DE3805884A1 - Substituted imidazolinones and imidazolinethiones - Google Patents

Abstract

Substituted imidazolinones and imidazolinethiones can be prepared by reduction of appropriate ketones and, if appropriate, subsequent hydrolysis, cyclisation, hydrogenation and isomer separation. The novel compounds can be used as active ingredients in medicaments.

Description

The invention relates to substituted imidazolinones and Imidazolinthione, interconnections for their preparation, their manufacture and their use in Medicines.

It is known that lactone derivatives isolated from fungal cultures Inhibitors of 3-hydroxy-3-methyl-glutaryl Coenzyme A reductase (HMG-CoA reductase) are [mevinolin, EP 22 478; US 42 31 938]. In addition, there are also certain Indole derivatives or pyrazole derivatives as inhibitors the HMG-CoA reductase [EP-A 1 114 027; U.S. patent 46 13 610] known.

There were substituted imidazolinones and imidazolinthione of the general formula (I),

in which

R¹- stands for cycloalkyl, or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵- are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R²- stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein R⁴ and R⁵ have the meaning given above, or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein R⁴ and R⁵ have the meaning given above,
R³- for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl, or
- stands for cycloalkyl, or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein R⁴, R⁵- are the same or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroalkyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
or
stand for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵
wherein R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein R⁴ and R⁵ have the meaning given above,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂- or -CH = CH-, and
A - for a group of the formula

stands in what
R⁶ means hydrogen or alkyl and
R⁷- hydrogen,
- An alkyl, aralkyl or aryl radical or
- means a cation.

Surprisingly, the substituted ones according to the invention show Imidazolinone and Imidazolinthione a significant pharmacological effect, especially a good one inhibitory effect on HMG-CoA reductase (3- Hydroxy-3-methyl-glutaryl coenzyme A reductase).

Cycloalkyl generally represents a cyclic Hydrocarbon residue with 3 to 8 carbon atoms. The cyclopropyl, cyclopentyl and is preferred Cyclohexyl ring. For example, be cyclopropyl, Cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl called.

Alkyl generally represents a branched hydrocarbon radical with 1 to 12 carbon atoms. Prefers becomes lower alkyl of 1 to about 6 carbon atoms. For example, methyl, ethyl, propyl, isopropyl, Butyl, isobutyl, pentyl, isopentyl, hexyl, isohexyl, Heptyl, isoheptyl, octyl and isooctyl called.  

Alkoxy generally represents one via an oxygen atom bound straight-chain or branched hydrocarbon residue with 1 to 12 carbon atoms. Prefers is lower alkoxy of 1 to about 6 carbon atoms. An alkoxy radical with 1 to is particularly preferred 4 carbon atoms. For example, methoxy, ethoxy, Propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, Isopentoxy, hexoxy, isohexoxy, heptoxy, isoheptoxy, octoxy or called isooctoxy.

Alkylthio generally represents one via a sulfur atom bound straight-chain or branched hydrocarbon residue with 1 to 12 carbon atoms. Prefers is lower alkylthio with 1 to about 6 carbon atoms. An alkylthio radical is particularly preferred with 1 to 4 carbon atoms. For example, methylthio, Ethylthio, propylthio, isopropylthio, butylthio, Isobutylthio, pentylthio, isopentylthio, hexylthio, Isohexylthio, heptylthio, isoheptylthio, octylthio or called isooctylthio.

Alkylsulfonyl is generally a straight chain or branched hydrocarbon radical with 1 to 12 carbon atoms, bound via a SO₂ group is. Lower alkylsulfonyl is preferred with 1 to about 6 carbon atoms. Examples include: methylsulfonyl, Ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, Butylsulfonyl, isobutylsulfonyl, pentylsulfonyl, Isopentylsulfonyl, hexylsulfonyl, isohexylsulfonyl.  

Aryl generally represents an aromatic radical with 6 to about 12 carbon atoms. Preferred aryl residues are phenyl, naphthyl and biphenyl.

Aryloxy generally represents an aromatic radical with 6 to about 12 carbon atoms through an oxygen atom is bound. Preferred aryloxy radicals are Phenoxy or naphthyloxy.

Arylthio is generally aromatic Residue with 6 to about 12 carbon atoms, the one Sulfur atom is bound. Preferred arylthio residues are Phenylthio or naphthylthio.

Arylsulfonyl is generally aromatic Radical with 6 to about 12 carbon atoms, which has a SO₂ group is bound. Examples include: Phenylsulfonyl, naphthylsulfonyl and biphenylsulfonyl.

Aralkyl generally represents one via an alkylene chain bound aryl radical with 7 to 14 carbon atoms. Alkyl radicals having 1 to 6 carbon atoms are preferred in the aliphatic part and 6 to 12 carbon atoms in the aromatic part. For example the following aralkyl radicals are mentioned: benzyl, naphthylmethyl, Phenethyl and phenylpropyl.

Aralkoxy generally represents an aralkyl radical 7 to 14 carbon atoms, the alkylene chain via  an oxygen atom is bound. Aralkoxy radicals are preferred with 1 to 6 carbon atoms in aliphatic Part and 6 to 12 carbon atoms in the aromatic Part. The following aralkoxy radicals may be mentioned, for example: Benzyloxy, naphthylmethoxy, phenethoxy and Phenylpropoxy.

Aralkylthio generally represents an aralkyl radical with 7 to about 14 carbon atoms being the alkyl chain is bound via a sulfur atom. Aralkylthio residues are preferred with 1 to 6 carbon atoms in aliphatic Part and 6 to 12 carbon atoms in the aromatic Part. Examples are the following aralkylthio residues called: Benzylthio, Naphtylmethylthio, Phenethylthio and phenylpropylthio.

Aralkylsulfonyl generally represents an aralkyl radical with 7 to about 14 carbon atoms, the alkyl chain is bound via a SO₂ chain. Prefers become aralkylsulfonyl radicals having 1 to 6 carbon atoms in the aliphatic part and 6 to 12 carbon atoms in the aromatic part. For example, the following are Aralkylsulfonyl radicals called: benzylsulfonyl, Naphthylmethylsulfonyl, phenethylsulfonyl and phenylpropylsulfonyl.

Alkoxycarbonyl can, for example, by the formula

being represented. Alkyl stands for a straight chain or branched hydrocarbon residue with 1 up to 12 carbon atoms. Lower alkoxycarbonyl is preferred with 1 to about 6 carbon atoms in the alkyl part. An alkoxycarbonyl is particularly preferred 1 to 4 carbon atoms in the alkyl part. For example the following alkoxycarbonyl radicals may be mentioned: methoxycarbonyl, Ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, Butoxycarbonyl or isobutoxycarbonyl.

Acyl generally represents phenyl or straight chain or branched lower alkyl having 1 to about 6 carbon atoms, which are bonded via a carbonyl group. Phenyl and alkyl radicals having up to 4 carbon atoms are preferred. Examples include: benzoyl, Acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, Butylcarbonyl and isobutylcarbonyl.

Halogen generally represents fluorine, chlorine, bromine or Iodine, preferably for fluorine, chlorine or bromine. Particularly preferred Halogen stands for fluorine or chlorine.

Heteroaryl is within the scope of the definition given above generally for a 5- to 6-membered aromatic Ring that acts as heteroatoms oxygen, sulfur and / or can contain nitrogen and the other aromatic rings can be fused. Prefers are 5- and 6-membered aromatic rings, one Oxygen, a sulfur and / or up to 2 nitrogen atoms  contain and optionally benzo-condensed are. The following are particularly preferred heteroaryl radicals: Thienyl, furyl, pyrolyl, pyrazolyl, pyridyl, pyrimidyl, Pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, Quinazolyl, quinoxalyl, phthalazinyl, cinnolyl, thiazolyl, Benzothiazolyl, isothiazolyl, oxazolyl, benzoxazolyl, Isoxazolyl, imidazolyl, benzimidazolyl, pyrazolyl, Indolyl, and isoindolyl.

If R⁷ is an alkyl, aryl or aralkyl radical, an ester group is formed.

Physiologically acceptable esters are preferred which easily becomes a free carboxyl group in vivo and a corresponding physiologically acceptable alcohol be hydrolyzed. These include, for example, alkyl esters (C₁ to C₆) and aralkyl esters (C₇ to C₁₀), preferred Lower alkyl esters and benzyl esters. In particular methyl esters, ethyl esters and propyl esters are preferred and benzyl ester.

R⁷ stands for a cation, preferably a physiologically compatible metal or ammonium cation is meant. Alkali or alkaline earth metal cations such as sodium, potassium, magnesium or calcium cations, and aluminum or ammonium cations, and non-toxic substituted ammonium cations from amines such as di-lower alkyl amines, tri-lower alkyl amines, dibenzylamine, N, N′-dibenzylethylene diamine, N are preferred -Benzyl- β - phenylethylamine, N-methylmorpholine or N-ethylmorpholine, dihydroabiethylamine, N, N'-bis-dihydroabiethylethylenediamine, N-lower alkylpiperidine and other amines that can be used to form salts.

In the context of the present invention preferably correspond the substituted imidazolinones and imidazolinthione the general formula

in which

R¹, R², R³, X, A and B have the meaning given above to have,

and the general formula

in which

R¹, R², R³, X, A and B have the meaning given above to have.

Imidazolinones and imidazolinthiones of the formula (I) are preferred
in which

R¹- stands for cyclopropyl, cyclopentyl or cyclohexyl, or
- represents lower alkyl, which can be substituted by fluorine, chlorine, bromine, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfonyl, lower alkoxycarbonyl, benzoyl, lower alkylcarbonyl, by a group of the formula -NR⁴R⁵,
in which R⁴ and R⁵ are identical or different and are lower alkyl, phenyl, benzyl, acetyl, benzoyl, phenylsulfonyl or lower alkylsulfonyl,
or by pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, pyrryl, indolyl, thienyl, furyl, imidazolyl, oxazolyl, thiazolyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio, benzylsulfonyl, phenylethylphenyl, ethyl, phenylsulfonyl, phenyl The heteroaryl and aryl radicals mentioned can be substituted up to twice in the same or different manner by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, trifluoromethyl or trifluoromethoxy,
R² stand for thienyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, benzothiazolyl, benzoxazolyl or benzimidazolyl which up to 2 can be substituted in the same way or differently by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy or lower alkoxycarbonyl, or
stand for phenyl or naphthyl, which can be substituted up to 4 times in the same or different manner by lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenyl, phenyloxy, phenylthio, phenylsulfonyl, benzyl, benzyloxy, benzylthio, benzylsulfonyl, phenethyl, phenylethoxy, phenylethylthonyl, phenylethylthio, phenylethylthio Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, lower alkoxycarbonyl or through a group of the formula -NR⁴R⁵,
where R⁴ and R⁵ have the meaning given above,
R³- for hydrogen or
- stands for benzoyl or lower alkylcarbonyl, or
- represents lower alkylsulfonyl, phenylsulfonyl or tolylsulfonyl, or
- stands for aminocarbonyl, lower alkylaminocarbonyl, di-lower alkylaminocarbonyl, phenylaminocarbonyl or lower alkoxycarbonyl, or
- stands for cyclopropyl, cyclopentyl or cyclohexyl or
- represents lower alkyl, which can be substituted by fluorine, chlorine, bromine, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfonyl, lower alkoxycarbonyl, benzoyl, lower alkylcarbonyl, by a group of the formula -NR⁴R⁵,
in which R⁴ and R⁵ are identical or different and are lower alkyl, phenyl, benzyl, acetyl, benzoyl, phenylsulfonyl or lower alkylsulfonyl,
or by pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, pyrrolyl, indolyl, thienyl, furyl, imidazolyl, oxazolyl, thiazolyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio, benzylsulfonyl, phenylethysylonethyl, phenylethysulfonyl, phenyl The heteroaryl and aryl radicals mentioned can be substituted up to twice in the same or different manner by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, trifluoromethyl or trifluoromethoxy,
are thienyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, benzothiazolyl, benzoxazolyl or benzimidazolyl, which up to 2 times the same - or can be substituted differently by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy or lower alkoxycarbonyl, or
- represent phenyl or naphthyl, which can be substituted up to 4 times in the same or different ways by lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenyl, phenyloxy, phenylthio, phenylsulfonyl, benzyl, benzyloxy, benzylthio, benzylsulfonyl, phenylethyl, phenylethoxy, phenylsulfonyl, phenylethyl Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, lower alkoxycarbonyl or through a group of the formula -NR⁴R⁵,
where R⁴ and R⁵ have the meaning given above
B - represents a group of the formula O or S,
X - represents a group of the formula -CH₂-CH₂ or -CH = CH-,
A - for a group of the formula

stands in what
R⁶ is hydrogen or lower alkyl, and
R⁷- alkyl (C₁ to C₆), aryl (C₆ to C₁₂) or aralkyl (C₇ to C₁₀) means, or
- means a physiologically compatible cation.

Compounds of the general are particularly preferred Formulas (I), in which

R¹- stands for cyclopropyl, cyclopentyl or cyclohexyl, or
- stands for methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl, which can be substituted by fluorine, chlorine, bromine, cyano, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert .Butoxy, methylthio, ethylthio, propylthio, isopropylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, trilfluoromethyl, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert.-butoxycarbonyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyrid, Phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio or benzylsulfonyl,
R²- represent pyridyl, pyrimidyl, quinolyl or isoquinolyl, which can be substituted by fluorine, chlorine, methyl, methoxy or trifluoromethyl, or - represent phenyl, which can be substituted up to 3 times by the same or different means by methyl, ethyl, propyl, Isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, methylthio, ethylthio, propylthio, isopropylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, phenyl, benzoxy , Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl or tert.butoxycarbonyl,
R³- represents hydrogen, cyclopropyl, cyclopentyl or cyclohexyl, or
represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl or isohexyl, which can be substituted by fluorine, chlorine, bromine, cyano, methoxy, ethoxy, propoxy, isopropoxy, butoxy, Isobutoxy, tert.butoxy, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, tert.butylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, ethoxycarbonyl, troxyboxyfoxy, troxycarbonyl Butoxycarbonyl, isobutoxycarbonyl, tert.butoxycarbonyl, benzoyl, acetyl, ethylcarbonyl, or by a group -NR⁴R⁵,
where R⁴ and R⁵ are identical or different and are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, phenyl, benzyl, acetyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl or phenylsulfonyl,
or by pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinoline, isoquinolyl, thienyl, furyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio or benzylsulfonyl, the heteroaryl and aryl radicals mentioned being fluorine, chlorine, methyl, ethyl, propyl Isopropyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, trifluoromethyl or trifluoromethoxy may be substituted, or
- stands for thienyl, furyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazolyl, isooxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, quinolyl, isoquinolyl, benzoxazolyl, benzimidazolyl or benzothiazolyl, with the radicals mentioned being, Propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, propoxycarbonyl, butoxycarbonyl or isobutoxycarbonyl. Butoxycarbonyl may be substituted, or
- stands for phenyl which is up to 3 times the same or different by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert .Butoxy, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, tert.Butylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert.Butylsulfonyl, phenyl, phenoxy, phenylthio, phenylsulphonyl, benzyl, benzyloxy, benzylthio, benzylsulphonyl , Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl or can be substituted by a group -NR⁴R⁵,
where R⁴ and R⁵ have the meaning given above,
or
R³- stands for benzoyl, acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert.butylsulfonyl, phenylsulfonyl or tolylsulfonyl,
- for aminocarbonyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butylaminocarbonyl, dimethyl, diethyl, dipropyl, diisopropyl, dibutyl or diisobutylaminocarbonyl, phenylaminocarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl , Isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl or tert.butoxycarbonyl,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂- or -CH = CH-,
A - for a group of the formula

wherein
R⁶ is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl, and
R⁷ means hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl or benzyl, or a sodium, potassium, calcium, or magnesium or ammonium cation.

The substituted imidazolinones and Imidazolinthione of the general formula (I) have multiple asymmetric carbon atoms and therefore can exist in various stereochemical forms. Both the individual isomers and their mixtures are the subject of the invention.

Depending on the meaning of group X or the rest A  result in different stereoisomers, which in the following should be explained in more detail:

• a) If the group -X- stands for a group of the formula -CH = CH-, the compounds according to the invention can exist in two stereoisomeric forms which can be E-configured (II) or Z-configured (III) on the double bond: whereZ for the rest stands where
  R¹, R², R³ and B have the meaning given above,
  A has the meaning given above and
  Those compounds of the general formula (I) which are E-configured (II) are preferred.
• b) The rest -A- stands for a group of the formula where R⁶ and R⁷ have the meaning given above,
  the compounds of the general formula (I) have at least two asymmetric carbon atoms, namely the two carbon atoms to which the hydroxyl groups are attached. Depending on the relative position of these hydroxyl groups to one another, the compounds according to the invention can be in the erythro configuration (IV) or in the threo configuration (V). whereX, Z, R⁶ and R⁷ have the abovementioned meaning.Both of the compounds in the erythro and in the threo configuration in turn each have two enantiomers, namely 3R, 5S isomer and 3S, 5R isomer (erythro form) and 3R, 5R isomer and 3S, 5S isomer (threo form).
  The erythro-configured isomers are preferred, particularly preferably the 3R, 5S isomer and the 3R, 5S-3S, 5R racemate.
• c) The rest -A- stands for a group of the formula in which
  R⁶ has the meaning given above, the substituted imidazolinones and imidazolinthiones have at least two asymmetric carbon atoms, namely the carbon atom to which the hydroxyl group is attached and the carbon atom to which the rest of the formula Z-X is attached,
  where Z and X have the meaning given above.

Depending on the position of the hydroxy group to the free Valence on the lactone ring can be substituted Imidazolinones and Imidazolinthione as cis-lactones (VI) or as trans-lactones (VII):

and

in which

Z, X and R⁶ have the meaning given above.

Both from the cis-lactone and from the trans-lactone there are again two isomers, namely that 4R, 6R isomers or the 4S, 6S isomer (cis lactone), and the 4R, 6S isomer or 4S, 6R isomer (trans Lactone). Preferred isomers are the trans lactones. The 4R, 6S isomer is particularly preferred (trans) and the 4R, 6S-4S, 6R racemate.

For example, the following isomeric forms of the substituted imidazolinones and imidazolinthiones may be mentioned:

in which

R¹, R², R³, R⁶ and R⁷ have the meaning given above to have.

The compounds of the general formulas (Ia) and (Ib) in which are very particularly preferred
R¹- stands for cyclopropyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl.
R²- stands for phenyl, which can be substituted up to twice in the same or different way by methyl or trifluoromethyl,
R³- for methyl, isopropyl, tert-butyl,
represents phenyl, which can be substituted up to twice in the same or different way by methyl, methoxy, fluorine, chlorine,
B - represents oxygen or sulfur,
X - for a group of the formula

stands and
A - for a group of the formula

stands in what
R⁶ means hydrogen and
R⁷ means hydrogen, methyl or ethyl or means a sodium or potassium cation.

In addition, a process for the preparation of the substituted Imidazolinone and Imidazolinthione the general formula (I)

in which

R¹, R², R³, A, B and X have the meaning given above to have,

found, which is characterized in that one Ketones of the general formula (VIII)

in which

R¹, R², R³ and B have the meaning given above, and
R⁷- is alkyl (C₁ to C₆), aryl (C₆ to C₁₂) or aralkyl (C₇ to C₁₀),

reduced,
in the case of the production of the acids, the esters are saponified,
in the case of the production of the lactones, the carboxylic acids are cyclized,
in the case of the preparation of the salts, either the esters or the lactones are saponified,
in the case of the production of the ethylene compounds (X = -CH₂-CH₂-) the ether compounds (X = -CH = CH-) are hydrogenated by customary methods,
and optionally separates isomers.

The process according to the invention can be illustrated by the following formula:

The reduction can be carried out with the usual reducing agents, preferred with those for the reduction of ketones suitable for hydroxy compounds are carried out. The reduction with is particularly suitable Metal hydrides or complex metal hydrides in inert Solvents, optionally in the presence of a trialkylborane. The reduction with complex is preferred Metal hydrides such as lithium boranate, sodium boranate, Potassium boronate, zinc boranate, lithium trialkylhydrido- borates, sodium trialkyl hydridoborates, sodium cyano-trihydro-borate or lithium aluminum hydride carried out. The reduction is very particularly preferred with sodium borohydride, in the presence of triethylborane carried out.

The usual organic solvents are suitable as solvents Solvents that are under the reaction conditions Don `t change. These preferably include ethers such as for example diethyl ether, dioxane, tetrahydrofuran or dimethoxyethane, or halogenated hydrocarbons such as for example dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, or hydrocarbons such as benzene, toluene or xylene. Likewise it is possible to use mixtures of the solvents mentioned.

The reduction of the ketone group is particularly preferred carried out to the hydroxy group under conditions at which the other functional groups such as  the alkoxycarbonyl group cannot be changed. The use of sodium borohydride is particularly suitable for this as a reducing agent, in the presence of Triethylborane in inert solvents such as preferably Ethers.

The reduction generally takes place in a temperature range from -80 ° C to room temperature (30 ° C), preferably from -78 ° C to 0 ° C.

The process according to the invention is generally described in Normal pressure carried out. But it is also possible that Carry out procedures under negative pressure or overpressure (e.g. in a range from 0.5 to 5 bar).

Generally the reducing agent is used in an amount from 1 to 2 mol, preferably from 1 to 1.5 mol, based on 1 mol of the keto compound used.

Under the reaction conditions given above generally the carbonyl group is reduced to the hydroxyl group, without reducing the double bond to the single bond he follows.

For the preparation of compounds of the general formula (I), in which X represents an ethylene grouping, can reduce the ketones (III) under such conditions be carried out, under which both the Carbonyl group and the double bond reduced becomes.  

In addition, it is also possible to reduce the Carbonyl group and the reduction of the double bond in two separate steps.

The carboxylic acids in the general formula (I) correspond to the formula (Ic)

in which

R¹, R², R³, R⁶, B and X have the meaning given above to have.

The carboxylic acid esters in the context of the general formula (I) correspond to the formula (Id)

in which

R¹, R², R³, R⁶, R⁷, B and X have the meaning given above, and
R⁷- stands for alkyl.

The salts of the compounds according to the invention in the context general formula (I) corresponds to formula (Ie)

in which

R¹, R², R³, R⁶, B and X have the meaning given above, and
M ^{n + stands} for an n -valent cation, in which n denotes 1 or 2.

The lactones in the general formula (I) correspond of the formula (If)

in which

R¹, R², R³, R⁶, B and X have the meaning given above to have.

To produce the carboxylic acids of the invention general formula (Ic) are generally the carboxylic acid esters of the general formula (Id) or the lactones the general formula (If) by customary methods saponified. The saponification is generally carried out by the esters or the lactones in inert solvents treated with conventional bases, generally initially the salts of the general formula (Ie) are formed, which is then treated in a second step with acid in the free acids of the general formula (Ic) can be transferred.

The usual bases are suitable for saponification inorganic bases. These preferably include alkali hydroxides or alkaline earth metal hydroxides such as Sodium hydroxide, potassium hydroxide or barium hydroxide, or alkali carbonates such as sodium or potassium carbonate or sodium bicarbonate, or alkali alcoholates such as Sodium ethanolate, sodium methoxide, potassium methoxide, Potassium ethanolate or potassium tert-butoxide. Especially sodium hydroxide or potassium hydroxide are preferred used.  

Water is suitable as a solvent for the saponification or the organic solvents customary for saponification. These preferably include alcohols such as methanol, Ethanol, propanol, isopropanol or butanol, or ether such as tetrahydrofuran or dioxane, or dimethylformamide or dimethyl sulfoxide. Alcohols are particularly preferred such as methanol, ethanol, propanol or isopropanol used. It is also possible to use mixtures of the above Use solvents.

The saponification is generally in a temperature range from 0 ° C to + 100 ° C, preferably from + 20 ° C to + 80 ° C.

In general, the saponification is carried out at normal pressure carried out. But it is also possible with negative pressure or work at overpressure (e.g. from 0.5 to 5 bar).

When the saponification is carried out, the base in generally in an amount of 1 to 3 mol, preferred from 1 to 1.5 mol based on 1 mol of the ester or Lactons used. It is particularly preferably used molar amounts of the reactants.

When carrying out the reaction arise in the first Step the salts of the compounds of the invention (Ie) as intermediates that can be isolated. The acids (Ic) according to the invention are obtained by treatment the salts (Ie) with conventional inorganic acids.  These preferably include mineral acids such as, for example Hydrochloric acid, hydrobromic acid, Sulfuric acid or phosphoric acid. It has with the Production of the carboxylic acids (Ic) is advantageous here proved the basic reaction mixture of saponification in a second step without isolating the Acidify salts. The acids can then be used in the usual way Way to be isolated.

For the preparation of the lactones of the formula according to the invention (If) are generally the carboxylic acids according to the invention (Ic) cyclized by conventional methods, for example by heating the corresponding acid in inert organic solvents, optionally in Presence of molecular sieve.

Hydrocarbons are suitable as solvents such as benzene, toluene, xylene, petroleum fractions, or tetralin or diglyme or triglyme. Preferred are benzene, Toluene or xylene used. Mixtures are also possible to use the solvents mentioned. Especially hydrocarbons are preferably used, in particular Toluene, in the presence of molecular sieve.

The cyclization is generally in a temperature range from -40 ° C to + 200 ° C, preferably from -25 ° C to + 50 ° C.

The cyclization is generally at normal pressure carried out, but it is also possible the procedure  to be carried out under vacuum or overpressure (e.g. in a range from 0.5 to 5 bar).

In addition, the cyclization is also carried out in inert organic Solvents, with the help of cyclizing or dehydrating agents. As a water-releasing Agents are preferred carbodiimides used. Preferred carbodiimides are N, N′-dicyclohexylcarbodiimide Paratoluenesulfonate, N-Cyclohexyl- N ′ - [2- (N ′ ′ - methylmorpholinium) ethyl] carbodiimide or N- (3-Dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride used.

The usual solvents are suitable here organic solvents. These preferably include ethers such as diethyl ether, tetrahydrofuran or dioxane, or Chlorinated hydrocarbons such as methylene chloride, chloroform or carbon tetrachloride, or hydrocarbons such as Benzene, toluene, xylene or petroleum fractions. Especially chlorinated hydrocarbons such as, for example, are preferred Methylene chloride, chloroform or carbon tetrachloride, or hydrocarbons such as benzene, toluene, xylene, or petroleum fractions. Be particularly preferred Chlorinated hydrocarbons such as methylene chloride, Chloroform or carbon tetrachloride used.

The reaction is generally in a temperature range from 0 ° C to + 80 ° C, preferably from + 10 ° C to + 50 ° C carried out.  

When performing the cyclization it turned out to be proved to be advantageous using the cyclization method use of carbodiimides as dehydrating agents.

The separation of the isomers into the stereoisomerically uniform constituents is generally carried out by customary methods as described, for example, by EL Eliel, Stereochemistry of Carbon Compounds, McGraw Hill, 1962. The separation of the isomers at the racemic lactone stage is preferred. The racemic mixture of the trans-lactones (VII) is particularly preferred here by treatment with either D - (+) - or L - (-) - α- methylbenzylamine by customary methods into the diastereomeric dihydroxyamides (Ig)

in which
Z and X have the meaning given above,

transferred, which is then, as usual, by chromatography or crystallization into the individual diastereomers can be separated. Subsequent hydrolysis the pure diastereomeric amides by customary methods, for example by treating the diastereomeric amides with inorganic bases such as sodium hydroxide or potassium hydroxide  in water and / or organic solvents such as Alcohols e.g. B. methanol, ethanol, propanol or isopropanol, give the corresponding enantiomerically pure dihydroxy acids (Ic) by cyclization as described above converted into the enantiomerically pure lactones can be. Generally applies to manufacturing of the compounds of the general formula according to the invention (I) in enantiomerically pure form that the configuration of the end products according to the method described above depends on the configuration of the starting materials.

The separation of isomers is to be exemplified in the following scheme:

The ketones (VIII) used as starting materials are New.

There has been a process for making the invention Ketones of the general formula (VIII)

in which

R¹, R², R³ and R⁸ have the meaning given above,

found, which is characterized in that one Aldehydes of the general formula (IX)

in which

R¹, R², R³ and B have the meaning given above,

in inert solvents with acetoacetic ester general formula (X)

in which

R⁸ has the meaning given above,

in the presence of bases.

The method according to the invention can, for example, by following formula scheme are explained:

The usual strongly basic bases come here Connections in question. These preferably include organolithium Compounds such as N-butyllithium, sec-butyllithium, tert-butyllithium or phenyllithium, or amides such as lithium diisopropylamide,  Sodium amide or potassium amide, or lithium hexamethyldisilyl amide, or alkali hydrides such as sodium hydride or potassium hydride. It is also possible to mix the use bases mentioned. Be particularly preferred N-butyllithium or sodium hydride or a mixture thereof used.

Possibly additions of metal halides such. B. Magnesium chloride or zinc bromide beneficial. Especially the addition of zinc bromide is preferred.

The usual organic solvents are suitable as solvents Solvents that are under the reaction conditions Don `t change. These preferably include ethers such as Diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane, or hydrocarbons such as benzene, toluene, xylene, Cyclohexane, hexane or petroleum fractions. Likewise it is possible to use mixtures of the solvents mentioned. Ethers such as diethyl ether are particularly preferred or tetrahydrofuran used.

The reaction is generally in a temperature range from -80 ° C to + 50 ° C, preferably from -20 ° C to room temperature carried out.

The process is generally carried out at normal pressure, however, it is also possible to use the vacuum method or perform at overpressure, e.g. B. in one Range from 0.5 to 5 bar.  

When performing the procedure, the acetoacetic ester generally in an amount of 1 to 2, preferred from 1 to 1.5 mol, based on 1 mol of the aldehyde used.

The acetoacetic esters used as starting materials Formula (X) are known or belong to known ones Methods are produced [Beilstein′s Handbuch der organic chemistry III, 632; 438].

Examples of acetoacetic esters for the process according to the invention are:
Methyl acetoacetate, ethyl acetoacetate, propyl acetoacetate, isopropyl acetoacetate.

The aldehydes used as starting materials general formula (IX) are new.

A method of making the Aldehydes of the general formula (IX)

in which

R¹, R², R³ and B have the meaning given above,

found, which is characterized in that one Imidazolinone and Imidazolinthione the general Formula (XI)

in which

R¹, R², R³ and B have the meaning given above,

in inert solvents in the presence of auxiliary substances with N, N-dialkylaminoacrolein of the formula (XII)

in which

Alkyl for a straight-chain or branched hydrocarbon residue has 1 to 6 carbon atoms,

implements.

The method according to the invention can, for example, by the following formula scheme can be clarified:

The usual organic solvents are suitable as solvents Solvents operating under the reaction conditions are stable. These preferably include hydrocarbons such as benzene, toluene, xylene, hexane, petroleum fractions,  Chlorobenzene or dichlorobenzene, or ethers such as diethyl ether, Dioxane or tetrahydrofuran, or chlorinated hydrocarbons such as methylene chloride, chloroform or carbon tetrachloride or acetonitrile. It is also possible Use mixtures of the solvents mentioned. Anhydrous acetonitrile or is particularly preferred Chloroform used.

Acid chlorides are generally used as auxiliaries. Phosphorus oxychloride or phosgene is preferred, particularly preferably used phosphorus oxychloride.

The reaction takes place in a temperature range of -20 ° C up to + 150 ° C, preferably from 0 ° C to + 100 ° C.

The process is generally carried out at normal pressure. However, it is also possible to use the vacuum process or with overpressure (e.g. in a Range from 0.5 to 5 bar).

When performing the process, the dimethylaminoacrolein generally in an amount of 2 to 6, preferably from 3 to 4 mol, based on 1 mol of Pyrroles used.

The imidazolinones and Imidazolinthiones of the general formula (XI) are known or can be based on known methods Aminoketones can be produced [EP-A-222 664].  

The amino ketones used as starting materials are known or can be prepared by known methods become [Methods of Organic Chemistry, Vo. 7 / 2c, 2251 ff (1977); J. Org. Chem. 33, 494 (1968)].

The compounds of the general formula (I) according to the invention have valuable pharmacological properties and can be used in medicines. In particular, the inhibitors of 3-hydroxy-3- methyl-glutaryl coenzyme A (HMG-CoA) reductase and as a result its inhibitors of cholesterol biosynthesis. they can therefore be used to treat hyperlipoproteinemia, Lipoproteinemia or atheriosclerosis can be used.

The new active ingredients can in a known manner usual formulations are transferred, such as tablets, Coated tablets, pills, granules, aerosols, syrups, emulsions, Suspensions and solutions using inert non-toxic, pharmaceutically suitable carriers or solvent. Here, the therapeutic active compound in a concentration from about 0.5 to 98% by weight, preferably 1 to 90% by weight, the total mixture is present, d. H. in quantities that are sufficient to the specified dosage range to reach.

The formulations are produced, for example by stretching the active ingredients with solvents and / or carriers, optionally using of emulsifiers and / or dispersants, where e.g. B. in the case of the use of water as a diluent optionally organic solvents as Auxiliary solvents can be used.  

Examples of auxiliary substances are: Water, non-toxic organic solvents, such as Paraffins (e.g. petroleum fractions), vegetable oils (e.g. Peanut / sesame oil), alcohols (e.g. ethyl alcohol, glycerin), Carriers such as B. natural stone powder (e.g. Kaolins, clays, talc, chalk), synthetic stone powder (e.g. highly disperse silica, silicates), Sugar (e.g. cane, milk and dextrose), emulsifier (e.g. polyoxyethylene fatty acid esters, polyoxyethylene Fatty alcohol ethers, alkyl sulfonates and aryl sulfonates), Dispersing agents (e.g. lignin, sulfite waste liquor, Methyl cellulose, starch and polyvinyl pyrrolidone) and Lubricants (e.g. magnesium stearate, talc, stearic acid and sodium lauryl sulfate).

The application is carried out in the usual way, preferably oral, parenteral, perlingual or intravenous. In the event of Oral use can of course take tablets in addition to the carriers mentioned, also additives such as sodium citrate, Calcium carbonate and dicalcium phosphate together with various additives, such as starch, preferably potato starch, gelatin and the like contain. Lubricants, such as magnesium stearate, Sodium lauryl sulfate and talc for tabletting can also be used. In the case of aqueous suspensions the active substances apart from the above-mentioned auxiliary substances with various flavor enhancers or colors be transferred.

In the case of parenteral use, solutions can be found of the active ingredients using suitable liquid  Carrier materials are used.

In general, it has been found to be beneficial in intravenous administration amounts of about 0.001 to 1 mg / kg, preferably about 0.01 to 0.5 mg / kg body weight to deliver effective results, and with oral application the dosage is about 0.01 to 20 mg / kg, preferably 0.1 to 10 mg / kg Body weight.

Nevertheless, it may be necessary from deviate from the amounts mentioned, depending on body weight or type of application route, individual behavior towards the drug, the type of wording and the time or interval at which the administration takes place. So in some cases it may be enough with less to get by as the aforementioned minimum amount, while in other cases the upper limit mentioned must be exceeded. Larger in the case of application In quantities it may be advisable to combine them in several To distribute individual doses throughout the day.

Example 1 2- (benzyl-methylamino) -1- (4-fluorophenyl) -1-oxo-ethane hydrochloride

A solution of 4-fluorophenacyl bromide (70.9 g, 0.33 mol) in 310 ml of diethyl ether is added dropwise to a solution of 81.8 g (0.68 mol) of N-methylbenzylamine in 220 ml of diethyl ether and the mixture is stirred over night. The precipitate is separated off, the filtrate is mixed with hydrochloric acid gas, residual methylbenzylamine hydrochloride is separated off, the filtrate is stirred with acetone, the product precipitating.
Yield: 52.8 g, 55% of theory
1 H-NMR (DMSO): δ = 2.85 (s, 3H, CH₃); 4.5 (br, 2H, CH₂); 5.1 (br, 2H, CH₂C = O); 7.3-8.2 (m, 9H, aromatics-H) ppm.

Example 2 1- (4-fluorophenyl) -2-methylamino-1-oxo-ethane hydrochloride

1.2 g of 10% palladium on carbon are added to a solution of 10 g (31 mmol) of the compound from Example 1 in 200 ml of glacial acetic acid under a nitrogen atmosphere. After the hydrogenation in a shaker (hydrogen absorption approx. 700 ml), the catalyst is filtered off, the solvent is distilled off, the product is washed with water and dried.
Yield: 7.2 g, 97% of theory
1 H-NMR (DMSO): δ = 2.6 (s, 3H, CH₃); 4.75 (s, 2H, CH₂); 7.3-8.2 (m, 4H, aromatic-H); 9.5 (br, 2H, NH) ppm.

Example 3 N- [2- (4-fluorophenyl) -2-oxo-ethyl] -N-methyl-N'-phenylurea

1.26 g (12.5 mmol) of phenyl isocyanate are added to a suspension of 3 g (12.5 mmol) of the compound from Example 2 in 30 ml of toluene, and 1.5 g (12.5 mmol) are slowly added dropwise at 0.degree ) Add triethylamine. It is stirred at 25 ° C. overnight. The toluene phase is washed with water, the product precipitating. After drying, 3.54 g are obtained.
Yield: 98.9% of theory
1 H-NMR (DMSO): δ = 2.8 (s, 2H, CH₂); 3.35 (s, 3H, CH₃); 3.6 (s, 1H, NH); 6.9-7.6 (m, 9H, aromatics-H) ppm.

Example 4 4- (4-fluorophenyl) -1-methyl-3-phenyl-4-imidazolin-2-one

3.5 g (12.2 mmol) of the compound from Example 3 are heated under reflux in 50 ml of glacial acetic acid, the solvent is removed and the residue is washed with water. After drying, 3.12 g are obtained.
Yield: 95.3% of theory
1 H-NMR (DMSO): δ = 3.3 (s, 3H, CH₃); 6.9 (s, 1H, imidazole-H); 7.0-7.5 (m, 9H, aromatics-H) ppm.

Example 5 (E) -3- [4- (4-fluorophenyl) -1-methyl-3-phenyl-4-imidazolin-2-one-5-yl] -p-rop-2-enal

1.54 ml (14 mmol) of N, N-dimethylaminoacrolein in 5.3 ml of acetonitrile are added dropwise to 1.37 ml (15 mmol) of phosphorus oxychloride in 8.5 ml of acetonitrile at 0 ° -5 ° C. in the course of 10 minutes under a nitrogen atmosphere. After 10 min, a solution of 1.3 g (5 mmol) of the compound from Example 4 in 10 ml of acetonitrile is added and the mixture is heated to boiling overnight. At 10 ° C., 3.7 g of sodium hydroxide in 50 ml of water / 50 ml of toluene are added, the aqueous phase is washed again with toluene, the organic phases are dried and, after crystallization from ether, 0.85 g is obtained.
Yield: 51.2% of theory
1 H-NMR (CDCl₃): δ = 3.6 (s, 3H, CH₃); 6.5 (dd, 1H, CH- CHO); 7.0-7.5 (m, 10H, aromatics-H, CH); 9.5 (d, 1H, CHO) ppm.

Example 6 Methyl- (E) -7- [4- (4-fluorophenyl) -1-methyl-3-phenyl-4- imidazolin-2-one-5-yl] -5-hydroxy-3-oxo-hept-6-enoate

Under nitrogen, dropwise to a suspension of 135 mg (5.6 mmol) sodium hydride in 14 ml tetrahydrofuran at -5 ° C 0.59 ml (5.4 mmol) methyl acetoacetate. After 15 min, 4.0 ml (5.6 mmol) of 15% n-butyllithium in n-hexane are added dropwise at -5 ° C., the mixture is stirred for 15 min, and a solution of 1.3 g (5.9 mmol) is added Zinc bromide in 20 ml THF, stirred for 15 min and added a solution of 0.6 g (1.8 mmol) of the compound from Example 5 in 6 ml tetrahydrofuran. After 30 min at -5 ° C., the mixture is hydrolyzed with saturated ammonium chloride solution, washed three times with dichloromethane, the organic phase is dried and, after removal of the solvent and washing of the residue with petroleum ether, 380 mg are obtained.
Yield: 48% of theory
1 H-NMR (CDCl₃): δ = 2.7; 3.0 (2d, 2H, CH₂); 3.5 (s, 5H, NCH₃, CH₂C = O); 3.7 (s, 3H, OCH₃); 4.65 (br, 1H, CHOH); 5.9 (dd, 1H, CH CHO); 6.4 (d, 1H, CH); 6.9-7.4 (m, 9H, aromatics-H) ppm.

Example 7 Methyl erythro- (E) -3,5-dihydroxy-7- [4- (4-fluorophenyl) -1- methyl 3-phenyl-4-imidazolin-2-one-5-yl] -hept-6-enoate

Air is blown at -30 ° C. for 5 min through a solution of 350 mg (0.8 mmol) of the compound from Example 6 and 1.12 ml (1.12 mmol) of triethylborane (1m in tetrahydrofuran) in 7 ml of tetrahydrofuran 42.3 mg (1.12 mmol) of sodium borohydride and slowly 0.76 ml of methanol are added, the mixture is stirred at -30 ° C. for 30 minutes, a mixture of 3 ml of 30% hydrogen peroxide solution and 6.5 ml of water is added to bring the temperature Does not exceed 0 ° C., diluted with water after 30 min, washed three times with ethyl acetate, the organic phase washed with sodium hydrogen carbonate solution, dried, the solvent removed in vacuo and, after chromatography on silica gel (ethyl acetate), obtained 60 mg.
Yield: 17% of theory
1 H-NMR (CDCl₃): δ = 1.6 (m, 2H, CH₂); 2.5 (m, 2H, CH₂C = O); 3.4 (s, 3H, NCH₃); 3.7 (s, 3H, CH₃); 4.2 (br, 1H, CHOH); 4.4 (br, 1H, CHOH); 5.9 (dd, 1H, CH CHOH); 6.3 (d, 1H, CH); 6.8-7.5 (m, 9H, aromatics-H) ppm.

Example 8 2- (benzyl-isopropylamino) -1- (4-fluorophenyl) -1-oxo-1-ethane hydrochloride id

Analogously to Example 1, 46.9 g of 2- (benzyl-isopropylamino) -1- (4-fluorophenyl) -1-oxo are obtained from 55 g (0.25 mol) of 4-fluorophenacyl bromide and 78 g (0.52 mol) of isopropylbenzylamine -1-ethane hydrochloride.
Yield: 57.5% of theory
1 H-NMR (DMSO): δ = 1.4 (dd, 6H, CH₃); 3.8 (m, 1H, CH); 4.4 (m, 2H, CH₂); 5.0 (m, 2H, CH₂C = O); 7.2-8.0 (m, 9H, aromatics-H) ppm.

Example 9 1- (4-fluorophenyl) -2-isopropylamino-1-oxo-ethane hydrochloride

Analogously to Example 2, 25.7 g of 1- (4-fluorophenyl) -2-isopropylamino-1-oxo-ethane hydrochloride are obtained from 44.8 g (0.14 mol) of the compound from Example 8.
Yield: 79.8% of theory
1 H-NMR (DMSO): δ = 1.3 (d, 6H, CH₃); 3.4 (m, 1H, CH); 4.8 (br, 2H, CH₂); 7.4-8.3 (m, 4H, aromatics-H) ppm.

Example 10 N- [2- (4-fluorophenyl) -2-oxo-ethyl] -N-isopropyl-N'-phenylurea

Analogously to Example 3, from 7.0 g (30.2 mmol) of the compound from Example 9 and 3.05 g (30.2 mmol) of phenyl isocyanate, 6.3 g of N- [2- (4-fluorophenyl) -2- oxo-ethyl] -N-isopropyl-N'-phenylurea.
Yield: 66.4% of theory
1 H-NMR (CDCl₃): δ = 1.2 (dd, 6H, CH₃); 2.9 (s, 1H, NH); 3.5 (dd, 2H, CH₂); 4.35 (m, 1H, CH); 6.9-7.6 (m, 9H, aromatics-H) ppm.

Example 11 4- (4-fluorophenyl) -1-isopropyl-3-phenyl-4-imidazolin-2-one

Analogously to Example 4, 5.3 g (16.9 mmol) of the compound from Example 10 are used to obtain 4.6 g of 4- (4-fluorophenyl) -1-isopropyl-3-phenyl-4-imidazolin-2-one.
Yield: 91.9% of theory
1 H-NMR (CDCl₃): δ = 1.4 (d, 6H, CH₃); 4.5 (m, 1H, CH); 6.45 (s, 1H, CH); 6.8-7.4 (m, 9H, aromatics-H) ppm.

Example 12 (E) -3- [4- (4-fluorophenyl) -1-isopropyl-3-phenyl-4-imidazolin-2-one-5-yl -] - pro 04853 00070 552 001000280000000200012000285910474200040 0002003805884 00004 04734p-2-enal

Analogously to Example 5, 2.0 g (6.8 mmol) of the compound from Example 11 gave 1.6 g of (E) -3- [4- (4-fluorophenyl) -1-isopropyl-3-phenyl-4- imidazolin-2-one-5-yl] prop-2-enal.
Yield: 67.7% of theory
1 H-NMR (CDCl₃): δ = 1.6 (d, 6H, CH₃); 4.6 (m, 1H, CH); 6.2 (d, 1H, CH CHO); 6.9-7.4 (m, 10H, aromatic-H, CH); 9.4 (d, 1H, CHO) ppm.

Example 13 Methyl- (E) -7- [4- (4-fluorophenyl) -1-isopropyl-3-phenyl-4- imidazolin-2-one-5-yl] -5-hydroxy-3-oxo-hept-6-enoate

Analogously to Example 6, 0.8 g (2.3 mmol) of the compound from Example 12 gives 1.1 g of crude product, after chromatography on silica gel (dichloromethane / methanol 10: 1), 0.8 g of methyl (E) is obtained. -7- [4- (4-fluorophenyl) -1-isopropyl-3-phenyl-4-imidazolin-2-one-5-yl] -5-hydroxy-3-oxo-hept-6-enoate.
Yield: 75% of theory
1 H-NMR (CDCl₃): δ = 1.6 (d, 6H, CH₃); 2.7; 3.0 (2d, 2H, CH₂); 3.4 (s, 2H, CH₂); 3.75 (s, 3H, CH₃); 4.4 (m, 1H, CH); 4.6 (m, 1H, CH-OH); 5.6 (dd, 1H, CH); 6.4 (d, 1H, CH); 6.8-7.4 (m, 9H, aromatics-H) ppm.

Example 14 Methyl erythro- (E) -3,5-dihydroxy-7- [4- (4-fluorophenyl) -1- isopropyl-3-phenyl-4-imidazolin-2-one-5-yl] -hept-6-enoate

Analogously to Example 7, 320 mg of methyl erythro- (E) -3,5-dihydroxy-7- [4- (4-fluorophenyl) -1- are obtained from 0.8 g (1.7 mol) of the compound from Example 13. isopropyl-3-phenyl-4-imidazolin-2-one-5-yl] -hept-6-enoate.
Yield: 40% of theory
1 H-NMR (CDCl₃): δ = 1.5 (m, 8H, CH₃, CH₂); 2.5 (m, 2H, CH₂); 3.7 (s, 3H, CH₃); 4.2; 4.4 (2m, 2H, CH); 4.5 (m, 1H, CH); 5.6 (dd, 1H, CH); 6.4 (d, 1H, CH); 6.8-7.3 (m, 9H, aromatics-H) ppm.

Application example Example 15

The enzyme activity determination was modified according to GC Ness et al., Archives of Biochemistry and Biophysics 197, 493-499 (1979). Male Ricorats (body weight 300-400 g) were treated for 11 days with altromin powder feed, to which 40 g colestyramine / kg feed was added. After decapitation, the liver was removed from the animals and placed on ice. The livers were crushed and in the Potter-Elvejem homogenizer 3 times in 3 volumes 0.1 m sucrose, 0.05 m KCl, 0.04 m K _x H _y phosphate, 0.03 m ethylenediaminetetraacetic acid, 0.002 m dithiothreitol (SPE) Buffer, pH 7.2, homogenized. The mixture was then centrifuged at 15,000 * g for 15 minutes and the sediment was discarded. The supernatant was sedimented at 100,000 g for 75 minutes. The pellet is taken up in ¼ volume of SPE buffer, homogenized again and then centrifuged again at 100,000 g for 60 minutes. The pellet is taken up with 5 times its volume in the SPE buffer, homogenized and frozen and stored at -78 ° C. (= enzyme solution).

For the test, the test compounds (or mevinolin as reference substance) were dissolved in dimethylformamide with the addition of 5% by volume of 1N NaOH and used in the enzyme test with 10 μl in various concentrations. The test was started after 20 minutes of pre-incubation of the compounds with the enzyme at 37 ° C. The test batch was 0.380 ml and contained 4 μmol glucose-6-phosphate, 1.1 mg bovine serum albumin, 2.1 μmol dithiothreitol, 0.35 μmol NADP, 1 unit glucose-6-phosphate dehydrogenase, 35 μmol K _x H _y phosphate, pH 7.2, 20 ul enzyme preparation and 56 nmol of 3-hydroxy-3-methyl-glutaryl coenzyme A (glutaryl-3 -13 C) 100,000 dpm.

After an incubation of 60 minutes at 37 ° C the Centrifuged and 600 µl of the supernatant on a 0.7 × 4 cm with a 5-chloride 100-200 mesh (anion exchanger) filled column applied. It was with 2 ml least Washed water and run plus wash water mixed with 3 ml of a scintillation solvent and counted in the LKB scintillation counter. IC₅₀ values were by applying the percent inhibition against the Concentration of the compound in the test by intrapolation certainly. To determine the relative inhibitory Potency became the IC₅₀ value of the reference substance mevinolin set as 100 and with the simultaneously determined IC₅₀ value of the test compound compared.

The active ingredients according to Examples 1 to 14 show in Comparison in mevinolin a higher effect.

Claims (15)

1. Substituted imidazolinones and imidazolinthiones of the general formula in which
R¹ - stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R² - stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl or
- stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
or
- represents heteroaryl, which can be substituted up to 3 times by identical or different halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂- or -CH = CH- and
A - for a group of the formula stands,
wherein
R⁶ means hydrogen or alkyl and
R⁷ - hydrogen,
- A methyl, aralkyl or aryl radical or
- means a cation. 2. Substituted imidazolinones and imidazolinthiones according to claim 1 of the formulas,
wherein
R¹ - stands for cyclopropyl, cyclopentyl or cyclohexyl or
- represents lower alkyl, which can be substituted by fluorine, chlorine, bromine, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfonyl, lower alkoxycarbonyl, benzoyl, lower alkylcarbonyl, by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ are the same or different and are lower alkyl, phenyl, benzyl, acetyl, benzoyl, phenylsulfonyl or lower alkylsulfonyl,
or by pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, pyrryl, indolyl, thienyl, furyl, imidazolyl, oxazolyl, thiazolyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio, benzylsulfonyl, phenylethylphenyl, ethyl, phenylsulfonyl, phenyl The heteroaryl and aryl radicals mentioned can be substituted up to twice in the same or different manner by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, trifluoromethyl or trifluoromethoxy,
R² - represents thienyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, benzoxazolyl, benzothazolyl, benzothazolyl, benzothazolyl, benzothazolyl, benzothazolyl, benzothazolyl, benzothazolyl, benzothazolyl, benzothazolyl may be substituted the same or different by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy or lower alkoxycarbonyl, or
represent phenyl or naphthyl, which can be substituted up to four times by the same or different substituents by lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenyl, phenyloxy, phenylthio, phenylsulfonyl, benzyl, benzyloxy, benzylthio, benzylsulfonyl, phenethyl, phenylethoxy, phenylethylsulfonyl, phenyl Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, lower alkoxycarbonyl or through a group of the formula -NR⁴R⁵,
in which
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
- stands for benzoyl or lower alkylcarbonyl or
- represents lower alkylsulfonyl, phenylsulfonyl or tolylsulfonyl or
- stands for aminocarbonyl, lower alkylaminocarbonyl, di-lower alkylaminocarbonyl, phenylaminocarbonyl or lower alkoxycarbonyl or
- stands for cyclopropyl, cyclopentyl or cyclohexyl or
- represents lower alkyl, which can be substituted by fluorine, chlorine, bromine, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfonyl, lower alkoxycarbonyl, benzoyl, lower alkylcarbonyl, by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ are the same or different and are lower alkyl, phenyl, benzyl, acetyl, benzoyl, phenylsulfonyl or lower alkylsulfonyl,
or by pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, pyrrolyl, indolyl, thienyl, furyl, imidazolyl, oxazolyl, thiazolyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio, benzylsulfonyl, phenylethysylonethyl, phenylethysulfonyl, phenyl The heteroaryl and aryl radicals mentioned can be substituted up to twice in the same or different manner by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, trifluoromethyl or trifluoromethoxy,
are thienyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, indolyl, isoindolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, benzothiazolyl, benzoxazolyl or benzimidazolyl, which up to 2 times the same - or can be substituted differently by fluorine, chlorine, bromine, lower alkyl, lower alkoxy, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy or lower alkoxycarbonyl, or
represent phenyl or naphthyl, which can be substituted up to four times by the same or different substituents by lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenyl, phenyloxy, phenylthio, phenylsulfonyl, benzyl, benzyloxy, benzylthio, benzylsulfonyl, phenethyl, phenylethoxy, phenylethylsulfonyl, phenyl Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, lower alkoxycarbonyl or through a group of the formula -NR⁴R⁵,
in which
R⁴ and R⁵ have the meaning given above,
B - represents a group of the formula O or S,
X - represents a group of the formula -CH₂-CH₂- or -CH = CH-,
A - for a group of the formula stands,
wherein
R⁶ means hydrogen or lower alkyl and
R⁷ - alkyl (C₁ to C₆), aryl (C₆ to C₁₂) or aralkyl (C₇ to C₁₀) means or - means a physiologically compatible cation. 3. Substituted imidazolinones and imidazolinthiones according to claims 1 and 2,
wherein
R¹ - stands for cyclopropyl, cyclopentyl or cyclohexyl or
- represents methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl, which can be substituted by fluorine, chlorine, bromine, cyano, methoxy; Ethoxy, propoxy, isopropoxy, butoxy, sec.-butoxy, tert.butoxy, methylthio, ethylthio, propylthio, isopropylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, butoxycarbonyl, butoxy. Butoxycarbonyl, benzoyl, acetyl, pyridyl, pyrimidyl, thienyl, furyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio or benzenesulfonyl,
R² - stands for pyridyl, pyrimidyl, quinolyl or isoquinolyl, which can be substituted by fluorine, chlorine, methyl, methoxy or trifluoromethyl, or
represents phenyl, which can be substituted up to three times in the same or different ways by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, methylthio, ethylthio, propylthio, isopropylthio, methylsulphonyl, ethylsulphonyl, propylsulphonyl, isopropylsulphonyl, phenyl, phenoxy, benzyl, benzyloxy, fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, Isospropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl or t-butoxycarbonyl,
R³ - represents hydrogen, cyclopropyl, cyclopentyl or cyclohexyl or
represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl or isohexyl, which can be substituted by fluorine, chlorine, bromine, cyano, methoxy, ethoxy, propoxy, isopropoxy, butoxy, Isobutoxy, tert.butoxy, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, tert.butylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, ethoxycarbonyl, troxyboxyfoxy, troxycarbonyl Butoxycarbonyl, isobutoxycarbonyl, tert.butoxycarbonyl, benzoyl, acetyl, ethylcarbonyl or through a group -NR⁴R⁵,
in which
R⁴ and R⁵ are the same or different and are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, phenyl, benzyl, acetyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl or phenylsulfonyl,
or by pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinoline, isoquinolyl, thienyl, furyl, phenyl, phenoxy, phenylthio, phenylsulfonyl, benzyloxy, benzylthio or benzylsulfonyl, the heteroaryl and aryl radicals mentioned being fluorine, chlorine, methyl, ethyl, propyl Isopropyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, trifluoromethyl or trifluoromethoxy may be substituted, or
- stands for thienyl, furyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazolyl, isooxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, quinolyl, isoquinolyl, benzoxazolyl, benzimidazolyl or benzothiazolyl, with the radicals mentioned being, Propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, propoxycarbonyl, butoxycarbonyl or isobutoxycarbonyl. Butoxycarbonyl may be substituted, or
- stands for phenyl which is up to 3 times the same or different by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert .Butoxy, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, tert.Butylthio, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert.Butylsulfonyl, phenyl, phenoxy, phenylthio, phenylsulphonyl, benzyl, benzyloxy, benzylthio, benzylsulphonyl , Fluorine, chlorine, bromine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert.butoxycarbonyl or can be substituted by a group -NR⁴R⁵,
in which
R⁴ and R⁵ have the meaning given above,
or
R³ - stands for benzoyl, acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert.butylsulfonyl, phenylsulfonyl or tolylsulfonyl,
- for aminocarbonyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butylaminocarbonyl, dimethyl, diethyl, dipropyl, diisopropyl, dibutyl or diisobutylaminocarbonyl, phenylaminocarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl , Isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl or tert.butoxycarbonyl,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂- or -CH = CH-,
A - for a group of the formula stands,
wherein
R⁶ means hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl and
R⁷ means hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl or benzyl or means a sodium, potassium, calcium or magnesium or ammonium ion. 4. Substituted imidazolinones and imidazolinthione according to claim 1 for therapeutic treatment. 5. Process for the preparation of substituted imidazolinones and imidazolinethiones of the general formula in which
R¹ - stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl or aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro, trifluoro, identical, or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R² - stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein
R⁴ and R⁵ have the meaning given above, or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl or
- stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl or aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro, trifluoro, identical, or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
or
- represents heteroaryl, which can be substituted up to 3 times by identical or different halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂- or -CH = CH-, and
A - for a group of the formula stands,
wherein
R⁶ means hydrogen or alkyl and
R⁷ - hydrogen,
- An alkyl, aryl or aralkyl radical or
- a cation means
characterized in that ketones of the general formula (VIII) in which
R¹, R², R³ and B have the meaning given above and
R⁷ represents alkyl (C₁ to C₆), aryl (C₆ to C₁₂) or aralkyl (C₇ to C₁₀),
reduced,
in the case of the production of the acids, the esters are saponified,
in the case of the production of the lactones, the carboxylic acids are cyclized,
in the case of the preparation of the salts, either the esters or the lactones are saponified,
in the case of the production of the ethylene compounds (X = -CH₂-CH₂-) the ethene compounds (X = -CH = CH-) are hydrogenated by customary methods,
and optionally separates isomers. 6. The method according to claim 5, characterized in that the reduction in the temperature range of -80 ° C up to + 30 ° C is carried out. 7. Medicaments containing substituted imidazolinones and imidazolinthione according to claim 1. 8. Medicament according to claim 7, containing 0.5 to 90% by weight of the substituted imidazolinones and Imidazolinthione. 9. Use of substituted imidazolinones and Imidazolinthions according to claim 1 for treatment of diseases. 10. Use of substituted imidazolinones and Imidazolinthions according to claim 9 for treatment of hyperlipoproteinemia, lipoproteinemia or Atherosclerosis. 11. Use of substituted imidazolinones and Imidazolinthions according to claim 1 for the preparation of drugs.   12. Ketones of the general formula in which
R¹ - stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - the same or different are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R² - stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl or
- stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl or aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro, trifluoro, identical, or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
- represents heteroaryl, which can be substituted up to 3 times identically or differently by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
or
- stands for aryl, which is up to 5 times the same or different by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluorocarbonylthio , Sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂ or -CH = CH-, and
R⁸ - represents alkyl, aryl or aralkyl. 13. Process for the preparation of ketones of the general formula in which
R¹ - stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R² - stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl or
- stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl or aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro, trifluoro, identical, or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
- represents heteroaryl, which can be substituted up to 3 times identically or differently by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
or
- stands for aryl, which is up to 5 times the same or different by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluorocarbonylthio , Sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
B - represents oxygen or sulfur,
X - represents a group of the formula -CH₂-CH₂ or -CH = CH- and
R⁷ - represents alkyl, aryl or aralkyl,
characterized in that aldehydes of the general formula (IX) in which
R¹, R², R³ and B have the meaning given above,
in inert solvents with acetoacetic ester of the general formula (X) in which
R⁸ has the meaning given above,
in the presence of bases. 14. Aldehydes of the general formula in which
R¹ - stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl or aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro, trifluoro, identical, or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R² - stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl or
- stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
- represents heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above, and
B - represents oxygen or sulfur. 15. Process for the preparation of aldehydes of the general formula in which
R¹ - stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl or aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro, trifluoro, identical, or different, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
R² - stands for heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or by a group of the formula -NR⁴R⁵ ,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
R³ - for hydrogen or
stands for acyl, alkylsulfonyl or arylsulfonyl, where the aryl radical can be substituted by alkyl or halogen, or
- stands for aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl or alkoxycarbonyl or
- stands for cycloalkyl or
represents alkyl, which can be substituted by halogen, cyano, alkoxy, alkylthio, alkylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfonyl, alkoxycarbonyl, acyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴, R⁵ - are identical or different and are alkyl, aryl, aralkyl, acyl, alkylsulfonyl or arylsulfonyl,
or by carbamoyl, dialkylcarbamoyl, sulfamoyl, dialkylsulfamoyl, heteroaryl, aryl, aryloxy, arylthio, arylsulfonyl, aralkoxy, aralkylthio or aralkylsulfonyl, the heteroaryl and aryl radicals of the latter substituents being up to 3 times the same, different by trifluoro, trifluoro same, different, by different or identical, Alkyl, alkoxy, alkylthio or alkylsulfonyl can be substituted,
- represents heteroaryl, which can be substituted up to 3 times identically or differently by halogen, alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, alkoxycarbonyl or a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above,
or
represents aryl, which can be substituted up to 5 times in the same or different ways by alkyl, alkoxy, alkylthio, alkylsulfonyl, aryl, aryloxy, arylthio, arylsulfonyl, aralkyl, aralkoxy, aralkylthio, aralkylsulfonyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, Trifluoromethylthio, alkoxycarbonyl, sulfamoyl, dialkylsulfamoyl, carbamoyl, dialkylcarbamoyl or by a group of the formula -NR⁴R⁵,
wherein
R⁴ and R⁵ have the meaning given above, and
B - represents oxygen or sulfur,
characterized in that imidazolinones and imidazolinthiones of the general formula (XI) in which
R¹, R², R³ and B have the meaning given above,
in inert solvents in the presence of auxiliaries with N, N-dialkylaminoacrolein of the formula (XII) in which
Alkyl represents a straight-chain or branched hydrocarbon radical having 1 to 6 carbon atoms,
implements.