PL72562B1 - Substd oxazoles and thiazoles[CH528531A] - Google Patents

Abstract

Preparation of subst. oxazoles and thiazoles of general formula (I) and their salts:- (X = O or S; R1 and R2 = phenyl- optn. subst. by one or more hal-, alkyl-, alkoxy-, nitro-, amino-, subst. amino-, halogenalkyl-, mercapto-, alkylthio-, alkylsulphonyl-, naphthyl- or heteroaryl, which may be subst. R3 = C2-6 aliphatic acid deriv. e.g. salt, ester or amide R1 R2 and R3 are situated in positions 2-, 4- and 5- preferably thiazoles (II) and oxazoles (XI) where R1 and R2 = phenyl-, chlorophenyl-, bromophenyl-, methylphenyl-, methoxyphenyl-, trifluormethylphenyl-, 1-naphthyl-, 2- or 3-thienyl-, 2- or 3-furyl- R3 = acetic acid, n-propionic acid, isopropionic acid, n-butyric acid and their salts, ester or amide) Anti-inflammatories. [CH528531A]

Description

Proprietor of the patent: John Wyeth and Brother Limited, Taplow (Great Britain) The method of producing new heterocyclic aromatic compounds. The subject of the invention is a method of producing new heterocyclic aromatic compounds. A well-known anti-inflammatory drug is phenylbutazone, which, however, has many disadvantages, for example, it causes ulcers. Another drug used in inflammation is aspirin, which, however, requires large doses and also has a highly ulcerative effect. These disadvantages are overcome by the compounds according to the invention. The process according to the invention produces a new group of trisubstituted heterocyclic aromatics of the general formula I, possibly in the form of pharmaceutically acceptable acid addition salts thereof, in which X is oxygen or Sulfur, R1 and R2 are the same or different and represent an unsubstituted phenyl radical, a phenylic radical substituted with one or more halogens, a lower alkyl group, a lower alkoxy, nitro, amine, substituted amine or lower halo-alkyl radicals , or an unsubstituted naphthyl or heteroaryl radical, and R8 is a straight or branched aliphatic acid radical with 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms in the chain, or derivatives thereof, one of the radicals R 1, R2 and R8 are in the 2-, 4- and 5- position, which means that one of the given radicals is in the formula 1. In the 2- position, the other radical in the 4- and third positions of the 2 given phases in position 5 *. The term "lower" denotes a radical containing 1-6, preferably 1-4 carbon atoms. The compounds of the present invention have pharmacological activity, for example anti-inflammatory activity with little or essentially no ulcerogenic activity, which have demonstrated animal testing and / or antibacterial activity, or are semi-products for the preparation of other substituted heterocyclic aromatic compounds. Examples of tests showing that the compound has anti-inflammatory activity are described by Winter et al. in Proc. Sco. Bio. Med. 111, 544 in (1962), Buttle et al. Nature 179, 629 (1957), Konzett and Rossler, Aren. Path. Pharmac. 195, 71 (1940) and Newbould, Brit. Jour. Pharm. Chemotl 21, 127-137 (1963). Examples of radicals R 1 and R 2 are: unsubstituted phenyl or phenyl substituted by fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, n-butyl or isobutyl, methoxy group , the amino group, especially dw ualkylamino such as dimethylamino, trifluoromethyl, methoxy and a halogen, or a methyl radical and a halogen (although in principle usually only one substituent is usually found in each phenyl ring 1- and 2-naphthyl, 2- and 3- -furyl, 2- and 3-thienyl and 2-, 3-, 4-pyridyl. Examples of R8 radicals are n-propionic acid, iso-TZMt72562 propionic, n-butyric and isobutyric acid radicals or unsaturated ethylene acids such as such as acrylic acid, or a salt, ester, amide, thioamide or derivative of hydroxamic acid. The compounds of the general formula I are obtained by methods known for the synthesis of such aromatic heterocyclic rings. According to the invention, the compounds of the general formula I may be prepared in the form of their acid addition salts, wherein X is oxygen or sulfur, R1 and R2 are the same or different, and each is an unsubstituted phenyl radical, a phenyl radical substituted with one or more halogens, lower alkyl, lower alkyl alkoxylate, substituted amino or halo-lower alkyl or unsubstituted naphthyl, thienyl or pyridyl radical, and R 3 is a straight chain or branched aliphatic acid radical having 2 to 6 carbon atoms in the chain or a derivative thereof such as a salt, ester, amide or derivative of hydroxamic acid, one of the radicals R1, R2 and Rs being in the 2-, 4- and 5-position of formula 1 and where the term "lower" denotes radicals having 1-6 carbon atoms is as follows that a halogen ketone of general formula 29 in which Hal is a halogen atom is reacted with a thioamide of general formula 30 or an amide of general formula 31 or a salt thereof in an inert, acidic or basic environment in the presence or absence of a solvent. or the keto amide of formula 32 or its imine isomer of formula 33 or 34 is cyclized by treatment with an oxygen or sulfur donor cyclizing agent such as sulfuric acid, phosphorus pentachloride, arbohydrogen, phosphorus pentosulfide, phosphoryl chloride or phosphorus pentoxide, in an acidic environment in the presence or absence of a solvent, or a ketoester of the general formula is reacted with ammonia, urea or an ammonium salt in an inert, acid or acid environment. in the presence or absence of a solvent or a ditone monooxime of general formula 36 is reacted with the aldehyde Rc-CHO in an acid medium to give a nitrone of general formula 37, which is then reduced, for example, by treatment with a trio Phosphorus chloride in the presence or absence of a solvent or a hydroxy ketone of general formula 38 is reacted with a nitrile of general formula RC-CN in the presence of a mineral acid such as sulfuric acid or the α-aminocetone of general formula 39 or a salt thereof is reacted with an iminoether of general formula 40 in an acid medium. In the formulas Ra, Rb and Rc in each case are selected from R1, R2 and R4, with R1 and R2 having the above meanings and R4 having the same meaning as R3 or being a precursor to a radical which is easily transformed into R3 by known methods, such as cyanoalkyl, malonic ester, hydroxy] kilo, alkylcarbonamide group. alkanecarboxylanalkyl, diazoketone, haloalkyl, formyl, carboxy, carboxyalkyl, alkali metal substituted alkyl or acrylic acid residue and if necessary, when R4 is not R3, R4 is converted into R3 or one group R3 into another R3 group by generally known methods. such as hydroxamation, esterification, amidation, hydrolysis, alcoholysis. chain expansion, CO2 cleavage, or reduction, and if desired converts a compound of formula I to a pharmaceutically acceptable acid addition salt. When R4 is not the same as R8 le & z is a precursor to R3, it may react with reagent 10 for transforming a group precursor into Rs as defined previously, or the R3 group may be transformed into another group by one of the following methods: a haloalkyl group, e.g. a chloromethyl group, is reacted with an alkali metal cyanide, e.g. sodium cyanide, with potassium and the resulting nitrile will be hydrolyzed to give the carboxyalkyl or alkylcarbonamide group R3 (chain expansion and hydrolysis); the haloalkyl group reacts with an alkali metal diester, such as the malonic acid diester, and after hydrolysis, carbon dioxide is split off, giving the carboxyalkyl group R3 (chain cleavage, hydrolysis and carbon dioxide separation; the COOH group reacts sequentially with with a halogenating agent, diazomethane and water or alcohol, ammonia or amine in the presence of a catalyst, e.g. colloidal silver or silver oxide (Arndt-Eister reaction) yielding the radical R3 carboxyalkyl, alkanoicalkyl carboxylate (chain extension, respectively) ; the nitro, ester or amide group reacts with the hydrolyzing agent to give the carboxyalkyl group R3 (hydrolysis); the acid group is esterified with alcohol to give the alkyl alkanecarboxylate 35 (esterification); the ester group reacts with the hydroxylamine to give hydroxamic acid (hydroxamic acid) An acidic group or a salt thereof, e.g. of an alkali metal or salt of an amine, reacts with an acyloxy chloride methyl e.g. with acetoxymethyl chloride to give the carboxyalkyl acyloxymethyl ester of R3 (esterification); the nitro group is hydrolyzed or alcoholized to give the acid, amide or ester group R3 (hydrolysis or alcoholysis); acid group: or a functional derivative thereof reacts with ammonia or an ammonium salt to result; heating to give an R3 alkylcarbonamide group (amidation); the nitro group reacts with hydrogen sulfide to give an alkylthiocarbonamide group (thioamidation); the hydroxymethyl radical reacts with the active agent. 50 halogenating to give the halomethyl radical, which is used in some two steps, or the hydroxymethyl radical is oxidized to the formyl radical, which is condensed with malonic acid or malonic ester in a Knoevenagel reaction, thereby cleaving carbon dioxide to give an acrylic acid or group, R3 ester (chain expansion and CO2 cleavage); a CnH2n-M group in which M is, an alkali metal atom reacts with a halogen aliphatic acid ester to give an alkanecarboxy / ylanalkyl group R3 which can be hydrolyzed to an R3 carboxyalkyl group (chain extension and hydrolysis); the methyl group is halogenated e.g. with N-bromosuccinimide and the chlorpwtetyl group is used in some two steps or is oxidized to a formyl group by Sommelet reaction and the formyl radical is condensed with malonic acid or an ester by a Knoevagla reaction by there is cleavage of the carbon dioxide to form an acrylic acid group or an ester group R8 (chain expansion and CO2 removal); acrylic acid or an ester group is reduced to propionic acid or an ester group R8 by catalytic hydrogenation (reduction). A particularly important group of compounds obtained according to the invention are those compounds in which X is sulfur, R1 is in position 2 -, R2 is in the 4-position and R8 is in the 5-position and is a saturated aliphatic acid radical having 2-6, preferably 2-4 carbon atoms. This group includes thiazoles of general formula II in which R1 and R2 are the same or different and each is unsubstituted phenyl, halophenyl, lower alkylphenyl, lower alkoxyphenyl, trihalomethylphenyl, naphthyl, thienyl or furyl radical, and R8 is a saturated aliphatic acid radical having 2 to 6 carbon atoms or a derivative thereof. It is preferred that R1 and R2 are phenyl, chloro- or bromophenyl, methylphenyl, methoxyphenyl, trifluoromethylphenyl, 1-naphthyl, 2- or 3-thienyl and 2- or 3-furyl and R8 is acetic, n-pfopionic or isopropionic acid. or a salt, ester or amide thereof. Compounds of general formula II are preferably obtained by reacting an alpha-haloketone of general formula III with a thioamide of general formula IV or 5, wherein R1, R2 and R4 are as defined above and Hal is a halogen atom, for example chlorine or bromine, and if necessary converts the resulting thiazole into another thiazole of the general formula 2. It has been found that it is particularly advantageous to react the acid of the general formula (i.e., when R4 contains a COOH group) , in particular acetic acid or n-propionic acid), where Hal is bromine, with the appropriate thioamide. The reactions are preferably carried out in a solvent at room temperature or above, e.g. up to the reflux temperature of the solvent. When the reactions are carried out in the absence of a base, and in the presence of an alcohol, for example ethanol, an ester is usually obtained which hydrolyzes to acid if necessary. On the other hand, if a different solvent is used, or if an alcohol and (especially isopropanol) as a solvent are used in the presence of a base (e.g. an alkali metal carbonate) the acid group R8 is obtained directly and thus the need for to perform hydrolysis if acid is required. In both cases, after completion of the reaction, it is advisable to add a base (for example, aqueous sodium carbonate solution) to the reaction mixture after completion of the reaction in order to facilitate the isolation of the product obtained. The alpha-halogen ketones of the general formula III are prepared in a known manner, for example by halogenation (eg bromination) of the products of the Friedel-Craft reaction between arbitrarily substituted aromatic (or heteroaromatic) hydrocarbons and the corresponding anhydrides, nA; with succinic, glutanic or methylsuccinic anhydride. Ether is preferably used as the halogenation solvent. The thioamides of general formula 4 and 5 can usually be obtained by the method of Fairfur et al. (Journal of the Chemical Society 1952, 742), from the appropriate nitriles. Alternatively, to cyclize the alpha-acyl and amino carbonyl compound of general formula 6, in which R1, R2 and R4 have the above meanings, where if necessary the radical R4 is replaced by the radical R3 after cyclization, phosphorus pentasulfide is used. The cyclization reactions are usually carried out at or above room temperature, e.g. temperatures 15 ° C. below the boiling point of the solvent are used. Compounds of formula 6 are obtained by reacting a compound of formula 7 (which can be scans by reacting aryl acetic acid in the form of an ester with an acetic ester in the presence of a base and by halogenating the product) with an amide of general formula VIII in the form of the sodium salt, in which R1, R2, Hal and R4 are as defined above. When in formula 3 or 7 R4 is the radical -COOH or a derivative thereof or a halogenomethyl radical, the product obtained initially is a thiazol of the general formula I, but R3 is replaced therein by the radical -R *. In such cases, to obtain a compound of general formula 1, radical R * needs to be exchanged for a radical R3, converting the resulting compound into a homologous compound as discussed above. After obtaining a thiazole of general formula 2, radical R8 is converted to another the radical R3 by any known method. For example, if R8 is an aliphatic acid ester radical, nitrile or amide, it can be obtained by hydrolyzing an acid if required. The ester can be obtained from the acid by reaction with alcohol and the hydroxamic acid derivative can be obtained from the ester by reaction with hydroxylamine. The acyloxymethyl ester is obtained by reacting an acid or a salt thereof (eg an alkali metal or amine salt) with a halogen acyloxymethyl derivative such as a halide acetoxymethyl derivative. The amide is obtained from the nitrile by hydrolysis, from the acid or a functional derivative thereof by reaction with ammonia, or from the ammonium salt by heating. 50 Thioamides are obtained from nitriles by reaction with hydrogen sulphide. Another group of compounds of general formula I, where X is sulfur atom, are thiazoles of general formula 9 and 10, in which R1 and R2 are the same or different, and each of the these represent unsubstituted phenyl, halophenyl, low alkylphenyl, low alkoxy phenyl, nitrophenyl, trihalomethylphenyl, naphthyl, thienyl or furyl radicals, and R8 is as defined above. The preferred radicals are the same as for thiazoles of general formula 2. Thiazoles of general formula 9 and 10 are obtained by methods known for the preparation of thiazoles, and a preferred method is analogous to that described above for compounds of general formula 2. Thus, In the process, an alpha-halo ketone of general formula 7 or 11 is reacted with a thioamide of general formula 12 or 13 (in which R1, R2 and R4 are as defined above) and, if necessary, replace The radical R 4 is the radical R *. Halogen ketones of general formula VII or 11 are obtained by halogenation of the corresponding ketoester or deoxybenzoin. The thioamides of the general formula 12 or 13 are known compounds or are obtained in a manner analogous to that used for the preparation of known compounds of this type. The compound of general formula 9 is preferably prepared by the above method using alpha-chloro. A tetro-ketone in which R 4 is an ester radical (eg an acetic acid or propionic acid ester radical, while the compound of general formula 10 is preferably obtained by the above method using a thioamide in which R 4 is an ester radical (eg ethyl ester). If R 4 in formula 13 is a benzoyloxymethyl radical, the radical formed on the thiazole can be converted into a hydroxymethyl radical and then either into a halomethyl radical, which can be reacted with a malonic ester and hydrolyzed, or into a formyl radical and then with the aid of Knoevenager reaction to the acrylate radical. All these subsequent transitions are known. Another group of general formula I are compounds in which X is t A preferred group of these compounds are oxazoles of the general formula 14, wherein R1 and R2 are the same or different, and each is an unsubstituted phenyl, halophenyl, low alkylphenyl, low alkoxy phenyl, trifluoromethylphenyl, naphthyl or thionyl radical and R1 is as defined above. Preferably R1 and R2 are phenyl, chloro- or bromophenyl, methylphenyl, methoxyphenyl, trifluoromethylphenyl, 1-naphthyl, 2- or 3-thienyl and 2- or 3-furyl, and Rs is n-propionic acid or n-butyric acid radical or a salt, ester or amide thereof. Compounds of general formula 14 are obtained by corresponding generally known methods for the formation of an appropriately substituted oxazole ring. Such methods are well known, see, for example, "Heterocyclic Compounds" Vol. 5, Robert E. Elderfield, 1957, edited by Wiley and Sons, pages 302 to 323. A generally known method for the preparation of oxazoles of general formula 14 is based on I ) avidson * of the oxazole synthesis and refers to the reaction of a ketone ester of general formula 15 with ammonia or a salt thereof, or with urea (where R1, R2 and R1 are as defined in formula 14) and, if necessary, exchange R4 to R *. Reactions may be carried out with or without a solvent. If a solvent is used, it is advisable to heat the solution to bring the temperature to the boiling point of the solvent, for example under a reflux condenser. Alternatively, heat the reactants in a sealed tube. The use of an ammonium salt (e.g., ammonium acetate) in glacial acetic acid is generally preferred over the use of urea, as the product is easier to process. New ketoesters of the general formula e 15, is obtained by esterifying alpha-hydroxy ketones of the general formula 16 or the corresponding compounds in which the OH group is replaced with halogen (e.g. bromine) with an esterifying agent capable of converting * an alpha-hydroxy group or an alpha-halo group into an alpha-O-CO-R4 group or into a spontaneously converting group into an alpha-COO-R4 group. For example, esterification of the αH group can be carried out with a suitable anhydride, acid, acid halide or other esterifying agent, or the halogen group can be reacted with a monobasic metal salt of the acid. For acylation of the hydroxy group it is highly recommended to use acid anhydrides ( for example, succinic or glutaric anhydride) or the corresponding acid chlorides. Esterification may be carried out by jointly heating the reactants at elevated temperature in solution or in a sealed tube. Temperatures up to 180 ° C are usually appropriate, for example 100-140 ° C. When an inert limited solvent (e.g. hydrocarbon) is used, the esterification should be carried out under a reflux condenser. A less preferred method for the preparation of compounds of the general formula 14, in which R * is a saturated aliphatic acid, involves the formation of an oxazole of the general formula 17 by the known method. or 18 (where R1 and R2 are as defined above, n is an integer from 1-5, and M is an alkali metal atom) and replacement of the substituent in position 2 with the required acid, e.g. by reaction of the compound of formula 17 with an ester of a halogen aliphatic acid, followed by hydrolysis or halogenation of the compound of formula 18, followed by reaction with nitrile or malonic ester and finally hydrolysis. The compound of general formula 18 can also be converted to an aldehyde by a Sommelef reaction, and then by reaction of the Knoevenager with the malonic acid ester, an acrylic kW derivative is obtained, which can be reduced to a propionic acid derivative. Less preferred methods known for the preparation of oxazoles may, if necessary, also be used for the preparation of new oxazoles of the general formula 14, in which R1, R2 and R1 are as defined above. These methods include processes such as the Robinson synthesis. Gabrier: alpha-acylaminoketone of general formula 19 is cyclized, for example, with a cyclizing agent such as sulfuric acid, phosphorus pentachloride, phosphonium chloride or phosphorus pentoxide. The starting material of general formula 19 is obtained from aminodeoxybenzoin and the corresponding acid chloride, or from the halogenated deoxybenzoin and the sodium amide salt. Japp synthesis: the hydroxy ketone of formula 10 is reacted with the appropriate nitrile of formula R 4 CN; The imino ether of general formula 20 is reacted with alpha-aminocetone or a salt thereof, of general formula NH2CHR1-CO-R *, for example in warm acetic acid. The starting materials of the general formula NH2-CHR1-CO-R * are obtained by the formation of a benzoyloxymethyl nitrile imino ether, eg. T The next group of oxazole compounds of general formula I are compounds of general formula 21, in which R1 and Rf are the same or different, and each of them represents the radicals: unsubstituted phenyl, halophenyl, low alkylphenyl, low alkoxy. and phenyl, nitrophenyl, haloalkylphenyl, naphthyl, JhienyU or furyl, and R8 and the lower are as defined in formula 1. The preferred radicals R1 and Rf are those given in formula 2. Oxazoles of general formula 21 are preferably obtained by reacting a ketone of general formula 22 with an amide of general formula 23 or a salt thereof (where R4 is exchangeable with R8, Hal is a halogen atom, and R1, Rf and R8 have the meaning given in formula 21) ao and if this is necessary by replacing the radical R4 with R8. It is preferable for this reaction if R4 is an ester (e.g., ethyl acetate). To obtain R4 in the 5-position, the amide of general formula 23 is first converted to an alkali metal salt and then the salt is reacted with the compound of formula 23. formula 22, preferably by heating its solution in the solvent. With extreme caution, it is possible to isolate the intermediate of general formula 24 and close the ring of this compound with a cyclizing reagent such as sulfuric acid, phosphonium pentachloride or phosphorus pentoxide. To obtain R4 in the 4-position, an amide with a general * formula 23 is heated directly with the compound of general formula 22. If the heating is carried out in the presence of an acid acceptor, for example an alkaline earth metal carbonate such as calcium carbonate, a compound of general formula 21 is formed simultaneously with the intermediate which it may be assumed that it is a compound of the general formula 25. The crude product may be treated with an acid, for example sulfuric acid, in order to cyclize the resulting intermediate. A further method of preparation involves the hydrolysis of the corresponding nitriles (which may or may not be obtained by the above method) preferably in the presence of alcohol. According to the invention, a very convenient method of carrying out this conversion involves cyclization of the compound of general formula 26 with a compound of the general formula R 1 -CHO (where R 1 and R 2 are as defined above, and R 6 is an alkyl radical such as a methyl radical or a hydroxyalkyl radical) and replacing R 5 with R 8. The resulting oxosol is a compound of general formula 21 in the form of an N-oxide with the radical R5 replacing the radical R8, this compound may be halogenated and reduced (e.g. with phosphorus trichloride) to obtain a compound of general formula 21, in which R8 represents a haloalkyl radical. A compound of this type can also be obtained by reacting a compound of the general formula 21 but wherein R8 is replaced with a methyl radical and reacting this compound with N-bromosuccinimide. In both cases, the haloalkyl compound formed can be reacted with an alkali metal cyanide and shedrolyzed. Oxazole of general formula 21 can also be obtained by reacting a compound of general formula 27 in which R 4 is halogen with malonic ester and cyclized by acid treatment or by cyclization of a compound of general formula 28 with ammonia, an ammonium salt or urea. R4 can then be exchanged for R8. Derivatives containing three carbon atoms in the chain of the radical R8. Obtained by reduction of the corresponding aryl derivatives. For example, 4- or 5-formyloxazoles can be obtained from chloromethyloxazoles by known methods, by heating them with malonic ester in dry pyridine and pouring the mixture into a dilute acid (eg HCl). In this way a 4 or 5 substituted acrylic acid is obtained, which can then be reduced, e.g. catalytically with hydrogen. In addition, if required, Arndt-Eistertf reactions can be carried out with the appropriate carbonyloxazole by formation of the chloride. acid, reacting this chloride with diazomethane and treating the diazoketone formed under known conditions to obtain acetic acid, its amide or ester (for example, treatment with water and a catalyst such as colloidal silver yields acetic acid). If a series of homologous compounds is required, it is possible to repeat the exchange of one group for a related group. The starting products of the above-mentioned reactions are known or can be obtained in a manner analogous to the methods used to prepare similar compounds. the desired product is not the required product but its derivative, it must be converted into the required compound in a known manner.It is obvious that in each of the above reactions the substituents present in the phenyl rings must be inert under the reaction conditions, and if necessary a blockade is applied during the reaction and then transforms the product into a compound of formula 1. Since the compounds of formula I contain a basic nitrogen atom, they can form salts with pharmaceutically acceptable acids (although they easily hydrolyze back to free principles), the process of the invention also comprises the preparation of such salts prepared by the method of the invention are used in a pharmaceutical preparation which also contains a non-toxic carrier. A pharmaceutically active form of the compound of the general formula X is a compound in which R8 is a carbpxyl acid group, which may be in the form of a salt or ester. The following examples illustrate the invention without limiting its scope. bromo-3-benzoylpropionic (40 mg) and thiobenzamide (21.3 g) are heated together under reflux in boiling ethanol <500 ml) for 8 hours. Then most of the ethanol is evaporated off and a solution of sodium carbonate (10 g) in water (300 ml) is added. The mixture is extracted with ether and the collected ether extracts are washed with water, dried over Na 2 SO 4 and evaporated to give light yellow needle-shaped crystals (46.1 g), mp 85-91 ° C. Recrystallization from ethanol yields pure ether ethyl 2,4-diphenylthiazolyl-5-acetic acid in the form of colorless needles. Yield 35.2 g (70%), melting point 95-96 ° C. Analysis. Found C, 70.6; H, 5.2; N, 4.3; S10.1. Gi9H17NO2S should contain: C, 70.6; H, 5.3; N, 4.3; S, 9.9%. Some of this ester was hydrolyzed to acid as given below in Example IV. Example II. Following the procedure of Example 1, 34) romo-3- (4'-methoxybenzoyl) propionic acid (11 g) and thiobenzamide (5.25 g) are reacted to give 2-phenyl-4- acid ethyl ester (4). '-methoxyphenyl) thiazolyl-5-acetic acid, which recrystallizes from ethanol as colorless needles. Yield: 8.2 g (62%), m.p. 67.5-68.5 ° C. Analysis: Determined C, 68.0; H, 5.4; N, 3.9; S, 9.2. C 20 H 19 NO 3 S should contain: C, 68.0; H, 5.4; N, 4.0; S, 9.1%. Some of this ester was hydrolyzed to acid as given below in Example V. Example III. Following the procedure described in Example 1, 3-bromo-3- (4'-chlorobenzoyl) propionic acid (29.2 g) and thiobenzamide (13.7 g) are reacted to give 2-phenyl-ethyl ester. 4- (4'-chlorophenyl) thiazolyl-5-acetic acid, which recrystallizes from ethanol as colorless needles. Yield 19.9 g (56%), melting point 69-70 ° C. Analysis: Determined C, 63.8; H, 4.7; N, 3.8; S, 9.1; C 19 H 16 ClNO 2 S should contain: C, 63.7; H, 4.5; N, 3.9; S, 9.0%. Some of this ester was hydrolyzed to acid as shown below in Example VI. Example IV. 2,4-diphenyl-thiazolyl-5-acetic acid ethyl ester (15 g) is dissolved in hot ethanol (150 ml) and potassium hydroxide (10 g) and water (20 ml) are added. After 1 hour, most of the ethanol is evaporated off and the solution is diluted with water. Concentrated hydrochloric acid is then added until the mixture becomes acidic and the oily body is constantly extracted with ether. The ether extracts are combined, washed with water, dried over Na 2 SO 4 and evaporated to give a viscous oil (13.5 g) which slowly crystallizes. Recrystallization from benzene gives colorless acicular crystals of 2,4-diphenyl-thiazolyl-5-acetic acid. Yield 12.2 g (89%), mp 152-153 ° C. Analysis. Found C, 69.4; H, 4.2; N, 4.7; S, 10.8. C17H13NO2S should contain: C, 69.2; H, 4.4; N, 4.7; S, 10.9%. Example V. Following the procedure. The ethyl ester of Example II (5 g) given in Example IV is hydrolyzed to 2-phenyl-4- (4'-methoxyphenyl) thiazolyl-5-acetic acid, which is recrystallized from benzene in the form of colorless needles. Yield 3.9 g (85%), mp 178.5-179.5 ° C. Analysis. Found C, 66.5; H, 4.5; N, 4.3; S, 10.0. Ci8H15NO3S should contain: C, 66.5; H, 4.6; N, 5 4.3; S, 9.9%. Example VI. Using the procedure of Example IV, the ethyl ester of Example III (10 g) is hydrolyzed to 2-phenyl-4- (4'-chlorophenyl) thiazolyl-5-acetic acid, which recrystallizes from benzene to form of colorless needles. Yield 4.9 g (63%), melting point 161-162 ° C. Analysis. Found C, 62.0; H, 3.7; N, 4.2; S, 9.8; Cl, 10.7. C 17 H 12 ClNO 2 S should contain: C, 62.0; 15 H, 3.7; N, 4.2; S, 9.7; Cl, 10.7%. Example VII. 3-Bromo-3-benzoylisoblastic acid (13.6 g) and thiobenzamide (6.9 g) are heated in isopropanol (75 ml) at 60 ° C for 30 minutes. Then sodium carbonate (2.5 g) is added ) And heating is continued for a further 10 minutes. After standing overnight, the mixture is washed with water and then the aqueous solution is decanted from the oil obtained. The oil is absorbed with ether and extracted with dilute aqueous sodium carbonate solution. The basic extract is washed with ether, acidified with hydrochloric acid to pH4, and the resulting oil is then extracted with ether. The ether extract is washed with water, dried over N 2 SO 4 and evaporated to give a light yellow, highly viscous oil which slowly crystallizes. Recrystallization from glacial acetic acid (water, gives crystals of alpha- (2,4-diphenylthiazolyl-5) propionic acid in the form of bars, Yield 8.6 g (55%), mp 142-144 ° C. Analysis Determined: C, 69.9, H, 4.9, N, 4.7, S, 10.3, C18H15NO2S should contain: C, 69.9, H, 4.9, N, 4.7; S, 10.3%. Example VIII Using the procedure 4o of Example VII, 3-bromo-3- (2'-thienyl) propionic acid (13.2 g) is reacted with thiobenzamide (6 , 9 g) and gives crystals of 2-phenyl-4- (2'-thiazolyl-5-acetic acid in the form of needles. Yield 7.2 g (48%), m.p. 134.5-135. 0 ° C. Analysis: Found: C, 59.9; H, 3.7; N, 4.5; S, 21.0. Ci5H11N02S2 should contain: C, 59.9; H, 3.7; N, 4.65; S, 21.3%. Example IX Using procedure 50 of Example VII, 3-bromo-3- (4-methylbenzoyl) propionic acid (27.1 g) is reacted with thiobenzamide (13.7 g) to give 2-phenyl-4- (4'-methylphenyl) -thiazolyl-5-acetic acid. osc 9.6 g (31%), mp 168-169 ° C from benzene. Analysis. Found C, 70.0; H, 5.1; N, 4.6; S, 10.6. C18H15NO2S should contain: C, 69.9; H, 4, &; N, 4.5; S, 10.3%. Example X 4-methoxythiobenzamide (4.2 g) 60 and 3-benzoyl-3-bromopropionic acid (6.4 g) are boiled under reflux in ethanol (50 ml. ) for 1 1/2 hours. After standing overnight at room temperature, the crystalline solid is separated. The entire reaction mixture was poured into the water with stirring, and an oily layer was separated. The aqueous layer is washed with ether (3 x 200 ml) and the extracts are combined with the oil, the ether phosphate is washed with sodium carbonate, dried over anhydrous sodium sulfate and evaporated to dryness. The result is a yellow oil that quickly crystallizes in the form of a light yellow crystalline solid. Recrystallization from industrial, contaminated (methyl alcohol) spirit gives ethyl ester of 2- (4'-methoxy-phenic) -4-phenylthiozolyl-5-acetic acid as a light yellow-white solid, mp 60.5-32 ° C. Yield 3.8 g (43%). Analysis. Found C, 67.7; H, 5.3; N, 3.8; S, 9.0. C 20 H 19 NO 3 S should contain: C, 68.1; H, 5.4; N, 4.0; S, 9.1 ° / o. Example XI. 2-methylthiobenzamide (5.7 g), 3-bromo-3- acid <2'-thienoyl) propionic (10 g) and anhydrous sodium carbonate (1.8 g) are heated together with stirring in isopropanol (55 ml) at 60 ° C for 30 minutes. The mixture is cooled further to 40 ° C and stirred for a further 60 minutes. After cooling to room temperature, the mixture is allowed to stand overnight and slowly poured into cold water (1 liter). In order to acidify the mixture, a few drops of concentrated hydrochloric acid are added and, after standing for a further 30 minutes, the resulting body is filtered off. The aqueous phase is extracted with ether and the collected extracts are combined with the solid. The ethereal solution is extracted thoroughly with a saturated aqueous sodium carbonate solution and the aqueous extract is acidified with concentrated hydrochloric acid. The oil precipitated out of the aqueous phase quickly crystallized and, after drying and recrystallization from benzene, 4- (2'-thienyl) -2- (2'-methylpyryl) thiazolyl-5-acetic acid was obtained. Yield 6.7 g (46.2%), mp 136-138 ° C. Anal. Found C, 61.0; H, 4.2; N, 4.3; S, 20.3. C16H13NO2S2 should contain: C, 60.9; H, 4.2; N, 4.4; S, 20.3%. Example XII. By repeating the procedure of Example XI, 4-chlorothiobenzamide (6.25 g) is reacted with 3-bromo-3- (4'-methoxybenzoyl) propionic acid (10.3 g) in isopropanol ( 50 ml) in the presence of sodium carbonate (1.8 g). After carrying out the procedure as described in that example (XI) and recrystallization from glacial acetic acid (water gives 2- (4'-chlorophenyl) -4- (4) -methoxyphenyl) thiazolyl-5-acetic acid Yield 7.5 g (57.1%), mp 199-201 ° C. Anal. Found: C, 60.0, H, 4.2, N, 3.7, S, 9 0; Cl, 9.7 C18Hi4ClNSO2 should contain: C, 60.1; H, 3.9; N, 3.9; S ,. 8.9; Cl, 9.9%. Example XIII. the procedure as in example 11 is reacted with 4-chlorothiobenzamide (14.6 g) with 3-benzoyl-3-bromopropionic acid (21.8 g) in isopropanol (127 ml) in the presence of "sodium carbonate (4, 3 g). After carrying out the operation as described in that example and recrystallization from benzene, the acid 2- <4 H -chlorophenyl) -4-phenylthiazolyl-5-acetic. Yield: 12.4 g (44.2%), mp 153-5 ° C. s 10 15 20 30 35 40 45 55 60 Cl, 10.8. C17H12C1NO2S should contain C, 61.9; H, 3.7; N, 4.3; S, 9.7; Cl, 10.8%. Example XIV. By repeating the procedure of Example XI, 4-chlorothiobenzamide (6.3 g) and 3 * bromo-3- {2'-thienoyl) propionic acid (10 g) are reacted in isopropanol (55 ml) in the presence of sodium carbonate. (1.8 g). Following the procedure described in that example (3 I) and recrystallization from benzene, 2- (4'-chlorophenyl) -4- (2'-thiazolyl-5-acetic acid is obtained. Yield 4.8 g (31.2%), mp 137-9 ° C. Analysis. Found C, 53.6; H, 3.2; N, 4.0; S, 19.0, Cl, 10.5. C15H10ClNO2S2 should contain: C, 53.6; H, 3.0; N, 4.2; S, 19.1; Cl, 10.6%. Example XV. By repeating the procedure of Example XI, 4-methoxythiobenzamide (6.0 g) and 3-bromo-3- (4'-methoxybenzoyl) propionic acid (10.3 g) are reacted in isopropanol (50 ml) in the presence of sodium carbonate (1.8 g). Following the procedure described in Example XI and recrystallization from glacial acetic acid, water gives 2,4-di- (4'-methoxyphenyl) thiazolyl acid -5 vinegar. Yield 8.0 g (56.3%), mp 176-8 ° C. Analysis. Found C, 64.3; H, 5.0; N, 3.9; S, 9.1. Ci9H17NSO4 should contain: C, 64.2; H, 4.8; N, 3.9; S, 9.0%. Example XVI. By repeating the procedure of how. In Example 11, 2-methylthiobenzamide (5.4 g) and 3-bromo-3- (4'-methoxybenzoyl) propionic acid (10.3 g) are reacted in isopropanol (50 ml) in the presence of sodium carbonate ( 1.8 g). By performing the procedure as described in that example, 4- (4'-methoxyenyl) -2- (2H-methylphenyl) thiazolylO'-5-acetic acid is obtained. Yield 5.4 g (44.6%), mp 140-1 ° C. Analysis. Found C, 67.2; H.5.1; N, 4.3; S, 9.4; C19H17NSO3 should contain: C, 67.2; H, 5.1; N, 4.1; S, 9.5%. Example XVII. 2-methylthiobenzamide (7.5 g), 3-benzoyl-3-bromopropionic acid (12.85 g) and isopropanol (75 ml) were heated with stirring for 30 minutes at 60 ° C. After cooling to 40 ° C., anhydrous sodium carbonate (2.5 g) was added to the orange-colored solution and the mixture was kept at 40 ° C. for a further 60 minutes. After standing overnight, the reaction mixture is poured slowly into cold water (1 liter) with stirring and a few drops of concentrated hydrochloric acid are added to acidify it. After standing for 30 minutes, the resultant semi-solid oil layer is separated. The aqueous phase is extracted with ether and the obtained extracts are combined with the oily layer. The obtained ether solution is extracted thoroughly with a saturated aqueous solution of acidic sodium carbonate and the aqueous extracts are acidified with concentrated hydrochloric acid. The obtained oily, rapidly crystallizing precipitate is obtained after drying the recrystalline. It is combined with benzene-petroleum ether (60-80 ° C) to give 2- (2'-methylphenyl) -4-phenylthiazolyl-5-acetic acid. Yield: 3.0 g (19.4%), mp 165-7 ° C. Analysis. Found C, 62.1; H, 3.8; N, 4.1; S, 9.8; * Analysis. Found C, 69.7; H, 5.0; N, 4.4; S, 10.5; 72,562 includes: C, 69.9; H, 4.9; Cj-g-iHisNO ^S should N, 4.5; S, 10.4% .- Ex y c l a d XVIII. The procedure of Example 17 was repeated with 3-methylthiobenzamide (7.5 g), 3-benzoyl-3-bromopropionic acid (12.85 g), isopropanol (75 ml) and sodium carbonate. (2.5 g) to obtain 2- (3'-methylphenyl) -4-phenylthiazolyl-5-acetic acid which is recrystallized from benzene petroleum ether. Yield 2 to 3 g ( 15%), mp 123-5 ° C. Analysis. Found C, 69.7; H, 4.9; N, 4.5; S, 10.3. C18H15NO2S should contain: C, 69.9; H ,. 4.9; N, 4.5; S, 10.3%. Example XIX. The procedure of Example XVII was repeated with 4-mer toxithiobenzamide (8.35 g), 3-benzoyl-3-bromopropionic acid (12.85 g), isopropanol (75 ml) and sodium carbonate (2 5 g) to give 2- (4'-methoxyphenyl) -4-phenyl-thiazolyl-5-acetic acid, which is recrystallized from benzene. Yield Qf6 g (40.6%), mp 149-152 ° C. Analysis. Found C, 66.4; H, 4.6; N, 4.2; S, 9.7; C18H15NO3S should contain: C, 66.4; H, 4.7; N, 4.3; S, 9.9%. Example XX The procedure of Example XVII is repeated using 2-chlorothiobenzamide (8.60 g) 3-benzoyl-3-bromopropionic acid (12.85 g). isopropanol (75 ml), sodium carbonate (2.5 g) to give 2- (2'-chlorophenyl) -4-phenylthiazolyl-5-acetic acid, which is recrystallized from benzene. Yield 4.6 g (27.6%), mp 168-71 ° C. Analysis. Found C, 62.0; H, 3.7; N, 4.2; S, 9.9; Cl, "- 10.8. C17H12N02SCl should contain; C, 61.9; H, 3.7; N, 4.3; S, 9.7; Cl, 10.8%. Returned to d XXI. The method is repeated. the procedure "presented in Example XVII, using 4-methylthipbenzamide (7.5 g), 3-benzoyl-3-bromopropionic acid (12.85 g), isopropanol (75 ml) and sodium carbonate (2, 5 g) to give 2- (4'-methylphenyl) -4-phenylthiazoilyl-5-acetic acid which is recrystallized from benzene. Yield 7.9 g (51.2%), mp 170-171 ° C. Analysis. Found C, 70.0; H, 5.0; N, 4.3; S, 10.5. C13H15NO2S should contain: C, 69.9; H, 4.9; N, 4.5; S, 10.4% .. Example XXII. The procedure of Example XVII was repeated using 1-thiaphthamide (14.1 g), 3-benzoyl-3-bromopropionic acid (19.3 g), isopropanol (115 ml) and sodium carbonate. May (3.75 g). to give 2- (1'-naphthyl) -4-phenylthiazolyl-5-acetic acid which is recrystallized from benzene / petroleum ether. Yield 8.6 g (29.7%), m.p. 145-8 ° C. Analysis. Found G, 73.1; H, 4.4; N, 4.1; S, 9.3. C21H13NO2S should contain: C, 73.2; H, 4.4; N, 4.0-; S, 9.3%. Example XXIII. The procedure of Example XVII was repeated using 3-trifluoromethylthiobenzamide (15.3 g), 3-benzoyl-3-bromopropionic acid (19.3 g); isopropanol (115 ml) and sodium carbonate (3; 75 g) to give 2- (3'-triflupromethylphenyl) -4-phenylthiazolyl-5-acetic acid se, which is' recrystallized from benzene / petroleum ether. 6.4 g 16 (23.4%), m.p. 15 25 30 35 40 50 55 60 Yield 143-5 ° C. Analysis. Found C, 59.6; H, 3.7; N, 3.8; F, 15.6; S, 8.6. C 18 H 12 NO 2 SF 3 should contain: C, 59.6; H, 3.3; N, 3.9; F, 15.7; S, 8.8%. Example XXIV. The procedure of Example XVII was repeated with 4-methoxythiobenzamide (6.3 g), 3-bromo-3- (2'-thienoyl) propionic acid (10.0 g), isopropanol (55 ml) 1 and sodium carbonate (1.8 g) to give 4- (2'-thienyl-2- (4'-methoxyphenyl) thiazolyl-5-acetic acid which recrystallizes from benzene. Yield 1.9 g (13.3 g) %), mp 149-151 ° C. Analysis Found: C, 58.0; H, 3.9; N, 4.3; S, 19.5. C16H13NO3S2 should contain: C, 58.0; H ± 4.0; N, 4.2; S, 19.4%. Example XXV The procedure of Example XVII is repeated, using 2-thiaphthamide (14.1 g), 3-benzoyl-acid 3-bfomopropionic acid (19.3 g), isopropanol (115 ml) and sodium carbonate (3.75 g) to give 2- (2'-naphthyl) -4-phenylthiazolyl-5-acetic acid which recrystallizes from benzene Yield: 14.0 g (50.6%), mp 171-2 ° C. Analysis Found: C, 72.9, H, 4.6, N, 3.9; S, 9.2, C21H15N02S should contain: C, 73.2; H, 4.4; N, 4.0; S, 9.3%. Example XXVI. The method is repeated after the steps given in Example XVII using 4-methoxythiobenzamide (22.5 g), 3-bromo-3- (2'-naphthyl) propionic acid (40.5 g), isopropanol (200 ml) and sodium carbonate (6.6 g) to give 2- (4'-methoxyphenyl) -4- (2'-naphthyl) thiazolyl-5-acetic acid which recrystallizes from glacial acetic acid / water. Yield 22.4 g (44.4%), mp 160-162 ° C. Analysis. Found C, 70.3; H, 4.5; N, 3.7; S, 8.4. C22H17NSO3 should contain: C, 70.4; H, 4.6; N, 3.7; S, 8.5%. Example XXVII. 4-benzoyl-4-bromobutyric acid (26.5 g) and 4-chlorothiobenzamide (16.7 g), refluxed in ethanol (80 ml) for 3 1/2 hours. . After cooling, the solvent is evaporated off and the residue is extracted with benzene. The benzene solution is washed with 2N sodium carbonate solution, the water then dried (MgSO 4) and evaporated to give beta-i [2- (4'-chloro-phenyl) -4-phenyl-thiazolyl-5] ethyl ester. propionic acid in the form of yellow oil. This ester is dissolved in hot ethanol (50 ml) and treated with a solution of potassium hydroxide (5.7 g) in ethanol (50 ml). After one hour, most of the solvent is evaporated off and water is added, then by adding With the addition of 2N-acetic acid, the pH is adjusted to 4. The mixture is extracted with ether and, together, the collected extracts are washed with 2N sodium carbonate solution. The alkaline solution is then acidified and extracted with ether. The ethereal solution was washed with water, dried (MgSO 4) and evaporated to give beta-i [2- (4, chlorophenyl) -4-phenylthiazolyl-5] propionic acid as a solid. Re * crystallization of z-benzene gives an acicular crystal, m.p. 177-178 ° C. ~ --c .- ^ Analysis. Found Cj 63.0; H, 4.2; N, - 4.0; S, 9.4; » 72562 U Cl, 10, L Gfgli, GlNOiS should contain: C, 6 &9; H, 4.1; N, 4.1; S, 9, *; Cl, 10.3 # fc. -¦ Fr ^ rjrtrf given in XXVII, 3-bromo-3- (l'-rnaltyl) propionic acid (30.7 g) is reacted with thiobenzamide, (13, 7 g) in ethanol to give 34.2 g of crude 4- (1'-naphthyl) - * 2H-phenyl-thiazolyl-5-acetic acid ethyl ester which is hydrolyzed to acid. This acid is then recrystallized from benzene to obtain 4.2 g (12%) of the acid 4- (l'- * <naphthyl) -2-phenylthiazolyl-5-acetic acid, m.p. 166-167 ° C: Analysis. Found C, 73.0; H, 4.6; N, 4.0; Si 9.4; C2iH15NSO2 should contain 6: C, 73.1; H, 4.4; ^ N, 4.1; S, 9.3% .: 15, ¦¦ Pr z y k l a d XXIX. Proceeding as in Example XXVII, 3-lbromo ^ 3- (2, -naphthyl) acid methyl ester. of propionic acid (29.6 g) is reacted with thiobenzamide (12.6 g) in ethanol to give crude 20 4r (2-naphthyl) -2-phenylthiazolyl-5-acetic acid methyl ester (31.8 g) which hydrolyzes then to acid. Recrystallizing from benzene, 9.9 g (31%) (in compound) are obtained with a melting point of 168-169 ° C. Analysis. Found C, 73.0; H, 4.4; N, 4.0; S, 9.4. 29 CJ21H15NSO2 should contain: C, 73.1; H, 4.4; N ,. 4.1; .S, 9.3%. Example XXX. Following the procedure outlined in Example XXVII, 4-benzyl-4-bromobutyric acid (27.1 g) is reacted with 4-methoxy-thiobenzamide (16.7 g) in ethanol to give the crude est-ester. beta-β [2- (4'-methoxyphenyl) -4-phenylthiazolyl-51-propionic acid ethyl ester (39.5 g) which is then hydrolyzed to the acid. Recrystallizing. from benzene, 6.9 g (21%) (as compound) are obtained, mp 174-175 ° C. Analysis. Found C, 67.1; H, 5.0; N, 4.0; S, 9.6; CigHjfNOaS should include; C, 67.2; H, 5.1; N, 4.1; S, 9.4%. Example XXXI. Following the procedure outlined in Example XVII, 4-benzoyl-4-bromobromic acid (27.1 g) is reacted with 2-methylthiobenzamide (15.1 g) in ethanol to give crude betai ethyl ester. [2- (2'-methylphenyl) -4-phenyl-thiazolyl-5] propionic acid (375 g), which is then hydrolyzed to the acid. Recrystallization from benzene yields 5.7 g (18%) (in compound) with a melting point of 107-109 ° C. Analysis Determined C, 70.6; H i: 5.4; N, 4, 2; S, 9.8. C19H17NO2S should contain: C, 70.0; II, 5.3; 50 IST, 4.3; ^ 9.9%., Example XXXII. 3-benzoyl-3-bromopropionic acid (29.5 g and thiobenzamide (15.7 g) are heated together under reflux in boiling methanol (300 ml) for 5 hours. On cooling, acicular ester crystals are formed. 2,4-diphenylthiazyl-5-acetic acid methylic acid Yield: g (70%), m.p., 122-123 ° C. Analysis Determined: N, 4.5; S, 10.6; tCi8Hi5N025 polyol. The inten contains N, (4.5; S, 10.3%.; •:,;. I £ r% y k-1 ad 3 £ XXm. 3-benzoyl-4-bromobutyric acid (27 , 1 g) and the thiobenzamide is heated, together under reflux with ethanol (300 ml), for 6 hours, then most of the methanol is evaporated off and water is added. The resulting mixture is extracted with ether and the combined extracts washed. solution of sodium carbonate, water and then dried (Na 2 SO 4). Evaporation of the solvent gives beta-(2,4-diphenylthiazolyl-5) propionic acid methyl ester (23.3 g) as a yellow oil. The ester dissolves - put in hot ethanol (200 ml) and treat the solution potassium hydroxide (10 g) in water (20 ml). After 1 1/2 hours the solution is partially evaporated and then poured into water. Acidification with concentrated hydrochloric acid gives an oil which is extracted with ether. The combined extracts are washed with water, dried (Na2SO4) and evaporated to give an oil which slowly solidifies. Yield 15.6 g (50%) Recrystallization from ethanol gives beta- (2,4-diphenylthiazolyl-5) propionic acid in the form of long, colorless needles, melting point 150 ° C. Analysis. Found C, 69.6; H, 5.0; N, 4.4; S, 10.2. C18H15NO2S should contain: C, 69.9; H, 4.9; N, 4.5; S, 10.3%. Example XXXIV. 2,4-diphenylthiazolyl-5-acetic acid methyl ester (1.9 g) in methanol (25 ml) and 0.88 ammonium hydroxide in a solution (25 ml) is heated in a sealed tube at 90 ° C for 5 hours. After cooling, the acicular acetic acid crystals of 2,4-diphenylthiazolyl-5-acetic acid are filtered off. Yield 0.6 g (33%). Recrystallization from benzene gives long needles, mp 209-210 ° C. Analysis. Found C, 69.1; H, 4.9; N, 9.7; S, 11.0. C17H14N2SO should contain: C, 69.5; H, 4.8; N, 9.5; S, 10.9%. Example XXXV. 4- (4'-chlorophenyl) -2-phenylthiazolyl-5-acetic acid (2.0 g) in dry tetrahydrofuran (50 ml) is cooled to 0 ° C and then dry triethylamine (0.68 g) is added dropwise, and then ethyl chloroformate (0.73 g) to obtain the mixed anhydride, the reaction temperature is kept between 0-5 ° C. After 0.5 hours, liquid ammonia (0.35 g c / L 0.88) was added dropwise. The mixture was stirred at room temperature overnight (14 hours) and then evaporated to dryness. Water and ethyl acetate are added to the resulting solid, and the ethyl acetate layers are separated, evaporated and dried to give a solid. The body is continuously washed thoroughly with benzene to leave the acetic acid amicium crystals of 4- (4'-chiorophenyl) -2-phenylthiazolyl-5-acetic acid. Yield 0.32 g (15%), mp 223-4 ° C. EXAMPLE XXXVI A. Benzoine (21.2 g) and succinic acid anhydride (10.0 g) are heated together at 120 ° C. C for 6 hours. After cooling, the glass-like body formed was continuously dissolved in ether and extracted with a dilute aqueous sodium carbonate solution. The basic extract is washed once with ether and then acidified with hydrochloric acid. The resulting oil is extracted with ether and the extract is washed with water, dried over Na 2 SO 4 and evaporated to give an oil which solidifies and forms pistil-shaped crystals of benzoin monosuccinate (27 g, 87%), mp 86-88 ° C. The sample for analysis is crystallized from aqueous acetone to give slides, mp 88.5-89.5 ° G. Example XXXVI B. Benrine monosuccinate (15: g). and ammonium acetate. (30 g) warms; reflux in boiling glacial acetic acid (100 ml) for 1 1/2 hours. After cooling, the solution is poured into water and the resulting precipitate is filtered off, washed with water and recrystallized from methanol to obtain crystals of beta- (4,5-diphenyloxazolyl-2) and propionic acid in the form of needles (11.7 g, 83%), mp 160.5-161.5 ° C. Analysis. Found C, 73.9; H, 5.4; N, 5 * O.C16S45NO3 should contain: C, 73.8; H "5.2; N, 48%, Ex. X; XXVIL A., Anisoine (13.6 g), anhydride, succinic acid (5.5 g) and tpluene (3 ml) are heated with stirring for 5 hours so that the temperature inside the reaction mixture was maintained. between 135-140 ° C. The mixture is allowed to cool, ether (100 ml) is added and undissolved succinic anhydride is separated by filtration. The filtrate is added to a stirred 0.5 N acid solution of sodium carbonate (250 ml), the organic layer is separated and extracted again with a Q.5 N NaHCO3 solution (2X50 ml). The combined aqueous layers are extracted once with ether (250 ml) and acidified with concentrated HCl. The resulting oil is extracted with ethyl acetate. (1 X 100, 2 X 50 mL) and the combined organic phases are washed thoroughly with water, dried (MgSO 4) and evaporated in vacuo to yield an anisoin monosuccinate as a foam. Yield 8.28 g (44.4%). Example XXXVII B. Aneurosin monosuccinate (5.52 g) and urea (2.05 g) in glacial acetic acid (30 ml) are heated under reflux for 3 hours. . The mixture was cooled and poured into ice / water (500 mL). The oil that separates is extracted with ethyl acetate (3 X 150 ml). The combined organic phases are washed with water until the wash liquid is completely neutral and then extracted with 0.5 N acidic sodium carbonate solution (3 x 75 ml). The combined aqueous extracts are extracted with ethyl acetate (100 ml). ), acidified with concentrated HCl, and the resulting oil was extracted with ethyl acetate (3 X 100 mL). After washing with water, drying (MgSO 4) and removing the solvent a sticky solid (3.96 g) is obtained. Recrystallization from benzene / gasoline (60-80) 'gives yellow-brown crystals of beta-i [4,5-di (4'-meftoxyphene; methyl) oxazoyl-2] propionic acid. Yield 2.65 g (50.7%), mp 78-82PC. The sample recrystallized for analysis (from benzene) had a melting point of 81.5-84 ° C. Analysis. Found C, 67.8; H, 5.8; N, 4.0%. C 20 H 19 NO 5 should contain: C, 68.0; H, 5; 4; N, 4.0%. The next sample was converted to sodium salt by recirculation with sodium hydroxide. * ¦ jPf zy cla d XXXVIII. By repeating the procedure of Example XXXVII A, but with 4 methoxybehzoin (12.1 g) which is reacted for 5 hours with succinic anhydride (5.5 g) at 135-140 ° C. 20 10 15 30 25 30 35 4 * 45 50 55 00 65 4-methoxybenzoin monosuccinate is obtained Yield 10 g (58.3%) The procedure of Example XXXVIII B is then repeated, but using the obtained monosuccinate (8.6 g), urea; (3.6, g) and glacial acetic acid (25 ml) and get. Beta-i [4- (4f-methoxyphenyl) -5-phenyloxazqlyl--2] propionic acid is present. Yield 64 g (75.1%). melting point 118-120 ° C. Analysis. Found C, 70.5; U, 5.4; N, 4.5. CigHijNOi should contain: C, 70.7; H 5.3; N, 4.3%. Example XXXIX. Repeating the procedure of Example XXCVII A but reacting 4'-chloro-4-methoxybenzoine (13.8 g with succinic anhydride (5.5 g) for 7 hours at 135-140 ° C. C the monosuccinate of 4-chloro-4-methoxybenzoin is obtained. The procedure of Example XXXVII is then repeated, but using the obtained monosuccinate (9.4 g), urea (3.6 g) and glacial acid. acetic (25 ml) and, there is obtained beta- [4- (4'-methoxyphenyl) -5- {4'-chlorophenyl) -oxazolyl-2] propionic acid. Yield 6.7 g (75 * 2%), mp 130.5-132.5 ° C. Analysis. Found C, 63.75; H, 4.5; N ,. 3.8; Cl, 9.9. C 19 H 16 ClNO 4 should contain: C, 63. $ H, 4.5; N, 3.9 ;; Cl, 10.1%. Example XL A. Benzoine (21.2 g) is reacted with glutaric acid anhydride (11.4 g) according to. as described in Example XXXVI to obtain the benzoin glutanic acid monoester (18.3 g, 56%) as an oil. It has an infrared spectrum consistent with its structure. Example XL B. Benzoin glutaric acid monoester (18.3 g) and ammonium acetate (30 g) are refluxed in glacial acetic acid (100 ml) for 2 1/2 hours. Separation as in Example XXXVI yields gamma- (4,5-diphenyloxazolyl-2) butyric acid (15.4 g, 89%) as acicular crystals, mp 125-126 ° C. Analysis. Found C, 75.4; H, 6.0; N, 4.5. C19H17NO3 should contain: C, 74; H, 5.6; N, 4.6%; Example XLI. The acid of example XXXVI (5 g) in anhydrous (100%) ethanol is heated under reflux with concentrated H 2 SO 4 (1 ml) for 16 hours. The mixture is cooled, evaporated in a vacuum to approximately 50 ml and poured into water (200 ml). The resulting body is constantly filtered off, washed with water; acidic sodium carbonate and one more time water (5.32 g); The solid is recrystallized from ethanol to give colorless needles of beta- (4,5-diphenyloxazolyl-2) propionic acid ethyl ester. Yield 4.4 g. After standing, an additional 0.21 g of the above substance crystallized from the mother liquor. Total yield 4.61 g (84.3%), mp 69.5-71 ° C. Analysis. Found C, 74.7; H, 6.1; N, 4.4. C 20 H 19 NO 3 should contain: C, 74.8; H, 6.0; N, 4.4%. Examples a d XLII. Isobutyl chloroformate (1.23 g) is added to a stirred suspension of beta- (4,5-diphenyloxazolyl-2-propionic acid (2.5 g) 21 in a mixture with dry tetrahydrofuran (10 ml), dry dioxane (10 ml) and triethylamine (0.85 ml, 9 mol.) cooled with ice. The mixture was stirred on ice for 30 minutes and then at room temperature for 1 hour. The mixture was cooled with ice, ammonia (c. in. 880 1 ml) and stirred for 16 hours. The mixture was poured into water (150 ml) and the resulting solid amide of beta-(4,5-diphenyloxazolyl-2) propionic acid was separated. 72%), mp 146-7 ° C. after recrystallization from ethanol. Analysis Determined: C, 74.2, H, 5.6, N, 9.6: C 18 H 16 N 2 O 2 should contain: C, 74.0; H, 5.5; N, 9.6 EXAMPLE XLIII By repeating the procedure of Example XXXVII A, but reacting 4'-chlorobenzoine (6.2 g) (the phenyl ring at the hydroxy group is substituted ) with acid anhydride, bur (2.75 g) at 135 ° -140 ° C. for 6 hours to give 4'-chlorobenzoin monosuccinate. Yield 6.24 g (69.7%) The procedure given in Pyrade XXXVII B is then repeated, but using the ester (6.24 g) obtained above, urea (3.0 g) and glacial acetic acid (20 ml) to give beta- | [5- (4'-chlorophenyl) -4-phenyloxazolyl-2] propionic acid. Yield 3.52 g (61.7%), the temperature is Mp 180-182 ° C. 30 Analysis. Found C, 66.1; H, 4.3; N, 4.1; Cl, 10.7.C18H14ClNO3 should contain: C, 66.0; H, 4.3; N, 4.3; Cl, 10.8 ° / o. Example XLIV. By repeating the procedure of Example XXXVIIA, but by reacting 4'-methylbenzoine (11.3 g) with succinic anhydride at 135-140 ° C for 5 hours, the monosuccinate 4 is obtained. '-methylbenzoine. Yield 11.0 g (67.2%). The procedure of Example XXXVIIB is then repeated, but using the above-prepared ester (7.5 g), urea (4.1 g) and glacial acetic acid (20 ml) to give beta-i acid. [4 - phenyl - 5 - (4'-methylphenyl) oxazolyl-2] propionic. Yield 4.1 g (63%), mp 169-170 ° C. Analysis. Found C, 74.3; H, 5.7; N, 4.6. Ci9H, 7NO3 should contain: C, 74.3; H, 5.6; N, 4.6%. 50 Example XLV. By repeating the procedure of Example XXXVIIA, but by reacting 4-chlorobenzoine (9.9 g) with succinic anhydride (4.5 g) for 5 hours at 135-140 ° C, the 4-chlorobenzoin monosuccinate. Yield 10.5 g (76%) The procedure of Example XXXVII B is then repeated, but using the ester obtained above (7.8 g), urea (3.75 g) and glacial acetic acid (20 ml) to obtain in beta- | [4- (4'-chlorophenyl) -5-phenyloxazolyl-2] propionic acid. Yield (56.4%), melting point 155-7 ° C. Analysis Found: C, 65.9; H, 4.3; Cl, 11.4, es 22 C18H14CINO3 should contain: C, 66.0; H, 4.3; Cl, 10.8%. Example XLVI. By repeating the procedure of Example XXXVIIA, but by reacting 4-Chlc with: succinic anhydride (4.05 g) at 135-140 ° C for 5 hours, 4-chloro monosuccinate is obtained. -L4 '- "methoxybenzonine. Yield 9.8 g (67%). The procedure of Example XXXVIIB is then repeated, but using the ester obtained above (9.2 g), and obtaining is beta- [4- (4'-chlorophenyl) -5- (4% methoxyphenyl) oxazolyl-2] propionic acid Yield 5.0 g (55.5%), mp 126-8 ° C Analysis Determined C, 63.7, H, 4.6, Cl, 10.05 Calculated for C 19 H 16 ClNO 4; C, 63.8, H, 4.5, N, 3, 9, Cl, 10 1%. Example XLVII. Beta-4,5-dPyphenyl-xazolyl-2) prapionic acid (5.8 g) is reacted in the presence of triethylamine (2.8 g) with acetoxyimethyl bromide (1 , 84 ml) in dimethylformamide (50 ml). The mixture was allowed to stand overnight at room temperature and then poured into water. The reaction mixture is extracted with ether, washed with water, acidic sodium carbonate and then again with water before drying (MgSO 4) and evaporated to give a solid. Yield 6.2 g. Another 1.1 g of the product was obtained after the second extraction. The product is recrystallized from ethyl acetate to obtain 5 g of acetoxymethyl ester of beta- (4,5-d-Wufenyl-oxazolyl-2) acid. propionic acid 5.0 g (68.1%), mp 86-86.5 ° C. Analysis. Found C, 69.2; H, 5.35; N, 4.05.C2iH19NO5 should contain: C, 69.0; H, 5; 2; N, 3.8%. Example XLVIII. 2-methoxythiobenzamide (4.20 g), 3-benzoyl-3-bromopropiOonic acid (6.40 g) and anhydrous sodium carbonate (1.2.5 g) are added to isopropanol (40 ml) and the mixture is stirred while maintaining the temperature. 60 ° C for 30 minutes and then for a further 1 hour stirring at 40 ° C. The mixture is cooled to room temperature and poured into water (500 mL). The mixture is acidified by adding a few drops of concentrated hydrochloric acid and the thick oil is separated. The aqueous phase is extracted with ether (2 x 100 ml) and the extracts obtained are combined with the oil. The resulting solution was extracted with a saturated solution of acidic sodium carbonate (3 x 100 ml) and the extracts acidified with concentrated hydrochloric acid. The pale yellow solid 2- (2'-methoxyphenyl) -4-phenylthiazolyl-5-acetic acid obtained is filtered off, dried and recrystallized from anhydrous acetic acid / water. Yield 6.4 g (78.3%), mp 179-180.5 ° C. Analysis. Found C, 66.4; H, 4.6; N, 4.5; S, 9.8, C18H15NO3S should contain: C, 66.45; H, 4.65; N, 4.3; P. 9.85%. Example XLIX A. By repeating the procedure of Example XLVIII, but using 4-chloro-2-methoxythiobenzamide (50 g), 3-benzoyl-3-bromopropionic acid (6.4 g ) anhydrous sodium carbonate (1.25 g) and isopropanol (40 ml) give 2- (4'-chloro-2, -methoxyphenyl) -4-phe- (72562 nylthiazolyl-5-acetic acid). 5 g (64.6Vt), mp 204-5 ° C. Analysis. Found C, 58.9; H, 3.9; N, 3.8; Cl, 10.1; S, 9.2. C17H ^ClNO5S should contain: C, 60.1; H R 3.9 *, N, 3.9; Cl, 9.85; S, 8.9%. * Example XLIX, B, 4-chloro-2-methoxyitobenzaniide is prepared as follows (This method is generally used for the preparation of thioamides). 4-chloro-2'-methoxybenzonitrile (26.5 g) is dissolved in the solution. dry pyridine »(22 ml) and triethylamine (21 ml) and purged hydrogen sulphide through the mixture until the nitrile is completely converted to thiamid (approximately 15 hours). The reaction mixture is poured into water (500 ml) and the resulting precipitate is filtered off. »After drying in air, the product recrystallizes from benzene. Yield 24.1 g (75.7%), melting point 149-150 ° C. Example L A. By repeating the procedure of example XLVIII, but using 2 * 2-chloro-6-methylthiobenzamide (4.65 g) 3-benzoyl-3-bromopropionic acid (6.4 g), anhydrous sodium carbonate (1.25 g) and isopropanol gives 2- (2H-chloro-6 / H-methylphenyl) acid - 4-phenylthiazolyl-5-acetic acid. Yield 5.4 g (63%), mp. 217-219 ° C. Analysis. Found C, 62.8; H, 4.2; N, 3.9; Cl, 10.3. Ci8Hi4ClNO2S should contain: C, 62.9; H, 4.1; N, 4.1; Cl, 10.3Vo. Example L B. 2-Chloro-6-methylthiobenzamide 30 is prepared as described for the corresponding thioamide in Example XLIX B, but using 2-chloro-6-methylbenzonitrile (58 g), dry pyridine (54 ml) and triethylamine (53 ml) and bubbling hydrogen sulfide for 10 hours. Yield 59.1 g (83%), m.p. 126-129 ° C. Example LI A. Repeating the procedure of example XLVIII, but using 4-methoxy-2-methylptiobenzamide (2.7 g) , 3-benzoyl-3-bromopropionic acid (3.85 g), anhydrous sodium carbonate (0.75 g) and isopropanol (22.5 ml) give 2- (4'-methoxy-2 'acid) -methylphenyl) -4-phenylthiazolyl-5-acetic. Yield 1.4 g (27.5%), mp 136-138 ° C. Analysis. Found C, 67.1; Hr 5.0; N, 3.9; S, 9.3. C19H17NO3S should contain: C, 67.2; II, 5.05; N, 4 * 1; S, 9.45%. Example LI B. 4-Methoxy-2-methylthiobenzamide was prepared as described in Example XLIX B, but using 4-methoxy-2-methylben- zonitrile (68.2 g ), dry pyridine (65 ml) and triethylamine (64.2 g) and bubbling hydrogen sulfide for 15 hours. Yield 60.3 g (71%), m.p. 124-126 ° C. Example LII A. By repeating the procedure of Example XLVIIIA but the *} 'ac stack of 4-chloro-2-methylthiobenzamide ( 4.65 g), 3-benzoyl-3-bromopropionic acid (6.4 g), anhydrous sodium carbonate (1.25 g) and isopropanol (40 ml) give: 2- (4'-chloro 2'methylphenyl) -4-phenyl-lotiazolyl-5-acetic. Yield 5.3 g (58%), melting point 175-177 ° C. Analysis. Found C, 63.05; H, 4.1; N, 4 * 1; Cl 10.3.C18H14CINO2S should include; C, 62.9; H, 4.1; N, 4.1; Cl, 10.3 ° / t. «Example OR. 4-Chloro-2-methylthiobenamide is prepared as described in Example XLIXB, but using 4-chloro-"2-methylbene" ojiitt3d 26 g), 4 dry pyridine (25.5 ml) and triethylamine: (25 ml) and bubbling hydrogen sulfide for 15 hours. Yield 22 g (69Vt) * mp 86- ^ 88 ° C. , _. ' ¦ ¦, '¦¦¦ i;: T ..- "rl? -: - Example LIII. 4-chloromethylor-2,5-f-diphenyl-oxazole is obtained by method K;: Bodenddrft and H. Tówliate, Arch. Pharm. 298 ( 1965) str0ftaf 293; This chloromethyl compound (14 g) is retained under a potassium cyanide reflux condenser; (Tg) boiling in ethanol -? (80 ml) in water (10 ml) for 5 hours before draining after the removal of some ethanol, water is added and the crystalline solid is filtered off. Recrystallization from ethanol gives 9.6 g of acicular crystals. Yield 72%; mp 137-138 ° C. »¦ / The resulting cyano compound (9 g) is boiled with 6N HCl for 90 minutes. After cooling, the crystals are separated and extracted with ether. The ethereal layer is washed with water, dried (MgSO 4 and evaporated to give 8.4: g of crystalline solid. Recrystallization from benzene gives 4.2 g of white, acicular crystals of 2,5-diphenyloxazoleUo-i4-acetic acid. Second crystals are obtained. on a batch of K (2.9 g) 1 and tetaystylize from benzene (petroleum ether (80-100 ° C. Yield 74%, m.p. 177-178 ° C. Example UVi By repeating the procedure of example XLVIII, but using 2-methylphenylthiobenzamide (20 g) 3-bromo-3- (2'-naphthoyl) propionic acid (40 5 g), anhydrous sodium carbonate (6.6 g) and isopropanol (200 ml) to give 4- (2'-naphthyl) -2- (2'-methylphenyl) thiazolyl-5-acetic acid, m.p. 171 —172PC. ; Example LV.A. By repeating the procedure of Example XLVIII, but using 2,4-dimethoxythiobenzamide (2.5 g), 3-Aenzoyl-3-bromopropionic acid (3.2 g), anhydrous sodium carbonate (0.6 g) and isopropanol (19 ml) gives 2- (2, 4'-dimethoxyphenyl) -4-phenylthiazolyl-acetic acid. Yield 2.0 g (44.4 ° C), mp 157-159 ° C. ; - Example LV. B. 2,4-dimethoxyttobenzamide is prepared as in Example XLIXB but using 2,4-dimethoxybenzpnitsril (7.7 g) Dry pyridine (7 ml) and triethylamine (7 ml) and bubbling hydrogen sulphide for 8 hours. 6.3 g (68%), - Example LVIA. By repeating the procedure of Example XLVIII but using 4- (N, N-dimethylamino) thiobenzamide (9.0 g), 3-benzoyl-3- bromopropionic acid (12.9 g), anhydrous sodium carbonate (2 5 g) and isopropanol <75t4 ml), 2- (4'-N, N-dimethylaminophenyl-M-phenylthiazolyl-5-acetic acid) is obtained Yield 2.1 g <-. (12.4%), after recrystallization from benzene four times, mp 144-146 ° C. Example LVIB., 4- (N, N-dimethylamino) thiobenzamide. ¬ clade XLIXB; but using 4- (N, N-dimethyl) benzonitrile (25 g), dry pyridine (23.8 ml) and triethylamine (23.5 ml) and bubbling hydrogen sulphide25 for 7 hours / Yield 27 g (87.6% ), mp 218 ° C. Example LVII. A. Repeating the procedure of Example XLVIII, but using 2,3-dimethylthiobenzamide (2.5 g), 3-benzil-3-bromopropionic acid (3.85 g), anhydrous sodium carbonate (ff. , 75 gj and isopropanol (22.5 ml) give 2- (2 ', 3'-dimethylphenyl) -4-phenylthiazolyl-16-5 acetic acid Yield 3.2 g (64.2%), m.p. 143 ° -14.5 ° C .; Example LVII. B. 2,3-Dimethylthiobenzanide was prepared as described in Example 2tLIX! B but using 2,3-dimethylbenzonitrile (100 fg), dry pyridine (117 ml) and triethylamine (114 g) and by bubbling hydrogen sulphide for 15 hours. Yield 116.2 g (92%), mp 137-13 ° C. Example LVIII A. By repeating the procedure of example XLVIII, but using 2,4-dichlorothiobenzamide (5.2 g), 3-benzoyl-3-bromopropionic acid (6.4 g), anhydrous sodium carbonate (1.25 g) and isopropanol (40 ml) the acid is obtained. - (2 ', 4'-Dichlorophenyl) -4-phenylthiazolyl-5-tetrahedron, m.p. 158-160 ° C Example 1 a d LVIII. B. 2,4-dichlorophenylthiobenamide was prepared as described in Example XLIXB, but using 2,4-dichlorobenzonitrile (12.5 g), dry pyridine (11 ml) and trimethylamine (10 ml) and by bubbling hydrogen sulfide for 16 hours; Example LIX. Repeating the procedure of Example XLVIII but using 4-chlorothiobenzamide (3.85 g), 3- (4'-chlorobenzoyl) -3-bromopropionic acid <6.6 g), anhydrous sodium carbonate (1.4 g) and isopropanol (35 ml) give 2,4-di- (4'-chlor] X) phenyl)) -thiazolyl-5-acetic acid. Yield 2 , 5 g (30.6%), m.p. 194-196 ° C. LX. Non-ethyl 3- (2'-chlorophenyl) propionate is prepared as described in JOC: 15.785 (1950) and brominated to give methyl 3-bromo-3- (2'-chlorobenzoyl) propionate. This derivative is reacted with thiobenzamide by repeating the procedure of Example XLVIII, and the resulting methyl ester is hydrolyzed to give 4j (2'-chlorophenyl) -2-phenylthiazolyl-5-acetic acid. Example 1 a d LXI. Ethyl 4-phenylacetoacetate (5.15 g) is brominated - (4 g) in anhydrous ether. After standing for than 18 hours at room temperature, water is carefully added. The ether layer is washed, dried and evaporated to obtain ethyl 4-bromo-4-phenyl acetoacetate. Yield 7.14 g. This ester (7.14 g) in acetone (20 ml) is treated with a solution of thiobenzamide (3.4 £) in acetone (30 ml) at room temperature and then boiled under coolant. feedback for 2 hours. After evaporation to dryness, water and ether are added and the ether extract is washed with an acid sodium carbonate solution and water, dried (MgSO 4) and evaporated to give 2,5-diphenylthiazolyl-acetic acid ethyl ester. Yield 8.07 g (approx. 100%). This ester (8.07 g) in ethanol (50 ml) is exposed to 72562 10 15 24 30 35 40 45 5S 55 60 65 with an aqueous solution of potassium hydroxide (2 g '10 ml). After heating for 15 minutes on a steam bath, the solution is allowed to stand at room temperature for 1 hour. The solution is evaporated to dryness and ether and water are added: After cleaning with charcoal, it is filtered, 'acidified, the crude 2,5-d-diphenyl-lyl-4-acetic acid is filtered off (-2 g)' and crystallizes from benzene. ¬ nu. Yield 2.5 g (33.5%), melting point 171 ° C (100 ° F). Example LXII. alpha-bromodezoxybenzoine (68.8 g) and benzyloxyacetic acid thioamide (68.3 g); is subjected to a co-reaction following the general rule given for '2-benzdyl oxymethyl-4-phenylthiazole in JACS 53, 1470 (1931). In this reaction, 2-benzoyloxymethyl-4,5-diphenylthiazole is obtained. Yield 58.5 g, m.p. 157-160 ° C. Benzoate (58.5 g) is heated on a steam bath for 30 minutes with potassium hydroxide (10 g) in ethanol and then poured into ice water. The oily solid is extracted with ether and the ethereal solution is evaporated to give 2-hydroxymethyl-4,5-diphenylthiazole. Yield 41.6 g (98.5%), mp 113-111 ° C. This compound, 12.9 g, is then treated with phosphorus oxychloride (20 ml) to give 2-chloramethyl-4,5-diphenylthiazole. Yield 13.7 g (88.4%), mp 76-78 ° C. '' '' f A hot solution of a chloromethyl compound (12.9 g) in anhydrous ethanol (100 ml) is added to the boiling db under the cooler, return to an ethanolic sodium dimethylmalonate solution (from 1.55 g of sodium and 10.7 g of diethylmalonia * M) * f After two hours of boiling under reflux, the crude 4,5-diphenylthiazolild-2-malonic acid diethyl ester is obtained (18 g). This compound is then subjected to Hydrolysis with potassium hydroxide (20 g) in water (20 ml) to give the acid as a yellow foam (12.8 g). From this, the 4,5-diphenylthiazolyl-2-propionic acid is obtained by heating to reflux for 1 1 hour in dry dimethyl formamide (25 ml), iodine spectrum <- red confirms the structure of the compound, mp 52-58 ° C. ",,. ¦ •. Example LXIII. Beinzamide (3.02 gj is added to a suspension of sodium hydroxide (1.2 g, 50% in oil) in benzene (200 ml) and the mixture is heated under reflux with stirring. V * hours. Ethyl 4-bromide-4-phenylacetate (7.14 g) obtained as outlined in example LXI, in benzene "" "(30 ml) is then added dropwise over 0.5 hours and heating continued for a further After 2 hours. Water is added, the benzene layer is washed with water, saturated NaCl solution, dried with MgSO4 and evaporated to give a brown solid (6.6 g). 7 Dissolve in concentrated sulfuric acid (25 ml ) And the solution is allowed to stand for 18 hours at room temperature, this solution is poured into an excess of water and ether is added. The ethereal layer is washed with saturated NaHCO 3 solution, water, dried (MgSO 4) and evaporated in to obtain the crude ester ¦ 2,4-diphenyloxazolyl-5-acetic acid. The crude ester 27 72562 28 (1.2 g) is dissolved in ethanol (20 ml) and potassium hydroxide is added (1 g) dissolved in water (5 ml). The solution is heated on a steam bath for 5 minutes and allowed to stand at room temperature for 2 hours. The solution is evaporated to obtain an oil, water and ether are added to the oil, and the aqueous layer is treated with charcoal, filtered and acidified to obtain 2,4-diphenyloxazolyl-5-acetic acid, the construction of which is confirmed by the infrared spectrum. Recipe 1 2- (4'-chlorophenyl) -4-phenylthiazolyl-5-acetic acid 125 mg, lactose 120 mg, magnesium stearate 5 mg. Capsules are made from the above by thoroughly mixing the components of the kit and filling this mixture with 250 mg hard gelatin capsules Recipe 2. 2- (4'-chlorophenyl) -4-phenylthiazolyl-5-acetic acid 125 mg, lactose 100 mg, avicel 30 mg, dry corn starch 40 mg, ma-stearate 5 mg. Tablets from the above kit are made by reducing the active ingredient to a particle size close to passing through a No. 40 screen (British Standard), sieving through a No. 40 screen (British Standard), mixing the ground material with the remaining ingredients. and pressing to form The active substances of e.g. LXIV and LXV can be replaced with other new compounds within the scope of the present invention, e.g. beta- (2,5-diphenyloxazolyl-2) propionic acid, 4- (2'-triethylO) -2H2 acid , -methylphenyl) thiazolyl-5-acetic acid or 2- (2'-chlorophenyl) -4-phenylthiazolyl-5-acetic acid, and. Example LXIV. N - (4,5-diphenyloxazolyl-2) propionic acid. A) Desylamine hydrochloride (20.0 g) in chloroform (200 ml) is mixed with a solution of acid sodium carbonate, the aqueous layer is separated and re-extracted further chloroform. The combined and dried (MgSO 4) chloroform extracts are boiled for 20 minutes with succinic anhydride (8.1 g), cooled and the colorless crystalline material by filtration and recrystallized from aqueous ethanol to give 11.0 g of the acid (N- (1,2-diphenyl -2-ethyloxy) amber, mp 180-182 ° (Analysis: Found: C = 69.5, H = 5.5, N = 4.5, calculated for C 18 H 17 NO C = 69.45. H = 5.5, N = 4.50). B) The above succinic acid (1.0 g) is mixed with sodium sulfuric acid (20 ml) at 50 ° C for 3 hours and cooled and poured into water (250 ml) and extracted with ethyl acetate. Washed and dried (MgSO4, the organic extract was evaporated to dryness and the residue recrystallized from aqueous methanol to give the desired acid, mp 160-162 ° C. Analysis: found C - 73.95, H = 5.3, N = 4.8 calculated for C 18 H 5 NO 8, C = 73.7, H = 5.15, N = 4.8 Vol. Example LXV. Acid 3- (2.4- diphenylthiazolyl-5) propionic, a) mixture of 2,4T-diphenyl-5-formylthia sol (13-27 g), malonic acid (5.2 g) and pyridine (5.0 ml) in absolute alcohol (50 ml) are boiled for 2 hours and then allowed to stand at room temperature for 18 hours. . The solid material is filtered off, washed with alcohol and ether and then dried to give 7.84 g. 3 ^ 2,4-diphenylthiazolyl-5) acrylic acid. B) A mixture of the above acrylic acid (3 * 07 g) and reduced palladium-on-charcoal (5.0 g of 10%) in ethanol (100 ml) is shaken in a hydrogen atmosphere for 1 hour, at the end of which a further amount of pre-unreduced palladium on charcoal ( 5.0 g of 10% strength) and the mixture is shaken again for 1 hour. After the addition of the third portion of prereduced palladium on charcoal (5.0 lOthyl), shaking was continued again for an hour. After removal of the catalyst by filtration and evaporation of the filtrate, 0.9 g of the title compound was obtained, m.p. 150 ° C. after recrystallization from ethanol, which was an identical product to the product of Example 33. 2,4-diphenyl-5. The formylthiazole used in part a) is reacted with thiobenzamide and ethyl-bromobenzoylacetate to give 2,4-diphenylthiazolyl-5-carboxylic acid ethyl ester which is reduced with lithium aluminum hydride in tetrahydrofuran to give the corresponding 5-hydroxymethyl compound which in turn reacts with phosphorus pentachloride and a chloromethyl compound prepared by reaction with hexamethyltriamine in alcohol followed by addition of water (Sommoelet reaction) gives the 5-formyl compound. Example LXVI. 3- (2,4-Diphenyctiazolyl-5) propionic acid. A) 2,4-Diphenylthiazolyl-5-acetic acid (5.0 g) is dissolved in the minimum volume of ethanol, the solution is strongly acidified with ethanolic hydrogen chloride and then added with ether to cause the hydrochloride salt of the starting material to crystallize. This hydrochloride was dissolved in thionyl chloride (2.0 ml), stirred at room temperature for 15 minutes and then heated in a water bath at 45 ° C for hour. The solution was evaporated to dryness to give the hydrochloride salt of the acidic starting material as a dark tar. b) A stirred and cooled suspension of the above acid chloride hydrochloride in ether (25 ml) is treated with a solution of diazomethane (1.42 g) in and triethylamine (3.4 g) in ether (75 ml). After stirring for 16 hours, the precipitated amine hydrochloride is filtered off and the filtrate is evaporated to dryness to give the crude di-azoketone. A solution of this diazoketone in dioxane (30 ml) is slowly added to a mixed solution of sodium carbonate (1.1 g), sodium thiosulfate (0.67 g) and silver oxide (0.45 g) in water (50 ml) at 50-60 ° C. Stirring is continued for 1 hour and the temperature rises to 90-100 ° C. After the reaction mixture has been cooled, it is acidified with dilute nitric acid to precipitate the crude title compound. Twice recrystallization from ethanol gives the title compound (1.3 g) with a melting point of 150 ° C. which is identical to that of Example 33.29 72562 for LXVII. N - (4,5-diphenyloxazolyl-2) propiohydroxamic acid. A solution of hydroxamine hydrochloride (0.382 g) in methyl alcohol (5.0 ml) is added to a stirred solution of sodium (0.243 g) in methyl alcohol (5.0 ml). The mixture is placed in the refrigerator for 1.5 hours. The sodium chloride is removed by filtration and the filtrate is added to the stirred solution of the ester of Example 41. After 16 hours at room temperature, the mixture is poured into a solution of 2N hydrochloric acid (5.0 ml) in water (150 ml). The colorless body is constantly filtered off, ears, recrystallized from ethyl acetate to give 1.07 g of titanium acid, m.p. 148 ° C (decomposed). Analysis: Found: C = 70.0, H = 5.4. N = 9.1. Calculated for C 18 H 16 N 2 O 3 C = 70.1, H = 5.2 N = 9.1%. Example IJXVTII. 4- {p-chlorophenyl) -2-phenylthiazolyl-5-acetate. N-butyl. A mixture of 4- (p-chlorophenyl) -2-phenyl-thiazolyl-5-acetic acid (5.43 g), n-butyl alcohol (50 ml) and concentrated sulfuric acid (1.0 ml) is heated to reflux for 16 hours. then treated with an equal amount of water and evaporated to a small volume. 200 ml of water are added to the mixture and the oil is extracted with ether. The organic extract is washed with water, sodium carbonate solution, water, dried (MgSO 4 and evaporated to give a yellow oil which is distilled under vacuum to give 4.95 g of ester with a boiling point of 205-218 ° C (0.1-0.15 mm, which solidifies into a solid with a melting point of 43-44 ° C after some time. Analysis: calculated for C21H20NO2S C = 65.3, H = 5.2, N = 3.6% found C = 65.4, H = 5.2, N = 3.8%. Example LXIX. 2,4-diphenyloxazolyl-5 acid acetic. a) A mixture of benzonitrile (3.18 g) and 2-hydroxypropiophenone (4.2 g) is allowed to stand at room temperature for 24 hours, then added with concentrated sulfuric acid (13.0 ml) and stirred at room temperature. At room temperature for 20 hours. Then the mixture is poured into water and after 1 hour the aqueous solution is decanted from the tar. The tar is washed with 2N sodium carbonate solution and extracted with benzene. The dry benzene extract is evaporated. that to give a red oily residue which is fractionally distilled under reduced pressure to give a fraction with a boiling point of 142-155 ° C / 0.5 mm which, on standing, slowly crystallizes and is recrystallized from the boiling crude oil fraction At 40-60 ° C, yielding 1.41 g of 2,4-diphenyl-5-methyloxazole, mp 69.5-70 ° C. Analysis: Found: C = 81.3, H = 5.7 , N = 5.9, calculated for C 16 H 18 NO C = 81.7, H = 5.6, N = 6.0%. b) The above compound 5-methyl (6.83%) in carbon tetrachloride (60 ml) is treated with N-bromosuccinimide (5.2 g) and a few benzoyl peroxide crystals and the resulting mixture is heated to a temperature of boiling until the heavy N-bromosuccinimide disappears and the lighter amberimide floats on the surface. The mixture is then filtered and evaporated to dryness to give a dark oily residue. This residue is extracted with boiling petroleum ether boiling at 80-100 ° C and the extract is evaporated to give the desired 2,4-diphenyl-5-bromomethyloxazole ( 8.7 g) in the form of a colorless oil which crystallizes on standing at room temperature. c) To a stirred suspension of sodium cyanide (1.55 g) in dimethylsulfoxide (70 ml) is added the 5-bromomethyl- compound (8.7 g) of recipe (b) in dimethylsulfoxide (110 ml) at room temperature. io and mixed for 2 days. The mixture is poured down into water (750 ml), extracted with ether and the extract is dried and evaporated to dryness. The residual nitrile is refluxed for 16 hours with a 20% solution of potassium hydroxide in water. The frosted solution is washed with ether and acidified to pH 7 by the addition of concentrated hydrochloric acid to give 1.0 g of the title compound. Example LXX. 2,5-diphenyloxazolyl-4-acetic acid. A) Benzimidomethyl ether at 100 ° C. is added to a stirred solution of ethyl α-amino benzoylacetate hydrochloride in glacial acetic acid. After stirring for 30 minutes at room temperature, the mixture is cooled in ice, diluted with water and extracted several times with ether. The ether extract is washed with dilute hydrochloric acid, dilute sodium hydroxide solution, dried with MgSO4 and evaporated to give the acid ethyl ester. 2,5-diphenyloxazolyl-30-4-carboxylic acid. b) The above ester (6.8 g) in sodium dried ether (60 ml) is added dropwise to a stirred suspension of lithium aluminum hydride (0.5 g) in ether (60 ml) at such a rate that to keep the boiling constant. After complete addition, the mixture is refluxed for 1 hour, cooled and the complex is decomposed by adding methanol (2 ml), then water (10 ml) and finally 2N hydrochloric acid. The ether layer was separated, washed with water, dried and evaporated to leave a 2,5-diphenyl-4-hydroxymethyl-oxazole residue. c) A suspension of the above hydroxymethyl compound (5.7 g) in dry methylene chloride (50 ml) is treated with thionyl chloride (2.0 ml). After 15 minutes at room temperature, the excess solvent and thionyl chloride are evaporated off to give a residue as 2,5-diphenyl-4-chloromethyloxazole. D) The above chloromethyl compound according to recipe (c) (14 g) is heated with potassium cyanide (7 g) in boiling ethanol (80 ml) and water (10 ml) for 6 hours and filtered while hot. After removing some of the ethanol, water is added and the crystalline solid is filtered off. Recrystallization from ethanol yields 9.8 g of needle-shaped crystals of 2,5-diphenyl-4-cyanomethyl oxazole, m.p. 137-138 ° C. e) The cyano compound of recipe (d) (9 g) is boiled with 6N hydrochloric acid for 90 minutes. After cooling, the crystals are separated and extracted with ether. The ether layer was washed with water, dried with MgSO 4 and evaporated to give 8.4 g of a crystalline product. Crystallization from benzene O 5 gives 4.2 white needle-shaped crystals which will be the title compound, mp 177-178 °. A second crop (2.9 g) is obtained and recrystallized from benzene and petroleum ether (bp 80-100 ° C). Example LXXI. 2,4-diphenylthiazolyl -5-acetic acid. A solution of acetamide (5.3 g) of Example 34 in a mixture of ethanol (49 ml) and: water (21 ml) containing sodium hydroxide (5.3 g) heated to boiling for 4 hours. The solvent is evaporated off and the residue is dissolved in water, washed with ether and acidified with concentrated hydrochloric acid. The oily material is extracted with ether, the combined ethereal extracts are washed with water, dried over MgSO4 and evaporated to give a viscous oil which slowly crystallizes. Recrystallization from benzene gives the title compound (3.0 g). mp 151-153 ° C. ¦ ¦ ¦ 'Example LXXII. Acid /? - (4,5-diphenylthiazolyl-2) propionic acid. A solution of succinic acid (7.0 g) obtained in Example 66 and anhydrous tin chloride (12.0 g) in chloroform (500 ml) are treated with dry hydrogen chloride for 1 minute, then hydrogen chloride and hydrogen sulfide are introduced simultaneously for 2 hours. The mixture is left at room temperature for 16 hours, then washed with water and extracted with 2N sodium carbonate solution. The basic extract is acidified with 2N hydrochloric acid, extracted with chloroform, the extract is dried with MgSO4 and evaporated to give the desired product which is identical to the product obtained in Example 62. Example LXXIII. 4- (p-Chloro) -2-phenyl-thiazolyl-5-acetic acid dimethylaminoethyl ester. ¦¦¦¦. ' 4- (p-Chlorophenyl) -2-phenyl-thiazolyl-5-acetic acid ethyl ester (14.32 g) and N, N-dimethylaminoethanol (50 ml) in dry benzene (300 ml) is heated to reflux. Using an azeotrope separator. Two small pieces of metallic sodium are added and the azeotrope is collected until a temperature of 81 ° C is reached (about 2.5 hours). The mixture is then heated to reflux for 1 hour. The cooled solution is evaporated under vacuum and pumped at 50 ° C under a high vacuum to remove excess ethanol. The residual brown oil is dissolved in dilute hydrochloric acid and washed 3 times with ether. The aqueous phase becomes alkaline and extracted with ether three times. The combined ethereal extracts are washed with water, concentrated in MgSO4, evaporated under vacuum and pumped under high vacuum at 50 ° C to constant weight. The light brown oil (13.4 g) is dissolved in dry ether, ethereal hydrogen chloride is added and a sticky yellow solid is collected. After crystallization from isopropyl alcohol, 9.36 g of dimethylaminoethyl ester are obtained as the hydrochloride in the form of colorless thin needles. mp 176-178 ° C (with decomposition). Analysis: Found: C = 57.7, H = 5.0, * N = 6.2. Calculated for C21H21ClN2O2S. HCl; C = 57.7, H = = 5.1, N = 6.4%, Example LXXIV. [Beta] - (4,5-diphenyloxazolyl-2) propionic acid dimethylaminoethyl ester. The mixture of the ester of Example 41 (48.2 g), dimethylaminoethyl alcohol (200 ml) and dry benzene (1000 ml) is heated to boiling using an azeotropic separator. The azeotrope (1-50 ml) is collected until the distillation temperature reaches -819C; 2 small pieces of metallic sodium are added and the mixture is heated again to the boil while collecting the azeotrope. When the temperature of the distillate reaches 81 ° C again, reflux is continued for 2 more hours and the mixture is evaporated in the steam at 50 ° C and 0.5 mm pressure to remove excess benzene and basic alcohol. The residual oil was dissolved in ether (250 ml), extracted with 2N hydrochloric acid (2 times 150 ml) and the ether extract made basic with 2N sodium hydroxide solution to yield the basic ester as an oil (394 g). The ester is dissolved in absolute ethanol (150 ml), treated with ethanolic hydrochloride (75 ml 1.5N) and then added with dry ether to initiate crystallization. Re-crystallization of the viscous solid from the ethyl alcohol-ether mixture and drying to constant weight under high vacuum yields 26.2 g of the title compound in the form of the hemihydrate hydrochloride, mp 118-124 ° C. 30 Analysis. Found: C = 64.3, H = 6.3, N = 6.8. Calculated for C24H24N2O3HCl. 1/2 H2C G = 64.4, H = 6.4, N = 6.8%. .-.- *. Example LXXV. 2- (p-Bromophenyl) -4- (p-fluoro-phenyl) thiazolyl-5-acetic acid. A mixture of β - bromo - / β - (p-fluorobenzoyl) propionic acid (13.75 g) and p-bromothiobenzamide (10.8 g) in dimethylformamide (13.75 g) and p-bromothiobenzamide ( 10.8 g) in dimethylformamide (12.5 ml) are heated at 70 ° C for 2 hours, poured into water 40 (500 ml) and the mixture is left overnight. The solid product is filtered off, washed well with water and recrystallized after drying. from benzene. Obtained 17.3 g of the title compound, mp 192-193 ° C. 45 Analysis Found: C = 52.3, H = 2.8, N = 3.6. Calculated for C17HnBrFNO2S. C = 52.0, H = 2.8, N = 3.6%. '["" ¦ Example LXXVI. N - (5-) p-Chlorophenyl (-4 - phenyloxazolyl - 2) propionic acid ethyl ester a) 4'-chlorobenzoin (6.17 g) and succinic anhydride (2.8 g) are reacted according to the method of Example 37 (a) to give 5.76 g of 4'-chlorobenzoin hernisuccinate 55 in the form of b) Reaction of 4'-chlorobenzoin hemisuccinate (5.76 g) and urea (2.5 g) in glacial acetic acid (20 ml) according to the method as in In the case of the method 37 (b), 2.13 g of the title ester 60 are obtained, m.p. 105-106 ° C. after recrystallization from a mixture of ethyl alcohol and petroleum ether. Analysis. Found: C = 67.4, H '= 5.2, N = 3.9, Cl = 9.9. Calculated for G20H18ClNO3, C = 67.5, H = - 65 = 5.1, N = 3.9, Cl2 = 10.0%. 5033 72562 34 Example LXXVII. O- (5-) o-chlorophenyl (-4-) 3,4-dimethoxyphenyl (oxazolyl-2) propionic acid. a) 2'-chloro-3,4-dimethoxybenzoine (15.35 g) and succinic anhydride (5.5 g) are reacted according to the method of Example 37 (a) to give 12.93 g of 2'-hemi-succinate chloro-3,4-dimethoxybenzoin. (b) Reaction of 2'-chloro-3,4-dimethoxybenzoin hemisuccinate (8.73 g) and urea (3.0 g) in glacial acetic acid (25.0 ml) according to the method of Example 37 (b) 5.1 g of the title acid are obtained, m.p. 118-120 ° C., after recrystallization from benzene. Analysis. Found: C = 61.9, H = 4.8, N = 3.6, Cl = 9.2. Calculated for C20H18ClNO3, C = 61.9, H = = 4.7, N = 3.6, Cl = 9.4%. Example LXXVIII. 2- (p-Isopropylphenyl) -4-phenylthiazolyl-5-acetic acid. A mixture of β-bromo-1-benzoyl-propionic acid (10.04 g) and p-isopropylthiobenzamide (6.99 g) in dimethylformamide (10.0 ml) is heated at 80 ° C for 1.25 hours and then poured into water (500 ml). The solid product was filtered off, washed well with water, and after drying it recrystallized from benzene, yielding 13.1 g of titanium acid, m.p. 146-147 ° C. Analysis. Found: C = 71.1, H = 5.7, N = 4.1. Calculated for C 20 H 19 NO 2 S, C = 71.3, H = 57, N = 4.2%. Example LXXIX. 4- (p-Chlorophenyl) -2- - (2'-pyridyl) thiazolyl-5-acetic acid. A mixture of pyridine-2-thiocarboxamide (2.36 g) and β - bromo - β - (p-chlorobenzoyl) propionic acid (5.0 g) in dimethylformamide (5 ml) is heated to 70 ° C for 1 hour and then poured into water (20 ml). After 0.5 hours, the solid product was filtered off, dried and recrystallized from ethanol to give 2.7 g of titanium acid, m.p. 202 ° C. (decomposition). y Analysis. Found: C = 58.0, H = 3.3, N = 8.4. Calculated for C16HnClN2O2S, C = 58.0, H = 3.4, N = 3.5%. Example LXXX. 4- (p-Chlorophenyl) -2- - (3'-pyridyl) thiazolyl-5-acetic acid. A mixture of pyridine-3-thiocarboxamide (2.76 g) and β-bromo-β- (p-chlorobenzoyl) propionic acid (5.83 g) in dimethylformamide (5 ml) was heated for 1 hour. day at 70 ° C and 15 minutes at 100 ° C. After pouring the mixture into water (400 ml), the solid is filtered off, dried, and crystallized twice from a mixture of dimethylformamide and ethanol to give 1.5 g of the title acid, mp 238 ° -239 ° C. (decomposition). Analysis. Found: C = 57.8, H = 3.3, N¦ = 8.4. Calculated. for C16H11C1N202S, C = 58.0, H = 3.4, N = 8.5%. Example LXXXI. 4- (p-Chlorophenyl) -2- - (4'-pyridyl) thiazolyl-5-acetic acid. A mixture of pyridine-4-thiocarboxamide (2.76 g) and β-bromo- (p-chlorobenzoyl) propionic acid (5.83 g) in dimethylformamide (5 ml) is heated for 1 hour in temperature of 70 ° C and then poured into water (400 ml). The solid product is filtered off, washed well with water, dried and then recrystallized several times from a mixture of dimethylformamide and ethyl alcohol, yielding 0.49 g of titular acid, mp 215-216 ° C (decomposition). Analysis. Found: C = 58.2, H = 3.2, N = 8.3. Calculated: for C16HnClN2O2S, C = 58.0, H = 3.4; N = 8.5%. Example LXXXII. 2- (p-Bromophyl) -4-phenylthiazolyl-5-acetic acid. The mixture of /? - bromide - /? - benzoylpropionic acid (6.4 g) and p-bromothio-benzamide (5.4 g) in dimethylformamide (10 ml) is heated at 70 ° C for 2 hours, poured into water (500 mL) and let the mixture stand overnight. The solid product is filtered off, washed well with water and, after drying, recrystallized from benzene to give 7.5 g of titanium acid, mp 173.5-174.5 ° C. Analysis. Found: C = 54.7, H = 3.2, N = • 3.7. Calculated for C 17 H 12 BrNO 2 S, C = 54.6, H = 3.2, N = 38%. 20 Example LXXXIII. 2- (p-bromophenyl) -4- (p-chlorophenyl) thiazolyl-5-acetic acid. A mixture of β - bromo - β - (p-chlorobenzoyl) propionic acid (7.28 g) and p-bromothiobenzamide (5.4 g) in dimethylformamide (10 ml) is heated to 70 ° C. poured into water (500 ml) for 2 hours and left the mixture overnight. The solid product is filtered off, washed well with water and, after drying, recrystallized from benzene, yielding 8.16 g of titanium acid, mp 202-30203 ° C. Analysis. Found: C = 49.9, H = 2.7, N = 3.5. Calculated for Ci3HuBrClNOaS, C = 50.0, H = 2.7, N = 3.4%. Example LXXXIV. 2- (p-Chlorophenyl) -35-5-phenylthiazolyl-4-acetic acid. A mixture of ethyl 4-bromo-3-oxp-4-phenylbutyrate (10.0 g) and p-chlorotipbenzamide (6.0 g) in ethyl alcohol (100 ml) was heated at reflux for 3 hours. Sodium hydroxide solution (8.0 g) in ethyl alcohol (15 ml) is added to the cooled solution and the resulting solution is heated in a steam bath for 5 minutes. The red solution is evaporated to dryness, the residue redissolved in water, washed with water. ether and then acidified with concentrated hydrochloric acid to give a white solid. Crystallization from benzene gave 5.3 g of titanium acid, mp 200-201 ° C. Analysis. Found: C = 61.8, H = 3.6, N = 4.3%. Calculated for C17H12C: INO2S, C = 61.9, H = 37, N = 4.2%. 'Example LXXXV. 4- (p-ehloroferiyio) -2-phenylthiazolyl-5-propionic acid. A mixture of β - bromo - / β - (p-chlorobenzoyl) butyric acid (14.2 g) and thiobenzamide (7.1 g) in dimethylformamide 55 (10 ml) is heated at 70 ° C for 2 hours, poured into water (500 ml) and the mixture left overnight. The solid product is filtered off, washed well with water and, after drying, crystallized from benzene to give 6.45 g of titanium acid, mp 143-144 ° G. Analysis. Found: C = 63.0, H = 4.1, N = 3.9 Calculated: C 18 H 14 Cl NO 2 S, C = 62.9, H = 4.1, N = 4.1%. Example LXXXVI. 4- (p-Fluorophenyl) -55 -2-phenylthiazQ-5-acetic acid. A mixture of β - 72 562 35 36 -bromo - N - (p-fluorobenzoyl) propionic acid (10.0 g and thiobenzamide (5.0 g) in dimethylformamide (10 ml) is heated at 70 ° C for 2 hours, poured into water (500 ml) and the mixture is left to stand overnight, the solid is filtered off, washed well with water and, after drying, recrystallized from benzene to give 7.49 g of titanium acid, mp 173-174 ° C. Analysis. Found: C = 65 , 1, H = 3.8, N = 4.8, S = 10.1. Calculated for C17H12FNO2S, C = 65.2, H * = ¦ 3.9, N = 4.5, S = 10.2 %. Example LXXXVII. 2- (p-Chlorophenyl) -4- (p-fluoro-phenyl) -thia, zolyl-5-acetic acid Mixture of 1-bromo-1 - (p-fluorobenzoyl) propionic acid (10.0 g) and p-chlorothiobenzamide (6.25 g) in dimethylformamide (10 ml of U is heated at 70 ° C for 2 hours, poured into water (500 ml) and the mixture is left overnight. The solid is filtered off and washed well with suction. water, and after drying it recrystallizes from benzene to give 4.3 g of titanium acid, m.p. enia 196—197 ° £. Analysis. Found: C = 38.85, H = 3.3, Cl = 9.9, N = 4.2, S = 9.2. Calculated for C17H11CirNO2S, C = 58.7, H = 3.2, Cl = 10.2, N = 4.0, S = 9.2%. Example LXXXVIII. 4- (p-bromophenyl) -2- (p-chlorophenyl) -thiazolyl-5-acetic acid. A mixture of 4-bromo-2-(p-bromobenzoyl) propionic acid (5.04 g) and p-chlorothiobenzamide (1.67 g) in dimethylformamide (10 ml) is heated at 70 ° C for 2 hours. , poured into water (500 ml) and left the mixture overnight. The solid product is filtered off, washed well with water and, after drying, recrystallized from benzene, yielding 1.42 g of titanium acid, m.p. 206-207 ° C. Analysis. Found: C = 49.7, H = 2.7, N = 3.5. Calculated for C17H11BrClNO2S. C = 50.0, H = 2.7, N = 3.4%. Example LXXXIX. 4- (p-Chlorophenyl) -2- (p-methoxyphenyl) -thiazolyl-5-acetic acid. A mixture of p-methoxythiobenzamide (8.4 g) and 1-bromo-1M p-chlorobenzoyl) propionic acid (14.6 g) in dimethylformamide (30 ml) is heated at 70 ° C. for 2 hours. The solution is then poured into ice-water to give a yellow solid which dissolves in excess sodium carbonate solution. Acidification with concentrated hydrochloric acid causes the precipitation of a precipitate which is filtered off, dried and recrystallized from ethyl alcohol to give a product having a melting point of 173-174 ° C (13.0 g). Analysis. Found: C = 60.0, H = 3.8, N = 3.8. Calculated for C 18 H 14 ClNO 3 S. C = 60.1, H = 3.9, N = 3.9%. Example XC. 4- (p-Chlorophenyl) -2- (p-dimethylaminophenylthiazolyl-5-acetic acid Mixture of ff-bromo-jff- (p-chlorobenzoyl) propionic acid (5.8 g) and p-dimethylaminothiobenzamide (3.6 g) in dimethylformamide (5.0 ml) is heated at 80 ° C for 1 hour, then poured into water and the mixture is left overnight. The solid product is filtered off, washed well with water and, after drying, recrystallized from ethanol. Mp to yield the title acid (2.8 g), mp 205-207 ° C. Analysis Found: C, 61.3, H = 4.7, N = 7.4. Calculated for C 19 H 17 ClN 2 O 2 S. C = 61.2, H = 4.6, 5 N = 7.5%. Example XCI. 4- (p-bromophenyl) -2-phenylthiazolyl-5-acetic acid. A mixture of thiobenzamide (3.43 g) in dimethylformamide (10 mL) and s2-bromo-N - (p-bromobenzoyl) propionic acid (8.4 g) was heated at 80 ° C for 1 hour, then poured into water and left overnight. wash, wash well with water and dry to obtain 1.86 g of titanium acid, melting point enia 178-180 ° C. 15 Analysis. Found: C = 54.9, H = 3.1, N = 3.9, S = 8.7, Br = 20.3. Calculated for C17H12BrNO2S. C = 54.55, H = 3.2, N = 3.75, S = 8.75, B = 21.35%. Example XCII. 2,4-di- (p-chlorophenyl) -thiazolyl-5-propionic acid. A mixture of 4 * bromo-4- (p-chlorobenzoyl) butyric acid (5.9 g) and p-chlorothioibenzamide (3.4 g) in dimethylformamide (10 ml) was heated at 95 ° C for 18 hours and then poured into water and left the mixture overnight. The solid is filtered off, washed well with water, dried, and recrystallized from a mixture of ethyl acetate and petroleum ether (bp 60-80 ° C) to give 3.3 g of the title acid, mp 179-181 ° C. .Analysis. Found: C = 57.1, H = 3.3, N = 3.4. Calculated for C 18 H 13 Cl 2 NO 2 S, C = 57.2, H = 3.5, N = 3.7%. Example XCIII. 5- (p-Chlorophenyl) -2-phenylthiazolyl-4-acetic acid ethyl ester. A mixture of 4-bromo-4- (p-chlorophenyl) -3-oxo-butyric acid (15.5 g) 0.048 mol), thiobenzamide (6.6 g, 0.048 mol) and anhydrous sodium carbonate (2 6 g) 0.048 equiv) in ethyl alcohol (60 ml) is heated to reflux for 3 hours and then evaporated to dryness under reduced pressure. 40 The residue is taken up in ethyl acetate, washed with water, dried (MgSO 4 and evaporated in vacuo to give 10.3 g of thiazole ester, mp 112-114 ° C (from ethyl alcohol). Analysis Found: C = 64.1. H = 4.5, N = 3.8. Calculated for C19H16C1NO2S. C = 63.75, H = 4.5, N = 3.9%. Example XCIV. Acid 5- (p-chlorophenyl) -2- -phenylthiazolyl-4-acetic acid A solution of 5- (p-chlorophenyl) -2-phenylthiazolyl-4-acetic acid ethyl ester (5.0 g, 0.014 mol) in hot ethyl alcohol (30 ml) was treated one portion of a solution of potassium hydroxide (5.0 g, 0.09 mol) in water (5 ml) and left at room temperature for 16 hours. After dilution with water (50 ml) and acidification with concentrated hydrochloric acid, a precipitate is obtained light yellow in color, which is filtered off, washed with water, dried and recrystallized from benzene to give 2.3 g of thiazole acid, mp 202.5-204.5 ° C. 60 Analysis Found: 62 , 1.1, H 3.6, N = 4.3. Calculated for C 17 H 12 ClNO 2 S. C = 61.9 , H = 3.7, N = = 4.25%. Example XCV. 3- (4,5-Di-) 1β-chlorophenyl (oxazolyl-2) propionic acid. A mixture of 4,4'-di-chlorobenzoin (3.85 feg) (obtained method described on 72562 sft by RE Lutz and RS Murphey, J. Am. Chem. Soc. (1949), 71, 478) and succinic anhydride (4, 0 kg) is suspended in dimethylformamide (6.1) and heated at 110-120 ° C under nitrogen for 2 hours. The solution is poured into a hot 2N hydrochloric acid solution and, after cooling, the aqueous layer is decanted, the organic residue is dissolved in diethyl ether and filtered. The ether paste is washed with water and extracted with 5N sodium carbonate solution. The carbonate extract is washed with ether and then acidified with the ethereal sulfur, washed with water, extracted, dissolved in fresh ether, washed with water, brine, dried with MgSO4 and evaporated to give the hemi-ester of 4,4'-dichlorobenzo-succinic acid as oil (4.13 kg). The hemi-ester (4.13 kg) and ammonium acetate (2 kg) are heated together in glacial acetic acid (5.1) at 100 ° C under nitrogen for 2 hours. to the hot acetic acid solution, hot water (1.7 L) was added and the solution was allowed to cool under nitrogen overnight (17 hours). The crystals formed are filtered off and recrystallized from aqueous acetic acid under nitrogen to give 3- (4,5-di-) -p-chloro-phenyl (-oxazolyl-2) propionic acid in the form of colorless crystals (1.70 kg). ) with a melting point of 192 ° C. Analysis. Found: C = 59.8, H = 3.6, N = 3.9 Calculated for C 18 H 13 Cl 2 NO 3. C = 59.7, H = 3.6, N = 3.9%. After the reaction, the mother liquor is evaporated, the residue is dissolved in ether and the ether extract is extracted with a normal N sodium hydroxide solution. The basic solution is washed with ether and then acidified with concentrated hydrochloric acid to give a white solid which is recrystallized from a mixture of benzene and kerosene with a boiling point of 60-80 ° C to obtain colorless needles of N- (1,2-di-) acid monoamide. p-chlorophenyl (ethanoneT2) succinic (1.25 kg), mp 161-162 ° C. Analysis. Found: C = 57.0, H = 4.0, N 3.9. Calibrated for C18H15Cl2NO4. C = 56.9, H = 4.0, N = = 3.7%. The above-mentioned iff-carbamylpropionic acid (50 g) is dissolved in concentrated sulfuric acid and the solution is stirred at 40-50 ° C for 2 hours. The solution is then poured onto ice, the resulting solid product is filtered off and recrystallized from aqueous acetic acid to obtain colorless needles of 3- (4,5-di) p-chlorophenyl (-oxazolyl-2) propionic acid (19.3 g) having a melting point of 192 ° C. Example XCVI. 3- (4,5-di-) p-chlorophenyl- (oxazolyl-2) propiamide. To the propionic acid solution of the example 97 (19.0 g). 5.7 g of ethyl chloroformate are added dropwise at 0 ° C. in a mixture of triethylamine (8 ml), dry tetrahydrofuran (170 ml) and dry dioxane (170 ml) at 0 ° C. The mixture is stirred for 30 minutes at 0 ° C. and then allowed to warm to room temperature for 1 hour. Then 10.0 ml of 0.980 ammonia solution is added and the mixture is stirred at room temperature for 17 hours and then poured into water to give a white solid. The solid is dissolved in ethyl acetate and washed with saturated acid sodium carbonate, brine, dried over MgSO 4 and evaporated to give a solid. After recrystallization from aqueous ethanol, white amide crystals (8.8 g) are obtained, m.p. 161-162 ° C. Analysis. Found: C = 59.9, H = 3.9, N = 7.6. Calculated for C18H14Cl2N2O2. C = 59.9, H = 3.9, N = 7.8%. 10 Example XCVII. 3- (4,5-Di) p-Chlorophenyl (oxazolyl-2) propionic acid ammonium salt b. 5 g of 3- {4,5-di-) p-chlorophenyl (oxazolyl-2-propionic acid) are dissolved in hot absolute ethanol (200 ml) and an excess of 0.880 ammonia solution is added. After 10 minutes of stirring, a white precipitate is filtered off, washed with ethanol and dried The solid product is crystallized from ethanol containing 0.8% ammonia to give colorless crystals of the ammonium salt (2.80 g), m.p. 192 ° C. 20 Analysis Found: C = 57.3 , H = 4.1, N = 7.0. Calculated for C18H16C12N2O3, C = 57.0, H = 4.25, N = 7.4%. Example XCVIII. Sodium salt of acid 3- &Lt; 4,5- -di-) p-chlorophenyl (oxazolyl-2) propionic acid. 25 A mixture of 3- (4,5-di-) p-chlorophenyl (oxazolyl-2) propionic acid (20.0 g), diethyl ether (400 ml) and sodium hydroxide (3.0 g) in water (40 ml) is stirred for 5 minutes, then the solid is filtered off, washed with ether and crystallized from hot water to give a colorless powder (20.2 g), m.p. 301-303 ° C. Analysis. Found: C = 54.7, H = 3.2, N = 3.6. Calculated for C 18 H 12 Cl 2 N Na 3. 1/2 H20. C = 55.0, H = 3.3, N = 3.6%. 35 Example XCIX. Salt of ethanolamine and 3- (4,5-di-) p-chlorophenyl (oxazolyl-2) propionic acid. 20.0 g of 3- (4,5-di-) p-chlorophenyl (oxazolyl-2) propionic acid are dissolved in methylene chloride (100 ml) and 3.4 g of ethanolamine are added. The solution is stirred at room temperature for 3 minutes and the resulting white solid is filtered off and crystallized twice from a chloroform-petroleum ether mixture (bp 40-60 ° C 45 containing traces of ethanolamine to give a colorless solid, m.p. 115 ° C. Analysis Found: C = 56.6, H = 4.7, N = 6.4 Calculated for C 20 H 20 Cl 2 N 2 O 2 C = 56.75, H = 4.8, 50 N = 6.6%. PL PL

Claims (13)

1. Claims 55 1. Process for the preparation of new heterocyclic aromatic compounds of general formula I, optionally in the form of pharmaceutically acceptable acid addition salts of these compounds, in which formula X is oxygen or sulfur, R1 and R2. are the same or different and represent unsubstituted phenyl radicals, a phenyl radical substituted with one or more halogens, lower alkyl, lower alkoxy, substituted amino or lower halogenalkyl radicals or unsubstituted naphthyl radicals, or A pyridyl radical and R8 is a radical prcetolancucnpwege or a branched aliphatic acid containing 2 ^ 6. carbon atoms in, lancuclui, or their derivatives, such as salt, esber, amj & juk derivative of hydroxamic acid, where the radicals H1, R2 and R8 are at positions, 2, A, and containing 1 ^ 6-carbon atoms characterized in that a halogenated cetorium of the general formula: 29, is carried out, in which Hal is a halogen atom, i.e. an amide. with the general formula 3% or amlelem. and generally on the level of 31 or their * ola, in a neutral alkaline or acidic condition in presence; or. , not © be $ Aosci, solvent; or cy & Erase. k € lj * | invd. .0 of the general formula 32 or its isomers and mimic isomers of formula 33 or 34 by teh. a cyclizing agent that releases oxygen and \ xb.s ^ ke ,: What, like acid. sulfur, phosphorus pentochlide, hydrogen sulphide, phosphorus pentosulphide, phosphorus phosphorus or. phosphorus pentoxide in walunjsaclj; acidic acids in the presence or absence of a solvent, or by reacting the general ketester with ammonia, urea or anionic soybean in an inert, acidic or alkaline medium, in the presence or absence of a solvent, or by reacting a monolith. 4 wuke.ton of general formula 36 with the aldehyde of formula RC.TCHQ w; in an acidic environment to give the snitron of the general formula 37, which is gradually reduced by treatment with phosphorus trichloride in the presence or absence of a solvent; - or by reacting bydoxyketone with general formula 38 with a nitrile of general formula RC-CN in the presence of a mineral acid such as sulfuric acid; or by reacting a-annoketone of general formula 38 or a salt thereof, with an iminoether of general formula 40 in an acidic environment, where the substituents Ra, BP and Rc are selected from R1, R * and R4, where R * and R2 are as defined above and R4 has the same meaning as R8 or is a radical precursor, which is easily transformed by known methods in R3, such as cyanoalkyl, malonic ester, hydroxyalkyl, alkylcarbonainide, alkanoiccarboxyalleyl, diazoketone, subhaloalkyl, formyl, metal carboxyl, alkali or an acrylic acid residue, and if necessary, when ft4 is not the same as R8, one R8 group is transformed into another R8 group by generally known methods such as hydroxamation, esterification, amidation, hydrolysis, alcoholysis, chain ignition, oxidation, carbon dioxide scavenging or reduction, and if desired, converting a compound of formula I to a pharmaceutically acceptable acid addition salt. 2. The method according to claim 1r, characterized in that in the case of the preparation of a thiazole of the general formula; optionally in the form of pharmaceutically acceptable acid addition salts thereof, in which formula X is sulfur and R1, RM and R8 are in the 2f, 4 and 5 positions, respectively, that is, the ovitphazole of the general formula II, wherein R1 and R2 are : Same or different, and each is non-i * substituted with one or two halogens, methyl, methoxyl, 4mmethylamino, or trifluoromethyl or? a thienyl radical and R 8 is the rhodnife of acetic acid or n-propionic acid; there are * £ reactions of the halo ketone in general; nJiftiiie £ 9, wi, which. R * represents, R * vm ~ H ^ n means -R4, whereby R4 has the same ** meaning as -R * or the equivalent halogen ketone in general formula 3 with thioaride of general formula 30, wherein Rc is R1 representing a thioamide of general formula 4 or 5 in which R4 is other than an acetic acid or acid radical; nypropionic acid and transforming it into such a radical known * way, t • • • 3. A process according to claim 1, characterized in that for the preparation of oxazole, the general Formula I and optionally in the form of pharmaceutically acceptable acid addition salts thereof, in which formula X represents an oxygen atom and -R1, R8 and R8 are respectively in the 4, $ -12 positions, i.e. oxazole of the general formula where R1 and R2 are the same or different and represent an unsubstituted phenyl radical or a substituted phenyl radical with one or two chloro atoms. Mayor, group. methyl, methoxyl, dimethid-amino or trifluoromethyl residue or thienyl radical, and R8 is acetic acid or n-propionic acid radical, ketester reactions of general formula 35 are carried out, where "Ra and r are the same or different and denote respectively R2 and R1. And Rc is R4, which has the same attachment as R8, or represents a radical convertible to R8, which is a compound of general formula 41, in which R4 is other than acetic acid and n -propionic and transforming it into such a radical, known way. • -¦'- " 4. The method according to p. For the preparation of oxazole having the general formula 1 and optionally in the form of pharmaceutically acceptable acid addition salts thereof; wherein; the formula X represents an oxygen atom, R1, R2 and R8 are in the 4, 5 and -2 positions, respectively, - the j ^ t of the oxazole of the general formula 14 in which R1 and R * are the same or different and represent an unsubstituted phenyl radical or a phenylic radical substituted with one or two halogens, methyl, methoxyl, dimethylamino or trifluoromethyl groups, or a thienyl radical and R * is an acetic acid or a 'n-ro' vertical acid radical, hydroxy ketabm reactions of general formula 38 are carried out, in which Ra and Rb: are the same or different and represent R2V- ^ R1, respectively, representing a hydroxy ketone of the general formula: W with a nitrile of formula RC-CN, in which Rc is R4 which has the same meaning as R8 or is a radical which can be converted into R8, * tO is a nitrile of the formula R4-CN, where when K4 is a radical other than the acetic or n-propionic acid radical it is transformed into such a radical in a known manner. - --l: ".? '¦ • 5. The method according to p. According to claim 1, characterized by; In the case of the preparation of oxazole of the formula I and, if appropriate, in the form of a phenyl substituent in the form of a phenyl radical, the pharmaceutically acceptable acid addition salt thereof, wherein X represents an oxygen atom. R1, R2 and R3 are in the 4-, 5- and 2- positions, respectively, i.e. the oxazole of the general formula wherein R1 and R2 are the same or different, and each is an unsubstituted phenyl radical or a phenyl radical substituted with one or with two halogens, a methyl group, a methoxy group, a dimethylamino group or a trifluoromethyl group, or the thienyl radical, and R3 is an acetic acid or n-propionic acid radical, the α-aminocetone of the general formula 39 is reacted, in which Ra and Rb are the same or different and are respectively with R2 and R1, that is, a -amino ketone of general formula 42 with an iminoether of general formula 40 in which Rc is R4, which has the same meaning as R3 or is a radical which can be converted into R3, ie the iminoether of formula 20, whereby when R4 is different from the acetic acid or n-propionic acid radical, it is converted to such a radical in a known manner. 6. The method according to p. For the preparation of oxazole of general formula I and optionally in the form of pharmaceutically acceptable acid addition salts thereof, in which formula X is oxygen, R1, R2 and R8 are in the 4-, 5- and 2-, i.e. oxazole of general formula 14, in which R1 and R2 are the same or different and represent an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogens, a methyl, methoxy, dimethylamino or trifluoromethyl radicals or a thienyl radical and R3 is acetic acid or n-propionic acid radical, "the cyclization of an oxygen donor cyclizing agent and a compound represented by the general formula 32 in which Ra and Rb are the same or different and are R2 and R1, respectively, and Rc is R4, are carried out. which has the same meaning as R3 or is a radical convertible to R3, i.e. a compound of the general formula 19, with the proviso that when R4 is other than acetic acid or n-propionic acid, and for example it is evolved in such a radical manner. 7. The method according to p. A process as claimed in claim 1, characterized in that for the preparation of oxazole of general formula I and optionally in the form of pharmaceutically acceptable acid addition salts thereof, in which formula X is sulfur, R1, R2 and R3 are in the 2-, 4- and 5-position - respectively, it is a thiazole of general formula II, in which R1 and R2 are the same or different and represent an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogens, a methyl, methoxy, dimethylamino group or trifluoromethyl residues or a thienyl radical, and R3 is an acetic or n-propionic acid radical, the cyclization reactions are carried out using a sulfur donor cyclizing agent and a compound of the general formula in which Rc and Rb are the same or different and represent R1 and R2, respectively, and Ra is R4, which has the same meaning as R3 or is a radical convertible to R3, that is a compound of the general formula 43, with the proviso that when R4 is other than acetic acid or n-propio, 35 40 50 55 new, it is transformed into such a radical known method. 8. The method according to p. 3. A process as claimed in claim 1, characterized in that for the preparation of a thiazole of the general formula I and optionally in the form of pharmaceutically acceptable acid addition salts thereof, in which formula X represents a sulfur atom, RJ, R2 and R3 sa in the 2-position. , 5- and 4-respectively, i.e. a thiazole of the general formula 9, in which R 1 and R 2 are of the same or different nature and represent an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogens, methyl, methoxy, dimethylamino groups or the rest With trifluoromethyl or the thienyl radical R 3 is an acetic or n-propionic acid radical, a halogen ketone of the general formula 29 is reacted in which Ra is R2 and Rb is R4 which has the same meaning as R3 or is a radical convertible to R3 is a halo ketone of formula VII with a thioamide of general formula in which Rc is R1, that is to say, a thioamide of formula II, whereby when R4 is other than acetic or n-propionic acid radical, the get him in such a radical by a known method. 9. The method according to p. A process as claimed in claim 1, characterized in that, for the preparation of compounds of general formula 1 and optionally in the form of pharmaceutically acceptable acid addition salts thereof, in which formula X is sulfur, R1, R2 and R3 are in the 4-, 5- and 2-positions - suitably, that is, a thiazole of the general formula in which R1 and R2 are the same or different and represent an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogens, methyl, methoxy, dimethylamino or trifluoromethyl residues or the radical thienyl and R3 is an acetic acid or n-propionic acid radical is carried out by reacting a halogen ketone of the general formula 29 in which Ra and Rb, which may be the same or different, represent R2 and R1 respectively, that is, a haloketone. of general formula 11 with a thioamide of general formula in which Rc is R4 which has the same meaning as R3 or is a radical convertible to R3, i.e. a thioamide of general formula 44, where R4 is different y than the acetic acid or n-propionic acid radical, it is transformed into such a radical in a known manner. 10. The method according to p. 3. The process of claim 1, wherein, for the preparation of the compound of general Formula 1 and optionally in the form of pharmacologically acceptable acid addition salts, wherein X is oxygen and R1 is in position 2, R2 is in position 5, R3 in position 4, wherein R1 and R2 are the same or different and represent an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogen atoms, a methyl, methoxyl group, dimethylamino or trifluoromethyl residue or a thienyl radical, and R3 is a radical acetic acid or n-propionic acid, a compound of formula 29 where Ra and Rb are R2 and R4 where R4 has the same meaning as R3 or is a radical giving R3, i.e. the compound of formula 7 is reacted with an amide of general formula 3172S6Z 44 or a salt thereof, in which Rc is R1, that is, an amide of formula 8, in which, if R4 is other than acetic or n-propionic acid radical, it can be converted to such a radical in a known manner. 11. The method according to p. 2. The process of claim 1, wherein for the preparation of the compound of general formula I and optionally in the form of pharmacologically acceptable acid addition salts, wherein X is oxygen, R1 is in position 2, R2 is in position 4 and Rs in position 5, where R1 and R2 are the same or different and represent an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogen atoms, a methyl or methoxy group, a dimethylamino or trifluoromethyl residue or a thienyl radical and R3 is an acetic acid radical or n-propionic, a haloketone of general formula 29, in which Ra and Rb are R2 and R4, respectively, where R4 has the same meaning as R3 or is a radical capable of converting to Rs, i.e. a compound of formula III, is reacted with an amide of general formula 31 or a salt thereof in which R c is R 1, i.e. with an amide of formula 8, and when R 4 is other than acetic or propionic acid, it is converted to such a radical in a known manner man. 12. The method according to p. 3. A compound according to claim 1, characterized in that, for the preparation of the compound of formula I, and optionally in the form of its pharmacologically unacceptable acid addition salts, in which formula X is oxygen and R1 is in the 2-position, R2 is in the 5-position. and Rs in position 4, with R1 and R2 being the same or different and representing an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogen atoms, a methyl or methoxy group, a dimethylamino or trifluoromethyl residue, or thienyl radical and R8 is acetic acid or n-propionic acid radical, a compound of general formula 32 in which Ra and Rb are R4 and R2, respectively, where R4 has the same meaning as R3 or represents a radical convertible to a radical R 3 and R c is R 1, that is, a compound of the general formula 6, where if R 4 has a meaning other than acetic acid or n-propionic acid radical, it is converted to this radical in a known manner. 13. The method according to p. A compound according to claim 1, characterized in that, for the preparation of the compound of general formula I, and optionally in the form of its pharmacologically acceptable acid addition salts, wherein X is oxygen and R1 is in position 2, R2 is in S position. R3 in position 4, with R1 and R2 being the same or different and representing an unsubstituted phenyl radical or a phenyl radical substituted with one or two halogens, a methyl or methoxy group, a dimethylamino or trifluoromethyl residue, and R3 is an acetic acid or n -propionic acid, reacting an oxygen-giving cyclizing agent with a compound of Formula 33, where Ra and Rc are the same or different, and are R2 or R1, respectively, and Rb is R4, which has the same meaning as R3 or is a radical that can be converted to such a radical, that is, to a compound of the general formula and, if R 4 is not an acetic or n-propionic acid radical, converts it into such a radical in a known manner. ® R * Hzor {R * R * Hxir & R ^ -CH-C-R * Na o Hzor 3 s and I Vzor4 SH Rf-C— nh 4 Hzor 5 R * - 'CH-R * Hzir 6m. i2p, 3 72562 MKP C07d 91/32 • Ul O Hzor 7 '- l-HH, Hzor 8 Hzor 9 UR * Hzor 40 R1-CH-C -R * IIH * lo Uzir U c ^ * ^ c R4 R1 Hzor U SH JW 6 yNH4 Uzir 45 n R5 Hzor t4 R - CH - C - RIU OH O Hzor 46 OR * O / li I II and R ^ -CO-CH - C - R * Hz6r /? KI. 12p, 3 72562 MKP C07d 91/32 O ^^ M Hzor ii CH5 H * 6r {8 R - C - CH —R * II i 0 NH i CO // zoV tf 4 SR —C NH ^ OoUil Hzor 20 V- Boron Zl RC NH2 R ^ -C - CH-R * I) IOH «1 Wior 2Z * 1s. OH R, C ^ NH R * C CH Rz 0V NH V V MODEL 23 R? CH C R4 0 NH R 'MODEL 24 MODEL 25 R * - C C R «0 NOH MODEL 26KI. 12p, 3 72562 MKP C07d 91/32 R * CH C R * NH V R2 C CH R4 R 'MODEL 27 R, MODEL 28 R- CH C R k Hal O MODEL 29 R -— c; NH, = 5 = Re c R «c ^ * HH FORMULA 30 FORMULA 31 Ra C CH Rb O NH / / c \ FORMULA 32 R- CH C Rb O NH Ra CH C Rb OO \ C ^ = NH FORMULA 33 CH C Rb OO \ - Re DESIGN 34 DESIGN 35KI. 12p, 3 72562 MKP C07d 91/32 R ° CC Rb O NOH FORMULA 36 rt -— ch cr "OH OO, N. FORMULA 37 FORMULA 38 R- C CH Rb O NH, p - c ^ NH" O Alkyl MODEL 39 FORMULA 40 r * —ch —— c — r 'oo FORMULA 41 R * C CH R' O NHi FORMULA 42 R4 C -CH R * O NH / \, R1 FORMULA 43. SH R4 CX ^ R «—C ^ NH NHZ MODEL 44 PL PL