PL147465B1 - Method of obtaining novel pyridazionoamine compounds - Google Patents

Description

The subject of the invention is a method for the preparation of new antiviral antiviral pyridazine compounds, useful in combating diseases caused by viruses in warm-blooded animals, including humans. such as rabies, hepatitis, cold sores and usually colds. Especially the latter disease is very common and is the main cause of absenteeism, which causes significant economic losses. The ability to effectively combat this disease would undoubtedly bring considerable relief and economic benefits. To date, however, no agent has been identified that would be effective against this disease. It has been found that numerous pyridazine-amine compounds according to the invention are antiviral and can be advantageously used to combat diseases caused by viruses. The compounds prepared by the process of the invention are new and some compounds of similar structure are discussed in the following publications. J. Med. Chem. 24, 59-63 (1981) describes numerous 1H-imidazolylpyridazines, and European Patent No. 55,583 and in U.S. Patent No. Am. Nos. 4,110,450, 4104,385 and 2,985,657, a number of piperazinyl-, pyrrolidinyl- and piperidinylpyridazines are discussed as starting products. It is also known from European Patent No. 9,655 that 3-chloro-6-i [4- (2-methoxyphenyl) -1-piperazinyl] -pyridazine and 1-chloro-4- (4-) hydroxypiperidineOi-phthalazine are starting products in various syntheses. Besides, in J. Med. Chem. 6, 541-544 71963 /, ibid. 8, 104-107 (1965) and ibid. 15, 295-301 (1972), it is stated that numerous substituted 1-piperazinylpyridazines are adrenolytic, antihistaminic and anesthetic. The invention differs from these known compounds by substituents on the pyridazine group, in particular that they have useful antiviral properties. The invention provides antiviral pyridazine carmines of the general formula I, in which R1 is hydrogen or halogen, group IH -imidazol-yl-yl, a (C 1-6) alkoxy group, a phenoxy group optionally having 1 or 2 substituents such as halogen atoms, (C 1-4) alkyl and nitro groups, phenyl (C 1-4) groups , "alkoxy, (C 1-4) alkylthio, phenylthio, hydroxy, mercapto, amine, IC 1 -C 1-4 alkylsulfinyl, (C 1-C 4) alkylsulfonyl, cyano, (C 1-4) alkoxycarbonyl or (C 1-4) alkyl) , R2 and R3 are the same or different and represent hydrogen atoms or / C1-C4 / alkyl groups, or R2 and R3 together form a bivalent group of formula -CH = CH-CH = CH-, and A is a bivalent group of formula 2, 3, 4 or 5, where in formulas 3, 4 and 5 min are identical or 147 465 147 465 3,4 different and represent integers 1-4, and the sum m + n is 3,4 Jub'5 and one of the hydrogen atoms "in the groups CmH2m, Cm.jHam-! and the CnH2n may be replaced with a (C1-C4) alkyl group, R4 in formula 3 is a phenyl radical, optionally having 1, 2 or 3 substituents, such as (C1-Cyalkyl radicals, halogen atoms, nitro group, (C1 -C1) alkoxy groups, (C1-C4) alkoxy carbonyl, trifluoromethyl, halogenphenylcarbonyl groups and hydroxyl group, (a) alkoxycarbonyl, a pyridinyl group which may be substituted with a JC ^C ^ 'alkyl radical or a cyano group, or R4 is also a cyclohexyl or cyclohexenyl group, optionally having 1 or 2 substituents, such as cyano and halophenyl groups, or R4 oz. For a quinolyl, phenyl (C 1 -C 6) alkyl, (C 1 -C 4 alkylphenyl) C 1 -C 4 alkyl or naphthalenyl group, R 5 in formula 4 represents a hydrogen atom, a (C 1 -C 6) alkyl radical, a phenyl radical optionally having 1 or 2 substituents, such as halogen atoms, and (C1-Cft) alkali groups alkoxy, trifluoromethyl and (C 1 -C 4) alkoxy groups, or R 5 is a hydroxyl group, a (C 1-4 g) alkoxy group which is optionally substituted with a piperidino group, a phenylamino group which may have 1 or 2 substituents such as (C 1 -C 4) alkyl radicals, halogen atoms, trifluorbmethyl, phenyl) C 1 -C 4 alkylamino groups, (C 1 -C 4 alkylphenyl), (C 1 -C 4 alkyl) amino, phenyl (C 1 -C 6 palkenyl) -, X: 1-C4-alkyl / amine, phenylcarbonyloxy, halo-phenoxy, amine, (C 1 -C 4 alkoxycarbonyl) amine or naphthalenyl, R 6 in formula 4 is hydrogen, (C 1 -C 4) alkyl, phenyl, which is optionally has 1 or 2 substituents, such as (C 1 -C 6'alkyl groups, halogen atoms, and C 1 -C 4) alkoxy groups and a trifluoromethyl group, a (C 1 -C 4) alkylcarbonylamino (C 1 -C 4) alkyl group, phenyl (C 1 -C 4) alkyl, which is optionally substituted by halogen, or R 6 is aracanocarbonyl, phenylaminocarbonyl, (C 1 -C 4) alkoxy rbonyl, halophenylcarbonyl (C1-C4) alkyl, phenylcarbonyl, which is optionally substituted with trifluoromethyl or halogen, phenyl, yc, C, alkyl, caribonyl, indoyl, thienyl, pyridyl or naphthalenyl R8 in formula V are the same or different and represent hydrogen atoms, C1-4alkyl groups, phenyl groups optionally having 1 or 2 substituents, such as halogen atoms and trifluoromethyl groups, or represent phenyl, C 1 -C 4 alkyl, thienyl, naphthalenyl or pyridyl groups, whereby: as defined above, but with the exception of the hydrogen atom, the hydroxyl group and the (C 1 -C 6) alkyl group, and when R 2 and R 8 are hydrogen and A is a group of formula II, then but with the exception of halogen, iii) when R 1 is chlorine, R 2 and R 8 are and A is a group of formula 3 then R 4 in formula 3 is as "given above". meaning, but with the exception of the 2-methoxy group and iv) when R 1 is chlorine and A is a group of formula 3, then R 4 in formula 3 has the meaning given above, but other than the a-met group. Tylophenyl and 2-methylphenyl / methyl. *. The compounds of formula I can be converted into pharmacologically acceptable compounds by reaction with suitable acids. The acid addition salts or the obtained acid addition salts can be converted into the free bases by treatment with alkali and / or the compounds of formula I can be prepared in stereoisomeric forms. a compound of formula 6, in which A is as defined above, is alkylated at the nitrogen atom with a compound of formula 7 in which R1, R2 and R8 are as defined above and W is the appropriate cleavage group. for example, a fluorine, chlorine, bromine or iodine atom, a sulfonyloxy group, for example a methylsulfonyloxy or 4-methylphenyloxy group, or a lower alkoxy group or a lower alkylthio group. nitrogen, preferably in an inert organic solvent such as aromatic hydrocarbon, nip. benzene, methylbenzene or dimethylbenzene, lower alkanol, e.g. methanol, ethanol or biitanol-1, ketone, e.g. 2-propanone or 2-methylpentanone, ether, e.g. 1,4-dioxane, di-ether ethyl or tetrahydrofuran, or in a bipolar aprotic solvent environment, e.g., N, N, N-dimethylformamide, N, N-dimethylacetanide, dimethyl sulfoxide, nitrobenzene or. lTffnetylpyrrolidinoneH2. It is preferable to use the addition of a base, for example an alkali metal carbonate, an alkali metal hydrogen carbonate, sodium hydride or an organic base, for example N, N-diethylethylamine or N- (1-methylethyl) -2-propylamine, thereby binding the acid which is released during the reaction. It is sometimes advantageous to use the addition of a salt of hydroiodic acid, in particular an alkali metal iodide. These alkylation reactions can also be carried out by mixing and / or melting the reaction components with one another, optionally in the presence of the above-mentioned bases. The use of a slightly elevated temperature accelerates the course of this reaction. The compounds of formula I are basic in nature and can therefore be converted into pharmacologically useful, non-toxic acid addition salts by themselves by treatment with appropriate inorganic or organic acids. for example, hydrochloric or hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, propionic acid, hydroxyacetic acid, N-hydroxypropionic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, etc. cis-ethylenedicarboxylic Hly2, fumaric, apple, tartaric, lemon, methanesulfonic, ethanesulfonic, benzenesulfonic, 4-methylbenzenesulfonic, cyclohexenylsulfamir 65 new, 2-hydroxybenzoic, 4-amino-2-hydro compounds by the formula convert to pharmacologically acceptable acids with appropriate acids. The acid addition salts or the obtained acid addition salts can be converted into the free bases by treatment with alkali and / or the compounds of formula I can be prepared in stereoisomeric forms. a compound of formula 6, in which A is as defined above, is alkylated at the nitrogen atom with a compound of formula 7 in which R1, R2 and R8 are as defined above and W is the appropriate cleavage group. for example, a fluorine, chlorine, bromine or iodine atom, a sulfonyloxy group, for example a methylsulfonyloxy or 4-methylphenyloxy group, or a lower alkoxy group or a lower alkylthio group. nitrogen, preferably in an inert organic solvent such as aromatic hydrocarbon, nip. benzene, methylbenzene or dimethylbenzene, lower alkanol, e.g. methanol, ethanol or biitanol-1, ketone, e.g. 2-propanone or 2-methylpentanone, ether, e.g. 1,4-dioxane, di-ether ethyl or tetrahydrofuran, or in a bipolar aprotic solvent environment, e.g. 1-methylpyrrolidinoneH2. It is preferable to use the addition of a base, for example an alkali metal carbonate, an alkali metal hydrogen carbonate, sodium hydride or an organic base, for example N, N-diethylethylamine or N- (1-methylethyl) -2-propylamine, thereby binding the acid which is released during the reaction. It is sometimes advantageous to use the addition of a salt of hydroiodic acid, in particular an alkali metal iodide. These alkylation reactions can also be carried out by mixing and / or melting the reaction components with one another, optionally in the presence of the above-mentioned bases. The use of a slightly elevated temperature accelerates the course of this reaction. The compounds of formula I are basic in nature and can therefore be converted into pharmacologically useful, non-toxic acid addition salts by themselves by treatment with appropriate inorganic or organic acids. for example, hydrochloric or hydrobromic acid, sulfuric, nitric, phosphoric, acetic, propionic, hydroxyacetic, [beta] -hydroxypropionic, pyruvic, oxalic, malonic, succinic acids. cis-ethylene dicarboxylic Hly2, fumaric, apple, tartaric, lemon, methanesulfonic, ethanesulfonic, benzenesulfonic, 4-methylbenzenesulfonic, cyclohexenylsulfamate 65 new, 2-hydroxybenzoic, 4-amino-2-hydrobenzoic, etc. Using free bases, treating with alkali. Numerous starting compounds and intermediates used in the reactions described above are known compounds or can be prepared by methods known, for example, from US Pat. No. 2 * 57 472, 2 979 507, 2 997 474 and 3 002976. Compounds of formula 6, in which A is a group of formula III, in which R 4 is a group o with the symbol R '- *', the meaning given above for R4, but with the exception of the hydrogen atom, ie compounds of formula IIa in which R4-V min are as defined above, can be prepared by alkylation of compounds of formula 9 in which m and n are as defined above and P is a protecting group, eg a lower alkoxycarbonyl group, an arylmethoxycanbonyl, an arylmethyl or an arylsulfonyl group. Compounds of formula VIII in which W and R4-a ** are alkylated as defined above. From the obtained compound of formula 10, in which m, n, R4-a and P are as defined above, by cleavage of the protecting group P, for example by hydrolysis in an alkaline or acid environment, the compounds of formula IIa described above are obtained. . The reactions shown in Scheme 1 are carried out analogously to the above-described reaction for the preparation of compounds of formula I from compounds of formula 617. Compounds of formula 10 can also be prepared by alkylation of compounds of formula 8a in which R4a is as defined above , compounds of formula 112 in which m, n, P and W have the meaning given above. This process is carried out using the known methods of alkylation at the azoite atom. Compounds of formula 6, in which A is a group of formula 4, in which min. hydrogen and R5 * P represents a group of the formula -NRBR10, i.e. an arylamino group, a lower alkyl aryl group, a lower alkyl arylalkylamino group, an e-aryl alkenyl / alkyl group The l-amine lower alkenyl and alkyl radical or the lower allkenyl arylalkenylamino group, i.e. the compounds of formula IIb, can be conveniently prepared by reducing and amination a ketone of formula 13, in which m, n and P have the meanings given above and the amines of formula 14 in which R9 and R10 are as defined above, followed by the removal of the protecting group P from the resulting product (O) in which m, n, R9, R10 and P are as defined above. This process is illustrated in Scheme 2 and is preferably carried out by hydrogenating in the presence of a catalyst the mixtures of the reaction components in an inert reaction medium according to known methods. in which min are as defined above, R5 is hydroxy and R6 is phenyl or lower, alkyl, can be prepared by reacting compounds of formula 13 with the appropriate Grignard compound in a suitable solvent. The compounds with the hydroxyl group obtained in this way can be deprotected or further reacted with a suitable acid solution to remove the water molecule and only then cleaved off the protecting group to form compounds of formula 6, wherein A represents the group represented by the formula 5 above. The antiviral activity of the compounds of formula I was demonstrated in the tests described below. Helium cells sensitive to rhinitis virus were inoculated in a medium with minimal nutritional value, hereinafter abbreviated as MBM, supplemented by the addition of 5% of fetal calf serum and nonspecific amino acids. ¬ the cells were cultured at 37 ° C, in an atmosphere containing 5% CO, and after 24 hours were treated with solutions of the test compounds in a solvent containing 1 part by volume of dimethyl sulfoxide in 7 parts by volume of MEM, supplemented with 10% by volume of deactivated calf serum. In comparative trials, cells were treated with the solvent given above, without the test compounds. Both samples were cultured at 37 ° C for 3 hours, followed by the addition of a standardized human rhinitis virus vaccine and further development. cultures were carried out at 33 ° C, allowing the virus to grow in Hela cells. The evaluation of the results was carried out only after the complete cytopathological effect was obtained in the comparative trials, that is, in those in which the cells with the virus were treated with the solvent alone. The antiviral activity was defined as the lowest concentration of the test compound in g / ml at which the reduction of the cytopathological effect was observed to be at least 75% compared to the virus activity in the control samples. The results of the tests are given in Table 1. The numbers of the compounds in this table correspond to Compound number Wg / ml n ~~ a 5 W 8 10 29 0.4 207 0.4 149 0.4465 8 Table 1 —cd. - 1 2 0.4 0.016 0.08 0.4 2 0.4 2 0.08 0.08 0.016 0.03 10 0.08 2 10 10 0.4 10 2 0.4 0.4 0.08 0 In addition, some of the compounds according to the invention have also been tested for their anesthetic and antitussive effects by carrying out the tail retraction motion tests and the writhing test described in Arzneim. Fara., 25, 1605 - .1609 71975, / and 15, 1-07 - '1 (17 / 1066/. Due to their properties, the compounds of formula 1 and their acid addition salts are useful as pharmacological agents in the treatment of diseases For this purpose, these compounds are used in the form of pharmaceutical compositions containing an effective amount of a compound of formula I or an acid addition salt thereof in admixture with a pharmacologically acceptable carrier or solvent that is suitable for They are prepared according to known methods, the acid addition salts of the compounds of formula 1 being more soluble in and bonded compounds, therefore, are better suited for the preparation of compositions with water as a carrier. 5W mg. Some compounds produced by the method according to the invention have several measures of asymmetry. Pure stereoisomers can be prepared by known methods, for example diastereomers can be separated by selective crystallization or by chromatography, while enantiomers can be separated by subjecting their salts to optically active 5 acids by selective crystallization. Pure sterile 25 91 236 93 96 238 101 104 222 223 241 145 231 112 210 1.13 209 247 274 120 250 273 273 259 126 212 275 147 465 9 10 rheisomers can also be produced by carrying out the process of the invention using stereoisomers. pure starting compounds. Preparation of the starting compounds. Example I. A mixture of 221 parts of 4-fluorocberium acetic acid nitrile, 700 parts of a 30% solution of sodium methanol and 900 parts of dimethylbenzene is mixed for 5 minutes, then 309 parts of methyl acrylate are added dropwise, accompanied by a reaction. exothermic and the temperature of the mixture rises to 65 ° C. It is then stirred under reflux overnight, then the methanol is distilled off until the temperature of the mixture reaches 1'10 ° C and then it is cooled. 1000 parts of a 6N hydrochloric acid solution are added dropwise and stirred in boiling under reflux within 5 minutes. The mixture is cooled down thoroughly, the layers are separated, the organic layer is dried, filtered and evaporated. The residue is mixed with 500 parts of acetic acid, 500 parts of water and 500 parts of hydrochloric acid solution and boiled under reflux for 4 hours, then cooled and extracted with trichloromethane. The extract is rinsed successively with water, dilute sodium hydroxide solution, and again with water until neutralized, then dried, filtered and evaporated. The remainder was recrystallized from 2-propanol, yielding 134.5 parts of (4-fluorophenyl) -4-ketocyclohexanecarboxylic acid nitrile with a melting point of 91.8 ° C (starting product 1). . A mixture of 17.6 parts 1M (phenylmethyl) piperazine, 8.4 parts 4-ethyl fluorobenzoate and 43 parts N, N-dimethylacetamide is boiled under reflux for 2 (2 hours, then cooled, poured into 500 parts of water and extracted three times with gasoline. The combined extracts are rinsed three times with plenty of water, dried, filtered and evaporated. The remainder is mixed with hexane, drained, washed with hexane and dried under reduced pressure, giving 12, 5 parts (77 ° 7 theoretical) of 4- [4- (phenylmethyl) -4-piperazinyl] benzoic acid ethyl ester (starting product 2). - / Methylamino / Hpiperidinecairboxylic-1, 13 parts / 3-chloro-lipropenyl / 45en-zene, 25.5 parts of sodium carbonate and 240 parts of 4-methylpentanone-2 are mixed and kept under reflux with a water separator for 2 days, then cooled, water added and the layers separated The organic material is dried, scrubbed, evaporated and the residue converted into the salt of oxalic acid in an environment of 2-propanol with 2-propanone. This salt is filtered off and dried to give 23.4 parts (Uri) of ethyl ester (E) 4- [imethyl- (3-rphenyl-2H-propenyl) -ammo] H1- piperidinecarboxylate oxalate, m.p. 160.2 ° C. CI \ pTO- starting product 3A Example IV. To a mixture of 19 parts 1- (phenylmethyl / H-piperidinol-4, 16.2 parts triethyl-). 5 amines and 180 parts of methylbenzene are slowly added dropwise, while stirring, 14 parts of benzoyl chloride, then stirred for 3 days at room temperature, the resulting benzoyl chloride is filtered off and washed with methylbenzene. The filtrate is evaporated and the oily residue is chromatographed on a silica gel column. With a mixture of trichloromethane and methanol (95: 5 by volume) eluting. The eluent is evaporated from the pure fractions and the residue is converted to the hydrochloride in 2-propanol. The salt was filtered off and dried to give 18 parts (54% of theory) of 1- (phenylmethyl) -4-p-peridinyl benzoate hydrochloride, mp 225.9 ° C (starting material 4). , Example 5 To a mixture of 7.8 parts of a 5% solution of sodium aeride in benzene and 135 parts of methylbenzene is added dropwise at 25 ° C (necessary cooling) a solution of 11.7 parts of benzyl cyanide in 45 parts of methylbenzene. then it is stirred at 30 ° C for 30 minutes, and then the solution is added dropwise 24 ,? parts of ethyl 1- (phenylmethyl) -4-piperidinecarboxylate in 45 parts of methylbenzene at 30 ° C. After the dropwise addition, it is stirred at 80 ° C. overnight, then cooled, 12 parts of ethanol are added, poured into ice water and the layers are separated. The aqueous phase is neutralized with acetic acid, the oily product is extracted with trichloromethane, the extract is dried, filtered and evaporated. - x- [1-Iienylmethyl) -4-piperidinyl] -methylidene] -benzene-acetic acid, m.p. 19 µL.8 ° C / starting product 57. 200 parts of acetic acid are carefully added to 200 parts of water with stirring and cooling Then 368 parts of sulfuric acid are slowly added dropwise. 90 parts of the nitrile obtained as described above are added to the mixture obtained as described above and stirred under reflux overnight, then the acetic acid is evaporated off and the residue is poured into it. to crushed ice. The mixture is made alkaline with concentrated ammonium hydroxide and the oily product is extracted with trichloromethane. The extract is dried, filtered and evaporated to give 79 parts (96-3% theoretically) of 2-phenyl-yl- [fll- (phenyiomethyl) -piperidinyl ethane (starting material 6). Example VI. Mixture of 93 parts of N- (2-chloroethyl) -IN- (3-chloropropyl) hamide of 4-non-ethylbenzenesulfonic acid, 30.3 parts of 2,3-drwumethylbenzenesulfonic acid, 63.6 parts of sodium carbonate , 1 part potassium iodide and 240 parts citelhexanol are mixed under reflux with a water separator for 2 days, then cooled, poured into water and extracted 15 20 25 30 35 40 45 50 55 60 147 465 11 h methylbenzene. The extractor is rinsed twice with water, dried, filtered and evaporated. The residue was recrystallized from 2-propanol with a small amount of tetrahydrofuran, filtered off the precipitate and dried, yielding 47.8 parts (53.3%) of theoretical yield (lu (2.3HdF) dimethylphenyl) Hhexaihydrate: yellow-4. - [(4H-methylphenyl) -sulfcnylol-1H- (1114-diazeipine, m.p. 86.12 ° C / starting product 77.12 ] -piperidine, m.p. 226.8 ° C (starting product 8), 1- [Mn-methylphenyto (h] ^ ^ methyl) -piperidine (starting product 9), 1- (3- ^ ^ dichlorophenyl) -hexaihydro-4- [M -methylphenyl] -sulfonyl] -1,4-diazepine (starting product 10), 1- (3-chlorophenyl) -rhexahydro-4- [(4-methylphenyl) -sulfonyl] -IH- 1,4-diazepine, melting point H16.6 ° C (starting product 11), hexahydroni (B-methylphenyl) = 4- [(4-methylphenyl) -silphonyl] -1H-1,4H-diazepine (starting product) 1127 and 'hexalhydphro-yl- [(4-methylphenyl) Hsulfonyl] -4- [3- (trifluoromethyl) phenyl] jsciowy 137.Example VII. To 180 parts of l - [/ 4-methylphenyl / nsullifonyl] -4- / 2,4,6-ttrimethyl (phenyl] -piperazine) in 460 parts of water, add dropwise, stir- ^ jiac, 675 parts of sulfuric acid - then it is stirred in the hay, boiling under a reflux condenser for 4 hours, then cooled, treated with an ammonium hydroxide solution and extracted with dichloromethane. The extract is dried, filtered and evaporated to give 70 parts of the 769% theoretical yield. (1- (2,4,6-thyrimethylphenyl) -piperrazine) (starting product 14). 4- (3-methylphenyl) -piperadine-x-bonamide-4 is prepared in a similar manner (starting product il- (2) (vumethylphenyl) -hexahydro-lH-11l4-diazapine "(starting product 16), hexahydro-1- (2-methoxyphenyl) hydrochloride - -lHsil, 4-diazepines melting at 176.6 ° C / starting product 17 / and and hydrochloride, 1- [3- (trifluoromethyl) -phenyl] - "! H- -1,4-diaisepine having a melting point of 101.1 pC (starting product 18). / Example VIII. A mixture of 7.9 parts of ethyl ester acid 3Hketopyrrolidinecarboxylic acid, 5.35 parts of 3-methylphenylamine, 1 part of a 4% solution in methanol and 200 parts of methanol are hydrogenated under atmospheric pressure, at 50 ° C, in the presence of 2 parts of 10% coal on carbon. After absorption of the calculated amount of hydrogen, the catalyst is filtered off and the filtrate is evaporated to give 12.4 parts (100% of theory) of ethyl ester of 3 - [(3-methylphenyl) amino] -pyrrolidine carboxylic acid. and (starting product 19). In a similar manner, the following was prepared: 151.6 ° C (starting product 20), N-phenyl-yl- (phenylmethyl) -piperidylamine-3) starting product 2HY, 3 - [(2,3-diithii3-ylphenyl) -amino acid ethyl ester] - pyrrolidinecarb-1 (starting product 212), hydrochloride of 4 - {[3- (trifluoromethyl) -phenyl] -amino} -piperidinecarboxylic acid (starting product 23), N-) 3-Methylphenyl (-1- (phenylmethyl) -piperidylamino-1 (starting product 24) and 3 - ([3- (trifluoromethyl) -phenyl] -amino} -pyiroilidine-carboxylic acid-1 (starting product) 25./ Example IX. 21 * 8 parts of ethyl chloroformate at room temperature are added dropwise to a solution of 152 parts of 3-methyl-1- (phenyiomethyl) -piperidinium-4 in 900 parts of toluene, then stirred and kept in a boiling state. She is kept under a reflux condenser overnight, and is cooled down thoroughly, rinsed with water and hydrochloric acid, dried, filtered and evaporated. The residue is distilled under reduced pressure to give H 2 O, 5 parts 783% of theoretical yield (3H-methyl-4-keto-pyropc-1-yidine-1-ethyl ester, boiling point 98- <105). ° C under a pressure of 133 Pa (starting product 26). Example X. Grigmard complex, prepared from a mixture of 4; 2 parts of 1-bromo-3-chlorobenzene and 5.4 parts of magnesium in 135 parts of tetrahydrofuran , is stirred under reflux and 19 parts of phenylmethyl / piiperidinone-3 are added dropwise, then stirred further under reflux for 1 hour, then cooled, blown into ice water with the addition of 12.5 parts of acetic acid and separates the layers. The aqueous layer is extracted with trichloromethane. Organic, the layer is rinsed with water, dried, filtered and evaporated. The residue is converted to the hydrochloride in propane (uH2), drained and dried to give 26 'parts (76% of theory) of 3- (3-chloro-phenyl) -l- (fsnylmethyl) -piperidinol-3 / hydrochloride starting product 27). In a similar manner, the following was prepared: ethyl 4-hydroxy-4- (2- (thienyl) piperidinecarboxylate), m.p. v146.2 ° e / starting product 267.4-hydroxy-4 ^: Hnaphthalenyl (nppiperidinecarboxylate-11-ethyl, m.p. 109 2-11-4.8 ° C (starting product 29), 3- [4-chloro-3- (trifluoromethyl) -phenyl] -3-hydroxy-pyrrolidinecarboxylate-yl-ethyl) starting product 30), 4-; hy.df1: oxy-4 - (2-naphthalenyl) (rhidinecarboxy-Lam-1-ethyl) (starting product 31), 3- (3-methylphenylM- (phenylmethyl) hydrochloride) -piperidin-3 (starting product 32), cis-α-methyl-4- (3-methylphenyl) -1- (phenylmethyl) n-peridinol-4 / starting product 33), cis-4- (3-f) luorophenyl (-4-hydroxy-3-methylpiperidine-1-ethyl carboxylate) (starting product 34), '13 14 7 465 14 cis-4H-hydroxy-3-imethyl-4- (2-tdenyl) -piperidine-1-ethyl carboxylate (starting product 35), 3-hydroxy-3- (2-thi'enyl / ipdperidinecarboxylate-ethyl Il) / product output 36 /,. 3- (3-fluorophenyl) -. 1-lienylmethyl) -piperidinol-S-hydrochloride (37 // 4- (2? 3H-dimethylphenyl) -4-hydroxypiperidine carboxyl-n -. 1 ethyl (starting 38), hydrochloride 3- (2,3-dimethylphenyl) - 'V-phenylmethyl) -piperidine, lu-3 (' 3ft 'starting product), 3- (3-methylphenyl) hydrochloride (-1' -) phenylmethyl) - -pyrrolidinol-3 / product starting 40 [3n [4] hloa: o ^ ^ (trifluoromethyl) phenyl] n3 ^ ydroxy-piperidinecarboxylate [beta] ethyl (starting product 41) [3- (3-trifluoromethyl) phenyl] phenylmethyl (- 3-pyrrolidinol-3 (starting product 42), 4-hydroxy-4- (3-methotosypheriyl) -3H-thiethylpiperidinecarboxylate-J. ethyl 7 starting product 43) and 3- (3-n-methoxyphenyl) -yl- (phenylmethyl) -ppro-lidinoyl-3 hydrochloride (pr. Example XI. 7 parts of 3- / 2,3H-di-methylphenyl / -1- (phenyldmethyl) -piperid-3rnol-3 hydrochloride in 200 parts of 6N hydrochloric acid are mixed and boiled under reflux overnight, then evaporated and left to rest. Water and ammonium hydroxide are added to the mixture to form the free base. The product is extracted with trichoromethane, the extract is rinsed with water, dried, filtered and evaporated. The residue is chromatographed on a silica gel column, eluting with trichloromethane and methanol (98: 2 by volume). The eluent is evaporated from the first fraction, yielding 0.7 parts (12P) of theoretical yield (5- (2y3-dimethylphenyl)) -1,2,3,4-tetrahydro-tetrahydro-trienylmethyl (pyridine) (starting product 45). The eluent was also evaporated from the second fraction, yielding 5.3 parts (9d% theoretical) (5- (2.3). dimethylphenyl (--. 1, 3 - (tetrahydro-1 - (phenylmethyl)) -pyrroline (starting product 46). Example Xli. 8 parts of 3- (3-methylphenyl hydrochloride) The fienylmethyl (n-pyrrolidinol-3) in 150 parts of 6 N hydrochloric acid is stirred and boiled under reflux for 3 hours, then cooled and evaporated. of theoretical theory (2 3'-ihyo-4 -'-hydrochloride) 3Hixve (Tylophenyl (H1- (phenylmethyl) -ilH- - pyrode (starting product 47). In an analogous manner * is prepared: 1 ^ 2.3 , 6-tetrahydr o-5- (3-methylphenyl) (N-phenylmethyl) -pyridine (starting material 48) and 5- (3-fluorophenyl) hydrochloride -4, 2,3,6-tetrahydro, -Wphenylmethyl) pyridine / starting product 49 /. ¦ * ~ '/ Example XIII. 10.9 parts of ethyl chloroformate are added dropwise to a solution of 13 parts of 3- / 3-chlorophenylo / Hl- / phenylmethyl / Hpiiperidinolne3 in 270 parts of toluene. boiling under the reflux condenser overnight. Then the mixture is cooled to room temperature, rinsed with water and hydrochloric acid, and the layers are separated. The organic layer is dried, filtered and evaporated, keeping the remaining 7 particles / 58% yield. Theoretical (3- (3-chlorophenyl) -α-hydroxy-1-ethyl-piperidinecarboxylate) starting product 507. "..". Example 14. Mixture III, 8 parts of N-y2,3-dimethylphenyl) (phenylmethyl) -piperidylamine-3 and 120 parts of methanol are hydrogenated under atmospheric pressure and at room temperature in the presence of 2 parts of 10% palladium on charcoal. on a silica gel co-column, eluting with a mixture of trichloromethane with methanol (99-1 to 95: 5 volumetric). The eluent is evaporated from the pure fractions and the residue is converted to s61 with oxalic acid in the propanol environment. 2 with propanone-2. The salt is filtered off and dried to give 1 part (79.5% of theory) of N- (2,3-divinethylenyl) -pdperidylamine-3 oxalate at 161 ° C. ° C / starting product 25 Prepared analogously: ethyl 4- (l-piperazinyl) benzoate having a melting point of '102.6 ° C. (starting product W, 4-piperidinyl benzoate hydrochloride) having a melting point of 236.8 ° C. (starting product 53), N-phenyl-3-piperidylamine with a temperature of tpp. 79.80C / starting product 547, - N- (3-methylphenylphenyl) -3-piperidylamine / starting material56 /, - "" 4 - [3-methylphenyl] -amino] Hpiperidinecarbonamide-4 / starting product 567, 2- hydrochloride phenyl-1- (4-piperidinyl) -ethanone, m.p. 198.6 ° C (starting product 57), 3- (3-methylphenyl) ipiperidine / starting product 587, 3- (3-methylphenyl hydrochloride) -pip9-ridinol-3 (starting product 59), "45 cis-3-methyl-4- (3H-methylphenyl) -piperidin-4) (starting product 60), ..-. - 3- (3-fluprophenyl) -piperidinol-3-hydrochloride (starting product 61), 3- (2,3-dimethylphenyl) -59-piperidinol-3-hydrochloride hemihydrate, m.p. 135.50C / starting product 62) 3- (2'-dimethylphenyl) -piperidine (starting product G3.1), ..-, 3- (3H-methylphenyl) (ipyroaddinol-3) starting product 64), 3- (3-methoxyphenyl) hydrochloride (Hpi, psridinol) -3 (starting material 65), 3- (3-fluorophenyl) -pyrrolidinol-3 hydrochloride. "(starting product 66) and • 60 3- (3-methoxyphenyl) ipyrrolidinol-3 hydrochloride (starting product 67). Example XV. 13.10 parts of 3 - [(2,3-dimethylphenyl) -amino] -pyrrolidinecarboxylate -lli-ethyl, 28 parts potassium hydroxide and 240 parts ** pflropanplu-2 are mixed and boiled under reflux for 6 hours, after which it is evaporated, the residue is dissolved in water and extracted with dichloromethane. , filtered and evaporated to give 6 parts (63% of theory) N- (2; 3-dimethylphenyl) -pyrrolidylamine-3 (starting product as). In an analogous manner: dihydrochloride hemihydrate (E) - N-methyl-N- - (3-phenyl-propen-2-yl) -4-piperidylaninine, m.p. 240.2 ° C. (starting product 60), N- [3- (tri? Uoromethyl) phenyl] - -piperidylamine-4 with a melting point of 253.2 ° C (starting product 70), oxalate 11:11 N- (3-methylphenyl) -pyrrolidylamine-3 with a melting point 180 ° C. (starting product 711). 4 (2-thienyl) 4-H-piperidinol-4, mp 146.9 ° C (starting product 727, 4- (1-naphthalenyl) -pipe ridinol-4, mp 185 ° -187.8 ° C. C (starting product 73), 3- [4-chloro-3- (tri (flluoromethyl) phenyl] -pyrrolidinol-3, m.p. 138.4-1142.1 ° C (starting product 74), 4- (2-) naphthalenide (ipiperidinol-4 (starting product 75), N- [3- (trifluoromethyl) phenyl] -pyrrolidylamine-3 dihydrochloride (starting product 76), cis-4- (3-starting product 77), cis-3-non-ethyl-4- (2-thienyl-7-piperidimol-4) (starting product 78), 3- (2-thienyl) -piperidinol-3 (starting product 79), hydrochloride. 3- (3-chlorophenyl) -piperidinol -3 (starting product 80), 4- (2,3-n-urethylphanyl O ') - piperidinol-4 (starting product 811), 4- (3-chlorophenyl)? 3-meitylp: peridinol-4 starting product 82), 3- [4 -chloro-3- (trifluoromethyl) -phenyl] -pipe! ryidine-3 (stock 83) and "4- (3Hmethoxyphenyl) -3-imethylpiperidinol-4 (starting product 84). Example XVI. 3 parts hydrochloride orc 3- (3-fluoro-phenyl) -piperidin-3-3 and 100 parts of 6 N hydrochloric acid are mixed and boiled under reflux for 3 hours, then the mixture is evaporated, the residue is dissolved in water. with ammonium hydroxide and extracted with trichloromethane. The extract is rinsed with water, dried, filtered and evaporated to give 2.2 parts (96% of theory) of 5- (3-fluoro-phenyl) - (1,2,3'-tetrahydropyridine / starting product 857 The following are prepared in an analogous manner: 4- [4K: chloro-3- (trifluoromethyl) -nyl] -Ily3,3,6-tetrahydropyridine (starting product 86) hydrochloride, 1,2,3,6-tetrahydro 4- (2-thienyl) -pyridine (starting product 87), 1,23,6-tetrahydro-4- [3 (trifluoromethyl-7-phenyl] -pyridine (starting product 88), hydrochloride 1,2 , 3,6-tetrahydro-4-71-naphthalenyl-7-10 15-piperidine, m.p. 277.5 ° C. (starting material 89), 1,2,3,6-tetrahydro-5- (3-) hydrochloride methylphenyl) -pyridine (starting product 90), 5, 3,4-dihy, dro-3- (2-thienyl) -ilH-pyrrole (starting product W) and, 3- (2-thienyl-7-pyrrolidine) (starting product 927. Example XVII. A mixture of 6.5 parts of hydrochloride. 5- (3H-fluorophenyl) Hl, 2.3.6-tetrahydro-1- (phenylmethyl) -pyridine and 120 parts of methanol is hydrogenated from atmospheric pressure at 50 ° C. in the presence of 1 part of 10% pallet on charcoal. After the calculated amount of hydrogen had been absorbed, the catalyst was filtered off and the filtrate was evaporated to give 4.5 parts (100% theoretical yield) of 3- (3-fluorophenyl) -piperidine hydrochloride (starting material 93) as a residue. : 4- (2-thienyl) -piperidine hydrochloride (starting material 94) and 3- (3-methylphenyl) -pyrrolidine hydrochloride (starting material 95). .25 Example XVIII. Mixture of 21 parts of N- (3-methylphenyl) -1- (phenylmethyl) -piperidylamine-4-dihydrochloride, 9 parts of paraformaldehyde, 15 parts of potassium acetate, 2 parts of 4% of thiophene solution in methanol and 500 parts of methanol are hydrogenated under atmospheric pressure at room temperature in the presence of 4 parts of 10% palladium on charcoal. After the calculated amount of hydrogen has been absorbed, the catalyst is filtered off, the filtrate is evaporated, and the residue is essentially released from the residue by treatment with ammonium hydroxide and the mixture is extracted with dichloromethane. The extract is dried, filtered, evaporated and the residue is chromatographed on a silica gel column, eluting with a mixture of trichloromethane and methanol (99: 1 by volume). The eluent is evaporated from the pure fractions, the residue is converted into the hydrochloride in 2-propanol and the separated salt is filtered off. There are obtained 2.4 parts (75% of theory) of N-methyl-N- (3H-methylphenyl) -l- (f3-nylmethyl) -piperidylamine-4 dihydrochloride hemihydrate with a melting point of 20 µl, 3 ° C / product starting 9S /. A mixture of 9 parts of the product obtained and 200 parts of methanol is hydrogenated under atmospheric pressure and room temperature in the presence of 2 parts of 10% palladium on charcoal. After uptake of the calculated amount of hydrogen, the catalyst is filtered off, the filtrate is evaporated and the residue is converted into the hydrochloride in the environment. propanol-2. The salt is drained and dried, yielding 1.5 parts / 60.9% theoretical yield; N-Methyc-N- (3H-methylphenyl) -H-piperidylamine-4 dihydrochloride monohydrate, m.p. 209.11 ° C. (starting material 977 '). 60 B. Manufacture of end products Example XIX, 3.1 parts of 3,6-dichloropyridazine, 5 parts of 1- (2-fluorophenyl) -piperazine, 3.2 parts of sodium carbonate, 0.1 parts of potassium iodide and 72 parts of N, N-dimethylformamide are stirred at 60 ° C for 2 days, then poured into water, sucked off the precipitate and dissolved in trichloromethane. The solution is dried, filtered and evaporated, and the residue is chromatographed on a silica gel column, eluting with a mixture of trichloromethane and methanol (98: 2 by volume). diisopropyl ether to obtain 4.5 parts (77 °) of theory (3-chloro-6- - [4- (2-fluorophenyl) -1-piperazinyl] -pyridazine, m.p. 148.0 ° C / compound No. 9 In an analogous manner, by using equivalent amounts of the appropriate starting products, the compounds of formula I are prepared in which R8 is hydrogen and R1, R2 and A have the meaning given in table 2. The number of each compound and its melting point in ° C. Nw of compound 1 10 U 12 are also given in Table 2. 13 14 15 16 17 18 19 20 21 22 23 R1 2 Cl formula 17, Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Tab R * 3 HHHH CHS H CH3 H, HH CH3 HHH ela 2 A 4 formula 16 formula 18 pattern 19 pattern 20 pattern 18 pattern 21 pattern 22 pattern 23 pattern 24 pattern 25 pattern 26 pattern 27 pattern 28 pattern 29 Melting point, ° C 5 107.9 177.7 119.8 226.2 152.7 149.8 163.5 101 , 4 156.8 160.6 176.6 122.7 107.5 69.8 Example XX. 2.7 parts of 3,6-difluoropyridazine, 4.6 parts of 1- [3- (trifluoromethyl) -phenyl] -piperazine, 3.2 parts of sodium carbonate and 90 parts of N, N-cfvumethylformamide are mixed at 60 ° C. overnight, then poured into water, the precipitate was filtered off, washed with water and recrystallized from 2-propanol. There are obtained 3 parts / 46 l% of theoretical yield / 3-fluoro-6- {4-i [3- (thyrifluoromethylY-phenylol ^ 1 ^ piperazinyl} -pyridines with a melting point of 131.5 ° C / compound No. 24 (Compound No. 25) was prepared in a similar manner: 3- [4- (2,3-dimethylphenyl) -1-piperazinyl] -6-fluoropyridazine with a melting point of 144.1 ° C (compound No. 25), 3- fluoro-6- [4- (3-methylphenyl) -1-piperazinyl] -pyridazine, m.p. 128.1 ° C (compound No. 26) and 3- [3,6-dihydro-4- (3- methylphenyl (-1V2H) -pyridinyl] -6-fluoropyridazine, m.p. 105.2 ° C (compound No. 27). 10 15 20 25 30 35 40 45 Example XXI. 4.5 parts of 3,6-dichloropyradazine, 5.2 parts of 1,2,3,6-tetrahydro-4- (3-methylphenyl) -pyridine, 5.3 parts of sodium carbonate and 72 parts of N The N-dimethylformamide is stirred at about 70 ° C. overnight, then evaporated, added to the residue with water and extracted with trichloromethane. The extract is dried, filtered, evaporated and the residue is filtered through silica gel, eluting with a mixture of trichloromethane and methanol (98: 2 by volume). The eluent was evaporated from the pure fractions, the residue was crystallized from 2-propanol, filtered and dried to give 24 parts (24% of theory) of 3-chloro -6- [3,6-dihydro-4- (3-). methylphenyl (-1 (2H-pyridinyl] -pyradazine, m.p. 122.2 ° C (compound No. 28)). In an analogous manner, by using equivalent amounts of the starting products, respectively, the compounds of formula 1 are prepared in which R2 and Rs are hydrogen, and -R1 and A have the meaning given in Table 3. This table gives the sequence number of the compound, form, as it is obtained, that is, an acid salt or a free base, as well as the melting point of the product in ° C. Compounds marked with the sign next to the number were obtained in the form of cis isomers. 55 60 65 / Compound number i 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 R1 ~~ 2 Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl ca Cl Cl Cl Cl v Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Ta A 3 ~~ pattern pattern pattern pattern pattern pattern pattern. pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern pattern bale pattern 30 31 32 22 33 34 35 36 37 38 18 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 3 Salt or base 4 rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule base rule HCl Melting point, ° C 5 183.3 133.5 221.9 i46, e 172.0 144.5 188.6 162.6 207.7 164.6 140.1 118.2 200.6 155.8 124.4 160.0 156.4 114.8 153, 1 177.3 262.5 161.3 149.5 145.9 203.5 149.6 167.2 164.7 ^ 218.01 58 59 60 61 62 63 64 65 66 67 68 69 7Q 71 72 73 74 75 76 77 78 79 80 81 <82 83 84 85 86 * 87 88 89 90 91 92 93 94 95- 97 * 98 99 100 * 101 102 103 104 105 106 107 108 109 110 l! Tl 112 1H3 114 115 116 117 118 2 Cl Cl Cl Cl Cl Cl Cl Cl Cl Qi ci Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl -Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl ca Cl Cl Cl CH3- o c- / o / - Cl Cl Cl Cl Cl la '3 ~~ pattern 57 pattern 59 pattern 59 pattern 60 pattern 61 pattern 62 pattern 63 pattern 64 pattern 65 pattern 66 • pattern 67 pattern 68 pattern 69 pattern 70 pattern 71 pattern 53 pattern 72 pattern 73 pattern 74 pattern 75 pattern 76 pattern 77 pattern 78 pattern 79 pattern 80 pattern 81 pattern 82 pattern 83 pattern 84 pattern 85 pattern 86 pattern 87 pattern 88 pattern 89 pattern 90 pattern 91 pattern 92 pattern 93 pattern 95 pattern 96 pattern 97 pattern 98 Pattern 99 Pattern 100 Pattern 101 Pattern 102 Pattern 103 Pattern 104 Pattern 105 Pattern 106 Pattern 107 Pattern 108 Pattern 109 Pattern 110 Pattern 18 Pattern 111 Pattern 1.10 Pattern 113 Pattern 114 Pattern 115 Table 3 - c 4 HCl rule HCl rule rule rule rule rule rule rule rule HC1 rule rule rule rule rule rule rule rule rule rule rule rule. principle 0 176.5 185.2 118.8 174.9 224.4 136.5 172.9 147.6 194.5 221.8 95.1 199.6 167.9 120.9 80.4 119; 0 120 , 8 178.7 140.4 163.2 148.0 237.8 126.0 173.8 '127.9 163.8 162.7 152.0 207.7 156.4 118.9 206.0 147, 0 137.5 134.7 154.0 153.3 160.5 148.1 182.7 156.8 175.0 201.8 200 208.4 169.4 105.1 161.5 123.1 156.6 138.4 185.5 136.5 106.2 147.3 196.1 266.7 147 465 20: .d. Table 3 - continued _ T 2 nr ~ i 5 ~~ 1 H9 Cl formula 116 base 173.7 5 120 -CN formula 18 base 179.8 121 Cl formula 117 base 204.5 122 Cl '"formula 118 HCl 196.1 123 Cl formula 119 base 125.1 124 CH3- 10 * OOC formula 120 base 159.6 10R W7 (Sr x. £ tO WiiUl 17 formula 120 base 164.8 126 Cl formula 121 base 156.6 128 Cl formula 123 base 210.7 15 129 J formula 124 base 145.4 130 -CN formula 124 base 138.0 131 Cl formula 125 base 131.4 133 Cl formula 127 base 91.7 20 - 4-./6-chloro-5- were also prepared in a similar way. methyl-3-pyridazinyl / -piperazinecarboxylan-1-ethyl with a melting point of 132.2 ° C / compound No. 135 /. Example XXII. 5 parts of 1- (3-methylphenyl) -piperazine dihydrochloride, 10.6 parts of sodium carbonate and 180 parts of N, N-dimethylformamide are stirred at 65 ° C for 1 hour 3.1 hours. 7.2 parts of 3,6-dibromopyridazine are added and stirring is continued at about 65 ° C overnight. Then the mixture is poured into ice-cold water, the precipitate is sucked off, dissolved in dichloromethane, rinsed solution twice water, dried, filtered and evaporated. The residue is drained and dried to give 4.1 parts (61.5%) of theoretical yield (3-bromo-6- [4-) methylphenyl (-1-piperazinyl] pyridazine, mp 145.7 ° C. (Compound No. 136). 40 the following compounds are anadogically prepared: 3H-bromo-6- [4- (2,3-dimethylphenyl) -1-piperazin-1] -pyridazine, m.p. 166.7 ° C (Compound No. 137), 45 3- bromo-6i [4- (3-chlorophenyl) -1-piperazinyl] -pyridazine melting point 158.7 ° C (compound No. 138), 3-bromo-6- [4 -, [3- (trifluoromethyl) - phenyl] -1-piperazinyl] -pyridazine, m.p. 50 154.3 ° C (compound No. 139), 3-bromo-6- [4- (2-methoxyphenyl) -1-piperazinyl] -pyridazine at mp 164.8 ° C (Compound No. 140), 3-bromo-6- [3- (trifluoromethyl) -phennyl] -1-piperidinyl] -pyridazine hydrochloride, m.p. 222.5 ° C (compound ID No. 141), 3-bromo-6H [3,6-dihydro-4-f [3- (trifluoromethyl) -phenyl] -1n (2H-pyridinyl] -pdidazine, m.p.1 # 0.6 ° C) compound no. 142 /, 63 l- (6- (bromo-3-pyridazinyl) -4 - "(3-chlorophenyl) -hexahydro-lH-l, 4-diazepine, m.p. 148.8 ° C (compound no. 143), 3-bromo-6-i [4-i (3-bromophenyl) -1-piperazinyl] -pyridazine with melting point. 179.8 ° C (compound 65 No. 144) and 147 465 21 22 3-bromo-6- [3,6-dihydro-4- (3-methylphenyl) -1- (2H) -pyridinyl] -pyridazine * mp 127.1 ° C (compound No. 145). Example XXIII. 4.5 parts of 3,6-dichloropyridazine, 4.9 parts of Nw [3- / trifluoro-methyl / -phenyl] -3-piperidylamine, 6.4 parts of sodium carbonate and 180 parts of N, N-dimethylformamide are mixed at a temperature of about 65 ° C overnight, then poured the mixture into ice water and extracted with dichloromethane. The extract is dried, filtered, evaporated and the residue is chromatographed on a silica gel column, eluting with a mixture of trichloromethane and methanol (99: 1 by volume). The eluent is evaporated from the pure fractions, the residue is recrystallized from 2-propanol, the precipitate is filtered off, retaining the filtrate. and after drying the precipitate 1.2 parts (16.8%) of theoretical yield (1- (6-chloro-3-pyridazinyl) -N- [3- (trifluoromethyl) -phenyl] -3- are obtained. piperidylamine melting at 92.6 ° C (compound No. 146). The product contained in the retained slurry is converted in the environment of propanol-2 into a salt with hydrochloric acid, the precipitate formed is filtered off, and after drying, 2.6 parts (32.9% of theoretical yield) are obtained. (6-chloro-3-pyridazinyl) -N- [3- (trifluoromethyl) -phenyl] -3-piperidylamine, m.p. 173.5 ° C (compound No. 147). 10 15 20 25 Example XXIV. 3 parts of 3,6-dichloropyridazine, 6.1 parts of N- [3- / trifluoromethyl'-phenyl] -4-pdperidylamine dihydrobromide, 6.4 parts of sodium carbonate and 180 parts of N, N-dimethylacetamide are mixed It is stirred at 60 ° C. for 24 hours, then cooled to room temperature, poured into water and extracted with toluene. The extract is rinsed with water, dried, filtered, evaporated and the residue is chromatographed on a silica gel column, eluting with a mixture of trichloromethane and methanol (97: 3 by volume). The eluent is evaporated from the pure fractions and the residue recrystallized from diisopropyl ether. After filtering and drying, 2.5 parts (47% of theory) (1- (6-chloro-3-pyridazinyl) -N- [3- (trifluoromethyl) -phenyl] -4-piperidylamine are obtained. having a melting point of 117.9 ° C (Compound No. 148). The compounds of formula I are prepared by proceeding in an analogous manner and using equal amounts of the appropriate starting products, in which R1 is chlorine and R2, R * and A have the meanings given in Table 4. In Compound No. 185, R 1 is bromine, not chlorine. This table lists the sequence numbers of the compounds, the form in which the compound was obtained, be it an acid salt or a free base. as well as the melting point of the product. Table 4 Compound number 1 R * 2 R5 3 A 4 Salt or base 5 Melting point, ° C 6 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 HHHHHH -CH = CH- -CH = CH- -CH = CH- -CH = CH- -CH = CH- -CH = CH- -CH = CH- HHHHHHH -CH = CH- HHHHHHHHHHH CH = CH- CH = CH- CH = CH- CH = CH- CH = CH- CH = CH- CH = CH- HHHHHH CH = CH- HHHHH 34 33 26 22 18 54 pattern 129 pattern 130 pattern 131 pattern 132 pattern 133 pattern 133 pattern 134 pattern 38 pattern pattern pattern pattern 135 pattern 136 pattern 137 pattern 138 pattern 139 pattern pattern pattern, pattern 141 pattern 142 pattern 143 pattern 144 140 29 25 27 rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule rule I / 2 / COOH / 2 rule rule * rule rule rule rule 209.7 184.7 127.0 197.4 160.5 124.4 209.2 178.6 170.2 167.2 167.0 135.6 225.6 196.3 155.5 195.1 157.1 137.1 136.8 155.9 218.5 132.7 130.2 121.7 156.2 170.4147 465 23 24 Table 4 - cont 1 175 176 177 178 179 180 181 '182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 2 HH * HHHHHHHH H- HHHHHHHHHHHHHHHHHH 3 HHHHHHHHHHHHHHHHHHHHHH formula 148 formula 148 formula 149 formula 149 pattern 150 pattern 151 pattern 152 pattern 153 pattern 154 pattern 155 pattern 156 pattern 157 pattern 158 j pattern 159 pattern 160 pattern 161 pattern 162 pattern 163 pattern 1641, pattern 165 pattern 166 pattern 167 pattern 94 pattern 122 pattern i2fi pattern 128 5 rule rule rule rule HBr.m / CH ^ CHCH rule rule rule rule rule FOOCCH = CHCOOH rule rule rule rule rule HCl rule rule rule rule rule rule rule rule rule rule 6 144.7 138.0 95.0 107.5 193.0 104.4 154.0 121.7 91.5 119.3 197.3 183.7 115.7 164.4 94.6 127.0 193.8 102.1 129.8 121.5 138.4 74.7 168, 0 115.1 179.5. 157.9 119.3 Example XXV. 5.2 parts of 3,6-diiodopyridazine, 3.5 parts of l- [3- (trifluoromethylb) -phenyl] -piperazine, 3.2 parts of sodium carbonate and 90 parts of N, N-dimethylacetamide are mixed at temperature At 70 ° C overnight, it is poured into water, the precipitate formed is filtered off and recrystallized from propanol (2i), giving 3.2 parts (48% of theory) of 3-iodo-6- [4H 3-i /, trifluoromethyl (phenyl] -1-piperazinyl] -pyridazine, melting point 144.6 ° C (Compound No. 202). The following compounds are prepared analogously: 3-iodo-6- [4- (3-methylphenyl) -1-piperazinyl] -pyridazine, m.p. 163.1 ° C (compound No. 20a ', 3- [4- (3-chlorophenyl) -yl-piperazinyl] - 6-iodopyridazine, m.p. 165.0 ° C (Compound No. 204), 3- [4- (2,3-dimethylphenyl) -1-piperazinyl] -6-iodopyridazine, m.p. 1.79.4 ° C. (compound No. 205) and 3-iodo-6- [N - [3-trifluoromethyl) -phenyl-1-piperidinyl] -pyridazine with a melting point of 106.8 ° C. (compound No. 206). Xxvi. A mixture of 4.6 parts of 1- [3- (trifluoromethyl) phenyl] piperazine, 6.4 parts of sodium carbonate and 160 parts of 2-methylpentanone is azeotroped to dry and then added 3.3 parts of 3,6-dichloro-pyridazine and stirring kept in the heat of boiling under a reflux condenser with a water separator. After 48 hours, the mixture is cooled, added to water and extracted with dichloromethane. The organic layer is dried, filtered, evaporated and the residue chromatographed on silica gel, eluting with a mixture of trichloromethane and methanol (99: 1 by volume). The eluent is evaporated from the pure fractions and the residue is recrystallized from 2-propanol to give 2.6 parts (37% of theoretical yield) (3-chloro-6 - [) 1- [3- (trifluoromethyl) n-phenyl] -1-piperazinyl] -pyridazine, m.p. 149.4 ° C. (Compound No. 207.) Example XXVII. A solution of 8 parts of ethyl piperazin-1-carboxylate and 5.6 parts of triethylamine in 25 parts of N, N-dimethylformamide is added dropwise to a solution of 7.5 parts of 3,6-dichloropyridazine in 75 parts of N, N-dimethylformamide. then stirred at about 50 ° C overnight and then cooled, poured into water and extracted with trichloromethane. Organic extract. dried, filtered, evaporated and the residue recrystallized from propanol-2 to give 3.6 parts of 4-y6-chloro-3-β: ridazinyl-piperazine-1-carboxylic acid ethyl ester, m.p. 123.8 ° C / Compound No. 208. 'Example XXVIII. 3.2 parts of 3-chloro-6- (methylsulfonyl) -pyridazine, 3 parts of 1- (3-methylphenyl) -piperazine, 2 parts of triethylamine and 180 parts of benzene are mixed and kept in a boil It was heated under reflux for 24 hours and then evaporated. Add water to the residue, filter the precipitate, wash it with water, dissolve it in trichloromethane, dry the solution, filter and evaporate. The residue recrystallizes. After drying, 5 parts (89% of theoretical yield) (3- [4- (3-methylphenyl) -1-piperazinyl] -6-methylsulfonyl) -pyridazine, m.p. 201 ° C / compound No. 209 /. The following compounds were prepared in a similar manner: 3- [4-i (3-methylphenyl-1-piperazinyl] -6- (methylisulfinyl) -pyridazine, m.p. 146.0 ° C (compound No. 210) , 3- [3,6-dihydro-4V3-methylphenyl] -1 (2H-pyridinyl] -6-methylsulfonyl) -pyridazine, mp 179.8 ° C (compound No. 2111) and 3- [3, 6-dihydro-3V3-methylphenyl (-1 (2H) -pyridinyl] -6- (methylsulfinyl) -pyridazine with a melting point of 131.0 ° C (Compound No. 212). Example XXIX 3.3 parts 3, 6-dichloropyridazyiiy, 3.3 parts of W2-pyridinyl / piperazine, 1.5 parts of sodium bicarbonate and 120 parts of ethanol are mixed and boiled under reflux for 2 days, then evaporated, and added to the remainder. water and extracted with dichloromethane. The extract is dried, filtered, evaporated, and the residue is The volume is chromatographed on a silica gel column, eluting with a mixture of trichloromethane and methanol, 1) 9: 1 by volume. The eluent is evaporated from the pure fractions and the residue is recrystallized from a mixture of propanol-2 and tetrahydrofuran to give 2.5 parts (45 "3") "theoretical" (3-chloro-6- [4-f / 2-pyridinyl ') -1-piperazinyl] -pyridazine, m.p. 194.7 ° C (compound No. 213). Example XXX. 3.2 parts of 3-chloro-6- (methylthio-pyridazine), J 3.14 parts of 1,2,3-tetrahydro-4-i (3-methylphenyl) -pyridine hydrochloride, 5.3 parts of carbonate of sodium and 80 parts of methanol-1 are mixed and boiled under reflux for 48 hours, then evaporated, added to the residue with water and extracted with trichloromethane. The extract is dried, filtered and evaporated, eluting with a mixture of trichloromethane and methanol (98: 2 by volume). As much as the eluent is evaporated from the pure fractions, the residue is recrystallized from propanol-2 and after drying 0.8 parts (18% of theory) of 3- [3,6-dihydro-4- (3-methylphenyl) are obtained. (2H) -pyridinyl] -6- (methylthio) -pyridazine, m.p. 129.8 ° C., Compound No. 214. Example XXXI. 3.9 parts of 3,6-dichloro-4,5-dimethylpyridazine, 4.2 parts of 1- (2,3-dimethylphenyl) -piperazine and 2.94 parts of potassium carbonate are mixed and kept on an oil bath. at 190 ° C for 4 hours, then cooled, mixed with water and with trichloromethane, and the layers were separated. The organic layer is dried, filtered, evaporated and the residue is recrystallized from 2-propanol. After drying, 2 parts (30% of theory) are obtained (3-chloro-6- [4-1,2,3-dimethylphenyl -Mi-piperazinyl] -4,5-dimethylpyridazine, m.p. 194.5 ° C) compound No. 217 /. In an analogous manner the following is prepared: and 4- (3-methylphenyl) -1- (6-methyl-3-pyridazinyl) -piperidinol-4 melting at 131.5 ° C 5 (compound No. 219). Example XXXII. 3.5 parts of N- / 6-chloro-3-pyridazinyl / -acetamide, 3.6 parts of 1- / 3-methylphenyl / -piperazine and 2.8 parts of potassium carbonate, mixed in an oil bath of at 160 ° C. for 7 hours, then cooled, added trichloromethane and water, and the layers were separated. The organic layer is dried, filtered, evaporated and chromatographed on. column of silica gel, eluting with a mixture of trichloromethane and methanol (97: 3 by volume. " and drying, 0.5 part of theoretical yield is obtained. Compound No. 220, /., Example XXXIII. 4 parts of 6-chloro-3V4-ethylphenoxy) -pyridazine and 6 parts of 1- (3-methylphenyl) -25-piperazine are mixed and kept at 110 ° C at for 3 hours, then left to stand overnight and then added with concentrated ammonium hydroxide and trichloromethane. The precipitate was filtered off and the filtrate was chromatographed on a silica gel column, eluting with a mixture of trichloromethane and methanol (95: 5 by volume). of the pure fractions, the eluent is evaporated, the residue is recrystallized from diisopropyl ether and after drying, 1.7 parts (27% of theoretical yield) of (3- (4-ethylphenoxy) -6-B4- (3-methylphenyl) -1-piperazinyl] -pyridazine are obtained with a melting point 1.06.6 ° C (compound 221). In an analogous manner: 222 (and, 3- [.sup.4 (3-methylphenyl) -piperazinyl] -6- (methylthio) -pyridazine, m.p. 145.0 ° C. (compound No. 223). The following compounds are prepared by methods analogous to those described in Examples XIX to XXXIII:. . 3- (3,5-dimethyl-phenoxy) -6-ylH-imidazolyl-1) pyridazine, m.p. 170 ° C (compound No. 50 2), 3- (1H-imidazolyl-li) -6- (4-methylphenoxy) -pyridazine, temperature! mp. 1'46 ° C (compound No. 3), 3- (ylH-imidazolyl-1-6-., '3-nitrophenoxy) -pyridazine, mp 172 ° C (compound No. 4), 55 3- / 4 -chlorophenoxy (-6-) ylH-imidazolyl-V-pyridazine, m.p.- '165 ° C (compound No. 5 /, 3- (4-bromophenoxy) -6.11H-imidazolyl-i / -pyidazine, mp 169 ° C (Compound No. 66, 1- (4-Fluorophenyl) -4- [? 4- (3-pyridazinyl) -1-piperazinyl] -cyclohexanecarbonitrile, m.p. 189.5 ° C (Compound No. 8), 1- (6-chloro-3-pyridazinyl Oi'-4-piperidinamine, m.p. 260 ° C, with signs of decomposition (compound No. 225), 65 3-chloro-6- [4-vl-phenylpropyl monohydride) -147,465 2T 28 -l-piperazinyl] -pyridazine, m.p. 206 ° C (Compound No. 226), 1-butanol (l.l.) 3-chlorc-4-methylp-6- monohydrochloride monohydrate [i4H, 3-phenylpropyl) - l-piperazinyl] -pyridazine, m.p. 186 ° C. (compound No. 227), 3-methoxy-6- [4- (3-phenylpropyl) -1-piperazinyl] -1-pyridazine, m.p. 78 ° C (compound No. 22a) 3-Methoxy-dihydrochloride monohydrate (3-phenylpropyl) - and pyl (-1-piperazinyl] -pyridazine, mp. 209.5 ° (Compound No. 229), X-acetyl-4- (6-chloro-3-pyridazinyl) -piperazine, m.p. 155 ° C (compound No. 230), 3-cMo (ro-6- [4- (2-phenylethyl) -1-pipirazinyl] -ipyridazine, mp: 141 ° C (compound No. 231), - 3-chloro 6- (4-cyclohexyl-1h-piperazinyl) -pyridazine, m.p. 188 ° C (Compound No. 233), 1K (6-chloro-3-pyridazinyl (N-N-) phenylmethyl-4-piperidinamine, melting point 93 ° C (Compound No. 234), -. "..-. 3-chloro-6- [3,6-dihydro-4- (3-methoxyphenyl-1,2H) -pyridinyl] -pyridazine, temperature mp 125 ° C (compound 235), 3-chloro-6- | 4-'3-chlorophenyl) -3,6-dihydro-1 (2H) -pi: -25 ridinyl] pyridazine, mp 135 ° C (compound No. 236) "\ 3-chioro-6- (3,4-dihydro-5-phenyl-1 / 2H-pyridinyl) - pyridazine, mp 147 ° C (Compound No. 237), "3-chloro-6- [3,4-dihydro-5- (3-methylphenyl) -1 (2H)" pyridinyl] -pyridazine, m.p. 160. 5 ° C (compound No. 238), -N 3-chloro-6- [| 4- (3-fluorophenyl) -3J6-dihydro-1 (2H) -pyridinyl] -pyridazine, m.p. 124 ° C 35 / compound No. 239 /, 3-chloro-6- [4- (2,3-dimethylphenyl) -3,6-dihydro-1- (2H) -pyridinyl] -pyridazine, m.p. 145 ° C (compound No. 240) , 3-chloro-6- [β-v'3-chiorophenyl) -3,6-dihydro-57-methyl-40 -l (2H) -pyridinyl] -pyridazine, m.p. 89.5 ° C (compound no. 241 (1,4-chloro-6-', 3,4-dihydro-5- [3H (trifluoromethyl') -phenyl] -1 (2H) -pyridinyl] -pyridazine, mp 164 ° C / compound No. 242), 45 3-chloro-6- [13,6-dihydro-5- [3- (trifluoromethyl) -phenyl] -1 (2H) -pyridinyl] -pyridazine, "mp 112 ° C. (compound No. 243), 3-chloro-6-i [? 5-i? 3-fluoro (phenyl) -3,6-dihydro-l '(2H) -pyridinyl] -pyridazine, m.p. 134 ° C 50 (compound No. 244), 3-chloro-6- [314 -dihydro-5- (3-methoxyphenyl) -1 (2H7-pyridinyl] -pyridazine, melting point 128 ° C (compound 245), 3-chloro-6- [5% 2,3-dimethylphenyl) -3 ; 4-dihydro-1-55 (2H) -pyridinyl] -pyridazine, m.p. 147.5 ° C (compound 246), 3-chloro-6- [3,6-dihydro-4- (2-na) monohydrochloride - phthalenyl and -1 (2H) -pyridinyl} -pyridazine,. melting point 187 ° C (Compound No. 247 ', 60 3-Chloro-6-B3- (3-methylphenyl) -2H-pyrrolyl-1 / 5H'-pyridazine, mp 199 ° C / Compound 24a ;, 3-chloro-6- [β 2,3-dihydro-4- (3-methylphenyl) -1H-pyrrolyl-i] -pyridazine, m.p. 194 ° C 15 (Compound No. 249), 3-chloro -6 -. 'I -3,6-dihydro-4- (2-phenylethyl) -1 (2H) -pyridinyl] -pyridazine, m.p. 104 ° C (compound No. 250), 3-chloro-6- [ 15- [4-chloro-3- (trifluoromephyl) -phenyl] -3,4-ddhydro-1,2H-pyridinyl] -pyridazine, m.p. 141.5 ° C (Compound No. 251), 3- chloro-6- [| 3- (3-fluorophenyl) -2,3-dihydro-1H-pyrrolyl-1] -pyridazine, m.p. 214 ° C (compound No. 252), 3-chlorQro-6- [3 - (3-fluoTophenyl) -2,5-dihydro-1H-pyroH-1] -pyridazine, m.p. 229 ° C (compound 253), 3- [1,6-o; ihydro-4- (3) -methylphenyl '- -1 (2H) -pyridinyl] - -6-methylpyridazine mp 124 ° C (compound 254), 3- [3,6-dihydro-4- (3-methylphenyl) -1v'2H) - pyridinyl] -6-methsypyridazine, temperature and melting. 115 ° C (compound No. 255), 3-butoxy-6- (3,6-dihydro-4- (3-methylphenyl) -1 (2H) -pyridinyl] -pyridazine, m.p. 97 ° C (compound No. 256 (3-butoxy-6- [4- (3-methylphenyl) -1-piperazinyl] -pyridazine, m.p. 104.5 ° C (Compound No. 257), '-. 3-methoxy-6- [4- (3-methylphenyl) -1-piperazinyl] -pyridazine, m.p. 136 ° C (compound No. 258. ', 3- [4- (3-fluorophenyl) -3, 4-dihydro-H (2H) -pyridinyl] - -6-methoxypyridazine, m.p. 84 ° C (compound 259), 3 - [? 3,6-dihydro-4V2,3-dimethylphenyl] -1 / 2H) - pyridinyl] -6-methoxypyridazine, m.p. 110 ° C. (Compound No. 260), 1- (6-methoxy-3-pyridazinyl) -4 (3-methylphenyl) -pperidinol-4, m.p. 126 ° C (compound No. 261), 3 - [1, 4-dihydro-4- (3-methylphenyl) -1 (2H) -pyridinyl] - -6-ethoxypyridazine, m.p. 85 ° C (compound No. 262) 1- (6-butoxy-3-pyridazinylcv'-4- (3-methylienyl) -pi-peridinol-4, m.p. 106 ° C (compound No. 263), 3- [β-ridazine, m.p. 123 ° C (compound No. 264), 3- (4-chlorophenoxy) -6-Q4-γ3-methylphenyl) -1-piperazinyl] -pyridazine, m.p. 131 ° C (compound No. 265), 3- [4- (3) -methylphenyl (-1-piperazinyl] -6-, 'thiophenyl) -pyridazine; mp 1 <35 ° C (compound 266), 3- [4- (3-methylphenyl) -1-piperazinyl] -6- (phenylmethoxy) -pyridazine, mp 158.5 ° C (compound No. 267 /, 4- (3-methylphenylcx '1- [? 6-phenylethoxy) -3-pyridase-. nyioJ-piperidinol-4, m.p. 125 ° C (Compound No. 268), 6- [4-hydroxy-4- (3-methylphenylo .'- 1-piperidinyl] -pyridazinol-3, mp 264 ° C / compound Compound No. 269), 6- [3,6-dihydro-4V3-methylphenyl. '-1 (2H) -pyridinyl] -pyridazinol-3, m.p. 178 ° G (Compound No. 270), 6- [ 4- (3-methylphenyl. VI-piperazinyl] - (2H-pyridase-147 465 29 30 non-3, m.p. 210 ° C) (compound No. 271i ', 3- [4- (4-methoxyphenyl) -1-piperazinyl ] -pyridazine, mp. 134 ° C (Compound No. 272), 6- [4- (3-methylphenyl] -1-piperazinyl] -thiopyridazine-3, mp 175 ° C (Compound No. 273). .'- ¦ • 1- [6-1-4- (3-methylphenyl] Z-1-piperazinyl] -3-pyridazinyl] -ethanone, m.p. 135 ° G (Compound No. 274) and 1- [| 3- [3,6-dihydro-4- (3-methylphenyl) -i-2H / -pyridinylq] -3-pyridazinyl] -ethanone, m.p. 114 ° C (compound No. 275). Claims 1. A method for the preparation of new pyridazineamine compounds - of the general formula I, in which R1 represents a hydrogen atom or a halogen, group 1H-imidaziolyl-1-o, group. / Ci phenoxy group; having optionally 1 or 2 substituents, such as halogen atoms, (C x -C4 alkyl groups or nitro groups), R2 and R8 are identical or different and represent hydrogen atoms or (C1-C * 'alkyl radicals) or R2 and R8 together. The bivalent group -CH = CH-CH = CH-, and A denotes a bivalent group of formula 2, 3, 4 or 5, where in the formulas 3, 4 and 5 min are the same or different and represent integers 1-4 , and the sum of m + n is 8, 4 or 5 and one of the hydrogen atoms in the groups CmH-m, Cm-iH2m-and or CnH2n may be replaced by a / Cj-C4 alkyl radical, R4 in formula 3 is a phenyl radical , optionally having 2 or 3 substituents, such as (Ci-C ^ alkyl radicals, halogen atoms, nineteen, (Ci-Ci. 'halogenophenylcarbonyl groups and hydroxyl group, or H4 represents a thiazole, pyrimidinyl, γCi ^^ "alkylcarbonyl, diphenylmethyl, (C-C, oxycarbonyl) group, which can be to be substituted by a (C1-Ca) alkyl radical or a cyano group, or R4 is also a cyclohexyl or cyclohexenyl group, which may have 1 or 2 substituents, such as cyano and halophenyl groups, R5 in Formula 4 represents a hydrogen atom, a (C 1 -C 6 alkyl) radical, a phenyl radical, optionally having 1 or 2 substituents such as halogen atoms, (C 1 -C 6) alkyl groups, trifluoromethyl and (C 1 -C 1) groups. C1-4 alkoxy or R5 represents a hydroxyl group, a (C1-C6 alkoxy group which is optionally substituted with a piperidine group, a phenydamino group which has optionally 1 or 2 substituents, such as (C1-4) alkyl radicals) , halogen atoms and trifHuoramethyl, or R5 is also a (phenyl) - -7Ci-C4.'a! lkylamino group, C1-C6 alkylphenyl / C1-C6 alkylamino, phenyl / C1-C (j / alkenyl) -:; C1-C4) alkylamino or phenylcarbonyloxy, R8 in the formula 4 is a hydrogen atom, a (C1-C6) alkyl radical, a phenyl radical that may have 1 or 2 substituents such as (C1-C8) alkyl groups, halogen atoms, 7C1-C4) alkoxy groups and trifluoromethyl groups, or R * is a (C1-C4) alkylcarbonylamino (C1-C4) alkyl group, phenyl group, (C1-C6) alkyl, which is optionally substituted by halogen, or R8 is also amino-carbonyl, phenylaminocarbonyl or (C1-C4) -alkoxycarbonyl, and R7 and R8 in formula 5 are the same or different and represent hydrogen atoms , (C 1 -C 4) alkyl groups or phenyl groups optionally having 1 or 2 substituents, such as (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy groups, halogen atoms and , trifluoromethyl, with the proviso that when A is a group of formula 4, wherein R is hydrogen, then R5 is as defined above, but with the exception of hydrogen, hydroxyl and (Cj-Cft) -alkyl group, and when R2 and R8 in formula 1 are hydrogen and A is the group of formula II, in which case R1 is as defined above, but with the exception of halogen and when R1 is chlorine, R2 and R8 are hydrogen and A is the group of formula III, then R4 in formula III is as defined above, but with the exception of the 2-methoxyphenyl group or the pharmacologically acceptable acid addition salts of the compounds of formula 1 and / or the sterepisomers of these compounds, characterized in that the amine of formula 6r in which The meaning of A is as defined above and is alkylated with a pyridazine derivative of formula VII in which W is a reactable cleavage group and R1, R2 and R8 are as defined above, the reaction being carried out by if necessary, in an inert solvent and, if necessary, in the presence of a base, and then 3 The resulting compound of formula I is optionally converted by reaction with a suitable acid into a pharmacologically acceptable acid addition salt, or the acid addition salt is converted by treatment with alkali on the free base of formula I and / or prepared these compounds appear as single stereoisomers. 2. A process for the preparation of new pyridazine amine compounds of general formula I, in which R 1 represents a hydrogen or halogen atom, a 1H-imidazoMl-1-group, a (C 1 -C 6) alkoxy group, a phenoxy group optionally having 1 or 2 substituents, such as halogen atoms, (C 1 -C 6 alkyl and nitro groups, phenylloyl-C 1 -C 4) alkoxy group, (C 1 -C 4) alkylthio, phenylthio, hydroxyl, mercapto, amino, (C 1 -C) Alkylsulfinyl, (C-C ^) alkylsulphonyl, cyano, (C-C-alkoxycarbonyl or (C-C) alkyl), R2 and R8 are the same or different and represent hydrogen atoms or (C) groups. 'alkyl, or R * and R8 together form a divalent group of formula -CH = = CH-CH = CH-, and A is a divalent group of formula 2, 3, 4; or 5, where in the formulas 3, 4 and 5 min are the same or different and represent integers 1-4, and the sum of m + n o is 3, 4 or 5 and one of the hydrogen atoms in the CmH2m groups , Cm-1H2111-1 and CnH2n may be replaced by a (C 1 -C 4) alkyl group, R 4 in formula 3 is a phenyl radical, optionally having 1, 2 or 3 substituents such as (C 1 -C 4) talkyl radicals , halogen atoms, nitro, groups 147 465 31 32 (C 1 -C 1) alkoxy,. (C 1 -C 4) alkexycarbonyl, trifluoromethyl, halophenyl carbonyl and hydroxy, or R 4 is thiazoyl, pyrimidinyl, (C 1 -C 4, alkylcarbonyl, diphenylmethyl, / C 1 -C 4 alkoxy) 5 4-cycarbonyl, a pyridinyl group which may be substituted with a (C 1 -C 4 alkyl radical) or R 4 is also a cyclohexyl or cyclohexenyl group, which optionally have 1 or 2 substituents, such as cyano and halogen-phenyl groups or R4 represents a quinolyl group, a phenyl (C 1 -C 6) alkyl group, a (C 1 -C 4 alkylphenyl), C 1-6 alkyl or naphthalenyl group, R 5 in the formula 4 is a hydrogen atom, a (C 1 -C 6) alkyl radical, a phenyl radical optionally having 1 or 2 substituents such as halogen atoms, (C 1 -C 6 alkyl groups, trifluoromethyl and (C 1 -C 4 'alkoxy) groups, or R 6 is hydroxy, (C 1 -C 6) alkoxy, which is optionally substituted piperidine group, phenylamino group that may have 1 or 2 substituents, such as (C 1 -C 6 alkyl radicals, halogen atoms and trifluoromethyl groups, phenyl) C 1 -C 4 alkyl-amino, (C 1 -C 6) alkylphenyl / C 1 -C 6 alkyl / amino, phenyl) -C 1-4 alkenyl / 1 / C 1-6 -C 4) alkyl / amino, phenyl- * 5-carcinyloxy-xytophyl * -halogen-phenoxy-amine, -C1-C4) alkoxycarbonylamino or naphthalenyl, in formula 4 is a hydrogen atom, / C 1 -C 6-, R8 radical in formula (4) represents a hydrogen atom, a (C 1 -C 6 'alkyl radical), a phenyl radical that optionally has 13 or 2 substituents, such as (C 1 -C 6' alkyl groups, halogen atoms, and (C 1 -C 6) groups; alkoxy and trifluoromethyl group, (C1-C4alkylcarbonylamim'Ci-C4-) alkyl group, phenyl / C1-Cgalyl group which is optionally substituted with halogen, or R6 is am: nocarbonyl, phenylaminocarbonyl, (C1-C4) alkoxycarbonyl, halophenylcarbonyl, X-1-C4) alkyl, phenylcarbonyl which is optionally substituted with trifluoromethyl or halogen, phenyl. 1C1-C4 (alkylcarbonyl, incolyl, thienyl, pyridyl or naphthalenyl), and R7 and Rs in formula 5 are the same or different and represent hydrogen atoms, .! or 2 substituents such as (C 1 -C 4) alkyl radicals, (C 1 -C 4) alkoxy groups, halogen atoms and trifluoromethyl groups, or represent phenyl (C 1 -C 4) alkyl, thienyl, naphthaienyl or pyridyl groups, where: when A is a group of formula IV, where R8 is hydrogen, then R8 is as defined above, but with the exception of hydrogen, hydroxy and (C1-C8) alkyl groups when R6 and R8 are hydrogen and A is the group of formula II, then R1 is as defined above, but with the exception of halogen, when R1 is chloro, R2 and R8. are hydrogen and A is a group of formula III, then R4 in formula III has the meaning given above, M but with the exception of 2-methoxy when R1 is chloro and A is a group of formula III, then R4 in formula III has the meaning given above, but other than the [alpha] -methylphenylpvd (2-methylphenyl) methyl group and 1 simultaneously R 1 represents a hydrogen atom or a halogen atom, a 1 H -imidazolyl-1-o group, a (C 1 -C 6) alkoxy group or a phenoxy group, optionally having 1 or 2 substituents, such as halogen atoms, -1Ci-C4 / alk: 1 groups or the nitro group, R * and R8 are the same or different and represent hydrogen or (C1-C4) alkyl radicals, or R * and R8 together form a bivalent -CH =, CHtCH = CH- group, and A is bivalent group of formula 2, 3, 4 or 5, where in the formulas 3, 4 and 5 min are the same or different and represent integers 1-4, and the sum m + n is 3, 4 or 5 'and one of the hydrogen atoms in the groups CmH2m, 0111-2112111—! or CnH2n may be replaced by a (C1-C4alkyl) radical, R4 in formula 3 is a phenyl radical, optionally having 1, 2 or 3 substituents, such as TC1-C41 "alkyl radicals, halogen atoms, nitro group, -C4'- alkoxy, (C1-6 alkoxycarbonyl, trifluoromethyl, chloro-phenylcarbonyl and hydroxyl groups, or R4 is thiazoyl, pyrimidinyl, (C1-6) alkylcarbonyl, diphenylmethyl,) Bonyl, a pyridinyl group which may be substituted with a (C1-C4) alkyl radical or a cyano group, or R4 is also a cyclohexy or cyclohexenyl group, which may have 1 or 2 substituents, such as cyano and halogenophenyl groups, R 5 in formula 4 represents a hydrogen atom, a (C 1 -C 6) alkyl radical, a phenyl radical, optionally having X or 2 substituents, such as halogen atoms,. Because R6 is hydroxy, fCi-Caf-alkoxy, kt Which is an optionally substituted piperidine group, a phenylamino group having optionally 1 or 2 substituents such as radicals, 'C1-G4alkyl, halogen atoms and trifluoromethyl, or also R8 is (phenyl) - / C1-C4,' alkylamino, (C 1-4) alkylphenyl (C 1-4) alkylamino, phenyl. 1 -C 1 -C 4 (alkyl) amino, phenyl (C 1 -C 6) alkenyl) (1-C 1 -C 4) alkylamino or phenylcarbonyl, R8 in formula 4 represents a hydrogen atom, a 7Ci-C6alkyl radical, a phenyl radical that may have 1 or 2 substituents such as (C1-C6) alkyl groups, halogen atoms, (CJ-C4 alkoxy groups and a trifluoromethyl group, or R8) is a (C 1 -C 4) alkylcarbonylamino- (C 1 -C 4 alkyl group, a phenyl) C 1 -C 6 alkyl group which is optionally substituted by halogen, or also. R8 is an aminocarbonyl, phenylamino-carbonyl or (C-C) alkoxycarbonyl group, and R7 and R8 in formula 5 are the same or different and represent hydrogen atoms, groups; C1-C4) alkyl or phenyl groups optionally having 1 or 2 under Representatives such as (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy groups, halogen atoms and trifluoromethyl groups, which compounds can also be prepared as pharmacologically acceptable acid addition salts and / or in the form of individual stereoisomers, characterized in that the amine of the formula 6 in which A is as defined above is alkylated with a pyridazine derivative of the formula 7 in which W is a reactive cleavable group and R1, R2 and R8 are as defined above, these reactions being carried out, if necessary, in an inert solvent and, if appropriate, in the presence of a base, and then the compound of the formula I obtained is optionally reacted with a suitable acid into a pharmacol The freely acceptable acid addition salt or acid addition salt is converted by treatment with alkali to the free base of formula I and / or the compounds are prepared as single stereoisomers. R 1, LA -CH = N-CH = CH- FI2 R3 Formula 2 Formula 1 R4 _CmH2mN ~ CnH2rT Formula 3 R5 R6 Crrf ^ m ^ Formula _Cm-iHaCm-i) "CnH2n 4 f R8 I 1 ¦cc- Formula 5 hKT a Formula 6 \ - R2 ~ CnH2n Iw Rl Formula 7 / Cnl ^ ra ... n4-a PN 'NH + WR \ CnH2n' Formula 9 H2N-R4 ~ Q Formula 8a Formula 8 Scheme 1 PN '/ CmH2m \ 4-a P-Nx NR CnH2n / Formula 10 / CmH2m \ .HN (N-R4_a XCnH2n / Formula 11a CmH2m-W ¦CnHe-nW Formula 12 'UJ0ZA1 ZZ JPZM -Z (2H3) - * (* H3) SH93-H3-Z? H3) - ^ H93-! 3-C) -N- ^ H3) 9Z JQ * MU J02AA fH «3-« J3-C) -n- «PH3) - [WHD) -9VZ] -N-? H0) Oc JP-zyW - * ( ZH3) (iftuftPMd-2-cH3-9) -INI - * (* H0) -ZPH3) (£ H93-Z13-C'3) -N- ^ H3) - -Z ^ H3), N,% «c ^ ', * ^ * H93-SH23-C) -N-2 (2H3) - H33-CH3-C) -HN-H3-Z (ZH3) -' vy 6y - "w -Z (2H3) £ Z J0 * An 81 JOZM (H ^ -jB-Z) -rl | - «? H3) -? H93-CH3-C) -N- ^ H3) -VzH0" • Lllj Ct7H93-cHz3-z) -N- ^ H3 6d-Ns ^ 2 ^ 3 z} DuueL | os Dx) and H V, SL -JOZM VI J92M n JOzM 6U-NX / u2hu3x ol ^ U2HU3X .3V / N_d -— cd-NH + 0 = 3. Nd sa * a \ 147 465 - (CH ^ -CH- (3-CH3-C6H4) (CH2) z- mor 28 - (CH2) 2-CH- (3-CF3-C6H4) (CH2) 2- 1 * ZOr 29 (CH2) 2-N- (4-CH30-CtH4) (CH2) 2-. Formula 30 - CH2-CH (CH3) -N- (A-CH30-C6H ^) (CH2) 2- Formula 3i ( CH2) 2-N- (2-t. Oiii) (CH2- Formula 32 ¦ (CHj-NC «H5 (CH ^ z- Formula 33 - (CH2VN- (2 ~ CH30-C6H4) Chip 34 -. (CH ^ -N- (4-CHs-C «H4) Formula 35 -XH2) 2-N- [3, A- (CH3) 2-C6H3i (CH2) 2- Formula 36 - (CH2) 2-N- (2 - piP ^ midynm) Pattern 37 '- (CH2) 2rN- [213-fCH ^ -CaH3] CH, and 2'2 Formula 39147 465 -CH2-CH (CH3) -N- (2-Cl-CsH4) Pattern 39 (CH 2 N- [AC 1 H 50 C (O) -Cf H 4 I (CH 2) 2- Formula 40 (CH 2 Nf 2 -f 3 H 4 -C H,] CH 2; Formula 41 CH 2 -CH (CH 3) -N- (4- CH3-C6H,) (CH2) 2- Formula 42 (CH2) 2-N - [(2-CH30) - (5-CF3) -CcH2 ttH2) 2- Formula 43 (tH2) 2-N-CH (C6H5) (CH2) 2- Formula 44 -CH2-CH (CHs) - ^ - (3-CHs-CfiH4) (CHa) a- Formula 45 - (CH2) 2-N- (3-r-C6H4) (CH2) 2 - Formula 46 ~ (CH2-rvJ - (3-CN-2- pir * ftjmjl) (CH2- Formula 47 - (CHjJr ^ l- C6H4-C (0) - (4-CI-C6H4) (CHa) i- Formula 48 -CH2-CH (CH3) -N- (4-Cl-C6H4) (CH2) 2- Formula 49 - (CHa), - N- [3, A- (CH30) 2-C6H3] (CH,) i-147 465 CH2-CH (CH3) -N-C6H5 (CH2- Chip 51 - (CH2) 2-N- (4-0H-C6H4) (CH2 ) 2- Formula 52 - (CH2-CH-NH-C6H5 (CH2) a- Formula 53 - (CH2) 2-rjJ- (3,5-Cl2-C6H3) (CH2) 2- Formula SA - (CH2) 2 -N- [3,5- (CH3) 2-C6H3l (CHzh- Formula 55 -CH2-CH-NH- [2,3- (CH3J2-C6H3l (C: h2) 3- "-CH2-CH-NH- (3-CH3-C6H4) Chip 56 (CHi) * - Formula 57 -CH2-CH-NH-C6Hs (ch2) 3- Formula 58 (CH2) 3 - ^ - (3-CI-C6H4) (CH2) 2- Formula 59 -CH2-CH-NH- (3-CH3-C6H4) (CH2) 3- Chip $ 0 (CH2) 2-N- (2,4-Cl2-C6H3) (CH *) a- Formula 61 - (CHJ , -rsi- [2,3 - (CHai) 2- C6Hj (CH2) 2- Formula 62147 465 - (CH2) 3-N- (3.5-Cl2-C6H3) (CH2) 2- Formula 63 Cd-ls - (CH2) 2-CC (O) -NH-C6H5 (CH2) 2- Formula 64 - (CH ^ 2-CH-N (CHi (3-CH3C6H4) (CH2) 2- Formula 65 OH - (CH2) 2 -C-CH2- (AC [-C6H4) (CH2) 2- Formula 66 OCH3 - (CH ^ -C-CgHs (CH ^ 3- OH "** ¦" - (CH2) 2-C- (3-CF3 -C6H4) (CH2) 2- Formula 6.8 CH2-NH-C (O) -CH3 - (ch2) 2-c - ^ - ch3-CgH4) (CH2) 2- Formula 69 CH3 - (CH2) 2-CH- ^ -CH2-CM = CH-C6H5 (CH2- Formula 70 OH - (CHz) 2-C- (3-Br-4-CI-C6H3) (CHt) a- Formula 71 - (CH2) 2-CH-0 -C (b) -C6H5 (CHa) 2- Formula 72 147 465 CH3 - (CH2) 2-C-CH2-CH3 (CH2) 2- Formula 73 C (O) -0CH3 - (CH2-C-NH- (3 -CF3-C6H4) (CH2) 2- Formula 74 -CH2-CH = C - (3-CF3-C6H4) (CH2 2- Formula 75 C6H5 OH - (CH2) 2-C - C6H5 - (CH2-C- (3-CH3C6h &lt;) (CHz) 2- (CH2V Formula 76 Moe 77 -CH2-CH-NH - [(2,3-CH3C6H3]). (^ hn - (CH2) 2-N- (2-CH3-C6H4) 2) 2 (CH2) 2- Formula 78 Formula 79 C (O) -NH2 - (CH2) LC- (3-CH3-C6H4) (CH2 - Formula 80 - (CH2-CH-C0- (3-CF3-CcH4) (CH2) 2- Formula 81 - (CH2) 3-N- (3-CH30-C6H4) (CH2) 2- Formula 82 - (CH2 ) 2-CH- (4-CH3-C6H4) (CH2) 2- Formula 83 OH -CH2-CH (CH3C - (3-CF3-C6H4) (CH2) 2- Formula 84147 465 QH *) - (CH2) 2 -C- (2-Hen ^ i; (CH2) z- Formula 85 -CH2-CH-NH- (3-CF3-C6H4) (CH2) 2-- Formula 86 - (CH2) 2-N- (2- quinolinyl) (CH2) 2- Chip 87 - (CH2yC- (2-thien4i) -CH2-CH Formula 88 -CI-12-CH- (4-CI-C6hU) (CH2) 3- Formula 89 OH (CH2) 2 -C- (3-Cl-C6H <) (CH2) 2- Formula 90 - (CH2-CH-0- (AF-C6H4) (CH2) 2- Formula 91 - (CH ^ 2-C- (4-Cl ; 3-CF, -C «Hs) -CH2-CH Formula 92 9H - (CH2) 2-C- (3-CH30-C6H4) (CH2- Formula 93 OH -CHa-CH (CH3) -C- (3 -CH3-C6H4) (CH2- Formula 95 - (CH2) 2-CH-NH- (3-CI-C6H4) (CH2j2- Formula 96147 465 OH -CH2-CH (CH3) -C- (3-F-C6H4 ) (CH2) 2 Formula 97 OH -CHrCH (CH1) - C- (2 - «« nyi) (CH2- Formula? 8 - (CH2) 2-CH- (1H-indoi-3-ii (CH2) 2- Formula 99 -C- (3-F-C6H4) (CH2) 2 (CH2) 2- Formula 10OOH '(CH2) 2-C- [2,3- (CH3) 2-C6H,] (CHL) 2- OH Formula 40i ~ (CH ^ C ~ (1-naphthalenyl (CH2- Formula 102 -CHrCH (CH,) - £ '(3-C6H ^ (CH2) 2- Formula 103 QH - (CH2) 2-C- (4-Cl, 3-CF3-C6H3) (CH2) 2- Formula 104 OH - (CH2) 2-C - (4-Br-C6H4) (CH2 - Formula 105 OH - (CHaJa-C-teH ^ s-CsHs (CH ^ - Formula 106147 465 (CH2) 2-C- (4-Cl-C6H4) (CHa) * - Formula 107 - (cH2yc- (A-avcsH4) (CH2) 2- Y / form 109 (CH2 / VC- (AF-C6H4) (CH2) 2- Formula 109 (CH2) 2-C- (1 - naphthalene ^ ) CH2-CH OH Formula 110 ¦ (CH2) 2-C- [4-CH (CH3) 2-C6H4] (CH2) 2) 2- Formula 111 OH (CH, -C- (CHiVC6H5 (CH2) 2- Formula 112 OH - (CH2) zC- (CH2) 2-C6H5 (CH2) 2- Formula 1-13 - (CHa) 2-C- (2-naphthaloyl) (CH2) 2- Formula 114 - (CH2) 2-N - (A-NO2-C6H4) (CH2- Formula 115 - (CH2) 2-C- (A-CH30-C6H4) (CH2) 2- Yizor 116147 465 (CH2) 2-C- (4-Cl-C6H4) -CHt- CH Formula 117 ¦CHrCHCCHaJ-C- (3-0CH3-C6H4) (CH2) 2- Formula 118 OH - (CH2) 2-C-CH3 - (CH2) 2-C- (3-CHjC6H4) (CH2 ) i- -CH2-CH Chip119 W ** i2 ° - (CH2) 2-N- (1-naphthalenes) (CH *) and- Formula 121 - (CH2) 2-C- (3-CH3-C6H4; CH2-C- (2-thienyl) -CH2-CH CH2-CH ^ or124 mÓti "- (CH2) 2-C- (2-p.ridinyl) (CH2) 2- Formula 125 - (CHspe- -CH2- Formula and - (CH2) 2 - (CH2) 2 C-CH3 ii II CH J27 -rjl- (A-Cl-CcH4) (CH1) i-. Formula 129 -N- (2-Cl-C6H4) (CH2) 2- Formula 130147465 (CH2 (CH2 (CH2 - and Ni - \ 3 ~ er (CH2J2- Formula -f \! - (4-F (CH2) 2- Formula -N- (3.4 I3O- / 3 / - c "/ 32" Cl; -CGH4) H4) r Cl 2 Hz) (CH2); Formula * 33 (CH "-N- [2 # 6- (CH3), - CtH,] (CH2- OH Formula 134 (CH2 ) 2-C- (3,4-Cl2-C6H3) (CH2) 2- Formula i35 C (O) O-CH2CH3 (CH2-C- (3-Cl-CH2H4) (CH2) 2- Formula -136 C (O) -NH2 - (CH2) 2-G-NH- (3-CH3-C6H4) (CH2) 2- Formula 137 - (CH2) 2-N- (3-Br-C6H4) (CH2) 2- Formula Y38 0- (CH2) 3- (lp, 'Pcr' and - (CH2) 2-t-C6H5 (CH2) 2- Formula 139 (CH2) 2-CH3 (CH2-C-C6Hs (CHa) 2- Formula MO - (CH2) 2-CH-C0-CH2-C6H5 (CH ^ Formula 141 147 465 - (CH2) 3-CH- (3-CF3-C6H4) CHf- Formula 142 - (CH2) 2-CH-CH2-C0 - (3-F-C6H4) (CH2) 2- Formula 143 - (CH2yC- (3-Cl-C6H4) ÓH2 Formula 144 - (CH2) 3-N- (3-CF3-C6H4) Formula 145 OH 9H-CH2 -C-CeH5 -CH2-C- (3-CF3-C6H4) (CH2) 3- (Ch2) 3- Formula -146 Formula 147 V - (CH2-C-C6H3 CH2- Formula ^ 43 H - (CH2) 3 -C- (3-CH3-C6H4) CH2- Formula U9 ~ (CH2) 3-C- (3-CH3-C6H4) CH2- Formula 150 QH - (CH ^ sC- (2-ene) CH2- Formula 151 - (CH2) 3-C- (3-Cl -C6H4) CH2- Formula 152 147 465 9H - (CH2 -CH- (4-Cl, 3-CFs-C, H,) CH; OH Formula 167 (CH2} 2-CH- (3-XH3-C6H4) CH3 CH Formula 9h ^ (CH2) 2-CH- (2-thienyl) CH2- Formula 422 - (CHa) a-CH-NH-C00C2H5 ( CH2) 2- Formula 126 - (CH2) 2-CH- (2-thiengl) ch2- Formula UB (CH2-C- (3-F-C6H4) CH2- Formula 153 pH (CHaJj-COFC ^ CH, - (CH2 -N - (CH2) 3 - C6H5 * "* 454 (CH2) 2- Formula 155 (CH2J3-C- [2,3- (CH3) 2-C6K J H2- on2 H and Yrthor 456 - (cul) 3- c-i2,3- (cu3yc6u.CH2- QH Formula 157 - (CH2) 2-C- (3-CH3-C6H4) CH2- Formula 158 - (CH2) 2-CH = C- (3-CH3-C6H4) CH2- Formula 159 147 465 - (CH2) 2-CH- (2-l-enyl) (CH2) 2- Formula 160 8t - (CH2) 3-CH- (3-0CH3-C6H4) CHz- Formula 161 - (CH2 ) 3-CH- (3-ÓCH3-C6H4) CH2- Formula <62 9M i-CH- ¦ (CH ^ -CH-fA-Cl ^ -CFa-CeH ^ CH2- Formula 163 (CH2) 3-CH = C - (3-F-C6H4) CH2- Formula 164 {CH2 -C-fc-FC1- (CH1-CH-CHHC, '* "&lt; 2 &gt; CH2-mOr <Formula 166 2 ~ PL

Claims (3)

1. Claims 1. A process for the preparation of new pyridazineamine compounds of general formula I, in which R1 is hydrogen or halogen, group 1H-imidaziolyl-1-o, group. / Ci phenoxy group; having optionally 1 or 2 substituents, such as halogen atoms, (C x -C4 alkyl groups or nitro groups), R2 and R8 are identical or different and represent hydrogen atoms or (C1-C * 'alkyl radicals) or R2 and R8 together. The bivalent group -CH = CH-CH = CH-, and A denotes a bivalent group of formula 2, 3, 4 or 5, where in the formulas 3, 4 and 5 min are the same or different and represent integers 1-4 , and the sum of m + n is 8, 4 or 5 and one of the hydrogen atoms in the groups CmH-m, Cm-iH2m-and or CnH2n may be replaced by a / Cj-C4 alkyl radical, R4 in formula 3 is a phenyl radical , optionally having 2 or 3 substituents, such as (Ci-C ^ alkyl radicals, halogen atoms, nineteen, (Ci-Ci. 'halogenophenylcarbonyl groups and hydroxyl group, or H4 represents a thiazole, pyrimidinyl, γCi ^^ "alkylcarbonyl, diphenylmethyl, (C-C, oxycarbonyl) group, which can be to be substituted by a (C1-Ca) alkyl radical or a cyano group, or R4 is also a cyclohexyl or cyclohexenyl group, which may have 1 or 2 substituents, such as cyano and halophenyl groups, R5 in Formula 4 represents a hydrogen atom, a (C 1 -C 6 alkyl) radical, a phenyl radical, optionally having 1 or 2 substituents such as halogen atoms, (C 1 -C 6) alkyl groups, trifluoromethyl and (C 1 -C 1) groups. C1-4 alkoxy or R5 represents a hydroxyl group, a (C1-C6 alkoxy group which is optionally substituted with a piperidine group, a phenydamino group which has optionally 1 or 2 substituents, such as (C1-4) alkyl radicals) , halogen atoms and trifHuoramethyl, or R5 is also a (phenyl) - -7Ci-C4.'a! lkylamino group, C1-C6 alkylphenyl / C1-C6 alkylamino, phenyl / C1-C (j / alkenyl) -:; C1-C4) alkylamino or phenylcarbonyloxy, R8 in the formula 4 is a hydrogen atom, a (C1-C6) alkyl radical, a phenyl radical that may have 1 or 2 substituents such as (C1-C8) alkyl groups, halogen atoms, 7C1-C4) alkoxy groups and trifluoromethyl groups, or R * is a (C1-C4) alkylcarbonylamino (C1-C4) alkyl group, phenyl group, (C1-C6) alkyl, which is optionally substituted by halogen, or R8 is also amino-carbonyl, phenylaminocarbonyl or (C1-C4) -alkoxycarbonyl, and R7 and R8 in formula 5 are the same or different and represent hydrogen atoms , (C 1 -C 4) alkyl groups or phenyl groups optionally having 1 or 2 substituents, such as (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy groups, halogen atoms and , trifluoromethyl, with the proviso that when A is a group of formula 4, wherein R is hydrogen, then R5 is as defined above, but with the exception of hydrogen, hydroxyl and (Cj-Cft) -alkyl group, and when R2 and R8 in formula 1 are hydrogen and A is the group of formula II, in which case R1 is as defined above, but with the exception of halogen and when R1 is chlorine, R2 and R8 are hydrogen and A is the group of formula III, then R4 in formula III is as defined above, but with the exception of the 2-methoxyphenyl group or the pharmacologically acceptable acid addition salts of the compounds of formula 1 and / or the sterepisomers of these compounds, characterized in that the amine of formula 6r in which The meaning of A is as defined above and is alkylated with a pyridazine derivative of formula VII in which W is a reactable cleavage group and R1, R2 and R8 are as defined above, the reaction being carried out by if necessary, in an inert solvent and, if necessary, in the presence of a base, and then 3 The resulting compound of formula I is optionally converted by reaction with a suitable acid into a pharmacologically acceptable acid addition salt, or the acid addition salt is converted by treatment with alkali on the free base of formula I and / or prepared these compounds appear as single stereoisomers. 2. A process for the preparation of new pyridazine amine compounds of general formula I, in which R 1 represents a hydrogen or halogen atom, a 1H-imidazoMl-1-group, a (C 1 -C 6) alkoxy group, a phenoxy group optionally having 1 or 2 substituents, such as halogen atoms, (C 1 -C 6 alkyl and nitro groups, phenylloyl-C 1 -C 4) alkoxy group, (C 1 -C 4) alkylthio, phenylthio, hydroxyl, mercapto, amino, (C 1 -C) Alkylsulfinyl, (C-C ^) alkylsulphonyl, cyano, (C-C-alkoxycarbonyl or (C-C) alkyl), R2 and R8 are the same or different and represent hydrogen atoms or (C) groups. 'alkyl, or R * and R8 together form a divalent group of formula -CH = = CH-CH = CH-, and A is a divalent group of formula 2, 3, 4; or 5, where in the formulas 3, 4 and 5 min are the same or different and represent integers 1-4, and the sum of m + n o is 3, 4 or 5 and one of the hydrogen atoms in the CmH2m groups , Cm-1H2111-1 and CnH2n may be replaced by a (C 1 -C 4) alkyl group, R 4 in formula 3 is a phenyl radical, optionally having 1, 2 or 3 substituents such as (C 1 -C 4) talkyl radicals , halogen atoms, nitro, groups 147 465 31 32 (C 1 -C 1) alkoxy,. (C 1 -C 4) alkexycarbonyl, trifluoromethyl, halophenyl carbonyl and hydroxy, or R 4 is thiazoyl, pyrimidinyl, (C 1 -C 4, alkylcarbonyl, diphenylmethyl, / C 1 -C 4 alkoxy) 5 4-cycarbonyl, a pyridinyl group which may be substituted with a (C 1 -C 4 alkyl radical) or R 4 is also a cyclohexyl or cyclohexenyl group, which optionally have 1 or 2 substituents, such as cyano and halogen-phenyl groups or R4 represents a quinolyl group, a phenyl (C 1 -C 6) alkyl group, a (C 1 -C 4 alkylphenyl), C 1-6 alkyl or naphthalenyl group, R 5 in the formula 4 is a hydrogen atom, a (C 1 -C 6) alkyl radical, a phenyl radical optionally having 1 or 2 substituents such as halogen atoms, (C 1 -C 6 alkyl groups, trifluoromethyl and (C 1 -C 4 'alkoxy) groups, or R 6 is hydroxy, (C 1 -C 6) alkoxy, which is optionally substituted piperidine group, phenylamino group that may have 1 or 2 substituents, such as (C 1 -C 6 alkyl radicals, halogen atoms and trifluoromethyl groups, phenyl) C 1 -C 4 alkyl-amino, (C 1 -C 6) alkylphenyl / C 1 -C 6 alkyl / amino, phenyl) -C 1-4 alkenyl / 1 / C 1-6 -C 4) alkyl / amino, phenyl- * 5-carcinyloxy-xytophyl * -halogen-phenoxy-amine, -C1-C4) alkoxycarbonylamino or naphthalenyl, in formula 4 is a hydrogen atom, / C 1 -C 6-, R8 radical in formula (4) represents a hydrogen atom, a (C 1 -C 6 'alkyl radical), a phenyl radical that optionally has 13 or 2 substituents, such as (C 1 -C 6' alkyl groups, halogen atoms, and (C 1 -C 6) groups; alkoxy and trifluoromethyl group, (C1-C4alkylcarbonylamim'Ci-C4-) alkyl group, phenyl / C1-Cgalyl group which is optionally substituted with halogen, or R6 is am: nocarbonyl, phenylaminocarbonyl, (C1-C4) alkoxycarbonyl, halophenylcarbonyl, X-1-C4) alkyl, phenylcarbonyl which is optionally substituted with trifluoromethyl or halogen, phenyl. 1C1-C4 (alkylcarbonyl, incolyl, thienyl, pyridyl or naphthalenyl), and R7 and Rs in formula 5 are the same or different and represent hydrogen atoms, .! or 2 substituents such as (C 1 -C 4) alkyl radicals, (C 1 -C 4) alkoxy groups, halogen atoms and trifluoromethyl groups, or represent phenyl (C 1 -C 4) alkyl, thienyl, naphthaienyl or pyridyl groups, where: when A is a group of formula IV, where R8 is hydrogen, then R8 is as defined above, but with the exception of hydrogen, hydroxy and (C1-C8) alkyl groups when R6 and R8 are hydrogen and A is the group of formula II, then R1 is as defined above, but with the exception of halogen, when R1 is chloro, R2 and R8. are hydrogen and A is a group of formula III, then R4 in formula III has the meaning given above, M but with the exception of 2-methoxy when R1 is chloro and A is a group of formula III, then R4 in formula III has the meaning given above, but other than the [alpha] -methylphenylpvd (2-methylphenyl) methyl group and 1 simultaneously R 1 represents a hydrogen atom or a halogen atom, a 1 H -imidazolyl-1-o group, a (C 1 -C 6) alkoxy group or a phenoxy group, optionally having 1 or 2 substituents, such as halogen atoms, -1Ci-C4 / alk: 1 groups or the nitro group, R * and R8 are the same or different and represent hydrogen or (C1-C4) alkyl radicals, or R * and R8 together form a bivalent -CH =, CHtCH = CH- group, and A is bivalent group of formula 2, 3, 4 or 5, where in the formulas 3, 4 and 5 min are the same or different and represent integers 1-4, and the sum m + n is 3, 4 or 5 'and one of the hydrogen atoms in the groups CmH2m, 0111-2112111—! or CnH2n may be replaced by a (C1-C4alkyl) radical, R4 in formula 3 is a phenyl radical, optionally having 1, 2 or 3 substituents, such as TC1-C41 "alkyl radicals, halogen atoms, nitro group, -C4'- alkoxy, (C1-6 alkoxycarbonyl, trifluoromethyl, chloro-phenylcarbonyl and hydroxyl groups, or R4 is thiazoyl, pyrimidinyl, (C1-6) alkylcarbonyl, diphenylmethyl,) Bonyl, a pyridinyl group which may be substituted with a (C1-C4) alkyl radical or a cyano group, or R4 is also a cyclohexy or cyclohexenyl group, which may have 1 or 2 substituents, such as cyano and halogenophenyl groups, R 5 in formula 4 represents a hydrogen atom, a (C 1 -C 6) alkyl radical, a phenyl radical, optionally having X or 2 substituents, such as halogen atoms,. Because R6 is hydroxy, fCi-Caf-alkoxy, kt Which is an optionally substituted piperidine group, a phenylamino group having optionally 1 or 2 substituents such as radicals, 'C1-G4alkyl, halogen atoms and trifluoromethyl, or also R8 is (phenyl) - / C1-C4,' alkylamino, (C 1-4) alkylphenyl (C 1-4) alkylamino, phenyl. 1 -C 1 -C 4 (alkyl) amino, phenyl (C 1 -C 6) alkenyl) (1-C 1 -C 4) alkylamino or phenylcarbonyl, R8 in formula 4 represents a hydrogen atom, a 7Ci-C6alkyl radical, a phenyl radical that may have 1 or 2 substituents such as (C1-C6) alkyl groups, halogen atoms, (CJ-C4 alkoxy groups and a trifluoromethyl group, or R8) is a (C 1 -C 4) alkylcarbonylamino- (C 1 -C 4 alkyl group, a phenyl) C 1 -C 6 alkyl group which is optionally substituted by halogen, or also. R8 is an aminocarbonyl, phenylamino-carbonyl or (C-C) alkoxycarbonyl group, and R7 and R8 in formula 5 are the same or different and represent hydrogen atoms, groups; C1-C4) alkyl or phenyl groups optionally having 1 or 2 under Representatives such as (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy groups, halogen atoms and trifluoromethyl groups, which compounds can also be prepared as pharmacologically acceptable acid addition salts and / or in the form of individual stereoisomers, characterized in that the amine of the formula 6 in which A is as defined above is alkylated with a pyridazine derivative of the formula 7 in which W is a reactive cleavable group and R1, R2 and R8 are as defined above, these reactions being carried out, if necessary, in an inert solvent and, if appropriate, in the presence of a base, and then the compound of the formula I obtained is optionally reacted with a suitable acid into a pharmacol The generally acceptable acid addition salt or acid addition salt is converted by treatment with alkali to the free base of formula I and / or these compounds are prepared as single stereoisomers. R1 ^ LA -CH = N-CH = CH- FI2 R3 Formula 2 Formula 1 R4 _CmH2mN ~ CnH2rT Formula 3 R5 R6 Crrf ^ m ^ Formula _Cm-iHaCm-i) "CnH2n 4 f R8 I 1 ¦cc- Formula 5 hKT a Formula 6 \ - R2 ~ CnH2n Iw Rl Formula 7 / Cnl ^ ra ... n4-a PN 'NH + WR \ CnH2n' Formula 9 H2N-R4 ~ Q Formula 8a Formula 8 Scheme 1 PN '/ CmH2m \ 4- a P-Nx NR CnH2n / Formula 10 / CmH2m \. HN (N-R4_a XCnH2n / Formula 11a CmH2m-W ¦CnHe-nW Formula 12 'UJ0ZA1 ZZ JPZM -Z (2H3) - * (* H3) SH93-H3- Z? H3) - ^ H93-! 3-C) -N- ^ H3) 9Z JQ * MU J02AA fH «3-« J3-C) -n- «PH3) - [WHD) -9VZ] -N-? H0) Oc JP-zyW - * (ZH3) (iftuftPMd-2-cH3-9) -INI - * (* H0) -ZPH3) (£ H93-Z13-C'3) -N- ^ H3) - -Z ^ H3), N,% «c ^ ', * ^ * H93-SH23-C) -N-2 (2H3) - H33-CH3-C) -HN-H3-Z (ZH3) -' vy 6y -" w -Z (2H3) £ Z J0 * An 81 JOZM (H ^ -jB-Z) -rl | - «? H3) -? H93-CH3-C) -N- ^ H3) -VzH0" • Lllj Ct7H93- cHz3-z) -N- ^ H3 6d-Ns ^ 2 ^ 3 z} DuueL | os Dx) iH V, SL -JOZM VI J92M n JOzM 6U-NX / u2hu3x ol ^ U2HU3X .3V / N_d -— cd-NH + 0 = 3.Nd sa * a \ 147 465 - (CH ^ -CH- (3-CH3-C6H4) (CH2) - mor 28 - (CH2) 2-CH- (3-CF3-C6H4) (CH2 ) 2- l * ZOr 29 (CH2) 2-N- (4-CH30-CtH4) (CH2) 2-. Formula 30 - CH2- CH (CH3) -N- (A-CH30-C6H ^) (CH2) 2- Formula 3i (CH2) 2-N- (2-t. "Oiii) (CH2- Formula 32 ¦ (CHj-NC" H5 ( CH ^ z- Formula 33 - (CH2VN- (2 ~ CH30-C6H4) Chip 34 -. (CH ^ -N- (4-CHs-C «H4) Formula 35 -XH2) 2-N- [3, A- (CH3) 2-C6H3i (CH2) 2- Formula 36 - (CH2) 2-N- (2-piP ^ midynm) Pattern 37 '- (CH2) 2rN- [213-fCH ^ -CaH3] CH, and 2' 2 Formula 39147 465 -CH2-CH (CH3) -N- (2-Cl-CsH4) Formula 39 (CH ^ N- [AC &lt; H50C (O) -CftH4l (CH2) 2- Formula 40 (CH ^ Nf ^ - fCH2 -CCH,] CH2 ;; Formula 41 CH2-CH (CH3) -N- (4-CH3-C6H,) (CH2) 2- Formula 42 (CH2) 2-N - [(2-CH30) - (5-CF3) -CcH2 ttH2) 2 - Formula 43 (tH2) 2-N-CH (C6H5) (CH2) 2- Formula 44 -CH2-CH (CHs) - ^ - (3-CHs-CfiH4) (CHa) a- Formula 45 - (CH2) 2 -N- (3-r-C6H4) (CH2) 2- Formula 46 ~ (CH2-rvJ - (3-CN-2- pir * ftjmjl) (CH2- Formula 47 - (CHjJr ^ l- C6H4-C (0 ) - (4-CI-C6H4) (CHa) i- Formula 48 -CH2-CH (CH3) -N- (4-Cl-C6H4) (CH2) 2- Formula 49 - (CHa), - N- [3 , A- (CH30) 2-C6H3] (CH1) i-147 465 CH2-CH (CH3) -N-C6H5 (CH2- Chip 51 - (CH2) 2-N- (4-0H-C6H4) (CH2 ) 2- Formula 52 - (CH2-CH-NH-C6H5 (CH2) a- Formula 53 - (CH2) 2-rjJ- (3,5-Cl2-C6H3) (CH2) 2- Formula SA - (CH2) 2 -N- [3,5- (CH3) 2-C6H3l (CHzh- Formula 55 -CH2-CH-NH- [2,3- (CH3J2-C6H3l (C: h2) 3- "-CH2-CH-NH- (3-CH3-C6H4) Chip 56 (CHi) * - Formula 57 -CH2-CH-NH-C6Hs (ch2) 3- Formula 58 (CH2) 3 - ^ - (3-CI-C6H4) (CH2) 2- Formula 59 -CH2-CH-NH- (3-CH3-C6H4) (CH2) 3- Chip $ 0 (CH2) 2-N- (2,4-Cl2-C6H3) (CH *) a- Formula 61 - (CHJ , -rsi- [2,3 - (CHai) 2- C6Hj (CH2) 2- Formula 62147 465 - (CH2) 3-N- (3.5-Cl2-C6H3) (CH2) 2- Formula 63 Cd-ls - (CH2) 2-CC (O) -NH-C6H5 (CH2) 2- Formula 64 - (CH ^ 2-CH-N (CHi (3-CH3C6H4) (C H2) 2- Formula 65 OH - (CH2) 2-C-CH2- (AC [-C6H4) (CH2) 2- Formula 66 0CH3 - (CH ^ -C-CgHs (CH ^ 3- OH "** ¦" - (CH2) 2-C- (3-CF3-C6H4) (CH2) 2- Formula 6.8 CH2-NH-C (O) -CH3 - (ch2) 2-c - ^ - ch3-CgH4) (CH2) 2 - Formula 69 CH3 - (CH2) 2-CH - ^ - CH2-CM = CH-C6H5 (CH2- Formula 70 OH - (CHz) 2-C- (3-Br-4-CI-C6H3) (CHt) a - Formula 71 - (CH2) 2-CH-O-C (b) -C6H5 (CHa) 2- Formula 72 147 465 CH3 - (CH2) 2-C-CH2-CH3 (CH2) 2- Formula 73 C (0) -0CH3 - (CH2-C-NH- (3-CF3-C6H4) (CH2) 2- Formula 74 -CH2-CH = C - (3-CF3-C6H4) (CH ^ 2- Formula 75 C6H5 OH - ( CH2) 2-C - C6H5 - (CH2-C- (3-CH3C6h <) (CHz) 2- (CH2V Formula 76 Moe 77 -CH2-CH-NH - [(2,3-CH3C6H3]). (^ hn - (CH2) 2-N- (2-CH3-C6H4) 2) 2 (CH2) 2- Formula 78 Formula 79 C (O) -NH2 - (CH2) LC- (3-CH3-C6H4) (CH2 - Formula 80 - (CH2-CH-C0- (3-CF3-CcH4) (CH2) 2- Formula 81 - (CH2) 3-N- (3-CH30-C6H4) (CH2) 2- Formula 82 - (CH2 ) 2-CH- (4-CH3-C6H4) (CH2) 2- Formula 83 OH -CH2-CH (CH3C - (3-CF3-C6H4) (CH2) 2- Formula 84147 465 QH *) - (CH2) 2 -C- (2-Hen ^ i; (CH2) z- Formula 85 -CH2-CH-NH- (3-CF3-C6H4) (CH2) 2-- Formula 86 - (CH2) 2-N- (2- quinolinyl) (CH2) 2- Chip 87 - (CH2yC- (2-thien4i) -CH2-CH Formula 88 -CI-12-CH- (4-CI-C6hU) (CH2) 3- Formula 89 OH (CH2) 2 -C- (3-Cl-C6H <) (CH2) 2- Formula 90 - (CH2-CH-0- (AF-C6H4) (CH2) 2- Formula 91 - (CH ^ 2-C- (4-Cl ; 3-CF, -C «Hs) -CH2-CH Formula 92 9H - (CH2) 2-C- (3-CH30-C6H4) (CH2- Formula 93 OH -CHa-CH (CH3) -C- (3 -CH3-C6H4) (CH2- Formula 95 - (CH2) 2-CH-NH- (3-CI-C6H4) (CH2j2- Formula 96147 465 OH -CH2-CH (CH3) -C- (3-F-C6H4 ) (CH2) 2 Formula 97 OH -CHrCH (CH1) - C- (2 - «« nyi) (CH2- Formula? 8 - (CH2) 2-CH- (1H-indoi-3-ii (CH2) 2- Formula 99 -C- (3-F-C6H4) (CH2) 2 (CH2) 2- Formula 10OOH '(CH2) 2-C- [2,3- (CH3) 2-C6H,] (CHL) 2- OH Formula 40i ~ (CH ^ C ~ (1-naphthalenyl (CH2- Formula 102 -CHrCH (CH,) - £ '(3-C6H ^ (CH2) 2- Formula 103 QH - (CH2) 2-C- (4-Cl, 3-CF3-C6H3) (CH2) 2- Formula 104 OH - (CH2) 2-C - (4-Br-C6H4) (CH2 - Formula 105 OH - (CHaJa-C-teH ^ s-CsHs (CH ^ - Formula 106147 465 (CH2) 2-C- (4-Cl-C6H4) (CHa) * - Formula 107 - (cH2yc- (A-avcsH4) (CH2) 2- Y / form 109 (CH2 / VC- (AF-C6H4) (CH2) 2- Formula 109 (CH2) 2-C- (1 - naphthalene ^ ) CH2-CH OH Formula 110 ¦ (CH2) 2-C- [4-CH (CH3) 2-C6H4] (CH2) 2) 2- Formula 111 OH (CH, -C- (CHiVC6H5 (CH2) 2- Formula 112 OH - (CH2) zC- (CH2) 2-C6H5 (CH2) 2- Formula 1-13 - (CHa) 2-C- (2-naphthaloyl) (CH2) 2- Formula 114 - (CH2) 2-N - (A-NO2-C6H4) (CH2- Formula 115 - (CH2) 2-C- (A-CH30-C6H4) (CH2) 2- Yizor 116147 465 (CH2) 2-C- (4-Cl-C6H4) -CHt- CH Formula 117 ¦CHrCHCCHaJ-C- (3-0CH3-C6H4) (CH2) 2- Formula 118 OH - (CH2) 2-C-CH3 - (CH2) 2-C- (3-CHjC6H4) (CH2 ) i- -CH2-CH Chip119 W ** i2 ° - (CH2) 2-N- (1-naphthalenes) (CH *) and- Formula 121 - (CH2) 2-C- (3-CH3-C6H4; CH2-C- (2-thienyl) -CH2-CH CH2-CH ^ or124 mÓti "- (CH2) 2-C- (2-p.ridinyl) (CH2) 2- Formula 125 - (CHspe- -CH2- Formula and - (CH2) 2 - (CH2) 2 C-CH3 ii II CH J27 -rjl- (A-Cl-CcH4) (CH1) i-. Formula 129 -N- (2-Cl-C6H4) (CH2) 2- Formula 130147465 (CH2 (CH2 (CH2 - and Ni - \ 3 ~ er (CH2J2- Formula -f \! - (4-F (CH2) 2- Formula -N- (3.4 I3O- / 3 / - c "/ 32" Cl; -CGH4) H4) r Cl 2 Hz) (CH2); Formula * 33 (CH "-N- [2 # 6- (CH3), - CtH,] (CH2- OH Formula 134 (CH2 ) 2-C- (3,4-Cl2-C6H3) (CH2) 2- Formula i35 C (O) O-CH2CH3 (CH2-C- (3-Cl-CH2H4) (CH2) 2- Formula -136 C (O) -NH2 - (CH2) 2-G-NH- (3-CH3-C6H4) (CH2) 2- Formula 137 - (CH2) 2-N- (3-Br-C6H4) (CH2) 2- Formula Y38 0- (CH2) 3- (lp, 'Pcr' and - (CH2) 2-t-C6H5 (CH2) 2- Formula 139 (CH2) 2-CH3 (CH2-C-C6Hs (CHa) 2- Formula MO - (CH2) 2-CH-C0-CH2-C6H5 (CH ^ Formula 141 147 465 - (CH2) 3-CH- (3-CF3-C6H4) CHf- Formula 142 - (CH2) 2-CH-CH2-C0 - (3-F-C6H4) (CH2) 2- Formula 143 - (CH2yC- (3-Cl-C6H4) ÓH2 Formula 144 - (CH2) 3-N- (3-CF3-C6H4) Formula 145 OH 9H-CH2 -C-CeH5 -CH2-C- (3-CF3-C6H4) (CH2) 3- (Ch2) 3- Formula -146 Formula 147 V - (CH2-C-C6H3 CH2- Formula ^ 43 H - (CH2) 3 -C- (3-CH3-C6H4) CH2- Formula U9 ~ (CH2) 3-C- (3-CH3-C6H4) CH2- Formula 150 QH - (CH ^ sC- (2-ene) CH2- Formula 151 - (CH2) 3-C- (3-Cl -C6H4) CH2- Formula 152 147 465 9H - (CH2 -CH- (4-Cl, 3-CFs-C, H,) CH; OH Formula 167 (CH2} 2-CH- (3-XH3-C6H4) CH 3. CH Formula 9h ^ (CH2) 2-CH- (2-thienyl) CH2- Formula 422 - (CHa) a-CH-NH-C00C2H5 (CH2) 2- Formula 126 - (CH2) 2-CH- (2 -tiengl) ch2- Formula UB (CH2-C- (3-F-C6H4) CH2- Formula 153 pH (CHaJj-COFC ^ CH, - (CH2-N - (CH2) 3 - C6H5 * «* 454 (CH2) 2- Formula 155 (CH2J3-C- [2,3- (CH3) 2-C6K J H2- on2 H and Yrtor 456 - (cul) 3-c-i2,3- (cu3yc6u. CH2- QH Formula 157 - ( CH2) 2-C- (3-CH3-C6H4) CH2- Formula 158 - (CH2) 2-CH = C- (3-CH3-C6H4) CH2- Formula 159 147 465 - (CH2) 2-CH- (2- l.enyl) (CH2) 2- Formula 160 8t - (CH2) 3-CH- (3-0CH3-C6H4) CHz- Formula 161 - (CH2) 3-CH- (3-ÓCH3-C6H4) CH2- Formula < 62 9M i-CH- ¦ (CH2 -CH-fA-Cl2 -CFa-CeH4CH2- Formula 163 (CH2) 3-CH = C- (3-F-C6H4) CH2- Formula 164 {CH4 - C-fc-FC ^ - (CHjrCH-CHHC, '* "^ and LH2 CH2- m0r <Formula 166 2 ~ PL PL