DE3022177A1 - 4,5-Di:hydro-6-acyl:amino-phenyl-3(2h)-pyridazinone derivs. - with thrombocyte aggregation inhibiting and antihypertensive activity - Google Patents

Abstract

-pyridazinone derivs. (I) are new. X is O or S; R1 is H or 1-3C alkyl; and R2 is 1-8C alkyl (opt. substd. by 1-4 halogen atoms, 1-4C alkoxy (sepd. from X by at least 2 C-atoms), 3-8C cycloalkyl (opt. carrying 1 or 2 1-3C alkyl gps.) or phenyl (opt. in turn carrying 1-3 substits. from 1-3C alkyl, 1-3C alkoxy, halogen, CF3 or NO2), 3-8C cycloalkyl (opt. mono- to tetra substd. by 1-4C alkyl), 3-8C alkenyl, 3-8C alkynyl or phenyl (opt. carrying 1-3 substits. from 1-4C alkyl, 1-4C alkoxy, halogen, CF3, CN and NO2). (I) have thrombocyte aggregation inhibiting and hypotensive properties. They can be used as antihypertensive agents and for the prophylaxis and treatment of thrombo-embolid diseases. Results of tests for pharmacological activity are given in the spec.

Description

'New Dihydropyridazinones, Process for Their Preparation

and therapeutic agents containing these compounds. The invention relates to new 6-aryl-4,5-dihydro-3 (2H) -pyridazinones, process for their preparation, pharmaceutical preparations containing these compounds and their use as drugs for thromboembolic diseases and as antihypertensive drugs.

6-Acylaminophenyl-4,5-dihydro-3 (2H) -pyridazinones are already several times has been described, for example, in DE-OS 1670 in positions 4 and 5 unsubstituted 6- (acylamino) phenyl-4,5-dihydro-3 (2H) -pyridazinones with antihypertensive and anti-inflammatory properties. For 6-phenyl-4,5-dShydro-3 (2H) -pyridazinone, which carry an alkyl group in the 4-position and in the p-position in the phenyl radical a group of the formula -NHR3, in which R3 is, for example, an acyl radical or a Ethoxycarbonyl radical, are substituted, are cardiovascular in DE-OS 23 04 977 and called anti-inflammatory properties. In DE-OS 21 50 436 and US-PS 3 824 271 and 3 888 901 are antihypertensive, in the 5-position by a Alkyl radical substituted 6- (alkanoylamino) -phenyl-4,5-dShydro-3 (2H) -pyridazinones described. Furthermore go from DE-OS 27 27 481 and the German patent application P 28 54 191.5 6- (p-Alkanoylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinones, which in the Alkanoyl group are substituted by one or more halogen atoms, as a drug because of their anti-platelet and antihypertensive properties emerged.

In DE-OS 2 123 246 antihypertensive, coronary widening and anti-inflammatory 6- (p-alkanoylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinones, the in Alkanoyl radical carry a substituted amino group, described. For 6-phenyl-4,5-dihydro-3 (2H) -pyridazinone, which is in the p-position in the phenyl radical a group of the formula -NHCONR1R2 in which the radicals R1 and R2 are identical or different and are, for example, hydrogen, an alkyl group or an aryl group, are substituted, in DE-OS 2,157,453 cardiovascular and anti-inflammatory Properties specified. Finally, in the Japanese patent application 53 124-279 antiallergic, membrane stabilizing and inhibiting platelet aggregation acting 6- [p- (alkoxycarbonylaminoalkyl) phenyl] -4,5-dShydro-3 (2H) -pyridazinones -described.

It has now been found that 6-aryl-4,5-dihydro-3 (2H) -pyridazinones of the general formula I, in which X is an oxygen atom or a sulfur atom, R1 is a hydrogen atom or an alkyl radical with 1 to 3 carbon atoms and R2 is an alkyl radical with 1 to 8 carbon atoms, optionally replaced by one to four halogen atoms, an alkoxy group with 1 to 4 carbon atoms Atoms in the alkyl which is separated from X by at least two carbon atoms, a cycloalkyl group with 3 to 8 carbon atoms in the ring, which optionally has one or two alkyl groups with 1 to 4 carbon atoms, or a phenyl radical which optionally one to three identical or different substituents from the group consisting of alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms in alkyl, halogen, trifluoromethyl or nitro, is substituted, a cycloalkyl radical with 3 to 8 carbon atoms in Ring, which is optionally substituted one to four times by alkyl radicals having 1 to 4 carbon atoms, an alkenyl radical having 3 to 8 carbon atoms, an alkynyl radical having 3 to 8 carbon atoms or a phenyl radical which is optionally one to three identical or various substituents n from the group alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, is substituted in alkyl, halogen, trifluoromethyl, cyano or nitro, mean having valuable pharmacological properties.

Alkyl radicals with 1 to 3 carbon atoms for R1 are, in particular, methyl and ethyl and propyl.

As unsubstituted alkyl radicals with 1 to 8 carbon atoms for the rest R2, straight-chain or branched, are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-methylbutyl and isopentyl called.

The preferred unsubstituted alkyl radicals for R2 are those which contain one to four carbon atoms.

Substituted by one to four halogen atoms, such as chlorine, bromine or fluorine Alkyl radicals with 1 to 8 carbon atoms for the radical R2, straight-chain or branched, are for example chloromethyl, bromomethyl, dichloromethyl, trifluoromethyl, l-chloromethyl, 2-bromoethyl, 2-fluoroethyl, 1,2-dichloroethyl, 1,1,2-trichloroethyl, 2,2,2-trichloroethyl, 2,2,2-tribromethyl, 2,2,2-trifluoroethyl, 2-bromopropyl, 3-chloropropyl, 2,3-dichloropropyl, 2,3-dibromopropyl, 3-bromo-2-chloropropyl, 2-chloroisopropyl, 2,2'-dichloroisopropyl, '2-chlorobutyl, 4-chlorobutyl, 1-chloromethylpropyl, 3, 4-dibromobutyl, 2-chloroisobutyl and 3-chloroisobutyl.

Of the haloalkyl radicals for R2, those are preferred which 1 to Contains 4 carbon atoms and one to three halogen atoms, in particular chlorine, bromine or fluorine.

Alkoxyalkyl radicals for R2 which are formed from the combination of one Alkoxy group with 1 to 4 carbon atoms in the alkyl and a straight-chain or branched one Alkylene group with 2 to 8 carbon atoms and in which the alkoxy group is arranged so that it is separated from X by at least a two-carbon chain are for Example 2-methoxyethyl, 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 2-butoxyethyl, 2-methoxypropyl, 2-ethoxypropyl, 3-methoxypropyl, 3-ethoxypropyl, 2-methoxyisopropyl, 2-ethoxyisopropyl, 2-methoxybutyl, 3-methoxybutyl, 4-methoxybutyl and 1,1-dimethyl-2-methoxyethyl.

The alkoxyalkyl radicals for R2 are preferably from the combination an alkoxy group with 1 to 3 carbon atoms.

For R2, straight-chain or branched alkyl radicals with 1 to 8 carbon atoms, optionally with up to two alkyl groups with 1 to 3 carbon atoms bearing cycloalkyl group with 3 to 8 carbon atoms in the ring are substituted, for example Cyclopropylmethyl, (l-methylcyclopropyl) methyl, (2-methylcyclopropyl) methyl, (2,3-dimethylcyclopropyl) methyl, Cyclobutylmethyl, (3-methylcyclobutyl) methyl, cyclopentylmethyl, cyclohexylmethyl, l-cyclopropylethyl, l-cyclobutylethyl, l-cyclopentylethyl, 2-cyclopropylethyl, 2-cyclobutylethyl, 2-cyclopentylethyl, 1-cyclopropylpropyl, 2-cyclopropyl-1-methylethyl, 2-cyclohexyl-1-methylethyl and 4-cyclohexylbutyl.

Of the cycloalkylalkyl radicals for R2, preference is given to those which are formed are from the combination of an optionally substituted cycloalkyl group with 3 to 6 carbon atoms in the ring and an alkylene group with 1 to 3 carbon atoms.

Alkyl radicals with 1 to 8 carbon atoms substituted by a phenyl group for the radical R2, straight-chain or branched, are, for example, benzyl, l-phenylethyl, 2-phenylethyl, l-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, l-methyl-2-phenylethyl, l-methyl-l-phenylethyl and 4-phenylbutyl.

The preferred phenylalkyl radicals for R2 are those which are formed are made up of the combination of a phenyl group and an alkylene group with 1 to 4 Carbon atoms.

Arylalkyl radicals for R2, which are formed from the combination of one one to three identical or different substituents from the group alkyl with 1 up to 3 carbon atoms, such as methyl, ethyl or propyl, alkoxy with 1 to 3 carbon atoms in the alkyl, such as methoxy or ethoxy, halogen, such as chlorine, bromine or fluorine, trifluoromethyl or Nitro-bearing phenyl group and a straight-chain or branched alkylene group with 1 to 8 carbon atoms are, for example, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, p-ethylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-ethoxybenzyl, m, p-dimethoxybenzyl, m, m ', p-trimethoxybenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, m-trifluoromethylbenzyl, o-nitrobenzyl, p-nitrobenzyl, 1- (m-methoxyphenyl) ethyl, 2- (2m, p-dimethoxyphenyl) ethyl, 2- (p-fluorophenyl) ethyl and 2- (o-nitrophenyl) ethyl.

The arylalkyl radicals for R2 are preferably selected from the combination of one substituted phenyl group and an alkylene group with 1 to 4 carbon atoms.

For the remainder of R2, one to four times come through as if necessary Alkyl radicals with 1 to 4 carbon atoms, such as methyl, ethyl or propyl, substituted Cycloalkyl groups with 3 to 8 carbon atoms in the ring, for example cyclopropyl, l-methylcyclopropyl, 2-methylcyclopropyl, 1-ethylcyclopropyl, 2,2-dimethylcyclopropyl, 1,2,2-trimethylcyclopropyl, Cyclobutyl l-methylcyclobutyl, 2-methylcyclobutyl, 3-methylcyclobutyl, l-ethylcyclobutyl, 2-ethylcyclobutyl, 1,2-dimethylcyclobutyl, 2,2-dimethylcyclobutyl, 3,3-dimethylcyclobutyl, Cyclopentyl, 1-methylcyclopentyl, 2-methylcyclopentyl, cyclohexyl and cycloheptyl into consideration.

The unsubstituted and substituted cycloalkyl radicals for R2 preferably contain 3 to 6 carbon atoms in the ring.

Of the alkenyl radicals with 3 to 8 carbon atoms, which can stand for R2, are allyl, but-2-enyl, but-3-enyl, 1-methylallyl, 2-methylallyl and pent-4-enyl called.

Preferred alkenyl radicals for R2 are those with 3 to 5 carbon atoms.

Alkynyl radicals with 3 to 8 carbon atoms for R2 are, for example, prop-2-ynyl, But-2-ynyl, but-3-ynyl, 1-methylprop-2-ynyl, pent-2-ynyl, pent-4-ynyl, 1-methylbut-2-ynyl, 1-methylbut-3-ynyl and 1, 1-dimethylprop-2-ynyl.

The preferred alkynyl radicals for R2 are those with 3 to 5 carbon atoms.

Examples of one to three identical or different substituents from the group consisting of alkyl having 1 to 4 carbon atoms, such as methyl, ethyl or propyl, alkoxy with 1 to 4 carbon atoms in alkyl, such as methoxy or ethoxy, halogen, such as chlorine, bromine or phenyl groups bearing fluorine, trifluoromethyl, cyano or nitro and which stand for R2 can, are o-tolyl, m-tolyl, p-tolyl, p-ethylphenyl, o, p-dimethylphenyl, o, m, p-trimethylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-ethoxyphenyl, o-ethoxy-p-ethylphenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, p-bromophenyl, p-fluorophenyl, m, p-dichlorophenyl, p-chloro-o-methylphenyl, m-trifluoromethylphenyl, p-cyanophenyl, o-nitrophenyl, m-nitrophenyl and p-nitrophenyl.

With regard to R1, preferred compounds are those in which R1 is for represents a hydrogen atom or a methyl group.

The dihydropyridazinones of the formula I are prepared by adding an aminophenyl-dihydropyridazinone of the formula II, in which R1 has the meanings given for formula I, with a compound of formula III, in which X and R2 have the meanings given for formula I and Y represents a halogen atom, in particular chlorine, is reacted in a manner known per se.

This reaction is carried out under conventional conditions. Usually using at least an equimolar amount of the haloformate or of the halothio formic acid S-ester of the formula III, expediently in the presence a solvent and optionally in the presence of an auxiliary base as the acid-binding one Medium and at temperatures between 0 and 140, preferably 10 to 100 ° C, optionally at the boiling point of the reaction mixture and, if appropriate, using of pressure.

The solvents used under the reaction conditions are inert solvents, such as aromatic hydrocarbons, for example benzene, toluene or xylene, cyclic ones aliphatic ethers, such as tetrahydrofuran or dioxane, or dialkylformamides, such as Dimethylformamide, into consideration. Auxiliary bases as acid-binding agents are expedient inorganic bases, such as sodium or potassium carbonate, sodium or potassium hydrogen carbonate, or tertiary organic amines such as triethylamine.

According to a further preparation, the new dihydropyridazinones of the formula I are obtained by adding an amino acid of the formula IV, in which R1 has the meanings given for formula I, with a compound of formula III, in which R2, X and Y have the meanings given above, and the resulting compound of the formula V is reacted cyclized with hydrazine.

For the preparation of the compounds V from the amino acids IV and the Haloformic acid esters or halothioformic acid S-esters III is among the above for the reaction of an aminophenyl dihydropyridazinone of the formula II with a Compound of formula III given conditions worked.

The cyclization of a compound of formula V with hydrazine, which is preferred is used as a hydrate, is advantageously carried out in one under the reaction conditions inert solvents, especially a lower alcohol such as methanol, ethanol or propanol, a cyclic aliphatic ether such as tetrahydrofuran or dioxane, or a dialkylformamide, such as dimethylformamide, and at temperatures from 60 to 140 ° C, preferably 80 to 1200C.

As a rule, per mole of a compound of the formula V 1 to 1.2 moles of hydrazine are used.

The compounds of the formula I can also be prepared by using an isocyanate of the formula VI, 'in which R1 has the meanings given for formula I and R3 is an alkyl radical having 1 to 3 carbon atoms, such as methyl, ethyl or propyl, preferably methyl or ethyl, with a compound of the formula VII, R2-XH VII in the R2 and X have the meanings given for formula I, and the resulting compound of formula VIII cyclized with hydrazine.

The reaction of an isocyanate of formula VI with a compound of the formula VII is carried out under conventional conditions. Usually using at least an equimolar amount of a compound of the formula VII, expediently in the presence of a solvent and optionally with additive one of those commonly used to accelerate isocyanate reactions Catalysts at temperatures between 0 and 140, preferably 20 to 1200C, optionally at the boiling point of the reaction mixture and, if appropriate, using of pressure.

The solvents used under the reaction conditions are inert solvents, such as aromatic hydrocarbons, for example benzene, toluene or xylene, aliphatic or aromatic chlorinated hydrocarbons, for 'game Methylene chloride or chlorobenzene, cyclic aliphatic ethers such as tetrahydrofuran or dioxane, or dialkylformamides, such as dimethylformamide, into consideration. Is the connection of the formula VII liquid, the reaction can also be carried out in excess VII as a solvent be performed.

Suitable catalysts for the reaction of an isocyanate of the formula VI with a compound of the formula VII are, for example, inorganic bases, such as Sodium or potassium carbonate, sodium or potassium hydrogen carbonate, alcoholates, such as sodium methylate or potassium tertiary butylate, tertiary organic amines such as triethylamine, Pyridine or 1,4-diazabicyclo2,2,2] octane, or metal compounds, for example Lead (IV), tin (II), tin (IV) or mercury (II) compounds. Of these Metal compounds as catalysts are tin (II), tin (IV) and mercury (II) compounds, such as tin octanoate, dibutyl tin diacetate, dibutyl tin dilaurate or phenyl mercury acetate, preferred.

The compounds of the formula II used as starting substances and also of the formula IV are known or can be selected from, for example, in the DE-OS 1,670,158 and 2,150,436 or U.S. Patents 3,824,271 and 3,888,901 Conditions are established.

Of the isocyanates of the formula VI used as starting substances, for example the compound in which R1 is hydrogen and R3 is an ethyl radical is known. Their synthesis is described in DE-OS 2,157,453. The amino acid of the formula IV, in which R1 stands for a hydrogen atom, is first converted into the compound of the formula IX by treatment with ethanol and hydrogen chloride convicted. IX is then reacted in a manner known per se with phosgene in a solvent which is inert under the reaction conditions, such as toluene or xylene, to give ethyl 3- (p-isocyanatobenzoyl) propionate (VI; R1 = II, R3 -CH). Starting from the amino acids of the formula IV, this process can also be used to prepare the other isocyanates of the formula VI.

Compounds according to the invention which are obtained by the processes mentioned are, for example: 4,5-dihydro-6- (p-methoxyearbonylsmflnophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-methoxy carbonylaminophenyl) -5-methyl-3- (2H) -pyridazinone; 4,5-dihydro-6- (p-ethoxy carbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-ethoxycarbonylaminophenyl) -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- (p-propoxy carbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p-propoxycarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-isopropoxy carbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-isoporpoxyearbonylaminophenyl) -5-methyl-3 (2H) -pyridazinone; 6- (p-butoxycarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (p-butoxycarbonylaminophenyl) -4, 5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- (p-isobutoxy carbonylaminophenyl) -5-methyl-3 (2H) -pyridazinone; 6- [p- (sec-butoxy) carbonylaminophenyl] -4,5-d-hydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (tert-butoxy) carbonylaminophenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-Chloromethoxy carbonylaminophenyl) -4,5-dShydro-3 (2H) -pyridazinone; 6- (p-Chloromethoxy carbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- (p-dichloromethoxycarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (p-dichloromethoxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- (p-trifluoromethoxy carbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p-trifluoromethoxy carbonylaminophenyl) -3 (2H) -pyridazinone; 6- [p- (1-chloroethoxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (1-chloroethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6-ep- (2-chloroethoxy-carbonylamino) phenyl] -4,5-dShydro-3 (2H) -pyridazinone; 6- [p- (2-chloroethoxy carbonylamino) phenyl] -4,5-d-hydro-5-methyl) -3 (2H) -pyridazinone; 6-ep- (2-bromoethoxy carbonylamino) phenyl] -4,5-d-hydro-3- (2H) -pyridazinone; 6- [p- (1-Bromoethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-fluoroethoxy carbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-fluororethoxycarbonylamino) phenyl] -5-3 (2H) -pyridazinone; 6- [p- (1,2-dichloroethoxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (1,2-dichloroethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1,1,2-trichloroethoxyearbonylamino) phenyl] -3 (2H) -pyr idazinone; 4,5-dihydro-5-methyl-6- [p- (2,2,2-trichloroethoxy carbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2,2,2-trifluoroethoxyearborylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2,2,2-trifluoroethoxy carbonylamino) phenyl] -3 (2H) -pyridazinone; 6- [p- (2-bromopropoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (3-chloropropoxy carbonylamino) phenyl] -4,5-d-hydro-5-methyl-3 (2H) -pyridazinone; 6-ep- (2,3-dichloropropoxy carbonylamino) phenyl] -4,5-d-hydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (2-chloroisopropoxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6-rp- (2-chloroisopropoxy carbonylamino) phenyl] -4,5-d-hydro-5-methyl-3 (2H) -pyridazinone; 6- (p- (2,2'-dichloroisopropoxy carbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (2-chlorobutoxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6-ep- (2-chlorobutoxyearbonylamino) phenyl] -4,5-dShydro-5-methyl-3 (2H) -pyriaazinone; 6- [p- (1-chloromethylpropoxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (1-chloromethylpropoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (1-chloroisobutoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl- = (2K) -pyridazinone; 4,5-dihydro-6- [p- (2-methoxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-methoxycarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-ethoxycarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-methoxypropoxy carbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (3-methoxypropoxy carbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (3-ethoxypropoxy carbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-methoxyisopropoxycarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclopropylmethoxy carbonylaminophenyl) -4,5-dShydro-3 (2H) -pyridazinone; 6- (p-Cyclopropylmethoxy carbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (1-methylcyclopropylmethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1-methylcyclopropylmethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (1-methylcyclopropylmethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2-methylcyclopropylmethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 6- (p-Cyclobutylmethoxy carbonylaminophenyl) -4,5-dShydro-3 (2H) -pyridazinone; 6- (p-Cyclobutylmethoxy carbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclopentylmethoxy carbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclohexylmethoxy carbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (1-cyclopropylethoxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (1-Cyclopropylethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3- (2H) -pyridazinone; 6- [p- (1-cyclobutylethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (2-Cyclopropylethoxy carbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (2-Cyclopropylethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (2-cyclobutylethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (1-Cyclopropylpropoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (2-cyclobutylpropoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2K) pyridazinone; 6- (p-Benzyloxycarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (p-Benzyloxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (1-phenylethoxycarbonylamino) phenyl] -3- (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1-phenylethoxycarbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2-phenylethoxy-carbonylamino) -phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1-phenylpropoxyearbonylamino) -phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2-phenylpropoxyearbonylamino) -phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p- (1-methyl-2-phenylethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p- (p-methylbenzyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (m-methoxyenzyloxyearbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (m, p-dimethoxybenzyloxycarbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 6- [p- (o-chlorobenzyloxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (m-chlorobenzyloxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (p-Chlorobenzyloxyearbonylamino) phenyl] -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (p-fluorobenzyloxyearbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (m-trifluoromethylbenzyloxyearbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (p-nitrobenzyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- [2- (m, p-dimethoxyphenyl) ethoxy carbonylamino] phenyl] -5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclopropyloxyearbonylaminophenyl) -4,5-dShydro-3 (2H) -pyridazinone; 6- (p-Cyclopropyloxyearbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (1-methylcyclopropyloxyearbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1-methylcyclopropyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-methylcyclopropyloxyearbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2-methylcyclopropyl-oxyearbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2,2-dimethylcyclopropyloxyearbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclobutyloxyearbonylaminophenyl) -4,5-dShydro-3 (2H) -pyridazinone; 6- (p-Cyclobutyloxyearbonylaminophenyl) -4,5-dShydro-5 - methyl-3 ( 2H) pyridazinone; 5-dihydro-5-methyl-6-p- (1-methylcyclobutyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2-methylcyclobutyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (3-methylcyclobutyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2,2-dimethylcyclobutyloxyearbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (3,3-dimethylcyclobutyloxyearbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclopentyloxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-chlorohexyloxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-allyloxycarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (p-Allyloxyearbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (But-2-enyloxyearbonylamino) phenyl] -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- [p-But-3-enyloxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1-methylallyloxycarbonylamino) phenyl] -3 (2H) -pyridyzinone; 4,5-dihydro-5-methyl-6- [p- (2-methylallyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (prop-2-ynyloxyearbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (prop-2-ynyloxyearbonylamino) phenyl] -3 (2H) pyridazinone; 6- [p- (But-2-ynyloxycarbonylamino) phenyl] -4,5-dihydro -3 (2H) -pyridazinone; 6- [p- (But-2-ynyloxyearbonylamino) phenyl] -4,5-dShydro - 5-methyl-3 (2H) -pyridazinone; 6- [p- (But-3-ynyloxycarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (But-3-ynyloxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (1-methylprop-2-ynyloxyearbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-5-methyl-6- [p- (1-methylprop-2-ynyloxazarbonylamino) phenyl] -3- (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (pent-2-ynyloxycarbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-6- [p- (1,1-dimethylprop-2-ynyloxycarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- (p-phenoxy carbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p-phenoxycarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (m-tolyloxazarbonylamino) phenyl] -3 (211) pyridazinone; 4,5-dihydro-6- [p- (o-methoxyphenoxy carbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (m-methoxyphenoxycarbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 6- [p- (o-Chlorophenoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (m-Chlorophenoxycarbonylamino) phenyl] -4,5-diohydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (p-Chlorophenoxycarbonylamino) phenyl] -4,5-diohydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (p-fluorophenoxy carbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (m-trifluoromethylphenoxy carbonylamino) phenyl] -3 (2H) -pyridazinone; 6- [p- (p-Cyanophenoxycarbonylamino) phenyl] -4,5-diohydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (o-nitrophenoxy carbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-5-methyl-6- [p- (p-nitrophenoxycarbonylamino) phenyl] -3 (2H) pyridazinone; 4,5-dihydro-6- (p-methylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p-methylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-ethylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-ethylmercaptocarbonylaminophenyl) -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- (p-propylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (propylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-isopropylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- (p-isopropylmercaptocarbonylaminophenyl) -5-methyl-3 (2H) -pyridazinone; 6- (p-Butylmercaptocarbonylaminophenyl) -4,5-dShyd ro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- (p-trifluoromethylmercatprocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p-trifluoromethylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 6- [p- (2-chloroethylmercaptocarbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone; 6- [p- (2-chloroethylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (2-Bromoethylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-fluoroethylmercaptocarbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2,2,2-trifluoroethylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2,2,2-trifluoroethylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 6- [p- (3-chloropropylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- [p-2,3-dichloropropylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-methoxyethylmercaptocarbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (2-ethoxyethylmercaptocarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclopropylmethylmercaptocarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (p-Cyclopropylmethylmercaptocarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-cyclobutylmethylmercaptocarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclopentylmethylmercaptocarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6-tp-Benzylmercaptocarbonylaminophenyl) -4,5-dShydro-3 (2H) -pyridazinone; 6- (p-Benzylmercaptocarbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone 4,5-dihydro-5-methyl-6- [p- (1-phenylethylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (2-phenylethylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (p-methylbenzylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-6- [p-methoxybenzylmercptocarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone; 6- [p- (p-Chlorobenzylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (p -fluorobenzylmercaptocarbonylAmS no) -phengl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (m-trifluoromethylbenzylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (p-nitrobenzylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 6- (p-Cyclopropylmercaptocarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (p-Cyclopropylmercaptocarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-cyclobutylmercaptocarbonylaminophenylj-4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-Cyclohexylmercaptocarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6- (p-Allymercaptocarbonylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone; 6- (fallylmercaptocarbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone; 6- [p- (But-2-enylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 6-Cp- (but-3-enylmercaptocarbonylamino) ph] -4,5-dihydro-5-methyl-3 (iH) -pyridazinone; 4,5-dihydro-6- [p- (prop-2-ynylmercaptocarbonylamino) -phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (prop-2-ynylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- (p-phenylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (p-polymercaptocarbonylamino) phenyl) -3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (o-methoxyphenylmercaptocarbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 6- [p- (p-Chlorophenylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-6- [p- (p-fluorophenylmercaptocarbonylamino) -phenyl] -5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (m-trifluoromethylphenylmercaptocarbonylmino) phenyl] -3 (2H) -pyridazinone; 6- [p- (p-Cyanophenylmercaptocarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone; 4,5-dihydro-5-methyl-6- [p- (p-nitrophenylmercaptocarbonylamino) phenyl] -3 (2H) -pyridazinone; It should be noted that the compounds of the formula I in which R1 is not equal to Is hydrogen, have an asymmetric carbon atom in the 5-position and can be obtained as racemates. The present invention is intended to include the enantiomers lock in. If separation is desired, it becomes advantageous at the stage a compound of the formula II according to known methods, e.g. formation of diastereomeric Salts with optically active auxiliary acids, such as dibenzoyltartaric acid or camphor - 10-sulfonic acid, carried out.

With a suitable radical R2, e.g. 2-methylcyclopropyl, also occurs in the compounds of the formula I have a geometric (cis-trans) isomerism. The present The invention relates to the respective cis and trans isomers and their mixtures.

The dihydropyridazinones of the formula I according to the invention are distinguished characterized by anti-platelet and antihypertensive properties. They are thrombo-embolic as antihypertensive agents and for prophylaxis and therapy Suitable for diseases.

The beneficial platelet aggregation-inhibiting effect can be im Compared to acetylsalicylic acid e.g. on the aggregation induced by collagen of thrombo- cytes of humans can be detected. As proof Because of the antihypertensive effect, rats are used under urethane anesthesia, for example. Dihydralazine, for example, serves as a reference substance.

The present invention accordingly also relates to therapeutic ones Agents or preparations which, in addition to conventional pharmaceutical carriers and diluents contain a compound of formula I as an active ingredient, and the use thereof Connections for therapeutic purposes.

The therapeutic agents or preparations are made with the usual Carriers or diluents and those commonly used pharmaceutically technical auxiliaries according to the desired type of application with a suitable dosage prepared in a known manner. This comes with humans Doses of 1 to 100 mg, preferably 5 to 50 mg, are possible, with oral administration is preferred.

Dosage forms that are suitable for oral administration are for example tablets, film tablets, coated tablets, capsules, pills, powders, solutions, Suspensions or depot forms.

For practical application, those to be used according to the invention are used Compounds processed with the usual carriers in galenic pharmacy. The corresponding tablets can, for example, by mixing the active ingredient with known auxiliaries, for example inert diluents such as dextrose, Sugar, sorbitol, polyvinylpyrrolidone, mannitol, calcium carbonate, calcium phosphate or Lactose, disintegrants such as corn, starch, alginic acid or polyvinylpyrrolidone, Binders, such as starch or gelatin, lubricants such as magnesium stearate or talc and / or Means to achieve the depot effect, such as carboxypolymethylene, carboxymethyl cellulose, Cellulose acetate phthalate or polyvinyl acetate can be obtained. The tablets can also consist of several layers (see L.G. Godman, A. Gilman, The PharmacologicaL Basis of Therapeutics).

Correspondingly, coated tablets can be made by coating analogously to the tablets manufactured cores with agents commonly used in dragee coatings, for example Polyvinylpyrrolidone or shellac, gum arabic, talc, titanium dioxide or sugar, getting produced. The coated tablet shell can also consist of several layers, where the excipients mentioned above for the tablets can be used.

The production of the new 6-aryl-4,5-dihydro-3 (2H) -pyridazinone will explained in more detail by the following examples.

Example 1 6.0 g (31.7 mmol) 6- (p-aminophenyl) -4,5-dihydro-3 (2H) -pyridazinone with 3.3 g (34.9 mmol) of methyl chloroformate in 100 ml of absolute toluene Maintained at 800C for 6 hours. It sucks off at 1000, washed first with toluene, then with water and recrystallized from diethylformamide / water. 3.3 g (42 % of theory) 4,5-dihydro-6- (p-methoxycarbonylaminophenyl) -3 (2H) -pyridazinone, beige Crystals, melting point 246 to 24700 (with addition).

Analysis for C12H13N3O3: calc .: C 58.3 H 5.3 N 17.0% found: C 58.1 H 5.3 N 16.8%.

Example 2 6. o g (29.5 mmol) 6- (p-aminophenyl) -4,5-dihydro-3- (2H) -pyridazinone with 3.3 g (34.9 mmol) of methyl chloroformate in 100 ml of absolute toluene Held at 800G for 6 hours. It sucks off at 1000, washed first with toluene, then with water and recrystallized from diethylformamide / water. 3.1 g (40 % of theory) 4,5-dihydro-6- (p-methoxycarbonylaminophenyl) -5-methyl-3 (211) -pyri dazinon, colorless crystals, melting point 228 to 2290C.

Analysis for C13H15N3O3: calc .: C 59.8 H 5.8 N 16.1% found: C 59.8 H 5.7 N 16.3%.

Example 3 a) 10.0 g (51.8 mmol) of 3- (p-aminobenzoyl) propionic acid become with 6.7 g (61.7 mmol) of ethyl chloroformate in 100 ml of absolute tetrahydrofuran Held at reflux for 10 hours. One sucks off at 1000 washes with water and recrystallized from diethylformamide / water. 7.8 g (57 % of theory) 3- (p-ethoxycarbonylaminobenzoyl) propionic acid, light beige crystals, Melting point 206-207 ° C.

Analysis for C13Hl5NO5: calc .: C 58.9 H 5.7 N 5.3% found: C 58.7 H 5.7 N 5.3%.

b) 3.5 g (13.2 mmol) 3- (p-ethoxycarbonylaminobenzoyl) propionic acid are refluxed with 0.66 g (13.2 mmol) of hydrazine hydrate and 50 ml of ethanol for 7 hours held. After suction at 1000 and drying under reduced pressure at 500C, 3.2 g (93% of theory) of 4,5-dihydro-6- (p-ethoxycarbonylaminophenyl) -3 are isolated (2H) -pyridazinone, colorless crystals, melting point 242 to 24300.

Analysis for C13H15N3O3 calcd .: C 59.8 H 5.8 N 16.1% found: C 59.6 H 5.9 N 16.1%.

Example 4 a) To 11.0 g (44.5 mmol) of ethyl 3- (p-isocyanatobenzoyl) propionate (DE-OS 21 57 453) are added with stirring 75 ml of absolute ethanol. Then will the reaction mixture was stirred for a further 2 hours at room temperature. After suction at 1000 ° C. and drying under reduced pressure at 500 ° C., 11.4 g are isolated (87% of theory) ethyl 3- (p-ethoxycarbonylaminobenzoyl) propionate, colorless Crystals, melting point 151 to 15200.

Analysis for C15H19NO5: calc .: C 61.4 H 6.5 N 4.8% found: C 61.5 H 6.3 N 4.9%.

b) 2.0 g (6.8 mmol) of ethyl 3- (p-ethoxycarbonylaminobenzoyl) propionate are refluxed with 0.34 g (6.8 mmol) of hydrazine hydrate and 20 ml of ethanol for 6 hours held. After suctioning off at 10 ° C and drying under reduced pressure at 50 ° C one receives 1.1 g (62% of theory) 4,5-dihydro-6- (p-ethoxycarbonylaminophenyl) -3 (2H) -pyridazinone, colorless crystals (identical to the compound from Example 3b).

Example 5 Example 1 is carried out using ethyl chloroformate (3.8 g (35.0 mmol)) instead of methyl chloroformate, so one obtains after recrystallization from dimethylformamide / water 3.7 g (45% of theory) 4,5-dihydro-6- (p-ethoxycarbonylaminophenyl) -3 (2H) -pyridazinone, almost colorless crystals (identical to the compound from Example 3b).

Example 6 Is used in Example 2 instead of methyl chloroformate Ethyl chlorameinate (3.8 g (35.0 mmol)) is used, so one obtains after recrystallization from dimethylformamide / water 3.5 g (43% of theory) 4,5-dihydro-6- (p-ethoxycarbonylaminophenyl ) -5-methyl-3 (2H) -pyridazinone> colorless crystals, melting point 219 to 22100.

Analysis for C14Hl7N303: calc .: C 61.1 H 6.2 N 15.3% found: C 61.0 H 6.3 N 15.5%.

Example 7 Example 2 is carried out with propyl chloroformate (5.45 g (44.5 mmol) carried out instead of methyl chloroformate, so obtained after recrystallization from dimethylformamide / water 3.5 g (41% of theory) 4,5-dihydro-5-methyl-6- (p-propoxycarbonylaminopehnyl) -3 (2H) -pyridazinone, light yellow Crystals, melting point 207-20800.

Analysis for C15H19N3O3: calc .: C 62.3 H 6.6 N 14.5% found: C 62.6 H 6.4 N 14.8%.

Example 8 6.0 g (29.5 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyri dazinon are mixed with 4.0 g (32.6 mmol) of isopropyl chloroformate in 100 ml of absolute toluene were refluxed for 16 hours. One sucks off at 1000 Washed first with toluene, then with water and crystallized twice from diethylformamide / water around. 4.3 g (50% of theory) of 4,5-dihydro-6- (p-isopropoxycarbonylaminopehnyl) -5-methyl-3 (2H) -pyridazinone are obtained, colorless crystals, melting point 246 to 2370C.

Analysis for C15H19N3O3: calc .: C 62.3 H 6.6 N 14.5% found: C 62.3 H 6.7 N 14.8%.

Example 9 Example 2 is carried out using butyl chloroformate (4.45 g (32.6 mmol)) instead of methyl chloroformate after two recrystallization from ethanol / water 3.0 g (33% of theory) 6- (p-butoxycarbonyl aminophenyl) -4, 5-dihyd ro-5- -methyl-3 (2H) -pyridazinone, colorless crystals, melting point 203 to 240 ° C.

Analysis for C16H21N3O3 calc .: C 63.3 H 7.0 N 13.9% found: C 63.0 H 6.9 N 14.0%.

Example 10 Example 2 is carried out using butyl chloroformate (4.45 g (32.6 mmol)) instead of methyl chloroformate after recrystallization from ethanol / water, 3.7 g (40% of theory) 4,5-dihydro-6- (p-isobutoxycarbonylaminophenyl) -5-methyl-3 (2H) -pyridazinone, colorless crystals, melting point 186 to 187 ° C analysis for C16H21N3O3: calc .: C 63.3 H 7.0 N 13.9% found: C 63.5 H 6.8 N 14.1%.

Example 11 Is used in Example 1 instead of methyl chloroformate 2-chloroethyl chloroformate (5.4 g (37.8 mmol)) is used to obtain after two recrystallization from ethanol / water 3.9 g (42% of theory) 6- [p- (2-chloroethoxyearbonylamino) phenyl] -4,5-dihydro-3 (2H) -pyridazinone, colorless crystals, melting point 232 to 2330C.

Analysis for 13g14ClN3 ° 3 0 calc .: C 52.8 H 4.8 Cl 12.0 N 14.2% found: C 53.0 H 4.9 Cl 11.8 N 14.4%.

Example 12 Example 2 is carried out using 2-chloroethyl chloroformate (4.65 g (32.5 mmol)) instead of methyl chloromic acid after recrystallization from ethanol / water 3.6 g (39% of theory) 6- [p- (2-chloroethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3- (2H) -pyridazinone, almost colorless crystals, melting point 206 to 207 ° C Analysis for C14H16ClN3O3: calc .: C 54.3 H 5.2 Cl 11.4 N 13.6% found: C 54.6 H 5.3 Cl 11.4 N 13.8%.

Example 13 Example 2 is used with chloromeinic acid 2-bromoethyl ester (6.1 g (32.5 mmol)) instead of methyl chloroformate is obtained after two recrystallization from methanol / water, 2.4 g (23% of theory) 6- [p- (2-Bromoethoxycarbonylamino) -phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinona light yellow crystals, melting point 218 to 220 ° C.

Analysis for C14H16BrN3O3: calc .: C 47.5 H 4.6 Br 22.6 N 11.9% found: C 48.0 H 4.7 Br 21.5 N 12.0%.

Example 14 Example 2 is carried out using 2,2,2-trichloroethyl chloroformate (6.9 g (32.6 mmol)) instead of methyl chloroformate, one obtains after two recrystallization from ethanol / water 3.8 g (34% of theory) 4,5-dihydro-5-methyl-6- [p- (2,2,2-trichloroethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone, almost colorless crystals, melting point 211 to 212 ° C analysis for C14H14Cl3N3O3: calc .: C 44.4 H 3.7 Cl 28.1 N 11.1% found: C 44.9 H 3.8 Cl 27.9 N 11.3%.

Example 15 Used in Example 1 instead of methyl chloroformate 2-methoxyethyl chloroformate (5.3 g (38.3 mmol)) is used to obtain after recrystallization from dimethylformamide / water 2.5 g (27% of theory) 4,5-dihydro-6- [p- (2-methoxyethoxycarbonylamino) phenyl] -3 (2H) -pyridazinone> colorless Crystals, melting point 221-222 ° C.

Analysis for C14H17N3O4: calc .: C 57.7 H 5.9 N 14.4% found: C 57.7 H 5.9 N 15.0%.

Example 16 Example 2 is carried out using 2-methoxyethyl chloroformate (6.2 g (44.7 mmol)) instead of methyl chloroformate, so isolated after two recrystallization from methanol 1.7 g (19% of theory) 4,5-dihydro-6- [p- (2-methoxyethoxycarbonylamino) phenyl] -5-methyl-3 (2H) -pyridazinone, yellowish crystals, melting point 216 to 21700.

Analysis for C15H19N3O4: calc .: C 59.0 H 6.3 N 13.8% found: C 58.9 H 6.2 N 14.1%.

Example 17 To a solution of 8.8 g (89.0 mmol) of phosgene in 50 ml absolute ether is added dropwise with stirring at 10 to 1500 3.2 g (44.4 mmol) (hydroxymethyl) cyclopropran, dissolved in 50 ml of absolute ether. Then the reaction solution still Stirred for 3 hours at room temperature. The excess is now removed first of the phosgene by a dry stream of nitrogen and then under reduced pressure Pressure at room temperature the ether. The remaining cyclopropylmethyl chloroformate is with 6.0 g (20.5 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl-3 - (2H) -pyridazinone and 100 ml of absolute toluene kept at 80 ° C. for 7 hours. One sucks off at 1000 Washed first with toluene, then with water and crystallized twice from dimethylformamide / water around. 3.0 g (34% of theory) of 6-p-cyclopropylmethoxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 are isolated (2H) -pyridazinone, colorless crystals, melting point 240 to 24100.

Analysis for C16H19N3O3: calc .: c63.8 H 6.4 N 13.9% found: C 63.6 H 6.2 N 14.2%.

In game 18 Example 2 is carried out using benzyl chloroformate (5.5 g (32> 2 mmol)) instead of methyl chloroformate, so obtained after recrystallization from ethanol / water 4.2 g (42% of theory) 6- (p-benzoyloxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone, colorless crystals, melting point 168 to 169 ° C. Analysis for C19H19N3O3 calc .: C 67.6 H 5.7 N 12.5% found: C 67.6 H 5.7 N 12.7%.

Example 19 To a solution of 11.5 g (116.3 mmol) phosgene in 100 5.0 g (69.3 ml) are added dropwise with stirring at 10 to 1500 ml of absolute ether mmol) cyclobutanol, dissolved in 80 ml absolute ether. Afterward the reaction solution is stirred for a further 3 hours at room temperature. Man removed now first the excess of the phosgene by means of a dry stream of nitrogen and then the ether under reduced pressure at room temperature. The one left behind Cyclobutyl chloramic acid ester is treated with 6.0 g (29.5 mmol) of 6- (p-aminophenyl) -4,5-dihydro-5-methyl-3 (2H) - pyridazinone and 180 ml of absolute tetrahydrofuran first for 20 hours at room temperature and then held at 40 to 4500 for another 4 hours. One sucks off at 1000, washed first with tetrahydrofuran, then with water and crystallized from dimethylformamide / water around. 2.8 g (31% of theory) 6- (p-cyclobutyloxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 are isolated (2H) -pyridazinone, colorless crystals, melting point 245 to 246 ° C Analysis for C16H19N3O3: calc .: 5 63.8 H 6.4 N 13> 9% found: C 63.4 H 6.3 N 14.2%.

Example 20 Used in Example 2 instead of methyl chloroformate Cyclohexyl chloroformate (7.2 g (44.3 mmol)) is used to obtain after two recrystallization from dimethylformamide / water 3.0 g (31% of theory) 6- (p-Cyclohexyloxycarbonylaminophenyl) -4,5-dihydro5-methyl-3 (2H) -pyridazinone, fast colorless crystals, melting point 194 to 195 ° C.

Analysis for C18H23N303: calc .: C 65.6 H 7.0 N 12.8% found: C 65.3 H 7.1 N 13.1%.

Example 21 Example 2 is carried out using allyl chloroformate (3.9 g (32> 3 mmol)) instead of methyl chloroformate, so obtained after recrystallization from methanol 3.0 g (35% of theory) 6- (p-allyloxycarbonylaminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone, light yellow crystals, melting point 206-207 ° C.

Analysis for C15H17N3O3 calc .: C 62.7 H 6.0 N 14.6% found: C 62.5 H 5.9 N 14.9%.

Example 22 Used in Example 1 instead of methyl chloroformate Phenyl chloroformate (5.96 g (38.1 mmol)) is used to obtain after recrystallization from dimethylformamide / water 2.4 g (24% of theory) 4,5-dihydro-6- (p-phenoxyearbonylaminophenyl) -3 (2H) -pyridazinone, almost colorless crystals, melting point 210 to 21200.

Analysis for C17H15N3O3: calc .: C 66.0 H 4.9 N 13.6% found: C 65.7 H 4.8 N 13.9%.

Example 23 Example 2 is carried out using phenyl chloroformate (5.0 g (31.9 mmol)) instead of methyl chloroformate, so isolated after recrystallization from dimethylformamide / water 3.9 g (41% of theory) 4,5-dihydro-5-methyl-6- (p-phenoxycarbonylaminophenyl) -3 (2H) -pyridazinone, almost colorless Crystals, melting point 200 to 202 ° C.

Analysis for C18H17N3O3: calc .: C 66.9 H 5.3 N 13.0 % Found: C 66.9 H 5.5 N 13.2%.

Example 24 5.0 g (24.6 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone are with 5.05 g (29.6 mmol) of chloroformic acid m-tolyl ester in 100 ml of absolute Toluene held at 80 ° C. for 6 hours. It sucks off at 1000, washed first with toluene, then with water and recrystallized twice from diethylformamide / water. Man isolated 2.5 g (30% of theory) 4,5-dihydro-5-methyl-6- [p- (m-tolyloxycarbonylamino) phenyl] -3 (2H) -pyridazinone quarter hydrate, almost colorless crystals, melting point 166 to 16700.

Analysis for C19H19N3O3 1/4 H20: calc .: C 66.8 H 5.7 N 12.3 0 15.2% Found: C 66.6 H 5.7 N 12.2 O 15.0%.

Example 25 In Example 24, m-toyl ester is used instead of chloramic acid O-methoxyphenyl chloroformate (5.5 g (29.5 mmol) was used and isolated in this way after recrystallization from dimethylformamide / water 3.0 g (35% of theory) 4,5-dihydro-6- [p- (o-methoxyphenoxyearbonylamino) phenyl] -5-methyl - 3 (2H) -pyridazinone, light yellow crystals, melting point 185 to 186 ° C.

Analysis for C19H19N3O4: calc .: C 64.6 H 5.4 N 11.9% found: C 64.6 H 5.3 N 12.2%.

Example 26 5.0 g (24.6 mmol) 6- (p-aminophenyl) -4,5-dihydro-3 (2h) -pyridazinone are stirred with 150 ml of absolute tetrahydrofuran by Heating to 600C dissolved. The solution is allowed to cool to room temperature, added 5.0 g (24.8 mmol) of p-nitrophenyl chloroformate are added and the mixture is first stirred Hours at room temperature and then a further 5 hours at reflux temperature. It is concentrated to approx. 70 ml, 100 ml of water are added and the mixture is filtered off with suction. After recrystallization 6.5 g (72% of theory) are isolated from dimethylformamide / water at room temperature 4,5-dihydro-5-methyl-6- [p- (p-nitrophenoxycarbonylamino) phenyl] -3 (2H) -pyridazinone, yellow crystals, melting point 177 to 17800.

Analysis for C18H16N4O5 calc .: C 58.7 H 4.4 N 15.2% found: C 58.5 H 4.4 N 15.2%.

Example 27 Example 1 is carried out using S-methyl chlorothioformate (5.3 g (47.9 mmol)) instead of methyl chloramic acid after recrystallization from dimethylformamide / water, 3.7 g (44% of theory) 4,5-dihydro-6- (p-methylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone, colorless Crystals, melting point from 2750G with addition.

Analysis for C12H13N3O2S calc .: C 54.7 H 5.0 N 16.0 s 12.2% found: C 55.0 H 5.2 N 16.3 s 11.5%.

Example 28 Used in Example 2 instead of methyl chloroformate S-methyl chlorothioameinate (3.6 g (32.6 mmol) used, so isolated one after recrystallization from ethanol / water 3.1 g (38% of theory) 4,5-dihydro-5-methyl- 6- (p-methylmercaptocarbonyl aminophenyl) -3 (2H) - -pyridazinone, colorless crystals, melting point 214 to 21,600 with decomposition.

Analysis for C13H15N3O2S: calc .: C 56.3 H 5.5 N 15.2 S 11.6% found: C 56.3 H 5.4 N 15.5 S 11.3%.

Example 29 Example 2 is carried out using S-ethyl chlorothioformate (4.15 g (33.3 mmol)) instead of methyl chloramic acid, so obtained after recrystallization from ethyl acetate 3.6 g (42% of theory) 4,5-dihydro-6- (p-ethylmercaptocarbonylaminophenyl) -5-methyl-3 (2H) -pyriaazinone, yellow-brown crystals, melting point 212 to 21300 with decomposition.

Analysis for C14H17N3O2S: calc .: C 57.7 H 5.9 N 14.4 s 11.0% found: C 57.8 H 6.0 N 14.3 s 10.5%.

Example 30 Used in Example 2 instead of methyl chloroformate S-propyl chlorothioformate (4.5 g (32.5 mmol) used, this gives after recrystallization from dimethylformamide / water 2.8 g (31% of theory) 4,5-dihydro-5-methyl-6- (p-propylmercaptocarbonylaminophenyl) -3 (2H) -pyridazinone, colorless crystals, melting point 195 to 19600.

Analysis for C15H19N3O2S: calc .: C 59.0 H 6.3 N 13.8 s 10.5% found: C 59.3 H 6.3 N 14.2 S 10.0%.

Example 31 5.0 g (24.6 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl-methyl-3 (2H) -pyridazinone are stirred in 150 ml of absolute tetrahydrofuran by heating to 600C solved.

The solution is allowed to cool to room temperature, 5.6 g (36.7 mmol) of chloramic acid 2-methoxypropyl ester and the mixture is stirred for a further 14 hours Reflux temperature after. You concentrate, add water and vacuum. After recrystallization 5.7 g (73% of theory) 4,5-dihydro-6- [p- (2-methoxypropoxycarbonylamino) -phenyl] -5-methyl-3 are isolated from dimethylformamide / water (2H) -pyridazinone, colorless crystals, melting point 173 to 175 ° C.

Analysis for C16H2lN304: calc .: C 60.2 H 6.6 N 13.2% found: C 60.4 H 6.5 N 13.4%.

Example 32 Is used in Example 31 instead of 2-methoxypropyl chloroformate Chloromeinsic acid 2-methoxyisopropyl ester used, it is isolated after Recrystallization from dimethylformamide / water 5.8 g (74% of theory) 4,5-dihydro-6- [p- (2-methoxyisopropoxycarbonylamino) phenyl] -5 - methyl-3 (2H) -pyridazinone, colorless crystals, melting point 208 to 210 ° C.

Analysis for C16H2lN304: calc .: C 60.2 H 6.6 N 13.2% found: C 60.4 H 6.5 N 13.6%.

Example 33 Example 31 is carried out using 3-ethoxypropyl chloroformate (6.1 g (36.6 mmol)) instead of 2-methoxypropyl chloroformate, see above receives after recrystallization from dimethylformamide / water 5.8 g (71% of theory) 4,5-dihydro-6- [p - (3-ethoxypropoxyearbonylamino) phenyl] -5) -methyl-3 (2H) - pyridazinone, colorless crystals, melting point 136 to 137 ° C.

Analysis for Cl7H23N304: calc .: C 61.2 H 7.0 N 12.6% found: C 61.4 H 6.9 N 12.6%.

Example 34 To a solution of 10.4 g (105 mmol) of phosgene in 100 ml of absolute ether are added dropwise with stirring at OOC 4.3 g (49.9 mmol) (Hydroxymethyl) cyclobutane. The reaction solution is then 1 hour at OOC touched. The mixture is stirred for a further hour at room temperature and then removed first the excess of the phosgene by a dry stream of nitrogen and afterwards the ether under reduced pressure at room temperature. The remaining cyclobutyl methyl chloroformate (6.9 g) is according to the method described in Example 31 with 5.0 g (24.6 mmol) 6- (p-Aminophenyl) -4,5-dihydro-5-methyl-3 (2H) - pyridazinone implemented. The work-up of the reaction mixture is also carried out analogously to Example 31. After this Recrystallization from dimethylformamide / water gives 5.5 g (71% of theory) 6- (p-Cyclobutylmethoxycarbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone, colorless crystals, melting point 199 to 2000C.

Analysis for C17H2lN303: calc .: C 64.8 H 6.7 N 13.3% found: C 64.6 H 6.5 N 13.5%.

Example 35 To a solution of 13.0 g (131.4 mmol) of phosgene in 100 ml of absolute ether are added dropwise with stirring at 0OC to 10 ° C. 5.9 g (51.7 mmol) (hydroxymethyl) cyclohexane. Then the reaction solution is 1 hour stirred at 0 ° C to 1000. The mixture is stirred for a further hour at room temperature and removed then first the excess of the phosgene by a dry stream of nitrogen and then the ether under reduced pressure at room temperature. The one left behind Cyclohexylmethyl chloramic acid (8.5 g) is given a value of 5.0 as in Example 31 g (24> 6 mmol) 6- (p-aminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone reacted. The reaction mixture is also worked up according to that in Example 31 described method.

After recrystallization first from dimethylformamide / water, then 2.1 is isolated from ethyl acetate / petroleum ether and finally from acetone / water g (25% of theory) 6- (p-Cyclohexylmethoxyearbonylaminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone, colorless crystals, melting point 223 to 2250C.

Analysis for C19H25N303: calc .: C 66.5 H 7.3 N 12.2% found: G 66.5 H 7.4 N 12.7%.

Example 36 To a solution of 9.9 g (100 mmol) of phosgene in 100 ml 4.3 g (49.9 mmol) of 1-cyclopropylethanol are added dropwise to absolute ether with stirring at OOC. The reaction solution is then stirred at OOC for 1 hour. One stirs another Hour at room temperature and then first removed the excess of phosgene a dry a stream of nitrogen and then under reduced pressure Pressure the ether at room temperature. The remaining 1-cyclopropylethyl chloramic acid (6> 6 g) is according to the method described in Example 31 with 5.0 g (24.6 mmol) 6- (p-Aminophenyl) -4,5-dihydro-5-methyl-3 (2H) - pyridazinone implemented. The work-up of the reaction mixture is also carried out analogously to Example 31. After recrystallization, is isolated first from dimethylformamide / water and then from ethanol / ether 1.3 g (17% of theory) 6- [p- (1-cyclopropylethoxycarbonylamino) phenyl] -4,5-dihydro-5-methyl-3 (2H) -pyridazinone, colorless crystals, melting point 223 to 22400.

Analysis for Cl7H2lN303: calc .: C 64.8 H 6.7 N 13.3% found: C 64.9 H 6.7 N 13.3%.

Example 37 To a solution of 9.8 g (99 mmol) of phosgene in 100 ml absolute ether is added dropwise with stirring at 0 ° to 50 ° C. 6.1 g (49.9 mmol) 2-phenylethanol. The reaction solution is then stirred at 5 to 1000 for 1 hour.

The mixture is stirred for a further hour at room temperature and then removed first the excess of the phosgene by a dry stream of nitrogen and then the ether under reduced pressure at room temperature. The one left behind 2-phenylethyl chloroformate (9> 1 g) is made according to that described in Example 31 Method with 5.0 g (24.6 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone implemented. Work-up is also carried out analogously to Example 31. After recrystallization from ethyl acetate / petroleum ether, 4.7 g (54% of theory) 4,5-dihydro-5-methyl-6- [p- (2-phenylethoxycarbonylamino) phenyl] -3 are obtained (2H) -pyridazinone, colorless crystals, melting point 163 to 164 ° C.

Analysis for C20H213O3: calc .: C 68.4 11 6.0 N 12.0% found: C 68.1 H 6.1 N 12.1%.

Example 38 To a solution of 9.9 g (100 mmol) of phosgene in 100 ml 6.9 g (49.9 mmol) of m-methoxybenzyl alcohol are added dropwise to absolute ether with stirring at -200C. The reaction solution is then stirred at 1000 for 1 hour. One stirs one another hour at room temperature and then first removed the excess of phosgene by a dry stream of nitrogen and then under reduced pressure the ether at room temperature. The remaining chloroformic acid m-methoxybenzyl ester (11 g) is according to the method described in Example 31 with 5.0 g (24.6 mmol) 6- (p-Aminophenyl) -4,5-dShydro-5-methyl-3 (2H) -pyridazinone converted. However, here stirred for only 8 hours at reflux temperature. It is worked up analogously to the example 31. After recrystallization from propanol, 7.3 g (81% of theory) are obtained 4,5-dihydro-6- [p- (m-methoxybenzyloxycarbonylamino) phenyl] -5 - methyl-3 (2H) -pyridazinone, colorless crystals, melting point 199 to 2000C.

Analysis for C20H21N304: calc .: C 65.4 H 5.8 N 11.4% found: C 65.4 H 5.9 N 11.4%.

Example 39 To a solution of 11.2 g (113 mmol) of phosgene in 100 ml Absolute ether is added dropwise with stirring at -200C to a solution of 7.1 g (49.8 mmol) of m-chlorobenzyl alcohol in 50 ml of absolute ether. Then the The reaction solution was stirred at -10 ° C. for 1 hour. One stirs one Further Hour at room temperature and then first removed the excess of phosgene a dry stream of nitrogen and then under reduced pressure at room temperature the ether. The remaining m-chlorobenzyl chloroformate (12.0 g) is dissolved in 50 ml of absolute tetrahydrofuran and at room temperature to one after the in the method described in Example 31 solution of 5.0 g (24.6 mmol) 6- (p-Aminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone in 100 ml of absolute tetrahydrofuran given. The reaction mixture is then refluxed for 14 hours held. Working up is analogous to Example 31. After recrystallization, first from chloroform / petroleum ether, then from acetone / water and finally from propanol / water 4.0 g (44% of theory) 6- £ p- (m-chlorobenzyloxycarbonylamino) phenyl] -4,5-d-hydro-5 "methyl-3 (2H) -pyridazinone are isolated, colorless crystals, melting point 165 to 16600.

Analysis for C19H18ClN3O3: calc .: C 61.4 H 4.9 Cl 9.5 N 11.3% found: C 61.5 H 5.0 Cl 9.9 N 11.5%.

Example 40 To a solution of 9.9 g (100 mmol) of phosgene in 100 ml absolute ether is added dropwise with stirring at -100C 2.8 g (49> 9 mmol) Prop-2-inol. The reaction solution is then stirred at -100 ° C. for 1 hour. Man stir for a further hour at room temperature and then first remove the excess of the phosgene by a dry stream of nitrogen and then under reduced pressure Pressure the ether at room temperature. The remaining prop-2-ynyl chloroformate (5.2 g) are at room temperature to one by the method described in Example 31 prepared solution of 5.0 g (24.6 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl- -3 (2H) -pyridazinone given in 150 ml of absolute tetrahydrofuran. Then the reaction mixture Maintained at reflux temperature for 1 hour. It is concentrated to about 70 ml and water is added closed and sucks. After recrystallization first from ethanol / water, then from Acetone / water and finally from ethanol, 2.9 g (41% of theory) 4,5-dihydro-5-methyl-6- [p- (prop - 2-ynyloxyearbonylamino) phenyl] -3 ( 2H) -pyridazinone, colorless crystals, melting point 204 to 205 ° C. Analysis for C15Hl5N303: calc .: C 63.1 H 5.3 N 14.7% found: C 63.3 H 5.4 N 15> 0% Example 41 To a solution of 9.9 g (100 mmol) of phosgene in 100 ml of absolute ether are added dropwise with stirring at -10 ° C 3.5 g (49.9 mmol) 1-methylprop-2-ynol. THEN THE REACTION SOLUTION WILL BE ENDED Stirred at -10 ° C for 1 hour.

The mixture is stirred for a further hour at room temperature and then removed first the excess of the phosgene by a dry stream of nitrogen and then the ether under reduced pressure at room temperature. The one left behind Chloramic acid 1-methylprop-2-ynyl ester (5.9 g) is prepared according to the method in Example 31 described method with 5.0 g (24.6 mmol) 6- (p-aminophenyl) -4,5-dihydro-5-methyl-3 (2H) -pyridazinone implemented. Work-up is also carried out analogously to Example 31. After recrystallization first from ethanol / water, then from ethyl acetate / petroleum ether and then still 1.7 g (23% of theory) of 4,5-dihydro-5-methyl-6- [p- (1-methylprop.) are isolated from dimethylformamide / water 2-ynyloxyearbonylamino) phenyl] -3 (2H) -pyridazinone, colorless crystals, melting point 206 to 207 ° C.

Analysis for C16H17N3O3: calc .: C 64.2 H 5.7 N 14.0% found: C 64.2 H 5.8 N 14.2% Formulation examples which are prepared in the usual way: 1. Tablets: active ingredient 10 mg polyvinylpyrrolidone (mean M.G. 25,000) 170 mg polyethylene glycol (mean M.G. 4,000-) 14 mg hydroxypropylmethylcellulose 40 mg talc 4 mg magnesium stearate 2 mg 240 mg The active ingredient is treated with polyvinylpyrrolidone in 10% aqueous solution moistened, geared through a sieve with a mesh size of 1.0 mm and at 50 ° C dried. This granulate is mixed with polyethylene glycol (mean M.G. 4,000), Hydroxypropylmethylcellulose, talc and magnesium stearate mixed and made into tablets a compressed 240 mg.

2. Example for coated tablets: active ingredient 10 mg lactose 90 mg corn starch 60 mg polyvinylpyrrolidone 6 mg magnesium stearate 1 mg 167 mg the Mixing the active ingredient substance with lactose and corn starch is inherent with an 8% aqueous solution of polyvinylpyrrolidone granulated through a sieve 1.5 mm at 50 ° C dried and again driven through a 1.0 mm sieve. The granulate thus obtained is mixed with magnesium stearate and pressed into tablet cores. The obtained tablet cores are coated in the usual way with a shell, which consists essentially of sugar and talc.

Claims (5)

Claims 1. Compounds of the formula I in which X is an oxygen atom or a sulfur atom, a hydrogen atom or an alkyl radical with 1 to 3 carbon atoms. and R2 is an alkyl radical with 1 to 8 carbon atoms, which is optionally replaced by one to four halogen atoms, an alkoxy group with 1 to 4 carbon atoms. Atoms in the alkyl which is separated from X by at least two carbon atoms, a cycloalkyl group with 3 to 8 carbon atoms in the ring, which optionally has one or two alkyl groups with 1 to 3 carbon atoms, or a phenyl radical which optionally has a to three identical or different substituents from the group alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms in the alkyl, halogen, trifluoromethyl or nitro, is substituted, a cycloalkyl radical with 3 to 8 carbon atoms in the ring , which is optionally substituted one to four times by alkyl radicals having 1 to 4 carbon atoms, an alkenyl radical having 3 to 8 carbon atoms, an alkynyl radical having 3 to 8 carbon atoms or a phenyl radical which is optionally one to three identical or different Substituents au s of the group alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms in alkyl, halogen, trifluoromethyl, cyano or nitro is substituted. 2. Compounds of formula I according to claim 1, in which R1 is a hydrogen atom or methyl and R2 is a hydrogen atom or an alkyl radical with 1 to 4 carbon atoms, an alkyl radical with 1 to 4 carbon atoms, one to three chlorine, bromine or fluorine atoms contains an alkyl radical with 2 to 4 carbon atoms, which is replaced by an alkoxy group with 1 up to 3 carbon atoms in the alkyl which is at least two carbon atoms removed from X, substituted is an alkyl radical with 1 to 3 carbon atoms, which is replaced by a cycloalkyl group with 3 up to 6 carbon atoms in the ring, optionally with one or two alkyl groups 1 to 3 carbon atoms is substituted, an alkyl radical with 1 to 4 carbon atoms, which by a phenyl group, optionally substituted according to claim 1, is substituted, or a cycloalkyl radical with 3 to 6 carbon atoms in the ring, optionally according to claim 1 substituted, an alkenyl radical with 3 to 5 carbon atoms, an alkynyl radical with 3 up to 5 carbon atoms, or a phenyl radical, optionally substituted according to claim 1, mean. 3. Compounds of formula I according to claim 1, in which R1 is a hydrogen atom or methyl and R2 is an alkyl radical having 1 to 4 carbon atoms, which is optionally 1-bis Is substituted 3 times by chlorine, bromine or fluorine, a cycloalkyl radical with 3 up to 6 carbon atoms in the ring and optionally substituted according to claim 1, or one Benzyl radical in which the phenyl ring is optionally substituted according to claim 1, mean. 4. Process for the preparation of compounds of the formula I according to claim 1, characterized in that a) an aminophenyl-dihydropyridazinone of the formula II in which R1 has the meanings given for formula I, with a compound of formula III in which X and R2 have the meanings given for formula I and Y represents a halogen atom, is reacted in a manner known per se, or b) that an amino acid of the formula IV in which R1 has the meanings given for formula I, with a compound of formula III in which R2, X and Y have the meanings given above, and the resulting compound of the formula V is reacted cyclized with hydrazine or c) that an isocyanate of the formula VI in which R1 has the meanings given for formula I and R3 represents an alkyl radical having 1 to 3 carbon atoms, with a compound of the formula VII R2-XH VII, in which R2 and X have the meanings given for formula I. and the compound of formula VIII obtained cyclized with hydrazine. 5. Therapeutic agent, characterized by a content of a compound of the formula I according to claim 1 as an active ingredient in addition to customary carriers and diluents.