PL127781B1 - Biologically active agent for utilization in stock-farming - Google Patents

Description

The subject of the invention is an active agent tasokigiezattie for use in animal breeding, containing as an active ingredient a substituted aromatic germ with two condensed layers! elements, one of which is a heterocycle containing oxygen as a heteroatom. It is known that certain chemical compounds inhibit lipogenesis in animals. Namely, Wiitiak et al. (LIP1DS, 11/1976) 384-391) described some benzofuran carboxylates, including ethyl 5-phenylbenzofuran-2-carboxylate and ethyl 5-phenyl^,3-dibydirken-2-carboxylate, having the property of inhibiting lipogenesis in animals. However, in typical tests for inhibiting lipogenesis in animals, these compounds show weak activity. It has now unexpectedly turned out that another GMP& compound with a completely different chemical structure has the same useful properties of inhibiting lipogenesis, and this activity is generally much higher than that of compounds known for this action, i.e. than the activity of ethyl ester 5-phenykh-2? r3^d? ihydJ*ob- ethyl benzofurancarboxylate. Some of this new group of biologically active compounds have already been described in the literature, but their useful property of inhibiting lipogenesis is never mentioned. According to the invention, a biologically active agent for use in animal breeding is a substance, the active ingredient of which is a compound of the general formula 1 or, optionally, an addition reaction with an acid, in which ^CE^CH* or -GH-OB4, M denotes a halogen atom, a nitro group, an amino group, a trifluoromethyl group, an alkyl group, or alcotas with 1-6 carbon atoms, a cycloyl group These are fatty acids with £-6 carbon atoms, fatty acids, benzyl acids or 2-phenyl ethyl carbon acids, including each of the mentioned groups, such as a group of carbon atoms, a carbon atom and a nitro group, n means 0 or 1, R1 and R2 represent a hydrogen atom or an alkyl group with 1-4 carbon atoms, and this at least one of them is surrounded by a hydrogen atom, R* stands for a phenylalkyl or alkyl group with 1-4 carbon atoms, a quaternary phenylalkyl or alkyl group with 1-4 carbon atoms, a group alkenyl, aOkinyqua or cycloalkyl with 3-6 carbon atoms, provided that when X is -NR, then Y is a substituent in position 2 of the ring containing oxygen, and in position 3 there is a hydrogen atom, and the condition is that that when X is -O-, -CH2- or -CH(OH)-, then Y is a substituent in the 2 or 3 position of the oxygen-containing ring, and there is an additional hydrogen atom in the 3 or 2 position Suitable animals for administration of the invention are domestic animals and fur animals, including dogs, cats, minks, sheep, goats, pigs, cattle, horses, mules and donkeys, but the invention is not limited to ¬ named animals. The intended effect is achieved by oral or parenteral administration of an effective amount of the agent according to the invention to the animal. Thus, the agent according to the invention can be administered orally by pouring into the throat, by intubation, with food and water, in the form of supplemented feed. or as a substance specially formulated for oral administration. Typical compositions may take the form of solutions, suspensions, emulsions, tablets, large pills, powders, granules, capsules, syrups or aromatic alcohol solutions. For parenteral administration, the agent may be in the form of solutions, suspensions or emulsions. The agent may also contain one or more inert carriers, e.g. water, edible oil, gelatin, lactose, starch, magnesium stearate, talc or vegetable gum. The dosage depends on the specific active compound and the specific animal to which the agent according to the invention is administered; - Generally, satisfactory effects are obtained at doses ranging from about 1 to about 500 mg per kg of animal weight. The active compounds may be administered in one or more doses on the same day or over several days. An individual dosage method should be selected for a given animal under professional supervision. 2,3-dihydro-N-(2-propylene)-1,4-benzodioxin-2-carboxyairndides of formula 2 are particularly useful for inhibiting the formation of fats, in where n is 0 or 1, R is a halogen atom, a rilitro, amino, methylsulfonylamino, trifluoromethyl group, an alkyl or alkoxy group with 1 to 6 carbon atoms, a cycloalkyl or cycloalkoxy group with 3 to 6 carbon atoms, a phenyl group or ferrioxy, and each of these groups may be substituted with one or two substituents selected from the group consisting of alkyl! with 1-6 carbon atoms, a halogen and a nitro group, and R1 and R2 independently represent a hydrogen atom or an alkyl group with 1-4 carbon atoms, with at least one of them representing a hydrogen atom. The term "halogen" "includes chlorine, fluorine, bromine and iodine, the middle of which, i.e. bromine and chlorine, are particularly preferred. Each of the alkyls present may be straight-chain or branched-chain." Of these compounds, in terms of the mentioned useful properties, particularly preferred compounds are those in which the formula n is 0 or 1, R is chlorine or bromine in the 6-position of the ring system, and R1 and R2 are hydrogen atoms. Compounds with the substituent R2 representing alkyl "can exist in the form of cis and trans isomers, and it has been found that the cis isomer of these compounds is active in terms of inhibiting the formation of acids, while the fish oil isomer is essentially inactive. Therefore, of the compounds 10 20 35 40 45 50 55 60 of the formula 1, in which R2 is alkyl, only their cis isomer turned out to be interesting. Moreover, in the compounds of the formula 2 there is "chirality associated with the asymmetric configuration in the 2-position of the 2,3 ring -dihydro-1,4-benzodioxyalic acid* and therefore the compounds of formula 2 can exist in two optically active forms when R2 is hydrogen and in the cis form when R2 is alkyl. Thus, this compound includes both individual optically active isomers and mixtures thereof. Since some of the compounds constituting the active substance of the invention are new, the information given below may prove to be very valuable to a person skilled in this field. Methods of preparing some specific compounds of formula 2 are described in the examples given below. Other typical compounds include, for example, the following: R 6-Br 6-trifluoromethyl 6-methoxy 6-cyclohexyl 6-cyclohexyloxy 6-phenyl e-phenoxy 6-amino 6Hmethylsulfonylamino 6-(4-chlorophenyl) 6-<4-chlorophenoxy ) 5-methoxy 8Hnetoxy 6-(benzoyl) 6^(4-chlorobenzoyl) 5-chloro 1 8-chloro and 6-acetyl H H.H . R1 H H H H H H H ' H H H H H H H H H H H H H H 1 *' and H H | H H H H H H H H H H H H H methyl methyl H propyl n-butyl isopropyl Some compounds from this group are known, and so 2,3-dihydro - N-(2-propylene)-1;4 - benzodioxin - 2-carboxamide was described by J. Koo et al. in J. Am. Chem. Soc., 77 5373 (1955). This compound and others can be obtained from an alkyl ester, preferably methyl or ethyl, of the appropriate acid by treating it in a solution, preferably in ethanol, with 2-propenamine. The reaction takes place at room temperature, however, to shorten the reaction time, the temperature can be increased, for example by carrying out the reaction in a mixture kept at boiling while returning the vapors. The above procedure was described by Koo et al. Preferably, a four- to six-fold excess of the amine is used. The desired product can be isolated by evaporation of the solvent and excess amine, followed by conventional methods such as selective extraction, crystallization and or dry column chromatography. The specific isolation and purification procedure is described in the examples cited.5 mm * Another method of preparing amides may involve treating the appropriate acidic acid with thionyl chloride to give the acid chloride, which is then reacted with a 7. amine; This method was also described by Koo et al. Thionyl chloride is eaten in excess and therefore also serves as a solvent. The reaction with thionyl chloride is preferably carried out by recycling the vapors of the mixture. After the reaction is completed, excess chloride and thionyl chloride are evaporated and the acid chloride is isolated. Other; procedure, consists in the action of amine, used in excess; to crude acid chloride, at tyre. to slow the reaction and/or provide an environment; a liquid solvent may be added, such as; as methylene chloride. The product from the reaction mixture is isolated as described above. The starting esters: (gd r.lldl)1 can be: - obtained; The method was described by Koo et al and DeMarchi (Example III), by treating the corresponding PiTtotelfechdin-of formula 3 with a methyl or ethyl ester corresponding to 2,3-dimetaphoric acid, -butyric acid, -butanecarboxylic acid; or pentanecarboxylic acid. Some derivative pyrocatechins (R=H, 4-methyl, 4-phenyl, 4(1,1-) are known as follows: ): R=4^Br. Btfocfifugfe: sie piffiokatechine; dibromide-kfem: cioksasam,. as; opijali Janosrakaja et al„ Zur.Obszczej Khim, 22, 1594 (1952) (Chemical Absteacts, 47, 8033b). r=4 -E. Sto^esie„metode;; Coarstfa et-aL, J. Qrg.Chem., 16, 1345 (195H (Ctenj Abs:, 48.6$95b), R=4-CF3. The benzoic acid reacts with triple phenylsulfur at 1GO*-120°C (Shf3^«l, J Am. C3hrnx Soe. 84? 3058 (1962). Oorg. Sym 44.- 39$ (19.64°C) lowers the pressure on the reaction mixture, resulting in the distillation of the product, which is then introduced into the presence of platinum carbon as a catalyst. R^4-methoxy. 2 ^Hydix3(xy*4-metc4Lsybenzaldehyde) is reacted: Dafcina, as described by Mr. Paflalsen^ Medd; Norsk. Farm, Selskap. 21, 157, (t95) (Chem. ; Abs, 54, 12481b( 1960)). Iz.Wyssz. Uczeb ZavediKhrim., Khim; Tekhnol., 245 (1972 (Ghenu AJbs., 77, 34072e (1972). (1935)), sodium peroxide and catalytic amounts of powdered copper at approx. 20°C for approx. 4 hours - the liquid is poured onto ice, the liquid is extracted with organic fluid, e.g. ether, the extract is dried and the solvent is removed, and the residue is distilled to obtain 4-feiróxsypdrokateohiny dimethyl ether. The product is treated with 100 mL of anhydrous aluminum chloride (sodium chloride) Janssen et al., ibid.), poured into hydrochloric acid with ice, and the solvent is extracted organic solvent, the solvent is removed under reduced pressure and the solid is subjected to fractionation to obtain the given 4-fefioxy-pyrocatechine. mjesfzfcna&ej^^4-jodc^,$^bi^(be! n^l€a^)^ benzene* in^ws&ooi^orz,^ nu (Annaly 3£lv 378) and, j0 and mercury in the procedure described below ^Jansse^ na et al., J. Ong. Chem., 20, 132G (1&55); powdered sodium chloride (made from Cyldbohekanoate and sodium hydride) and catalytic amounts of powdered copper, poured on ice, extracted and dissolved with a dissolver, e.g. distilled to obtain diphosyl ether 4-cycle effyioic ypyrocateccin. This product is hydrogenated in an ethanol solution in the presence of palladium on carbon, filtered off from the catalyst, the solvent is filtered off and the 4-cyclohelphisyl ypiffocatechine is distilled off under a given vacuum. Ethyl 2,3*-dihydiro^l,4-ben3L-d'ioxin-2-carboxylate is nitrated in an immiscible solvent. with water: e.g. in hefesain, pentane or petroleum ether, ZQPfa< nitrous acid, at a temperature of 10-60°C and evaporates; 2i3-dihydi? o-6- -riteo^l4^benzodio! xyno^2^k»rbetesjj^^ eftiylMi, which is given, undergoes chemical crystallization. This compound is treated with water in the presence of alcohol in the presence of iPAUaide in the presence of carbonate, (R^=aoiino) is separated by ,, filtration of the catalytic converter, removal of the solvent and crystallization of the residue. Ziwdazek R=^am4no 30 (described above) is treated. methanesulphonic chloride in an organic solvent: e.g. toluvite containing an acid-binding compound, e.g. triethylamine or pyridine. The product is isolated by pouring the mass onto ice and filtering off the solid, which crystallizes from an organic solvent, e.g., ethanol. The starting acids, in which the formula R1 is alkyl, can in the reaction of the appropriate pyrocatechin with l-cWoroA3.-epoik^-2^JdloBi5Qp3Jne-W 43 in the presence of aqueous hydroxide. sodium, in, tenp, akole» 1O0°C. In this way: 2-alpha-1-benzodioxin-2-methanol can be oxidized to the corresponding acidyl resin. Jones, (mixture of carbon dioxide and aqueous acids) Preferably alcohol; it is used as a solution in a solvent such as acetone and the reagents are mixed together at a low temperature, m, in the range of 5-10°C, and then the mixture is heated, e.g. to room temperature, in order to slow down the reaction. 50 Above. The method of obtaining acids is illustrated in Example II. This example also describes how this product can be isolated from the reaction mixture and purified. The preparation of compounds of formula 2 is illustrated by Examples Ir-VII. In every. burn products and their compounds; The results were confirmed on the basis of chemical and spectral analyses. The second group of compounds inhibiting the production of fats is represented by formula 4, in which X is -CO-NH-CH2-CH-CHi or -GO0R4, n is. 0.1 or 2, R denotes a secondary halogen, a nitro, amino, methylsulfoirylamino, trifluoromethyl, alkyl or alkoxy group with 1-6 carbon atoms or a cycloalkyl group with 3-6 carbon atoms, R4 denotes an alkyl group with 1-4 carbon atoms, alkenyl, alkynyl or cycloalkyl xx 3-6 carbon atoms or phenylalkyl, R2 is a hydrogen atom or an alkyl group with 1-1 carbon atoms, and Rs is a hydrogen atom or a phenylalkyl group. The term "lower halogen" means bromine, chlorine and fluorine, of which chlorine is particularly preferred. Each of the alkyls mentioned may have a straight or branched chain. In a phenylalkyl group, the alkyl moiety may contain up to four carbon atoms, preferably one to two carbon atoms connecting the phenyl group with the nitrogen atom located in the ring.' Of the above compounds, due to the mentioned useful properties, those in which n is 0 or 1, R is a substituent attached to the 6-carbon of the ring, R4 is an ethyl group, R2 is a hydrogen atom, and Rs denotes a hydrogen atom or a benzyl group. The compounds of formula 4 are substituted carboxamides or esters, are of a basic nature and therefore can form salts with acids, e.g. with hydrohalides, which are pharmacologically acceptable, also exhibiting the above-mentioned useful properties. The preparation of typical compounds of formula 4 is illustrated by the examples given below. Examples of initiating esters include the following groups: R4kfetic), R*=H, R3=H, n=1, R=6-bromo, 5-chlorine , (5-chloro, 7-chloro, 8-chloro. ¦&*==ethyl, R2=methyl, R«=H, n=0." R*=ethyl, R*=H, R»=H, n= 2. R=6,7-dichloro, * 6-nitro. 8-chloro, 6-chloro, 8-me- *'*Xtyio, 6nnitro, 8 methyl, 6,8-dichloro. n«=H, R»=H, n=0, R*=methyl or butyl, R4-butyl, R*=H, R»=benzyl, n=0. &4=ethyl, R2=ethyl, Ra=H, n=l, R=6-nitro.R4==propyl, R2=H, R*=H, n=l, R=6-methylsulfonylamino. R*=ethyl, R2=H, R*=benzyl, n=1, R=6-nitro.' Preferred substituents with the symbol R are hydrogen and chlorine atoms, methyl, nitro, amino, methylsulfonylamino, trifluoromethyl, methoxy and cyclohexyl groups. 3,4-dhydiro-2H-1,4-benzo- ethyl ester. xazineT2Hcarboxylic acid is known from British Patent No. 1,057,658. Esters for which R4 does not represent an ethyl group can be obtained by Fischer-Speier acid esterification, that is, by treating the appropriate acid with an appropriate alcohol in a solvent such as toluene, in the presence of catalytic amounts of an acid such as sulfuric acid, hydrochloric acid or p-toluenesulfonic acid. The starting acids can be obtained from the ethyl esters by conventional hydrolysis. The starting R*-alkyl esters can be obtained by condensation of the ester methyl or ethyl of the appropriate 2,3-dibromobutyric acid, buitanecarboxylic acid, or pentanecarboxylic acid with the appropriate 4-R-2-aminophenol, in the presence of a base, e.g. potassium carbonate, in a solvent, e.g. acetone, at room temperature or slightly higher. Some of the starting 8 phenols (7v=H, Cl, CH3 CH3O, NOz) are known. Methods for preparing other phenols are described in Examples XIII and XV, and by Katz et al. in J.Org. Chem., 19 758 (1954). 5 The starting phenols with the substituent R=cyclohexy can be obtained from 4-cycloalkyl phenols, similarly to the preparation of trifluoromethylphenol (Example XV). Phencles in which the R substituent is a methylsylfonylamino group can be prepared from the phenol R=amino by the action of methanesulfonic chloride in a solvent such as methylene chloride in the presence of a base, e.g. triethylamine or pyridine, as given in Example XIV The preparation of esters of formula 4 is described in Examples 15 and 15. X-XVII. The products and their starting compounds were identified on the basis of chemical and spectral analysis. Of the substituted carboxamides of formula 4, the preferred ones are 3,4-dihydro-N-(2-propanyl)-2H-1,4-20-benzoxaseTLO-2 - carboxamides covered by the formula 5, in which n is 0, 1 or 2, R is lower halogen, nitro, amino, methylsulfonylamino, trifluoromethyl, alkyl and alkyl groups with 1-6 carbon atoms or cycloalkyl 25 o 3 - 6 carbon atoms, R2 is a hydrogen atom or an alkyl group with 1-4 carbon atoms and R8 is a hydrogen atom or an alkyl group with 1-4 carbon atoms. Lower halogens include chlorine, fluorine and bromine, with chlorine being the most preferred. Any of the above. alkyl groups may have a straight or straight chain. branched. Of the above compounds, those 35 are preferred because of their useful properties, especially those for which n=0 or 1, R=C1, alkyl or CF3, R2=H, and R*=H or methyl Compounds of formula 5 have basic properties, so they form salts with acids such as hydrohalides, which are pharmacologically acceptable and also effective as inhibitors of fat formation in mammals. Compounds of formula 5, where R2 is a group alkyl, can exist as cis and trans geometric isomers depending on the mutual spatial arrangement of R2-alkyl and carboxamide. Moreover, chirality occurs in these compounds due to the asymmetric spatial configuration in the 2-position of the 3,4-dihydro-1,4-benzoxiazine ring. Due to this, there are two active optical isomers of these compounds with the formula 5, in which R2 is a hydrogen atom and four optically active isomers for compounds of formula 5 in which R2 is alkdl, two for each pair of geometric isomers. Therefore, individual geometric and optically active isomers, as well as mixtures thereof, may be used. The preparation of some typical compounds of formula 5 is illustrated by the examples given. Other typical compounds of this group have the following substituents: R2=H, R'=H, n=1, R=6-methoxy, 6-cyclohexyl, 6-amino, 7-methyl, 5-chloride or 8-chloro.R*=methyli, R»=H, n=0. R2==methyl, R8=methyl, n=0 R2=H, R*=butyLo, n=0 :/~TV'"'"lJ9 R2H, R*=isopropyl, n*=l, R=6-chloro R=H, R*=ethyl, n=l, R=6-bromo R2=H, R8=isobutyl, n«l, R=6-methyl R2=propyl, R3—H, n=l, R= 6-chloro R2=H, R2^=H, n=2, R=6,7-dichloro, ¦ 6,8-dichloro, 6-chloro-8^methyl, 6-ritro-8-methyl, 6-nitro -8-chloro. Preferably R is in the 6-position of the ring and represents chlorine; methyl-nitro, amino, methylsulfonylamino, V-fluoromethyl, methoxy, cyclohexyl or M hydrogen. Compounds belonging to this group can be obtained by reacting an alkyl ester, preferably methyl or ethyl, of the appropriate carboxylic acid in a solution of an appropriate organic solvent , e.g. in ethanol, with 2-propenamine. The reaction takes place at room temperature, but in order to shorten the reaction time the temperature can be increased, e.g. Preferably, the amine is used in a four- to six-fold excess. The product can be isolated by evaporation of the sulfate and excess amine and then subjected to selective extraction, crystallization and/or dry column chromatography in the usual manner. These methods are also discussed in the referenced formulations. 3,4-dihydro-2H-1,4-oei^so-xazine-2-carboxylic acid ethyl ester is known from British patent no. 1057568. Other esters for which R2 is alkyl and can be obtained by condensing the methyl or ethyl ester of the appropriate 2,3-dibromobutyric acid, -butanecarboxylic acid or -pentanecarboxylic acid with the appropriate 4-R-2-aminophenol in the presence of; 35 base, e.g. potassium carbonate, in a solvent such as acetone, at a temperature slightly above room temperature. Some of the starting phenols (R=H, chloro, methyl, ?methoxy, nitro) are known. Methods for preparing other phenols have been described* in Examples XXIV and XXV, and by Katz% et al. in J.Org. Chem. 19, 758 (1954). The starting phenols in which the substituent R is cycloalkyl can be prepared from 4-cycloalkylphenols, similarly to the preparation of trifluorophenol .5 (Example XXV). Compounds with the substituent R=methylconylamino can be obtained from the corresponding LR-amino compound by treating it with methanol-methyl chloride as described in Example 24. 50 Example XX illustrates the preparation of starting esters with the substituent R3 = alkyl, by first treating the appropriate ester in a dimethylamine solution with thallium ethoxide and then with the appropriate alkyl halide (R8 = halo). The preparation of compounds of formula 5 is described in Examples XIX-XXV. The products and starting compounds were identified on the basis of chemical and spectral analysis. 60 The third group of compounds that preferably inhibit the formation of fats in mammals is represented by formula 6, in which X is ^O-, -CHjr or ^CH(OH)-, n is zero or one, R is halogen, nitro, amino, trifluoromethyl^methyl - ^sulfonylamino, adkdl or alkoxy, with 1-6 carbon atoms, cycloalkyl with 3-6 carbon atoms; phenoxy, benzyl or 2-phenylethyl, each of these groups may be substituted with one or two substituents, such as 1-carbon alkyl, halogen and nitro, provided that that when X is -CH(0H-, then the compound has the cis configuration, and when however, bromine and chlorine are preferred. Each of the mentioned alkalis may have a straight or branched chain. Of the above compounds, in terms of inhibiting the formation of fats, those compounds for which a) n = 0 and X means - are preferred. CH2- or b) n=1, R is chloro, phenyl or cycloalkyl, and X is -CH2-. For compounds containing -G- but one substituent X, hR substituents as defined for formula 2 are preferred, and when OH)-, then the preferred substituents R are chlorine, phenyl and cyclohexyl. In formula 6, the aminocarbonyl group can be attached to the carbon atom in the 2nd or 3rd position of the ring. -Due to chirality, these compounds can exist in two optically different forms. These isomers and their mixtures are also within the scope of the invention. The compound of formula 6, where n=*0 and X is -O-, was described by J. Koo et al in J. Am, Chem. Soc., T7 5373 (1955). Compounds with the formula ly in which n=1, ethyl pionate, following DeMarchi et al. Graaz. X3him: Jtal., 35, 1477—54 (1965). The prepared 2,3-dihydro-6-halo-1,4-benzoxazine-2-caroxyoxylic acid ethyl ester is reacted with 2-propeatinine in the manner described by tKoo et al (Ibid.). A mixture of 6- and 7-chloro-esters is obtained. A mixture of these esters treated with an amine gives a mixture of 6- and 7-chloro! carboalimides, which can be converted accordingly. Thus, compounds of formula 6 can be prepared by heating an alkyl ester, preferably methyl or ethyl ester, of a suitable carboxylic acid in a solution of a suitable solvent, e.g. in ethanol, with 2-propenamine. The reaction takes place at room temperature, but in order to shorten the reaction time, higher temperatures can be used, for example by maintaining the mixture at a boil while returning the vapors. The teri method was described in the mentioned publication by Koo et al. Preferably, a four- to six-fold excess of the amine is used. The product can be isolated by evaporation of the solvent and excess amine, followed by conventional methods such as extraction, selective crystallization and/or dry column chromatography. . These methods, applied in specific cases, are described in the examples given below. Another method of preparing amides involves reacting the appropriate carboxylic acid with thionyl chloride and treating the obtained acid chloride with an amine. This method was described by R6woiez Koo et al. An excess of thionyl chloride, which also acts as a solvent, is used in the reaction, and the treatment with thionyl chloride is preferably carried out by recycling the vapors of the reaction mixture. After the reaction is completed, the excess thionyl chloride is evaporated and the acid chloride obtained is isolated. It is also possible to treat the crude acid chloride with an excess of the amine using a suitable solvent, e.g. methylene chloride, to slow down the reaction and/or create a liquid reaction medium. The final atmide product can be isolated in the usual manner as described above. The starting pyrocatechins R=H, 4-chloro are known, the rest can be obtained as follows (depending on the meaning of the substituent R and its place of substitution, in this case n=1): R=4-Br. Pdrocatechin is brominated using dioxane bromide according to the procedure of Jabovskaja et al., Zhuir. Obszczei Khim, 22 1594 (1952). (Chemical Abstracts, 47, 8033 b). r=4-F. The method of Gorset et al. is used. J. Org. Chem, 16, 1345 (1951) (Chem. Abs. 46, 6095 b). Compounds of formula 6 in which X is -CH2- can be obtained similarly, starting from acid esters or chlorides and 2-propenamine. , ¦ - Starting acids and esters for compounds of formula 6, in which the carbonyl group is substituted at the carbon in the 2-position. Opasali Witiak et al., J. Med. Chem., 14 (1971) and Witiak et al., Jr. Med. Chem, 18 934^-42 (1975). Haylor et al., J. Chem. Soc. London, described 2H-1-benzopyranocarboxylic acid-3, which can be hydrogenated to the desired starting acid in which the aminocarbonyl group is bonded to the 3-carbon (n=0). other starting carboxylic acids and esters can be obtained analogously by the following methods: a) Acids with a carboxyl group in the 2-position can be prepared by reacting the appropriate 4-R-phenol with α-bromo-y-butylanolactone to obtain 3-(4-R-phenoxy )-dihydro-2(3H)-furanonium, which when treated with Jones' reagent gives 2-(4-R-phenoxy)-propane dicarboxylic acid. This acid cyclizes sodium under the influence of sulfuric acid to obtain 6-R-3,4-dihydro-4-keto-2H-1-benzbpdranocarboxylic acid-2, from which by hydrogenation (zinc-mercury analgam, hydrochloric acid) is obtained given carboxylic acid. b) fisters with an alkoxycarbonyl group in the 3-position of the ring can be obtained by treating the appropriate salicylic chloroaldehyde with acrylonitrile (aqueous sodium hydroxide) to obtain 6-halo-3,4-dihydiro-4-hydroxy-2H-1 - benzopi- ranan-3-catfbonitrile; which is heated with methanol. and hydrochloric acid to give 6-halo-2H-1-benzopyranecarboxylic acid-3 methyl ester, which is hydrogenated. (hydrogen, methanol, 10B/o palladium on carbon catalyst) to the required ester. The preparation of typical benzodioxin and benzopyran compounds of formula 6 is described in the examples given. Another group of typical compounds are those of formula 6, in which n-1, the aminocarbonyl group is in the 2-position, and R=fluoro, trifluoromethyl, methyl, methoxy, nitro, amino, methylsulfonylamino, phenoxy, s n=1, the aminocarbonyl group is in in the 3-position, and R = methoxy, amino, methylsulfonylamino. Compounds without the R substituent can be obtained by reacting the appropriate carboxylic acid chloride with 2-propenamine. The starting acid chlorides for this reaction are obtained by treating the appropriate acid with thionyl chloride. The excess of thionyl chloride used acts as a solvent. These reactions are preferably carried out by recycling the vapors of the mixture. After the reaction is completed, the excess thionyl chloride is evaporated and the acid chloride is isolated from the residue in the usual manner. The acid chloride, either as a crude product or purified, is then treated with the excess amine, optionally using a solvent such as methylene chloride to slow the reaction and or create a liquid environment. The amide formed is isolated in the usual manner. 25 Some starting carboxylic acids and esters are known: Witiak et al., J. Med. Chem. 14, 758-66 (1971), Witiak et al., J. Med. Chem. 18, 934-^42 (1975), Taylor et al., J. Chem. Soc., London, 1950, 2724—5. ^ The compound constituting the active substance of the invention can also be prepared by heating with 2Hpropenoa! mL of the alkyl ester, preferably methyl or ethyl, of the appropriate carboxylic acid in a solution of a suitable 3.0 solvent, e.g. ethanol. Although the reaction takes place at a relatively low temperature, it is preferably carried out by recycling the vapors of the mixture. Amine is preferably used in an excess of 4-6 times. The product is isolated by evaporation first of the solvent and excess amine, and then using conventional methods such as selective extraction, crystallization and/or dry column chromatography. Other carboxylic acids and esters, not discussed above or in the cited literature, are obtained by analogous methods: a) Acids with a carboxyl group in the 2-position of the ring and having an R substituent other than phenyl or cycloalkyl are prepared by treating the appropriate |0 4-R-phenyl with a-bromo-y-maslanolactone to obtain 3- (4-R-phenoxy)dihydro-2-(3H-furanone), which is in turn treated with Jones' reagent. The 2-(4-R-phenoxy)propane dicarboxylic acid thus prepared is cyclized under the influence of sulfuric acid to form 6-R-3,4-dihydro-4-keto-2H-1-benzopyranocarboxylic acid- 2, which is reduced (Zn-Hg analgam, hydrochloric acid) to the required starting carboxylic acid. The preparation of the starting ester with the R substituent being phenyl 65 or cyclohexyl is described by Witiak et al., ibid. (1975). b) Esitra with an alkoxycarbonyl group bonded to the ring carbon in position 3 are obtained, for example, by reacting the appropriate salicylaldehyde with acrylenitrile (aqueous sodium hydroxide) oi to obtain 6-R-3,4-dinydro-4-hydroxy-2H- l-13 127#81i'i 14 -b^r:z»piirap.oikarlaQniitrile-3, which-is-heated-with-methanoleum-. and acid. -:- salt.- We will get the quaau ester frR- H-lrb^W'P#! aino&^ turns (hydro, ethanol, 10% palladium on carbon) into an ester; ^tan,^wiapego,:po4a4any. starting compound. 5 Relationships of Mw^.r^w -.:which. IX - means ¦¦.-CH(OH)-, can be obtained by treating borane-* with a semi-product constituting an alkyl ester. *.. acid.: - 3.4*dinydff03^^etQi-2H*lfb^ L ksylpwegG^2. 10 The starting ester: R=^nitro can be prepared by - nitration. acid H=:JI proceeding according to Roncaoeio et al., J. Heterocyclic Thorny, 10, 623 (1973); and then esterifying the obtained acid with ethyl alcohol containing a small addition of sulfuric acid, egg catalyst, when returning the vapors, the reaction mixture. Output. esterkR^amaiRO mosna^otraymaói re-- diiikaj4-c- ester R=? nitro, by way of hydrogenation; 20 of this ester in a solution of ethanol containing 10% palladium on carbon, the starting ester can be v/ycreates&*treating . este? ^ :-. R=amrao lymph-matjdeauu, .containing rose*. amount of £-v;C5 triethylamine,. equalmolar-^amount of ciattjhkrku,\me-K. t-1-nosiulfonyl* Methods of preparing compounds; We have given examples XXVII-XXXVIII. Of the discussed new sciences? g^egfi^jtjeu 30 pattern. 7, wherein the respective symbols denote: ., X = -NRj-, -CH2- or -CH(Oii)4 ..N =f 0 or h . R =f '€hlóTX)WleG, aiitro* . amino-triyl-alkyl, tylsulfonylamirvO, in alkali or alcohol with 1-6, 35 carbon atoms, oykloalkyl, 0 3-6- atoms*-, carbon-,-: phenyl fenodMyv"ben^yljx"l*U.ii- f«*y49-i- - ethyl,»at -tyim. each--from these groups jfóLOz$/J? ye v substituted* jeduypv or idw#mav /alkUW„i,r: o 1^6 aiaanaclj^weglay . ¦ 40 R1 = hydrogen-, k-j = hydrogen, or alkali. 1^-L^a.tomach^carbon- R3 ==, Water? ~ or alkyd. 1-4 carbon atoms, optionally in the form of salt. iehlocawco^^K^^n, with the exception that .whenvrX sozna-g^a:¦¦^NRf-y.. 45 then the carboxamide group and the 2.*in position-3 ^yate^fe^o-give a hydrogen atom, and that when X is denoted by CH? ^ -., or ±CH(OH) -r then the substituent^ is.-w-po-. of position 6, R1 and R* mean. hydrogen-atoms and gcupa:,150 carboxycarium-mdioium*¦ .is-in-position Z or 1&fe-resistance,}, respectively at-carbon in position-3* or 2, finds aie. . additional hydrogen atom, -and #e ^d,y,: CH2 or carbon, fenyl, -ienaksyv^ ben^lfti4ub02^eji^^F,... ethyl, and each of these groups may contain one or two bases of this 1—0 ^toma^h (.wasla+^hlQ? fmm,ti., gr^&u,. nitrowa^, with the limitation that when there is a r^^te^^izon^e^u^s, Among these new compounds, there are only 1 of them - those for which JZ =? = TCH-,;n? rflr-, are preferred. . or . The "new groups" of Awia^Jcój^ represent /.-wzAr-A in which,,n. =0,? 4 or 2,. R=rP, Cl,-... Br, nitro, amino,,, m^. (.1—4)S,. and,; their, salts %, chlorine "Paw^do-. ramie..,;. KoEzystaie. are the differences for iwhich R2, and -H8, means hydrogen atoms or R2 means wooVJ'r. a. K3 berayl;.piraz-.'te, for which. R stands for;,-water^X or bases;,w. po^jcjB^-.a,, iUikimri ..j^^fthl^.lmatjrt^.. . i- cy^lp^ek^i- Zwic^kiL::c^ Ayzorjcjc. <^.mozna, P,tr^yr|ia^,f^pps,qbam4 ; o. are the same above and illustrated in the accompanying examples.:;Nizej PiO4an^,pr7^^ao^rr^JQP^. ^0- .. &daraij«pumpkin^^ c^la^^Ainfoiinac^jny^h. <. thighs tow^ueir^^dzii^inft^ of the center* according to the results. /.&a , przyfedy^XXXJ^^^^IX. ,. Example d^, J. (2,3.^il^<^q-N-f2T.prop^lep(Q)-iAz -bejiiZOdi^teaif! a^M^^lW . Cl). ¦¦ ¦ r Rozfw#.jgi2;i#ptjsUle-1yJUwegQ- ^wasi^^^^-d^hydro- . -l,4^ben^e^io^ya^-2^kairbpksy^. (Koofjet ^1.,... i 5,7;^ ^wpr^eiia^ mhG^ under ^eter^ec-., Scvn^Qtrz,xmaAO zwia^eJsr,Vw poetec^WatoPft.JtóeJteKl... o teapa®^tpp^^,5^,5-^57°iC CKpo,iJ.ijnni: ^9 -^l°vC). . At:^l^d jll. {,,3T4ihy4rQrN,r(2rpr/qpeny^9)-:3- met^p-L4*enz^ A.Mieflizan^a,;*?,^-^^ l-chlpd:o~23- , '-epato^3r^e&i^ JSt, ,? y^4p.Am.^lni:jnr: ^1^0, l§4)tW; 100? ni..ItfA ,solution of the water ^J^dlOri9tte^^r^from the month^a^PiJ^g^ext^w.under the chill^w%^a^4j)(^a v.prz« with ^^ sodium hydroxide, dried (MgSCU) and evaporated, v;^zpypzgz^ln^...,#ozQRtalff4c distilled in vacuum^^^ . ^Use^^ ^za^je^jaca^^ O^o 2,3-dihydro-2-methyl-1,4-benzodioxin-2 - methanol and 30? /fcr!%4-di^r%3^ -2-atol,jM 2 g^miJe^^ Piyif ... The mixture was stirred at 100°C for a long time at room temperature overnight, and the liquid was quickly mixed with water and extracted: (wpda and extracted with an aqueous solution of sodium carbonate acid. Then the combined carbonate extract was acidified with concentrated hydrochloric acid and extracted with ether. Combined extracts* ¦ - the ether was washed, water, dried (MgSO*}, half of the evaporated solvent, the residue - 4-crystallised - 15 127 781 16 from the ether-hexane mixture to obtain 2,3-dihydiro - 2-methyl-1 acid, 4-Benzodioxincarboxyl-2 (2A). 3.0 g of compound 2A were dissolved in 15 ml of thionyl chloride and the solution was refluxed for 45 minutes. After evaporating the excess thionyu chloride; the liquid residue was cooled with ice and 20 ml of 2-propenamine were carefully added thereto. The resulting solution was stirred at room temperature for 4 hours and, after evaporating the excess amine, the residue was shaken with methylene chloride and water. The organic layer was separated, dried (MgSO4) and, after evaporating the solvent, the residue was chromatographed on a dry column filled with silica gel, using solvent no. 3 as an eluent, i.e. a mixture of 4:30:66; hexane. As a result of chromatography and after crystallization from the ether-hexane mixture, compound 2 was obtained in the form of a white solid with a temperature of 67-68°C, Example 3. 6-chloro-2,3-dihydiro-N- (2-propylene)-1,44-enzodioxin-2-carboxamide (3A) and isomer-7(3B). 4-chlorocatechin was condensed with ethyl 2,3-dibromopropionate as described by F. DeMarchi and in., Gazz. Chim. Ital. 95, 1447-54 (J965). The obtained product contained approximately 70% of the 7-chloro isomer and 30% of the 6-chloro isomer of 2,3-dihydro-1 acid ethyl ester ,4-benzDdioxincarboxylic acid-2. A solution of 10 g of the obtained mixture of isomers and 9.1 g of 2-propenamine in 50 ml of ethanol was heated under reflux for 20 hours. After evaporating the solvent, the product obtained in the form of a resin was chromatographed on a dry column filled with silica gel, using Solvent No. 3 as the eluent. A number of bands showing fluorescence in ultraviolet were obtained in the column. These bands were separated by cutting the contents of the column at appropriate locations and each portion was extracted with the appropriate solvent, methylene chloride or acetone. Each extract was filtered and, after evaporation of the solvent, crystallized from the ether-hexane mixture. Two white, crystalline products were obtained, one of which was compound 3A (mp. 2-73°C) and the other was compound 3B {temp. topn. 60.5-61.5°C). EXAMPLE IV. The cis isomer of 2,3-dihyde(ro-3-methyl-N-(2-propenyl)-1,4-benzodiokisine-2-carboxamide (4) was prepared in the manner described by Koo et al. ibid. Mixed diastereoisomers of 2,3-dihydro-3-methyl-1,4-benzodioxynorcarboxylic acid-2 ethyl ester were prepared from catechin and ethyl 2,3-dibromobutyrate, containing approximately 67% of the cis isomer and 33% of the trans-isomer A solution of 7 g of this mixture and 14 g of 2-propenamine in 100 ml of ethanol was refluxed for 24 hours. After evaporation of the solvent, the residue was chronatogirafed on a dry column filled with silica gel, using solvent No. In Example 3, a yellow liquid was obtained as one fraction. The product was crystallized again from a mixture of ether-hexane and obtained in the form of a white, crystalline solid with a melting point of 70.5°C. 72.5°C cis isomer of compound 4, as determined by the analysis of the spectrum of M. R. J. Example V. 6-(1,1-dimethylethyl)2,3-dihydro-N -(2-pro mid (5) To mixture 23 g of 4-butyl catechin, 56 g of potassium carbonate and 200 ml of acetone were added slowly, while stirring at 25° C., 40 g of ethyl 2,3-dibromopropionate. The hot mixture was connected to a reflux condenser and heated for 4 hours. The mixture was filtered and the resulting precipitate was dissolved in water. The solution was extracted with toluene. Then the toluene extract was combined with the acetone filtration and the solvents were evaporated in vacuo. The residue was subjected to vacuum distillation to obtain a mixture of 6- and 7-(1,1-dimethylethyl)23-dihydro-1,4-benzodioxincarboxylic acid-2 acid ethyl esters (5A), boiling at 141-142°C under a pressure of 0.1 Torr. A mixture of 13.2 g of compound 5A and 8.5 g of 2-propenamine was left at room temperature for 19 hours, and then the excess amine was distilled off from it in a vacuum. The residue was extracted with pentane and the extract was allowed to stand overnight. The precipitated crystals were collected, from which, after crystallization from hexane, compound 5 was obtained in solid form, with a melting point of 95-96°C. Example VI. 2,3-dihydiro-6-methyl-N-(2-propenyl)-1,4Hbenzodioixin-2-carboxamide (6) and its equivalent 7-methyl (7). To a mixture of 24.8 g of 4-methylkaitechin, 23 g of potassium carbonate and 250 ml of acetone, 15 g of ethyl 2,3-dibromopropionate were slowly added, while stirring and heating under reflux. Then, 20 g of potassium carbonate and 27.2 g of ethyl 2,3-dibromopropionate were added to the mixture in three portions over an hour, after which the mixture was heated under reflux for 6 hours and left for about 2 days. The mixture was filtered and the precipitate was washed with acetone. The solvent was evaporated from the mixture of acetone from the washing and the filtrate, and the residue was distilled off in vacuo. A mixture of ethyl esters of 2,3-dihydro-6-(i7)methyl-1,4-benzodioxincarboxylic acid-2 acids (6A) was obtained with a boiling point. 124-126.5°C with a glow of 0.045 Tr. A mixture of 11.1 g of product 6A, 20 g of 2-propenamine and 50 ml of ethanol was stirred at room temperature for 24 hours, then the solvent and excess amine. The residue was chromatographed on a dry silica column using 4:30:50 (volume) tetrahydrofuran, ethyl acetate and hexane as the eluent. The obtained liquid product was crystallized from an ether-hexane mixture, dissolved in ether. The solution was cooled and, after filtration, a precipitate was obtained - product 6B. After some time, the crystals precipitated in the mother solution. These crystals were filtered off, obtaining the product 6C with a melting point. 69-7l°C. Product 6B was dissolved in ether and the resulting solution was cooled. After draining the precipitated! crystals, they were crystallized (sequentially from ether and a mixture of pentane-di-m 12X781 and chloride, with methyl, obtaining product 62 in the form of white needles with a top temperature Tfr -79.5? C. assuming that the less symmetrical isomer has a different melting point; product 6D is assumed to be the fr-methyl isomer and product 6C as the 7-metal isomer. Example Vii: 7-nuoro-2-dihydro-N -(2-propenyl)-i,4-benzodioxin-2-carboxamides (8) 24 g of 4-fluorocatechin, obtained as described by Corsei J. et al., J. Org, Cham., 16, 1345 (1951), was mixed with 57 g of ethyl 2,3-dibromopropionate at 15° C. and the mixture was allowed to stand for 2 hours (during this time, the temperature; the mixture was rising). The mixture was then heated to reflux. , for 3.5 hours, cooled and filtered. The solvent was evaporated from the filtrate and the filtrate residue was obtained in the form of a paste. The filtrate was treated successively with water and methyl chloride. After separation of the layers, the solvent was evaporated. organic layer; and the residue was distilled in vacuo. Mixed ethyl esters of 2,3-dihydro-6(and 7)s-flu2oro-1,4-benaodioxynecarbaxyric acid-2 were obtained. (8A) with a boiling point* of 116-120°C at a pressure of 0.1 Torr. 25 A mixture of 7 g of the product and 10 g of 2-propyl alcohol was left at room temperature overnight. The mixture was evaporated under solvent under reduced pressure, the residue was extracted first with pentene and then with cyclohexane. After; After evaporating under reduced pressure, the soluble substance, soluble in eyldahetesan, was crystallized from pontoon, obtaining product 8 in the form! *dad's body with top temperature, 54^5*JC.Pnzyclade VIII. 3,4-di-bydra-4^benzyl-2H-1,4^benzoxazinecarboxyl-2-acid ethyl ester (9) was prepared by condensation of o-aminoienol in the manner described in British Patent No. 1,057,528 and ethyl 2,3-disubromoate, carried out in dry acetone with potassium carbonate - 3,4-hydro-2H-11;benzoxstine:aT-boxylic acid-2 {^A) ethyl ester hydrochloride . This compound was obtained in the form of white crystals with a melting temperature. r86-188°C (according to British Patent No. 1057,528, the melting point of the compound is 18"-135°C). ^ none 5.3 g of Zzion 9® and *.2&g. the whole thing was stirred at a temperature of 100°C for 5 hours. The precipitated thallium bromide was filtered off, and the residue was evaporated under reduced elu«nfc a mixture of r*6:8Q* {e.g. temp.. to^n. 83.5-84.5°e.Pr Ly ksl-aid Dl Bfeter ot&lowg acid &ahtafo -3,4rdihydoo^H:- l,4^ttQ (10). In 500! m£ anhydrous , acetone; containing * 42.0 g of anhydrous carbonate in the fields, 43.0 g of 2^mino-4K+ chloride dissolved? toiu., Hiaztwtorr heated to a boiling point and slowly added 23 g of AantaMfacomopco* ethyl pionate* Then to the boiling pot HUftwagriU was added* in three portions of tite astm t carbonate* and* to make the total amount of entrium; amounted to 12 g and the whole was heated under a refrigerator for 21 hours. After removing the precipitate and evaporating the filtrate, the solids were dissolved in water and the solution was extracted with ether. After the extract was suffocated, tere, (MgSO2 and evaporation of the solvent, pafco»talos6. knystaiiso^ water from ethanol and chloromatags was refined onto a calumnift filled with silica gel, using an eluent mixture of 4*3QtW (tu. ottji). ethyl acetates and: hait'niil Ptodulst was crystallized first from ethanol, then from ether; compound V0 was obtained in the form of bilayer crystals with a temperature of 85.5^-88.5^C: Example fi-n^tyl^314^da]iydwr2Hi-l,i-lan^xazine-carboxylate-2 (11).Ba» hot mixture LO^O- g bapy rLu: potassium;, 56.6 g 2~amico- 400 ml of dry acetone and 500 ml of dry acetone were added in 100 ml of water, 200 ml of 200 ml of 200 ml of 200 ml of 2000 ml of 2000 ml of 2000 ml of sodium chloride, similar to that in Example X, supplemented several times and heated under reflux. 17 ^Month. After? pra«sietz«niu miesnadai^ and oo^ar^naniu from- filtrate rotT^iMBcraliyte. ^) by diluting it with pressure, a liquid posophthalic DsA.ifitóa was obtained and dissolved in HHnpBcafcia® 5-10PC 30 ml IN solution. ^RidEHKktteisku sodium. Bodiwóc oztKcaterotnift 30 minutes ago The combined ethanol axiracts after extraction (Mg(S0)) were treated in a teapot with a gaseous liquid. The precipitated ooid was dephtized, transformed with acetate and crystallized. Vimmm*&k of ethanol. OtEz^mano/sudafik U in the form of white crystals at a top temperature of 158-160°C. Example XI. Ethyl ester of peat-3^-dihydrylpo acid 2H-1,4,-benzo (12), It gives a very good lift & anhydrous veganate, l&fit g 4rn4ta^^2raminQfea3jQlu and 50X1 ml of dry/1KBtttoou added dropwise with 29»2 g of 2,3-nivubromapropinaate Tr^toeieie and matfizanin, reactionary was heated under the chller for 17 fancy. methylene, then the solvent was evaporated from each e-ratrafet, and the residues were removed using thin-layer chromatography method. ov- dlicts. These products were combined and, after cryaftaflation, compound 12 was obtained from them in the form; solid with melting point 88^-»°C.1# 127 781 2 Example XII. 6-amino-3,4-dahydro-2H-1,4-benzoxazinecarboxylic acid-2 acid ethyl ester hydrochloride (13). Two 1-gram portions of 10% palladium-carbon catalyst i were added to 10 g of compound 4 in 700 ml of ethanol. The mixture was hydrogenated for 2 hours at approximately 3.5 atm (50 psig). Fresh catalyst was added to the mixture four more times; and hydrogenation was continued. The analysis was performed using thin layer chromatography. The present study showed that the nitro group was completely reduced to the amino group. The mixture was filtered, filtered, the filtrate was evaporated and part of the obtained liquid (13A) was dissolved in ethanol. Then ether was added to the obtained solution and, after cooling the mixture in an ice bath, hydrogen chloride gas was passed through it until the precipitation of the precipitate ended. The precipitate was filtered off, washed with ether and after crystallization from ethanol, compound 13* was obtained in the form of a solid with a melting point. 222°C (decomposition). Example XIII. 3,4-Di-hydro-6-[i(methylsulfonyl)amino]-2H-1,4-benzoxaziriocarboxylic acid-2 ethyl ester (14) Mixture of 14.7 g of product 13A and 7.3 g of triethyl ailine 8.3 g of methanesulfonyl chloride were added to 200 ml of methylene chloride at a temperature of 0-5°C. The mixture was stirred for 2 hours, washed with water, dried, filtered and evaporated, the liquid was dissolved. The residue was mixed with 100 ml of ethanol, filtered and the precipitate crystallized. from ethanol, obtaining compound 14 in the form of a solid with a melting point of 149-151°C. ; Example XIV. 6-(trifluoromethyl)^3,4-dihydiro-2H-1,4-benzoxazinocarboxylic acid-*2(15) ethyl ester, solution 164.0 g of 2-nitro-4-(trifluoromethyl)-chloroberizenju in 200 ml of dimethyl sulfoxide, 87.6 g of finely powdered sodium hydroxide were added for 8 hours while stirring in a room temperature meter and the mixture was left to stand overnight. Then the mixture was poured into 1.5 filters of cold water and the whole was acidified with concentrated acid. salt solution to pH 1. An oil separated from the mixture, which after separation was dissolved in ether. The solution was dried (MgSo4) and, after evaporation, the solvent was mixed with a cold sodium hydroxide solution under reduced pressure. The obtained mixture was extracted with petroleum ether. the aqueous water was acidified with concentrated hydrochloric acid and the resulting oil was separated and dissolved in ether. After drying (MgS04) and evaporating the dissolved solvent, 2-nitrbium-4-(trifluorometh^^ (15A) was obtained from the solution. 3 82 1.2 g of compound 15A was dissolved in 300 ml of ethanol and 0.5 g of platinum oxide catalyst was added to the solution. The mixture was hydrogenated at a pressure of approximately 50 psig, with occasional additions of catalyst. The resulting mixture was filtered and the solvent was evaporated from the filtrate. The residue was crystallized from water to obtain 2-3-nine-4-trifluoromethylphenol. (15B). t After 48J g of compound 15B in 320 ml of acetone, 11.4 g of potassium carbonate were added. The mixture was heated to the boil and 18.2 g of ethyl 2,3-dibromopropicoate were added dropwise. This was repeated three times, and then the mixture was refluxed for 17 hours. After filtering the mixture and evaporating the solvent 5 from the filtrate under reduced pressure, the residue was dissolved in ether. The solution was washed with dilute sodium hydroxide, dried (MgSO4) and the solvent was evaporated. The residue was washed with petroleum ether, dried, mixed with ether and filtered. . Part of the solvent was evaporated from the filtrate and the solution was cooled. Crystals formed in the solution, from which, after filtration and crystallization from ether, a 1% compound was obtained with a melting point of 105-107°C. ls Example XV. 6-methox/-2,3-dihydro-2H-1,4-benzoxazinecarboxylic acid-2(16) ethyl ester 336.4 g of 2-nitro-4-methoxyaniline were heated under reflux for 20 hours with 200 g of sodium hydrogen oxide and 10 g of arsenic trioxide in 6500 ml of water. The resulting solution was cooled in an ice bath and acidified with concentrated hydrochloric acid to pH 1. The precipitate was filtered off, washed with water and, after drying over P205 under reduced pressure, 2-nitro-4-methoxyphenol (16A) was obtained at RT. 78-80°C. 193.1 g of compound 16A were mixed with 1400 ml of water and 513 ml of ammonium hydroxide were added to the mixture. Then, 595 g of powdered sodium dithionite were added to the mixture in portions over 50 minutes and the mixture was stirred for 2 hours. The formed precipitate was filtered off and dried over P2O5 under reduced pressure to obtain 4-methoxy-2-aminophenol (16B) with a melting point of 134^136°C, a mixture of 56 g of compound 16B and 58.4 g of potassium carbonate in 650 ml of dry dimethylformamide was heated to 60°C and 104 g of ethyl 2,3-dibromopropionate was added thereto. The mixture was kept at 60°C for 48 hours, then 4 liters of it was poured into 4.5 liters of ice-water and extracted with ether. The extract was washed with water and then with 0.1 N sodium hydroxide solution, dried (MgSCU) and the solvent was evaporated under reduced pressure. The residue was chromatographed on a small column of silica gel, using 1:9, 1:4 and 1:1 (volume) mixtures of ether and hexane as eluents. The last fraction was dissolved in ether. After cooling, the solution a precipitate formed, which after filtration was crystallized in a mixture of ether and petroleum ether (30-60°C) to obtain compound 16 in the form of almost white crystals with a melting point of 59-61°C. Example XVI. Acid ethyl ester 6 -cyclohexyl-2,3-dihydro - 2H - 1,4 - benzoxazinecarboxylic acid-2 (17) To a solution of o-nitrophenol in 1500 ml of 85% sulfuric acid was added slowly, over an hour, while stirring at room temperature, 90 g of cyclohexainol and the mixture was heated at 70°C for 4 hours. The mixture was diluted with 2000 ml of ice water and extracted with 6000 ml of benzene. 2/3 of the solvent was evaporated from the extract under reduced pressure. The concentrated solution was washed with water, dried (MgSOi) and evaporated under reduced pressure. The residue was stirred with 300 g of silica gel and purified with 2300 g of silica gel and chromatographed with petroleum ether on a dry column. Four fractions were isolated and extracted with ether. The ether was evaporated from the extract of the second fraction and 4-cyclohexyl-2-nitrophenol (17A) was obtained in the form of a yellow liquid. 25^5 g of compound 17A were dissolved in a mixture of 200 ml of methanol, 200 ml of methylene chloride and 400 ml of water. 86 ml of ammonium hydroxide were added to the solution, followed by 82 g of sodium dithionite in portions. The mixture was refluxed for 5 hours and 300 ml of methylene chloride was added. The methylene layer was separated, dried (MgSO) and the methylene chloride was evaporated. The residue was washed with petroleum ether and an insoluble white precipitate was collected which, after drying, was identified as 4-cyclohexyl-2-aminophenol (17B) with a melting point of 103-105°C. To 15.9 g of compound 17B in 90 ml of dry acetone, 6.9 g of anhydrous potassium carbonate were added. The mixture was heated to boiling and 11.6 g of 2,3-dwTJbromopropioniana were slowly added thereto. This procedure was repeated and the mixture was refluxed for 24 hours. The mixture was filtered, the filtrate concentrated and taken up in ether. The ether layer was separated, dried (MgSO3) and the solvent was evaporated. The residue was mixed with petroleum ether, filtered and the filtrate solvent was evaporated. The residue was crystallized from hexane to obtain compound 17 with a melting point of 119-121°C. Example XVII. 3,4-dihydro-N-(2-propylene)-2H-1,4-berisoxazine-2-carboxamide (18) Proceeding as described in British Patent No. 1,057,528, was prepared by condensation of aminophenol and ethyl 2,3-dibromopyroprionate, carried out in dry acetone with potassium carbonate, 3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ester hydrochloride (18A). This compound was obtained in the form of white crystals with a melting point of 186-188°C (according to British Pat. No. 1,057,528, the melting point of the compound is lfl--1G5CC). To produce the free base (18B). compound 18A was treated with sodium acid carbonate. A solution of 7.3 g of compound 18B and 6.84 g of 2-propenamine in 50 ml of ethanol was stirred for 3 days at room temperature. After evaporation of the solvent and excess amine, the residue was shaken with ether and water. After separating the ether layer, the aqueous layer was extracted with ether. The combined ether solutions were washed with water, dried (MgSOa) and concentrated to give compound 18 as white crystals with a melting point of 90-91°C.Example 2CVIII. 3,4-dihydro-4^methyl-N-(2.-propenyl)- 2H-1,4 - benzoxazino - 2 - cairboxamide (19) To a solution of 2.6 g of compound 19B in 50 ml of ethanol was added dropwise, while stirring at room temperature, a solution of 3.76 g of thallium ethanol in 50 ml of ethanol. The resulting mixture was stirred at room temperature for 24 hours and a solution of 1.8 g of methyl iodide in 50 ml of dibutylformamide was added. The mixture was stirred at room temperature for 82 hours and filtered. 10 15 20 25 30 35 40 45 0 II 60 After evaporation of the solvent filtrate, the product was obtained in the form of a gum. This product was mixed with ethanol containing a small amount of sulfuric acid as a catalyst and refluxed overnight. The resulting mixture was cooled, neutralized with sodium acid carbonate and the solvent was evaporated. The residue was shaken off with tfrod and methylene chloride. The methylene chloride layer was separated and the aqueous layer was extracted with methylene chloride. The combined methylene solutions were washed with water, dried (MgSO4) and the solvent was evaporated. The liquid obtained from the residue was chromatographed on a dry spindle gel column using a 4:30:66 (volume) mixture of tetrahydrofuran, ethyl acetate and hexane as eluent. During chromatography, the faster moving main component was isolated, which was then dissolved in ether and treated with halogen gas to form the hydrochloride salt. The product obtained in the form of a resin was separated and triturated with ethanol. After cooling, the hydrochloride of 2,4-dihydro-4-methyl-2H-1,4-benzoxazinecarboxylic acid-2 (2A) ethyl ester (2A) separated from the solution in the form of white crystals with a melting point of 8°-93°C. A solution of 1.1 g of compound 19A and 5 ml of 2-propenamine in 25°C ethanol was heated under reflux for 16 hours, then the solvent and excess amine were evaporated. The residue was passed through a silica gel column eluting with solvent no. 3. Evaporation of the solvent gave compound 19 as a light yellow liquid. The boiling point of a liquid is not determined. Example XIX. 6-chloro-3,4-dihydro-N-(2-propenyl)-2]H-1,4-benzoxazine-2^carboxamide (20) 43.0 g of 2-amino-4-chlorophenol were dissolved in 500 ml of anhydrous acetone, containing 42.0 g of anhydrous potassium carbonate. The solution was heated to a boil and 23.0 g of ethyl 2,3-dibromopropionate were added dropwise. Then, to the boiling solution, enough ester and carbonate were added in three portions to make the total ester was 85.8 g and carbonate 124 g. The whole was heated under reflux for 21 hours. The precipitate was filtered from the mixture and washed with acetone. The solvent was evaporated from the filtrate and the residue was dissolved in water. The obtained solution was extracted with ether. Extract The ester was dried (MgSQ4) and, after evaporation of the solvent, the residue was passed through a silica gel column using solvent no. chloro* -3,4-dihydro-2|i-l,4 -. benzoxazinecarboxylic acid-2 (20A), in the form of white crystals with a melting point of 85.5-86.5°C. Treating the compound 20A with 2-propenamine as described in Example 1 produced compound 20 in the form of white plates with a melting point of 114-14.5°C. Example XX. 6-methyl-3,4-dihydro-N-(2-propenyl)-2H-1,4-benaoixazine-2-carboxamide (21) After a boiling mixture of 19.0 g of anhydrous potassium carbonate, 56.6 g of 2-amiTKHp-cresol and 500 ml of su-r 23: 2,3-dual ethyl propionate and potassium carbonate powtfe-glfcao-and torzyferateife: in the mixture, there were 7.6 g of potassium carbonate, and 118 g of 2.3 ^dwu- 5 bror}e^rp53*a#iatt! U;-e£y/Hv ^iC#z%iir*§roge-zgwano poal chłodnia, .zw^tpLa, for,47 igodzfei-i, r^zesawano, From pr^S£CB*:^dde^yipwanq under: reduce Oiiyin €is-, nienjtea^-TOzp^wsc^l^kf - pozo&t&losk-rozejef^czpno.-at temperature 5-:10° (£ 300 {ml* lNrrpzt^oru^wp^rp-r v . sodium oxide; and ek^traihow.an^v e-teren\v-in the amount of 4X gas tanks, q^]^p/W[pdojru,. in a perature of 5^-10°(Q.( Precipitate was precipitated, which was extracted after filtration! ;aceto^ep^^^ horizontal^^ 15 was crystallized from ethanol to obtain 6-methyl-3,4-dihydro-2Jl-1,4-benzazinecarboxylic acid-2 ethyl ester hydrochloride (21A) in the form of white crystals at mp 158-160° C. 42.4 g of compound 21A and 38 g of 2-proamine were mixed in 156 liters of ethanol, and the mixture was stirred at room temperature for 90 minutes. After removal After removing the solvent, under reduced pressure, the remaining solution was shaken with ether: and - water. After drying the ether solution (MgSO4), approximately half of the solvent was evaporated. A precipitate formed, from which, after filtration and drying under reduced pressure, the compound 21 was obtained, melting point: 16-415°C - Example. XXI. 6^nitro-3,4-dihydro-N-(2-pro-m penylh2H<-1,4-*benzoxazine-2-carboxamide (? 2) Mature; mixture of 19 £ Ipeaw^dn-egp potassium carbon, 70.9 g of 4-nitE0^2^aminofe^ol, and 500^thqL dry, acetone, 29.2 g of ethyl dibropropionate were added dropwise. ethyl and potassium carbonate were repeated a number of times so that in the end, the mixture contained 76 g of potassium carbonate and 118 g of ethyl 2,3-dibramopropionate. The mixture was heated to reflux for 17 hours, then filtered. The filtrate was concentrated under vacuum, washed with a dilute hydroxyl solution, extracted with methylene chloride, and the dissolved solvents were evaporated. Thin-layer chromatography showed the identity of both products, these products were mixed together and after crystallization from ether, the acid ethyl ester, 6-nitro-3,4-dir hydro-2H1,4-bettzoxazinecarium, was obtained from them. ^l^ylcarbon^, (22A,) in the form of a solid, with a temperature of 88-^90oC. A mixture of 10.0- g of the ^22A compound, 9.1 g of 2-propenamine and 35 ml ethanol was stirred at room temperature for 3 days. After evaporating the solvent under reduced pressure, the residue was washed with ether, dried and crystallized from ethanol, obtaining compound 22 in the form of orange-*, 55-piece crystals with a temperature of -mp. 142^144°C r.Example XXII. 3,4-dihydxo^-&(methylsulfCrnylamino]-N-<2-propenyl)-2H-1,4-benzoxazine-2-carl^oxamide (23) To 10 g of compound 22A in 700 ml of ethanol was added, in two 1-gram portions of 10% palladium on carbon as a lysing agent. The mixture was hydrogenated for 1.2 hours under a pressure of approximately 3.5 atmospheres. To the mixture, fresh catalyst was added four more times and hydrogenation was continued. The analysis of 24 preparations; the method showed , that the groups were reduced to: g-ruo, aminoal\.r ^iezanjne prze,- saezona: and: pp zate^aiu^zesaczu, received inftfio ppcl^od-. ; for change^w^^^Lw will pour ^%? «? wei of liquid,, MiGiSzandna 14.7^g of compound]^.!,? ^^ larój^tylor, sr/ii :i/ in 200 ml of methylene chloride was added ^w 4em-. ;,eratvdrLze - 0 -5? C - 8.3 g of metanos'Ulfonyl chloride. :: Mixture: stirred for ^j.^ hours after ,part 0- washed, water,-^ was washed, boiled and evaporated, the linseed was washed, the phosphorus was washed, a little water was washed, and After crystallization from ethanol, the derivative of methylated polymeric acid (<23B^ in the pos.) remains solid with a melting point of 149-151°C. Mixture: 7 .3 g of compound 23B, 20.:ml.: 2-pro-T enamine and 10 mLetanoU* were stirred at room temperature for -20._hours:. The resulting precipitate was filtered off, dried and after crystallization, from a 6:1 mixture (volume) of ethanol and acetoin, compound 23 was obtained in the form of white crystals - mp. 178—180°€. P rszyk-l/aji., XXIII.A $ - trifluoromethyl - 3,4-di-hydrp-N-(3-propenyl) 2H7IA - benzoxazino - 2-carbo,samiide,,(24) For solution-164 .0.g 2-nitror4t^(tr6ifluorpmethyl)T. -chlorobenzene in 220 ml of dimeyl sulfoxide were added in portions over 3 hours while stirring at an alcoholic temperature. were brought in for the night. t Then - the mixture was poured. to 1.5 liters of cold water and the whole was acidified with concentrated hydrochloric acid (to pH 1-). An oil was formed which was separated and dissolved in ether. The solution was stewed (Mg2O under reduced pressure). The quantities were mixed with an impurity solution of sodium hydrogen chloride. The mixture was extracted with petroleum solution and the aqueous layer was acidified with concentrated hydrochloric acid. The following formed: and dissolved in ether; the solution was taken up with MgSOl) and after evaporation, the 2-nitro-4-(trifluorornatyl)enpl, 82.2 g of the compound and dissolve 4A in 300 ml of ethanol. Add 0.5% of platinum oxide as a catalyst to a solution and mix hydrogenated under pressure of approx. 3.5 atmospheres (50 liters, setting aside some time - portions of the catalyst. The reaction mixture was sifted, filtered, concentrated and after crystallization from water, 2-amino-4-(trifluororrietyl)-ienpl-^B). To 48.7 g of reconnaissance, 24 B in 320 ml of acetone, 11.4 Lg of potassium carbonate were added, and the mixture was heated to September and added tooplaii 18.2 2,3-dwubrpm- pror^o^iaffljU^yl. the administration of methyl 2,3-dibromopropionate and pptassium carbonate was repeated three times so that the total amount of tyAuv 2,3-dibromopropionate was present in the mixture; was 72.8 g of potassium carbonate; 45.6, h. . The reaction mixture was then heated under reflux for 17 hours and filtered. After evaporating the filtrate under reduced pressure, the solvent was dissolved in the air. The solution was washed with dilute sodium hydroxide solution and dried. (MgSO1) and the solvent was evaporated and the residue was washed with petroleum ether, dried and dissolved in ether. Part of the solvent was evaporated from the ether solution and the concentrated residue was cooled. After filtration and crystallization of the precipitated crystals from ether, 6-trifluoromethyl-3,4-dihydro-2H-1,4-benzoxazinecarboxylic acid-2 ethyl ester (24C) was obtained, m.p. 105-107°C. A mixture of 20.6 g of compound 24C, 25.7 g of 2-propamine and 34 ml of ethanol was stirred at room temperature for 36 hours. The excess amine and solvent were evaporated under reduced pressure and the solid residue was mixed with 150 ml of ether. After filtration, and the undissolved precipitate was removed, the filtrate was poured into petroleum ether and the mixture was cooled. The separated viscous product was filtered off, and the filtrate, after evaporating the solvent, was triturated with petroleum ether to obtain an almost white powder. The product was chromatographed on a dry column packed with silica gel, using ether as eluent. The band with the higher Rf was cut out and after extraction from ether and evaporation of the solvent a solid residue was obtained which was crystallized from a miscible 4:5 (volume) ether and hexane. Thin layer chromatography showed the presence of two components. The obtained product was purified by chromatography on a wet column. filled with silica gel, using a 1:4 mixture (part by volume) of petroleum ether and ethyl ether as the eluent. After evaporating the solvent, the residue was crystallized from a 75:10Q mixture (volume) of ether and hexane, obtaining compound 24.j in the form of a solid with a melting point of 95-97°C. Example XXIV. 6 - chloro-3,4-dihydiro-N-(2- -propenyl)-2H-1-benzopyran-2-carboxamide (25) Solution 3.1 g of 6-chloro-3,4-dihydro-2H-l acid - -benzopyranecarboxylic acid-2 (25A) Witiak et al. (1971), ibid. in 15 ml of thionyl chloride was heated under reflux for 45 minutes. The excess thionyl chloride was evaporated and the liquid residue was dissolved in 50 ml of methylene chloride. To the obtained solution, while stirring, a solution of 2.5 g of 2-propenamine in 10 ml of methylene chloride was added dropwise, and the mixture was stirred at room temperature overnight. Then the mixture was washed with water, dried (MgSOO and after evaporation of the solvent, the solid residue was chromatographed on a dry column filled with silica gel, using solvent no. 3 as an eluent, i.e. a mixture of 4:30:66 (part, volume) ethyl acetate and hexane. The product was crystallized from methylene chloride and hexane to obtain compound 25 as a light yellow precipitate, mp 112.5-114°C. Example 25. 3,4-d4&ydTO-N-(2-propenyl )- -2H-1-benzopyran-3-carboxamide (26) Solution of 10.4 g of 2H-1-benzopyranocarboxylic acid-3 methyl ester (Taylor et al. ibid.) in 50 ml of methanol, containing 300 mg of 10% pala ¬ carbon on carbon Catalyst, hydrogenation was carried out in a Parr apparatus for 1.5 hours at a pressure of approximately 3.1 atm (44 psig) at the beginning of the process. After filtering the mixture through a pad of celite and evaporating the filtered solvent, the residue was distilled in vacuo to obtain 3,4-hydro-2H-1-bemopi^iiocar4xyl acid methyl ester. it (26A), in the form of a wine-colored liquid with a boiling point of 86-88°C under a pressure of 0.01 Torr. A solution of 5 g of the compound 26A and 5.7 g of 2-prOpenamines in 50 ml of ethanol was heated under reflux for 66 days. After evaporation of the solvent, the product was treated with charcoal and crystallized from an ether-hexane mixture. Compound 26 was obtained in the form of white crystals with a melting point of 114 5^- io —:i5.5°C. Example XXVI. 3,4^hydro-N-(2-pcropenylóU-2H-l-benzopyran-2-carboxamide (27) From chromancarboxylic acid-2 ethyl ester (Witiak et al. 1971) and 2-propenamine, as is described in the last part of Example XXV, compound 27 was prepared in the form of white crystals with a melting point of 76-77°C. Example XXVII 3,4-dihydro-6-phenyl-N-(2-propenyl)- zH-l-benzopyran-2-carboxamide (28) 20 From 3,4-dihydro-6-phenyl-2H-l-benzopyranocarboxylic acid-2 ethyl ester (Witiak et al. 1975) and 2-propenamine, as described in the last part of Example XXV, compound 28 was prepared in the form of a white solid with a melting point of 123-25-124°C. Example XXVIII 6-cyclohexyl-3,4-dihydro-N-(2-propenyl) -2H-l -benzopyran-2 - carboxamide (29) From 6-cyclohexic-3,4-di- M hydro-2H-l -benzopyranocarboxylic acid-2 ethyl ester (Witiak et al. 1975) and 2-propenamine, also in the manner described in the last part of Example XXV, compound 29 was prepared in the form of white crystals with a melting point of 93-94° C. 33 Example XXIX. 6-chloro-3,4-dihydro-N-(2.-propenyl)-2H-1^benzopyran-3^arboxamide (30) To a boiling mixture of 50 g of 3-chloro-6-hydroxy-benzaldehyde and 62 ml of acrylonitrile in 50 ml of water were added dropwise over 3 hours, while stirring, a solution of 12.8 g of sodium hydroxide in 120 ml of water. Then 62 ml of acrylonitrile were added and the mixture was heated under reflux for 2 hours and then left to stand overnight at room temperature. . The obtained crystals were filtered, washed with water and, after drying, crystallized from ethanol. After filtration, the solution was cooled and tables of 6-chloro-3,4-dihydro-4-hydroxy-(2H)-1-benzopi* morning-3 were obtained. -cafrbonitrile (30A). A mixture of compound 30A with 250 ml of methanol boiling down with 2 ml of sulfuric acid was heated under reflux for 4 days. After evaporating the solvent, the residue was chromatographed on a dry column filled with silica gel, using solvent no. 2H-1-benzopyranocarboxylic acid-3 (30B), in the form of light yellow needles with a melting point of 106 - N -109°c- 700 mg of compound 30B were dissolved in 75 ml of ethyl acetate and the solution was hydrogenated for 8 hours in the presence of 10% palladium on carbon as a catalyst, applying pressure at the beginning of the process of about 2.5 years (30 psig). The reaction mixture was filtered and, after evaporating the solvent, 6-chloro-3,4-dihydro-2H-1-benzopyrancarboxylic acid-3 methyl ester (30C) was obtained as a yellow liquid. The boiling point of the product has not been determined. A mixture of 500 mg of the 30C compound, 5 ml of 2-propamine and 25 ml. ethanol was heated to reflux for 28 hours. After evaporating the solvent, the residue was dissolved in methylene chloride. The solution was triturated with hexane and cooled to give a solid which was dissolved in ethanol. The solution was passed through a short silica gel column and the eluent was evaporated from the solvent. The residue was crystallized from a mixture of methylene chloride and hexene to obtain compound 30 in the form of white needles with a melting point of 171-171.5°C. Example XXX. 6-chloro - 4 - hydroxy-N-(2- -propenyl)-2H-1-benzopyran-2-carboxamide (31) Solution 512 mg of 6-chloro- -3,4-dihydro-4-hydroxy- ethyl ester 2H-1-benzopyran-2-carboxylic acid, which was prepared by treating sodium borohydride with 6-chloro-3,4-dihydro-4-lketo-2H-1-benzopyran-2-carboxylic acid ethyl ester Witiak et al . ibid.), 570 mg of 2-propenamine and 20 ml of ethanol were stirred at room temperature for 72 hours. The mixture was then stirred and heated on a steam bath for 3 hours and the solvent was evaporated. The residue was crystallized from a mixture of methylene chloride and hexane to obtain compound 31 in the form of white crystals with a melting point of 129-130.5°C,. Example XXXI. Carboxamides of formula II have been found to inhibit fat production in mammalian tissues. The effectiveness of these compounds was confirmed by immersing samples taken from the liver or adipose tissue in a liquid medium containing radioactive glucose and the tested compound for a certain period of time, and then separating fat from these samples and determining the radioactive carbon content using the scintillation method. The tests were carried out with liver and adipose tissue, because in some animals fat production occurs mainly in the liver tissue, while in others - in adipose tissue. The tests were carried out on animals such as pigs, sheep, rabbits, cats and dogs. The following procedure was followed: tissue walls (200 mg for liver, 150 mg for adipose tissue) were incubated for 2. hours at 37°C by shaking in 3 ml of Krebs-Ringer sodium bicarbonate solution. The solution contained calcium ions at a concentration of 0.5 n, 60 micromoles of glucose, 0.5 microcuries of glucose-U14C, 300 microunits of insulin and 5% dimethyl sulfoxide (DMSO). The test compound was added in the form of a solution or suspension in DMSO in such an amount that the concentration of the test compound in the mixture subjected to incubation was 100 mL! crograms/ml of mixture. Incubations were completed with the addition of 0.25 ml of 1N sulfuric acid. The mixture was then extracted with 25 ml of chloroform ethanol in a stack. vol. 2:1, the extracts were washed as per Folch. et. al. (J. Biol. Chem., 226, 497-509, 1957), air-dried and counted in a liquid scintillator using 15 ml of solvent (2 parts of toluene containing 10 15 20 30 40 41 50 15 60 65 of 0.4% New England Nuclear Omnifluor and 1 part Triton X-100). Triplicate tests and a control test were carried out, which differed only in that the test compound was not present in the solution. From the data obtained, the percentage and percentage of fat synthesis by the tested compound was calculated. The compound - was tested for all the animals mentioned, the other three compounds only for pigs. Based on the above and other tests carried out, it was found that that in pigs there is little lipogenic activity in the liver tissue, it was also found that in pigs adipose tissue uses glucose to create fats and that it is the main site of fatty acid synthesis. The results obtained from tests carried out with adipose tissue and glucose are presented in Table 1. They present the percentage inhibition of fat formation in relation to the comparative sample in which the tested compound did not occur. Table 1 - - Compound 1 2 3 3a 4 5 6 7 8 Inhibition (°/o) 75 41 64 38 68 1 36 80 55 72 In sheep, both tissues showed low fat production. There was a greater utilization of glucose for fat in the liver than in adipose tissue. Compound 1 inhibited glucose utilization by the liver by 27% and by adipose tissue by 50%. In rabbits, compound 1 inhibited glucose utilization by liver by 32% and by adipose tissue by 30%. In cats, compound 1 caused a 35% inhibition production of fat from glucose in the liver and showed no inhibition of glucose absorption in adipose tissue. In dogs, adipose tissue turned out to be more active than the liver in terms of fat production. Compound 1 caused a 54% inhibition of fat formation from glucose in adipose tissue. In vivo studies were also performed with compound 1 in pigs to determine the inhibition of fat synthesis in adipose tissue. Piglets weighing approximately 20 kg were given a constant dose of approximately 25 mg/kg of animal weight per day for 7 consecutive days. The agent was formulated to contain 10% by weight. active compound and was prepared in the form of coarse granulate containing 4% by weight. plasden as a granulation aid and lactose as a carrier. Control animals were also administered an equivalent amount of lactose alone. The daily dose of the agent or lactose was added to 1.2 kg of food, which was divided into three parts and administered at 8:00 a.m., 12:00 p.m. and 4:00 p.m. For biopsy, samples (approximately 1 g) were taken from the subcutaneous fatty tissue on the back near the neck, before the start of administration, after 7 days of administration and 6 days after discontinuation of the drug. Sections were prepared from the collected samples and tested in vitro for lipogenesis using radioactive glucose as a substrate. Incubations were performed as above but without DMSO and the test compound. Compared to control animals, it was found that the tested compound did not significantly affect lipogenesis on day 7, but significantly reduced it on day 13. Example XXXII. Sections of 150 mg originating from the adipose tissue of a guinea pig were incubated for 2 hours at 37°C by shaking in 3 ml of Krebs-Ringer bicarbonate solution containing calcium ions at a concentration of 0.5 n, 60 micromoles of glucose, 0.5 microcuria of glucose-U14C, 300 micro-units of insulin and 5% DMSO. The compounds to be tested were added as a solution or suspension in DMSO in such quantity that their concentration was 100 micrograms per milliliter of the incubated solution. Incubation was interrupted by the addition of 0.25 ml of 1N sulfuric acid, and the mixture was extracted with 25 ml of chloroform/methanol. in a pile. vol. 2:1, the extracts were washed as reported by Polch et al. (J. Biol. Chem. 226, 497-509, 1957), air-dried and counted in a liquid scintillator using 15 ml of solvent (2 parts of toluene containing 0.4% w/v New England Nuclear Omnifluor and 1 part of Triton X-100). Triplicate tests and control tests were performed in which the ingredients and their amounts were the same as in the actual samples, except for the tested compounds. From the data obtained, the percentage inhibition of fat synthesis was calculated for the individual tested compounds. The results are presented in Table 2, in the form of percentage inhibition relative to the control. Table 2 1 Compound 9A 9 10 11 12 13 14 15 Inhibition (%) 62 53 28 18 74 43 76 31 Example XXXIII. The effectiveness of the compounds whose preparation is illustrated in Examples XVII-XXIII was confirmed by placing samples of pig fat tissue in a liquid medium containing radioactive glucose and the tested compound for some time, then separating fat from the sample treated in this way and determining the amount of reactive carbon taken. scytillation counting method The research was carried out with adipose tissue, because in pigs the main site of lipogenesis, i.e. fatty acid synthesis, is adipose tissue. 127 781 are The research was carried out according to the following general procedure: 150 milligrams of pork fat tissue trimmings were incubated at 37°C for 2 hours and shaken with 3 ml of Krebsa-Ringer hydrocarbon solution containing calcium ions at a concentration of 0.5 N, 60 micromoles of glucose, 0.5 microcuries of glucose-U14C, 300 units of induliin and 5% DMSO. The compounds to be tested were added in solution or suspension in DMSO and were present in the incubation mixture at a concentration of 100 micrograms/ml. Incubations were interrupted by the addition of 25 ml of In sulfuric acid, the mixture was extracted using 25 ml of a chloroform: toluene mixture (in the ratio 15 by volume 2: 1), washed according to Folch et al. (J. Biol. Chem., 226, 497-509), air-dried and were calculated using a liquid scintillator and 15 ml of solvent (2 parts of toluene containing 0.4% w/v New Englamd Nuclear Omni-20 fluorine and 1 part of Triton X-100). Triplicate trials were carried out, accompanied by appropriate control trials, i.e. those in which all ingredients, amounts and conditions were as in the actual trials, but without the use of the test compound. From the data obtained, the percentage inhibition of fat synthesis by individual compounds was calculated. . The results are summarized in Table 3 as percentage inhibition relative to controls. Table 3 Compound 18 19 20 21 22 23 24 Inhibition (°/o) 1 51 40 63 1 57 20 40 57 40 Example XXXIV. Tests for determining the inhibition of lipogenesis by the compounds of Examples 24-XXX were performed as follows: Tissue walls (200 milligrams from liver, 150 milligrams from adipose tissue) were incubated at 37° C. for 2 hours by shaking in 3 ml of Krebs' bicarbonate solution. -Ringer, containing 0.5 N concentration of calcium ions, 60 micromoles of glucose, 0.5 microcuries of glucose-U14C, 300 micromoles of insulin and 5% DMSO. The test compound was added in the form of a solution or suspension in DMSO and was present in the incubation mixture at a concentration of 100 micrograms/ml. At the end of the incubation, 0.25 ml of acid was added. su sulfur. After incubation, the mixture was extracted using a total of 25 ml of a mixture of chloroform: methanol (2:1, v/v). The extracts were washed (Folch et al., J. Biol. Chem., 226, 497-509, 1957). were air-dried and counted in a liquid scintillator using 15 ml of solvent (2 parts of toluene containing 0.4°/© w/v New England Nuclear Amndfluor and 1 part of Triton X-100). Triplicate tests were performed, accompanied by control tests, differing from the tests proper only in that no test compound was added. From the obtained 12^781 data, the percentage inhibition of fat synthesis was calculated for each tested compound. Compound 26 was tested in all animals, the remaining six only in pigs... Based on the above determinations and other tests, it was concluded; lipogenic activity in pigs. in the liver it is negligible; It was also found that in pigs the adipose tissue uses glucose for lipogenesis and that this is the main site of fatty acid synthesis. Results that have been obtained from tests carried out on tissue. fat and glucose are presented in Table 4, as percentage inhibition of lipogenesis compared to the control sample. Table 4 Compound .25 26 27 28 29 ¦ . . thirty . 31 Inhibition (%) 1 59 83 72 76 1 40 1 67 55 | Patent claims 1. Biologically active agent for use in animal breeding, characterized in that it contains as an active substance a compound of the general formula 1 or, optionally, its acid addition salt, where X is -O-, -CH2 -, or -CH(OH)-, Y is -CO-NH-CH2-CH=CH2 or COOR4, where when X is -O- then Y is COOR4, R is halogen, nitro, amino ava, methylsulfonylamino, trifluoromethyl, alkyl or alkoxy with 1 to 6 carbon atoms, cycloalkyl or cycloalkoxy with 3 to 6 carbon atoms, phenyl, phenoxy, benzyl or 2-phenylethyl, each of these groups optionally being substituted with one or two identical or different substituents such as an alkyl group having from 1 to 6 carbon atoms, a halogen atom and a nitro group, n is zero or one, R1 and R2 independently represent a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, where at least one of these symbols represents a hydrogen atom, R4 represents a phenylalkyl group, an alkyl group with 1 to 4 carbon atoms, or an alkenyl, alkynyl or cycloalkyl group with 3 to 6 carbon atoms with this with the limitation that when Y is -CO-NH-CH2-CH=CH2 and X is -CH-(OH). then this compound occurs in the form of a cis isomer and when the Y group is a substituent in the 2 or 3 position of the ring containing oxygen, an additional hydrogen atom appears in the 3 or Z position, respectively. 2. Biologically active agent for use in animal breeding , characterized in that it contains as an active substance a compound of the formula 2, in which n is zero or one, R is a halogen atom, a nitro group, an amino group, a methylsulfonylamino group, a trifluoromethyl group, an alkyl group or an alkoxide group. up to 6 carbon atoms, cycloalkyl alkyl or cycloalkoxy from 3 to 6 carbon atoms, phenyl 20 25 30 36 55 60 65 or fe::cksy, each of these groups having the same substance; optionally substituted with one or two substituents such as an alkyl group of from 1 to 6 carbon atoms, a halogen atom or a nitro group, and R1 and R5 independently represent a hydrogen atom or an "alkyl group" and from 1 to 4 carbon atoms*, with at least - rr.^ one of these symbols represents a hydrogen atom. 3. Agent according to claim 2, characterized by; that it contains a compound of formula 2, in which R1 and R* represent both water atoms, and the remaining bases have the meanings given above. 4. The agent according to claim 2, distinguished in that it contains a compound of formula 2, in which the substituent R occurs in position 6 and denotes a chlorine atom, brormine, methoxy, cyclohexyl, 'cyclohexyloxy, 4-chlorophenyl or 4-chlarophenoxy, and the remaining the substituents have the meanings given above. 5. Agent according to claim. 2, characterized in that it contains a compound of formula 2 in the form of a cis isomer. 6. Biologically active agent for use in animal breeding, characterized in that as an active substance it contains a compound of formula 4, in which Y is -CO-NH-CHa-CH=CH2, n is zero, one or two, R means a fluorine, chlorine, bromine atom, a nitro, amino, methylsulfonylamino, trifluoromethyl, alkyl or alkoxy group with from 1 to 6 carbon atoms or a cycloalkyl group with from 3 to 6 carbon atoms, R2 means a hydrogen atom or an alkyl group with from 1 to 6 carbon atoms 4 carbon atoms, and R8 represents a hydrogen atom or an alkyl group of from 1 to 4 carbon atoms, optionally in the form of a salt with hydrogen halide. 7. The agent according to claim 6, characterized in that it contains a compound of formula 4, in which R is a substituent in position 6. 8. Agent according to claim 6. 6, characterized in that it contains a compound of formula 4, wherein R is a methyl, methoxy or cyclohexyl group. 9. The agent according to claim 6, characterized in that it contains a compound of formula 4, in which R8 is a benzyl group and the remaining symbols have the meanings given above. 10. Biologically active agent for use in animal breeding, characterized in that as an active substance it contains a compound of the formula 4, in which Y is -COOR4, n is zero, one or two, R is a fluorine, chlorine or bromine atom, a group nitro, amine, methylsulfonylamino, trifluoromethyl, alkyl or alkoxy from 1 to d carbon atoms or cycloalkyl from 3 to 6 carbon atoms, R4 is an alkyl group from 1 to 4 carbon atoms, alkenyl, alkynyl or cycloalkyl from 3 to 6 carbon atoms carbon or a phenylalkyl group, R2 is a hydrogen atom or an alkyl group of from 1 to 4 carbon atoms, and R8 is a hydrogen atom or a phenylalkyl group, optionally in the form of a salt with a hydrogen halide. 11. The agent according to claim 10, characterized in that it contains a compound of formula 4, wherein in the -COOR4 group, R4 is an ethyl group and R, R1, &*, Y and n have the meanings given above. 12. The agent according to claim 10, characterized in that it contains a compound of formula 4, wherein R* is a benzyl group and Y, R, R* and n have the meanings given above. 127 781 33 13* Agent according to claim 10. 10, characterized in that it contains a compound of formula 4, in which the R substituent is in the 6-position. 34 14. Agent according to claim 10. 10, characterized in that it contains a compound of formula 4, in which R is a methyl, methoxy or cyclohexyl group.O-^/R '<££ WZdR 1 R1if <« ['°^:hC-NH-CH2-CH = CH, ^0' R' FORMULA 2 (R)n OH 04 FORMULA 3 (R)n- ^ 4 C-NH-CH2-CH=CH 8 OZGraf. Z.P. Dz-wo, z.139 (80+15) 10.85 C«n» IM tl PL PL PL

Claims (12)

1. Patent claims 1. Biologically active agent for use in animal breeding, characterized in that it contains as an active substance a compound of the general formula 1 or, optionally, its acid addition salt, in which X is -O-, -CH2-, or -CH(OH)-, Y means -CO-NH-CH2-CH=CH2 or COOR4, where when X is -O- then Y means COOR4, R means halogen atom, nitro group, amine, methylsulfonylamino, trifluoromethyl, alkyl or alkoxy with 1 to 6 carbon atoms, cycloalkyl or cycloalkoxy with 3 to 6 carbon atoms, phenyl, phenoxy, benzyl or 2-phenylethyl, each of these groups optionally being ¬ optionally substituted with one or two identical or different substituents, such as an alkyl group having 1 to 6 carbon atoms, a halogen atom and a nitro group, n is zero or one, R1 and R2 independently represent a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, wherein at least one of these symbols represents a hydrogen atom, R4 represents a phenylalkyl group, an alkyl group with 1 to 4 carbon atoms, or an alkenyl, alkynyl or cycloalkyl group with 3 to 6 carbon atoms with the limitation that when Y is -CO-NH-CH2-CH=CH2 and X is -CH-(OH). then this compound exists in the form of a cis isomer and when the Y group is a substituent in the 2 or 3 position of the ring containing oxygen, an additional hydrogen atom appears in the 3 or Z position, respectively. 2. "Biologically active agent" for use in animal breeding, characterized in that as an active substance it contains a compound of the formula 2, in which n is zero or one, R is a halogen atom, a nitro group, an amino group, a methylsulfone- lamino, trifluoromethyl, alkyl or alkoxy with 1 to 6 carbon atoms, cycloalkyliave or cycloalkoxy with 3 to 6 carbon atoms, phenyl 20 25 30 36 55 60 65 or fe::cksy, each of these groups gesture; optionally substituted with one or two substituents such as an alkyl group of from 1 to 6 carbon atoms, a halogen atom or a nitro group, and R1 and R5 independently represent a hydrogen atom or an "alkyl group" and rr/a of from 1 to 4 atoms carbon*, and at least one of these symbols represents the hydrogen atom. 3. The agent according to claim 2, characterized by; that it contains a compound of formula 2, in which R1 and R* represent both water atoms, and the remaining bases have the meanings given above. 4. The agent according to claim 2, distinguished in that it contains a compound of formula 2, in which the substituent R occurs in position 6 and denotes a chlorine atom, brormine, methoxy, cyclohexyl, 'cyclohexyloxy, 4-chlorophenyl or 4-chlarophenoxy, and the remaining the substituents have the meanings given above. 5. Agent according to claim. 2, characterized in that it contains a compound of formula 2 in the form of a cis isomer. 6. Biologically active agent for use in animal breeding, characterized in that as an active substance it contains a compound of formula 4, in which Y is -CO-NH-CHa-CH=CH2, n is zero, one or two, R means a fluorine, chlorine, bromine atom, a nitro, amino, methylsulfonylamino, trifluoromethyl, alkyl or alkoxy group with from 1 to 6 carbon atoms or a cycloalkyl group with from 3 to 6 carbon atoms, R2 means a hydrogen atom or an alkyl group with from 1 to 6 carbon atoms 4 carbon atoms, and R8 represents a hydrogen atom or an alkyl group of from 1 to 4 carbon atoms, optionally in the form of a salt with hydrogen halide. 7. The agent according to claim 6, characterized in that it contains a compound of formula 4, in which R is a substituent in the 6-position. 8. The agent according to claim 6, characterized in that it contains a compound of formula 4, wherein R is a methyl, methoxy or cyclohexyl group. 9. The agent according to claim 6, characterized in that it contains a compound of formula 4, in which R8 is a benzyl group and the remaining symbols have the meanings given above. 10. Biologically active agent for use in animal breeding, characterized in that as an active substance it contains a compound of the formula 4, in which Y is -COOR4, n is zero, one or two, R is a fluorine, chlorine or bromine atom, a group nitro, amine, methylsulfonylamino, trifluoromethyl, alkyl or alkoxy from 1 to d carbon atoms or cycloalkyl from 3 to 6 carbon atoms, R4 is an alkyl group from 1 to 4 carbon atoms, alkenyl, alkynyl or cycloalkyl from 3 to 6 carbon atoms carbon or a phenylalkyl group, R2 is a hydrogen atom or an alkyl group of from 1 to 4 carbon atoms, and R8 is a hydrogen atom or a phenylalkyl group, optionally in the form of a salt with a hydrogen halide. 11. The agent according to claim 10, characterized in that it contains a compound of formula 4, wherein in the -COOR4 group, R4 is an ethyl group and R, R1, &*, Y and n have the meanings given above. 12. The agent according to claim 10, characterized in that it contains a compound of formula 4, in which R* is a benzyl group, and Y, R, R* and n have the meanings given above. 127 781 3313. * Agent according to claim 10. 10, characterized in that it contains a compound of formula 4, in which the R substituent is in the 6-position. 3414. The agent according to claim 10. 10, characterized in that it contains a compound of formula 4, wherein R is a methyl, methoxy or cyclohexyl group. O-^/R '<££ WZdR 1 R1if <« ['°^:hC-NH-CH2-CH = CH, ^0' R' FORMULA 2 (R)n OH 04 FORMULA 3 (R)n- ^ X-H R2 RJ FORMULA U127 781 -0^-H li r7pC-NH-CH2-CH=CH2 FORMULA 5 (R)r 4 C-NH-CH2-CH=CH X"^H FORMULA 6 IRW X^R 1 O ¥ - C-NH-CH2-CH= CH2 PATTERN 7 °r nJch I- R2 R3 0 II — f L WZ(5R 8 OZGraf. Z.P. Dz-wo, z. 139 (80+15)10.85 C«n» IM tl PL PL PL