SI8912292A - Preparation procedure of new piperazinyl-alkyl-3(2h)-pyridazinones - Google Patents

Abstract

The invention relates to a process for preparing new ones piperazinylalkyl- (3-2H) -pyridazinones of the formula subst. phenyl, naphthyl, pyridyl or thiazolyl and their pharmaceuticals useful salts derived from o Sl 8912292 A I, where R1 is hydrogen, phenyl, benzyl unsubstituted. or subst. hydroxy, piperidine, morpholine, or -NR4R5, wherein R4 and R5 are the same or different and are hydrogen, methyl or ethyl, substituted alkyl, R2 and R3 are hydrogen, halogen, alkoxy or alkyl, at which is at least one hydrogen, hydrogen, alkyl, phenyl, benzyl or phenylethyl, B nesubst. or with hydroxy, alkyl or -NR 4 R 5 subst. alkylene which may be enclosed in an alicyclic 4- to 7-ring, Re and Rg, which may be the same or different, are hydrogen or alkyl and Z is unsubstituted or alkyl, alkoxyl, bezyloxyl, trifluoromethyl, halogen, nitro, cycloalkoxy, alkylthio, trifluoromethylthio or with the group -NR4R5 (HI) HM ------- B ------- and ΙΠ \ __ f II and lil respectively. by converting the corresponding compounds of formula I. The end products are useful in medicines for treatment hypertension, heart failure and peripheral disorders circulation.

Description

CL PHARMA AKTIENGESELLSCHAFT

Novel piperazinylalkyl-3 (2H) -pyridazinones and method for their preparation

Technical field of the invention

The present invention relates to novel piperazinylalkyl-3 (2H) -pyridazinones and their pharmaceutically useful salts, and to their preparation and use as blood pressure lowering agents.

A technical problem

There was a need for new piperazinylalkyl-3 (2H) -pyridazinones to lower blood pressure and for a technologically advanced process for their preparation.

The state of the art

It is known that alpha-recepto blockade may be used as a blood pressure lowering agent. So e.g. describe, in DE-PS 19 42 405, aryl-substituted piperazinylpropylenamino-uracil, which have a blood pressure lowering effect, and block the effect of adrenaline- and norepinephrine-induced blood pressure rise on despinalized rats.

Description of solution to a technical problem with implementation examples

The subject of the invention are novel piperazinylalkyl-3 (2H) -pyridazinones of the formula

R, o

II

M_ B- N N- Z

R in which they represent residues

R _i is hydrogen, phenyl, benzyl, unsubstituted or mono- or polysubstituted by hydroxy, piperidino, morpholino, or a group NR ₄ R ₅ in which R ₄ R ₅ may be the same or different and represent hydrogen, methyl or ethyl, substituted (C -C1-6alkyl,

R 2 and R _{3 are} hydrogen, halogen, (C 1 -C 4 -alkoxy or (C 1 -C 4 -alkyl), wherein at least one of R ₂ or R ₃ is hydrogen,

R _{6 is} hydrogen, (C 1 -C 4 -alkyl, phenyl, benzyl or phenylethyl,

B is unsubstituted or mono- or polysubstituted by hydroxyl, (Cj-C ^ -alkyl, or a group NR ₄ R ₅ substituted (Cj-C ^ -alkylene which is unsubstituted or may be joined to an alicyclic 4 to 7-membered ring,

R _g and R ₉ , which may be the same or different, are hydrogen or (C 1 -C 4 -alkyl and

Z is unsubstituted or mono- or polysubstituted by a (C-C ^ alkyl, (Cj-C ^ alkoxy, benzyloxy, trifluoromethyl, halogen, nitro, (C ₃ -C ₇₎ -cycloalkoxy, (Cj-CJ-alkoxy, trifluoromethylthio, or with the group NR ₄ R ₅ substituted phenyl, naphthyl, pyridyl or thiazolyl, as well as their pharmaceutically usable salts, characterized in that

a) a compound of formula

I in which R _{p is} R ₂ and R ₃ as defined above and M represents a cleavable group is converted with the compound of formula

wherein R ₆ , B, R _g , R ₉ and Z are as defined above, or

b) in a compound of formula I in which one of the residues R2 or R ₃ is halogen and the remaining residues, as defined above, are replaced by halogen at R2 or R ₃ by means of a hydrohalic hydrogen halide or a compound of formula I, v which one of the residues R 1 or R ₃ represents halogen and the remaining residues as defined above is converted with an alkali metal alcoholate, converting the halogen at R 2 or R ₃ to a residue having the meaning (C ₁ -C ₆ ) -alkoxy, or

d) in a compound of formula I, in which R6 has the meaning of i-propyl, sec-butyl, tert-butyl or benzyl and the remaining residues as defined above are cleaved R _x with acids, or

e) pyridazine of formula

T iv in which R ₂ , R ₃ , R ₆ , B, R _g , R ₉ and Z are as defined above and R _{7 has the} meaning of (GpC 1 -C 6 alkyl), upon ether cleavage with acid, is converted to the corresponding 3- ( 2H) pyridazinone, or

f) a compound of formula I, in which R ^ is hydrogen and one of the radicals R or R ₃ represents halogen, and the other radicals, as defined above, is alkylated by reaction with an alkylating reagent in the 2-position of the pyridazine ring and

g) optionally, the compound of formula I obtained according to a) to e) is converted into its pharmaceutically acceptable salts.

The term (C 1 -C 1 -C 6 -alkyl includes all straight and branched, saturated or hydrocarbons having 1 to 6 carbon atoms, such as methyl, isopropyl, tert-butyl, neopentyl, hexyl and the like.

In the (C ₁ -C ₆ ) -alkoxy group, the alkyl residue has the above meaning.

The term (C ₁ -C ₇ ) -alkylene refers to a divalent, straight or branched, or saturated hydrocarbon residue having 1 to 7 carbon atoms, where, in the presence of at least four carbon atoms, the alkylene chain can optionally be concluded to be alicyclic , a saturated ring of 4 to 7 carbon atoms, such as e.g. cyclobutylene, cycloheptylene. In the (C1-C4) cycloalkoxy group, the cycloalkyl radical has the meaning of a saturated, alicyclic hydrocarbon radical having from 3 to 7 carbon atoms.

By halogen we mean fluorine, chlorine, bromine or iodine.

Of the compounds of formula I, preferred are those wherein they represent residues

R 1 is hydrogen, methyl, ethyl, tert-butyl, benzyl, 2-hydroxyethyl or 2-dimethylaminoethyl,

And R2 is hydrogen, chlorine, bromine or methoxy, where at least one of the radicals R 2 or R ₃ represents hydrogen,

R _{6 is} hydrogen, methyl or ethyl,

B straight (C 1 -C 4 -alkylene,

R _g and Rp are hydrogen and

By unsubstituted or mono- or polysubstituted with methyl, (C1-C4-alkoxy, benzyloxyl, trifluoromethyl, fluoro, chloro or nitro substituted phenyl, or unsubstituted pyridyl-2.

Particularly preferred is compound 2-methyl-4-chloro-5 - ((2- (4- (2-methoxy-phenyl) piperazinyl) ethyl) amino) -3 (2H) -pyridazinone.

Compounds of formula I may, in the case where R _{1 is} hydrogen, occur in whole or in tautomeric form. Also, these tautomeric forms are an integral part of the present invention.

As the cleavage group M according to variant a) of the process, all commonly used cleavage groups such as halogen, p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl and the like are suitable. Preferably, compounds of formula II are used wherein M is chlorine or bromine.

The reaction of variant a) of the process is carried out in such a way that the compound of formula II or its tautomer is converted with the compound of formula III in a diluent inert under reaction conditions, at temperatures between about 20 and 150 ° C, or without a solvent in the melt. Diluents, for example, are suitable. DMF, DMSO, acetonitrile, benzene, toluene, acetone, diethyl ketone, acetone, amyl acetate, ethylene glycol dimethyl ether, diethylene glycodimethyl ether, tetraline or alcohols such as methanol, ethanol, hexanol, decanol, dioxane or tetrahydrofuran. The reaction lasts between about 2 and 200 hours, with higher reaction temperatures resulting in shorter reaction times and vice versa. Preferred reaction conditions are the metabolism of the reaction participants in acetonitrile over a period of 5 to 50 hours, with the addition of at least one mole of potassium hydrogen carbonate as the acid-binding agent, at reflux temperature.

When metabolizing a compound of formula II with a compound of formula III, positional isomers are formed because R ₂ behaves as a cleavage group. Separation of positional isomers is carried out by conventional methods in chemistry, preferably by recrystallization and column chromatography.

According to variant b) of the process, halogen at R ₂ or R _{3 is} replaced by hydrated dehalogenation with hydrogen. It is preferably carried out in solution with the addition of a precious metal catalyst or Raney nickel. The use of palladium on charcoal as a catalyst was of particular interest. Alcohols such as methanol, ethanol, hexanol and the like, esters such as methyl acetate, ethyl acetate and the like, glacial acetic acid or aqueous hydrochloric acid or sodium hydroxide are suitable as solvents. We operate at pressures common to catalytic hydration, preferably at pressures from normal to about 5 bar. The temperature may be, depending on the compound used and the pressure used, between about 0 ° C and 120 ° C; pre-present operation at 20 to 70 ° C. Hydrogenation is carried out to the calculated stoichiometric hydrogen uptake, with the slight excess of hydrogen being in most cases not harmful.

According to Embodiment c), the reaction is carried out with an alkali metal alcoholate, preferably sodium methylate, in a polar diluent such as DMF, DMSO, in cyclic ethers such as dioxane or tetrahydrofuran, in diethyl ether, diethylene glycodimethyl ether, or in alcohols using the base alcohol alcohol, especially preferred. The digestion is carried out at temperatures from about 80 to 200 ° C and can be optionally carried out in a pressure vessel at pressures of about 2 to 10 bar. The reaction lasts about 6 to 120 hours depending on the type of starting compounds and the reaction partners, especially depending on the pressure and temperature. Preferably, the reaction is carried out in a methanolic solution without pressure at reflux temperature for 30 to 60 hours.

The cleavage of Rj according to variant d) of the process can be carried out with inorganic or organic acids. Examples of inorganic acids are HC1 and HBr, whereby these acids can be used both in aqueous solution and dissolved in ice. Examples of organic acids include trifluoroacetic acid, trifluoromethanesulfonic acid and methanesulfonic acid. The cleavage is carried out by heating in said acids at temperatures of about 50 to 120 ° C, preferably at reflux temperature; The reaction takes about 0.5 to 12 hours depending on the type of starting compounds and the remaining reaction parameters.

The conversion of pyridazine of formula IV by ether cleavage into 3 (2H) -pyridazinone of formula I according to variant e) of the process can be carried out with the acids indicated in variant d) of the process. Preferably, compounds of formula IV in which R _{7 is} methyl are used. The reaction is carried out depending on the type of starting compounds and other reaction parameters over a period of 5 minutes to 6 hours at about 50 to 120 ° C, preferably at the reflux temperature of the acid used.

The metabolism of a compound of formula I in which the residue R 1 represents hydrogen, in variant f) of the alkylating reagent process, is carried out in aqueous-alkaline solutions, with alcohols such as methanol or ethanol being added as co-solvents, cyclic ethers, e.g. THF, dioxane, DMF or DMSO. The reaction may be carried out at temperatures from about 20 to 120 ° C, preferably at 20 to 70 ° C. The reaction lasts - depending on the type of starting compounds and other reaction parameters -1 to 12 hours, preferably 1 to 4 hours.

The preparation of the compounds obtained by variants a) to f) of the process is carried out in the usual way by evaporation, precipitation with water, precipitation as salt, recrystallization or by preparative column chromatography. The latter method is particularly important when, according to variant a) of the process, the substituent R2 behaves as a cleavable group under the given reaction conditions, thereby producing positionally isomeric end products.

In the conversion of a) to f), the compounds of formula I obtained are bases and can be converted into their pharmaceutically useful salts in the usual way with inorganic or organic acids. The formation of salts can be carried out e.g. by dissolving the compound of formula I in a suitable solvent, such as e.g. in water, acetone or acetonitrile, in alcohols such as methanol, ethanol, hexanol, decanol, or in mixtures of these alcohols with ethers, preferably diethyl ether, at least an equivalent amount of the desired acid is added, a good stirring is made and the precipitated salt is filtered off, or distilling off the solvent in vacuo. Optionally, the acids can be recrystallized after isolation.

Pharmaceutically useful salts are e.g. salts with inorganic acids such as e.g. hydrochloric, hydrobromic, sulfuric, phosphoric or nitric acid, or with organic acids such as citric, tartaric, maleic, fumaric, succinic, malic, methanesulfonic, aminosulfonic, acetic, benzoic acid and the like.

The pyridazinones used as starting materials are known, or can be prepared by methods known per se, to give:

4,5-dichloro-3 (2H) -pyridazinone and 4,5-dichloro-2-methyl-3 (2H) -pyridazinone by condensation of mucocloric acid with hydrazine or methylhydrazine according to F. Reichenbacher and K.Drury, DE-PS 10 86 238, further 4,5-dichloro-2-hydroxyethyl-3 (2H) -pyridazinone and 4,5-dichloro-2diethylaminoethyl-3 (2H) -pyridazinone as analogues of 4,5-dichloro-2-dimethylaminoethyl3 ( 2H) -pyridazinone by analogous reaction after R. Schoenbeck and E. Kloimstein, Monatsh. Chem. 99.15 (1968).

The piperazinylalkyl derivatives used as starting materials are known or can be prepared by analogous methods. Thus, 4-aryl- and 4-heteroaryl-piperazine derivatives bearing the cyanalkyl residue in position 1 can be reduced by catalytic hydrogenation to the desired aminoalkylpiperazine derivatives. The preparative methods to be used are described e.g. in:

Houben-Weyl, Methoden der Organischen Chemie, vol. XI, 1, pages 24 - 108 and 272 289, Georg Thieme Verlag Stuttgart (1957), further in Jp. Kokai 82 42 679, US-PS 3,398,151, FR-PS 2,261,756 and DE-OS 23 34 009.

Pyridazines of formula IV can be prepared by the method described in Example 14.

3,4,6-Dichloropyridazine is obtained after R.H. Mazzoni and P.E. Spoerri, J.Am.Chem.Soc. 76,2201 (1954).

The novel compounds of formula I and their pharmaceutically useful salts exhibit excellent inhibition of peripheral alpha receptors (alpha ₁ -adrenoceptors) in vitro models. In addition, many of the test substances have a beneficial effect on central 5HT-1A receptors.

On the basis of these pharmacological properties, new compounds may be used alone or in admixture with other active substances in the form of conventional galenic preparations in medicinal products for high blood pressure and heart disease.

The compounds of formula I are intended for use in humans and for administration in a conventional manner, such as e.g. orally or parenterally. They are preferably administered orally, with a daily dose of about 0.015 to 15 mg / kg body weight, preferably 0.15 to 1.5 mg / kg body weight. For intravenous administration, the daily dose is about 1.5 to 1500 mcg / kg body weight, preferably about 15 to 150 mcg / kg body weight. However, depending on the patient's general condition and age, the corresponding Formula I substance, the type of disease and the type of formulation, the attending physician may also prescribe higher or lower doses.

The compounds of formula I may be administered alone or in conjunction with other pharmaceutically effective substances, the content of the compounds of formula I being between about 0.1 and 99%. Generally, pharmaceutically effective compounds are present in admixture with suitable, inert, auxiliary and / or carrier materials or diluents, such as e.g. pharmaceutically acceptable solvents, gelatin, arabic gum, milk sugar, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycol, petrolatum and the like.

The pharmaceutical preparations may be in solid form, e.g. as tablets, dragees, suppositories, capsules and the like, in semi-solid form, e.g. as lubricants, or in liquid form, e.g. as solutions, suspensions or emulsions. In the present case, they are sterilized and contain excipients such as preserving, stabilizing or emulsifying agents, salts for the change of osmotic pressure and the like.

In particular, pharmaceutical compositions may contain the compounds of the invention in combination with other therapeutically valuable substances. Thus, the compounds of the invention can be formulated e.g. together with the abovementioned excipients and / or carriers or diluents into combination preparations.

In the following, the foregoing compounds are predominantly in the form of their salts and / or solvates, with numerical data indicating the respective stoichiometric ratio. In the UV spectrum, the first digit represents the frequency and the number in brackets (the second number) indicates extinction.

Abbreviations used:

sh (oulder) in the UV spectrum of the soil .: melting point% of theory:% of theoretical (value)

C1 (ccl): C1 (total) eq .: equivalent calc .: calculated found: found sbl .: sublimation recrystallization: recrystallization recast: recast

EXAMPLE 1:

2-methyl-5-bromo-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone and

2-methyl-4-bromo-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

3.0 g (0.0112 mol) of 2-methyl-4,5-dibromo-3 (2H) -pyridazinone, 2.64 g (0.0112 mol)

1- (2-Aminoethyl) -4- (2-methoxyphenyl) -piperazine and 1.2 g (0.0112 mol) of finely powdered potassium hydrogen carbonate were heated in 100 ml of dimethylformamide with good stirring for 20 hours at 80 ° C; then hot suction from inorganic and concentrated by pump to a stream of water vapor. The remaining brown oil was dissolved in 0.5 N HCl, extracted three times with ether, the aqueous phase was adjusted to alkaline and partitioned between water and chloroform. After drying with sodium sulfate and concentrating the chloroform phase, 4.74 g of a brown oil are left, which is separated on silica gel (Matrex Silica Si60, 0.020 0.045 mm) by preparative column chromatography with methylene chloride-methanol 40: 1.5. 0.67 g of 2-methyl-5-bromo-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone, 14, appears as the first fraction. 2% of theory; by adding an equivalent amount of fumaric acid in absolute ethanol, fumarate is obtained as a colorless, crystalline substance from the ground. 185-186 ° C; C 49.5%, H 5.3%, Br 15.3%, N 12.6%, O 17.3%; UV v 0.1 N HCl: 208 (4.63), 226 (S, 4.40), 286 (S, 3.95), 302 (4.07).

Further elution gave 2.07 g of 2.07 g of 2-methyl-4-bromo-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone, which dissolved in absolute ethanol and fumaric acid added. A colorless crystalline fumarate (2.3 eq.) Was obtained from m.p. 125 - 129 ° C C 43.8% of theory .; C 46.3%, H 5.0%, Br 11.9%, N 9.9%, 0 26.9%; UV v 0.1 N HCl: 212 (4.63), 226 (S, 4.40), 282 (S, 3.83), 302 (S, 3.71).

EXAMPLE 2:

2-methyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone and

2-methyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

10.0 g (0.0559 mol) of 2-methyl-4,5-dichloro-3 (2H) -pyridazinone, 13.2 g (0.0559 mol)

1- (2-Aminoethyl) -4- (2-methoxyphenyl) -piperazine and 5.6 g (0.0559 mol) of potassium hydrogen carbonate are heated in 200 ml of acetonitrile with stirring for 20 hours at reflux, suction dried from inorganic and cooled. . The precipitate was 7.7 g

2-methyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone, 36.5% of theory, as colorless, crystalline precipitate which, after recrystallization from ethanol, gives

6.8 g (32.2%) of pure base. By treatment with ethereal HCl in ethanol, it is converted to dihydrochloride, m.p. 210 to 220 ° C; C 45.9%, H 5.7%, Cl (cel) 23.6%, Cl-16.0%; a colorless, crystalline substance; UV v 0.1 N HCl: 210 (4.55), 230 (4.30), 300 (4.17). Cooling the acetonitrile mother liquor yields a white crystalline precipitate 4.5 g of 2-methyl-4-chloro-5 - ((2- (4- (2methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone, 21, 3% of theory, which is converted into dihydrochloride from the soil by dissolving in isopropanol and adding ether hydrochloric acid. 218-225 ° C and recrystallization from isopropanol is obtained in pure form, m.p. 223-227 ° C, colorless crystals, 14.3% of theory .; C 48.0%, H 5.7%, Cl '(whole) 23.5%, Cl15.7%, N 15.0%, O 7.8%;

UV in ethanol: 210 (4.5), 230 (4.57), 286 (4, oo), 304 (S, 3.81).

EXAMPLE 3:

2-t-butyl-4-chloro-5 - ((2- (3- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone and

2-t-Butyl-5-chloro-4 - ((2- (3- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone

15.0 g (0.055 mol) of 1-aminoethyl-4- (3-trifluoromethylphenyl) piperazine and 15.2 g (0.069 mol) of 2-t-butyl-4,5-dichloro-3- (2H) -pyridazinone are heated with 6.9 g (0.069 mol) of finely powdered potassium hydrogen carbonate in 100 ml of acetonitrile, excluding moisture for 96 hours at reflux and stirring well until boiling; filtered from a solid, evaporated in vacuo, partitioned between ether and 1 N HCl, extracted with an acidic phase twice more with ether, then adjusted with sodium hydroxide solution to alkaline and extracted again with chloroform 3 times, dried with an organic phase with sodium sulfate and evaporate- solvent; the residue is weighed 30.1 g and preparative column chromatographed on silica gel (Matrex Silica Si60, 0.020-0.045 mm) with eluent methylene chloride-methanol 40: 1. We get it

18,8 g

2-t-butyl-4-chloro-5 - ((2- (3- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone as a fraction; 74.6% of theory. Of this, 3.80 g is dissolved in 50 ml of acetone and with ether hydrochloric acid is converted into 3.55 g of readily water-soluble, colorless, crystalline hydrochloride (2.8 HCl-eq.) From the ground. 124 -127 ° C; 54.0% of theory; C 42.4%, H 6.0%, Cl (whole) 23.0%, Cl 16.7%, F 9.2%, N 11.9%, O 7.5%; UV in ethanol: 206 (4.39), 210 (4.4), 216 (4.37), 258 (4.08), 304 (4.12). As the second fraction, 8.3 g of isomeric 2-t-butyl-5-chloro-4 - ((2- (3- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone are eluted; 32.9% of theory; 1.50 g of this fraction was precipitated into 50 ml of absolute ethanol and excess hydrochloric acid to give 1.20 g of dihydrochloride from the soil. 187 to 190 ° C as an easily water-soluble, colorless, crystalline substance. 22.6% of theory; C 47.4%, H 5.5%, C1 (whole) 20.0%, Cl 13.2%, F 10.3%, N 13.2%, O 3.6%; UV in ethanol: 212 (S, 4.39), 232 (4.52), 256 (4.19), 290 (3.97), 304 (S, 3.86).

EXAMPLE 4:

2-methyl-4-chloro-5 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone and

2-methyl-5-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

10.0 g (0.040 mol) of 1-aminopropyl-4- (2-methoxyphenyl) -piperazine and 7.9 g (0.044 mol) of 2-methyl-4,5-dichloro-3 (2H) -pyridazinone are heated together with 4 , 4 g (0.044 mol) of potassium hydrogen carbonate in 100 ml of freshly distilled dioxane for 10 hours at 80 ° C and then stirred for 3 days at room temperature. After filtration of the inorganic material, it was concentrated in vacuo, the residue dissolved in aqueous hydrochloric acid and extracted several times with ether; The aqueous phase was adjusted with sodium hydroxide solution to alkaline, shaken 3 times with chloroform, dried with sodium sulfate to give 15.7 g of the isomer mixture after concentration in vacuo. Separate column chromatography on silica gel (Matrex Silica Si6Q 0.020 - 0.045 mm) with ether-methanol 40: 5 as mobile phase. As a fraction, 7.43 g of 2-methyl-4-chloro-5 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone, 47.5 Dissolve 5,0 g in absolute ethanol and add ethanolic hydrochloric acid, yielding 5.6 g of dihydrochloride from the soil. 205-220 ° C; C 48.7%, H 6.5%, Cl (whole) 22.8, Cl 15.3%, N 15.0%, O 7.0%; UV v 0.1 N HCl: 210 (4.49), 230 (4.54), 282 (3.93), 302 (S, 3.85). Upon further elution, 5.95 g of 2-methyl-5-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl) 12 was isolated as a 2nd fraction12

1) propylamino) -3- (2H) -pyridazinone, 38.1% of theory. After dissolution in absolute ethanol and the addition of ethanolic hydrochloric acid, 4.0 g of this product gives 3.9 g of dihydrochloride from the soil. 226-228 ° C; 37.1% of theory; C 49.0%, H 6.5%, C1 (whole) 22.9, Cl · 15.3%, N 14.8%, O

6.8%; UV v 0.1 N HCl: 204 (4.48), 230 (S, 4.54), 286 (S, 3.95), 302 (3.85), 312 (S, 4.04).

EXAMPLE 5

2-methyl-4-chloro-5 - ((6- (4- (2-methoxyphenyl) piperazinyl-1) hexyl) amino) -3 (2H) -pyridazinone and

2-methyl-5-chloro-4 - ((6- (4- (2-methoxyphenyl) piperazinyl-1) hexyl) amino) -3 (2H) -pyridazinone

5.8 g (0.020 mol) of 1-aminohexyl-4- (2-methoxyphenyl) -piperazine and 4.45 g (0.025 mol) of 2-methyl-4,5-dichloro-2-methyl-3 (2H) -pyridazinone are heated with 2.50 g (0.025 mol) of finely powdered potassium hydrogen carbonate in 100 ml of absolute ethanol, excluding moisture for 48 hours at reflux with good stirring until boiling; remove the inorganic precipitate by filtration, concentrate the filtrate in vacuo, acidify with 1 N HCl, extract the acidic aqueous phase 3 times with ether, then adjust with sodium hydroxide to alkaline, and re-extract 3 times with chloroform, dry the organic phase with sodium sulfate and evaporate the solvent in vacuo; the residue of 10.0 g is preparative column chromatographed on silica gel (Waters Prep-Pak) with eluent methylene chloride-methanol-conc. ammonia 40: 1.5: 0.1. First eluting 3.70 g of 2-methyl-4-chloro-5 - ((6- (4- (2-piperazinyl) hexyl) amino) -3- (2H) -pyridazinone as fraction 1; 42.6% of theory Dissolve 2.00 g of this in 50 ml of ethanol and convert with ether hydrochloric acid to 2.20 g of water-soluble, colorless dihydrochloride, mp 160 - 175 ° C; 38.0% of theory; C 50.3%, H 6.8%, Cl (whole) 19.4, Cl-13.1%, N 13.2%, O 10.3%; UV in ethanol: 212 (4.46), 216 (4.45, S), 234 (4.50), 286 (3.96), 304 (3.87, S) Eluting 4.1 g of isomeric 2-methyl-5-chloro-4 - ((6- ( 4- (2-methoxyphenyl) piperazinyl-1) hexyl) amino) -3- (2H) -pyridazinone; 47.2% of theory. From this fraction was dissolved 2.00 g in 50 ml of ethanol and converted with ether hydrochloric acid into 1 , 50 g of water-soluble, colorless, crystalline dihydrochloride, mp 153-165 ° C; 19.7% of theory; C 52.3%, H 6.8%, Cl (whole) 20.6, Cl '13, 8%, N 13.9%, O 6.4%; UV in ethanol: 212 (4.47), 216 (4.44), 240 (4.29), 302 (4.14), 312 (3 , 89, S).

EXAMPLE 6

2-methyl-4-chloro-5 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone and

2-methyl-5-chloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone

10.0 g (0.038 mol) of 4-aminobutyl-2-methoxyphenyl-piperazine and 8.5 g (0.048 mol) of 2-methyl-4,5-dichloro-3 (2H) -pyridazinone together with 4.75 g (0.048 moles) of potassium hydrogen carbonate are dissolved in 70 ml of anhydrous dimethyl sulfoxide and maintained at 80 ° C for 15 hours; dilute with 200 ml of water and extract several times with chloroform. The organic phase was washed 3 more times with water and then extracted with 1 N HCl. The aqueous phase was basified, shaken with chloroform, dried with sodium sulfate to give 16.9 g of the product mixture after concentration in vacuo. Further separation was performed by preparative silica gel column chromatography (Matrex Silica Si60 0.020 - 0.045 mm) with ether-methanol 40: 5 as the mobile phase. 5.50 g (35.7% of theory) of 2-methyl-5-chloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (1) was isolated as fraction. 2H) pyridazinone, 30.1% of theory; it is dissolved in absolute ethanol and ethanolic hydrochloric acid is added thereto to give the dihydrochloride from the soil. 205 - 207 ° C; C 50.1%, H 6.5%, cl (calc) 21.5, Cl '14.5%, N 14.4%, O 7.0%; UV in ethanol: 206 (4.43), 210 (4.50), 244 (4.15), 296 (4.12), 312 (4.09). Upon further elution, 8.40 g of 2-methyl-4-chloro-5 - ((4- (4- (4- (2-methoxyphenyl) piperazinyl-1) amino) -3 (2H) -pyridazinone, appears as the 2nd fraction, 54.6% of theory; after dissolution in absolute ethanol and addition of ethanolic hydrochloric acid, it gives a colorless, crystalline dihydrochloride, mp 183 - 192 ° C; C 50.10%, H 6.1%, Cl (calc.)

21.8%, Cl '14.9%, N 14.9%, O 7.0%; UV in ethanol: 210 (4.41), 218 (4.42), 232 (4.46), 236 (4.45), 286 (3.96).

EXAMPLE 7

2-methyl-4-chloro-5 - ((2- (4- (2,6-dimethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone and

2-methyl-5-chloro-4 - ((2- (4- (2,6-dimethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

9.2 g (0.039 mol) of 1-aminoethyl-4- (2,6-dimethylphenyl) -piperazine and 8.8 g (0.049 mol) of 2-methyl-4,5-dichloro-3 (2H) -pyridazinone are heated together with 4.9 g (0.049 mol) of finely powdered potassium hydrogen carbonate in 100 ml of toluene, with a moisture exclusion of 20 hours at reflux and stirring well until boiling; filtered from inorganic material, concentrated in vacuo, dissolved in 1 N HCl, extracted 3 times with ether, the alkaline phase adjusted to alkaline, extracted 3 times with chloroform, the organic phase dried with sodium sulfate and the solvent evaporated; the residue of 15.7 g was preparatively column chromatographed on silica gel (Waters Prep-Pak) with eluent methylene chloride-methanol 40: 1. 5.70 g of 2-methyl-4-chloro-5 - ((2- (4- (2,6 (dimethylphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone, 32.6% are obtained theoretically, as 1st fraction; of which 3.80 g is dissolved in 50 ml of absolute ethanol, ether hydrochloric acid is added and 3.00 g of readily water-soluble, colorless, crystalline dihydrochloride from the soil is converted. 235-242 ° C; 32.6% of theory; C 50.7%, H 6.3%, C1 (calc.) 23.2, Cl '15.4%, N 15.6%, O 4.2%; UV in ethanol: 220 (4.40), 232 (4.49), 290 (3.85), 311 (3.81).

7.40 g of 2-methyl-5-chloro-4 - ((2- (4- (2,6 (dimethylphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone is obtained as the second column fraction, 42.3% of theory; 4.0 g was dissolved in 50 ml of absolute ethanol, precipitated with excess hydrochloric acid and gave 2.40 g of an easily water-soluble, colorless, crystalline hydrochloride from the ground. 225-232 ° C; 24.9% of theory; C 55.5%, H 6.8% Cl (calculated) 17.3, Cl * 6.6%, N 17.2%, O 3.2%; UV in ethanol: 212 (4.35), 216 (4.34), 233 (4.11), 304 (4.09), 312 (4.03).

The following compounds are prepared analogously to Examples 1-7:

5-chloro-4 - ((2- (4-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.75 HC1; solvate: 1.25 H ^ O

Tal .:

251 - 256 [deg.] C., Recrystallization: ethanol

Yield: 76.2% of theory.

C: calc .: 41.95, found:41.8

H: calc .: 5.64, found.2

Cl, calc .: 27.32, found:26.6

Cl ': calc .: 20.03, found: 19.9

N: calc .: 14.39, found: 14.2

A: calc .: 9.68, found: 9.0

UV: solvens: ethanol,

214 (4.39), 302 (3.91), 312 (3.85)

2-methyl-5-chloro-4 - ((2- (4-phenylpiperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 1.6 HC1; solvate: 0.1 Ufi

Melting point: 218-220 ° C, recrystallization: ethanol

Yield: 23.5% of theory.

C: calc .: 50.05, found: 50.0

H: calc .: 5.88, found: 6.1

Cl: Calc .: 22.59, Found: 22.5

C1 ': calc .: 13.9, found: 14.1

N: calc .: 17.17, found: 17.2

A: Calc .: 4.31, Found: 4.2

UV: solvens: 0.1 N HC1,

2o4 (4.48), 232 (4.24), 300 (4.11)

2-methyl-5-chloro-4- (methyl- (2- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Sol .: 2.0 HCl; solvate: 0.5 H ₂ O Melting point: 224 - 231 ° C, recrystallization: ethanol Yield: 41.1% of theory.

C: Calc .: 48.16, Found: 48.6

H: calc .: 6.17, found: 6.1

Calc .: 22.45, Found: 22.3

Cl: Calc .: 14.96, Found: 15.1

N: calc .: 14.78, found: 14.6

A: Calc .: 8.44, Found: 8.4

UV: solvens: 0.1 N HC1,

210 (4.36), 218 (4.36), 236 (4.37), 280 (S, 3.95), 300 (4.03)

2-methyl-5-chloro-4 - ((2- (4- (2-methoxy-5-methylphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridine zinone

Salt: 1.5 fumarate;

melting point: 140 -144 ° C, recrystallization: acetone

Yield: 25.5%

C: calc .: 53.05, found: 53.5

H: calc .: 5.70, found: 6.0

Cl: Calc .: 6.26, Found: 6.5

N: calc .: 12.37, found: 12.6

A: Calc .: 22.61, Found: 22.4

UV: solvens: 0.1 N HC1,

206 (4.44), 226 (4.27), 298 (4.08), 310 (S, 4.02)

2-methyl-5-chloro-4 - ((2- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Salt: 1.5 fumarate;

M.p .: 151 -154 ° C, recrystallized: acetone

Yield: 27.6% of theory.

C: Calc .: 53.05, found: 53.0 H: Calc .: 5.70, found: 5.9 Cl: Calc .: 6.26, found: 5.8 N: Calc .: 12.37, found: 12.2 A: Calc .: 22.61, found: 23.1 UV: solvens: 0.1 N HC1,

204 (4.51) 226 (S, 4.22), 300 (4.47)

2-methyl-5-chloro-4 - ((2- (4- (3-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Sol.:2,0HCl;

M.p .: 161 -169 ° C, chromatographic purified yield: 31.5% of theory.

C: Calc .: 47.96, found: 47.9 H: Calc .: 5.80, found: 5.9 Cl: Calculated: 23.59, found: 23.5 Cl ·: Calc .: 15.73, found: 15.5 N: Calc .: 15.54, found: 15.5 A: Calc .: 7.10, found: 7.2

UV: solvens: ethanol,

214 (4.48), 248 (S, 4.06), 304 (4.18), 312 (S, 4.1)

2-methyl-5-chloro-4 - ((2- (4- (2-benzyloxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazone Sol .: 2.0 HCl; solvate: 1.0 H ₂ O M.p .: 126 -139 ° C,

Yield: 51.5% of theory. (crude), 19% of theory. (clean)

C: Calc .: 53.20, found: 53.4 H: Calc .: 5.39, found: 5.7 Cl: Calc .: 19.63, found: 19.2 cr: Calc .: 13.09, found: 12.8 N: Calc .: 12.92, found: 12.7

A: Calc .: 8.89, Found: 9.0

UV: solvens: 1N HC1,

210 (4.58), 234 (S, 4.18), 300 (4.08), 311 (S, 3.99)

2-methyl-4-chloro-5 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) .3 (2H) -pyridazinone Sol .: 2.0 HBr; solvate: 1.5 H ₂ O m.p .: 208 - 213,

Yield: 17.6% of theory,

C: Calc .: 37.06, found 36,9 H: Calc .: 4.94, found 4.5 Cl: Calc .: 6.44, found 6.0 N: Calc .: 12.71, found 12.6 A: Calc .: 10.16, found 10.6 Nr: Calc .: 29.01, found 29.4

UV: solvens: INHC1,

206 (4.55), 230 (S, 4.17), 235 (S, 4.10), 300 (4.10), 311 (S, 4.02)

2-methyl-5-chloro-4 - ((2- (4- (2-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Sol .: 1.0 fumarate; solvate: 0.5 H ₂ O Melting point: 185 - 187 ° C, recrystallization: ethanol yield: 23.5% of theory.

C: Calc .: 54.26, found: 53.9 H: Calc .: 6.00, found: 6.0 Cl: Calc .: 7.28, found: 7.7 N: Calc .: 14.38, found: 14.3 A: Calc .: 18.07, found: 18.1

UV: solvens: 0.1 N HC1

208 (4.43), 230 (4.20), 300 (4.10), 312 (S, 4.00)

2-methyl-5-chloro-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino-3 (2H) -pyridazinone Salt: 1.15 HC1; solvate: 0.5 H ₂ O Melting point: 175 -197 ° C, rec .: ethanol Yield: 26.8% of theory.

C: calc .: 46.32, found: 46.7

H: calc .: 5, oo, found: 5.0

Cl: Calc .: 16.33, found: 16.5 Cl ': Calc .: 8.73, found: 8.5 N: Calc .: 15.00, found: 15.1 A: Calc .: 5.14, found: 5.1 F: Calc .: 12.21, found: 11.6

UV: solvens: ethanol,

208 (4.49), 219 (S, 4.37), 238 (4.06), 256 (4.16), 304 (4.17)

2-methyl-5-chloro-4 - ((2- (4- (4-chloro-3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) pyridazinone

Salt: 2.0 HC1; solvate: 0.2 H ₂ O

Tal. 185 -188 ° C, conversion: ethanol, diethyl ether

Yield: 25.6% of theory. (crude), 22.1% of theory. (clean)

C: Calc .: 41.04, found: 41.6 H: Calc .: 4.29, found: 4.3 Cl: Calc .: 26.92, found: 26.8 Cl ': Calculated: 13.5, found: 13.5 N: Calc .: 13.29, found: 13.3 A: Calc .: 3.64, found: 3.7 F: Calculation: 10.82, found: 10.3

2-methyl-5-chloro-4 - ((2- (4- (3-chlorophenyl) piperazinyl) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.0 HC1; solvate: 0.15 H ₂ O

Melting point: 195 ° C (sbl), chromatographed

Yield: 32.9% of theory.

C: Calc .: 44.59, found 44,7 H: Calculated: 5.13, found 5.2 Cl: Calc .: 30.97, found 30.6 Cl ': Calc .: 15.48, found 15.4 N: Calc .: 15.29, found 15.5 A: Calculated: 5.15, found 5.1

UV: solvens: ethanol,

210 (4.39), 216 (4.40), 235 (S, 4.04), 258 (4.13), 304 (4.15)

2-methyl-4-chloro-5 - ((2- (4- (3,5-dichlorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Sol .: 1.0 HC1;

Melting point: 191 - 201 ° C, conversion: ethanol, diethyl ether Yield: 42.6% of theory.

C: Calc .: 45.05, found: 45.3 H: Calc .: 4.67, found: 4.7 Cl: Calc .: 31.29, found: 31.0 Cl ': Calc .: 7.82, found: 7.8 N: Calc .: 15.45, found: 15.3 A: Calculated: 3.53, found: 3.2

2-methyl-5-chloro-4 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino-3 (2H) -pyridazinone Salt: 1 HBr; solvate:

M.p .: 210 - 214 ° C, recrystalline: ethanol Yield: 34.1% of theory.

Salt: 1 HBr; solvate:

C: Calc .: 45.70, found 45,9 H: Calculated: 4.96, found 4,8 Cl: Calc .: 7.94, found 8.1 N: Calc .: 15.68, found 15.5 A: Calc .: 3.58, found 3.6 F: Calc .: 4.25, found 3.9 Br-: Calc .: 17.89, found 18,2

UV: solvens: 0.1 N HC1,

208 (4.24), 230 (4.28), 300 (4.08), 312 (S, 3.98)

2-methyl-5-chloro-4 - ((2- (4- (4-fluorophenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.2 H ₂ O Melting point: 189 -195 ° C, recrystalline: ethanol Yield: 15.8% of theory.

C: Calc .: 46.16, found: 46.6 H: Calc .: 5.33, found: 5.3 Cl: Calc .: 24.04, found: 24.0 C1-: Calculated: 16.03, found: 16.2 N: Calc .: 15.83, found: 15.8 A: Calc .: 4.34, found: 4.6

found: 4.6

F: calc .: 4.29,

UV: solvens: ethanol,

206 (4.32), 240 (4.27), 304 (4.12), 312 (S, 4.08)

2-methyl-5-chloro-4 - ((2- (4- (4-nitrophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 0.9 HCl;

M.p .: 237-240 ° C; recrystallization: ethanol

Yield: 17.9% of theory.

C: Calc .: 47.97, found: 48.2 H: Calc .: 5.19, found: 5.2 Cl: Calc .: 15.82, found: 16.0 C1-: Calc .: 7.50, found: 7.6 N: Calc .: 19.74, found: 19.8 A: Calc .: 11.28, found: 10.8

UV: solvens: ethanol,

204 (4.34), 232 (4.18), 304 (4.09), 312 (S, 4.06), 382 (4.20)

2-t-Butyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.5 fumarate;

M.p .: 162-165 ° C, conversion: MeOH, acetone Yield: 14% of theory. C: Calc .: 54.59, found: 54.5 H: Calc .: 6.11, found: 6.3 Cl: Calc .: 5.97, found: 6.1 N: Calc .: 11.79, found: 11.7 A: Calc .: 21.55, found: 21.3

UV: solvens: O, 1NHC1,

208 (4.65), 282 (S, 3.94), 300 (4.01)

2- (2-dimethylaminoethyl) -5-chloro-4- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) pyridazinone

Salt: 2.95 HBr; solvate: 3.0 H ₂ O

M.p .: 168 -178 ° C, recrystallized: ethanol

Yield: 26.1% of theory.

C: calc .: 34.65, found: 34.8

H: Calculated: 5.53, found: 5.3 N: Calc .: 11.55, found: 11.5 A: Calc .: 10.99, found: 10.9 Br-: Calc .: 32.39, found: 32.5 UV: solvens: 0.1 N HC1,

206 (4.42), 230 (4.12), 285 (3.79), 302 (4.04), 312 (3.86)

2-hydroxyethyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazine non

Salt: 2.0 HC1; solvate: 0.45 H ₂ O

M.p .: 171 -181 ° C, recrystallized: acetone

Yield: 25.6% of theory.

C: Calc .: 46.68, found: 46.4 H: Calculated: 5.96, found: 5.8 Cl: Calc .: 21.75, found: 21.7 C1-: Calc .: 14.50, found: 14.5 N: Calc .: 14.32, found: 14.1 A: Calc .: 11.29, found: 11.0

UV: solvens: 0.1 N HC1,

208 (4.52), 232 (S, 4.14), 304 (4.10)

2- (2-hydroxyethyl) -5-chloro-4 - ((2- (4- (3-trifluoromethyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridine azinone

Salt: 2.0 HC1; solvate: 0.85 H ₂ O M.p .: 113 -120 ° C; recrystallization: acetone Yield: 6.9% of theory,

C: Calc .: 42.73, found: 43.3 H: Calc .: 5.04, found: 5.0 Cl: Calc .: 19.91, found: 19.4 Cl ': Calc .: 13.28, found: 12.9 N: Calculated: 13.11, found: 13.1 A: Calc .: 8.39, found: 8.5 F: Calc .: 10.67, found: 10.7

UV: solvens: ethanol

206 (4.41), 240 (4.09), 258 (4.17), 304 (4.18), 312 (S, 4.11)

2-methyl-5-chloro-4 - ((2- (4- (pyridyl-2) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.45 H ₂ O Melting point: 200 - 210 ° C, recrystallization: ethanol Yield: 19.5% of theory.

C: Calc .: 44.71, found: 44.6 H: Calculated: 5.60, found: 5.5 Cl: Calc .: 24.74, found: 24.9 Cl ': Calc .: 16.49, found: 16.7 N: Calculated: 19.55, found: 19.6 A: Calculated: 5.40, found: 5.4

2-methyl-5-chloro-4- (methyl - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridine azinone

Salt: 1.0 fumarate; solvate: 1.0 H ₂ O

M.p .: 159 -165 ° C, recrystalline: ethanol

Yield: 40.8% of theory.

C: calc .: 52.98, found: 52.8

H: calc: 7.04, found 6.4

Cl: Calc .: 6.52, Found: 6.4

N: calc .: 12.87, found: 13

A: Calc .: 20.58, Found: 21.5

2-methyl-5-chloro-4 - ((3- (4- (2-hydroxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridinone

Salt: 1.0 fumarate;

M.p .: 193-197 ° C, rec .: ethanol

Yield: 34.3% of theory.

C: Calc .: 54.38, found: 54.5 H: Calculated: 5.95, found: 6.1 Cl: calc .: 7,, found: 7.2 N: Calc .: 13.79, found: 13.7 A: Calc .: 18.9, found: 18.5

2-methyl-5-chloro-4 - ((3- (4- (2-ethoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridine azinone

Salt: 2.0 HC1;

M.p .: 220 - 223 ° C,

Yield: 39% of theory.

H: Calc .: 6.54, found: 6.5 Cl: Calc .: 21.58, found: 21.4 Cl ': calcd. : 14,39, found: 14.4 N: Calc .: 14.21, found: 14.4 A: Calc .: 6.49, found: 6.9

UV: solvens: 0.1 N HC1.2O6 (4.45), 226 (S, 4.16), 302 (4.10), 312 (S, 4.02)

2-methyl-5-chloro-4 - ((3- (4- (2-methylphenyl) -1) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 1.0 fumarate;

Tal .: 184 -186 ° C, Yield: 30% of theory. C: Calc .: 56.15, found: 55.6 H: Calc .: 6.15, found: 6.2 Cl: Calc .: 7.21, found: 7.3 N: Calc .: 14.24, found: 14.4 A: Calc .: 16.26, found: 16.5

UV: solvens: 0.1 N HC1

206 (4.42), 230 (4.14), 302 (4.08), 312 (S, 3.99)

2-methyl-5-chloro-4 - ((3- (4- (2-fluorophenyl) piperazinyl-1) propyl) amino) -2 (2H) -pyridazinone Salt: 1.0 fumarate;

M.p .: 161 -163 ° C, recrystallization: ethanol Yield: 28.3% of theory. C: Calc .: 53.28, found 53,3 H: Calc .: 5.49, found 5.5 Cl: Calc .: 7.15, found 7.1 N: Calc .: 14.12, found 13,8 A: Calculated: 16.13, found 16.6 F: Calculated: 3.83, found 3.7

UV: solvens: 0.1 N HC1,

204 (4.4), 230 (4.24), 302 (4.11), 313 (S, 4.17)

2-methyl-5-chloro-4 - ((3- (4- (4-fluorophenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Salt: 2.0 HC1; solvate: 3.0 H ₂ O Melting point: 216 ° C (sbl), crystalline: ethanol Yield: 22.5% of theory.

C: Calc .: 42.66, found 42,2 H: Calc .: 6.17, found 6.0 Cl: Calc .: 20.98, found 21.3 Cl ·: Calc .: 13.99, found 14,0 N: Calculated: 13.82, found 14.2 A: Calc .: 12.63, found 12,8 F: Calculated: 3.75, found 3.5

2-methyl-5-chloro-4 - ((2- (4- (pyridyl-2) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.15 H ₂ O Melting point: 219 - 226 ° C, recrystallized: ethanol Yield: 14.4% of theory.

C: Calc .: 46.57, found: 46.5 H: Calc .: 5.87, found: 5.8 Cl: Calc .: 24.26, found: 24.3 Cl ·: Calc .: 16.17, found: 16.2 N: Calc .: 19.17, found: 19.2 A: Calc .: 4.20, found: 4.2

UV: solvens: ethanol,

206 (4.24), 250 (4.26), 304 (4.24)

4-chloro-5 - ((2- (4- (3-trifluoromethyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 2.0 H ₂ O

M.p .: 173 -176 ° C; recrystallized: ethanol

Yield: 60.3% of theory,

C: calc .: 39.98, found: 40.3

H: calc .: 4.93, found: 4.2

Cl: Calculated: 20.82, found: 21 Cl: Calculated: 13.88, found: 14.1 N: Calculated: 13.71, found: 13.9 A: Calc .: 9.40, found: 9.5 F: Calc .: 11.16, found: 11.1

2-methyl-4-chloro-5 - ((2- (4-phenylpiperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.85 HCl; solvate: 0.7 H ₂ O m.p .: 171 -180 ° C, recrystallized: ethanol Yield: 39% of theory,

C: Calculation: 47.72, found: 48.2 H: Calc .: 6.00, found: 6.3 Cl: Calc .: 23.61, found: 23.2 Cl: Calc .: 15.33, found: 15 N: Calc .: 16.37, found: 16.1 A: Calc .: 6.36, found: 6.2

UV: solvens: 0.1 N HC1,

206 (4.41), 230 (4.57), 288 (3.92)

2-methyl-4-chloro-5 - ((2- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Salt: 1.75 fumarate;

M.p .: 103 - 105 ° C, crystalline: acetone

Yield: 37.6% of theory.

C: Calc .: 52.48, found: 52.3 H: Calc .: 5.59, found: 6.1 Cl: Calculated: 5.96, found: 5.9 N: Calc .: 11.77, found: 12 A: Calc .: 24.20, found: 23.7

UV: solvens: O, 1NHC1,

210 (4.49), 228 (4.57), 282 (3.99), 304 (S, 3.81)

2-methyl-4-chloro-5 - ((2- (4- (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Salt: 1.25 fumarate;

Tal. 80 - 83 ° C, crystalline: acetone

Yield: 27.3% of theory,

C: Calc .: 53.68, found: 53.6 H: Calc .: 5.82, found: 6.3 Cl: Calc .: 6.60, found: 6.6 N: Calculated: 13.04, found: 13.4 A: Calculated: 20.85, found: 20.1

UV: solvens: 0.1 N HC1,

212 (4.52), 228 (4.58), 286 (4.03), 304 (S, 3.80)

2-methyl-4-chloro-5 - ((ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazine

Salt: 2.0 HC1;

M.p .: 178 -183 ° C, crystalline: ethanol

Yield: 31.9% of theory. (crude), 22.5% of theory. (clean)

C: Calc .: 50.17, found 50.4 H: Calc .: 6.32, found 6,3 Cl: Calc .: 22.21, found 22 C1-: Calc .: 14.81, found 14.7 N: Calc .: 14.63, found 14,8 A: Calc .: 6.68, found 6.5

2-methyl-4-chloro-5 - ((2- (4- (3-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.2 H ₂ O

M.p .: 170 -174 ° C, conversion: ethanol, diethyl ether Yield: 47% of theory, C: Calc .: 47.58, found 47,6 H: Calc .: 5.86, found 6,1 Cl: Calc .: 23.41, found 22,9 Cl ': Calc .: 15.6, found 15.1 N: Calc .: 15.41, found 15.2 A: Calc .: 7.75, found 7,6

UV: solvens: ethanol,

214 (4.6), 232 (4.56), 250 (S, 4.09), 290 (3.97), 304 (S, 3.89)

2-methyl-4-chloro-5 - ((2- (4- (2-ethoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone salt: 1.0 fumarate;

M.p .: 197 -199 ° C, recrystallized: acetone Yield: 35.2% of theory.

C: Calc .: 54.38, found: 54.2 H: Calculated: 5.95, found: 6 Cl: Calc .: 6.98, found: 6.9 N: Calc .: 13.79, found: 13.6 A: Calculated: 18.9o, found: 19.3

2-methyl-4-chloro-5 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.25 HBr; solvate: 1.33 H ₂ O M.p .: 191 -195 ° C,

Yield: 22.6% of theory,

C: Calc .: 35.82, found: 35.9 H: Calc .: 4.76, found: 4.6 Cl: Calc .: 6.22, found: 6.1 N: Calc .: 12.29, found: 11.8 A: Calc .: 9.36, found .. 11.6 Br ': Calc .: 31.54, found: 30.0

UV. solvens: 1N HC1,

208 (4.54), 230 (4.53), 282 (3.96), 302 (S, 3.8)

2-methyl-4-chloro-5 - ((4- (2-hydroxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazine

Salt: 2.75 HC1; solvate: 3.25

M.p .: 157 -167 ° C, recrystallized: ethanol

Yield: 78.9% of theory.

C: Calc .: 40.28, found: 40.8 H: Calc .: 6.24, found: 5.9 Cl: Calc .: 24.77, found: 24.5 Cl ·: Calc .: 18.17, found: 17.9 N: Calculated: 13.05, found: 12.8 A: Calc .: 15.65, found: 16.0

UV: solvens: ethanol,

214 (4.80), 230 (4.88), 286 (4.30), 305 (S, 4.09)

2-methyl-4-chloro-5 - ((2- (4- (2-benzyloxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 1.8 HC1; solvate: 1.5 t ^ O

M.p .: 154-159 ° C, recrystallized: ethanol

Yield: 49.1% of theory. (crude), 25.2% of theory. (clean)

C: calc .: 46.22, found: 46.2 H: calc .: 4.82, found: 5.3 Cl: Calc .: 5.68, found: 5.1 N: calc .: 11.23, found: 10.6 A: calc .: 8.98, found: 8.9 No: 1.8 Calc .: 23.06, found: 23.9

UV: solvens: 0.1 N HC1,

208 (4.67), 230 (4.54), 284 (3.96), 304 (S, 3.82)

2-methyl-4-chloro-5 - ((2- (4- (2-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 fumarate; solvate: 2.75 H ₂ O M.p .: 149 -155 ° C, recrystallized: ethanol Yield: 46.3% of theory.

C: Calc .: 48.52, found: 48.7 H: Calc .: 5.87, found: 5.6 Cl: Calc .: 5.51, found: 5.6 N: Calc .: 10.88, found: 10.7 A: Calc .: 29.21, found: 29.4

UV: solvens: 0.1 N HC1,

204 (4.29), 210 (4.45), 230 (4.53), 286 (3.89), 302 (S, 3.59)

2-methyl-4-chloro-5 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) -ethyl) amino) -3 (2H) -pyridazine non

Salt: 3.0 HC1; solvate: 2.25 H ₂ O

M.p .: 120-112 ° C, conversion: ethanol, diethyl ether

Yield: 38.4% of theory, C: Calc .: 38.33, found: 38.7 H: Calculated: 5.05, found: 4.6 Cl: Calc .: 25.15, found: 25.4 Cl ·: Calc .: 18.89, found: 19.1

N: Calc .: 12.42, found: 12.4 A: Calc .: 8.93, found: 9.3 F: Calc .: 10.07, found: 9.6 UV: solvens: ethanol,

208 (4.44), 232 (4.51), 256 (4.20), 294 (3.95), 304 (S, 3.91)

2-methyl-5-chloro-4 - ((2- (4- (3,5-dichlorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 0.75 HCl; solvate: 0.35 H ₂ O

M.p .: 208 - 221 ° C, ref. : ethanol, diethyl ether Yield: 50.3% of theory, C: Calc .: 45.34, found 45,2 H: Calc .: 4,800, found 4.7 Cl: Calc .: 29.52, found 30.0 Cl ': Calc .: 5.90, found 6,3 N: Calc .: 15.55, found 15.3 A: Calc .: 4.80, found 4.7

2-methyl-4-chloro-5 - ((2- (4- (3-chlorophenyl) piperazinyl) ethyl) amino) -3 (2H) -pyridazinone salt: 1.25 HCl; solvate: 0.4 H ₂ O

Melting point: 211 - 219 ° C, purified by chromatography

Yield: 32.9% of theory,

C: Calc .: 46.93, found: 47.2 H: Calc .: 5.23, found: 5.3 Cl: Calc .: 26.48, found: 26.0 Cl'-: Calc .: 10.19, found: 10.1 N: Calc .: 16.10, found: 16.3 A: Calc .: 10.19, found: 10.1

2-methyl-4-chloro-5 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino) -2 (2H) -pyridazinone Salt: 1.0 Hbr; solvate: 0.65 H ₂ O m.p. 240 - 243 ° C, crystalline: ethanol. Yield: 42.4% of theory.

H: calc. : 44,54, found. : 44.6

Cl, calcd: 5.12, found.2

N: calc .: 15.28, found 15.0

A: Calc .: 5.76, Found: 5.6

F: calc .: 4.14, found: 3.6

Br ': calc .: 17.43, found: 17.5

UV: solvens: 0.1 N HC1,

212 (S, 4.30), 230 (4.56), 288 (3.89), 304 (S, 3.78)

2-methyl-4-chloro-5 - ((2- (4- (4-fluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 2.25 Ufi Melting point: 155 -161 ° C, recrystallized: ethanol Yield: 18.7% of theory.

C: Calc .: 42.60, found 42,9 H: Calc .: 5.78, found 5,3 Cl: Calc .: 22.19, found 22,4 C1 ': Calc .: 14.79, found 14.7 N: Calc .: 14.61, found 14,8 A: Calc .: 10.85, found 11,0 F: Calculated: 3.96, found 3.6

UV: solvens: ethanol,

204 (4.34), 208 (4.34), 232 (4.54), 292 (3.93), 304 (S, 3.89)

2-methyl-4-chloro-5 - ((2- (4- (4-nitrophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 0.7 HCl; solvate: 0.1 H ₂ O

M.p .: 242-251 ° C; recrystallized: ethanol

Yield: 10.7% of theory.

C: Calc .: 48.60, found: 48.8 H: Calc .: 5.25, found: 5.4 Cl: Calc .: 14.34, found: 14.3 Cl ': Calculated: 20.00, found: 19.8 A: Calculated: 11.80, found: 11.7

UV: solvens: ethanol,

208 (4.28), 232 (4.47), 296 (3.81), 312 (3.83), 382 (4.13)

2-methyl-4-chloro-5 - ((2- (4- (pyridyl-2) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.35 H ₂ O

M.p .: 222 - 229 ° C, crystalline: ethanol Yield: 36.6% of theory.

C: Calculation: 44.89, found: 45.1 H: Calc .: 5.58, found: 5.5 Cl: Calc .: 24.85, found: 24.8 Cl ·: Calc .: 16.56, found: 16.7 N: Calc .: 19.63, found: 19.6 A: Calculated: 5.05, found: 5, o

2-t-butyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.5 fumarate; solvate: 1.2 H ₂ O M.p .: 220 - 224 ° C,

Yield: 66.5% of theory,

C: Calc .: 52.67, found: 52.5 H: Calc .: 6.29, found: 6.3 Cl: Calc .: 5.76, found: 5.9 N: Calc .: 11.38, found: 11.4 A: Calc .: 23.91, found: 23.9

UV: solvens: 0.1 N HC1,

212 (4.68), 230 (4.64), 282 (4.02), 312 (S, 3.68)

2- (dimethylaminoethyl) -4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) -ethyl) anino) -3 (2H) pyridazinone

Salt: 2.0 fumarate; solvate: 2.5 H ₂ O

Melting point: 110-115 ° C,

Yield: 52.2% of theory.

C: Calculation: 48.91, found: 49.1 H: Calc .: 6.23, found: 5.9 Cl: Calc .: 4.88, found: 5.0 N: Calculated: 11.80, found: 11.8 A: Calc .: 28.08, found: 28.2

UV: solvens: 0.1 N HC1,

210 (4.49), 232 (4.57), 282 (3.95), 309 (S, 3.81)

2-hydroxyethyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino3 (2H) -pyridazine

Salt: 2.9 HCl; solvate: 2.7 H ₂ O Melting point: 130 -141 ° C, crystalline: acetone Yield: 47.3% of theory.

C: Calc .: 40.17, found: 40.6 H: Calc .: 6.09, found: 5.8 Cl: Calc .: 24.34, found: 24.4 Cl ·: Calc .: 18.10, found: 18.3 N: Calc .: 12.33, found: 12.6 A: Calc .: 16.05, found: 16.4

UV: solvens: ethanol,

212 (4.58), 232 (4.54), 286 (4.00), 304 (S, 3.85)

2-hydroxyethyl-4-chloro-5 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridine

Salt: 2.75 HC1; solvate: 2.0 Ufi

M.p .: 117-112 ° C, recrystallized: ethanol

Yield: 29.1% of theory.

C: Calc .: 39.20, found 39,2 H: Calculated: 5.15, found 4.5 Cl: Calculated: 22.84, found 23,2 Cl ·: Calc .: 16.75, found 16.6 N: Calculated: 12.03, found 12,0 A: Calc .: 10.99, found 11.3 F: Calc .: 9.79, found 9.8

UV: solvens: ethanol,

206 (4.41), 234 (4.48), 256 (4.19), 294 (3.99), 304 (S, 3.95)

2-phenyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.0 Hbr; solvate: 0.5 ethanol. 1H ₂ O M.p .: 140 -147 ° C, crystalline: ethanol yield: 33.5% of theory,

C: calc .: 51.30, found:51.7

H: calc .: 5.74, found: 5.8

Cl: Calc .: 6.31, found: 6.2 N: Calc .: 12.46, found: 12.2 A: Calc .: 9.97, found: 10.1 Br ': Calc .: 14.22, found: 14.0

2-methyl-4-chloro-5- (methyl - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridine azinone

Salt: 1.0 fumarate; solvate: 0.5 H ₂ O

M.p .: 169-173 ° C; recrystall., ethanol

Yield: 6.1% of theory.

C: Calc .: 54.28, found: 54.0 H: Calc .: 6.26, found: 6.2 Cl: Calc .: 6.68, found: 6.6 N: Calculated: 13.19, found: 13.5 A: Calc .: 19.58, found: 19.3

2-methyl-4-chloro-5 - ((3- (4- (2-hydroxy-4-methylphenyl) -piperazinyl-1) -propyl) amino) -3 (2H) -pyridazinone

Salt: 1.0 fumarate; solvate: 0.5 H ₂ O

M.p .: 175 -181 ° C, crystalline: ethanol

Yield: 69.1% of theory.

C: Calc .: 53.44, found: 52.7 H: Calc .: 6.04, found 6.3 Cl: Calc .: 6.86, found: 6.9 N: Calculated: 13.55, found: 13.7 A: Calc .: 20.12, found: 20.4

2-methyl-4-chloro-5 - ((3- (4- (2-ethoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridine azinone

Salt: 2.4 HCl; solvate: 2.2 H ₂ O M.p .: 196 - 203 ° C, yield: 48.1% of theory,

C: Calculation: 46.1, found: 45.8 H: Calc .: 6.78, found: 6.5 Cl: Calculated: 22.03, found: 22.5

Cl ': Calc .: 15.55, found: 15.3 N: Calculated: 12.80, found: 12.9 A: Calc .: 12.28, found 12.3

2-methyl-4-chloro-5 - ((3- (4- (2-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone salt: 1.0 fumarate; solvate: 0.5 H ₂ O Melting point: 176- 184 ° C Yield: 40% of theory.

C: Calc .: 55.14, found: 54.7 H: Calc .: 6.24, found: 6.2 Cl: Calc .: 7.08, found: 7.3 N: Calculated: 13.98, found: 14.1 A: Calc .: 17.56, found: 17.7

UV: solvens: O, 1NHC1

208 (4.47), 232 (4.56), 290 (3.88), 302 (S, 3.84)

2-methyl-4-chloro-5 - ((3- (4- (2-fluorophenyl) piperazinyl-1) propyl) amino) -2 (2H) -pyridazinone salt: 1.0 fumarate; solvate: 1.0 H ₂ O

M.p .: 176 - 179 ° C, ref. Yield: 42.1% of theory. : ethanol, acetone C: Calc .: 51.41, found 51,2 H: Calc .: 5.69, found 5.4 Cl: Calc .: 6.90, found 7.1 N: Calculated: 13.63, found 13.7 A: Calc .: 18.68, found 18,8 F: Calc .: 3.70, found 3.8

UV: solvens: 0.1 N HC1

204 (4.39), 232 (4.59), 290 (3.89), 305 (S, 3.86)

2-methyl-4-chloro-5 - ((3- (4- (4-fluorophenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Salt: 3.0 HC1; solvate: 1.5 H ^ O

M.p .: 132-139 ° C, recrystallized: acetone

Yield: 34.7% of theory.

C: calc .: 41.88, found: 42.2

H: calc .: 5.47, found: 5.6

Cl: Calc .: 27.47, found: 27.2 Cl ·: Calc .: 20.6, found: 20.8 N: Calculated: 13.57, found: 13.7 A: Calc .: 7.75, found: 7.9 F: Calc .: 3.68, found: 3.4

2-methyl-4-chloro-5 - ((3- (4- (pyridyl-2) piperazinyl-1) propyl) amino) 3 (2H) -pyridazinone

Salt: 2.0 HC1; solvate: 0.35

Melting point: 200 - 214 ° C, recrystallized: ethanol

Yield: 42.1% of theory.

C: Calc .: 46.19, found 45,9 H: Calc .: 5.86, found 5.7 Cl: Calc .: 24.06, found 24.4 Cl ·: Calc .: 16.04, found 16.3 N: Calculated: 19.01, found 19,1 A: Calc .: 4.89, found 4.9

2-methyl-4-chloro-5 - ((6- (4- (2-methoxyphenyl) piperazinyl-1) hexyl) amino) -3 (2H) -pyridazinone

Salt: 2.0 HC1; solvate: 1.5 H2O

M.p .: 160-175 ° C; recrystallized: ethanol

Yield: 38.0% of theory,

C: Calc .: 49.4, found: 50.3 H: Calc .: 49.4, found .. 6.8 Cl: Calc .: 19.88, found: 19.4 Cl ': Calc .: 13.25, found: 13.1 N: Calc .: 13.09, found: 13.2 A: Calc .: 10.47, found: 10.3

UV: solvens: ethanol,

212 (4.46), 216 (S, 4.45), 234 (4.50), 286 (3.96), 304 (S, 3.87)

EXAMPLE 8

2-methyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

3.0 g (0.00794 mol) of 4-chloro-2-methyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone are dissolved in 10 ml of absolute ethanol, 1.38 g (0.01 mol) of potassium carbonate and 0.3 g of Pd / C (10%) are added and hydrogenated at room temperature until hydrogen precipitation is stopped. After filtration of the catalyst and inorganic material, the mixture was evaporated in vacuo to give 2.5 g of 2-methyl-5 - ((2- (4- (2methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone (91.7 %), as a colorless, crystalline residue, which is dissolved in hot isopropanol and ether hydrochloric acid is added. 2.0 g (66.3% of theory) of hydrochloride are obtained from m.p. 237-245 ° C; C 55.6%, H 7.0%, Cl (whole) 9.3,%, C1 '9.3%, N 18.3%, O 9.8%.

EXAMPLE 9

4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) pyridazinone

1.66 g (0.00312 mol) of 6-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) pyridazinone is hydrated in 100 ml of ethanol with 0.0046 mol of NaOH and 100 mg of 10% palladium on charcoal at 60 ° C for 1 hour until hydrogen uptake is stopped; is filtered off from the catalyst, evaporated and extracted with hot absolute alcohol, which is then acidified with alcoholic hydrochloric acid. 1.28 g of 2-methyl-4 - ((2- (4- (2methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone (81.5% of theory) are obtained as a colorless crystalline hydrochloride. from the ground. 235-244 ° C (decomposition); C 40.3%, H 6.4%, Cl 24.3%, N 13.9%, O 15.0%.

In an analogous way, we prepare:

4 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone salt: 1.0 HBr;

M.p .: 253-260 ° C, recrystallized: ethanol

Yield: 73.3% of theory.

C: Calc .: 48.49, found: 48.5 H: Calculated: 5.60, found: 5.8 N: Calculated: 5.60, found: 17.5 A: Calc .: 8.07, found: 8.4 Nr: Calculated: 20.16, found: 20.1

2-methyl-4 - ((2- (4-phenylpiperazinyl-1) ethyl) amino) -3 (2H) pyridazinone salt: 3.2 HCl; solvate: 2.6 H ₂ O Melting point: 225 - 230 ° C, recrystallized: ethanol Yield: 59.7% of theory.

C: Calc .: 42.81, found: 43.1 H: Calc .: 6.64, found: 5.7 Cl ·; Calc .: 23.79, found: 24.0 N: Calc .: 14.68, found: 14.9 A: Calculated: 12.08, found: 12.3

UV: solvens: ethanol.,

206 (4.33), 252 (4.08), 298 (4.16), 310 (S, 3.97)

2-methyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.0HCl;

M.p .: 130-139 ° C, recrystallized: ethanol

Yield: 66% of theory,

C: Calc .: 51.93, found: 51.7 H: Calc .: 6.54, found: 6.6 Cl ': Calculated: 17.03, found: 17.1 N: Calc .: 16.82, found: 16.7 A: Calculation: 7.69, found: 7.9

UV: solvens: INHC1,

200 (3.81), 204 (3.88), 220 (4.14), 282 (S, 4.05), 296 (4.12)

2-methyl-4- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 1 fumarate; solvate: 0.33 H ₂ O

M.p .: 140-144 ° C, conversion: ethanol, diethyl ether

Yield: 46.3% of theory. C: Calc .: 58.41, found: 58.3 H Calc .: 6.86, found: 7.0 N: Calc .: 14.19, found: 14.1 A: Calc .: 20.53, found .. 20.5

2-methyl-4 - ((2- (4- (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.0HCl;

M.p .: 235 ° C (sbl), crystalline: ethanol

Yield: 49.4% of theory.

C: Calc .: 52.58, found: 52.2 H: Calc .: 6.83, found: 7.2 Cl ·: Calc .: 16.34, found: 16.6 N: Calc .: 16.14, found: 16.0 A: Calc .: 8.11, found: 8.0

UV: solvens: O, 1NHC1

214 (4.57), 224 (S, 4.55), 282 (4, o3)

2-methyl-4 - ((2- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.25 fumarate; solvate: 2 H ₂ O mp: 161 -164 ° C, crystalline: acetone yield: 70.1% of theory.

C: Calc .: 53.52, found: 53.7 H: Calc .: 6.74, found: 6.5 N: Calculated: 13.00, found: 13.0 A: Calc .: 26.73, found: 26.8

UV: solvens: 0.1 N HC1

206 (4.35), 210 (4.34), 290 (4.15)

2-methyl-4 - ((6- (4- (2-methoxyphenyl) piperazinyl) hexyl) amino) -3 (2H) -pyridazinone

Salt: 3.0 HC1;

M.p .: 225 - 228 ° C, conversion: ethanol, diethyl ether

Yield: 32.3% of theory.

C: Calculation: 47.75, found: 47.8 H: Calc .: 6.23, found: 6.2 Cl ': Calc .: 23.49, found: 23.1 N: Calc .: 14.47, found: 15.5 A: Calc .: 7.07, found: 7.4

2-methyl-4 - ((2- (4- (2-ethoxyphenyl) piperazinyl-1) ethyl) amino) 3 (2H) -pyridazinone Salt: 2.0 HCl;

M.p .: 196 - 204 ° C,

Yield: 66.4% of theory.

C: Calc .: 53.03, found: 52.5 H: Calc .: 6.79, found: 6.9 Cl ·: Calc .: 16.48, found: 16.3 N: Calc .: 16.27, found: 16.2 A: Calc .: 7.45, found: 8.0

UV: solvens: 0.1 N HC1,

208 (4.28), 227 (S, 4.02), 288 (4.05)

2-methyl-4 ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.25 HBr; solvate: 3.2 H ₂ O M.p .: 188 -196 ° C,

Yield: 32.3% of theory.

C: Calc .: 35.88, found: 36.1 H: Calc .: 5.61, found: 5.1 N: Calc .: 12.31, found: 12.3 A: Calc .: 14.62, found: 14.6 Br ': Calc .: 31.59, found: 31.9

UV: solvens: 1N HC1,

206 (4.46), 225 (S, 4.11), 288 (4.15), 304 (S, 4.01)

2-methyl-4 - ((2- (4- (2,6-dimethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.0 HC1; solvate: 0.6 H ₂ O

M.p .: 235-240 ° C, recrystallized: ethanol

Yield: 47.7% eoret. C: Calc .: 53.67, found: 53.7 H: Calc .: 7.16, found: 7.3 Cl ': Calc .: 16.69, found: 16.4 N: Calc .: 16.47, found: 16.5 A: Calc .: 6.02, found: 6.01

2-methyl-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino-3 (2H) -pyridazinone

Salt: 2.2 HCl; solvate: 3.4 H ₂ O

Mp .: 124-133 ° C, recrystallized: ethanol

Yield: 59.8% of theory.

C: calc .: 41.35, found: 41.8

H: Calc .: 5.97, found: 5.9 Cl ': Calc .: 14.92, found: 15.5 N: Calculated: 13.40, found: 13.4 A: Calc .: 13.46, found: 14.0 F: Calc .: 10.90, found: 10.4

UV: solvens: ethanol,

204 (4.4), 258 (4.20), 300 (4.20), 312 (S, 4.05)

2-methyl-4 - ((2- (4- (2-chlorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazone Salt: 1.2 HCl;

M.p .: 240 - 248 ° C,

Yield: 95.5% of theory.

C: Calc .: 54.43, found 54,4 H: Calc .: 6.23, found 6.4 Cl: Calc .: 11.34, found ll, o N: Calc .: 18.67, found 18.5 A: Calc .: 4.27, found 4.4 F: Calculated: 5.06, found 5.1

2-methyl-4 - ((2- (4- (4-fluorophenyl) piperazinyl-1) ethyl) amino) 3 (2H) -pyridazinone Sol .: 2.6 HCl; consultant: 2.6 H2O Melting point: 236 - 240 ° C, recrystallized: ethanol Yield: 81.7% of theory.

C: Calc .: 43.17, found: 43.6 H: Calc .: 6.35, found: 5.7 Cl ': Calc .: 19.49, found: 19.9 N: Calc .: 14.81, found: 15.1 A: Calc .: 12.18, found: 12.3 F: Calc .: 4.02, found: 3.4

UV: solvens: ethanol,

206 (4.28), 234 (4.03), 244 (4.03), 300 (4.18), 312 (S, 4.06)

2-t-butyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.0 HBr; solvate: 0.1 H ₂ O

M.p .: 238-242 ° C, recrystallized: ethanol

Yield: 86.5% of theory.

C: Calc .: 45.93, found: 46.1 H: Calc .: 6.09, found: 6.2 N: Calc .: 12.75, found: 12.5 A: Calc .: 6.12, found: 6.4 Br ': Calc .: 29.47, found: 28.8

UV: solvens: 0.1 N HC1

206 (4.51), 225 (S, 4.24), 290 (4.20), 312 (S, 3.76)

2-t-butyl-4 - ((2- (4- (3-trifluoromethyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl;

Tal .: 194 -198 ° C; cross. ethanol Yield: 48.8% of theory. C: Calc .: 50.81, found 50.9 H: Calc .: 6.09, found 6.2 Cl ': Calc .: 14.28, found 14.2 N: calcd: 14.11 found 14.2 A: Calc .: 3.22, found 3.2 F: Calc .: 11.48, found 11.4

UV: solvens: ethanol,

206 (3.79), 260 (4.13), 298 (4.10)

2- (2-dimethylaminoethyl) -4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Salt: 3.0 HBr; solvate: 1.5 I ^ O

M.p .: 231-237 ° C, conversion: ethanol, diethyl ether

Yield: 41.7% of theory. (crude), 34.8% of theory. (clean)

C: Calc .: 37.63, found: 37.8 H: Calc .: 5.71, found: 5.6 N: Calc .: 12.54, found: 12.4 A: Calc .: 8.35, found: 8.4 Br ': Calc .: 35.76, found: 35.8

UV: solvens: 0.1 N HC1

208 (4.43), 229 (S, 4.17), 285 (S, 4.26), 296 (4.28), 312 (S, 4.12)

2-hydroxyethyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 3.15 HCl; solvate: 3.4 H ₂ O Melting point: 181 -190 ° C, recrystallization: ethanol,

Yield: 34% theory.

C: calc .: 41.53, found:41.6

H: calc .: 6.78, found: 6.5

Cl ': calcd. : 20,32, found : 20,4

N: Calc .: 12.74 Found 12.8

A: calc. : 18.63, found: 18.7

UV: Solvens: Ethanol 210 (4.44), 300 (4.15), 312 (S, 3.95)

2- (2-hydroxyethyl) -4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1-) ethyl) amino) -3 (2H) -pyridine zinone

Salt: 2.4 HCl; solvate: 1.35 H ₂ O

M.p .: 121 -129 ° C; recrystallization: acetone

Yield: 84.1% of theory.

C: Calc .: 43.61, found.44 H: Calc .: 5.41, found: 5.3 Cl ': Calc .: 16.26, found : 16,3 N: Calc .: 13.38, found: 13.6 A: calcd. : 10,24, found : 10,4 F: Calc .: 10.90, found: 10.4

UV: solvens: ethanol

206 (4.34), 211 (S, 4.27), 260 (4.21), 300 (4.21), 312 (S, 4.06)

2-methyl-4 - ((2- (4- (pyridyl-2) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.4 HCl; solvate: 0.65 H ₂ O Melting point: 235 - 237 ° C, recrystallization: ethanol Yield: 89% of theory.

C: Calc .: 46.67, found.46,7 H: Calc .: 6.29, found: 6.2 Cl ': calcd. : 20,66, found 20:20 N: Calc .: 20.41, found : 20,1 A: Calc .: 6.41, found: 6,4

UV: solvens: ethanol

204 (4.10), 252 (4.26), 300 (4.26)

4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solv. 0.1 H ₂ O M.p .: 245 - 256 ° C,

Yield: 81.9% of theory.

C: calcd. : 51,61, found.51,4 H: Calc .: 6.55, found: 6.6 Cl ': calcd. : 17,10, found : 17,1 N: Calc .: 16.72, found: 16.7 A: Calc .: 8.02, found: 8.0

4 - ((3- (4- (2-ethoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) pyridazinone Salt: 2.1 HCl;

M.p .: 258-269 ° C Yield: 20.3% of theory.

C: Calc .: 50.99, 50,9 H: Calc .: 6.89, found: 6.7 Cl ·: calcd. : 16,64, found: 17.0 N: Calc .: 15.65, found : 15.7 A: Calc .: 9.83, found: 9.9

2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino-3 (2H) -pyridazinone Salt: 2.85 HCl; : ethanol. Gain: 86.2% of theory.

C: Calc .: 47.87, found.47,5 H: Calc .: 6.67, found: 6.8 Cl ': Calc .: 21.20, found.:21,l N: Calc .: 14.69, found: 14.7 A: Calc .: 9.57, found: 9.8

2-methyl-4 - ((3- (4- (2-hydroxy-4-methylphenyl) piperazinyl-1) -propyl) amino) -3 (2H) -pyridazine

Salt: 1.0 fumarate;

M.p .: 176-180 ° C, recrystallization: ethanol

Yield: 21.9% of theory.

C: Calc .: 57.25, found 57.7

H: calc .: 6.48, found: 6.8

N: calc .: 14.51, found 14.2

A: Calc .: 21.55, found:21.0

2-methyl-4 - ((3- (4- (2-ethoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 2.8 HCl; solvate: 1.75 H ₂ O M.p .: 202-205 ° C,

Yield: 97.3% of theory.

C: Calc .: 48.59, found.48.5

H: Calc .: 7.24, Found: 7.1

Cl ·: Calc .: 19.12, Found: 19.4

N: calc. : 13.49, found.13.5

A: calc. found

UV: solvens. 0.1 N HCl

206 (4.35), 296 (4.15), 312 (S, 3.92)

2-methyl-4 - ((3- (4- (2-fluorophenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazone

Salt: 1.1 HC1;

M.p .: 232 - 238 ° C Yield: 97.2% of theory.

C: calcd. : 56.08, found 56.1 H: Calc .: 6.56, found 6,7 Cf: Calc .: 10.12, found 10.2 N: Calc .: 18.17, found 18,1 A: Calc .: 4.15, found 4.2 F: Calculated: 4.93, found 4.7

2-methyl-4 - ((3- (4- (4-fluorophenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.45 H ₂ O Melting point: 210 - 212 ° C, recrystalline: ethanol Yield: 84.4% of theory.

C: calc .: 50.70, found: 50.9

H: Calc .: 6.36, Found: 6.4

Cl: Calc .: 16.63, found: 16.9 Cl ': Calc .: 16.63, found: 16.9 N: Calc .: 16.42, found: 16.9 A: Calc .: 5.44, found: 5.6 F: Calculated: 4.46, found: 4.3

2-methyl-4 - ((3- (4-pyridyl-2) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.6 H ₂ O

Melting point: 214 - 219 ° C, recrystallization: ethanol Yield: 97.1% of theory. C: Calc .: 49.54, found 50,1 H: Calc .: 6.65, found 7.0 Cl: Calc .: 17.2, found 16.6 Cl ': Calc .: 17.2, found 16.6 N: Calc .: 20.39, found 19,9 A: Calc .: 6.21, found 6.4

4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Salt: 3.0 HCl; solvate: 0.38 H ₂ O M.p .: 170-182 ° C,

Yield: 79.6% of theory.

C: Calc .: 48.21, found 48,2 H: Calc .: 6.54, found 6.4 Cl: Calc .: 22.39, found 22.3 Cl ·: Calculated: 22.39 found 22.3 N: Calc .: 14.79, found 14.7 A: Calc .: 8.04, found 8.0

2-methyl-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; solvate: 0.25 H ₂ O Melting point: 193 - 202 ° C, recrystallization: ethanol

Yield: 76.7% of theory. C: Calc .: 53.51, found: 53.2 H: Calc .: 7.07, found: 7.3 Cl: Calculated: 15.80, found: 15.8

Cl: N: A: Calc .: 15.80, Calc .: 15.60, Calc .: 8.02, Found: 15.8 Found: 15.3 Found: 7.8 5 - ((2- (4- (3-trifluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 3.0 HC1; solvate: 0.3 H ₂ O Tal .: 197 - 205 ° C, clear .: acetone Yield: 66.9% of theory. C: Calc .: 42.35, found: 42.7 H: Calculated: 4.93, found: 4.9 Cl: Calc .: 22.06, found: 21.5 Cl: Calc .: 22.06, found: 21.5 N: Calc .: 14.53, found: 14.8 A: Calc .: 4.31, found: 4.5 F: Calculated: 11.82, found: 11.6 2-methyl-5 - ((2- (4-phenylpiperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 3.25 HCl; Solvate: 1.15 H ₂ O Melting point: 251-256 ° C, recrystall. ethanol Yield: 76.2% of theory. C: Calc .: 45.11, found: 44.9 H: Calc .: 6.36, found: 5.8 Cl: Calc .: 25.46, found: 25.9 Cl ': Calc .: 25.46, found: 25.9 N: Calc .: 15.47, found: 15.7 A: Calc .: 7.60, found: 7.7

UV: solvens: ethanol,

204 (S, 4.59), 208 (4.62), 230 (4.66), 252 (S, 4.23), 284 (4.23)

2-methyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.0 HCl; solvate: 0.4 H ₂ O m.p. : 237-245 ° C,

Yield: 91.7% of theory.

C: calc .: 55.85, found: 55.6

H: calc .: 6.98, found: 7

Cl: Calcd .: 9.16 found: 9.3 Cl ': Calcd .: 9.16 found: 9.3 N: Calc .: 18.09, found: 18.3 A: Calc .: 9.92, found: 9.8

2-methyl-5 - ((2- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.5 fumarate; solvate: 0.5 H ₂ O Melting point: 176-178 ° C, recrystalline: acetone Yield: 84.1% of theory.

C: Calc .: 55.55, found: 55.6 H: Calc .: 6.34, found: 6.5 N: Calculated: 12.96, found: 12.8 A: Calc .: 25.16, found: 25.1 UV: solvens: 0.1 N HC1,

198 (4.34), 212 (4.53), 224 (4.53), 280 (4.01)

2-methyl-5 - ((2- (4- (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.0 fumarate;

M.p .: 183-185 ° C, recrystallized: acetone

Yield: 76.8% of theory.

C: calc .: 58.34, found: 58.0

H: calc .: 6.60, found: 6.8

N: calc .: 14.79, found: 14.7

A: Calc .: 20.27, Found: 20.5

UV: solvens: 0.1 N HC1,

210 (4.5), 288 (4.02), 304 (S, 3.83)

2-methyl-5- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 3.0 HC1; solvate: 3.0 H2O

M.p .: 125-130 ° C, conversion: isopropanol, diethyl ether

Yield: 62.3% of theory.

C: Calc .: 44.91, found: 19.6 H: Calc .: 7.16, found: 6.8 Cl: Calc .: 19.88, found: 1 9 , 6 Cl ': calcd. : 19,88, found: 19.7

N: calc .: 13.09 found: 13.1

A: Calc .: 14.96, Found: 15.7

2-methyl-5 - ((2- (4- (2-ethoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.0 fumarate: solvate: 0.6 H ₂ O m.p. : 175- 178 ° C,

Yield: 64.8% of theory.

C: Calc .: 57.04, found: 56.8 H: Calc .: 6.70, found: 6.7 Cl: calcd. : 14,46, found: 14.5 N: calcd. : 14,46, found: 14.5 A: Calc .: 21.80, found: 22.0

UV: solvens: INHCI,

208 (4.51), 224 (4.51), 276 (4.02)

2-methyl-5 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3- (2H) -pyridazinone Salt: 3.15 HBr; solvate: 1.3 i ^ O

M.p .: 190-198 ° C, recycle .: Yield: 44.2% of theory. ethanol C: Calculated: 33.60, found: 33.7 H: Calc .: 4.77, found: 4.8 N: Calc .: 11.52, found: 11.5 A: Calc .: 8.69, found: 8.7 Br ': 3.15, calcd .: 41.42, found: 41.3

UV: solvens: IN HCI, 210 (4.63), 224 (4.53), 280 (4.03)

2-methyl-4 - ((2- (4- (2-methylphenyl) piperazinyl-1) ethyl) amino) 3 (2H) -pyridazinone Salt: 1.5 fumarate:

M.p .: 178-182 ° C, recrystallization: ethanol

Yield: 93% of theory.

C: Calc .: 57.48, found: 57.8 H: calculated: 6 „23, found: 6.2 N: Calculated: 13.96, found: 13.9 A: Calc .: 22.33, found: 22.4

2-methyl-5 - ((2- (4- (2,6-dimethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.0 HC1; solvate: 2.1 H ₂ O Melting point: 260 ° C, (sbl), recrystallization: ethanol

Yield: 73.7% of theory.

C: Calc .: 50.46, found: 51 H: Calc .: 7.40, found: 7.4 C1-: Calc .: 15.68, found: 15.2 N: Calc .: 15.49, found: 15.1 A: Calc .: 10.97, found: 11.3

UV: solvens. ethanol,

206 (4.26), 214 (4.35), 224 (4.38), 232 (4.38), 280 (3.88)

2-methyl-4 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.5 fumarate;

M.p .: 267-169 ° C, recrystall. Yield: 92% of theory. ethanol C: Calc .: 54.65, found: 54.5 H: Calc .: 5.58, found: 5.8 N: Calculated: 13.85, found: 13.9 A: Calc .: 22.16, found: 22.4 F: Calc .: 3.76, found: 3.3

2-methyl-5 - ((2- (4- (4-fluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 3.0HCl; solvate: 0.7 H ₂ O Melting point: 162-168 ° C, recrystalline: ethanol Yield: 73.5% of theory.

C: Calc .: 45.05, found: 45.5 H: Calc .: 5.87, found: 5.7 Cl ': Calc .: 23.46, found 22.9 N: Calc .: 15.45, found: 15.6 A: Calc .: 6.00, found: 6.3 F: Calc .: 4.19, found: 4.0

UV: solvens: ethanol,

208 (4.40), 218 (4.39), 230 (4.50), 286 (3.94)

2-methyl-5 - ((2- (4- (pyridyl-2) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 3.0 HCl; solvate: 0.5 H ₂ O

M.p .: 260 ° C, (sbl), recrystallized: ethanol

Yield: 80.9% of theory.

C: Calc .: 44.40, found: 44.4 H: Calc .: 6.06, found: 6.1 Cl: Calc .: 24.58, found: 24.4 N: Calc .: 19.42, found: 19.5 A: Calculated: 5.55, found: 5.6

2-t-Butyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.5 fumarate:

M.p .: 173-177 ° C,

Yield: 79.2% of theory.

C: Calc .: 57.95, found: 57.6 H: Calc .: 6.66, found: 6.7 N: Calc .: 12.51, found: 12.4 A: Calc .: 22.87, found: 23.3

UV: solvens: 0.1 N HC1,

210 (4.48), 226 (4.50), 276 (4.05)

2-t-butyl-5 - ((2- (4- (3-trifluoromethyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 3.0HCl; solvate: 0.2511.0

Mp: 228-230 ° C; recrystallization: acetone Yield: 77.2% of theory. C: Calc .: 46.94, found: 47.0 H: Calc .: 5.91, found: 5.9 Cl ·: Calc .: 19.79, found: 19.7 N: Calculated: 13.03, found: 13.2 A: Calculated: 3.72, found: 3.8 F: Calc .: 10.61, found: 10.4

UV: solvens: ethanol

210 (S, 4.43), 222 (S, 4.50), 230 (4.53), 258 (4.23), 278 (S, 4.05)

2- (2-dimethylaminoethyl) -5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Salt: 2, 1 HBr; solvate: 0.1 H ₂ O

Mp: 236-246 ° C; recrystallization: isopropanol Yield: 42.4% of theory.

C: Calc .: 44.08, found: 44.1 H: Calc .: 6.04, found: 6.4 N: Calc .: 14.69, found: 14.5 A: Calc .: 5.87, found: 5.9 Br-: 2.1 Calc .: 29.32 Found: 29.1

2-hydroxyethyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 3.0 HCl; solvate: 0.6 H ₂ O

M.p .: 190-200 ° C; recrystallization: ethanol Yield: 70.2% of theory. C: Calc .: 46.23, found: 46.4 H: Calc .: 6.37, found: 6.2 Cl: Calc .: 21.55, found: 21.2 N: Calc .: 14.19, found: 14.0 A: Calc .: 11.67, found: 11.5

2- (2-hydroxyethyl) -5 - ((2- (4- (3-trifluoromethyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 2.15HCl; solvate: 1.05 H ₂ O

Mp: 190-194 ° C; recrystallization: acetone Yield: 88.2% of theory. C: Calc .: 44.86, found: 44.9 H: Calculated: 5.60, found: 5.3 Cl ·: Calc .: 14.98, found: 15.3 N: Calculated: 13.77, found: 14.0 A: Calc .: 9.59, found: 9.8 F: Calc .: 11.20, found: 10.7

UV: solvens: ethanol, 212 (4.33), 218 (4.31), 232 (4.35), 258 (4.14), 294 (3.91)

2-Phenyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.0 HBr; solvate: 0.1 H ₂ O M.p .: 272-276 ° C ,;

Yield: 85.4% of theory.

C: calc .: 56.58, found: 56.8

H: calc .: 5.82, found: 5.9

N: Calc .: 14.34, found: 14.3 A: Calc .: 6.88, found: 7.3 Br ': Calc .: 16.37, found: 16.4

2-methyl-5 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino-3 (2H) -pyridazinone Salt: 3.0 HC1; solvate: 1.45 H ₂ O

M.p .: 241-248 ° C; conversion: ethanol, acetone Yield: 61.7% of theory. C: Calc .: 46.29, found: 46.1 H: Calc .: 6.52, found: 6.8 Cl ·: Calc .: 21.58, found: 21.6 N: Calc .: 14.21, found: 14.3 A: Calc .: 11.20, found: 11.2

UV: solvens: ethanol,

212 (4.56), 218 (S, 4.51), 230 (4.51), 284 (4.01) 1-methyl-5 - ((3- (4- (2-ethoxy-4-methylphenyl) ) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 3.25HCl; solvate: 3.1 H ₂ O M.p .: 218-227 ° C;

Yield: 65.4% of theory.

C: Calc .: 45.05, found: 44.9 H: Calc .: 7.28, found: 7.1 Cl ': Calc .: 20.58, found: 20.6 N: Calc .: 12.51, found: 12.6 A: Calc .: 14.57, found: 14.8

UV: solvens: 0.1 N HC1.212 (4.49), 228 (4.46), 280 (3.98)

2-methyl-4 - ((3- (4- (2-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 1.0 fumarate:

Mp 194-197 ° C; recrystallization: ethanol

Yield: 94.6% of theory.

C: Calc .: 60.38, found: 60.4 H: Calc .: 6.83, found: 7.0 N: Calc .: 15.31, found: 15.1 A: Calc .: 17.49, found: 17.2

2-methyl-5 - ((3- (4- (4-fluorophenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 3.0 HCl; solvate: 0.9 H ₂ O M.p .: 176-181 ° C ,; recrystallization: ethanol Yield: 76.8% of theory.

C: Calc .: 45.90, found: 46.1 H: Calc .: 5.97, found: 6.3 Cl ': Calc .: 22.58, found: 22.4 N: Calc .: 14.87, found: 15.1 A: Calc .: 6.03, found: 6.6 F: Calculated: 4.03, found: 3.5

2-methyl-5 - ((3- (4- (pyridyl-2) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Salt: 3.0HCl;

Mp: 232-239 ° C; recrystallization: ethanol

Yield: 70.6% of theory.

C: Calc .: 46.64, found: 46.8 H: Calc .: 6.22, found: 6.3 Cl: Calc .: 24.29, found: 23.9 Cl- ': Calc .: 24.29, found: 23.9 N: Calculated: 19.20, found: 19.4 A: Calculated: 3.65, found: 3.6

2-methyl-5 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Salt: 3.0HCl; solvate: 1.0 H2O M.p .: 168-176 ° C ,; recrystallization: ethanol Yield: 66.8% of theory.

C: Calc .: 48.15, found: 47.6 H: Calc .: 6.87, found: 6.8 Cl- ': Calc .: 21.32, found: 21.3 N: Calc .: 14.04, found: 14.0 A: Calc .: 9.62, found: 9.4

2-methyl-5 - ((6- (4- (2-methoxyphenyl) piperazinyl) hexyl) amino) -3 (2H) -pyridazinone Salt: 3.0 HCl; solvate: 0.15 H ₂ O

M.p .: 174 - 185 ° C, conversion: ethanol, diethyl ether Yield: 79.2% of theory.

EXAMPLE 10

5-methoxy-2-methyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

4.2 g (0.011 mol) of 5-chloro-2-methyl-4 - ((2- (4- (2-methoxyphenyl) -piperazinyl-1) ethyl) amino) 3 (2H) -pyridazinone was refluxed for 50 hours in methanol in which 0.010 moles of sodium methylate is dissolved and then evaporated in vacuo. The residue was taken up in water, precipitating 1.6 g of 5.methoxy-2-methyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl) ethyl) amino) -3 (2H) -pyridazinone (38 , 9% of theory). It is filtered off with suction, dried, dissolved in acetone and converted with the addition of fumaric acid at a reflux temperature of 1.50 g (24.5% of theory) of the fumarate salt, m.p. 144-148 ° C C 54.0%, H 6.1%, N 12.5%, O 27.4%; UV v 0.1 N HCl: 208 (4.42), 226 (s, 4.22), 300 (4.47).

EXAMPLE 11

5-chloro-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

4.25 g (0.0093 mol) of 2-t-butyl-5-chloro-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone are stirred with 50 ml conc. of aqueous hydrochloric acid at room temperature for 72 hours, basified and extracted 3 times with chloroform, evaporated the organic phase, dried with sodium sulfate and triturated with acetone. The crystalline precipitate of 5-chloro-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone was 2.40 g (47.7% of theory). By dissolving in 100 ml of hot abs. alcohol and the addition of ether hydrochloric acid were converted to 2.20 g (46.7% of theory) of the dihydrochloride from the soil. 220-223 ° C;

C 40.6%, H 4.2%, Cl (whole) 21.1%, Cl-14.2%, F 11.5%, N 13.9%, O 8.7% UV v 0.1 N HC1; 208 (4.42), 226 (S, 4.22) 300 (4.47).

The following substance is prepared in an analogous manner:

4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.5 fumarate; solvent: 2.0 H ₂ O Melting point: 211 - 213 ° C, crystalline: ethanol Yield: 58.5% of theory.

C: calc .: 48.13, found: 48.3

Η: Calc .: 5.62, Found: 5.4

Cl: Calc .: 6.18, Found: 5.6

N: calc .: 12.20, found: 12.4

A: calc .: 27.87, found: 28.3

UV: solvent: O, 1N HC1,

210 (438), 228 (4.42), 280 (3.81), 304 (3.72)

EXAMPLE 12

2-methyl-6-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

6.0 g (0.0159 moles of finely cured 6-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino-3 (2H) -pyridazinone were suspended in 100 ml of 2N NaOH and at 60 DEG C., stirred for 2 hours with 1.51 ml of dimethylsulfate (0.0159 mol) and then cooled, extracted several times with chloroform, dried the organic phase and evaporated 3.50 g (56.2% of theory) crystallized from the oily residue overnight .) impure 2-methyl-6-chloro-4 - ((3- (4- (2methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone, which was purified by preparative chromatography on silica gel (Waters Prep Pak The pure fraction was dissolved in isopropanol and ether hydrochloric acid was added and 0.85 g (11.2% of theory) of white, crystalline dihydrochloride, mp 218-229 ° C; C 40.6%, H 4.2. %, Cl (whole) 21.1%, Cl-14.2%, F 11.5%, N 13.9%, O 8.7%.

EXAMPLE 13

6-chloro-2-ethyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

1.80 g (0.00474 mol) of finely ground 6-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl) propyl) amino-3 (2H) -pyridazinone was suspended in 80 ml of 2N NaOH, added 1.8 ml (0.014 mol) of ethyl iodide and stirred for 90 minutes at room temperature; then 1.8 ml of ethyliodide was added again and stirred for a further 2 hours. The solvent was evaporated, taken up in water and extracted with chloroform. an oil which, when dissolved in ethanol and the addition of ethanol hydrochloric acid, gives 0.70 g (30.6% of theory) of pure dihydrochloride 6-chloro-2-ethyl-4 - ((3- (4- (2methoxyphenyl) piperazinyl- l) propylamino) -3 (2H) -pyridazinone, mp 202-207 ° C; as a white crystalline substance; C 49.4%, H 6.4%, Cl (cel) 21.8%, Cl- 14.6%, N 14.3%, O 7.7%.

EXAMPLE 14

6-chloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone

4.00 g (0.00985 mol) of 6-chloro-3-methoxy-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -pyridazine was dissolved in 40 ml of ice and 40 was added. ml of 63% HBr. Boil for 2 hours at reflux, add 200 ml of water, neutralize with 30% KOH at pH 6 and suction off the precipitated matter and rinse well with water. 3.85 g (99.7% of theory) of 6-chloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone are obtained, purified by recrystallization from ethanol with the addition of charcoal, ethanolic hydrochloric acid was added immediately to the solution and that 3.26 g (68.7% of theory) of pure dihydrochloride, m.p. 247252 ° C; C 47.2%, H 6.0%, Cl (whole) 21.9%, Cl-14.6%, N 14.4%, O 10.0%.

The starting compounds necessary for carrying out the said example are prepared as follows:

6-chloro-3-methoxy-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) aminopyridazine

3.28 g (0.008 mol) of 3,6-dichloro-4 - ((4- (4- (2-methoxyphenyl) -1-piperazinyl) butyl) amino) pyridazine and 0.32 g (0.008 mol) of sodium methylate are stirred in 150 ml of methanol for 144 hours at 50 ° C. It is then evaporated in vacuo, dissolved in chloroform and shaken off with water. The solvent was evaporated, dissolved in ether, clearly filtered and precipitated with ether HCl hydrochloride 6-chloro-3-methoxy-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) pyridazine, 3.14 Eq. HCl) m.p .: 139-150 ° C, yield: 91.1% of theory.

3,6-Dichloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) pyridazine

9.25 g (0.050 mol) of 3,4,6-trichloropyridazine are stirred for 96 hours at room temperature with 6.90 g (0.050 mol) of anhydrous powdered potassium carbonate and 13.15 g (0.050 mol) of 1- (4-aminobutyl) -4- (2-Methoxyphenyl) piperazine in 1350 ml of dry acetonitrile. It is then sucked off and the filtrate is concentrated in vacuo. The residue was taken up in ethanol and precipitated with ether HCl trihydrochloride 3,6-dichloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl) butyl) amino) pyridazine m.p .: 155-170 ° C; gain: 54.2 Theory.

The following compounds are prepared in an analogous manner:

6-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Salt: 2.1 HC1; Solvate: 1.16 H ₂ O

Tal. 241-247 ° C;

Yield: 86.8% of theory.

C: calc. 44.26, found 44,6

H: calc. 5.77, found 5,3

Cl: calc. 23.82, found 23,7

Cl -: Calc. 16.1

N: calc. 15.18, found 15.1

A: calc. : 10,96, found. 10.9

2-methyl-6-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) -amino) 3 (2H) -pyridazinone Salt: 2.0 HCl; Solvate: 0.05 H ₂ O M.p .: 232 - 237 ° C Yield: 63.0% of theory.

C: calc. 47.79, found: 47.8 H: calc. 5.82, found: 5.8 Cl: Calc .: 23.67, Found: 23.5 Cl-: Calc .: 15.83, Found: 15.8 N: Calc .: 15.48, found: 15.4 O: calculated: 7.24, found: 7.2

6-chloro-4 - ((2- (4- (2-iso-propoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Salt: 1.0 HBr; Solvate: 0.3 F ^ O Melting point: 280 - 295 ° C, recrystalline: ethanol Yield: 12.7% of theory.

C: Calc .: 47.72, found: 48.1 H: Calc .: 5.82, found: 6.0 Cl: Calc .: 7.41, found: 6.6 N: Calc .: 14.64, found: 14.6 A: Calc .: 7.70, found: 8.0

Calcd .: 16.71 Found: 16.7

UV: solvent: 1NHC1,

210 (4.48), 234 (S, 4.08), 246 (S, 3.94), 288 (4.13), 309 (S, 3.82)

6-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HCl; Solvate: 0.35 H ₂ O M.p .: 267 - 275 ° C;

Yield: 88.1% of theory.

C: Calc .: 47.3, found: 47.2 H: Calc .: 5.89, found: 5.8 Cl: Calc .: 23.27, found: 23.1 C1-: Calc .: 15.51, found: 15.5 N: Calc .: 15.32, found: 15.3 A: Calc .: 8.23, found: 8.2

6-chloro-4 - ((3- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) propyl) amino-3 (2H) -pyridazinone Salt: 2.0 HBr; Solvate: 3.5 H ₂ Oh

Mp .: 191-195 ° C, recrystallized: ethanol Yield: 81.3 Theories. C: Calc .: 37.08, found: 37.3 H: Calc .: 5.72, found: 5.2 Cl: Calculation: 5.75, found: 5.5 N: Calc .: 11.35, found: 11.4 A: Calc .: 14.27, found: 14.7 Br-: Calc .: 25.91, found: 25.9

UV: solvent: O, 1N HC1,

206 (4.6), 226 (S, 4.19), 288 (4.28), 09 (S, 4.03)

2-Methyl-6-chloro- (3- (4- (4- (2-ethoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Salt: 2.0 HC1

M.p .: 211 - 215 ° C; Yield: 7.9% of theory. C: Calc .: 50.17, found: 50.3 H: Calc .: 6.32, found: 6.4 Cl: Calc .: 22.21, found: 21.9 C1-: Calc .: 14.81, found: 14.6

N: calc .: 14.63,

A: Calc .: 6.68, Found: 14.5 Found: 7.1

6-chloro-2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino-3 (2H) -pyridazinone

Salt: 2.0HCl

M.p .: 218 - 229 ° C

Yield: 14.5% of theory.

C: Calc .: 47.62, found: 47.1 H: Calc .: 6.23, found: 6.0 Cl: Calc .: 22.19, found: 22.7 C1-: Calc .: 14.80, found: 15.0 N: Calc .: 14.61, found: 14.7 A: Calc .: 9.35, found: 9.5

6-chloro-2-ethyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1-yl) amino) -3 (2H) -pyridazone Salt: 2.0 HCl; Solvate: 0.35 H ₂ O M.p .: 202 - 207 ° C Yield: 30.6% of theory.

C: Calc .: 49.51, found: 49.4 H: Calc .: 6.38, found: 6.4 Cl: Calc .: 21.92, found: 21.8 C1-: Calc .: 14.62, found: 14.6 N: Calc .: 14.44, found: 14.3 A: Calc .: 7.75, found: 7.7

6-chloro-2-hydroxyethyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino-3 (2H) -pyridine zinone

Salt: 2.0 HC1; Solvate: 1.0 H ₂ O

M.p .: 168-175 ° C Yield: 25.8% of theory. C: Calc .: 46.84, found: 47.5 H: Calc .: 6.29, found: 5.8 Cl: Calc .: 29.74, found: 20.5 C1-: Calculated: 13.83, found: 13.9 N: Calc .: 13.66, found: 13.5

EXAMPLE

Determination of the affinity of compounds of formula I for alpha ₁ -adrenoreceptors.

The affinity of compounds of general formula I for alpha-adrenoreceptors was determined by the method described by R.S. Williams, D.F.Dukes, and R.F.Lefkovvitz in J.Cardiovasc. Pharmacol. 3, 522 - 531 (1981). According to this method, the competitive ejection of tritiated prazosin (2- (4- (2-furoyl) -1-piperazinyl) -4-amino-6,7-dimethoxy-quinazoline on the membranes of rat hearts by test substances was determined as IC ^ (50 % inhibitory concentration) is that concentration that causes a 50% inhibition of the specific binding of tritiated Prazosin to alpha ^ adrenoreceptors of rat heart membranes.

From the IC ^ value, we found the concentration-independent inhibitory constants Kja ^ corresponding to the data in Y.Cheng and H.W. Prusoff v Biochem.Pharmacol. 22, 30993108 (1973).

The results of these investigations are summarized in the following table:

TABLE I

Inhibition constants at alpha-l-adrenoreceptor:

2-methyl-5-bromo-4 - ((2- (4- (2-methoxyphenyl) piperazin-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 1.33

2-methyl-4-bromo-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 5.88

2-methyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 1.51

2-methyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 07.57

2-methyl-4-chloro-5 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Ki = 32.2

2-methyl-5'-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 3.48

2-methyl-4-chloro-5 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Ki = 6.05

2-methyl-5-chloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Ki = 2.15

5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 2.95

2-methyl-5-chloro-4 - ((2- (4- (phenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 86.7

2-methyl-5-chloro-4 - ((2- (4- (2-methoxy-5-methylphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridine zinone

Ki = 6.01

2-methyl-5-chloro-4 - ((2- (4- (2-methoxy-4-methylphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridine zinone

Ki = 22.4

2-methyl-5-chloro-4 - ((2- (4- (2-benzyloxyphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 2.54

2-methyl-5-chloro-4 - ((2- (4- (2-hydroxyphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 2.55

2-methyl-5-chloro-4 - ((2- (4- (2-methylphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 1.21

2-methyl-5-chloro-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino-3 (2H) -pyridazine

Ki = 47.3

2-methyl-5-chloro-4 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino-3 (2H) -pyridazinone Ki = 2.51

2-t-butyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino-3 (2H) -pyridazinone Ki = 42.2

2- (2-dimethylaminoethyl) -5-chloro-4 - ((2- (4- (2-methoxyphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 15.8

2-hydroxyethyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazine non

Ki = 2.42

2-methyl-5-chloro-4- (methyl-N- (3- (4- (2-methoxyphenyl) -piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Ki = 12.9

2-Methyl-5-chloro-4 - ((3- (4- (2-hydroxy-4-methylphenyl) -piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Ki = 5.34

2-methyl-5-chloro-4 - ((3- (4- (2-ethoxy-4-methylphenyl) -piperazinyl-1) propyl) amino) -3 (2H) -pyridine azinone

Ki = 4.99

2-methyl-5-chloro-4 - ((3- (4- (2-methylphenyl) -piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 4.45

2-methyl-5-chloro-4 - ((3- (4- (2-fluorophenyl) -piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 4.89

4-chloro-5 - ((2- (4- (2-methoxyphenyl) -piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 5.43

2-methyl-4-chloro-5 - ((2- (4-phenylpiperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 4.05

2-methyl-4-chloro-5 - ((2- (4- (2-methoxy-4-methyl-phenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 31.4

2-methyl-4 "chloro-5 - ((2- (4 (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 6.98

2-methyl-4-chloro-5- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 37.1

2-methyl-4-chloro-5 - ((2- (4- (2-ethoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 7.59

2-methyl-4-chloro-5 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 15.4

2-methyl-4-chloro-5 - ((4- (2-hydroxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 20.8

2-methyl-4-chloro-5 - ((2- (4- (2-benzyloxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone. Ki = 2.0

2-methyl-4-chloro-5 - ((2- (4- (2-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 6.27

2-methyl-4-chloro-5 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazino n

Ki = 94.2

2-methyl-4-chloro-5 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 28,2

2-t-Butyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 12.8

2- (dimethylaminoethyl) -4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) -ethyl) -amino) -3 (2H) pyridazinone

Ki = 17.3

2- (hydroxyethyl) -4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridine zinone

Ki = 10.8

2- (phenyl) -4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 4.48

2- (methyl) -4-chloro-5- (methyl-N - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) pyridazinone

Ki = 3.55

2- (methyl) -4'-chloro-5 - ((3- (4- (2-hydroxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -p iridazinone

Ki = 4.33

2- (methyl) -4-chloro-5 - ((3- (4- (2-ethoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridinone

Ki = 3.78

2- (methyl) -4-chloro-5 - ((3- (4- (2-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 31.4

2- (methyl) -4-chloro-5 - ((3- (4- (2-fluorophenyl) piperazinyl4) propyl) amino) -3 (2H) -pyridazinone Ki = 32,8

2- (methyl) -5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazinone Ki = 190.0

4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazinone Ki = 42.2

4 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazinone Ki = 84.0

2-methyl-4 - ((2- (4-phenylpiperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazinone Ki = 90.3

2-methyl-4 - ((2- (4 (2-methoxyphenyl) piperazinyl-1) propyl) ethyl) amino) -3 (2H) -pyridazinone Ki = 15.7

2-methyl-4- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) propyl) ethyl) amino) -3 (2H) -pyridazino n

Ki = 68.0

2-methyl-4 - ((2- (4- (2-methoxy-5-methylphenyl) piperazinyl-1) propyl) ethyl) amino) -3 (2H) -pyridinone

Ki = 73.6

2-methyl-4 - ((2- (4- (2-ethoxyphenyl) piperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazone Ki = 13.6

2-methyl-4 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazinone Ki = 65.5

2-methyl-4 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) propyl) amino) -3 (2H) -pyridazinone

Ki = 21.4

2-t-butyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 60.8

2-hydroxyethyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 17.7

4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 26.1

4 - ((3- (4- (2-ethoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 13.0

2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 24.7

2-methyl-4 - ((3- (4- (2-hydroxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazino n

Ki = 20.9

2-methyl-4 - ((3- (4- (2-ethoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazone Ki = 13.6

2-methyl-4 - ((3- (4- (2-fluorophenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazone Ki = 30.2

4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Ki = 4.64

2-methyl-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Ki = 11.8

2-methyl-5 - ((2- (4-phenylpiperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 157.0

2-methyl-5 - ((2- (4 (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 82.6

2-methyl-5- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 20,6

2-methyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 103,0

2-methyl-5 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 65.8

2-methyl-5 - ((2- (4- (2-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 48,4

2-methyl-4 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 89.4

2-t-Butyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 6.03

2-hydroxyethyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 128.0

2-phenyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 61.6

2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 40.5

2-methyl-5 - ((3- (4- (2-ethoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 23,3

2-methyl-4 - ((3- (4- (2-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 49.3

2-methyl-5 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Ki = 5.38

2-methyl-5-methoxy-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 7.83

4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 5.43

6-chloro-2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 11.0

6-chloro-2-ethyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 18.0

6-chloro-4 - ((4- (4- (2-methoxyphenyl) piperazinyl-1) butyl) amino) -3 (2H) -pyridazinone Ki = 3.34

6-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 12.8

2-methyl-6-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 5.63

6-chloro-4 - ((2- (4- (2-iso-propoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 10.0

6-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 11.0

6-chloro-4 - ((3- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 7.49

2-methyl6-chloro-3 - ((3- (4- (2-ethoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Ki = 6.5

6-chloro-2-hydroxyethyl-4 - ((3- (4- (2-rnetoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone

Ki = 9.6

Comparative substance:

6- (3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -1,3-di-methyluracil (

URAPIDIL)

Ki = 110.0

EXAMPLE B:

Determination of the affinity of compounds of formula I for 5-HT-1A receptors.

The affinity of compounds of general formula I for 5-HT-1A receptors was determined by the method described by H. Gozlan, S. Elmestikawy, L. Pichat, J. Glowinski, and M. Hamon in Nature 305, 140-142 (1983 ). According to this method, competitive ejection of tritiated 8-OHDPAT (8-hydroxy- (di-n-propylamino) tetralin) on the membranes of rat brain by test substances is measured and determined as lC ^ (50% inhibitory concentration), the concentration that causes 50% inhibition of specific binding of tritiated 8-OH-DPAT to

5-HT-1A receptors in rat brain membranes.

From the IC- ₅₀ values, we found the concentration-independent inhibitory constants Κ, -alfaj and Kj-5HT-1A, corresponding to the data of Y. Cheng and HW Prusoff in Biochem.Pharmacol. 22.3099-3108 (1973).

The results of these investigations are summarized in the following table:

TABELAH

Inhibition constants at the 5-HT1A receptor

2-methyl-5-bromo-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 16.2

2-methyl-4-bromo-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 33.6

2-methyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 16.6

2-methyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 63.2

2-methyl-4-chloro-5 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 50.7

2-methyl-5-chloro-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 1,40

2-methyl-5-chloro-4 - ((2- (4- (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Ki = 85.1

2-methyl-5-chloro-4 - ((2- (4- (2-methoxy-4-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridinone

Ki = 126.0

2-methyl-5-chloro-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 8.31

2-methyl-5-chloro-4 - ((2- (4- (2-fluorophenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 80,8

2-t-Butyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 9.45

2-hydroxyethyl-5-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazine non

Ki = 25.6

4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 27.0

2-methyl-4-chloro-5 - ((2- (4-phenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 106.0

2-methyl-4-chloro-5 - ((2- (4- (2-phenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 36.8

2-methyl-4-chloro-5 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 28.5

2-t-Butyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 39.4

2- (dimethylaminoethyl) -4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) pyridazinone

Ki = 118

2- (hydroxyethyl) -4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridine zinone

Ki = 86.3

2-Phenyl-4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 75.8

2-methyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 43.6

2-methyl-4- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone

Ki = 40.7

2-methyl-4 - ((2- (4- (2-methoxy-5-methylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 186.0

2-methyl-4 - ((2- (4- (2-hydroxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 36.5

2-methyl-4 - ((2- (4- (3-trifluoromethylphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 4,56

2-hydroxyethyl-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 18,2

2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 15.9

2-methyl-5- (ethyl- (2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 24,2

2-t-butyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 65.8

2-hydroxyethyl-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 55,8

2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 55,3

2-methyl-5-methoxy-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 90.8

4-chloro-5 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 27.0

6-chloro-2-methyl-4 - ((3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino) -3 (2H) -pyridazinone Ki = 46.6

2-methyl-6-chloro-4 - ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone Ki = 28,4

Comparative substance:

6- (3- (4- (2-methoxyphenyl) piperazinyl-1) propyl) amino-1,3-dimethyluracil (URAPIDIL) Ki = 93.1

Claims (4)

A process for the preparation of novel piperazinylalkyl-3 (2H) -pyridazinones of the formula o N R R R. '2 R 'Rq in which the radicals are hydrogen, phenyl, benzyl, unsubstituted or mono- or polysubstituted with hydroxy, piperidine, morpholino, or with the group NR ₄ R ₅ , in which R ₄ R _{5 is} evenly the same or different and represents hydrogen, methyl or ethyl substituted (C _r C ₆₎ -alkyl, R 2 and R _{3 are} hydrogen, halogen, (C 1 -C 4 -alkoxy or (C 1 -C 4 -alkyl), at least one of the residues R 2 and R ₃ being hydrogen, R _{6 is} hydrogen, (C 1 -C 4 -alkyl, phenyl, benzyl or phenylethyl, B is unsubstituted or mono- or polysubstituted by hydroxy, (C ^ - ^ J-alkyl, or a group NR ₄ R ₅ is substituted (C ^ -C ^ alkylene which is unsubstituted or may be joined to an alicyclic 4 to 7-member ring, R _g and R <>, which may be the same or different, are hydrogen or (C ₁ -C ₆ ) -alkyl, and Z unsubstituted or mono- or polysubstituted by (C ₁ -C ₆ ) -alkyl, (C ₁ -C ₆ -alkoxy, benzyloxy, trifluoromethyl, halogen, nitro, (C 1 -C 6 -cycloalkoxy, (C 1 -C 6) -alkylthio, trifluoromethylthio, or with the group NR ₄ R ₅ substituted phenyl, naphthyl, pyridyl or thiazolyl, as well as their pharmaceutically usable salts, characterized in that a) a compound of formula o R. '3 II in which R _{p is} R2 and R ₃ as defined above and M represents a cleavable group, is converted by a compound of formula R I HH III wherein R ₆ , B, R _g , Ry and Z are as defined above, or b) in a compound of formula I, in which one of the residues R2 or R ₃ is halogen and the remaining residues, as defined above, are substituted for halogen at R ₂ or R ₃ by hydrated dehalogenation with hydrogen, or c) a compound of formula I in which one of the residues R2 or R ₃ is halogen and the remaining residues as defined above are converted with an alkali metal alcohol, converting the halogen at R 2 or R ₃ to a residue having the meaning (C ^ C ₆ ) -alkoxy, or d) in a compound of formula I, in which R1 has the meaning of i-propyl, sec-butyl, tert-butyl or benzyl and the remaining residues as defined above are cleaved R _x with acids, or e) pyridazine of formula R «Κλ M K N - z \ _ / IV wherein R ₂ , R ₃ , R ₆ , B, R _g , R ₉ and Z are as defined above and R _{7 has the} meaning of (C 1 -C ₆ ) -alkyl, upon ether cleavage with acid, is converted to the corresponding 3- (2H) pyridazinone, or f) a compound of formula I in which R is hydrogen and one of the radicals R 2 or R ₃ represents halogen, and the other radicals, as defined above, is alkylated by reaction with an alkylating reagent in the 2-position of the pyridazine ring and g) optionally, the compound of formula I obtained according to a) to e) is converted into its pharmaceutically acceptable salts. 2. Piperazinylalkyl-3 (2H) -pyridazinones of formula o e- N N— z Rj is hydrogen, phenyl, benzyl, unsubstituted or mono- or polysubstituted with hydroxy, piperidine, morpholino, or with the group NR ₄ R ₅ in which R ₄ R _{5 is} slightly the same or different and represents hydrogen, methyl ah ethyl, substituted (C _r C ₆ ) -alkyl, R and R is hydrogen, halogen, (C ^ is -C alkoxy or (C ^ -C ^ alkyl, wherein at least one of the radicals R and R ₃ represents hydrogen, R _{6 is} hydrogen, (C 1 -C 4 -alkyl, phenyl, benzyl or phenylethyl, B is unsubstituted or mono- or polysubstituted by hydroxy, (C ^ -C ^ alkyl or a group NR ₄ R ₅ substituted (Cj-C ^ -alkylene which is unsubstituted or may be joined to an alicyclic 4 to 7-membered ring, R _g and R ₉ , which may be the same or different, are hydrogen or (C 1 -C 4 -alkyl and Z unsubstituted or mono- or polysubstituted by (C ₁ -C ₄ -alkyl, (C ₁ -C ₄ -alkoxy, benzyloxy, trifluoromethyl, halogen, nitro, (C ₃ -C ₇ ) -cycloalkoxy, (C ₁ -C ₄ ) -alkylthio, trifluoromethylthio, or a group NR ₄ R ₅ substituted phenyl, naphthyl, pyridyl or thiazolyl, as well as their pharmaceutically useful salts. Compounds of formula I according to claim 2, in which they represent residues R _{1 is} hydrogen, methyl, ethyl, tert-butyl, benzyl, 2-hydroxyethyl or 2-dimethylaminoethyl, R ₂ and R _{3 are} hydrogen, chlorine, bromine or methoxy, with at least one of R 2 or R ₃ being hydrogen, R _{6 is} hydrogen, methyl or ethyl, B straight (C ₂ -C ₆ ) -alkylene, R ₈ and R _{9 are} hydrogen as well as their pharmaceutically useful salts. 4.2-methyl-4-chloro-5 ((2- (4- (2-methoxyphenyl) piperazinyl-1) ethyl) amino) -3 (2H) -pyridazinone For CL PHARMA AKTIENGESELLSCHAFT: 20994-ΧΙΙ-89-1Ζ The invention relates to a process for the preparation of novel piperazinylalkyl- (3-2H) -pyridazinones of the formula ABSTRACT where hydrogen, phenyl, benzyl are unsubstituted. or subst. hydroxy, piperidine, morpholine or -NR ₄ R ₅ where R ₄ and R _{5 are the} same or different and are hydrogen, methyl or ethyl, substituted alkyl, R2 and R1 are hydrogen, halogen, alkoxy or alkyl, with at least one hydrogen, R _{6 is} hydrogen, alkyl, phenyl, benzyl or phenylethyl, B nesubst. or with hydroxy, alkyl or -NR ₄ R ₅ subst. alkylene which may be enclosed in an alicyclic 4- to 7-ring, R ₈ and R p, which may be the same or different, are hydrogen or alkyl and With nesubst. or with alkyl, alkoxyl, bezyloxyl, trifluoromethyl, halogen, nitro, cycloalkoxy, alkylthio, trifluoromethylthio or with the group -NR ₄ R ₅ subst. phenyl, naphthyl, pyridyl or thiazolyl and their pharmaceutically useful salts, derived from o oz. by converting the corresponding compounds of formula I. The end products are useful in the treatment of hypertension, heart failure and peripheral circulation disorders.