PL89374B1 - - Google Patents

Description

The present invention relates to a process for the preparation of ureidophenoxyalkanolamine derivatives of the formula general 1, in which Ri is an unbranched alkyl radical of 1-6 carbon atoms, a branched radical 3-8 carbon alkyl such as isopropyl, isobutyl, III-order. butyl, III-order. amylic, isoamyl or isohexyl, an alkenyl radical with 3-6 carbon atoms such as allyl, methylalil or crotyl or cycloalkyl radical with 3-7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopene back, cyclohexyl or cycloheptyl, R2 is a hydrogen atom, an unbranched alkyl radical of 1-6 carbon atoms, branched alkyl radical of 3-8 carbon atoms such as isopropyl, isobutyl, III-butyl, isoamyl, III-amyl or isohexyl, cycloalkyl radical of 3-7 atoms carbon such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, or an alkenyl radical having 3-6 carbon atoms, such as allyl, methylallyl or crotyl, the radicals ureido and alkanolamine can stand to each other in ortho, meta or para positions, as well as salt of the above compounds with tolerable inorganic or organic acids.

Examples of organism tolerated inorganic and organic acids that make up the the compounds according to the invention, the salts are: hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric, acetic, dichloroacetic, propionic, benzyl, salicylic, oxalic, malonic, adipic, maleic, fumaric, tartaric, lemon, ascorbic.

The definition of the compounds of general formula I includes both pure stereoisomers and mixtures thereof.

Compounds of general formula I have a specific O-adrenergic blocking action significantly stronger than those described by D. Dunlop and R.G. Schanks (Brit. J. Pharmac. Chemother. 32, 201-210, 1968) for 1- (4- acetaminophenoxy) -2-hydroxy-3-isopropylaminopropane. / The compounds were tested in cats under chloralose-urethane anesthesia. Shrinkage force register ** • was determined as the maximum rate of pressure increase (dp / dt max) in the left ventricle using a steel catheter. Systolic and diastolic blood pressure were recorded concurrently with the heart rate. Research on an isolated, physiologically working atrium of a guinea pig heart, was performed by the method W. Schaumann, R. Boden and W. Bartsch (Arch. Exp. Pharmak u. Path. 255, 328, 1966). Blocking measurement2 89374 isoprenaline-type on the bronchial system was carried out on guinea pigs after induction histamine contraction, and the anti-arrhythmic activity was tested in the aconitine test on rats.

The results obtained are illustrated in Table I, where the chemical compound of the formula is listed in column 1 general 1f characterized by the radicals Ri and R2, or the name of the comparative compound. In column 2 ED50 for inhibition of positively chronotropic isoprenaline effects was given (1 / ug / kg) in mg / kg, intravenously, in column 3 the ED50 for inhibition of positively isotropic isoprenaline effects (1 / mg / kg), intravenously, is given, in column 4 the ED50 for inhibition of the positively isotropic isoprenaline effect (0.015 / mg / kg) is given in g / ml on an isolated atrium of the heart, column 5 lists the dose in mg / kg for oral dosing starting j3-blockade of the guinea pig bronchial system, column 6 describes aconitine arrhythmia hearts on a rat; dose in mg / kg to inhibit arrhythmias by 73%.

Columns 7-9 show side effects on the cat's circulatory system when dosed intravenously as 2.5 mg / kg, percent of the original value. Column 7 is frequency, column 8 is systolic blood pressure, column 9 gives dp / dt max.

T a b l i c a I R, R2 i-C3H7 CH3 1.3 0.43 1.19 - none + 5% + 5% + 8% i-C3H7 C2H5 1.8 1.4 1.57 - none + 9% + 14% + 53% i-C4H9 CH3 0.92 1.0 1.55 - none + 8% + 9% + 42% t-C4H9 C2H5 t-C4H9 Cyclohexyl i-C3H7H l- (4-acetammonophenoxy) - -2-hydroxy-3-isopropyl- Aniinopropane 0.72 0.66 2.6 0.29 0.18 3.1 1.70 0.24 , 3 , 0 , 0 - lack -twenty lack -2% + 2% + 8% + 2% + 1% + 4% -6% -10% + 33% 4.3 1.8 1.2 5.0 none -6% -3% -2% As can be seen from the data shown in Table I, ureidophenoxyalkanolamines of the general formula have a blocking effect of the | 3-adrenergic type, inhibiting only positive inotropic and chronotropic strong isoprenaline effect. Doses of 20 times the ED50 do not lower blood pressure induced isoprenaline, while blockers of 1-isopropylamino-3- (1-naphthyloxy) receptors panol-2 most strongly block the effect of isoprenaline on peripheral vessels. Also effect on / 3-stimulant the effect of isoprenaline on the bronchial system is noticed only at very high doses.

Also with oral dosing (5 mg / kg) for example 1- [4- (3-cyclohexylureido) phenoxy] -2-hydro- x-3-isopropylpropane can be reduced by 50% caused by isoprenaline increase in the frequency of the heartbeat, and about 76% isoprenaline positivelyimotropic.

From the point of view of potency, compounds of general formula 1 are preferable to 1- (4-acetaminophenoxy) - -2-hydroxy-3-isopropylaminopropane. For example, in the rat aconitine test 1- (4-acetaminophenoxy) - • 2-hydroxy-3-isopropylaminopropane does not counteract cardiac arrhythmias in doses up to 40 mg / kg, while some ureidoalkanolamines of general formula I exhibit this type of activity.

The side effect of compounds of general formula I on the cardiovascular system is negligible. These relationships are not they develop bradycardia, lower blood pressure and decreased contractile force, while these phenomena occur clearly in the case of intravenous dosing of the cat with 1-isopropylamino-3 - (-1-naphthyloxy) propanol — 1. Some compounds of general formula 1 show a specific activity consisting in blocking 0-receptors, having great medicinal importance. It is possible to perform with the compounds of general formula 1 therapy, consisting in blocking / 3-receptors while maintaining bronchospasm or excluding cardiac side effects from treatment with O-pacemakers. Maybe in shock conditions as a result of mobilization endogenous catecholamine with j3-blockade of the peripheral-vascular system, dysregulation of the vascular system occurs circulation. This phenomenon is prevented by specific β-receptors of the general formula 1, which it cannot use there is a predominance of the alpha-sympathicotonic effect in the peripheral vascular system.

According to the invention, compounds of general formula I are obtained as follows: phenoxyalkanol- amines of general formula II are reacted with the compound in the form of a racemate or optically active isomer of general formula III, in which the formulas R {and R2 are as defined above, R3 is a hydrogen atom, and R4 is an alkoxy group of 1-4 carbon atoms, optionally substituted phenoxy, alkylthio- with 1-4 carbon atoms, optionally substituted phenoxy, alkylthio- with 1-4 atoms 89374 3 carbon, optionally substituted phenylthio, amino unsubstituted or substituted with a radical R2, 9ruPS hydrazine or halogen or also R3 and R4 together represent an additional C-N bond, which at least one of the symbols At and A2 represents a hydrolytically cleavable protecting group, such as an aliphatic acyl group, (e.g., acetyl), aromatic acyl (e.g., benzoyl), alkoxycarbonyl (e.g. tertiary butoxycarbonyl, ethoxycarbonyl), cycloalkoxycarbonyl (e.g. cyclopentyloxy- carbonyl or cyclohexylcarbonyl), arylalkyloxycarbonyl (e.g. benzoyloxacarbonyl) or also A! and A2 may collectively constitute one hydrolytically cleavable protecting group such as carbonyl, oxalyl, alkylidene of general formula R5-c-R6 where each of R5 and R6 represents a hydrogen atom or an alkyl moiety of 1-6 C atoms or R5 and R6 taken together are - (CH2) lt-, where which n is the number 4-6. The reactions are carried out at a temperature of 0 ° C to 200 ° C, preferably between room temperature to 150 ° C, and then the current protective groups in an acid or alkaline environment are split off, optionally by heating and, if appropriate, the resulting racemic mixtures are separated into their forms optically active.

According to the definitions of the radicals R3 and R4, the compounds of the general formula 3 are esters of carbamic acids, esters of thiocarbamic acids, urea, mono- or symmetrically disubstituted derivatives urea, semicarbazides, carbamic acid halides or isocyanates.

The compounds of the general formula I are also prepared by the method according to the invention, so that the phenoxylac The noloamine of general formula II is reacted in the form of a racemate or optically active isomer with a compound of general formula III in which Rt and R2 are as defined above, R3 is an atom hydrogen, and R4 is an alkoxy group of 1-4 carbon atoms, optionally substituted phenoxy, alkylthio having 1-4 carbon atoms, optionally substituted phenylthio, amino unsubstituted or substituted with R2, hydrazino or halogen, or R3 and R4 together are an additional C-N bond, and at least one of the symbols Ai and A2 represents a hydrogenolytically cleavable group a protective agent such as: α-aralkyl, alkoxycarbonyl, cycloalkoxycarbonyl or α-aralkoxycarbony- at a temperature of 0 ° C to 200 ° C, preferably at room temperature to 150 ° C, and hydrogenolytic cleavage the removable protective groups are cleaved off by catalytic hydrogenation and, if appropriate, the resulting mixtures racemics are separated into their optically active forms.

Hydrolytic cleavage of protective groups can be performed in the presence of a catalytic a track of a noble metal such as platinum or palladium! or in the presence of Raney nickel, in an inert environment, with respect to the catalyst, diluent or solvent used, for example alcohol, aqueous alcohol, dioxane or acetic acid solution. When a noble metal is used, the hydrogenolysis occurs acceleration or to a greater extent if additionally catalysts such as hydrochloric acid are used or oxalic acid.

The compounds of the general formula I are also prepared by the method according to the invention, so that the phenoxyalkaline The noloamine of general formula II is reacted in the form of a racemate or optically active isomer with a compound of the general formula III in which the formulas R 1 and R 2 are as defined above, R 3 is an atom hydrogen, and R4 is an alkoxy group of 1-4 carbon atoms, optionally substituted phenoxy, alkylthio having 1-4 carbon atoms, optionally substituted phenylthio, unsubstituted or substituted with R2, hydrazino or halogen, or R3 and R4 together are additional C-N bond, and each of the symbols Aj and A2 represents a hydrogen atom at a temperature of 0-200 ° C, preferably at room temperature to 150 ° C and the optionally obtained racemic mixtures are separated on their optically active forms.

In case A is hydrogen, substitution on a compound of formula may be preferable general 2 a compound of general formula 3 in the presence of an equimolar amount of acid.

The process according to the invention can be carried out under various reaction conditions.

For example, substitutions may be made in the absence or presence of an inert solvent or thinner, at room temperature or with heat applied. If it is needed, reactions can be carried out in a closed vessel, under pressure.

Depending on the substituents of the compounds to be reacted, they can be changed over a wide range optimal conditions in terms of temperature and solvent.

The starting products can, if the method of obtaining them is not described, be obtained generally known ways.

The compounds of general formula I obtained can be converted into tolerated addition salts the body with inorganic or organic acids, such as hydrochloric, hydrobromic, hydroiodic acid, sulfuric, nitric, phosphoric, acetic, propionic, dichloroacetic, benzyl, benzoic, amber, 4 89374 formic, salicylic, oxalic, malonic, adipic, maleic, fumaric, tartaric, lemon Iu6 ascorbic.

Addition salts of compounds of general formula I can be converted by treatment with inorganic bases in free relationships.

If the synthesis gives compounds of general formula I in the form of racemates, these are known they can be separated into optically active components by means. Optically active compounds can be obtained by carrying out reactions with optically active substrates.

The method according to the invention is illustrated by the following examples.

EXAMPLE 1 0.5 g of 1- (4-aminophenoxy) 2-hydroxy-3-isopropylaminopropane is dissolved in the stirring 2.2 ml of 1N hydrochloric acid and 5 ml of acetone are added, and 0.3 g of cyclohexyl isocyanate is added to the solution. After For 16 hours, acetone is distilled off, 5 ml of water are added and the solution is filtered. The sodium hydroxide is precipitated 1- [4- (3-cyclohexylureido (phenoxy] -2-hydroxy-3-isopropylaminopropane, which, after recrystallization from iso- propanol melts at 156-158.5 ° C.

Example II. Mixture 2.4 g 1- (4-aminophenoxy) -2-hydroxy-3-MI-pre-butylaminopropane, 24 ml acetone and 1.25 g of cyclohexyl isocyanate were heated under reflux for one hour. Next the solvent is distilled off, the residue is dissolved in water with the addition of dilute hydrochloric acid (to pH 4) and the solution seeps. 1- [4- (cyclohexylureido) -fe * is precipitated by the addition of sodium hydroxide (to pH 12) oxy] -2-hydroxy-3-III-tert-butylamino-propane, which melts after recrystallization from isopropanol at 142-143.5 ° C.

The same result is obtained when carrying out the reactions in the presence of glacial acetic acid. Apply on 1 mole of 1- (4-aminophenoxy) -2-hydroxy-3-11-tert-butylaminopropane 1-2 moles of glacial acetic acid.

Example III. 4.8 g of 1- (4-aminophenoxy) -2-hydroxy-3-III-tert-butylaminopropane dissolve while stirring at room temperature in a mixture of 48 ml of water and 20 ml of 1N hydrochloric acid. Next 2.5 g of cyclohexylisocyanate are added and the mixture is stirred for 15 hours at room temperature.

The solution is filtered and the 1- [4- (3-cyclohexylureido) -phenoxy] is precipitated by adding sodium liquor to pH 12. -2-hydroxy-3-III-pure-butylaminopropane which, after recrystallization from isopropanol, melts at round 142-144 ° C.

Example IV. 5 g 1-l4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3- (N-benzyl-N-III-order-butyl- amino) -propane, 100 ml of glacial acetic acid and 0.5 g of platinum dioxide are shaken in 6 hours at room temperature under nitrogen atmosphere. Then the catalyst is filtered off, distilled under a vacuum Glacial acetic acid and the residue dissolved in 250 ml of water with hydrochloric acid to pH 2. Solution filtered and by adding sodium liquor to pH 12 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydro- xy-3-III-order-butylaminopropane, which after recrystallization from isopropanol melts at 142-144.4 ° C.

Cleavage of the benzyl group in 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3- (N-benzyl-N- III- order-butylamino) -propane can also be carried out as follows: 5 g stock is shaken with 100 ml of glacial acetic acid and 1 g of palladium on carbon for 8 hours at 50 ° C and under a pressure of 50 atm of hydrogen and then proceeds as described above.

Cleavage of the benzyl group in 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3- (N-benzyl-N- III- tert-butylamino) propane can also be carried out as follows: 5 g 1- [4- (3-cyclohexylurei c) -phenoxy] -2-hydroxy-3- (N-benzyl-N-1H-tert-butylamino) propane, 100 ml ethanol and 1 g nickel catalyst Raney is shaken for 8 hours at 50 ° C and 50 atm of hydrogen. Then it drifts away catalyst, ethanol distills, and the resinous residue is dissolved in 250 ml of water with acid salt. After filtering, 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydro is precipitated with sodium liquor. xy-3-lll-row. d.-butylaminopropane which melts at temperature on recrystallization from isopropanol 142-144 ° C.

When used as a starting product 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3- (N-benzyl-N-III- Rare-butylamino) -propane is obtained as follows: Solution containing 3.65 g of 1- (4-aminophenoxy) -2-hydroxy-3- (N-benzyl-N-III-rare-butyral) hydrochloride Amino) propane in 90 ml of water is mixed with 25 g of cyclohexylisocyanate and stirred for 16 hours at a temperature of reaction turn. The solution is then filtered and 1- [4- (3-cyclohexylureido) - phenoxy] -2-hydroxy-3- (N-benzyl-N-III-order-butylamino) -propane in yellow resin form, which is used in without purification by cleavage of the benzyl group 89 374 Example V. Similarly as in examples I-IV, the compounds listed in Table I are obtained Table II Relationship Melting temperature WHAT 1- (4-urcidofcnooxy) -2-hydroxy-3-isopropyl- aminopropane 1- (4-ureidophenoxy) -2-hydro- xy-3-IIl-tert-butylaninopropane 1- [4- (3-methylureido) -phenoxy] -2-hydroxy- 3-isopropylaninopropane l-I4- (3-ethylureido) -phenoxy] -2-hydroxy- -3-Tertiary-butyl [alpha]] Thinopropane 1- [4- (3-cyclohexylureido) -phenoxy-2-hydro- xy-3-isopropylaminopropane 1- [4- (3-methylureido) -phenoxy] -2-hydroxy- -3-III-tertiary-butylannopropane l-I4- (3-cyclohexylureido) -phenoxy-2- hydroxy-3-tertiary-butylanipropane 1- [4- (3-n-hexylureidoKenoxy | -2-hydro- xy-3-isopropylaminopropane 1- [4- (3-isopropylureidoHenoxy] -2-hydro- xy-3-isopropylaminopropane 1- [4- (3-allylourcido) -phenoxy] -2-hydroxy- -3-isopropylaminopropane l- [4- (3-tier-butylourcido) -fcnooxy) -2- -hydroxy-3-isopropylaninopropane 1- [4- (3-isoamylourcido) -phenoxy-2-hydroxy- -3-isopropylaminopropane 1- [4- (3-crotylureido) -phenoxy-2-hydroxy- -3-isopropylaminopropane 1- [4- (3-cyclopentyl-uureido) -phenoxy] -2-hydro- xy-3-isopropylaminopropane 1-14- (3-cyclohcptyloureido) -phenoxy-2-hydro- xy-3-isopropylaminopropane 1- [4- (3-cyclopropylureido) -phenoxy] -2-hydro- xy-3-isopropylaminopropane 1- [4- (3-hexenyl- (2) -ureido) -phenoxy] -2- -hydroxy-3-isopropylaninopropane 1- (2- (3-cyclohexylurcido) -fcnooxy J-2-hydro- xy-3-tertiary-butylaninopropane H3- (3-cyclohexylureido) -phenoxy] -2-hydro- xy-3-tertiary-butylaminopropane l- [4- (3-cyclohcksyloureido) -phenoxy | -2-1iydro- xy-3-n-hexylaminopropane 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydro- xy-3-mctyloaniinopropaJi 1- [4- (3-cyclohexylureido) -fcnooxy] -2-hydro- xy-3-n-butylaminopropane 1- [4- (3-cyclohexylureido) -phenoxy | -2-hydro- xy-3-cyclohexylancinopropane 1- [4- (3-cyclohcksylureido) -phenoxy) -2-hydro- xy-3-II-order-butylaminopropane 1- (4- (3-cyclohexylureido) -phenoxy-2-hydro- xy-3-isoamylaninopropane 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydro- xy-3-crotylaminopropane 141.5-142.5 207 (with distribution) 154-156 122-124 157-160 140-143 143-145 146-149 154-156 145-147 141.5-143 124-127 140.5-143.5 157.5-160 145-148 141-143.5 157.5-159.5 188.5-181.5 151-154 160-163 170-172 160-163 156-158 127 ^ 130 157-159 155-1576 89374 1- | 4- (3-cycloliexylurcido) -phenoxy J-2-liydro- x-3-cy clopentylaniyelopropane 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydro- xy-3-cycloheptylaniinopropane 1- (4- (3-cyclohexylureido) -phenoxy-2-liydro- xy-3- (1,1,3,3-tetramethylbutyl) aminopropane H4- (3-cyclohexylureido) -fcnooxy] -2-hydro- xy-3-hexnyl- (2H-aminopropane) 1- [4- (3-cyclohexylureido) -phenoxy] -2-liydro- xy-3-cyclopropylaminopropane 1- [4- (3-ethylureido) phenoxy] -2-hydroxy -3-allylaninopropane 142.5 131- 131- 156 154- 120 -144.5 133.5 133.5 -159 156.5 -123 Example VI. A mixture of 1 g of 1- [4- (3-cyclohexylureido) phenoxy] -2-hydroxy-3-11 1-tert-butylamine nopropane, 0.4 g of benzoic acid and 5 ml of methanol are heated to boiling, giving a clear solution.

After cooling, 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3-III-a.-butylamino- benzoate is precipitated. propane, mp 194-198 ° C.

Replacing 0.4 g of benzoic acid, 0.2 g of succinic acid is obtained analogously 1- [4- (3-cyclohexylureido) phenoxy] -2-hydroxy-3-11 1-tert-butylaminopropane succinate at mp 202-204 ° C.

By replacing 0.4 g of benzoic acid with 0.3 g of tartaric acid, the same way is obtained 1 - [4- (3-cyclohexylureido) phenoxy] -2-hydroxy-3-11 1-tert-butylaminopropane, m.p. 213-215 ° C.

Example VII. A mixture of 1 g of 1- [4- (3-cyclohexylureido) phenoxy] -2-hydroxy-3-III-order. butylami- nopropane, 0.2 ml of glacial acetic acid and 5 ml of isopropanol are heated for a short time to boil. After cooling, 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3-III-tert-butyl acetate is precipitated. aminopropane which, after recrystallization from isopropanol, melts at 162 ° -165.5 ° C.

By replacing 0.2 ml of glacial acetic acid with 0.4 g of salicylic acid, 1- [4- (3-th *) salicylate is obtained clohexylureido) phenoxy] β-2-hydroxy-3-III-pred. butylaminopropane, which, after recrystallization from isopropane panol melts at 133-135 ° C.

The corresponding melting point formate is obtained in a similar manner with formic acid 171-174 ° C.

Example VIII. 7.2 g 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3-III-t-butylaminopropa nu, 36 ml of water and 10 ml of 2N nitric acid are heated to 80 ° C, the solution is filtered and cooled.

1- [4- (3-cyclohexylureido) phenoxy] -2-hydroxy-3-1 11-tertiary butylaminopropane nitrate is precipitated. recrystallization from isopropanol-water 98: 2 melts at 172-176 ° C.

Replacing 10 ml of nitric acid with 2 ml of concentrated hydrochloric acid gives 1- [4- (3-cyclic) hydrochloride lohexylureido) phenoxy] -2-hydroxy-3-III-butylaminopropane which, after recrystallization from 98% iso propanol melts at 208-212.5 ° C.

Example IX. For a solution of 10 g of 1- [4- (3-cyclohexylureido) phenoxy] -2-hydroxy -3-111-butyl tert. of aminopropane in 50 ml of methanol, 1.55 ml of 17.8 N sulfuric acid are added. Inert sulfate 1- [4- (3-cyclohexylureido) -phenoxy] -2-hydroxy-3-l 11-tert.butylaminopropane which "melts decomposing at 245 ° C.

Example X. Solution 10 g of 1- [4- (3-cyclohexylureido) phenoxy] -2-hydroxy -3-111-t-butylamino propane in 50 ml of methanol, 13.8 mol of 85% phosphoric acid are added. After a while the official loses himself phosphate of the above base, which after recrystallization from the methanol-water system 5: 1 melts at the temperature of 210-212.5 ° C.

Claims (6)

Patent claims 1. A method for the preparation of ureidophenoxyalkanolamine derivatives of the general formula I, in which R] is an unbranched alkyl radical of 1-6 carbon atoms, a branched alkyl radical of 3-8 carbon atoms, an alkenyl radical of 3-6 carbon atoms or a cycloalkyl radical of 3-6 7 carbon atoms and R2 is a hydrogen atom, an unbranched alkyl radical of 1-6 carbon atoms, a branched lower alkyl radical of 89 374 7 of 3-8 carbon atoms, a cycloalkyl radical of 3-7 carbon atoms or an alkenyl radical of 3-6 carbon atoms , wherein ureido and alkanolamine radicals may be ortho, meta or para to each other in the form of racemates or optically active isomers, as well as salts of the above compounds with organism-tolerated inorganic or organic acids, characterized in that phenoxyalkanolamine of general formula II, in the form of a racemate or optically active isomer, is reacted with a compound of general formula III, in which formulas R 1 and R 2 are as defined above, R3 is hydrogen and R4 is an alkoxy group with 1-4 carbon atoms, optionally substituted phenoxy group, alkylthio group with 1-4 carbon atoms, optionally substituted phenylthio- group, amino group unsubstituted or substituted by R2, hydrazine group or a halogen atom, or R3 and R4 together represent a C-N bond, and at least one of the symbols At and A2 represents a hydrolytically cleavable protecting group such as an aliphatic or aromatic acyl group, Iowa alkoxycarbony, cycloalkoxycarbonyl or aralkyloxycarbonyl or Ax and A2 together are a hydrolytically cleavable protecting group such as a carbonyl, oxalyl or alkylidene group of the general formula R5-C-R6, wherein each of R5 and R6 is hydrogen or a remainder of an alkyl group of 1-6 C or R5 atoms and R6 together represent the group - (CH2) n-, n being the number 4-6, at a temperature of 0-200 ° C, preferably at room temperature to 150 ° C, and hydrolytically cleaved The protective groups are cleaved in an acidic or alkaline environment, optionally by heating, and the racemic mixtures obtained, if appropriate, are separated into their optically active forms. 2. The method according to claim The process of claim 1, wherein the reactions are carried out in the presence of an equimolar amount of acid. 3. Process for the preparation of ureidophenoxyalkanolamine derivatives of the general formula I, in which Rj is an unbranched alkyl radical of 1-6 carbon atoms, a branched alkyl radical of 3-8 carbon atoms, an alkenyl radical of 3-6 carbon atoms or a cycloalkyl radical of 3-7 carbon atoms and R2 represents a hydrogen atom, an unbranched alkyl radical of 1-6 carbon atoms, a branched lower alkyl radical of 3 to 8 carbon atoms, a cycloalkyl radical of 3 to 7 carbon atoms or an alkenyl radical of 3 to 6 carbon atoms, where ureido and alkanolamine radicals may be in ortho, meta or para positions in relation to each other, in the form of racemates or optically active isomers, as well as salts of the above compounds with organism-tolerant inorganic and organic acids, characterized in that phenoxyalkanolamine with of general formula 2 in the form of a racemate or optically active isomer is reacted with a compound of general formula III, in which the formulas Rj and R2 are as defined above R3 is hydrogen and R4 is an alkoxy group of 1-4 carbon atoms, an optionally substituted phenoxy group, an alkylthio group of 1-4 carbon atoms, an optionally substituted phenylthio group, an amino group unsubstituted or substituted by R2, a hydrazine group or halogen, or R3 and R4 together represent an additional C-N bond, and at least one of the symbols A! and A2 is a hydrogenolytically cleavable protecting group such as an α-aralkyl, alkoxycarbonyl, cycloalkoxycarbonyl, or α-aralkoxycarbonyl group at 0 ° C to 200 ° C, preferably at room temperature to 150 ° C, and the hydrogenolytically cleavable protecting groups are cleaved off by catalytic hydrogenation, preferably in the presence of noble metals such as platinum or palladium, or in the presence of Raney nickel, and optionally the racemic mixtures obtained are separated into their optically active forms. 4. The method according to p. The process of claim 3, wherein the reactions are carried out in the presence of an equimolar amount of acid. 5. Process for the preparation of ureidophenoxyalkanolamine derivatives of the general formula, in which R 1 is an unbranched alkyl radical of 1-6 carbon atoms, a branched alkyl radical of 3-8 carbon atoms, an alkenyl radical of 3-6 carbon atoms or a cycloalkyl radical of 3-7 carbon atoms and R2 represents a hydrogen atom, an unbranched alkyl radical of 1-6 carbon atoms, a branched lower alkyl radical of 3-8 carbon atoms, a cycloalkyl radical of 3-7 carbon atoms or an alkenyl radical of 3-6 carbon atoms, where ureido and alkanolamine radicals may be in ortho, meta or para positions in relation to each other, in the form of racemates or optically active isomers, as well as salts of the above compounds with organism-tolerant inorganic and organic acids, characterized in that phenoxyalkanolamine with of general formula II in the form of a racemate or optically active isomer, is reacted with a compound of general formula III, in which formulas R 1 and R 2 are as defined above ane, R3 is hydrogen, and R4 is an alkoxy group of 1-4 carbon atoms, an optionally substituted phenoxy group, an alkylthio group of 1-4 carbon atoms, an optionally substituted phenylthio group, an amino group unsubstituted or substituted by R2, a hydrazine group or halogen, or R3 and R4 taken together mean an additional C — N bond, and each of the symbols A! and A2 is a hydrogen atom at 0 ° -200 ° C, preferably at room temperature to 150 ° C, and the optionally obtained racemic mixtures are separated into their optically active forms. 6. The method according to p. The process of claim 5, wherein the reactions are carried out in the presence of an equimolar amount of acid. R2-NH-C0-NH ^ Q ^ O-CHj-CHOH-CH ^ NH-R, W2OR 1 R, - N-CHo-CH-CHo-ChT ^ A, 0-A2 2 Hsor 2 Ro-NC-0 1 I R3 R <Chip 3 Work Typographer. UP PRL, circulation 120 + 18 Price: PLN 10