DE2945238A1 - N-aminocarbonyl or thiocarbonyl fused heterocyclic cpds. - useful for treating diseases of lipid metabolism - Google Patents

Abstract

The use of urea derivs. of formula (I) for treating diseases of lipid metabolism is new (Y is R or the gp. Q. n1 and n2 are 3-9. l is 0 or 1. R is up to 20C aliphatic hydrocarbyl (linear, branched or cyclic opt. unsatd. opt. substd. by halo, hydroxy, alkoxy, alkoxycarbonyl or opt. substd. aryl). R1 is H or lower alkyl. R2 is lower alkyl. R3, R4 and R5 are each H, halo, hydroxy, cyano, alkyl, alkoxy, alkoxycarbonyl, alkylthio, alkylsulphonyl, alkylsulphinyl, alkylcarbonyl (all lower), or opt. substd. aryl or aryloxy. X is oxygen or sulphur. A is -CR'R"-, -CR'R"-CH2-, -CR'=CH- or -Z-CR'R". Z is O, N(R") or -S(O)m. R' and R" are each H or lower alkyl. R"' is lower alkyl. m is 0-2). Cpds. (I) are new when R1 and R2 are 1-2C alkyl; R3, R4 and R5 are each H, chloro bromo-triflyoromethyl, alkyl, alkylthio, or alkoxy (all 1-4C), phenoxy or chlorophenoxy; A is -CR'R"-, -CR'R"-CH2-, -O.CR'R"- or -S.CR'R"-, with R' and R" each H, methyl, or ethyl, X is oxygen and (a) R is 6-18C alkyl or alkenyl (linear, branched or cyclic) opt. substd. by chloro, fluoro, 1-4C alkoxy or phenyl, or (b) R is the gp. Q. Cpds. include N.n.dodecyl aminocarbonyl -2,2,4-trimethyl 1,2,3,4-tetrahydroquinoline. Some (I) are already known to have phytotoxic activity and some are used as antidotes for iron poisoning. They are now found to have a strongly inhibiting action on lipid absorption in humands and animals so can be used to treat hyperlipidaemia. The usual daily dose is 1-50 mg per kg.

Description

Use of alkyl urea derivatives in pharmaceuticals

tools for the treatment of lipid metabolism disorders The present The invention relates to the use of known and new alkyl urea derivatives in drugs to influence lipid metabolism, as well as some new compounds from this class of substances.

Some of the alkyl urea derivatives useful in the present invention are already known (see M. Mazza et al, Farmaco, Ed. Sci. 32, No. 1, 54-66 (1977)). Phytotoxic effects have already been described for these known compounds. Some derivatives of ethoxiquin can also be used as iron poisoning inhibitors can be used (see DT-OS 2 802 630). Their effect on lipid metabolism, in particular their lipid absorption inhibiting effect is not yet known become.

The present invention relates to the use of alkyl urea derivatives of the general formula (I) in which R stands for a straight-chain, branched, cyclic, saturated or unsaturated aliphatic hydrocarbon radical having up to 20 carbon atoms, which is optionally substituted by halogen, hydroxy, alkoxy, alkoxycarbonyl or optionally substituted aryl, R1 is hydrogen or lower alkyl, R2 is lower alkyl and R3, R4 and R5 are identical or different and each represent hydrogen, halogen, hydroxy, cyano, lower alkyl, lower alkoxy, lower alkoxycarbonyl, lower alkyl mercapto, lower alkylsulphonyl, lower alkylsulphinyl, lower alkylcarbonyl, optionally substituted aryl or optionally substituted aryloxy, X is oxygen or sulfur and A stands for one of the following radicals where R 'and R "are the same or different and are each hydrogen or lower alkyl, R"' is lower alkyl and m is 0, 1 or 2, in the treatment of disorders of lipid metabolism and in the production of drugs that influence lipid metabolism and some new compounds this group of substances.

Surprisingly, the alkylurea derivatives show the general Formula (I) has a strong lipid absorption inhibiting effect. With knowledge of the stand the technology could not be expected that compounds of this class of substances as lipid absorption inhibiting agents can be used.

The first use of the compounds according to the invention in the Combating hyperlipemia enables the treatment of patients who have Intolerance or habituation to already known lipid absorption inhibitors demonstrate. They therefore represent an enrichment for pharmacy.

The alkyl urea derivatives of the general formula (I) according to the invention are prepared in a manner known per se by a) an amine of the general formula (II) in which A and R1 to R5 have the meaning given above with a compound of the general formula (III) RN = C = X (III) in which R and X have the meaning given above, in an inert organic solvent at temperatures between 200 and 1200C, or b) an amine of the general formula (II) with phenyl chloroformate of the formula (IV) ClCOOC6H5 (IV) at temperatures between 0 ° and 500C, and the resulting phenylcarbamic acid ester of the general formula (V) in which A and R1 to R5 have the meaning given above directly or after their isolation with an amine of the general formula (VI) H2N-R (VI) in which R has the meaning given above in an inert organic solvent at temperatures between 20 and 1400C implements.

Variant b provides alkyl urea derivatives in which X is oxygen.

The present invention preferably relates to the use of alkyl urea derivatives of the general formula (I) in which R is a straight-chain, branched, cyclic, saturated or unsaturated aliphatic hydrocarbon radical having 4 to 20 carbon atoms, which is optionally substituted with halogen, hydroxy, alkoxy or alkoxycarbonyl in each case 1 to 6 carbon atoms in the alkoxy radical, or is substituted by phenyl, the phenyl radical in turn optionally carrying 1 or 2 substituents from the group halogen, trifluoromethyl, hydroxy, alkyl with 1 to 2 carbon atoms or alkoxy with 1 to 2 carbon atoms, R1 for hydrogen or Alkyl with 1 to 4 carbon atoms, R² stands for alkyl with 1 to 4 carbon atoms, R³, R4 and R5 are identical or different and each represent hydrogen, halogen, hydroxy, cyano, trifluoromethyl, alkyl, alkylmercapto, alkylsulfonyl, alkylsulfinyl, Alkylcarbonyl, alkoxy and alkoxycarbonyl, the aforementioned A Alkyl and alkoxy radicals each contain 1 to 4 carbon atoms, or represent phenyl or phenoxy, where the phenyl radicals are optionally substituted 1 or 2 times by halogen, trifluoromethyl or alkoxy having 1 to 2 carbon atoms, X is oxygen or sulfur and A is one of the the following remains: where R 'and R "are identical or different and each represent hydrogen or alkyl having 1 to 4 carbon atoms, R"' represents alkyl having 1 to 4 carbon atoms and m represents 0 or 2.

Of particular interest are the new alkyl urea derivatives of the general formula (I) in which R represents straight-chain, branched or cyclic alkyl or alkenyl having 6 to 18 carbon atoms, the alkyl and alkenyl groups mentioned being optionally substituted by chlorine, bromine, or fluorine Alkoxy with 1 to 4 carbon atoms, or stands for phenyl, R1 and R² are identical or different and each stand for alkyl with 1 or 2 carbon atoms, R3, R4 and R5 are identical or different and each represent hydrogen, chlorine, bromine, trifluoromethyl, Alkyl, alkyl mercapto or alkoxy, the alkyl and alkoxy radicals mentioned each containing 1 to 4 carbon atoms, or phenoxy or chlorophenoxy, A stands for one of the following radicals: where R 'and R "are identical or different and each represent hydrogen, methyl or ethyl and X represents oxygen.

The making of the new compounds from the by the general The class of substances defined in formula (I) is also carried out according to methods known per se according to the abovementioned process variants a and b, with the starting materials used isocyanate derivatives, amines and phenylcarbamic acid esters of the general Formulas (III), (V) and (VI) are known or prepared by known methods can be tvgl. R. Wagner et al. Synthetic organic chemistry, Wiley, New York, (1953), pp. 640, 645, 653 and Beilstein, Volume XX, 2nd supplementary work, pp. 180, 192, 21Q7.

The compounds of the general formula (I) show an advantageous one Inhibition of lipid absorption in humans and animals. When consuming fatty food they lead to a lower alimentary hyperlipemia, with simultaneous inhibition the absorption of cholesterol, so that it is particularly useful in the treatment of disorders of lipid metabolism, such as hyperlipoproteinemia, atherosclerosis or obesity can be used can.

The following test arrangement can be used to demonstrate the advantageous effect show in rats: To produce alimentary hyperlipemia, one group receives 2.5 ml / kg of olive oil administered orally by rats (control group). A corresponding Group of others Rats received at the same time as the olive oil application the active substance is administered as a suspension in tragacanth mucus with the sludge probe. Another control group of rats received only tragacanth mucus applied.

The concentrations are 2 hours after the application of olive oil the serum triglycerides determined in all three groups of rats (method: J. Ziegenhorst, Klin. Chem. 21, (1975) 1627). They only show two hours after the application of fat rats treated with olive oil (group 1) versus rats without fat application (Group 3) a marked increase in serum triglycerides. With this increase, the is set equal to 100%, the decreased serum triglyceride increases are the compared with animals treated with active substance and olive oil (group 2). It was found that even low dosages. of the urea derivatives according to formula (I) cause a significant decrease in serum triglycerides. In addition to the strong lipid absorption inhibitor The compounds are also extremely well tolerated.

The present invention includes pharmaceutical preparations, which in addition to non-toxic, inert pharmaceutically suitable carriers one or contain several compounds of the above formula or those of one or more There are compounds of the above formula as well as processes for making these preparations.

The present invention also includes pharmaceutical preparations in dosage units. This means that the preparations in Form of individual parts, e.g. tablets, dragees, capsules, pills, suppositories and Ampoules, the active ingredient content of which is a fraction or a multiple correspond to a single dose. The dosage units can be, for example, 1, 2, 3 or Contains 4 single doses or 1/2, 1/3 or 1/4 of a single dose. A single dose preferably contains the amount of active ingredient that is administered in one application and which is usually a whole, a half or a third or a Corresponds to a quarter of a daily dose.

Among non-toxic, inert pharmaceutically acceptable carriers are solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of any kind to understand.

Preferred pharmaceutical preparations are tablets, coated tablets, Capsules, pills, granules, solutions, suspensions and emulsions and pastes called.

Tablets, coated tablets, capsules, pills and granules can be the or contain the active ingredients in addition to the usual carriers, such as (a) fillers and extenders, e.g. starches, milk sugar, cane sugar, glucose, mannitol and silicic acid, (b) binding agents, e.g. carboxymethyl cellulose, alginates, gelatine, polyvinylpyrrolidone, (c) humectants, e.g. glycerine, (d) disintegrants, e.g. agar-agar, calcium carbonate and sodium bicarbonate, (e) dissolution retarders, e.g. paraffin; and (f) absorption accelerators, e.g. quaternary Ammonium compounds, (g) wetting agents, e.g. cetyl alcohol, glycerol monostearate, (h) Adsorbents, e.g. kaolin and bentonite and (i) lubricants, e.g. Talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures the substances listed under (a) - (i).

The tablets, coated tablets, capsules, pills and granules can be used with the customary coatings and casings, optionally containing opacifying agents be and also be composed so that they only or the active ingredient or preferably in a certain part of the intestinal tract, possibly delayed using e.g. polymer substances and waxes as embedding compounds can be.

The active ingredient (s) can optionally be combined with one or more of the above-mentioned carriers are also in microencapsulated form.

Solutions and emulsions can, in addition to the active ingredient or ingredients, the customary carriers, such as solvents, solubilizers and emulsifiers, e.g. Water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, Benzyl benzoate, propylene glycol, 13-butylene glycol, dimethylformamide, oils, in particular Cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerine, Glycerin formal, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.

The solutions and emulsions can also be used for parenteral administration are in sterile and blood isotonic form.

In addition to the active ingredient (s), suspensions can include the usual carriers, such as liquid diluents, e.g. water, ethyl alcohol, propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methane hydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.

The formulation forms mentioned can also contain colorants and preservatives as well as additives that improve smell and taste, e.g. peppermint oil and eucalyptus oil, and sweeteners such as saccharin.

The therapeutically active compounds are intended to be in those listed above pharmaceutical preparations in a concentration of about 0.1 to 99.5, preferably from about 0.5 to 95 percent by weight of the total mixture.

The pharmaceutical preparations listed above can except Compounds of the above formula also contain other active pharmaceutical ingredients.

The manufacture of the pharmaceutical preparations listed above takes place in the usual way by known methods, e.g. by mixing the Active ingredients with the carrier (s).

The present invention also includes the use of the compounds of the above formula as well as the use of pharmaceutical preparations containing a or contain several compounds of the formula given above, in which Human and veterinary medicine for preventing, ameliorating and / or curing diseases of lipid metabolism.

The active ingredients or the pharmaceutical preparations can be taken orally or parenterally, preferably orally, are administered.

In general it has been used in both human and veterinary medicine Proven to be advantageous, the active ingredient (s) in amounts of about 0.1 to about 100, preferably 1 to 50 mg / kg of body weight per 24 hours, divided over 1 to 6 administrations, to be administered before and / or during and / or after the meal.

A single dose preferably contains the active ingredient (s) in quantities from about 0.1 to about 20 mg / kg body weight. However, it may be necessary to deviate from the dosages mentioned, depending on the type and the body weight of the object to be treated, the type and severity of the disease, the type of preparation and application of the drug as well as the period or the interval within which the administration takes place. So it may in some In some cases, it is sufficient to get by with less than the above-mentioned amount of active ingredient, while in other cases the amount of active ingredient listed above must be exceeded. the Determination of the required optimal dosage and type of application of the Active ingredients can easily be made by any person skilled in the art on the basis of their specialist knowledge.

The following formulation examples illustrate the preparation of Medicinal preparations to be used according to the invention: Examples for tablet production 1. 100 mg of the compound of Example 1 are added with 69 mg lactose and 30 mg corn starch mixed, then with a paste 15 mg corn starch kneaded and pressed through a sieve with a mesh size of 3 - 5 mm. It is then dried in a dryer at 60-800C.

The granules obtained are passed through a sieve with a mesh size of 0.8 mm Beat another 15 mg corn starch, 10 mg lime and 1 mg magnesium stearate mixed in and with the help of a conventional tablet press to round tablets 9 mm in diameter and a total weight of 240 mg.

2. '00mg of the compound of Example 13 with 97 mg of secondary Calcium phosphate mixed with an aqueous gelatin solution containing 2 mg gelatin contains kneaded. Then it is pressed through a sieve with a mesh size of 3 - 5 mm and dried at 60 - 800C. The dry granulate is sieved (0.8 mm), then 20 mg wheat starch and 1 mg magnesium stearate mixed in and tabletted in a known manner. Round tablets with a diameter of 8 mm and a total weight of 320 are obtained mg.

Of particular interest are the new alkyl urea derivatives of the general formula (I) in which the substituents have the following meanings: R denotes straight-chain, branched or cyclic alkyl or alkenyl each having 6 to 18 carbon atoms, optionally substituted by chlorine, bromine, fluorine or alkoxy with 1 to 4 carbon atoms, R1 and R2 are methyl or ethyl, R3, R4 and R5 are hydrogen, chlorine, bromine, trifluoromethyl, phenoxy, chlorophenoxy, alkyl, mercaptoalkyl or alkoxy each having 1 to 2 carbon atoms, X is oxygen and A is one of the following leftovers: -OCH2-, SUCH2 where R 'and R "are each methyl or ethyl.

Examples of new compounds that may be mentioned are: N-n-HeXylaminocarbonyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline, N-n-octylaminocarbonyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline, N-2-ethylhexylaminocarbonyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinol in, N-n-tetradecylaminocarbonyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline, N-3-n-butoxypropylaminocarbonyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline, N-n-hexylaminocarbonyl-2-methylindoline, N-n-hexylaminocarbonyl-2,2-dimethylindole N-n-dodecylaminocarbonyl-2,2-dimethylindoline, N-n-octylaminocarbonyl-2,2,4-trimethyl-6-phenoxy-1,2,3,4-tetrahydroquinoline, N-n-Octylaminocarbonyl-2,2,4-trimethyl-6-butoxy-1,2,3,4-tetrahydroquinoline.

Preparation examples Example 1 (variant a) 0.1 mol of 2,2,4-trimethyl-1,2.3-4-tetrahydroquinoline are dissolved in 50 ml of ether and mixed with 0.1 mol of n-dodecyl isocyanate. Afterward a spatula tip of diazabicyclooctane is added and the mixture is left at 20 to 250 ° C. for 7 days stand, cools to -70 ° C and sucks the precipitate. You get N-n-Dodecylaminocarbonyl-2.2.4-trimethyl-1 .2.3.4-tetrahydroquinoline of melting point 48-50 "C.

Yield: 66% of theory.

Example 2 (variant a) 1 mol of 2-methylindoline is dissolved in 300 ml of toluene dissolved and mixed with 1 mol of methyl isocyanate, the temperature not exceeding 250C increases. The mixture is left to stand for 1 day and the precipitate obtained is then filtered off with suction. Man receives N-methylaminocarbonyl-2-methylindoline with a melting point of 158-1600C.

Yield: 89% of theory.

Example 3 (variant b) A solution of 0.1 mol of 2-methylindoline, 0.12 Mole of triethylamine, 100 ml of toluene and 0.1 mole of phenyl chloroformate becomes 10 Held at 40 ° C. for hours, then cooled to 200 ° C. and poured with 250 ml of water 15th Stirred for minutes. The toluene phase is separated off and the solvent is evaporated off Vacuum, dissolve the residue in 100 ml of n-hexylamine and heat this solution 6 Hours under reflux at 1300C. After cooling, the solvent is at 50 ° C./10 Torr evaporated and the residue taken up in 250 ml of toluene. Then will the solution successively with 200 ml each of 1N sodium hydroxide solution, 1N hydrochloric acid and water extracted. After the solution has been concentrated, the residue is recrystallized from petroleum ether.

N-n-hexyl-aminocarbonyl-2-methylindoline with a melting point is obtained 57-590C.

Yield: 53% of theory.

The compounds of the following table are obtained analogously to Example 1.

Tabel: Example AXR R1 R² R³, R4, R5 MP Yield Remarks. (° C) in% of theory 4 -S-CH2- O n-C12H25 CH3 CH3 H 102-104 24 5 -C-CH- O n -C12 H25 CH3 CH3 H 70-71 36 CH3 6 -C-CH- O n-C12H25 CH3 CH3 2-Cl 94 oil CH3 7 -C-CH- O n -C12 H25 CH3 CH3 2-OC2H5 56-57 71 CH3 8 -C-CH2- O n-C12H25 CH3 CH3 2-OC2H5 56- 57 98 CH3 9 -C-CH2- O n-C16H33 CH3 CH3 H 62-63 41 CH3 10 -C-CH2- O n-C18H27 CH3 CH3 H 62-64 35 CH3 11 -C-CH2- O CH3 CH3 CH3 H 105-107 77 CH3 12 -C-CH2- O iso-C3H7 CH3 CH3 H 79-81 31 CH3 Table (continued) Example AXR R1 R² R³, R4, R5 MP Yield Remarks. (° C) in% of theory 13 -C-CH2- O (CH2) 6-Cl CH3 CH3 H 71-73 68 CH3 14 -C-CH2- O n-C4H9 CH3 CH3 H 48-50 54 CH3 15 -C-CH2- O i-C4H9 CH3 CH3 H 68-70 42 CH3 16 -CH2- O iso-C3H7 H CH3 H 129-131 92 17 -CH2- O n-C4H9 H CH3 H 99-101 73 18 -CH2- O tert-C4H9 H CH3 H 133-135 76 19 -CH2- O (CH2) 6-Cl H CH3 H 74-76 89 20 -CH2- O n-C12H25 H CH3 H 78- 80 91 21 -CH2- S allyl H CH3 H 98 oil

Claims (9)

Claims 1. Use of alkyl ureas of the general formula (I) in which R stands for a straight-chain, branched, cyclic, saturated or unsaturated aliphatic hydrocarbon radical having up to 20 carbon atoms, which is optionally substituted by halogen, hydroxy, alkoxy, alkoxycarbonyl or optionally substituted aryl, R1 is hydrogen or lower alkyl, R² is lower alkyl and R³, R4 and R5 are identical or different and each represent hydrogen, halogen, hydroxy, cyano, lower alkyl, lower alkoxy, lower alkoxycarbonyl, lower alkyl mercapto, lower alkylsulphonyl, lower alkylsulphinyl, lower alkylcarbonyl, optionally substituted aryl or optionally substituted aryloxy, X is oxygen or sulfur and A stands for one of the following radicals where R 'and R "are the same or different and each signify hydrogen or lower alkyl, R"' signifies lower alkyl and m signifies 0, 1 or 2, in medicaments for the treatment of disorders of lipid metabolism. 2) Use of alkyl ureas of the general formula (1), in which R is a straight-chain, branched, cyclic, saturated or unsaturated aliphatic hydrocarbon radical with 4 to 20 carbon atoms, which is optionally replaced by halogen, hydroxy, alkoxy or alkoxycarbonyl with 1 to 6 Carbon atoms in the alkoxy radical, or substituted by phenyl, the phenyl radical in turn optionally carrying 1 or 2 substituents from the group halogen, trifluoromethyl, hydroxy, alkyl with 1 to 2 carbon atoms or alkoxy with 1 to 2 carbon atoms, R1 for hydrogen or alkyl with 1 up to 4 carbon atoms, R2 represents alkyl with 1 to 4 carbon atoms, R3, R4 and R5 are identical or different and each represents hydrogen, halogen, hydroxy, cyano, trifluoromethyl, alkyl, alkylmercapto, alkylsulfonyl, alkylsulfinyl, alkylcarbonyl, alkoxy and alkoxycarbonyl , the aforementioned alkyl and alkoxy radicals each having 1 to 4 carbon atoms hold, or stand for phenyl or phenoxy, where the phenyl radicals are optionally substituted 1 or 2 times by halogen, trifluoromethyl or alkoxy with 1 to 2 carbon atoms, X is oxygen or sulfur and A stands for one of the following radicals: where R 'and R "are identical or different and each represent hydrogen or alkyl having 1 to 4 carbon atoms, R"' represents alkyl having 1 to 4 carbon atoms and m represents 0 or 2. 3) Alkylurea derivatives of the general formula (I) in which R stands for straight-chain, branched or cyclic alkyl or alkenyl with 6 to 18 carbon atoms, the alkyl and alkenyl groups mentioned being optionally substituted by chlorine, bromine, fluorine or alkoxy with 1 to 4 Carbon atoms, or represents phenyl, R1 and R2 R1 and R2 are identical or different and each represent alkyl with 1 or 2 carbon atoms, R3, R4 and R5 are identical or different and each represent hydrogen, chlorine, bromine, trifluoromethyl, alkyl, Alkylmercapto or alkoxy, where the mentioned alkyl and alkoxy radicals each contain 1 to 4 carbon atoms, or they represent phenoxy or chlorophenoxy, A stands for one of the following radicals: where R 'and R "are identical or different and each represent hydrogen, methyl or ethyl and X represents oxygen. 4) Alkyl urea derivatives of the general formula (I), in which R stands for straight-chain, branched or cyclic alkyl or alkenyl with 6 to 18 carbon atoms each, which is optionally substituted by chlorine, bromine, fluorine or alkoxy with 1 to 4 carbon atoms, R1 and R² are identical or different and each represent methyl or ethyl, R3, R4 and R5 are identical or different and each represent hydrogen, chlorine, bromine, trifluoromethyl, phenoxy, chlorophenoxy, alkyl, mercaptoalkyl or alkoxy each having 1 to 2 carbon atoms, X stands for oxygen and A stands for one of the following radicals: -OCH2-, -SCH2- where R 'and R "are each methyl or ethyl. 5) Process for the preparation of compounds of the general formula (I) according to Claims 1 and 3, characterized in that a) an amine of the general formula (II) in which A and R1 to R5 have the meaning given above with a compound of the general formula (III) RN = C = X (III) in which R and X have the meaning given above, in an inert organic solvent at temperatures between 200 and 1200C, or b) an amine of the general formula (II) with phenyl chloroformate of the formula (IV) ClCOOC6H5 (IV) at temperatures between 0 ° and 500C, and the resulting phenylcarbamic acid ester of the general formula (V) in which A and R1 to R5 have the meaning given above directly or after their isolation with eiram amine of the general formula (VI) H2N-R (VI) in which R has the meaning given above in an inert organic solvent at temperatures between 20 and 1400C implements. 6) Medicaments containing at least one compound according to claim 3. 7) Medicines influencing lipid metabolism containing at least a compound according to claim 1. 8) Process for the production of drugs that influence lipid metabolism, characterized in that compounds according to claim 1, optionally under Use of customary auxiliaries and carriers converted into a suitable application form. 9) Use of compounds of the general formula (I) according to claim 1 in the treatment of diseases of the lipid metabolism, characterized in that that these compounds are administered to humans or animals if necessary.