DE3527036A1 - 6-Arylalkenylpyridazinones - Google Patents

Abstract

Novel 6-arylalkenylpyridazinones of the general formula (I) <IMAGE> in which R<1> to R<6> are as defined in Patent Claim 1, and their salts show positive-inotropic effects.

Description

The invention relates to new 6-Arylalkenylpyridazinone general formula I, wherein
R ^{1 is} a phenyl group or one to four times through R, OH, SH, OR, SR, SO-R, SO ₂ -R, O-SO ₂ -R, S-SO ₂ -R, NH ₂ , NH-R , NR ₂ , NH-CO-R, F, Cl, Br, J, CF ₃ , NO ₂ , CN and / or CO-NH ₂ substituted phenyl group,
R alkyl with 1 to 6 carbon atoms, alkenyl or alkynyl with 2 to 6 carbon atoms,
R ² and R ³ H or alkyl with 1 to 3 carbon atoms,
R ⁴ and R ^{7 are} each H or alkyl having 1 to 4 carbon atoms and
R ⁵ and R ⁶ each denote H or together a CC bond,
in which further
R ¹ can only be p-tolyl or p-methoxyphenyl if one of the radicals R ² to R ^{7 is} different from H,
as well as their salts.

The invention was based on the object of providing new compounds with valuable properties to be found, in particular those used in the manufacture of medicines can be. That job was done by providing of the compounds of formula I dissolved.

It has been found that the compounds of formula I valuable pharmacological when well tolerated Possess properties. So show up, for example Effects on the circulatory system, especially positive inotropic ones, antihypertensive and heart-relieving effects.

The positive inotropic effect can be demonstrated in vitro on the barbiturate inadequate heart-lung preparation from guinea pigs (Method see H.J. Schliep, et al., 8th Internat. Congress of Pharmacology, Tokyo 1981, Abstr. of papers No. 923) as well as in the in vivo experiment as an increase in left ventricular Rate of pressure increase of the barbiturate anesthetized dog after intravenous administration (W. Diederen and R. Kadatz, Arzneimittelforschung 31 (I), 146-150, 1981) and the awake, instrumented with a Konigsberg recorder Hundes (method see J. Mahler et al., Circulations 50, 720-727, 1974) observed after oral administration become.

The substances reduce the on the carotid loop of the awake mixed-breed dog measured blood pressure (methodology see E.C. van Leersum, Pflüger's archive 142, 377-395, 1911) in nephrogenic hypertensive animals (methodology see I.H. Page, Science 89, 273-274, 1939) im 10-day continuous test with oral administration of doses that may be lower than 2 mg / kg / animal, depending on the dose to a lowered level.

Furthermore, the catheter-wearing (method cf. J.R. Weeks and J.A. Jones, Proc.Soc.Exptl.Biol.Med. 104, 646-648, 1960) spontaneously awake hypertensive rats (strain SHR / NIH / -MO / CHB-EMD) directly measured arterial blood pressure after a single intragastric administration from 10 mg / kg dose-dependently lowered. Even on the anesthetized cat can reduce the antihypertensive effects after intravenous Application by direct measurement of the carotid pressure be verified.

The heart-relieving effect can be seen from the anesthetized Increases observed in dogs after intravenous administration the total vascular capacity (H. Suga et al., Pflügers Archiv 361, 95-98, 1975).

Antithrombotic and platelet aggregation inhibitors also occur and affecting the shape of the erythrocytes Properties on. Influence on platelet function in the sense of an aggregation inhibition can at the Rat ex vivo in the Born test (Nature 194, 927-929, 1962). The antithrombotic effect shows up in the prolongation of the bleeding time Stella (Thrombos. Res. 7, 709-716, 1975) in the reduction of the thrombus weight in the case of the cold-induced Thrombosis of the jugular vein in the rat according to Meng (Ther. Ber. 47, 69-79, 1975) and the increase in the complete thrombosis the mensenterial venules of the rat, corresponding to one Modification of the Kovacs method (Microvasc. Res. 6, 194-201, 1973). The beneficial effect on erythrocyte deformability is in the Nucleoporefilter according to Schmid- Schönbein (Pflüger's Archiv 338, 93-114, 1973) can be detected. There can also be beneficial effects on the Fibrinolysis / euglobulin lysis time after v. Kaulla (Progr. Chem. Fibrinol. Thrombol. 1, 131-149, 1975; ed. J.F. Davidson, Raven Press, N.Y.).

The compounds of formula I can therefore be used as medicaments used in human and veterinary medicine. They can also be used as intermediate products for production other active pharmaceutical ingredients can be used.

The invention relates to the 6-arylalkenylkpyridazones of formula I.

In this formula, R preferably denotes alkyl having 1 to 4 carbon atoms, in particular methyl. The radical R ¹ preferably denotes one through R, OH, OR, SR, SO-R, SO ₂ -R, F, Cl, Br, I and / or CF ₃ , in particular through OR, SR, SO-R, SO ₂ -R and CF ₃ mono- or disubstituted phenyl group. Preferred meanings of R ² and R ³ are each H or methyl, in particular R ² = R ³ = H. The radicals R ⁴ and R ^{7 are} preferably each H or methyl, in particular R ⁴ = CH ₃ and R ⁷ = H. Die preferred meaning for the radicals R ⁵ and R ⁶ is in each case H.

In the case of multiple substitutions of the benzene ring, the substituents are preferably different, but they can also be the same. They are preferably in the 4 and / or 3 position, but they can also be in the 2, 5 or 6 position. The double bond substituted by the radicals R ² and R ³ preferably has the trans configuration, but it can also have a cis configuration.

Accordingly, the invention particularly provides those compounds of the formula I in which at least one of the radicals mentioned is one of those indicated above has preferred meanings.

The invention also relates to a method for Preparation of the 6-arylalkenylpyridazinones of the formula I, characterized in that a carboxylic acid of the general Formula II,

R ^{<<1 <<-CR <<2 <<=} CR ^{<<3 <<-CO-CR <<4 <<R <<5 <<-CR <<6 <<R <<7 <<-} COOH <@, ° uII

wherein R ¹ to R ^{7 have} the meaning given for formula I,
or a reactive derivative of such a carboxylic acid reacted with hydrazine or a reactive hydrazine derivative,
and that a double bond in the 4 (5) position is optionally introduced into a tetrahydropyridazinone of the formula I (R ⁵ = R ^{7 = H) obtained by treatment with dehydrating agents,}
or that a 1,2-diketone of the general formula III,

wherein R ¹ to R ^{4 have} the meaning given for formula I, reacts with hydrazine and acetic acid or acethydrazide,
or that a hydrazone of the general formula IV,

wherein R ¹ and R ^{4 have} the meaning given for formula I, reacts with acetic acid,
or that an oxo compound of the general formula V with a phosphonate of the general formula VI,

wherein R to R ^{7 have} the meaning given for formula I, converts,
and / or that thioethers of the formula I, in which at least one of the substituents is SR, are oxidized to the corresponding sulfoxides or sulfones,
and their salts, characterized in that the basic compounds of the formula I are converted into the associated acid addition salt using an acid.

The compounds of the formula I are prepared otherwise according to methods known per se, as described in the literature (e.g. in standard works such as Houben-Weyl, Methods of Organic Chemistry, Georg-Thieme-Verlag, Stuttgart) are described under reaction conditions, as they are known for the aforementioned implementations and are suitable. One can also use known, Variants not mentioned here are used do.

The starting materials of the formula II can after per se known methods are produced, for example by reacting benzaldehydes or alkylphenones with Levulinic acid or its derivatives.

Instead of the carboxylic acids of the formula II, their reactive derivatives can also be used in the reaction according to the invention. As such, the esters are particularly suitable, for. B. the alkyl esters, in which the alkyl group preferably has 1-4 carbon atoms, in particular the methyl and ethyl esters. Furthermore, z. B. the nitriles of the acids of the formula II. B. the acid halides of the acids of formula II can be used, for. B. the acid chlorides or acid bromides. Further suitable reactive derivatives of the carboxylic acids of the formula II can be formed in situ during the reaction without being isolated. These include, for example, the hydrazones of the formula R ¹ -CR ² = CR ³ -C (= N- NH ₂ ) -CR ⁴ R ⁵ -CR ⁶ R ⁷ -COOH and the hydrazides of the formula R ¹ - CR ² = CR ³ - CO-CR ⁴ R ⁵ -CR ⁶ R ⁷ -CO-NH-NH ₂ .

The starting materials of the formulas III and IV can be used according to known methods are produced, for example by reacting benzaldehydes or alkylphenones with Mesoxalaldehyde acid or its derivatives or homologues to compounds of the formula III or with mesoxalaldehyde hydrazone or its derivatives or homologues for Compounds of Formula IV.

Suitable reactive derivatives of hydrazine are z. B. hydrazine hydrate, acethydrazide, semicarbazide or Carbacic acid ester.

For the reaction with the carboxylic acids of the formula II it is advantageous to use one equivalent of hydrazine or a reactive hydrazine derivative that simultaneously can serve as a solvent. Is more expedient however, it is necessary to add an additional inert solvent. Inert solvents are preferably suitable Alcohols such as methanol, ethanol, isopropanol, n-butanol, Isoamyl alcohol, glycols and their ethers such as ethylene glycol, Diethylene glycol, ethylene glycol monomethyl or -monoethylether (methylglycol or ethylglycol), also Ethers, especially water-soluble ethers such as tetrahydrofuran, Dioxane or ethylene glycol dimethyl ether (diglyme); also water and mixtures of these solvents with one another, especially mixtures with water, e.g. B. aqueous Ethanol. The reaction temperatures are expedient between about 20 and 200 ° C, preferably between 20 and 100 ° C, the reaction times between about 1 and 48 hours.

For the reaction with 1,2-diketones of the general formula III can use the same solvent and reaction conditions be applied, provided the reaction mixture becomes one of the applied amounts of hydrazine at least equivalent amount of acetic acid added, wherein the acetic acid is preferably in excess. 1,2-Diketones of the formula III are particularly advantageous with acethydrazide to give the arylalkenylpyridazinones according to the invention of formula I implemented. The implementation takes place advantageously with an excess of acethydrazide, which can also serve as a solvent. It is however, it is also useful, additionally one of the mentioned add inert solvent.

Acetic acid can be used to convert hydrazones of the formula IV or their reactive derivatives such as. B. Esters, in particular methyl or ethyl acetate, or Acid chlorides, such as. B. acetyl chloride or bromide applied become. It is advantageous to use an excess of acetic acid or its derivatives at the same time can serve as a solvent. However, it is also expedient, in addition, one of the inert solvents mentioned to add.

From z. B. trialkyl phosphites and corresponding halomethylpyridazinones such as in Kosolapoff, Organophosphorous Compounds, John Wiley, New York, chap. 7, dialkyl phosphonates of the formula IV obtained described can be mixed with known aldehydes and ketones of the formula V, in which each R to R ^{7 have} the meaning given for the formula I, in the presence of a base among the z. B. Organic Reactions, Vol. 25, John Wiley, New York, 1978, chap. 2, conditions described are converted to the compounds of the formula I according to the invention. The bases used are, for example, alkali metal amides such as potassium or sodium amide or other suitable organic bases such as lithium diisopropylamide or sodium methylsulfinylmethylide. The reaction is expediently carried out in an inert solvent. Suitable inert solvents are preferably ethers such as diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran or dioxane and amides such as dimethylformamide, hexamethylphosphoric triamide, dimethylacetamide or N-methylpyrrolidone, and also sulphoxides such as dimethyl sulphoxide or sulfolane and hydrocarbons such as pentane, hexane, cyclohexane. Depending on the reactivity of the phosphonate anion used, the reaction temperatures are expediently between about -10 and about 150 ° C., preferably between 20 and 100 ° C., and the reaction times between about 1 and 48 hours.

Sulphoxides and sulphones of the formula I in which at least one of the ^{radicals substituting the phenyl group R 1 is} SOR or SO ₂ R can be prepared by oxidation of corresponding thioethers of the formula I in which at least one of the substituents is SR.

Depending on the reagent chosen and the conditions used, oxidation is carried out to the corresponding sulfoxides (one of the substituents is SO) or to the corresponding sulfones (one of the substituents is SO ₂ ), using methods known per se from the literature and the reaction conditions can easily be taken from the literature in detail. If the sulfoxides are to be obtained, oxidation is carried out, for example, with hydrogen peroxide, peracids, Ce (IV) compounds such as (NH ₄ ) ₂ Ce (NO ₃ ) ₆ or electrolytically under relatively mild conditions and at relatively low temperatures (about -80 to + 40 °). If, on the other hand, the sulfones are to be obtained, the same oxidizing agents are used under stronger conditions and / or in excess and, as a rule, at higher temperatures. The usual inert solvents can be present or absent in these reactions. Suitable inert solvents are, for example, water, aqueous mineral acids, aqueous alkali solutions, lower alcohols such as methanol or ethanol, esters such as ethyl acetate, ketones such as acetone, lower carboxylic acids such as acetic acid, nitriles such as acetonitrile, hydrocarbons such as benzene, chlorinated hydrocarbons such as chloroform or CCl ₄ .

A preferred oxidizing agent is 30% aqueous Hydrogen peroxide. This leads to the application of the calculated Amount in solvents like acetic acid, acetone or ethanol at temperatures between -20 and 30 ° to the Sulphoxides, in excess at higher temperatures, preferably in acetic acid or in a mixture of acetic acid and acetic anhydride, to the sulfones.

Another preferred oxidizing agent is 3-chloroperbenzoic acid. This leads to the application of the calculated Amount in solvents such as halogenated hydrocarbons at temperatures below 0 ° to the sulfoxides, in excess at temperatures between 0 ° and room temperature to the sulfones.

A base of the formula I can be converted into the associated with an acid Acid addition salts are transferred. For this Acids come into question, the physiologically harmless ones Deliver salts. So can inorganic acids can be used, e.g. B. sulfuric acid, nitric acid, hydrohalic acids such as hydrochloric acid or hydrobromic acid, Phosphoric acids such as orthophosphoric acid, Sulphamic acid, also organic acids, in particular aliphatic, alicyclic, araliphatic, aromatic or heterocyclic monobasic or polybasic carbon, Sulfonic or sulfuric acids, e.g. B. formic acid, acetic acid, Propionic acid, pivalic acid, diethylene acetic acid, Malonic acid, succinic acid, pimelic acid, fumaric acid, Maleic acid, lactic acid, tartaric acid, malic acid, benzoic acid, Salicylic acid, 2- or 3-phenylpropionic acid, citric acid, Gluconic acid, ascorbic acid, nicotinic acid, Isonicotinic acid, methane or ethanesulphonic acid, ethanedisulphonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalene mono- and disulfonic acid, Lauryl sulfuric acid.

The free bases of the formula I can, if desired, from their salts by treatment with strong bases such as Sodium or potassium hydroxide, sodium or potassium carbonate be set free.

The compounds of formula I can be one or more Centers of asymmetry included. In this case they lie usually in racemic form. Preserved Racemates can be mechanically or by methods known per se chemically separated into their optical antipodes. Preferably, from the racemic mixture through Reaction with an optically active separating agent diastereomers educated. Suitable release agents are, for. B. optically active acids, such as the D and L forms of tartaric acid, Diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, Malic acid, lactic acid or the various optically active camphorsulfonic acids such as β-camphorsulfonic acid.

Of course it is also possible to use optically active compounds of the formula I according to the methods described above obtained by using raw materials, which are already optically active.

The invention also relates to the use of the Compounds of the formula I and their physiologically harmless Salts for the manufacture of pharmaceuticals Preparations, in particular by non-chemical means. Here they can work together with at least one fixed, liquid and / or semi-liquid carrier or excipient and optionally in combination with one or more other active ingredients in a suitable dosage form to be brought.

The invention also relates to means, in particular pharmaceutical preparations containing at least a compound of the formula I and / or one of its physiological harmless salts.

These preparations can be used as medicinal products in human or veterinary medicine. As carriers organic or inorganic substances come into question, which are suitable for enteral (e.g. oral), or parenteral topical application and with the new compounds do not react, for example water, vegetable Oils, benzyl alcohols, alkylene glycols, polyethylene glycols, Glycerol triacetate, gelatin, carbohydrates such as Lactose or starch, magnesium stearate, talc, petroleum jelly.

Tablets, in particular, are used for oral use Pills, coated tablets, capsules, powder, granules, syrups, Juices or drops, for rectal use suppositories, for parenteral use solutions, preferably oily or aqueous solutions, also suspensions, emulsions or implants, for topical application ointments, Creams or powders. The new connections can too lyophilized and the lyophilizates obtained z. B. to Manufacture of injectables are used.

The specified preparations can be sterilized and / or auxiliaries such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for Influencing the osmotic pressure, buffer substances, Contain color, flavor and / or flavoring substances. you can, if desired, also one or more others Contain active ingredients, e.g. B. one or more vitamins.

The invention also relates to the use of the Compounds of the formula I in the fight against diseases, especially heart failure and arterial Hypertension, as well as its use in therapeutic Treatment of the human or animal Body.

The substances according to the invention are used in the Usually in analogy to known positive inotropic effects Substances such as amrinone administered, preferably in dosages between about 5 and 500 mg, in particular between 20 and 100 mg per dosage unit. The daily Dosage is preferably between about 0.1 and 10 mg / kg body weight. The special dose for everyone however, certain patient depends on the most diverse Factors, for example the effectiveness of the used special connection, from age, body weight, general health, gender, diet, the time and route of administration, the rate of elimination, Drug combination and severity the respective disease to which the therapy applies. Oral application is preferred. Compared to previously used for the therapy of heart failure Digitalis glycosides are made up of the compounds of Formula I through improved therapeutic breadth and peripheral relief.

example 1

4.5 g of 3-methyl-6- (3-methoxy-4-methylthiophenyl) -4-oxohex- 5-enoic acid (obtained from methyl levulinic acid and 3- Methoxy-4-methylthiobenzaldehyde in toluene under piperidine and glacial acetic acid addition on the water separator) and 2 g Hydrazine hydrate in 70 ml of ethanol for 2 hours Stirred at 20 ° C. The solution is concentrated in vacuo, in Dichloromethane taken up, shaken out with soda solution, dried and evaporated to a residue. After recrystallization from ethanol one receives 4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one; F: 155-156 ° C.

Analogously to Example 1, the reaction of the corresponding 4-oxo-hex-5-enoic acids with hydrazine hydrate gives:
4,5-dihydro-6- [2- (2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxyphenyl) ethenyl] pyridazin-3-one, m: 130-131 ° C
4,5-dihydro-6- [2- (3,4-dimethoxyphenyl) ethenyl] pyridazin-3-one, m: 155-156 ° C
4,5-dihydro-6- [2- (3,4-methylenedioxyphenyl) ethenyl] pyridazin-3-one, m: 166-167 ° C
4,5-dihydro-6- [2- (2-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allylthio-4-methylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allylthio-3-methylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-4-propargyloxyphenyl) -ethenyl] -pyridazin-3-one, mp 199-201 °
4,5-dihydro-6- [2- (2-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one, m.p. 148-149 ° C
4,5-dihydro-6- [2- (3-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3,4-dimethoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2,3,5-trimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (4-methylthiophenyl) ethenyl] pyridazin-3-one, m.p. 176 ° C
4,5-Dihydro-5-methyl-6- [2- (2-methoxyphenyl) ethenyl] pyridazin-3-one, m.p. 110 ° C
4,5-dihydro-5-methyl-6- [2- (3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (3-chloro-4-methoxyphenyl) ethenyl] pyridazin-3-one, m.p. 165 ° C.
4,5-dihydro-5-methyl-6- [2- (4-methoxyphenyl) ethenyl] pyridazin-3-one, m: 158 ° C
4,5-Dihydro-5-methyl-6- [2- (2,3-dimethoxyphenyl) ethenyl] pyridazin-3-one, m.p. 152 ° C.
4,5-dihydro-5-methyl-6- [2- (2,4-dimethoxyphenyl) ethenyl] pyridazin-3-one, m: 132-133 ° C
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxyphenyl) ethenyl] pyridazin-3-one, m.p .: 129-130 ° C
4,5-dihydro-5-methyl-6- [2- (3,4,5-trimethoxyphenyl) ethenyl] pyridazin-3-one, m: 178 ° C
4,5-dihydro-5-methyl-6- [2- (2-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylthio-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylthio-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (3-methoxy-4-propargyloxyphenyl) ethenyl] pyridazin-3-one, m.p .: 136 ° C
4,5-dihydro-5-methyl-6- [2- (2-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one, m.p .: 140 ° C
4,5-dihydro-5-methyl-6- [2- (2-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (4-methoxy-3-methylthiophenyl) -ethenyl] -pyridazin-3-one, m.p. 162 ° C
4,5-dihydro-5-methyl-6- [2- (3,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,3,5-trimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-allyloxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allyloxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allyloxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-allylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargyloxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargyloxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargyloxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylthio-4-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylthio-3-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-3-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-4-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-5-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-6-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-2-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-5-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-6-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-2-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-3-methylthiophenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,5-dimethoxy-4-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxy-5-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,5-dimethoxy-4-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,3,5-trimethoxy-4-methylthiophenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-allyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-allylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargyloxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-allylthio-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [1-methyl-2- (4-allylthio-3-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargylthio-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargylthio-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3,4-dimethoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2,3,5-trimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one

Example 2

To the solution of 11.2 g of semicarbazide hydrochloride in 300 ml of water are added to 26.4 g of 3-methyl-6- (4-methylthiophenyl) - 4-oxo-hex-5-enoic acid (made from methyl levulinic acid and 4-methylthiobenzaldehyde as in Example 1 described) and 100 ml of 1N sodium hydroxide solution. It is stirred for 6 hours at 75 ° C and then acidified by adding dilute hydrochloric acid. The unusual one Semicarbazone is filtered off and poured into 250 ml Sulfolane dissolved. Three hours of heating at 120 ° C causes the ring closure. After pouring the reaction mixture 4,5-dihydro-5-methyl- 6- [2- (4-Methylthiophenyl) ethenyl] pyridazin-3-one filtered off be, F: 167 ° C.

Analogously to Example 2, the reaction of the corresponding 4-oxo-hex-5-enoic acids with semicarbazide hydrochloride gives:
4,5-dihydro-5-methyl-6- [2- (2-hydroxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-hydroxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-hydroxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-hydroxy-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-hydroxy-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-hydroxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-hydroxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-hydroxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-mercaptophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-mercaptophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-mercaptophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-aminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-aminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-aminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-hydroxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-hydroxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-hydroxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-hydroxy-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-hydroxy-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-hydroxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-hydroxy-4-methylsulfinylphenyl] ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-hydroxy-4-methylsulfonylphenyl] ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-mercaptophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-mercaptophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-mercaptophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-aminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-aminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-aminophenyl) ethenyl] pyridazin-3-one

Example 3

To the suspension of 3.9 g of sodium amide in 280 ml dry tetrahydrofuran is added dropwise at room temperature the solution of 23.5 g of 4,5-dihydropyridazine-3- on-6-yl-methyl) -dimethylphosphonate (made from 4,5-Dihydropyridazin-3-one-6-carboxylic acid methyl ester by reduction with lithium borohydride to 4,5-dihydro- 6-hydroxymethylpyridazin-3-one, reaction with phosphorus tribromide to 6-bromomethyl-4,5-dihydropyridazin-3-one and its reaction with trimethyl phosphite) in 80 ml of the same solvent. After stirring for 30 minutes 14.1 g of 4-chlorobenzaldehyde are added and the mixture is heated another 5 hours to reflux.

The solvent is then removed in vacuo. The residue is digested with water and filtered and recrystallized from ethanol. So 4,5-dihydro- 6- [2- (4-chlorophenyl) ethenyl] pyridazin-3-one receive; F: 237-238 ° C.

Analogously to Example 3, reaction of the corresponding phosphonates of the formula VI with the oxo compounds of the formula V is obtained
4,5-dihydro-6- [2- (4-methylaminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-dimethylaminophenyl) -ethenyl] -pyridazin-3-one, m .: 210-212 ° C
4,5-dihydro-6- [2- (4-acetamidophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-fluorophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-fluorophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-fluorophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-bromophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-iodophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-trifluoromethylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-trifluoromethylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-trifluoromethylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-nitrophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-cyanophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-carbamoylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-carbamoylphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [3-methyl-4-methoxyphenyl) -ethenyl] -pyridazin-3-one, m: 133-134 ° C
4,5-Dihydro-5-methyl-6- [2-chloro-4-methylthiophenyl) -ethenyl] -pyridazin-3-one, m: 145-147 ° C
4,5-dihydro-5-methyl-6- [2- (4-methylaminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-dimethylaminophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-acetamidophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-fluorophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-fluorophenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (4-fluorophenyl) -ethenyl] -pyridazin-3-one, m.p. 168 ° C
4,5-dihydro-5-methyl-6- [2- (4-chlorophenyl) ethenyl] pyridazin-3-one, m: 175 ° C
4,5-dihydro-5-methyl-6- [2- (4-bromophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-iodophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-trifluoromethylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-trifluoromethylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-trifluoromethylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-nitrophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-cyanophenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-carbamoylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-carbamoylphenyl) ethenyl] pyridazin-3-one

Example 4

29 g of 4,5-dihydro-5-methyl- obtained according to Example 1 6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazine 3-one are dissolved in 300 ml of glacial acetic acid and with 6.7 g 30% hydrogen peroxide added. After 10 hours Stirring at room temperature, the precipitated is filtered off 4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylsulfinylphenyl) - ethenyl] pyridazin-3-one ab; F: 175-176 ° C.

Analogously to Example 4, the sulfoxides are obtained by reacting the corresponding thioethers obtained according to Example 1, 2 or 3 with hydrogen peroxide
6- [2- (2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Allylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Allylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Allylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Allylsulfinyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Allylsulfinyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (3-propargylsulfinyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-propargylsulfinyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3,5-Dimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (3,4-Dimethoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2,5-Dimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
6- [2- (2,3,5-trimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allylsulfinyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allylsulfinyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-propargylsulfinyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-propargylsulfinyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3,5-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3,4-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2,5-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2,3,5-trimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (4-methylsulfinylphenyl) ethenyl] pyridazin-3-one, m.p. 178 ° C
4,5-dihydro-5-methyl-6- [2- (2-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfinyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfinyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfinyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfinyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (3-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one, m.p. 175 ° C
4,5-dihydro-5-methyl-6- [2- (4-methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [2- (4-methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one, m.p. 205 ° C
4,5-dihydro-5-methyl-6- [2- (3,5-dimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,5-dimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,3,5-trimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2-allylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfinyl-4-methoxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfinyl-3-methoxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfinyl-4-methoxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfinyl-3-methoxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-3-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-4-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-5-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-6-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-2-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-5-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-6-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-2-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-3-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,5-dimethoxy-4-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxy-5-methylsulfinylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,5-dimethoxy-4-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,3,5-trimethoxy-3-methylsulfinylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-allylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-allylsulfinyl-4-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-allylsulfinyl-4-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargylsulfinyl-4-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargylsulfinyl-4-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-6-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxy-2-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3,5-dimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3,4-dimethoxy-5-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2,5-dimethoxy-4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2,3,5-trimethoxy-3-methylsulfinylphenyl) ethenyl] pyridazin-3-one

Example 5

29 g of 4,5-dihydro-5-methyl- obtained according to Example 1 6- [2- (3-methylthio-4-methoxyphenyl) ethenyl] pyridazine 3-one are dissolved in 250 ml of glacial acetic acid, with 10 g of 85% Hydrogen peroxide added and 6 hours 50 ° C stirred. The precipitate is filtered off and obtained 4,5-dihydro-5-methyl-6- [2- (3-methylsulfonyl- 4-methoxyphenyl) ethenyl] pyridazin-3-one.

Analogously to Example 5, the sulfones are obtained by reacting the corresponding thioethers obtained according to Example 1, 2 or 3 with hydrogen peroxide
6- [2- (2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Allylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Allylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Allylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Allylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Allylsulfonyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (3-propargylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-propargylsulfonyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one, m.p. 184 ° C
6- [2- (3-Methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3,5-Dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (3,4-Dimethoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2,5-Dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
6- [2- (2,3,5-trimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-allylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-allylsulfonyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-propargylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-propargylsulfonyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2-methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3-methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (4-methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3,5-dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (3,4-dimethoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2,5-dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-6- [2- (2,3,5-trimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfonyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfonyl-3-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,5-dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,5-dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,3,5-trimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-allylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-propargylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-allylsulfonyl-4-methoxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-allylsulfonyl-3-methoxyphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-propargylsulfonyl-4-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-propargylsulfonyl-3-methoxyphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-3-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-4-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-5-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2-methoxy-6-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-2-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-4-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-5-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3-methoxy-6-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-2-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (4-methoxy-3-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,5-dimethoxy-4-methylsulfonylphenyl) -prop-1-enyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (3,4-dimethoxy-5-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,5-dimethoxy-4-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [2- (2,3,5-trimethoxy-4-methylsulfonylphenyl) prop-1-enyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-allylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-Dihydro-5-methyl-6- [1-methyl-2- (3-allylsulfonyl-4-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-allylsulfonyl-3-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-propargylsulfonyl-4-methoxyphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-propargylsulfonyl-3-methoxyphenyl) -ethenyl] -pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-3-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2-methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3-methoxy-6-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxy-2-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (4-methoxy-3-methylsulfonyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3,5-dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (3,4-dimethoxy-5-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2,5-dimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one
4,5-dihydro-5-methyl-6- [1-methyl-2- (2,3,5-trimethoxy-4-methylsulfonylphenyl) ethenyl] pyridazin-3-one

Example 6

The mixture of 26.0 g obtained according to Example 1 4.5- Dihydro-6- [2- (3,4-dimethoxyphenyl) ethenyl] pyridazine 3-one, 25 g 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and 250 ml of tetrahydrofuran is added for 10 hours under nitrogen heated to reflux. Then you free in vacuo from the solvent and chromatographed the Basic aluminum oxide residue with dichloromethane as an eluent. After crystallization from ethanol becomes 6- [2- (3,4-diethoxyphenyl) ethenyl] pyridazin-3-one receive; F: 201 ° C.

Analogously to example 6 one obtains by reacting the corresponding 4,5-dihydropyridazinones with DDQ:
6- [2- (2-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (4-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (3-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2,4-Dimethoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (3,4,5-trimethoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Allyloxyphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Allyloxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Allyloxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Propargyloxyphenyl) ethenyl] pyridazin-3-one
6- [2- (3-Propargyloxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Propargyloxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Allylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-Allylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (4-Allylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2-propargylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-propargylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (4-propargylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-Hydroxy-4-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (4-Hydroxy-3-methoxyphenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2-Methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3-Methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (4-Methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (4-Methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3,5-Dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (3,4-Dimethoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2,5-Dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
6- [2- (2,3,5-trimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one

Example 7

27.4 g of 4,5-dihydro-5-methyl- obtained according to Example 1 6- [2- (3,4-dimethoxyphenyl) ethenyl] pyridazon-3-one, 25 g of selenium dioxide and 300 ml of ethanol are used for 12 hours heated to reflux in a nitrogen atmosphere. The solvent is then drawn off under reduced pressure Pressure is removed and the residue is chromatographed with dichloromethane of basic aluminum oxide. Crystallization of the Residue from ethanol gives 5-methyl- 6- [2- (3,4-dimethoxyphenyl) - ethenyl] pyridazin-3-one; F: 210-211 ° C.

Analogously to Example 7, the following are obtained by reacting the corresponding 4,5-dihydro-5-methylpyridazinones:
5-methyl-6- [2- (2-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-methoxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-methoxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-methoxyphenyl) ethenyl] pyridazin-3-one; F: 237 ° C
5-methyl-6- [2- (2,4-methoxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3,4,5-methoxyphenyl) ethenyl] pyridazin-3-one; F: 221 ° C
5-methyl-6- [2- (2-allyloxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-allyloxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-allyloxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-propargyloxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-propargyloxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-propargyloxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-allylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-allylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-allylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-propargylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-propargylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-propargylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-hydroxy-4-methoxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-hydroxy-3-methoxyphenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-methoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3-methoxy-6-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-methoxy-2-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (4-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (3,4-dimethoxy-5-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2,5-dimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
5-methyl-6- [2- (2,3,5-trimethoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one

The following examples relate to pharmaceuticals Preparations, the compounds of the formula I or their contain physiologically harmless salts:

Example A: tablets

A mixture of 1 kg of 4,5-dihydro-6- [2- (4-methylthiophenyl) - ethenyl] pyridazin-3-one 4 kg lactose, 1.2 kg Potato starch, 0.2 kg talc and 0.1 kg magnesium stearate is compressed into tablets in the usual way, such that each tablet contains 50 mg of active ingredient.

Example B: coated tablets

Tablets are pressed analogously to Example A, which then in the usual way with a coating of sucrose, Potato starch, talc, tragacanth and color coated become.

Example C: capsules

10 kg of 4,5-dihydro-6- [2- (3-methoxy-4-methylthiophenyl) - ethenyl] pyridazin-3-one in the usual way in hard gelatin capsules, so that each capsule contains 50 mg of active ingredient.

Example D: ampoules

A solution of 1 kg of 4,5-dihydro-6- [2- (4-methoxy-3-methylthiophenyl) - ethenyl] pyridazin-3-one hydrochloride in 30 l Double distilled water is sterile filtered into Ampoules filled, lyophilized under sterile conditions and sealed sterile. Each ampoule contains 20 mg Active ingredient.

Similarly, tablets, coated tablets, capsules or ampoules are available, the one or more of the remaining active ingredients of formula I and / or their physiologically harmless Contain salts.

Claims (7)

1. 6-Arylalkenylpyridazinones of the general formula I, wherein
R ^{1 is} a phenyl group or one to four times through R, OH, SH, OR, SR, SO-R, SO ₂ -R, O-SO ₂ -R, S-SO ₂ -R, NH ₂ , NH-R , NR ₂ , NH-CO-R, F, Cl, Br, J, CF ₃ , NO ₂ , CN and / or CO-NH ₂ substituted phenyl group,
R alkyl with 1 to 6 carbon atoms, alkenyl or alkynyl with 2 to 6 carbon atoms,
R ² and R ³ H or alkyl with 1 to 3 carbon atoms,
R ⁴ and R ⁷ each denote H or alkyl having 1 to 4 carbon atoms and R ⁵ and R ⁶ each denote H or together a CC bond,
in which further
R ¹ can only be p-tolyl or p-methoxyphenyl if one of the radicals R ² to R ^{7 is} different from H,
as well as their salts. 2. a) 4,5-Dihydro-6- [2- (4-methylthiophenyl) ethenyl] pyridazin-3-one
b) 4,5-dihydro-6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] pyridazin-3-one
c) 4,5-dihydro-6- [2- (4-methoxy-3-methylthiophenyl) ethenyl] pyridazin-3-one
d) 4,5-dihydro-5-methyl-6- [2- (4-methylthiophenyl) ethenyl] pyridazin-3-one
e) 4,5-Dihydro-5-methyl-6- [2- (4-methylsulfinylphenyl) ethenyl] pyridazin-3-one
f) 4,5-dihydro-6- [2- (3-methoxy-4-methylthiophenyl) ethenyl] -5-methyl-pyridazin-3-one
g) 4,5-dihydro-6- [2- (3-methoxy-4-methylsulfinylphenyl) ethenyl] -5-methyl-pyridazin-3-one
h) 4,5-dihydro-6- [2- (4-methoxy-3-methylthiophenyl) ethenyl] -5-methyl-pyridazin-3-one
i) 4,5-Dihydro-6- [2- (4-methoxy-3-methylsulfinylphenyl) ethenyl] -5-methyl-pyridazin-3-one. 3. Process for the preparation of 6-arylalkenylpyridazinones of the general formula I according to claim 1, characterized in that a carboxylic acid of the general formula II, R ^{<<1 <<-CR <<2 <<=} CR ^{<<3 <<-CO-CR <<4 <<R <<5 <<-CR <<6 <<R <<7 <<-} COOH <@, ° uIIworin R ¹ to R ^{7 have} the meaning given for formula I,
or a reactive derivative of such a carboxylic acid reacts with hydrazine or a reactive hydrazine derivative,
and that a double bond in the 4 (5) position is optionally introduced into a tetrahydropyridazinone of the formula I (R ⁵ = R ^{7 = H) obtained by treatment with dehydrating agents,}
or that a 1,2-diketone of the general formula III, wherein R ¹ to R ^{4 have} the meaning given for formula I, reacts with hydrazine and acetic acid or acethydrazide,
or that a hydrazone of the general formula IV, wherein R ¹ to R ^{4 have} the meaning given for formula I, reacts with acetic acid,
or that an oxo compound of the general formula V with a phosphonate of the general formula VI, wherein R to R ^{7 have} the meaning given for formula I, converts,
and / or that thioethers of the formula I, in which at least one of the substituents is SR, are oxidized to the corresponding sulfoxides or sulfones,
and their salts, characterized in that the basic compounds of the formula I are converted into the associated acid addition salt using an acid. 4. Process for the production of pharmaceutical preparations, characterized in that one connects of the general formula I together with at least a solid, liquid or semi-liquid carrier or excipient and optionally together with one further active ingredient in a suitable dosage form brings. 5. Pharmaceutical preparation, characterized by a content of a compound of general Formula I. 6. Compounds of general formula I according to claim 1 to fight disease. 7. Use of compounds of the general formula I in the fight against disease.