2H, s), 6.95 (ÍH, d, J = 8.2Hz), 7.26-7.35 (2H, m), 8 , 25 (HH, d, J = 8.6Hz), 8.48 (HH, dd, J = 1, 3, 8.6Hz), 9.44 (HH, m). EXAMPLE 98 4- [(3-Chloro-4-methoxyphenethyl) amino] -1- (2-hydroxy-7-azaspiro [3.5] non-7-yl) -6-f-talazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.58-1.66 (2H, m), 1.67-1.78 (4H, m), 2.14-2.23 (2H, m) , 2.92-3.01 (2H, m), 3.07 (2H, s), 3.11 (2H, s), 3.70-3.82 (3H, m), 3.80 (3H , s), 4.08-4.18 (HH, m), 7.06 (HH, d, J = 8.4Hz), 7.26 (HH, dd, J = 2.0, 8.4Hz) , 7.43 (HH, d, J = 2.0Hz), 8.19 (HH, d, J = 8.4Hz), 8.44 (HH, dd, J = 1, 2, 8.4Hz), 9,55 (ÍH, s), 10,47 (ÍH, s broad), 13, 9 (ÍH, s broad). Example 99 4- [(3-Chloro-4-methoxyphenethyl) amino] -1- [4- (2-hydroxyethoxy) piperidino] -6-phthalazinecarbonitrile hydrochloride XH-NMR (400MHz, DMSO-de) d: 1.68-1.77 (2H, m), 2.00-2.06 (2H, m), 2.76 (2H, t, J = 8, 0Hz), 3.03 (2H, t, J = 12.0Hz), 3.32 (10H, m), 3.75 (2H, d, J = 8.0Hz), 3.81 (3H, s) , 7.07 (HH, d, J = 8.6Hz), 7.25 (HH, d, J = 8.6Hz), 7.43 (HH, s), 8.24 (HH, d, J = 8.6Hz), 8.45 (HH, d, J = 8.6Hz), 9.32 (HH, s). Example 100 4- [(3-Claro-4-methoxifenetii) amino] -1- [4-fluoro-4- (hydroxymethyl) piperidino] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMSO-d6) d: 1.82-2.06 (4H, m), 2.83-2.94 (2H, m), 3.04-3.14 (2H, m) , 3.24-3.30 (HH, m), 3.49 (2H, dd, J = 10.2, 6.0Hz), 3.54-3.60 (HH, m), 3.64- 3.70 (2H, m), 3.80 (3H, s), 5.03 (HH, dd, J = 6.0, 6.0Hz), 7.05 (HH, d, J = 12.6Hz ), 7.19 (HH, dd, J = 12.6, 2.0Hz), 7.32 (HH, d, J = 2.0Hz), 7.40-7.45 (HH, m), 8 , 08 (ÍH, d, J = 8,4Hz), 8,18 (ÍH, d, J = 8,4Hz), 8,82 (ÍH, s broad). Example 101 (endo) -4- [(3-Chloro-4-methoxyphenethyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl) -6-phthalazinecarbonitrile ? -NMR (400MHz, DMSO-d6) d: 1.78-1.94 (4H, m), 2.14-2.28 (4H, m), 2.92 (2H, t, J = 7, 0Hz), 3.67 (2H, c, J = 7.0Hz), 3.82 (3H, s), 4.04 (HH, m), 4.09 (2H, m), 4.49 (HH) , d, J = l, 8 Hz), 7.06 (l, d, J = 8.4 Hz), 7.20 (l, d, J = 2.2, 8.4 Hz), 7.27 (l, m), 7.33 (HH, d, J = 2.2Hz), 8.11 (HH, d, J = 8.6Hz), 8.17 (HH, dd, J = 1, 5, 8.6Hz) ), 8.80 (ÍH, d, J = 1, 5Hz).

Example 102 4- [(3-Chloro-4-methoxyphenethyl) amino] -1- [3- (hydroxymethyl) tetrahydro-lH-l-pyrrolyl] -6-phthalazinecarbonitrile XH-NMR (400MHz, DMS0-d6) d: 1.68 (HH, m), 2.00 (HH, m), 2.40 (HH, m), 2.92 (2H, t, J = 7 , 5Hz), 3.37-3.70 (8H, m), 3.82 (3H, s), 4.69 (IH, d, J = 5.3Hz), 7.06 (1H, d, J = 8.6Hz), 7.16 (1H, m), 7.20 (IH, dd, J = 2.0, 8.6Hz), 7.33 (IH, d, J = 2.0Hz), 8 , 15 (1H, dd, J = 1, 3, 8.6Hz), 8.25 (1H, d, J = 8, 6Hz), 8.78 (1H, m).

Example 103 4- [(3, -Dichlorobenzyl) amino] -1- (4-hydroxy-piperidino) -6-phthalazinecarbonitrile hydrochloride ? -NMR (400MHz, DMSO-d6) d: 1.61-1.72 (2H, m), 1.90-2.00 (2H, m), 3.01-3.18 (2H, m) , 3.40-3.52 (2H, m), 3.72-3.80 (HH, m), 4.75 (2H, d, J = 5.2Hz), 7.49 (HH, dd, J = 8.6, 2.0Hz), 7.66 (HH, d, J = 8.6Hz), 7.79 (HH, d, J = 2.0Hz), 8.25 (1H, d, J = 8.6Hz), 8.47 (HH, dd, J = 8.6, 1.0Hz), 9.36 (HH, d, J = l, 0Hz), 10.24 (ÍH, broad). Example 104 1- [6-Bromo-4- [(3-chloro-4-methoxybenzylamine] -1-phthalazinyl] -4-piperidinol hydrochloride ? -NMR (400MHZ, DMSO-d6) d: 1.59-1, 68 (2H, m), 1.85-1.94 (2H, m), 2.94-3.08 (2H, m) , 3.45-3.55 (2H, m), 3.70-3.76 (1H, m), 3.83 (3H, s), 4.69 (2H, d, J = 4.8Hz) , 7,14 (ÍH, d, J = 8.4Hz), 7.44 (IH, d, J = 8.4Hz), 7.59 (IH, s), 8.01 (IH, d, J = 8.8Hz), 8.26 (HH, d, J = 8.8Hz), 9.18 (HH, s). Example 105 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (1H-1-pyrazolyl) -1-phthalazinyl] -4-piperidinol hydrochloride ? -NMR (400MHZ, DMSO-d6) d: 1.6-1.75 (2H, m), 1.85-2.0 (2H, m), 2.95-3.1 (2H, m) , 3.3-3.55 (2H, m), 3.7-3.8 (1H, m), 3.82 (3H, s), 4.68-4.77 (2H, m), 6 , 72 (ÍH, m), 7,14 (ÍH, d, J = 8.4Hz), 7.48 (IH, d, J = 7.6Hz), 7.63 (IH, s), 7.93 (IH, d, J = 1, 6Hz), 8.22 ( 1H, d, J = 8.8Hz, 8.61; iH, dd, J = 1, 6, 8.8Hz), 8.97 (1H, s), 9.46 (1H, m).

Example 106 7- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (1H-1-pyrazolyl) -1-phthalazinyl] -7-azaspiro [3.5] nonan-2-ol hydrochloride 1 H-NMR (400MHz, DMSO-d 6) d: 1.55-1.68 (2H, m), 1.68-1.80 (4H, m), 2.14-2.25 (2H, m) , 3.0-3.2 (4H, m), 3.82 (3H, s), 4.14 (H, hep., J = 7.2Hz), 4.72 (2H, m), 6, 72 (ÍH, t, J = 2Hz), 7,14 (ÍH, d, J = 8,4Hz), 7,47 (ÍH, d, J = 8,4Hz), 7,62 (ÍH, s), 7.93 (HH, d, J = 1, 6Hz), 8.20 (HH, d, J = 9.2Hz), 8.60 (HH, dd, J = 2.0, 9.2Hz), 8 , 94 (ÍH, d, J = 2.4Hz), 9.43 (1H, s).

Example 107 [1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (1H-1-pyrazolyl) -1-phthalazinyl] -4-fluoro-4-piperidinyl] me-tanol hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.85-2.0 (2H, m), 1.95-2.1 (2H, m), 3.05-3.2 (2H, m) , 3.4-3.6 (2H, m), 3.51 (2H, d, J = 20Hz), 3.83 (3H, s), 4.74 (2H, d, J = 5.2Hz) , 6.72 (ÍH, t, J = 1, 6Hz), 7,14 (ÍH, d, J = 8,8Hz), 7,48 (ÍH, d, J = 8,4Hz), 7,64 ( ÍH, s), 7.93 (ÍH, d, J = l, 6Hz), 8.25 (1H, d, J = 9.2Hz), 8.61 (1H, dd, J = 2.0, 9 , 2Hz), 8.95 (ÍH, s), 9.44 (ÍH, s). Example 108 1- [4- [(3-Bromo-4-methoxybenzyl) amino] -6- (1H-1-pyrazolyl) -1-phthalazinyl] -4-piperidinol hydrochloride 1H-NR (400MHz, DMSO-d6) d: 1.6-1.74 (2H, m), 1.87-2.0 (2H, m), 2.9-3.1 (2H, m) , 3.4-3.55 (2H, m), 3.7-3.8 (1H, m), 3.81 (3H, s), 4.65-4.8 (2H, m), 6 , 72 (HH, m), 7.10 (HH, d, J = 8.8Hz), 7.53 (1H, d, J = 8.0Hz), 7.79 (HH, s), 7.93 (ÍH, d, J = 1, 2Hz), 8,21 (ÍH, d, J = 8,8Hz), 8,61 (ÍH, d, J = 8,8Hz), 9,00 (ÍH, d, J = 2.8 Hz), 9.51 (ÍH, s).

Example 109 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (1 H-1,2,3-triazol-1-yl) -1-phthalazinyl] -4-piperidinol hydrochloride XH-NMR (400MHz, DMSO-d6) d: 1.62-1.75 (2H, m), 1.9-2.0 (2H, m), 3.0-3.1 (2H, m 3 , 3-3.58 (2H, m 3.7-3.8 (1H, m) 3.83 (3H, s), 4.73 (2H, d, J = 5, 6Hz), 7.15 (1H, d, J = 8.8Hz), 7.46 (HH, d, J = 8.4Hz), 7.62 (HH, s), 8.13 (HH, m), 8.32 (1H, d, J = 8.8Hz), 8.68 (HH, d, J = 9.2Hz), 9.17 (HH, s), 9.56 (1H, s). Example 110 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazinecarbaldehyde 06-methyloxime hydrochloride ? -NMR (400MHz, DMS0-d6) d: 1.60-1.70 (2H, m), 1.87-1.70 (2H, m), 2.96-3.05 (2H, m) , 3.30-3.50 (2H, m), 3.68-3.78 (HI, m), 3.83 (3H, s), 3.99 (3H, s), 4.66-4 , 73 (2H, m), 7.14 (HH, d, J = 8Hz), 7.42 (HH, dd, J = 2.8Hz), 7.57 (HH, d, J = 2Hz), 8 , 13 (ÍH, d, J = 8Hz), 8.28 81H, d, J = 8Hz), 8.39 (1H, s), 8, 94 (ÍH, s broad). EXAMPLE 111 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazinecarbaldehyde 06-ethylxime hydrochloride ? -NMR (400MHz, DMSO-de) d: 1.28 (3H, t, J = 6Hz), 1.60-1.73 ; 2H, m 1.87-1.98 (2H, m), 2.94-3.06 (2H, m 3.39-3.52 (2H, m), 3.68-3.78 (HH, m), 3.83 (3H, s), 4.25 (2H, c, J = 6Hz), 4.67-4.74 (2H) , m), 7.13 (HH, d, J = 9Hz), 7.42 (1H, d, J = 9Hz), 7.58 (HH, s), 8.13 (HH, d, J = 8Hz ), 8.30 (1H, d, J = 8Hz), 8.39 (HH, s), 8.97 (HH, s).

Example 112 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -6-phthalazinecarbaldehyde 6-benzyl oxime hydrochloride ? -NMR (400MHz, DMSO-d6) d: 1.59-1.71 (2H, m), 1.87-1.96 (2H, m), 2.94-3.05 (2H, m) , 3.37-3.51 (2H, m), 3.68-3.78 (HH, m), 3.82 (3H, s), 4.67-4.76 (2H, m), 5.27 (2H, s), 7.13 (HH, d, J = 9Hz), 7.29-7.48 (6H, m), 7.59 (1H, s), 8.12 (HH, d, J = 9Hz), 8.29 (HH, d, J = 9Hz), 8.45 (1H, s), 9.04 (ÍH, s broad). Example 113 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3-fluoro-3- (hydroxymethyl) tetrahydro-lH-1-pyrrolyl] -6-phthalazinecarbonitrile hydrochloride 1H-NMR (400MHz, DMSO-d6) d: 2.09-2.28 (2H, m 3.50-4.05 (6H, m), 3.81 (3H, s), 4.66 (2H, s), 7.11 (1H, d, J = 8.0Hz), 7.43 (IH, d, J = 8 , 0Hz), 7.58 (HH, s), 8.43 (HH, d, J = 8.4Hz), 8.53 (HH, s), 9.45 (HH, s). Example 114 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-l-oxa-8-azaspiro [4.5] deca-8-yl) -6-phthalazinecarbonitrile hydrochloride ? -NMR (400MHz, DMS0-d5) d: 1.65-1.85 (3H, m), 1.87-2.01 (2H, m), 3.16-3.63 (8H, m) , 3.82 (3H, s), 4.32 (HH, s), 4.73 (2H, d, J = 4.8Hz), 7.13 (HH, d, J = 8.4Hz), 7 , 48 (HH, d, J = 8.0Hz), 7.62 (HH, s), 8.23 (HH, d, J = 8.0Hz), 8.44 (HH, d, J = 8, 0Hz), 9.57 (ÍH, s), 10.78 (1H, s). Example 115 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [2- (1-hydroxycyclopentyl) -1-ethynyl] -6-phthalazinecarbonitrile 1H-NR (400MHz, DMSO-d6) d: 1.69-1.86 (4H, m), 1.97-2.04 (4H, m), 3.82 (3H, s), 4.75 (2H, d, J = 5.4Hz), 5.60 (IH, s), 7.10 (IH, d, J = 8.8Hz), 7.36 (IH, dd, J = 8.8, 1.2Hz), 7.49 (1H, d, J = 1, 2Hz), 8.19 (IH, d, J = 8.8Hz), 8.31 (IH, dd, J = 8.8, 0 , 6Hz), 8.52 (HH, t, J = 5.4Hz), 8.97 (HH, d, J = 0.6Hz). Example 116 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [2- (1-hydroxycyclopentyl) ethyl] -6-phthalazinecarbonitrile hydrochloride 690 mg of 4- [(3-chloro-4-methoxybenzyl) amino] -1- [2- (1-hydroxycyclopentyl) -1-ethi-nyl] -6-phthalazinecarbonitrile was dissolved in 200 ml of tetrahydrofuran, 50 ml of tetrahydrofuran were added. mg of Pd 1Q% -C and the mixture was stirred for 0.5 h in a hydrogen atmosphere. The reaction solution was filtered through Celite and the filtrate was evaporated. The resulting residue was purified by silica gel column chromatography to obtain 400 mg of 4- [(3-chloro-4-methoxybenzyl) amino] -1- [2- (1-hydroxycyclopentyl) ethyl] -6- phthalazinecarbonitrile. This product was converted into the usual form in the hydrochloride. ? -NMR (400MHz, DMSO-d6) d: 1.47-1.78 (8H, m), 1.89-1.94 (2H, m), 3.24-3.33 (2H, m), 3.84 (3H, s), 4.74 (2H, d, J = 4.4Hz), 7.15 (1H, d) , J = 8.4Hz), 7.45 (HH, dd, J = 8.4, 2.0Hz), 7.60 (1H, d, J = 2.0Hz), 8.46 (HH, d, J = 8.8Hz), 8.55 (ÍH, dd, J = 8.8, 1.2Hz), 9.40 (ÍH, broad). The following compounds were obtained in the same way. Example 117 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-3-methylbutyl) -6-phthalazinecarbonitrile hydrochloride ? -NMR (400MHz, DMSO-d6) d: 1.17 (6H, s), 1.73-1.80 (2H, m), 3.17-3.24 (2H, m), 3.80 (3H, s), 4.78 (2H, d, J = 4.4Hz), 7.10 (HH, d, J = 8.4Hz), 7.48 (HH, dd, J = 8.4, 1.8Hz), 7.62 (HH, d, J = 1, 8Hz), 8.43 (HH, d, J = 8.6Hz), 8.51 (1H, dd, J = 8.6, 1 , 2Hz), 9,63 (ÍH, broad), 10,30 (ÍH, broad). Example 118 1- (3-Amino-3-methylbutyl) -4- [(3-chloro-4-methoxybenzyl) amino] -6-phthalazinecarbonitrile dihydrochloride ? -NMR (400MHz, DMSO-d6) d: 1.37 (6H, s), 2.00-2.19 (2H, m), 3.21-3.56 (2H, m), 3.84 (3H, s), 4.78 (2H, d, J = 4.4Hz), 7.15 (HH, d, J = 8.4Hz), 7.46 (HH, d, J = 8.4Hz) , 7.61 (HH, s), 8.15-8.29 (4H, m), 8.48 (1H, d, J = 8.8Hz), 8.56 (HH, d, J = 8, 8Hz), 9.38 (1H, broad).

Example 119 4- [(3-Chloro-4-methoxybenzyl) amino] -1- [3- (dimethylamino) propyl] -6-phthalazinecarbonitrile dihydrochloride ? -NMR (400MHz, DMSO-d6) d: 2.11-2.19 (2H, m), 2.74 (3H, s), 2.75 (3H, s), 3.16-3.29 (4H, m), 3.85 (3H, s), 4.80 (2H, d, J = 5.2 Hz; 7.16; IH, d, J =, 4Hz), 7.48 (IH, dd, J = 8.4, 2.0Hz), 7.63 (IH, d, J = 2.0Hz), 8, 49 (HH, d, J = 8.4Hz), 8.56 (HH, dd, J = 8.4, 1.4Hz), 9.47 (HH, d, J = 1, 4Hz), 10.56 (2H, broad).

Claims (36)

Claims

1. A phthalazine compound represented by the formula (I), a pharmacologically acceptable salt thereof or a hydrate thereof: where R1 and R2 are the same or different from each other and represent a halogen atom, a C1 to C4 alkyl group which may be substituted with a halogen atom, a hydroxyl group, a C1 to C4 alkoxy group which may be substituted with a halogen atom, or a cyano group; X represents a cyano group, a nitro group, a halogen atom, a thiocarbamoyl group, a hydroxyimino group which may be substituted with a Cl to C4 alkyl group, an arylalkyl group (Cl to C4) or a carboxyalkyl group (Cl to C4) ), or a heteroaryl group which may be substituted with 1 to 3 substituent groups selected from the following substituent groups A; Y represents: i) a group represented by the formula (II):

R3 A i D - (cH) m-w (II) wherein ring A represents a 4 to 8 membered amine ring, which may be substituted with a methyl group and may have a double bond; D represents a single bond or an oxygen atom; R3 represents a hydrogen atom, a Cl to C4 alkyl group or a halogen atom; m represents an integer of 0 or 1 to 3; represents an amino group, a hydroxyl group, a cyano group, a carboxyl group that may be protected, or a Cl to C4 alkoxy group; ii) a group represented by the formula (III): wherein ring B represents an amine ring of 4 to 8 members which may have a double bond and n and p are equal or different from each other and represent an integer from 0 to 3; iii) a group represented by the formula (IV): where the ring G represents a 4 to 8 membered amine ring which may have a double bond, E represents a hydroxyl group, a halogen atom, a Cl to C4 alkyl group or a Cl to C4 alkoxy group; J is the formula (CHR) qQ (where R represents a hydrogen atom a Cl to C4 alkyl group, Q represents a hydroxyl group, a halogen atom, a carboxyl group which may have a protective group, a carbamoyl group or a group azolyl which does not contain a hetero atom other than a nitrogen atom, q is an integer of 0 or 4), or E and J can form a 3 to 6 membered ring together with the carbon atom to which they are attached , the ring optionally having a heteroatom and optionally having a substituent group; iv) a group represented by the formula (V): where M represents a bond or a Cl to C4 alkylene group which may be substituted with a hydroxyl group, a carboxyl group, a Cl to C4 alkyl group or a Cl to C4 alkoxy group; the ring K represents a 5- to 8-membered amine ring formed together with M, and the ring L represents a 5- to 8-membered alkyl ring which may have a substituent group and which may have an oxygen atom; v) a group represented by the formula (VI): wherein the ring P represents a 5-7 membered amine ring and R5 represents a hydrogen atom or a Cl to C4 alkyl group which may be substituted with a halogen atom, a hydroxyl group or a carboxyl group; vi) an alkynyl group, an alkenyl group or an alkyl group, all of which may have a substitution group; vii) a phenyl group which may be substituted with 1 to 3 substituent groups selected from the following substituent groups A; or viii) a pyridyl group, a pyrimidyl group, a thienyl group, a thiazolyl group or a furyl group, all of which may be substituted with 1 to 3 substituent groups selected from the following substituent groups A; (substituent group A) a Cl to C4 alkyl group which may be substituted with a halogen atom, a cyano group, a nitro group or a hydroxyl group; a Cl to C4 alkoxy group which may be substituted with a halogen atom, a cyano group, a nitro group or a carboxyl group which may have a protecting group; a hydroxyl group that can have a protective group; a carbamoyl group which may be substituted with a lower alkyl group; a halogen atom, and an amino group which may be substituted with an acyl group Cl to C4, an alkylsulfonyl group Cl to C4 or an arylsulfonyl group which may have a substituent group; 1 is an integer from 1 to 3; with the proviso that the following cases be excluded: the case where 1 is 1 or 2, X is a cyano group, a nitro group or a chlorine atom, R1 is a chlorine atom, R2 is a group methoxy, ring A is a 5- or 6-membered amine ring, D is a single bond, m is 0 and is a carboxyl group which may have a protecting group or an alkoxy Cl to C4 group; the case where 1 is 1, R1 is a chlorine atom, R2 is a methoxy group, ring A is a 5 or 6 membered saturated amine ring, D is a single bond and W is a hydroxyl group; the case where 1 is 1, ring B is an amine ring of 5 or 6 members and both n and p are 0; the case where 1 is 1, E and Q are hydroxyl groups and q is 0, and the case where 1 is 1, X is a chlorine atom and Y is a phenyl group substituted with a methoxy group. 2. The phthalazine compound claimed in Claim 1, wherein R1 is a halogen atom, a C1 to C4 alkyl group which may be substituted with a halogen atom or a cyano group and R2 is a halogen atom, a hydroxyl group or a Cl to C4 alkoxy group, a pharmacologically acceptable salt thereof or a hydrate thereof.

3. The phthalazine compound claimed in Claim 1 or 2, wherein Y is represented by the formula (II): (where ring A, D, R, and m have the same meanings as defined above), a pharmacologically acceptable salt thereof or a hydrate thereof.

4. The phthalazine compound claimed in Claim 1 or 2, wherein Y is represented by the formula (III): (where ring B, n and p have the same meanings as defined above), a pharmacologically acceptable salt thereof or a hydrate thereof.

5. The phthalazine compound claimed in Claim 1 - or 2, wherein Y is represented by the formula (IVJ: (where the ring G, E and J have the same meanings as defined above), a pharmacologically acceptable salt thereof or a hydrate thereof.

6. The phthalazine compound claimed in Claim 1 or 2, wherein Y is represented by the formula (V): (wherein M, ring K and ring L have the same meanings as defined above), a pharmacologically acceptable salt thereof or a hydrate thereof.

7. The phthalazine compound claimed in Claim 1 or 2, wherein Y is represented by the formula

(SAW) : ÑOR5 (VI) (where the ring P and R have the same meanings as defined above), a pharmacologically acceptable salt thereof or a hydrate thereof. 8. The phthalazine compound claimed in Claim 1 or 2, wherein Y is an alkynyl group, an alkenyl group or an alkyl group, all of which may have a substituent group, a pharmacologically acceptable salt thereof or a hydrate thereof .

9. The phthalazine compound claimed in Claim 1 or 2, a pharmacologically acceptable salt thereof or a hydrate thereof, wherein Y is a phenyl group which may be substituted with the above substituent group A.

10. The claimed phthalazine compound in Reivinication 1 or 2, a pharmacologically acceptable salt thereof or a hydrate thereof, wherein Y is a pyridyl group, a pyrimidyl group, a thienyl group, a thiazolyl group or a furyl group, all of which may be substituted with the above substituent group A.

11. The phthalazine compound claimed in any of Claims 1 to 3, wherein Y is a group represented by the formula (II), the ring A is a 4- to 8-membered amine ring that can be have a double bond, is a hydroxyl group, m is an integer of 0 or 1 to 3 and i) D is a single bond and R3 is a halogen atom or ii) D is an oxygen atom and R3 is a hydrogen atom, hydrogen, a salt of it pharmacologically acceptable or a hydrate thereof.

12. The phthalazine compound claimed in any of Claims 1, 2 and 4, wherein Y is the group re-presented by the formula (III), ring b is a 6-membered amino ring, n is O or l and is , a pharmacologically acceptable salt thereof or a hydrate thereof.

13. The phthalazine compound claimed in any one of Claims 1, 2 and 5, a pharmacologically acceptable salt thereof or a hydrate thereof, wherein Y is the group represented by the formula (IV), E and J form a ring of 3 to 6 members which may have a heteroatom and may have a substituent group together with the carbon atom to which they are attached and the G ring is a 4 to 8 membered amine ring which may have a double bond.

14. The phthalazine compound claimed in any of Claims 1, 2 and 5, wherein Y is the group represented by the formula (IV); E is a hydroxyl group, a halogen atom, a Cl to C4 alkyl group or a Cl to C4 alkoxy group; J is represented by the formula - (CHR) qQ (where R4 is a hydrogen atom or a Cl to C4 alkyl group, Q is a hydroxyl group, a halogen atom, a carboxyl group which may have a protective group, a group carbamate or an azolyl group which does not contain a hetero atom other than a nitrogen atom and q is an integer of 0 or 1 to 4), and ring G is an amine ring of 4 to 8 members which may have a double link, a pharmacologically acceptable salt or a hydrate thereof.

15. the phthalazine compound claimed in any of Claims 1, 2 and 6, wherein Y is the group represented by the formula (V), the rings K and L have the same meanings as defined above and M is an alkylene group C1 to C4 substituted with a hydroxyl group, a carboxyl group, a C1 to C4 hydroxyalkylene group or a carboxyalkylene group (Cl to C4), a pharmacologically acceptable salt or a hydrate thereof.

16. The phthalazine compound claimed in any of Claims 1, 2 and 8, wherein Y is an alkynyl group which may have a substituent group and which has a triple bond, a pharmacologically acceptable salt or a hydrate thereof.

17. The fused phthalazine compound claimed in Claim 1, wherein the compound is selected from the following group, a pharmacologically acceptable salt or a hydrate thereof: 1) 1- (4-aminopiperidino) -4- [(3-chloro- 4-methoxybenzyl) amino] -6-ftalazinacarbonitrilo, 2) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [(4-hydroxy-4-hi-droximetil) piperidino] -6-ftalazinacarbonitrilo, 3 ) 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (4-cyanopiperidin-none) -6-phthalazinecarbonitrile, 4) 4- [(3-chloro-4-methoxybenzyl) amino] -1- ( 4-cyanophenyl) -6-phthalazinecarbonitrile, 5) 4- [4- [(3-chloro-4-methoxybenzyl) amino] -6-cyanophthalazin-1-yl] phenylcarboxamide, 6) 4- [(3-chloro-4 -metoxifenetil) amino] -1- (4-cianopiperidi-no) -6-ftalazinacarbonitrilo, 7) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (2-pyridyl) -6-ftalazinacarbonitrilo , 8) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-pyridyl) -6-phthalazinecarbonitrile, 9) 4- [(3-chloro-4-methoxybenzyl) amino] -1 - (4-pyridyl) -6-phthalazine carbonitrile, 10) 4- [(3-chloro-4-methoxyphenethyl) amino] -1- (2-pyridyl) -6-phthalazinecarbonitrile, 11) 4- [(3-chloro-4-methoxyphenethylamino)] -1- ( 3-pyridyl) -6-phthalazinecarbonitrile, 12) 4- [(3-chloro-4-methoxyphenethyl) amino] -1- (4-pyridyl) -6-phthalazinecarbonitrile, 13) 4- [(3-chloro-4- methoxybenzyl) amino] -1- (2-hydroxy-7-aza-spiro [3.5] non-7-yl) -6-phthalazinecarbonitrile, 14) 4- [(3-chloro-4-methoxyphenethyl) amino] -1- (2-hydroxy-7-azaspiro [3.5] non-7-yl) -6-phthalazinecarbonitrile, 15) 4- [(3-bromo-4-methoxybenzyl) amino] -1- (2-hydroxy-7-aza- spiro [3.5] non-7-yl) -6-phthalazine, 16) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (2-hydroxy-6-aza-spiro [3.4] oct-6) -yl) -6-phthalazinecarbonitrile, 17) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (1-fluoro-2-hydroxyethyl) piperidino] -6-phthalazinecarbonitrile, 18) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4-fluoro-4- (hydroxymethyl) piperidino] -6-phthalazinecarbonitrile, 19) 4- [(3-chloro-4-methoxybenzyl) amino] -1 - [4- (hydroxymethyl) -4-methox ipiperidino] -6-ftalazinacarbonitrilo, 20) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (hidroxieto-xi) piperidino] -6-ftalazinacarbonitrilo, 21) 4- [(3-chloro -4-methoxybenzyl) amino] -1- (3-hydroxy-3-methyl-1-butynyl) -6-phthalazinecarbonitrile, 22) 1- (3-amino-3-methyl-1-butynyl) -4- [(3-chloro-4-methoxy-benzyl) amino] -6-phthalazinecarbonitrile, 23) 4- [(3-chloro-4-methoxybenzyl) amino] -1 - [(3-hydroxy-3-methyl-butyl) -6-ftalazinacarbonitrilo, 24) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-hydroxyimino-piperidino) -6-ftalazinacarbonitrilo, 25) 4- [(3-bromo-4-methoxybenzyl) amino] -1- (4-hydroxypiperidino) -5-ftalazinacarbonitrilo, 26) 1- (4-hydroxypiperidino) -4- [(4-methoxy-3-methylbenzyl) amino] -6-ftalazinacarbonitrilo, 27) 1 - (4-hydroxypiperidino) -4- [[4-methoxy-3- (trifluoromethyl) benzyl] amino] -6-phthalazinecarbonitrile, 28) 1- (4-hydroxypiperidino) -4- [(3-iodo-4-methoxybenzyl) ) -amino] -6-phthalazinecarbonitrile, 29) 1- [4-fluoro-4- (hydroxymethyl) piperidino] -4- [(4-methoxy) 3-methylbenzyl) amino] -6-ftalazinacarbonitrilo, 30) 4- [(3-bromo-4-methoxybenzyl) amino] -1- [4- (hidroxime-til) piperidino] -6-ftalazinacarbonitrilo, 31) 4- [ (3-chloro-4-methoxybenzyl) amino] -1- [4- (fluoromethyl) -4-hydroxypiperidino] -6-phthalazinecarbonitrile, 32) 4- [(3-chloro-4-methoxybenzyl) amino] -1- ( 4-hydroxypiperi-dino) -6-phthalazinecarbaldehyde 06-methyloxime, 33) 1- [4- [(3-chloro-4-methoxybenzyl) amino] -6- (lH-1-pyrazol-yl) -1-phthalazinyl] 4-piperidinol, 34) 4- [(3-cyano-4-methoxybenzyl) amino] -1- (4-hydroxypiperi-dino) -6-phthalazinecarbonitrile, 35) (endo) -4- [(3-chloro- 4-methoxybenzyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2.1] oct-8-yl) -6-phthalazinecarbonitrile and 36) (sin) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (9-hydroxy-3-azabicyclo [3.3.1] non-3-yl) -6-phthalazinecarbonitrile.

18. The ftalazine fused compound claimed in Claim 1, wherein the compound is selected from the following group, a pharmacologically acceptable salt or a hydrate thereof. 1) 4- [(3-Chloro-4-methoxybenzyl) amino] -1- (2-pyridyl) -6-phthalazinecarbonitrile, 2) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-pyridyl) -6-phthalazinecarbonitrile, 3) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-pyridyl) -6-phthalazinecarbonitrile, 4) 4- [(3 -chloro-4-methoxyphenethyl) amino] -1- (2-pyridyl) -6-phthalazinecarbonitrile, 5) 4- [(3-chloro-4-methoxyphenethylamino)] -1- (3-pyridyl) -6-phthalazinecarbonitrile, 6) 4- [(3-chloro-4-methoxyphenethyl) amino] -1- (4-pyridyl) -6-phthalazinecarbonitrile, 7) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (2 -hydroxy-7-azaspiro] 3.5] non-7-yl) -6-phthalazinecarbonitrile, 8) 4- [(3-chloro-4-methoxyphenethyl) amino] -1- (2-hydroxy-7-aza-spiro [ 3.5] non-7-yl) -6-phthalazinecarbonitrile, 9) 4- [(3-bromo-4-methoxybenzyl) amino] -1- (2-hydroxy-7-aza-spiro [3.5] non-7-yl) ) -6-phthalazinecarbonitrile, 10) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (2-hydroxy-6-aza-spiro [3.4] oct-6-yl) -6-phthalazinecarbonitrile, ) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (1- fluoro-2-hydroxyethyl) piperidino] -6-phthalazinecarbonitrile, 12) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4-fluoro-4- (hydroxymethyl) piperidino] -6-phthalazinecarbonitrile, 13 ) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (hydroxymethyl) -4-methoxypiperidino] -6-phthalazinecarbonitrile, 14) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (hydroxyethoxy) piperidino] -6-phthalazinecarbonitrile, 15) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-3-methyl-1-) butynyl) -6-phthalazinecarbonitrile, 16) 1- (3-amino-3-methyl-l-butynyl) -4- [(3-chloro-4-methoxy-benzyl) amino] -6-phthalazinecarbonitrile, 17) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-3-methyl-butyl) -6-phthalazinecarbonitrile, 18) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-hydroxyimino-piperidino) -6-phthalazinecarbonitrile, 19) 4- [(3-bromo-4-methoxybenzyl) amino] -1- (4-hydroxypropi-dino) -6-phthalazinecarbonitrile, 20) 1- (4- hydroxypiperidino) -4- [(4-methoxy-3-methylbenzyl) -amino] -6-phthalazinecarbonitrile, 21) 1- [4-fluoro-4- ( hydroxymethyl) piperidino] -4- [(4-methoxy-3-methylbenzyl) amino] -6-phthalazinecarbonitrile, 22) 4- [(3-chloro-4-methoxybenzyl) amino] -1- [4- (fluoromethyl) - 4-hydroxypiperidino] -6-phthalazinecarbonitrile, 23) 4- [(3-chloro-4-methoxybenzyl) amino] -1- (4-hydroxypiperi-dino) -6-phthalazinecarbaldehyde 06-methyloxime, 24) 1- [4- [(3-Chloro-4-methoxybenzyl) amino] -6- (lH-1-pyrazol-yl) -1-phthalazinyl] -4-piperidinol, 25) 4- [(3-cyano-4-methoxybenzyl) amino] -1- (4-hydroxypiperi-dino) -6-phthalazinecarbonitrile, 26) (endo) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (3-hydroxy-8-azabicyclo [3.2 .1] oct-8-yl) -6-phthalazinecarbonitrile and 27) (sin) -4- [(3-chloro-4-methoxybenzyl) amino] -1- (9-hydroxy-3-azabicyclo [3.3.1] non-3-yl) -6-phthalazinecarbonitrile.

19. A prophylactic and therapeutic agent for erectile dysfunction, containing the claimed phthalazine compound-in any of Claims 1 to 18, a pharmacologically acceptable salt thereof or a hydrate thereof as an active component.

20. A therapeutic agent for erectile dysfunction, containing the compound phthalazine represented by the formula (VII), a pharmaceutically acceptable salt thereof or a hydrate thereof as an active component: where 1 'is an integer from 1 to 3; R represents a halogen atom, a Cl to C4 alkyl group which may be substituted with a halogen atom or a cyano group; X1 represents a cyano group, a nitro group or a halogen atom; Y1 represents: i) a group represented by the formula (VIII) -N * AAll - (CH2) ml- (vpi) wherein the Al ring represents a 5 or 6 membered amine ring, ml is an integer of 0 or 3 and Z represents an amino group, a hydroxyl group which may have a protecting group, a carboxyl group which may have a group protector, a Cl to C4 alkoxy group or a cyano group; ii) a group represented by the formula (IX): where the ring Bl represents an amine ring of 5 or 6 members and ni and pl are integers of 0 or 1 to 3; iii) a thiomorpholino group, where its morpholino group or its sulfur atom may be oxidized; iv) a phenyl group which may be substituted with 1 to 3 substituent groups selected from the following substituent groups Al; v) a heteroaryl group which is a pyridyl group, a pyrimidyl group, a thienyl group or a furyl group, all of which may be substituted with 1 to 3 substituent groups selected from the following substituent groups Al; or vi) a group of formula -N (R7) - (CH2) S-Het, where R7 represents a lower alkyl group, Het represents a pyridyl group or a pyrimidyl group, all of which may be substituted with 1 to 3 substituent groups selected from the following substituent groups Al, and s is an integer of 0 or 1 to 3; (substituent group Al) a lower alkyl group substituted with a halogen atom, a cyano group, a nitro group or a hydroxyl group; a lower alkoxy group which may be substituted with a halogen atom, a cyano group, a nitro group or a hydroxyl group; a cyano group; a nitro group; a carboxyl group which may have a protecting group; a hydroxyl group which may have a protecting group; a carbamoyl group which may be substituted with a lower alkyl group; a halogen atom, and a phenyl group which may be substituted with an alkyl group, an alkoxy group, a halogen atom or an amino group.

21. A prophylactic and therapeutic agent for erectile dysfunction, containing the phthalazine compound claimed in Claim 20, a pharmaceutically acceptable salt thereof or a hydrate thereof as an active component, wherein Y1 is: i) a group depicted by the formula (VIII): where the ring Al, Z and ml have the same meanings as defined above; ii) a group represented by the general formula (IX): where the ring Bl, ni and pl have the same meanings as defined above; or iii) a thiomorpholino group, where its sulfur atom may be oxidized.

22. The prophylactic or therapeutic agent for erectile dysfunction claimed in Claim 20, which contains the compound phthalazine, a pharmacologically acceptable salt thereof or a hydrate thereof as an active component, wherein Y1 is a phenyl group or a group heteroaryl which is a pyridyl group, a pyrimidyl group, a thienyl group or a furyl group, all of which may be substituted with 1 to 3 substituent groups selected from the above substituent group Al.

23. The prophylactic and therapeutic agent for erectile dysfunction claimed in Claim 20, which contains the compound phthalazine, a pharmacologically acceptable salt thereof or a hydrate thereof as an active component, wherein Y1 is the formula -N (R7) - (CH2) S-Het (where Het represents a group pyridyl which may be substituted with 1 to 3 substituent groups selected from the above substituent groups Al and R7 and s have the same meanings than those defined above.

24. The therapeutic agent for erectile dysfunction as claimed in Claim 20, which contains the compound phthalazine, a pharmacologically acceptable salt thereof or a hydrate thereof as an active component, wherein the compound is selected from the following group: 1) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (3- hydroxy-methylpiperidino) phthalazine, 2) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (3,4-dihydroxypiperidino) phthalazine, 3) 4- (4-aminopiperidino) -1- (3-Chloro-4-methoxybenzyl) -ami-no-6-cyanophthalazine, 4) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-l- (4-methoxypi-peridino) phthalazine, 5) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (4-hydroxy-4-hydroxymethylpiperidino) phthalazine, 6) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1 - (4,4-dihydroxyethylpiperidino) phthalazine, 7) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (4-cyanopiperidino) phthalazine, 8) 4- (3-chloro -4-methoxybenzyl) amino-6-cyano-l- [(3R) -hydro-xypyrrolidino] phthalazine, 9) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-l- (3-hydroxy) methylpyrrolidino) phthalazine, 10) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-l- (3, 4-dihi-droxipyrrolidino) phthalazine, 11) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-l- (2-methoxy-methylpyrrolidino) phthalazine, 12) 1-oxide of 4- [4- ( 3-chloro-4-methoxybenzylamino) -6-cyano-noftalazin-1-yl] thiomorpholine, 13) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (4-methoxy-phenyl) phthalazine , 14) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (4-cyanophenyl) phthalazine, 15) 4- [4- (3-chloro-4-methoxybenzylamino) -6- cyanophthalazin-1-yl] phenyl-4-carboxamide, 16) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-1- (2-pyridyl-methyl) aminophthalazine, 17) 4- (3-chloro -4-methoxybenzyl) amino-6-cyano-l- [N-methyl-N- (2-pyridylmethyl) amino] phthalazine, 18) 4- (3-chloro-4-metaxifenethyl) amino-6-cyano-1- (4-cyano-piperidino) phthalazine, 19) 4- (3-chloro-4-methoxyphenethyl) amino-6-cyano-l- (3-hydro-ximethylpiperidino) phthalazine, 20) 4- (3-chloro-4-) methoxyphenethyl) amino-6-cyano-l- (4-hydroxymethylpiperidino) phthalazine, 21) 4- (3-chloro-4-methoxybenzyl) amino-6-cyano-l-phenylphthalazine, 22) 4- (3 -chloro-4-methoxybenzyl) -6 -cyano-l- (2-pyridyl) phthalazine, 23) 4- (3-chloro-4-methoxybenzyl) -6-cyano-l- (3-pyridyl) phthalazine, 24) 4- (3-chloro-4-) methoxybenzyl) -6-cyano-1- (4-pyridyl) phthalazine, 25) 4- (3-chloro-4-methoxyphenethyl) -6-cyano-1- (2-pyridyl) phthalazine, 26) 4- (3- chloro-4-methoxyphenethyl) -6-cyano-1- (3-pyridyl) phthalazine and 27) 4- (3-chloro-4-methoxyphenethyl) -6-cyano-1- (4-pyridyl) phthalazine.

25. A prophylactic and therapeutic agent for female sexual dysfunction or dysmenorrhea, containing the phthalazine compound claimed in any one of Claims 1 to 24, a pharmacologically acceptable salt thereof or a hydrate thereof as an active component.

26. Use of the phthalazine compound claimed in any one of Claims 1 to 18, a pharmacologically acceptable salt thereof or a hydrate thereof to produce a therapeutic agent for erectile dysfunction.

27. A process for producing a compound of formula (XI): (where X, Y3, R1, R2 and 1 have the same meanings as defined above), which consists in the step of reacting a compound represented by the formula (X): (where Hal represents a halogen atom and R1, R2, 1 and X have the same meanings as defined above) with a compound of formula Y3-B (0H) 2 (where Y3 represents a phenyl group, a pyridyl group, a pyridomethyl group, a thienyl group or a furyl group, all of which may have a substituent group selected from the above substituent groups Al).

28. A pharmaceutical composition comprising a pharmacologically or clinically effective dose of the phthalazine compound claimed in Claim 1 or obtained by the method claimed in Claim 27, a pharmacologically acceptable salt thereof or a hydrate thereof and pharmacologically acceptable carriers.

29. A method for preventing and treating erectile dysfunction, which consists of the step of administering a pharmacologically or clinically effective dose of the phthalazine compound claimed in Claim 1, a pharmacologically acceptable salt thereof or a hydrate thereof to a patient who suffers from erectile dysfunction.

30. A method for preventing and treating female sexual dysfunction or dysmenorrhea, which is the step of administering a pharmacologically or clinically effective dose of the phthalazine compound claimed in Claim 1, a pharmacologically acceptable salt thereof or a hydrate thereof. a patient suffering from female sexual dysfunction or dysmenorrhea.

31. Use of the phthalazine compound claimed in Claim 1, a pharmacologically acceptable salt thereof or a hydrate thereof to prevent and treat erectile dysfunction.

32. Use of the phthalazine compound claimed in Claim 1, a pharmacologically acceptable salt thereof or a hydrate thereof to prevent and treat female sexual dysfunction or dysmenorrhea. A method for preventing and treating erectile dysfunction, which consists in the step of administering a pharmacologically or clinically effective dose of the phthalazine compound claimed in Claim 20, a pharmacologically acceptable salt thereof or a hydrate thereof to a patient who suffers from erectile dysfunction. 34. A method for preventing and treating female sexual dysfunction or dysmenorrhea, which is the step of administering a pharmacologically or clinically effective dose of the phthalazine compound claimed in Claim 20, a pharmacologically acceptable salt thereof or a hydrate thereof. a patient suffering from female sexual dysfunction or dysmenorrhea. 35. Use of the phthalazine compound claimed in Claim 20, a pharmacologically acceptable salt thereof or a hydrate thereof to produce a therapeutic agent for erectile dysfunction. 36. Use of the phthalazine compound claimed in Claim 20, a pharmacologically acceptable salt thereof or a hydrate thereof to produce a therapeutic agent for female sexual dysfunction or dysmenorrhea.