MXPA00005232A - Thienopyrimidines - Google Patents

Abstract

The invention relates to thienopyrimidines of formula (I) wherein R1, R2, R3, R4, X and n have the meanings given in claim 1, and to their physiologically compatible salts. Said thienopyrimidines and their salts display a phosphodiesterase V-inhibition and can be used for treating diseases of the cardiovascular system and for treating and/or as a therapy for disturbances in potency.

Description

TIENOPIRIMIDINAS Description of the invention: The invention relates to the compounds of formula wherein R1, R2 independently represent H, A or Hal, with one of the radicals R1 or R2 being always? H, R1 and R2 together, also represent alkylene of 3 to 5 carbon atoms, R3, R4 independently represent H, A, OA or Hal, R3 and R together, also represent alkylene of 3 to 5 carbon atoms, -O-CH2- CH2-, -0-CH2-0- or -0-CHz-CH2-0-, represents Rs or R6 monosubstituted with R7, represents straight or branched chain alkylene © and from 1 to 10 carbon atoms, in which or two CH2 groups can be replaced by -CH = CH-, or -CsH4- (CH2) m- groups, represents the alkyl-alkylene-alkylene of 6 to 12 carbon atoms, REF .: 119584 R 'represents COOH, COOA, CONH2, CONHA, CON (A) 2 or CN, A represents alkyl of 1 to ß C atoms, Hal represents F, Cl, Br or I m is 1 6 2 and n is 0, 1, 2 or 3, and their salts acceptable from the physiological point of view. Derivatives of pyridine are known, for example, from European Patent No. 201,188 or from World Patent No. 93/06104. The aim of the invention was to develop new compounds with valuable properties, in particular compounds that can be used in the manufacture of medicines. It was found that the compounds of formula I and their salts are well tolerated and possess very valuable pharmacological properties. In particular, these compounds show a specific inhibition of cGMP-phosphodiesterase (FDE V). Quinazolines with an inhibitory activity of cGMP-phosphodiesterase are described, for example, in J.-Med.Che. 36, p.3765 (1993) and in ibid.37, p. 2106 (1994). The biological activity of the formula I compounds can be determined, for example, according to the methods described in world patent No. 93/06104. The affinity of the compounds of the invention for the GMPc- and AMPc-phosphodiesterase is determined by means of the ICso values (concentration of the inhibitor necessary to reach a 50% inhibition of the enzymatic activity). The determinations can be carried out according to known methods and using isolated enzymes (eg W. J. Thompson et al., Biochem 1971, 10, page 311). To carry out the tests, a modified batch method of W.J. Thompson and M.M. Apple an (Biochem., 1979, 18, p.5228). Therefore, the compounds are suitable for the treatment of diseases of the cardiovascular system, in particular of heart failure, and for the treatment and / or therapy of potency disorders (erectile dysfunction). The use of the substituted pyrazolopyrimidinones for the treatment of impotence is described, for example, in World Patent No. 94/28902. The compounds are effective as inhibitors of the contractions induced by phenylephrine in rabbit cavernous body preparations. This biological activity can be checked, for example, according to the method of = crypto by F. Holmguist et al. in J. Urol., 150, pp. 1310 to 1315 (1993).

The efficacy of the compounds of the invention for the therapy and / or the treatment of the potency disorders is demonstrated through the inhibition of the contraction. The compounds of formula I can be used in medicine and veterinary medicine as active substances of the medicaments. They can also be used as intermediate products in the preparation of other active substances of medicines. Accordingly, the compounds of formula I and also a process for preparing the compounds of formula I, according to claim 1, and their salts, are a subject of the invention, characterized in that a) a compound of formula II is reacted wherein R1, R2 and X have the indicated meanings, and L represents Cl, Br, OH, SCH3 or an esterified and reactive OH group, with a compound of formula III, where R3, R4 and n have the indicated meanings, or b) in a compound of formula I a residue X is transformed into another residue X either, for example, by hydrolyzing an ester group to a COOH group or by transforming a COOH group into an amide or a cyano group, and / or by transforming a compound of formula I into one of its salts. The residues R1, R2, R3, R4, R5, Re, R7, X, L and n that appear in this text have the meanings indicated for the formulas Z, II and III, unless otherwise indicated. A represents alkyl of 1 to 6 carbon atoms. In the formulas indicated, the alkyl moiety preferably has a straight chain dl, 2, 3, 4, 5 or 6 carbon atoms and preferably represents methyl, ethyl or propyl, then preferably isopropyl, butyl, isobutyl, sec-butyl or tertbutyl, but also n-pentyl, neopentyl, isopentyl or hexyl. X represents a Rs or Re residue monosubstituted with R7 represents a straight or branched chain alkylene radical of 1 to 10, preferably 1 to 8 carbon atoms, with alkylene radical being preferred, for example, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, pentylene, 1-, 2- or 3-methylbutylene, 1,1-, 1,2- or 2,2-dimethylpropylene, 1-ethylpro-pylene, hexylene, 1-, 2-, 3- or 4-methylpentylene, 1 , 1-, 1,2-, 2,2-, 2,3- or 3,3-dimethylbutylene, 1- or 2-ethylbutylene, 1-ethyl-1-methylpropylene, l-ethyl-2-methylpropylene, 1, 1,2- or 1,2,2-trimethyl-ropylene, straight or branched chain heptylene, octylene, nonylene or decylene. R5 also represents, for example, 2-butenylene or 3-hexenylene. Rs represents cycloalkylalkylene of from 6 to 12 C atoms, preferably, for example, cyclopentylmethylene, cyclohexylmethylene, cyclohexylethylene, cyclohexylpropene or cyclohexylbutylene. One of the radicals R: or R2 preferably represents H, while the other preferably represents propyl or butyl, but in particular preferably ethyl or methyl. R1 and R2, together, also preferably represent propylene, butylene or pentylene. Hal preferably represents F, Cl or Br, but also I. The residues R3 and R4 may be the same or different and are preferably in the 3 or 4 position of the phenyl ring. For example, they independently represent H, alkyl, F, Cl, Br or I, or together represent an alkylene such as, for example, propylene, butylene or pentylene, and then also ethyleneoxy, methylenedioxy or ethylenedioxy. Each may also preferably represent alkoxy such as, for example, methoxy, ethoxy or propoxy. The rest R5 preferably represents, for example, COOH, COOCHs, COOCzHs, CONH2, CON (CH3> 2 / CONHCH3 or CN.) All the residues that appear repeatedly in the present invention can be the same or different, ie Accordingly, a particular object of the invention are those compounds of formula I in which at least one of the mentioned moieties has one of the preferred meanings indicated above, Some preferred groups of compounds can be represented by the partial formulas the a Id that are indicated below, which correspond to the formula I and in which the remains that are not explicitly detailed have the meaning indicated for the formula I, namely: in the X represents Rs or Rs substituted with COOH or COCA, in 'Ib R1, R2 independently represent H, A or Hal, being at least one of the radicals Rx or R2 always? H, R3 and R4, together, represent alkylene of 3 to 5 atoms e C, -O-CH2-CH2-, -0-CH2-0- or -0-CH2-CH2-0-, represents Rs or Rs substituted with COOH or COOA; in R1, R2 independently represent H, A or Hal, with at least one of the radicals R1 or R2 always? H, R3, R4 independently represent H, A, OA or Hal, R3 and R4, together, represent alkylene of 3 to 5 carbon atoms, -0-CH2-CH2-, -0-CH2-0- or -O- CH2-CH2-O-, represents Rs or R6 substituted with COOK or COOA, n is 1 or 2; in Id R1, R2 independently represent H, A or Hal, where one of the residues R1 or R "always? H, R1 and R2, together, also represent alkylene of 3 to 5 C atoms, R5, R4 independently represent H , A, OA or Hal, R3 and R4, together, also represent -O-CK2-0-7 represents R5 monosubstituted with R ', represents straight or branched chain alkylene and from 1 to 10 carbon atoms, or -CßH4 -CH2-, R represents COOH or COOA, A represents alkyl of 1 to 6 carbon atoms, Hal represents F, Cl, Br or I, m is 1 and n is 1 or 2. In general, both the compounds of formula I as the starting substances for their preparation are prepared according to methods known per se, as described in the literature (for example, in certain works such as Houben-Weyl, "Methoden der organische Chemie" (Methods of Chemistry Organic), Georg-Thieme-Verlag, Stuttgart) and under reaction conditions that are known and suitable for the reactions mentioned. It is also possible to make use of known variants of these methods that are not detailed in this text. "In the compounds of formulas II or III, the residues R1, R2, R3, R4, X and n have the meanings indicated, in particular, have the preferred meanings indicated above. When L represents an esterified and reactive OH group, said group is preferably alkylsulfonyloxy of 1 to 6 carbon atoms (preferably methylsulfonyloxy) or aryisulfonyloxy of 6 to 10 carbon atoms (preferably phenylsulfonyloxy or p-tolylsulfonyloxy, then also 2-naphthalenesulfonyloxy) .

The compounds of formula I can be prepared preferably by reacting compounds of formula II with compounds of formula III. If desired, the starting materials can be prepared in situ, but in such a way that instead of isolating them from the reaction mixture they are directly reacted to form the compounds of formula I. Otherwise, it is also possible to out the reaction in stages. In general, the starting compounds of formula II and III are known. If they are not known, they can be prepared according to methods known per se. The compounds of formula II can be prepared, for example, by reaction of P0C1: with compounds obtained from thiophene derivatives and from esters of CN-substituted alkylenecarboxylic acids (Eur. J. Med.

Chem., 23, p. 453 (1988). In particular, the reaction of the compounds of formula II with the compounds of formula III is carried out in the presence or absence of an inert solvent and at temperatures comprised between ca. -20 and approx. 150 °, preferably between 20 and 100 °. It is advisable to add an acid trapping agent, for example, an alkali metal or alkaline earth metal hydroxide, carbonate or bicarbonate or another salt of a weak acid and an alkali metal or alkaline earth metal, preferably a potassium, sodium or calcium salt. It may also be convenient to add an organic base such as triethylamine, dimethylamine, pyridine or quinoline, or an excess of the amine component. As the inert solvent, for example, hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene are suitable; chlorinated hydrocarbons such as trichlorethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or disxane; glycol ethers such as ethylene glycol mono-methyl ether (methyl glycol), ethylene glycol monoethyl ether (ethyl glycol) or ethylene glycol ethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide, N-methylpyrrolidone or dimethylformamide (DMF); nitrii such as acetoni-trile; sulfoxides such as dimethylsulfoxide (DMSO); nitro compounds such as nitromethane or nitrobenzene; esters such as ethyl acetate or mixtures of the solvents mentioned. It is also possible to transform a compound of formula I into a radical X in another radical X, for example by hydrolyzing an ester or a cyano group to a COOH group. The ester groups can be saponified, for example, with NaOH or KOH in water, water-THF or water-dioxane, at temperatures between 0 and 10-0 °. The carboxylic acids can be converted, for example with thionyl chloride, into the corresponding acid chlorides, which in turn can be converted into the corresponding carboxylic acid amides. The latter can be subjected to known methods of water separation to obtain the corresponding carbonitriles. An acid of formula I can be converted into its salt by the addition of a base, for example, by reacting equivalent amounts of the acid and the base in an inert solvent such as ethanol and then concentrating by evaporation. For this reaction it is necessary to take into account in particular the bases that form acceptable salts from the physiological point of view. By using a base (for example sodium or potassium hydroxide or carbonate), the acid of formula I can be converted into its corresponding metal salt, in particular its alkali metal or alkaline earth metal salt, or its corresponding ammonium salt. - For this reaction, organic bases which form physiologically acceptable salts, such as, for example, ethanolamine, are also used. On the other hand, a base of formula I can be transformed into its salt by the addition of an acid, for example, by reacting equivalent amounts of the base and the acid in an inert solvent such as ethanol and then concentrating by evaporation. For this reaction, it is necessary to take particular account of the acids that form salts that are acceptable from the physiological point of view. Therefore, inorganic acids such as, for example, sulfuric acid, nitric acid, hydrocides such as hydrochloric or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulphemic acid, and also acids can be used. organic, in particular, mono- or polybasic aliphatic, alicyclic, -Rypiphatic, aromatic or heterocyclic carboxylic, sulphonic or sulfuric acids, such as, for example, formic, acetic, propionic, pivalic, diethylacetic, aionic, succinic, pimelic acids, fumaric, maleic, lactic, tartaric, malic, citric, gluconic, ascorbic, nicotinic, isonicotinic, methanesulfonic or ethanesulfonic, ethanedisulfonic, 2-hydroxyethane-sulphonic, benzenesulfonic, p-toluenesulfonic, naphthalene-disulfonic and naphine-alenmonosulfonic, lauryl-sulfuric. Salts of physiologically unacceptable acids, for example picrates, can be used to isolate and / or purify the compounds of formula I.

Another object of the present invention is the use of the compounds of formula I and / or their physiologically acceptable salts in the preparation of pharmaceutical preparations, in particular by non-chemical methods. In this way, these compounds can be brought into a suitable dosage form together with at least one excipient or auxiliary solid, liquid and / or semi-liquid product and optionally in combination with one or more different active substances. Another object of the invention are the medicaments of formula I and their physiologically acceptable salts which act as inhibitors of phosphodiesterase v. Also the subject of the invention are pharmaceutical preparations containing at least one compound of formula I and / or one of its salts acceptable from the physiological point of view. These preparations can be used in medicine and veterinary medicine as medicines. Excipients can name organic or inorganic substances which are suitable for enteral (eg oral), parenteral or topical application and do not react with the novel compounds, for example water, vegetable oils the benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate, gelatin, carbohydrates such as lactose and starch, magnesium stearate, talc, petrolatum. For oral administration, tablets, pills, capsules, powders, granules, syrups, juices or drops are mainly used for administration by rectal administration of suppositories, for parenteral administration, solutions, preferably oily or aqueous solutions. , also suspensions, emulsions or implants, and for topical application ointments, creams or powders. The new compounds can also be freeze-dried and the lyophilized products thus obtained can be used, for example, for the preparation of injectable preparations. The aforementioned preparations can be sterilized and / or contain auxiliary substances such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifying agents, salts for influencing the osmotic pressure, pH regulating substances, dyes, flavors and / or one or more substances different active ingredients, for example, one or several vitamins. The compounds of formula I and their physiologically acceptable salts can be used to combat diseases in which an increase in the level of cGMP (cyclic guanosine monophosphate) stops or prevents inflammation and relaxes the muscles. In particular, these compounds can be used for the treatment of diseases of the cardiocirculatory system and for the treatment and / or therapy of potency disorders. In general, the substances are administered in doses between approximately 1 and 500 mg, in particular between 5 and 100 mg per dosage unit. The daily dose preferably ranges from about 0.02 to 10 mg / kg body weight. However, the particular dose for each patient depends on a wide variety of factors, namely: the efficacy of the particular compound being administered, age, body weight, general health, sex, diet , of the moment and of the administration form, of the speed of excretion, of the combination of medications and of the severity of the disease to which the therapy is applied. Oral administration is preferred. -. All temperatures indicated in this text are given in ° C. In the examples that follow, the expression "is worked or treated in the usual manner" means the following: if necessary, water is added, the pH is optionally adjusted to values between 2 and 10 according to the constitution of the final product, it is extracted with ethyl acetate or dichloromethane, the phases are separated, the organic phase is dried over sodium sulfate, concentrated by evaporation and purified by chromatography on silica gel and / or recrystallization.

Mass spectrometry (EM): The (electron impact ionization) M * FAB (fast atom bombardment, "Fast Atom Bombardment"): (M + H) * Example 1 For 5 hours are agitated at 110 ° 1, 9 g of methyl 3- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -propionate [obtained by cyclization of -amino-4, 5, 6, 7-tetrahydrobenzothiophen-3-carboxylic acid methyl with 3-cyanopropionate gives methyl and subsequent chlorination with phosphorus oxychloride / dimethylamino] and 2.3g of 3-chloro-4-methoxybenzylamine ("A") in 20 ral of N-methylpyrrolidone. The solvent is then removed and the mixture is worked in the usual manner. 2.6 g of 3- [4- (3-chloro-4-methoxybenzylamino) -5,6,8,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2 are obtained il] -propionats of methyl in the form of a colorless oil. By analogous reaction of "A" with methyl 3- (4-chloro-5,6-cyclopenteno- [1] -benzothieno- [2,3-d] -pyridin-2-yl) -propionate the 3- [4- (3-Chloro-4-methoxy-benzylamino) -5,6-cyclopentene- [1] -ben? Otieno- [2,3-d] -pyrimidin-2-yl] -propionate from methyl; with methyl 3- (4-chloro-5,6-cycloheptene- [1] -benzothieno-. {2, 3-d] -pyridin-2-yl) -propionate is obtained 3- [4- Methyl 3- (3-chloro-4-methoxy-benzyl) -no) -5,6-cyclohep- teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -propionate; with 3- (4-chloro-β-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -propio-nato methyl, 3- [4- (3-chloro-4-methoxy is obtained methyl-benzylamino) -β-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionate; with 3- (4-chloro-5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) -propionate methyl is obtained 3- [4- (3-chloro-4-methoxy -benzylamino) -5, methyl ß-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionate; with 3- (4-chloro-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -propio-nato methyl is obtained 3- [4- (3-chloro-4-methoxy methyl-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionate; 3- [4- (3-Chloro-4-methoxy-benzylamino) - 3- (4,6-dicyl-thieno- [2,3-d] -pyrimidin-2-yl) -propionate) Methyl 6-chloro-thieno- [2,3-d] -? Irimidin-2-yl] -propionate; with 2- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -acetic acid methyl ester is obtained on 2- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -acetic acid methyl ester. By analogous reaction of 3,4-methylenedioxybenzyl amine with 3- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) - methyl propionate is obtained 3- [4- (3, -methylenedioxy-benzylamino) -5,6,7,8-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin-2- il] -propionate methyl; with 3- (4-chloro-5, β-cyclopenteno- [l] -benzothieno- [2, 3-d] -pyridin-2-yl) -propionate-ethyl, 3- [4- ( Methyl 3, 4-methylenedioxy-benzylamino) -5,6-cyclopentene- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -propionate; with 3- (4-chloro-5,6-cycloheptene- [l] -benzothieno- [2,3-d] -pyridin-2-yl) -propionate methyl is obtained 3- [4- (3 , Methyl 4-methylenedioxy-benzylamino) -5,6-cyclohep- teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -propionate; 3- [4- (3, -methylenedioxy-benzylamino) - is reacted with methyl 3- (4-chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -propio-nato. Methyl 6-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionate; with 3- (4-chloro-5,6-dimethyl-thieno- [2, 3-d] -pyrimidin-2-yl) -prospionate, methyl 3- [4- (3,4-methylenedioxy-benzylamine Methyl) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionate; with 3- (4-chloro-β-ethyl-tieno- [2,3-d] -pyrimidin-2-yl) -propio-nato-methyl, 3- [4- (3,4-methylenedioxy-benzylamine is obtained. Methyl) -6-ethyl-thien- [2, 3-d] -pyrimidin-2-yl] -propionate; with 3- (4,6-dichloro-thieno- [2,3-d] -pyrimidin-2-yl) -propionate methyl is obtained 3- [4- (3,4-methylenedioxy-benzylamino) -6- methyl clsro-thieno- [2, 3-d] -pyrimidin-2-yl] -propionate. By analogous reaction of "A" with 4- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -butanoate methyl is obtained in 4- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butanoate methyl; with 4- (4-chloro-5, β-cyclopenteno- [1] -benzothieno- [2,3-d] -pyridin-2-yl) -butanoate methyl is obtained on 4- [4- (3 -chloro-4-methoxy-benzylamino) -5,6-cyclopentene- [1] -benzothieno- [2,3-d] -pyrimidin-2-ii] -butanoate methyl; with 4- (4-chloro-5,6-cycloheptene- [l] -benzothieno- [2,3-d] -pyridin-2-yl-methylbutanoate yields 4- [4- (3- methyl chloro-4-methoxy-benzylamino) -5, β-cyclohep-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butanoate; with 4- (4-chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -butane-methyl ate yields 4- [4- (3-chloro-4-methoxy -benzylamino) -6-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -butanoate methyl; with 4- (4-chloro-5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) -butanoate methyl, 4- [4- (3-chloro-4-methoxy is obtained. -benzylamino) -5,6-dimethyl-thieno- [2, 3-d] -pyrimidin-2-yl] -butanoate ethyl; with 4- (4-chloro-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -butane-methyl ate yields 4- [4- (3-chloro-4-methoxy -benzyamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -butanoate methyl; with methyl 4- (4, ß-dichloro-thieno- [2,3-d] -pyrimidin-2-yl) -butanoate yields 4- [4- (3-chloro-4-methoxy-benzylamino) - Methyl 6-clso-thieno- [2, 3-d] -pyrimidin-2-yl] -butanoate. By analogous reaction of 3,4-methylenedioxybenzyl amine with 4- (4-chloro-5,6,7,8-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl) - methyl butanoate yields 4- [4- (3, -methylenedixy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2- il] -methylbutanoate; with 4- (4-chloro-5,6-cyclopenteno- [l] -benzothieno- [2,3-d] -pyridin-2-yl) -butanoate methyl is obtained on 4- [4- (3 , Methyl 4-methylenedioxy-benzylamino) -5,6-cyclopenteno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butanoate; with 4- (4-sloro-5,6-cycloheptene- [1] -benzothieno- [2,3-d] -pyridin-2-yl) -butanoate methyl is obtained on 4- [4- (3 , Methyl 4-methylenedioxy-benzylamino) -5, β-cycloheptyl- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butanoate; with methyl 4- (4-chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -butane-ato yields 4- [4- (3, -me, Inedioxy-benzylamino Methyl) -6-methyl-thieno- [2, 3-d] -pyrimidin-2-yl] -butanoate; with 4- (4-chloro-5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) -bu-tanoa or methyl is obtained on 4- [4- (3, 4- Methylenedioxy-benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -butanoate methyl; with 4- (4-chloro-6-ethyl-thieno- [2,3-d] -? irimidin-2-yl) -butane-methyl azole is obtained - 4- [4- (3,4-methylenedioxy) methyl-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -butanoate; with methyl 4- (4,6-dichloro-thieno- [2,3-d] -pyrimidin-2-yl) -butanoate yields 4- [4- (3,4-methylenedioxy-benzylamino) -6- methyl chloro-thieno- [2,3-d] -pyrimidin-2-yl] -butanoate. By analogous reaction of "A" with 5- (4-chloro-5,6,7,8-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl) -valearyl methyl is obtained on 5- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valayl methyl; with 5- (4-chloro-5,6-cyclopenteno- [1] -benzothieno- [2,3-d] -pip-midin-2-yl) -valeriato de methyl, the 5- [4- (3 -chloro-4-methoxy-benzylamino) -5,6-cyclopentene- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; with 5- (4-chloro-5,6-cycloheptene- [1] -benzothieno- [2,3-d] -pyridrithin-2-yl) -valearyl methyl ester, 5- [4- (3 -chloro-4-methoxy-benzylamino) -5,6-cycloheptene- [1] -benzothieno "[2,3-d] -pyrimidin-2-yl] -valearyl methyl; with 5- (4-chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -valearyl methyl, 5- [4- (3-chloro-4-metsx? benzylamino) -6-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; - (4-Chloro-5, β-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) methyl valerate affords 5- [4- (3-chloro-4-methoxy) benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; with methyl 5- (4-chloro-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -vale-riatp you get • 5- [4- (3-chloro-4- methoxy-benzylamino) -β-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; - (4, ß-dichloro-thieno- [2,3-d] -pyrimidin-2-yl) -valearyl methyl is obtained 5- [4- (3-chloro-4-methoxy-benzylamino) - 6-Chloro-thieno- [2,3-d] -pyrimidin-2-yl] -valeryate of methyl. By analogous reaction of 3,4-methylenedioxybenzyl amine with 5- (4-chloro-5, β, 7, 8-tetrahydro- [1] -benzothieno- [2,3-d] -? Irimidin-2-yl) Methyl valerate gives 5- [4- (3,4-methylenedioxy-bepcylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidine- 2-yl] -valentyl methyl; with 5- (4-chloro-5,6-cyclopentene- [1] -benzothieno- [2, 3-d] -pyridin-2-yl) -valentium methyl is obtained on 5- [4- (3 , -methylenedioxy-benzylamino) -5, β-cyclopenteno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; with 5- (4-chloro-5, β-cisloheptene- [1] -benzothieno- [2,3-d] -piri-midin-2-ii) - methylvalerate is obtained on 5- [4- (3 , 4-methylenedioxy-benzylamino) -5, β-cyclohep- • dye- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; 5- (4-Chloro-6-methyl-thieno- [2, -d] -pyrimidin-2-yl) -valearyl methyl ester affords 5- [4- (3,4-methylenedioxy-benzylamino) -6 -methyl-thieno- [2,3-d] -pyrimidin-2-yl] -valearyl of ethyl; - (4-Chloro-5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) -valearyl of methyl, 5- [4- (3,4-methylenedioxy-benzylamine ) -5,6-Dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; with 5- (4-chloro-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -vale-methyl-riet, 5- [4- (3,4-methylenedioxy-benzylamine is obtained. ) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valearyl methyl; - (4,6-Dichloro-thieno- [2,3-d] -pyrimidin-2-yl) -valearyl methyl ester affords 5- [4- (3,4-methylenedixy-benzylamino) -6- chloro-thieno- [2, -d] -pyrimidin-2-yl] -valerate of methyl. By analogous reaction of "A" with methyl 7- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -heptanoate was obtains 7- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl ] -methyl heptanoate; with 7- (4-chloro-5,6-cyclopenteno- [l] -benzothieno- [2,3-d] - iri-midin-2-yl) -methyl heptane gives 7- [4- (3 methyl-chloro-4-methoxy-benzylamino) -5,6-cyclopentene- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; with 7- (4-chloro-5,6-cycloheptene- [1] -benzothieno- [2,3-d] -pyridin-2-yl) -methyl heptane gives 7- [4- (3 -chloro-4-methoxy-benzylamino) -5,6-cycloheptylene- [1] -benzstieno- [2,3-d] -pyrimidin-2-yl] -heptanoate methyl; with 7- (4-chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -heptanoate methyl is obtained 7- [4- (3-chloro-4-methoxy-benzylamino Methyl) -6-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; With 7- (4-chloro-5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) heptanoate methyl, 7- [4- (3-chloro-4-methoxy) is obtained. benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoate methyl; with 7- (4-chloro-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -heptane-ats of methyl is obtained 7- [4- (3-chloro-4-methoxy methyl-benzylamino) -β-ethyl-thien- [2,3-d] -? irimidin-2-yl] -heptanoate; with 7- (4-chloro-β-chloro-thieno- [2,3-d] -pyrimidin-2-yl) -heptanoate methyl is obtained 7- [4- (3-chloro-4-methoxy-benzylamino Methyl) -6-chloro-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoate. By analogous reaction of 3,4-methylenedioxybenzyl-aane with 7- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] - 'pyrimidin-2-yl ) -heptanoafeo of methyl is obtained 7- [4- (3, -methylenedioxy-benzylamino) -5, 6, 7, 8-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin- 2-yl] -heptanoate methyl; with 7- (4-chloro-5, β-cyclopenteno- [1] -benzothieno- [2,3-d] -pyridin-2-yl) -heptanoate methyl is obtained on 7- [4- (3 , Methyl 4-methylenedioxy-benzylamino) -5, β-cyclopenteno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; with 7- (4-chloro-5., 6-cisloheptene- [1] -benzothieno- [2,3-d] -pyridin-2-yl) -heptanoate methyl is obtained on 7- [4- ( 3, 4-methylenedioxy-benzylamino) -5,6-cyclohexetheno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; with 7- (4-chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -heptanoate methyl is obtained 7- [4- (3,4-methylenedioxy-benzylamino) - Methyl 6-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; With 7- (4-chloro-5, β-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl) -heptanoate methyl, 7- [4- (3,4-methylenedioxy-benzylamine is obtained. ) -5, methyl ß-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; with 7- (4-chloro-β-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -heptanoate methyl is obtained 7- [4- (3,4-methylenedioxy-benzylamino) - Methyl 6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoate; with 7- (4,6-dichloro-thieno- [2,3-d] -pyrimidin-2-yl) -heptanoate methyl is obtained 7- [4- (3, -methylenedioxy-benzylamino) -6-chloro -thien- [2,3-d] -pyrimidin-2-yl] -heptanoate methyl. By analogous reaction of "A" with 2- [4- (4-chloro-5,6,7,8-te-trahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-ii) -cyclohexyl-1-yl] -acetic acid methyl ester is obtained on 2-. { 4- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -cycle - hexyl-1-il} methyl acetate; With 2- [4- (4-chloro-β-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -cy-clohexyl-1-yl] -acetic acid methyl ester, 2- is obtained. { 4- [4- (3-Chloro-4-methoxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -cyclohexyl-1-yl} -methyl acetate. By analogous reaction of 3,4-methylenedioxybenzyl amine with 2- [4- (4-chloro-5,6,7,3-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2- il) -cyclohexyl-1-yl] -acetic acid methyl ester is obtained on 2-. { 4- [4- (3, -methylenedioxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -cyclohexyl-1-yl } -methyl acetate. By analogous reaction of benzylamine with methyl 3- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2, 3-d] -pi-rimidin-2-yl-propionate is obtained methyl 3- (4-benzylamino-5,6,7,8-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl) -propionate; with 4- (4-chloro-5,6,7, S-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl) -butanoate methyl is obtained on 4- (4- methyl benzylamino-5, 6, 7, 8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -butanoate; with 5- (4-chloro-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -valearyl methyl is obtained on 5- (4- benzylamino-5, 6, 7, 8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -valearyl ethyl; 4- (4-Chloro-6-methyl-thieno- [2,3-d] -pyrimidin-2-yl) -butane-methyl ester yields 4- r -benzylamino-6-methyl-ene- [2,3-d] -pyrimidin-2-yl] -butanoate methyl; - (4-Chloro-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -valearyl methyl ester affords 5- [4-benzylamino-6-ethyl-thieno- [2] , 3-d] -pyrimidin-2-11] -valentine of methyl. Example 2 2.2 g of 3- [4- (3-clsro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothien- [2, 3-d] are dissolved. ] -pyrimidin-2-yl-methyl-propionate in 20 ml of ethylene glycol monomethyl ether, and after adding 10 ml of 32% NaOH, is stirred for 5 hours at 110 °. 20% HCl is added and then extracted with dichloromethane. After adding petroleum ether, 2.0 g of 3- [4- (3-chloro-4-methoxy-benzylamino) -5, β, 7, 8-tetrahydro- [1] -benzothieno- [2] are obtained. , 3-d] -pi-rimidin-2-yl] -propionic, mp 229 °. The precipitated crystals are dissolved in 30 ml of isoprospanol and then mixed with 0.5 g of ethanolamine. After crystallization, 1.35 g of the ethanolamine salt of 3- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2, 3-d] -pyrimidin-2-yl] -pro-pionic, mp 135 °. The carboxylic acids indicated below are obtained by. Analogous reaction of the esters indicated in Example 1: 3- [4- (3-Chloro-4-methoxy-benzylamir.o) -5,6-cyclopen-dye- [1] -benzothieno- [2,3-] d] -pyrirnidin-2-yl] -propionic; 3- [4- (3-Chloro-4-methoxy-benzylamino) -5,6-cyclohep-teno- [l] -benzothieno- [2, -d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3-Chloro-4-methoxy-benzylamino) -6-methyl-thi-ene- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3-Chloro-4-methoxy-benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3-Chloro-4-methoxy-benzylamino) -β-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3-Chloro-4-methoxy-benzylamino) -β-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -propionic acid; 2- [4- (3-Cl? ro-4-methoxy-benzylamino) -5,?, 7, 8-te-trahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-acid il] -acetic, ethanolamine salt, mp 126 °; 3- [4- (3,4-methylenedioxy-benzylamino) -5, β, 7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3, 4-methylenedioxy-benzylamino) -5,6-cyclopen-teno- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3,4-methylenedioxy-bensylamino) -5, β-cyclohep-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3,4-methylenedioxy-benzylamino) -β-methyl-ti-enc- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3,4-Methylenedioxy-benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3, -methylenedioxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -propionic acid; 3- [4- (3,4-methylenedioxy-benzylamino) -β-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -propionic acid; 4- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3-Chloro-4-methoxy-benzylamino) -5, β-cyclopen-dye- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3-Chloro-4-methoxy-benzylamino) -5,6-cyclohep-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3-Chloro-4-methoxy-benzylamino) -6-methyl-thi-ene- [2,3-d] -pyrimidin-2-yl] -butyric acid, ethanolamine salt m.p. 142 °; 4- [4- (3-chloro-4-methoxy-benzylamino-no) -5,6-dimethyl-thieno- [2, 3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3-Chloro-4-methoxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -butyric acid, ethanolamine salt, m.p. 170 °; 4- [4- (3-Chloro-4-methoxy-benzylamino) -β-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3, -methylenedioxy-benzylamino) -5,6,7,8-te-trahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butyric acid, ethanolamine salt, mp 114 °; 4- [4- (3, 4-methylenedioxy-benzylamino) -5,6-cyclopen-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3,4-methylenedioxy-benzylamino) -5,6-c-clohep-teno- [l] -benzothieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3,4-methylenedioxy-benzylamino) -6-methyl-ti-ene- [2,3-d] -pyrimidin-2-yl] -butyric acid, ethanolamine salt, m.p. 170; 4- [4- (3,4-methylenedioxy-benzylamino) -5, β-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3, 4-methylenedioxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; 4- [4- (3, 4-methylenedioxy-benzylamino) -6-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -butyric acid; - [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,3-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid , pf 165 °; ethanolamine salt, m.p. 112 °; - [4- (3-Chloro-4-methoxy-benzylamino) -5,6-cyclopen-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3-chloro-4-methoxy-benzylamino) -5, β-cyclohep-teno- [l] -benzothieno- [2,3-d] -pyrimidin-2-ii] -valeric acid; - [4- (3-Chloro-4-methoxy-benzylamino) -6-methyl-t-ene- [2, 3-d] -pyrimidin-2-yl] -valeric acid, ethanolamine salt p.f. 156 °; - [4- (3-Chloro-4-methoxy-benzylamino) -5,6-dimethyl-thieno-T 2, 3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3-Chloro-4-methoxy-benzylamino) -β-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valeric acid, ethanolamine salt, m.p. 156 °; - [4- (3-Chloro-4-methoxy-benzylamino) -6-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3,4-methylenedioxy-benzylamino) -5,6,7,8-te-trahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3, 4-methylenedioxy-benzylamino) -5,6-cyclopen-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; 5- [4- (3,4-Methylenedioxy-benzylamino) -5,6-cyclohep-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3,4-methylenedioxy-benzylamino) -6-ptethyl-thio-ene- [2,3-d] -pyrimidin-2-yl] -valeric acid, ethanolamine salt, m.p. 167 °; - [4- (3, 4-methylenedioxy-benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3, 4-methylenedioxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; - [4- (3, 4-methylenedioxy-benzylamino) -β-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -valeric acid; 7- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-te-trahydro- [l] -benzothieno- [2, 3-d] -pyrimidin-2-yl] -heptanoic, ethanolamine salt, mp 130 °; 7- [4- (3-Chloro-4-methoxy-benzylamino) -5,6-cyclopen-dye- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3-Chloro-4-methoxy-benzylamino) -5,6-cyclohep-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3-Chloro-4-methoxy-benzylamino) -6-methyl-thi-ene- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3-Chloro-4-methoxy-benzylamino) -5, β-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3-Chloro-4-methoxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3-Chloro-4-methoxy-benzylamino) -6-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3,4-methylenedioxy-benzylamino) -5,6,7,8-te-trahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid , salt of ethanolamine, mp 137 °; 7- [4- (3, 4-methylenedioxy-benzylamino) -5,6-cycloc-en-teno- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3,4-methylenedioxy-benzylamino) -5,6-cyclohep-dye- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3, 4-methylenedioxy-benzylamino) -6-methyl-thi-ene- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3, 4-methylenedisxy-benzylamino) -5,6-dimethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3, 4-methylenedioxy-benzylamino) -6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 7- [4- (3, 4-methylenedioxy-benzylamino) -6-chloro-thi-ene- [2,3-d] -pyrimidin-2-yl] -heptanoic acid; 2- acid. { 4- [4- (3-chloro-4-methoxy-benzylamino) -5, β, 7, 8-tetrahydro- [1] -benzstieno- [2,3-d] -pyrimidin-2-yl] -cyclohex- il} -acetic; 2- acid. { 4- [4- (3-chloro-4-methoxy-benzylamino) -6-ethyl-ti-ene- [2,3-d] -pyrimidin-2-yl] -cydohexyl} -acetic; 2- acid. { 4- [4- (3,4-methylenedioxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2, 3-d] -? Irimidin-2-yl] -cydohexyl} -acetic; 3- (4-benzylaminor5,6,7,7-tetrahydro- [1] -benzothi-ens- [2,3-d] -pyrimidin-2-yl) -propionic acid, ethanolamine salt, m.p. 126 °; 4- (4-Benzylamino-5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) -butyric acid, ethanolamine salt, m.p. 133 °; - (4-Benzylamino-5,6,7,8-tetrahydro- [l] -benzothi-ene- [2,3-d] -pyrimidin-2-yl) -valeric acid, ethanolamine salt, m.p. 135 °; ' 4- (4-Benzylamino-6-methyl-thieno- [2,3-d] -pyridi-din-2-yl) -butyric acid, ethanolamine salt, m.p. 165 °; - (4-Benzylamino-6-ethyl-thieno- [2,3-d] -pyrimidin-2-yl) -valeric acid, ethanolamine salt, m.p. 162 °. Use 3 1 equivalent of 3- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,3-tetrahydro- [l] -benzothieno- [2, 3-d] - is stirred. ? irimidin-2-yl] -propionic and 1.2 equivalents of thionyl chloride for 2 hours in dichloromethane. Then the solvent is removed and 3- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothi-ene- [2, 3] chloride is obtained. -d] -pyrimidin-2-yl] -propionyl.

It is passed through aqueous ammonia, stirred for one hour and after working the product in a usual manner, 3- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothiens- [2, 3-d] -pyrimidin-2-yl] -propium araide. , 4 A 0o dissolves 1 equivalent of DMF and 1 equivalent of oxalyl chloride in acetonitrile. Then 1 equivalent of 3- [4- (3-chloro-4-methoxy-benzylamino) -5,6-7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidine- is added. 2-yl] -pro-pionamide. It is stirred for one hour. After working the mixture in a usual manner, 3- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2, 3-d] is obtained. ] -pyridin-2-yl] -propionitrile. EXAMPLE 5 The compounds indicated below are obtained in a manner analogous to that described in examples 1 and 2: 6- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8 -te-trahydro- [1] -benzothieno- [2, 3-d] -pyrimidin-2-yl] -hexanoic, mp 165"; '2- [4- (3-chloro-4-methoxy-benzylamino) -5,6,7,8-te-trahydro- [l] -benzothieno- [2, 3-d] -? irimidin-2-' acid il] -propionic, ethanolamine salt, mp 150 °; 4- [4- (3-Chloro-4-methoxy-benzylamino) -5, β, 7,8-te-trahydro- [1] -benzothieno- [2, 3-d] -pyrimidin-2-yl] -2, 2-dimethyl-butyric, ethanolamine salt, mp 130 °; 4- [4- (3,4-methylenedioxy-benzylamino) -5,6,7,8-te-trahydro- [1] -benzothieno- [2, .3-d] -pyrimidin-2-yl] - 2, 2-dimethyl-butyric, ethanolamine salt, mp 126 °; - [4- (3-Chloro-4-hydroxy-benzylamino) -5,6,7,8-te-trahydro- [1] -benzothieno- [2, 3-d] -pyrimidin-2-yl] -valerianic, pf 179 °; - [4- (3,4-dichloro-bensylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid , ethanolamine sai, mp 136 ° -; - [4- (3-chloro-4-isopropyloxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -valeric acid, salt of ethanolamine, mp 118 °; 2- [4- (4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl acid ) -phenyl] -acetic, ethanolamine salt, mp 119 °; 2- [4- (4- (3,4-Methylenedioxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl) - acid phenyl] -acetic, mp 214 °. The following examples relate to pharmaceutical preparations: Example A: Injection vials The pH of a solution of lOOg of an active substance of formula I and 5 g of disodium hydrogen phosphate in 3 1 of bidistilled water is adjusted to 6.5 with 2N hydrochloric acid, then it is filtered under sterile conditions, the bottles are filled with the solution, lyophilized and the bottles are closed under sterile conditions. Each bottle for injection contains 5 mg of the active substance. Example B: suppositories A mixture composed of 20 g of an active substance of formula I, 100 g of soya lecithin and 1400 g of cocoa butter is melted, then the melt is poured into the molds and allowed to cool. Each suppository contains 20 mg of active substance. Example C: solution A solution is prepared with 1 g of an active substance of formula I, 9.38 g of NaH2P0 < x 2H20, 28.48 g of Na2HP04 x 12 H20, 0.1 g of benzalkonium chloride and 940 ml of bidistilled water. The pH is adjusted to 6.8, brought to a volume of 1 1 and sterilized by irradiation. This solution can be used in the form of eye drops.

Example D: Ointment In aseptic conditions 500 mg of an active substance of formula I are mixed with 99.5 g of Vaseline. Example E: tablets • A mixture composed of 1 kg of an active substance of formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed in the form of tablets, such that each tablet contains 10 mg of the active substance. Example F: Dragees The tablets are formed analogously to that described in Example E and then coated in the usual manner with a bath of sucrose, potato starch, talc, tragacanth and dye. Example G: capsules With 2 kg of an active substance of formula I, hard gelatine capsules are filled, so that each capsule contains 20 mg of the active substance. Example H: ampoules A solution of 1 kg of an active substance of formula I in 60 1 of bidistilled water is filtered under sterile conditions. The ampoules are filled with this solution and then lyophilized and closed under sterile conditions. Each ampoule contains 10 mg of the active substance. Example I: aerosol inhalant solution 14g of an active substance of formula I are dissolved in 10 1 of isotonic NaCl solution. With this solution, commercial containers that have a vaporizer ecan-nism are filled. The solution can be inhaled by the mouth or nose. "Each spray (approx.O, ml) corresponds to a dose of approximately 0.14 mg.It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is the which is clear from the present description of the invention.

Claims (3)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Compounds of formula I characterized because; R1, R2 independently represent H, A or Hal, being one of the radicals R1 or R2 always? H, R1 and R2, together, also represent alkylene of 3 to 5 carbon atoms, R3, R4 independently represent H, A, OA or Hal, R3 and R4, together, also represent alkylene of 3 to 5 carbon atoms, -O-CH2-CH2-, -0-CH2-0- or -0-CH2-CH2-0-, X represents Rs or R6 which is substituted with R7, R represents straight or branched chain alkylene and from 1 to 10 C atoms, in which one or two CH? can be replaced by -CH = CH-, or -C6H4- (CH2) -, R represents cycloalkylalkylene groups of 6 to 12 carbon atoms, R7 represents COOH, COOA, CONH2, CONHA, CON (A) 2 or CN, A represents alkyl of 1 to 6 C atoms, Hal represents F, Cl, Br or I m is 1 or 2. and n is 0, 1, 2 or 3, and their salts are acceptable from the physiological point of view.
2. 2. Compounds of formula I, according to claim 1 (a) 3- [4- (3-Clsro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothiene acid - [2,3-d] -pyrimidin-2-yl] -propionic; (b) 4- [4- (3,4-Methylenedioxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl acid ] -butyric; (c) 7- [4- (3, 4-ethylenedioxy-benzylamino) -5,6,7,8-tetrahydro- [l] -benzothieno- [2, 3-d] -pyrimidin-2-yl acid ] -heptanoic; (d) 7- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2 acid -yl] -heptanoic; (e) 5- [4- (3-Chloro-4-methoxy-benzylamino) -5,6,7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2 acid -il] -valerianic; (f) 5- [4- (3-Chloro-4-methoxy-benzylamino) -6-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -valeric acid; (g) 4- [4- (3-chloro-4-methoxy-benzyl-aryl-no) -6-methyl-thieno- [2,3-d] -p'-rimidin-2-yl] -butyric acid; (h) 4- [4- (3,4-Methylenedioxy-benzylamino) -β-methyl-thieno- [2,3-d] -pyrimidin-2-yl] -butyric acid; (i) 2- acid. { 4- [4- (3-chloro-4-methoxy-benzylamino) -5, β, 7,8-tetrahydro- [1] -benzothieno- [2,3-d] -pyrimidin-2-yl] -cyclo- hexyl-1-yl] -acetic; (k) 5- [4- (3,4-Methylenedioxy-benzylamino) -6-methyl-thieno- [2, 3-d] -? irimidin-2-yl] -valeric acid; and its salts acceptable from the physiological point of view.
3. 3. Process for preparing compounds of formula I, according to claim 1, and their salts, characterized in that a) a compound of formula II is reacted wherein R1, R2 and X have the indicated meanings, and L represents Cl, Br, OH, SCH3 or an esterified and reactive OH group, with a compound of formula III, [III), wherein R3, R4 and n have the indicated meanings, or b) in a compound of formula I a residue X is transformed into another residue X either, for example, by hydrolyzing an ester group to a COOH group or by transforming a COOH group into an amide or in a cyano group, and / or because a compound of formula I is converted into one of its salts. . - Process for obtaining pharmaceutical preparations, characterized in that a compound of formula I according to claim 1 is carried, and / or one of its salts physiologically acceptable to a suitable dosage form, together with at least one excipient or solid, liquid or serailiquid auxiliary product. 5. Pharmaceutical preparation, characterized in that it contains at least one compound of formula I, according to claim 1, and / or one of its salts acceptable from the physiological point of view. ß-- Compounds of formula I, according to claim 1, and their physiologically acceptable salts for combating diseases of the cardiocirculatory system and for the treatment and / or therapy of potency disorders. 7. Medicaments of formula I, according to claim 1, and physiologically acceptable salts thereof which act as inhibitors of phosphodiesterase V. 8. Use of the compounds of formula I, according to claim 1, and / or its physiologically acceptable salts for preparing a medicament. 9. Use of the compounds of formula I, according to claim 1, and / or of their physiologically acceptable salts for combating diseases.