NO801930L - AMINOBENZOIC ACID DERIVATIVES FOR USE AS INTERMEDIATES - Google Patents

Description

This invention relates to the preparation of new aminobenzoic acid derivatives with the general formula

and their physiologically compatible acid addition salts with inorganic or organic acids. The new aminobenzoic acid derivatives can be used as medicines and also as intermediates for the production of new anti-inflammatory compounds.

The new aminobenzoic acid derivatives and their physiologically compatible acid addition salts exhibit valuable pharmacological properties, in addition to a secretolytic and/or antitussive, in particular an anti-ulcer effect and an inhibitory effect on gastric juice secretion. Furthermore, they are valuable intermediates for the production of antiphlogistically active compounds. These are obtained by reacting an antiphlogistic, which contains a carboxyl group, with a compound of the above general formula I.

In the above general formula I means

a hydrogen, fluorine, chlorine or bromine atom,

1*2 and R^, which may be the same or different, linear or branched alkyl groups of 1 to 6 carbon atoms which may be substituted with a phenyl group or a dialkylamino group of 1 to 3 carbon atoms in each alkyl part, pyridyl or cycloalkyl groups of 5 to 7 carbon atoms, or R 2 and R 4 together with the intervening nitrogen atom, a pyrrolidino-, piperidino-, hexamethyleneimino-. morpholino, N-arylpiperazino or N-alkylpiperazino group, where the alkyl group may contain 1 to 3 carbon atoms, or

one of the radicals R^ or R^ also a hydrogen atom,

A a cycloalkylene group of 5 to 7 carbon atoms, a linear alkylene group of 2 to 10 carbon atoms which may be substituted with 1 or 2 alkyl groups of each 1 to 3 carbon atoms, with 1 or 2 car alkoxy groups of a total of each

2 to 4 carbon atoms, with 1 or 2 phenyl groups, med

1 to 4 hydroxy groups and/or with a group of the formula

where R^, R2 and R^ are as indicated above, or may be interrupted by an oxygen or sulfur atom, by a sulfoxide, sulfonyl, benzene, cyclohexane, pyridine, piperazino or imino group, where the imino group may be substituted with an alkyl group of 1 to 6 carbon atoms or with a phenyl or phenylalkyl group of 1 to 3 carbon atoms in the alkyl part, X an oxygen atom or an imino group, and Y a hydroxy or amino group, a chlorine, bromine or iodine atom, a residue with the formula

where R^, R^ and R^ are as indicated above, and Z means an oxygen atom or an imino group, or together with the carbon atoms in the a- and 3-position in the residue A, if these contain at least 3 carbon atoms, an oxiranyl group or a 1 ,3- dioxolanyl group with the formula

where R^ and R^, which may be the same or different, mean hydrogen atoms, alkyl groups with 1 to 3 carbon atoms or phenyl groups.

Among the meanings mentioned in the definition of the residues R^ to R,., A and X, thus come into consideration for the group

the meanings methylamino-, ethylamino-, n-propylamino-, isopropylamino-, n-butylamino-, tert.butylamino-, n-pentylamino-, n-hexylamino-, dimethylamino-, diethylamino-, di-n-propylamino-, . diisopropylamino-, di-n-butylamino-, di-n-pentylamino-, di-n-hexylamino-, ethylmethylamino-, ethylpropyl-amino-, ethylbutylamino-, propy1-isopropylamino-, propyl-butylamino-, methyl-cyclopentylamino-, methyl-cyclohexylamino-, methyl-cycloheptylamino-, ethyl-cyclopentylamino-, ethyl-cyclohexylamino-, ethyl-cycloheptylamino-, propy1-cyclopentylamino-, propy1-cyclohexylamino-, propyl-cycloheptylamino-, cyclopentylamino-, cyclohexylamino-, cycloheptylamino-, dicyclo -hexylamino-, benzylamino-, methylbenzylamino-, ethyl-benzylamino-, cyclohexyl-benzylamino-, dibenzylamino-, phenylethylamino-, methylphenylethylamino-, ethyl1-phenylethylamino-, propyl-phenylethylamino-, phenylpropylamino-, phenylamino-, methyl-phenylamino-, ethyl1-phenylamino-, 2-(dimethylamino)-ethylamino-, 2-(diethylamino)-ethylamino-, 2-(dipropylamino)-ethylamino-, 3-(dimethylamino)-propylamino-, 3-(dipropylamino)-propylamino-, N-methyl-2-(dimethylamino)-ethylamino-, N-ethyl-2-(diethylamino)-ethylamino-, pyridylamino-, pyrrolidino-, piperidino-, hexamethyl nimino, morpholino, N-methyl-piperazino, N-ethylpiperazino, N-propyl-piperazino, N-isopropyl-piperazino or N-phenyl-piperazino group,

for A the meanings 1,2-cyclopentylene-, 1,3-cyclopentylene-, 1,2-cyclohexylene-, 1,3-cyclohexylene-, 1,4-cyclohexylene-, 1.2-cycloheptylene-, 1,3-cycloheptylene-, 1,4-cycloheptylene-, ethylene-, n-propylene-, n-butylene-, n-pentylene-, n-hexylene-, n-heptylene-, n-octylene-, n-nonylene-, n-decylene-, 1-methylethylene-, 2-methyl-ethylene-, 1,2-dimethyl-ethylene-, 1-methyl-propylene-, 2-methyl-propylene-, 3-methyl-propylene-, 1,2-dimethyl-propylene- , 1.3- dimethyl-propylene-, 2-methyl-2-propyl-propylene-, 1-methyl-butylene-, 1-methyl-pentylene-, 1-methoxycarbonyl-ethylene-, 2-methoxy-carbonyl-ethylene-, 1 -ethoxycarbonyl-ethylene-, 2-ethoxycarbonyl-ethylene-, 1,2-diethoxycarbonyl-ethylene-, 1-ethoxycarbonyl-propylene-, 2-ethoxycarbonyl-propylene-, 3-ethoxycarbonyl-propylene-, 1- propoxycarbonyl-ethylene-, 2-propoxycarbonyl-ethylene-, 2-hydroxy-propylene-, 2-hydroxy-butylene-, 3-hydroxy-butylene-, 2,3-dihydroxybutylene-, 2-hydroxy-pentylene-, 2,3,4-trihydroxy-

pentylene-, 2 , 3 , 4 , 5-tetrahydroxy-n-hexylene-, 1-hydroxymethyl-ethylene-, 2-hydroxymethyl-ethylene-, 2-[4-amino-3-bromo-5-diethylaminomethyl-benzoyloxymethyl]- ethylene-, 2-f4-amino-3-bromo-5-(N-cyclohexyl-ethylaminoinethyl)-benzoyloxymethyl]-ethylene-, diethylene oxide-, diethylene sulfide-, diethylene sulfoxide-, diethylene sulfonyl-, N,N-diethyleneamino-, N,N-diethylene-methylamino-, N,N-diethylene-ethylamino-, N,N-diethylene-propylamino-, N,N-diethylene-isopropylamino-, N,N-diethylene-butylamino-, N,N-diethylene -tert.butylamino-, N,N-diethylene-hexylamino-, N,N-diethylene-phenylamino-, N,N-diethylene-benzylamino-, N,N-diethylene-phenylpropylamino-, ethylene-propylene oxide-, N-ethylene -N-propylene-methylamino-, N-ethylene-N-butylene-ethylamino-, pyridine-bis-methylene-, cyclohexane-bis-methylene-, xylylene-, N,N'-diethylene-piperazino- or N-ethylene- N'-propylene-piperazino group,

for R. and R5 , the meanings hydrogen atom, methyl, ethyl, propyl, isopropyl or phenyl group, and

for X, the meanings oxygen atom or imino group.

Preferred compounds of the general formula I are

those where

R^ means a chlorine or bromine atom,

R 2 and R 4 , which may be the same or different, mean alkyl groups of 1 to 4 carbon atoms, cycloalkyl groups of 5 to 7 carbon atoms, benzyl-, 2-diethylaminoethyl- or

pyridyl groups, or R2 and R^ together with the intervening nitrogen atom mean a pyrrolidino, piperidino, hexamethyleneimino, morpholino or N-methyl-piperazino group, or

one of the radicals R2 or R^ means a hydrogen atom,

A means a linear or branched alkylene group of 2 to 10

carbon atoms which may be substituted with 1 to 4 hydroxy groups and/or with 1 or 2 alkoxycarbonyl groups with a total of 2 or 3 carbon atoms each, an ethylene group substituted with 1 or 2 phenyl groups, a cyclohexylene-, pyridine-2,6-bis-methylene-, cyclohexane-1,4-bis-methylene or p-xylylene group or a linear alkylene group with 4 to 6 carbon atoms which between the C atoms 2 and 3 or 3 and 4 is interrupted by an oxygen or sulfur atom, with a sulfoxide, sulfonyl -, amino, phenylamino, benzylamino, piperazino or an alkylamino group with 1 to 4 carbon atoms,

X means an oxygen atom or an imino group, and

Y means a hydroxy or amino group, a chlorine or bromine atom, a residue of the formula where R^, R_ and R^ have the meanings given above, and Z means an oxygen atom or an imino group, or together with the carbon atoms in a- and 3 -position in the residue A, if this contains at least 3 carbon atoms, forms an oxiranyl group or a 1,3-dioxolanyl group with the formula

and their physiologically compatible acid addition salts.

Valuable pharmacological properties are especially demonstrated

of the compounds of the general formula I where Y means a hydroxy or amino group or a residue of the formula

Aminobenzoic acid derivatives of the general formula I with particularly valuable pharmacological properties are those where R^ denotes a bromine atom,

R2 means an alkyl group with 1 to 4 carbon atoms,

R^ denotes a hydrogen atom, an alkyl group of 1 to 3 carbon atoms or a cycloalkyl group of 5 to 7 carbon atoms, or R 2 ° 9 R 3 together with the intervening nitrogen atom

means a pyrrolidino or hexamethyleniraino group,

A means a linear or branched alkylene group of 2 to 9

carbon atoms which may be substituted with 1 to 4 hydroxyl groups and/or with 1 or 2 alkoxycarbonyl groups with

in total each 2 or 3 carbon atoms, a cyclohexylene group or a linear alkylene group with 4 carbon atoms, which between C atoms 2 and 3 is interrupted by an oxygen atom, an amino or methylamino group,

X means an oxygen atom or an imino group, and

Y means a hydroxy group or a residue of the formula

where R 1 , R 2 and R 2 have the meanings given above, and their physiologically compatible acid addition salts.

According to the invention, the new compounds with the general formula I are prepared by the following methods: Reaction of a carboxylic acid with the general formula

where R^, R2 and R^ are as stated at the outset, or salts or reactive derivatives thereof, with a connection with the general formula

where A, X and Y are as indicated at the beginning, or the group HX together with the carbon atoms in the a- and (3-position in the residue A forms an oxiranyl group, or reactive derivatives thereof.

The turnover thus includes the acylation of a compound

with the general formula III with a carboxylic acid of the general formula II or with functional derivatives thereof, optionally in the presence of an acid-activating and/or water-attracting agent, reaction of a carboxylic acid of the general formula II with a reactive derivative of a compound of the general formula formula III or alkylation of a salt of a

carboxylic acid of the general formula II with a corresponding functional derivative of a compound of the general formula III.

As functional derivatives of a carboxylic acid with the general formula II, e.g. in view of its alkyl, aryl or aralkyl esters such as the methyl, ethyl, phenyl or benzyl ester, its imidazolides, its acid halides such as the acid chloride or acid bromide, its anhydrides, its mixed anhydrides with aliphatic or aromatic carboxylic acids or carboxylic acid esters, e.g. e.g. acetic acid, propionic acid or the carboxylic acid ethyl ester, its acyloxytriphenylphosphonium salts, its N-acyloxyimide or, if the amino group is in the 2-position, also its isatoic anhydrides; as reactive derivatives of a compound of the general formula III

taking into account its phosphazo derivatives, if HX means an amino group, and if HX means a hydroxy group, its epoxides, halides such as chloride, bromide or iodide,

its sulfonic acid esters such as of methanesulfonic acid or p-toluenesulfonic acid or its esters with aliphatic or aromatic carboxylic acids such as of acetic acid, propionic acid or benzoic acid; and as salts of a carboxylic acid of the general formula II come into consideration its alkali and alkaline earth metal salts such as the sodium, potassium or calcium salt or, its silver salt.

As water Extraction and/or acid activating agents

comes e.g. considering a chloroformic acid ester such as chloroformate ethyl ester, thionyl chloride, phosphorus trichloride, phosphorus pentoxide, N,N'-dicyclohexylcarbodiimide, N,N'-carbonyldiimidazole, N,N<1->thiony1-diimidazole or boron trifluoride etherate.

The reaction is suitably carried out in a solvent such as dichloromethane, chloroform, carbon tetrachloride, ether, dioxane, tetrahydrofuran, benzene, toluene, dimethylformamide or methanol, optionally in the presence of an inorganic base such as sodium carbonate or a tertiary organic base such as triethylamine or pyridine , which at the same time can also serve as a solvent, possibly in the presence of an acid activating agent at temperatures between

-25 and 250°C, preferably at temperatures between -10°C and the boiling temperature of the solvent used. A possibly in situ formed functional derivative of a compound with de

general formulas II and III do not need to be isolated, and furthermore the reaction can also be carried out without a solvent and/or in the presence of a reaction accelerator such as sodium hydride or 4-dimethylaminopyridine. Furthermore, water formed during the reaction can be removed by azeotropic distillation,

e.g. by.heating with toluene on a water separator,

optionally in the presence of a drying agent such as magnesium sulfate or molecular sieves.

However, it has proved particularly advantageous to carry out the reaction with an alkali salt of a carboxylic acid of the general formula II with a compound of the general formula III where HX means a chlorine or bromine atom, in the presence of a reaction accelerator such as alkali iodide, e.g. . sodium or potassium iodide, or in the presence of a phase transfer catalyst such as a so-called crown ether, e.g. 15-krona-5.

If, according to the invention, a compound with the general formula I is obtained where Y together with the carbon atoms in the a- and 3-position in the residue A, if this contains at least

3 carbon atoms, form an oxiranyl group or a 1,3-dioxolanyl-

group with the formula

can this be transferred by means of hydrolysis to a corresponding dihydroxy compound, or a compound with the general formula I where Y means a residue with the formula

can by partial hydrolysis be transferred to a corresponding hydroxy compound, or

a compound of the general formula I where Y means a hydroxy group can be transferred by means of a halogenating agent such as a phosphorus or thionyl halide to the corresponding halogen compound.

The subsequent hydrolysis is carried out in the presence of an acid

such as acetic acid, hydrochloric acid or sulfuric acid, optionally in a solvent such as water/isopropanol, water/dioxane, water/tetrahydrofuran or water/dimethylformamide at temperatures between 0 and 100°C, but preferably at temperatures between 20 and 50°C.

The subsequent partial hydrolysis is conveniently carried out

in a solvent such as isopropanol, tetrahydrofuran, dioxane or dimethylformamide, preferably in the presence of an equivalent base, e.g. an equivalent of caustic soda, caustic soda or potassium carbonate, at temperatures between 20 and 150°C, preferably between 25 and 75°C.

The subsequent transfer of a hydroxy compound to

the corresponding halogen compound is conveniently carried out with thionyl chloride, thionyl bromide, phosphorus trichloride or phosphorus pentachloride, optionally in a solvent such as methylene

chloride, chloroform or dimethylformamide, at temperatures up to the boiling temperature of the reaction mixture.

Furthermore, the new compounds of the general formula I can be transferred with inorganic or organic acids to their physiologically compatible acid addition salts with 1 to 3 equivalents of the relevant acid. Suitable acids are e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, maleic acid or fumaric acid.

The compounds with the general formulas II and III used as starting materials are known from the literature or can be prepared by methods known per se. The benzoic acids with the general formula II are e.g. described in British patent 1,469,187 or can be produced by the methods described there.

As mentioned at the outset, the new aminobenzoic acid derivatives of the general formula I and their salts represent valuable intermediates for the preparation of new anti-inflammatory compounds (see patent (application 80.1931)). These are obtained by reacting an antiphlogistic containing a carboxyl group with a compound of the general formula I prepared according to the invention, i.e. by combining the carboxyl group with the group Y in a compound of the general formula I. Antiphlogistics that are suitable for this purpose, is e.g. the following: 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid, (+)-6-methoxy-a-methyl-2-naphthaleneacetic acid,

2-[(2,6-dichlorophenyl)amino]-phenylacetic acid,

3- benzoyl-α-methyl-phenylacetic acid,

α-methyl-4-(2-methylpropyl)-phenylacetic acid,

2-Fluoro-α-methyl-[1,1<1->biphenyl]-4-acetic acid,

4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)-α-methyl-phenylacetic acid, acetylsalicylic acid,

2-[(2,6-dichloro-3-methylphenyl)amino]-benzoic acid,

2-[(3-chloro.r-2-methylphenyl)amino]-benzoic acid,

5- benzoyl-α-methyl-2-thiopheneacetic acid,

1- methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-acetic acid, 5-fluoro-2-methyl-1-[[4-(methylsulfinyl)phenyl]methylene]-1H-inden-3- acetic acid,

6,11-dihydro-ll-oxo-dibenz[b,e]oxepin-3-acetic acid , 6,11-dihydro-ll-oxo-dibenz[b,e]oxepin-2-acetic acid, α-methyl-5- oxo-5H-dibenzo[a,d]cycloheptene-2-acetic acid, 2-(4-chlorophenyl)-a-methyl-5-benzoxazoleacetic acid, 6-chloro-a-methyl-9H-carbazole-2-acetic acid,

α-ethyl-4-(2-methylpropyl)-phenylacetic acid,

α-methyl-3-phenoxy-phenylacetic acid,

2-(2,4-dichlorophenoxy)-phenylacetic acid,

Y-oxo-[1,1'-biphenyl]-4-butyric acid,

2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid, 1,3,4,9-tetrahydro-1-propyl-pyrano[3,4-b]indole-1 -acetic acid, 1,8-diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, 2-[[4,5-bis(4-chlorophenyl)-2- oxazolyl]thio]-propionic acid, 2-[[3-(trifluoromethyl)phenyl]amino]-benzoic acid,

1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrole-3-acetic acid, 3- chloro-α-methyl-4-(2-thienylcarbonyl)-phenylacetic acid, 2- t(3-chloro-2- methylphenyl)amino]-3-pyridinecarboxylic acid, 2-[[2-methyl-3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic acid 4-(4-chlorophenyl)-2-phenyl-5-thiazoleacetic acid,

3-chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)-α-methyl-phenylacetic acid, 10-methyl-1OH-phenothiazine-2-acetic acid,

7-Methoxy-a,10-dimethyl-10H-phenothiazine-2-acetic acid, 5-chloro-3-meth<y>l-benzo[b]thiophene-2-acetic acid,

α-methyl-4-(2-thienylcarbonyl)-phenylacetic acid,

3-chloro-4-cyclohexyl-Y-oxo-phenylbutyric acid,

2-[(2,3-dimethylphenyl)amino]-benzoic acid and

2-[[3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic acid.

Furthermore, the new aminobenzoic acid derivatives of the general formula I and their physiologically compatible acid addition salts produced according to the invention exhibit valuable pharmacological properties, in addition to a secretolytic and/or antitussive effect, in particular an anti-ulcer effect and an inhibitory effect on gastric juice secretion.

As examples, the following compounds were investigated with respect to their biological effects: A = 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl oxy]-2,3-dihydroxy-n-propane hydrochloride,

B = 0,N-bis-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl]-L-serine methyl ester,

C = 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2-hydroxy-ethane hydrochloride,

D = 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-4-hydroxy-n-butane hydrochloride,

E = 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzamido]- ethane dihydrochloride,

F = 1-(4-amino-3-bromo-5-hexamethyleneimino-benzoyloxy)-5-hydroxy-n-pentane dihydrochloride,

G = 1-[4-amino-3-bromo-5-(N-ethyl-1-cyclopentylaminomethyl)-benzoyloxy]-2-hydroxy-ethane hydrochloride,

H = 1-[4-amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-benzoyloxy]-2-hydroxy-ethane hydrochloride,

I = 1-[4-amino-3-bromo-5-(N-ethyl-cycloheptylaminomethyl)-benzoyloxy (-2-hydroxy-ethane hydrochloride,

K = 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl]-D-mannitol hydrochloride,

L = 2-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl]-(+)-tartaric acid diethyl ester hydrochloride,

M = N-[2-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-ethyl]-N-(2-hydroxyethyl)-methylamine and

N = 2-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2<1->hydroxy-diethyloxide

1. Anti-ulcer effect

The anti-ulcer effect was determined as anti-gastritis-

effect on rats (Goldenberg et al, Gastroenterology 69,

636 (1975)). Fasting female rats with a body weight of 200 to 230 g received 100 mg/kg of the test compound (test group) or the suspension agent 1% tylose in a corresponding amount (control group) orally per pharyngeal tube.

After 1 hour, all animals received 3 ml of a 50% ethanol solution orally. After a further 4 hours, the rats were euthanized, and the mucosal changes in the stomach were assessed visually on a scale from 0 = no changes to 5 = numerous streak-like bleeding erosions. The reduction of the bleeding erosions by treatment with the test compound compared to the controls was calculated as a percentage.

2. Acute toxicity

For 3 female mice and 3 male mice per compound, with a body weight of 20 to 26 g, the toxic effect of each time 1000 mg/kg of the test compound by single oral intake was determined (observation time: 14 days).

The following table contains the values found:

Due to their biological properties, the compounds of the general formula I and their physiologically compatible acid addition salts are thus suitable for the treatment of inflammatory conditions in the gastric mucosa, and can be prepared for pharmaceutical use, possibly in combination with other active substances, in ordinary pharmaceutical preparations such as tablets, dragees, capsules, powders, suppositories, ampoules, drops or suspensions. The single dose for humans is 25 to 250 mg, preferably 50 to 150 mg, 2 to 4 times a day. Example 1 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2,3-dihydroxy-n-propane 70 g (0.185 mol) 4-amino-3-bromo-5 -(N-ethyl-cyclohexylaminomethyl)-benzoic acid sodium salt is suspended in 250 ml of 1-chloro-2,3-dihydroxy-n-propane and heated with stirring for 3 hours to 110-120°C. Then the main amount of excess 1-chloro-2,3-dihydroxy-n-propane is distilled off at a pressure of 0.02 mm Hg, the residue is dissolved in a mixture of methylene chloride: methanol: conc. ammonia (90/10/1) and chromatographed over silica gel. The viscous oil obtained is dissolved in 130 ml of isopropanol, and after dilution with 200 ml of acetic acid ethyl ester, it is transferred with ethereal hydrochloric acid to the hydrochloride, which crystallizes at 0-5°C within 24 hours. The crystals are filtered off, washed with a little ether and dried.

Melting point of the hydrochloride: 167-173°C.

Example 2

1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2-hydroxy-ethane 41 g (0.1 mol) 4-amino-3-bromo-5-(N- ethyl-cyclohexylaminomethyl)-benzoyl chloride-hydrochloride is dissolved in 250 ml of ethylene glycol and heated for 1 hour to 105°C after the addition of 17 g (0.22 mol) of pyridine. After cooling to room temperature, dilute with 1 liter of water, after adding caustic soda, extract with ether, dry the ether solution over sodium sulphate and evaporate to dryness. The residue is chromatographed over silica gel (ethyl acetate). Evaporation of the eluate gives a resin which crystallizes by rubbing with petroleum ether and is recrystallized from ethanol.

Melting point: 72-75°C.

Example 3

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzamido]-3- hydroxy- n- propane

Dissolve 30 g (0.073 mol) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride in 400 ml of tetrahydrofuran and slowly add dropwise to a solution of 15 g

(0.2 mol) of 3-amino-n-propanol in 300 ml of tetrahydrofuran. The mixture is stirred for 1/2 hour at 50°C and then evaporated in vacuo. The residue is distributed between water and chloroform, the chloroform phase is separated, dried and evaporated. The residue is dissolved in isopropanol, acidified with ethanolic hydrochloric acid and diluted with ether. The hydrochloride is suctioned off and dried.

Melting point of the hydrochloride: 110-113°C.

Example 4

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzamido]-4- hydroxy- n- butane

27.5 g (0.067 mol) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride are dissolved in 400 ml of tetrahydrofuran and slowly added dropwise to a solution of 12 g (0.135 mol) of 4- amino-butanol. The mixture is stirred for 1/2 hour at 50°C and then evaporated in vacuo. The residue is distributed between water and chloroform, the chloroform phase is separated, dried and evaporated. The residue is purified by chromatography on silica gel (chloroform:methanol (9/1)). When the eluate is evaporated, an oil is obtained.

IR spectrum (methylene chloride): amide-CO 1650 cm

UF spectrum (ethanol): ^max 285 nm.

Example 5

1- f4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2, 3- dihydroxy- n- propane

2.1 g (0.05 mol) of 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2,3-epoxy-n-propane is dissolved in 100 ml of water and 100 ml of methanol. The obtained resolution is set to

pH 2-3 with sulfuric acid and boil for 2 hours under reflux

cooling after adding approx. 20 mg iron(III) chloride.

After cooling, the reaction mixture is neutralized and evaporated

to dryness in vacuo and the residue is purified by chromatography on silica gel (methylene chloride: methanol: conc. ammonia (90/10/1)).

The oil obtained is dissolved in isopropanol and brought to crystallization as hydrochloride by adding ethereal hydrochloric acid and acetic acid ethyl ester.

Melting point of the hydrochloride: 167-173°C.

Example 6

1-( 4- amino- 3- bromo- 5- diethylaminomethyl- benzoyloxy)- 6- chloro- n- hexane

Dissolve 5.2 g (0.013 mol) of 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-6-hydroxy-n-hexariin in 15 ml of chloroform and stir with 15 ml of thionyl chloride for 3 hours at 60° C. The reaction mixture is evaporated, and the residue is taken up in chloroform. The organic phase is washed with sodium bicarbonate solution, dried and evaporated. The residue obtained is dissolved in isopropanol,

and the hydrochloride is precipitated with ethereal hydrochloric acid.

Melting point of the hydrochloride: 121-122°C.

Example 7

N- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyl]- L- serine- methyl ester

A solution of 27.4 g (0.07 mol) 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoic acid hydrochloride in 250 ml dimethylformamide is added portionwise 13 g (0.08 mol) N, N<1->carbonyldiimidazole under stirring and at room temperature. After the addition is complete, the reaction mixture is heated to 50°C, and this temperature is maintained for 1 hour. After cooling to room temperature, a solution of 12.5 g (0.08 mol) L-serine methyl ester hydrochloride and 8.1 g (0.08 mol) triethylamine in 100 ml dimethylformamide is added with further stirring and stirred in another 16 hours. The solvent is then removed in vacuo and the residue is distributed between water and chloroform. The chloroform phase is washed with water, dried over sodium sulphate and evaporated in vacuo. A pale yellow oil remains which is chromatographed over silica gel (500 g silica gel, chloroform: ethyl acetate = 3/1). A colorless foam is obtained.

UV spectrum (ethanol): A maK , s 230 nm (shoulder), 290 nm.

Example 8

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyl3- D- mannitol

8.25 g (8.9 mmol) of 1,6-bis-[4-amino-3-bromo-5-(N-ethyl-cyclohexy1-aminomethyl)-benzoyl]-D-mannitol dihydrochloride are dissolved in 250 ml of tetrahydrofuran and 100 ml of water. At room temperature, a solution of 13.5 ml of 2N caustic soda in 100 ml of tetrahydrofuran is added dropwise while stirring. The reactive ion solution is stirred for 2 1/2 hours at room temperature, after thin-layer chromatographic determination, 300 ml of ether is added and after a short period of shaking, the formed phases are separated. The organic phase is then extracted with 2N hydrochloric acid, the aqueous hydrochloric acid extracts are made alkaline with concentrated ammonia and extracted with ether. The ether extracts are washed with water, dried over magnesium sulphate and evaporated in vacuo. After subsequent chromatography of the evaporation residue over silica gel (chloroform: methanol: conc. ammonia = 9/1/0.1), the fractions obtained are evaporated to dryness in vacuum, the evaporation residue is dissolved in 150 ml of ethyl acetate, and the solution is added to the calculated amount of a ethereal hydrochloric acid. After extraction, the hydrochloride obtained is recrystallized from methanol/ethyl acetic acid ester.

Melting point for the hydrochloride: 153-160°C (dec.).

Example 9

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2, 3- dihydro- n- propane

9.8 g (0.025 mol) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoic acid hydrochloride are suspended in 10 g (0.135 mol) of 2,3-epoxy-n-propanol and heated for 3 hours to 60°C after adding 250 mg of iron(III) chloride. The reaction mixture is distributed between water and chloroform, the chloroform phase is separated,

dried and evaporated to dryness. The residue is purified by chromatography

on silica gel (methylene chloride/methanol: conc. ammonia = 90/10/1). The eluate is evaporated, the residue is dissolved in isopropanol, and the hydrochloride is brought to crystallization with ethanolic hydrochloric acid/acetic acid ethyl ester.

Melting point for the hydrochloride: 167-173°C.

Example 10

1- [ 4- amino- 3- bromo- 5- ( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2- chloro- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 2-chloro-ethanol analogously to example 2.

Melting point for the hydrochloride: 162-164°C.

Example 11

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2- chloro- ethane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2-hydroxy-ethane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 162-164°C.

Example 12

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-3- chloro- n- propane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-3-hydroxy-n-propane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 185-187°C.

Example 13

1-[ 4- amino- 3- bromo- 5- (N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-4- chloro- n- butane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-4-hydroxy-n-butane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 158-160°C.

Example 14

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-5- chloro- n- pentane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyloxy]-5-hydroxy-n-pentane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 141-142.5°C.

Example 15

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy3 - 7- chloro- n-heptane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-7-hydroxy-n-heptane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 129-131°C.

Example 16

1- [ 4- aminl- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-8- chloro- n- octane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-1-cyclohexylamino-.methyl)-benzoyloxy]-8-hydroxy-n-octane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 114-117°C.

Example 17

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-3- hydroxy- n- propane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,3-propanediol in the presence of pyridine and triethylamine analogously to example 2.

Melting point of the hydrochloride. 184-185°C.

Example 18'

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-4- hydroxy- n- butane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,4-butanediol in the presence of pyridine and triethylamine analogously to example 2.

Melting point for the hydrochloride: 148-150°C.

Example 19

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-5- hydroxy- n- pentane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,5-pentanediol in the presence of pyridine and triethylamine analogously to example 2.

Melting point for the hydrochloride: 158-160°C.

Example 20

1-[ 4- amino- 3- bromo- 5-( N- ethyl1- cyclohexylaminomethyl)- benzoyloxy]-6- hydroxy- n- hexane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,6-hexanediol in the presence of pyridine and triethylamine analogously to example 2.

Melting point of the hydrochloride: 98-101°C.

Example 21

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-7- hydroxy- n-heptane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,7-heptanediol in the presence of triethylamine and 4-dimethylaminopyridine analogously to example 2. Melting point of the hydrochloride: 102- 104°C (dec.).

Example 22

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-8- hydroxy- n- octane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,8-octanediol in the presence of triethylamine and 4-dimethylaminopyridine analogously to example 2. Melting point of the hydrochloride: 99- 103°C.

Example 23.

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-4- hydroxy- cyclohexane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,4-cyclohexanediol in the presence of pyridine and triethylamine analogously to example 2.

IR spectrum (methylene chloride): ester-CO 1700 cm

UV spectrum (ethanol): X max 230 nm, 298-300 nm.

Example 24

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2- hydroxy- n- propane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,2-propanediol in the presence of pyridine analogously to example 2. Oil.

IR spectrum (methylene chloride). ester-CO 1710 cm

UV spectrum (ethanol) : 230 nm (shoulder), 297 nm.

Example 2 5

2- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-3- hydroxy- n- butane

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 2,3-butanediol in the presence of pyridine analogously to example 2. Oil.

IR spectrum (methylene chloride): ester-CO 1705 cm

UV spectrum (ethano<l>)<:>A niciK s<2>30 nm (shoulder), 2.99 nm.

Example 26

N, O- bis-[ 4-amino- 3- bromo- 5-( N- ethyl- cyclohexylamino)- benzoyl]- L- serine- methyl ester Prepared from 4-amino-3- bromo-5-(N-ethyl- cyclohexylaminomethyl)-benzoic acid-imidazolide and L-serine methyl ester analogously to example 7. Foam.

IR spectrum (methylene chloride) : amide-CO 1660 cm 1

ester-CO 1710 and 1730 cm"1 UV spectrum (ethanol): A maK s230 nm (shoulder), 295 nm.

Example 2 7

2-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyl]-( + )- tartaric acid diethyl ester

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and (+)-tartaric acid diethyl ester analogously to example 2. Oil.

C24H35BrN2°7 <543'5)

Calculated: C 53.04, H 6.49, Br 14.70, N 5.15

Found: 53.30 6.59 14.55 5.12

Example 28

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2, 3- epoxy- n- propane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoic acid sodium salt and 2,3-epoxy-propyl chloride analogously to example 1. (The product was purified by chromatography on

silica gel). Oil.

IR spectrum (methylene chloride): ester-CO 1705 cm

UV spectrum (ethanol) : ^aks 300 nm'

Example 29

2- [ 4- amino- 3- bromo-5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2'- hydroxy- diethyl oxide

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 2,2'-dihydroxydiethyl oxide analogously to example 2. Oil.

C20H31BrN2°4 (443'4)

Calculated: C 54.18, H 7.05, Br 18.02, N 6.32

Found: 53.90 7.19 18.25 6.26

Example 30

N-[ 2-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-ethyl]- N-( ?- hydroxyethyl)- methylamine

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and N-methyl-diethanolamine analogously to example 2. Oil.

C21H34BrN3°3 (456'4)

Calculated: C 55.26, H 7.51, Br 17.51, N 9.21

Found: 55.30 7.62 17.75 9.06

Example 31

1-[ 2-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-ethyl]- 4-( 2- hydroxyethyl)- piperazine

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,4-bis-(2-hydroxyethyl)-piperazine analogously to example 2. Oil.

IR spectrum (methylene chloride): ester-CO 1710 cm

N-alkyl 2830 cm"<1>

UV spectrum (ethanol): X ITlcl, K S 300 nm.

Example 32

1- [ 3-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy3 - propyl]- 4-( 2- hydroxyethyl)- piperazine

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoic acid sodium salt and 1-(3-chloropropyl)-4-(2-hydroxyethyl)-piperazine analogously to example 1.

Melting point for the trihydrogen maleate: 144-146°C (dec.).

Example 33

1, 6- bis-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyl]- D-mannitol- dihydrochloride

Prepared from 2 mol of 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1 mol of D-mannitol analogously to example 2. The dihydrochloride sintered from 130°C and was decomposed at 220°C.

IR spectrum (KBr): ester-CO 1710 cm"<1>

N-alkyl 2840 cm"<1>

UV spectrum (ethano<l>)<:>A ma, Ks<2>30 nm, 295 nm.

Example 34

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2- hydroxy- 3- chloro- n- propane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoic acid hydrochloride and epichlorohydrin analogously to example 9. Oil.

IR spectrum (methylene chloride). ester-CO 1710 cm

UV spectrum (ethanol) : ^ma]<s300 nm.

Example 35

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzmido]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and ethanolamine analogously to example 4. Melting point for the hydrochloride: from 65°C (dec.).

Example 36

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzamido]-5- hydroxy- n- pentane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 5-amino-pentanol-1 analogously to example 4. Oil.

IR spectrum (methylene chloride): amide-CO 1650 cm 1.

UV spectrum (ethano<l>)<:>^max ^85•

Example 37

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzamido]-6- hydroxy- n- hexane

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 6-amino-hexanol-1 analogously to example 4. Oil.

IR spectrum (methylene chloride): amide-CO 1650 cm<1>

UV spectrum (ethanol): A ma, K s 285 nm.

Example 38

trans- 1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)-benzamido]- 4- hydroxy- cyclohexane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 4-trans-hydroxy-cyclohexylamine in the presence of pyridine and triethylamine analogously to example 4. Melting point of the dihydrochloride: 176°C ( split.).

E xample 3 9

N-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyl]-D- glucosamine

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and D-glucosamine analogously to example 3. Melting point: 100-190°C (slow decomposition during foaming).

<C>22<H>24<B>rN3°6(516'5)

Calculated: C 51.16, H 6.64, Br 15.47, N 8.14

Found: 51.00 6.87 15.30 8.00

Example 40

1-[4-amino- 3- bromo- 5-( N-e thyl- cyclohexylaminomethyl)- benzmido]- 2-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy] ethane Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and ethanolamine in the presence of triethylamine analogously to example 2.

Melting point for the dihydrochloride: from 170°C (decomp.)

Example 41

1- [ 4-amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzamido]-2- amino- ethane Prepared from 4-amino-3-bromo-5-(N-ethyl- cyclohexylaminomethyl)-benzoyl chloride -hydrochloride and ethylenediamine analogously to example 4.

Melting point: from 85°C (dec.).

Example 4 2

1, 2-bis-[4-amino-3-bromo-5-(N-ethyl- cyclohexylaminomethyl)-b enzamido]- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and ethylenediamine analogously to example 4. Melting point: 218-219°C.

Example 4 3

1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2-chloroethane Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2-hydroxyethane and thionyl chloride analogously with example 6. Melting point for the hydrochloride: 142-145°C.

Example 44

1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-3-chloro-n-propane Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-3-hydroxy- n-propane and thionyl chloride analogously to example 6. Melting point for the hydrochloride: 167-168°C.

Example 4 5

1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-4-chloro-n-butane Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-4-hydroxy-n -butane and thionyl chloride analogously to example 6. Melting point for the hydrochloride: 159-162°C.

Example 46

1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-5-chloro-n-pentane Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-5-hydroxy-n -pentane and thionyl chloride analogously to example 6. Melting point for the hydrochloride: 117-119°C.

Example 47

1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-6-chloro-n-hexane Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-berizoyloxy)-6-hydroxy-n -hexane and thionyl chloride analogously to example 6. Melting point for the hydrochloride: 121-122°C.

Example 48

1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2-hydroxyethane Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2 .

Melting point for the hydrochloride: 151-152°C.

Example 4 9

1-( 4- amino- 3- bromo- 5- diethylaminomethyl- benzoyloxy)- 3- hydroxy-n- propane

Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl chloride hydrochloride and 1,3-propanediol in the presence of pyridine and triethylamine analogously to Example 2.

Melting point for the hydrochloride: 139-141°C.

Example 50

1-( 4- amino- 3- bromo- 5- diethylaminomethyl- benzoyloxy)- 4- hydroxy-n- butane

Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl chloride hydrochloride and 1,4-butanediol in the presence of pyridine and triethylamine analogously to example 2.

Melting point for the hydrochloride: 163-165°C.

Example 51

1-( 4- amino- 3- bromo- 5- diethylaminomethyl- benzoyloxy)- 5- hydroxy-n- pentane

Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl chloride hydrochloride and 1,5-pentanediol in the presence of pyridine and triethylamine analogously to Example 2.

Melting point for the hydrochloride: 137.5-138.5°C.

Example 52

1-( 4- amino- 3- bromo- 5- diethylaminomethyl- benzoyloxy)- 2, 3-dihydroxy- n- propane

Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoic acid sodium salt and 3-chloro-1,2-propanediol analogously to example 1.

Mass spectrumM+ 374/6 m/e (monobromine)

Calculated: ci5H23<B>rN2°4(374/5)

Example 53

1- ( 4- amino- 3- b. rom- 5- diethylaminomethyl 1- benzoyloxy) - 2- hydroxy-3- chloro- n- propane

Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoic acid

and epichlorohydrin analogously to example 9.

IR spectrum (methylene chloride): ester-CO 1715 cm

UV spectrum (ethanol): ^ max 230 nm, 298-300 nm.

Example 54

1-( 4-amino- 3-bromo- 5- hexamethyleneiminomethyl- benzoyloxy)- 5- chloro-n- pentane

Prepared from 1-(4-amino-3-bromo-5-hexamethyleneiminomethyl-benzoyloxy)-5-hydroxy-n-pentane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 160-162°C.

Example 5 5

1-[ 4- amino- 3- bromo- 5-( N- ethyl1- cyclopentylaminomethyl)- benzoyloxy]-5- chloro- n- pentane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-cyclopentylamino-methyl)-benzoyloxy]-5-hydroxy-n-pentane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 131-133°C.

Example 56

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cycloheptylaminomethyl)- benzoyloxy]-5- chloro- n- pentane

Prepared from 1-[4-amino-3-bromo-5-(N-ethyl-cycloheptylaminomethyl)-benzoyloxy]-5-hydroxy-n-pentane and thionyl chloride analogously to example 6.

Melting point for the hydrochloride: 156-158°C.

Example 5 7

1-[ 4- amino- 3- bromo- 5-( N- cyclohexy1- n- propylaminomethyl)- benzoyloxy]- 5- chloro- n- pentane

Prepared from 1-[4-amino-3-bromo-5-(N-cyclohexyl-n-propyl-aminomethyl)-benzoyloxy]-5-hydroxy-n-pentane and thionyl chloride analogously to example 6.

Example 5 8

1-(4-amino-3-bromo-5-dimethylaminomethyl-benzoyloxy)-2-hydroxyethane Prepared from 4-amino-3-bromo-5-dimethylaminomethyl-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2 .

Melting point for the hydrochloride: 80-81°C.

Example 59

1-( 4- amino- 3- bromo- 5- iso propyl aminomethyl- benzoyloxy)- 2- hydroxyethane

Prepared from 4-amino-3-bromo-5-isopropylaminomethyl-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 90-93°C.

Example 60

1- [ 4- amino- 3- bromo- 5-( N- methyl1- n- propylaminomethyl)- benzoyloxy]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-methyl-n-propylaminomethyl)-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 124-128°C.

Example 61

1-( 4- amino- 3- bromo- 5- tert. butylamino methyl- benzoyloxy)- 2- hydroxyethane

Prepared from 4-amino-3-bromo-5-tert.butylaminomethyl-benzoyl-chloride-hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 192-194°C.

Example 6 2

1-( 4- amino- 3- bromo- 5- cyclohexylaminomethyl- benzoyloxy)-2- hydroxyethane

Prepared from 4-amino-3-bromo-5-cyclohexylaminomethyl-benzoyl-1-chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point of the dihydrochloride: 149°C (dec.)

Example l 6 3

1- [ 4- amino- 3- bromo- 5-( N- cyclohexy1- methylaminomethyl)- benzoyloxy]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-cyclohexy1-methylaminomethyl)-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 169-171°C.

Example 64

1- [ 4- amino- 3- bromo- 5-( N- ethyl1- cyclopentylaminomethyl)- benzoyloxy]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cyclopentylaminomethyl)-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to Example 2.

Melting point for the hydrochloride: 186-187°C.

Example 65

1- [ 4- amino- 3- bromo- 5-( N- ethyl l- cycloheptylaminomethyl)- benzoyloxy]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cycloheptylaminomethyl)-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 166-168°C.

Example 66

1- [ 4- amino- 3- bromo- 5-( N- cyclohexy1- n- propylaminomethyl)- benzoyloxy]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-cyclohexyl-n-propylamino-methyl)-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 194-196°C.

Example 67

1-[ 4- amino- 3- bromo- 5-( 4- pyridylaminomethyl)- benzoyloxy]- 2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(4-pyridylaminomethyl)-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 217-218°C.

Example 6 8

1-(4-amino-3-brom-5-pyrroidinomety1-benzoyloxy)-2-hydroxyethane Prepared from 4-amino-3-bromo-5-pyrrolidinomethyl-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 213-214°C

Example 69

1-(4-amino-3-bromo-5-piperidinomethy1-benzoyloxy)-2-hydroxyethane Prepared from 4-amino-3-bromo-5-piperidinomethy1-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 214-216°C.

Example 70

1-(4-amino-3-bromo-5-morpholinomethyl-benzoyloxy)-2-hydroxyethane Prepared from 4-amino-3-bromo-5-morpholinomethyl-benzoyl chloride hydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the hydrochloride: 179-181°C.

Example 71

1-[ 4- amino- 3- bromo- 5-( 4- methyl- piperazinomethyl)- benzoyloxy]- 2-hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(4-methyl-piperazinomethyl)-benzoyl chloride dihydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point for the dihydrochloride: 163-165°C.

Example 72

1-( 4- amino- 3- bromo- 5- hexamethyleneiminomethyl- benzoyloxy)-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-hexamethyleneiminomethyl)-benzoyl-chloride-dihydrochloride and ethylene glycol in the presence of pyridine analogously to example 2.

Melting point of the hydrochloride: 209°C (dec.).

Example 73

1- [ 4- amino- 3- bromo- 5- ( 2- diethylaminoethylaminomethyl)- benzoyloxy]-2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(2-diethylaminoethylaminomethyl)-benzoyl chloride dihydrochloride and ethylene glycol in the presence of pyridine analogously to Example 2.

Melting point for the dihydrochloride: 87-90°C (dec.).

Example 74

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cycloheptylaminomethyl)- benzoyloxy]-5- hydroxy- n- pentane

Prepared from 4-amino-3-bromo-5-(N-ethyl1-cycloheptylaminomethyl)-benzoyl chloride hydrochloride and 1,5-pentanediol in the presence of pyridine analogously to Example 2.

Melting point for the hydrochloride: 162-163°C.

Example 75

1-[ 4- amino- 3- bromo- 5-( N- cyclohex yl- n- propylaminomethyl)- benzoyl oxy]-5- hydroxy- n- pentane

Prepared from 4-amino-3-bromo-5-(N-cyclohexy1-n-propylamino-methyl)-benzoyl chloride hydrochloride and 1,5-pentanediol in the presence of triethylamine and 4-dimethylamino-pyridine analogously to example 2. Melting point for the hydrochloride: 140-142°C.

Example 76

4-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy-methyl]-2,2-dimethyl-1,3-dioxolane 5 g (0.013 mol) 4-amino-3-bromo -5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy-ethane is heated in 20 g of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane with the addition of 0.1 g of sodium hydride for 3 hours at 100°C. The ethanol formed during the reaction is distilled off.

After cooling, the reaction mixture is distributed between water and methylene chloride, the organic phase is separated, dried over sodium sulphate and evaporated. The remaining residue is dissolved in hot isopropanol, and after standing for a long time during cooling, crystals are obtained which are suctioned off, washed with a little isopropanol and dried.

Melting point: 78-83°C.

Example 77

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl- benzoyloxy]-2, 3- dihydroxy- n- propane

4.7 g (0.1 mol) of 4-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl-benzoyloxymethyl]-2,2-dimethyl-1,3-dioxolane are dissolved in 30 ml of dioxane. To this solution is added 2N hydrochloric acid to pH 0.6 and allowed to stand for 48 hours at room temperature. It is then made slightly alkaline with 2N ammonia solution and extracted 3 times with methylene chloride. The organic phase is dried over sodium sulfate and evaporated, the residue is dissolved in isopropanol and transferred with ethereal hydrochloric acid to the hydrochloride, which crystallizes out after standing for a long time during cooling.

Melting point: 167-173°C.

Example 78

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2, 3- dihydroxy- n- propane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy-ethane and glycerol analogously to example 76. The reaction can be carried out without solvent or in a solvent such as ethylene glycol diethyl ether.

Melting point for the hydrochloride: 167-173°C.

Example 79

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-1- phenyl- 2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoic acid sodium salt and 1-phenyl-2-hydroxy-ethyl chloride analogously to example 1. Oil.

UV spectrum (ethanol): A rticiK, . s 230 nm, 297 nm.

Example 80

1- [ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-2- phenyl- 2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and phenyl-ethylene glycol analogously to example 2. Oil.

UV spectrum (ethanol): ^max 293 nm.

Example 81

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-1, 2- diphenyl- 2- hydroxy- ethane

Prepared from 4-amino-3-bromo-5-(N-ethyl-1-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,2-diphenyl-ethylene glycol. analogous to example 2. Oil.

UV spectrum (ethanol): , 295 nm.

max

Example 82

1- [ 4- amino- 3- b. rum- 5- ( N- ethyl- cyclohexylaminomethyl) - benzoyloxy ] - 2- hydroxymethyl- 2- methyl- n- pentane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 2,2-bis-hydroxymethyl-n-pentane analogously to example 2. Oil.

UV spectrum (ethanol): A , 288 nm.

^ max.

Example 83

2-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzo yloxy-methyl]- 6- hydroxymethyl- pyridine

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 2,6-bis-hydroxymethyl-pyridine analogously to example 2. Oil.

UV spectrum (ethano<l>)<:>A IT13.K, .S 230 nm, 298 nm.

Example 8 4

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy-methyl3- 4- hydroxymethyl- benzene

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,4-bis-hydroxymethyl-benzene analogously to example 2. Oil.

UV spectrum (ethanol): A maK. s 295 nm.

Example 85

1-[ 4- amino- 3- bromo- 5-( N- ethyl- cyclohexylaminomethyl)- benzoyloxy-methyl]- 4- hydroxynrety1- cyclohexane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,4-bis-hydroxymethyl-cyclohexane analogously to example 2. Oil.

UV spectrum (ethanol): A max, s294 nm.

Example 86

1-( 4- amino- 3- bromo- 5- dimethylaminomethyl- benzoyloxy)- 5- hydroxy-n- pentane

Prepared from 4-amino-3-bromo-5-dimethylaminomethyl-benzoyl chloride hydrochloride and 1,5-dihydroxy-n-pentane analogously to Example 2, with in the presence of triethylamine and 4-dimethylaminopyridine instead of pyridine.

Melting point for the hydrochloride: 155-157°C.

Example 87

1-( 4- amino- 3- bromo- 5- fluoropholinomethy1- benzoyloxy)- 5- hydroxy-n- pentane

Prepared from 4-amino-3-bromo-5-morpholinomethyl-benzoyl chloride hydrochloride and 1,5-dihydroxy-n-pentane analogously to example 86. Melting point for the hydrochloride: 205-207°C.

Example 88

1-( 4- amino- 3- bromo- 5- piperidinomethyl- benzoyloxy)- 5- hydroxy-n- pentane

Prepared from 4-amino-3-bromo-5-piperidinomethy1-benzoyl chloride hydrochloride and 1,5-dihydroxy-n-pentane analogously to example 86. Melting point for the hydrochloride: 186-188°C.

Example 89

1-[ 4- amino- 3- bromo- 5-( 4- methyl- piperazinomethyl)- benzoyloxy]- 5- hydroxy- n- pentane

Prepared from 4-amino-3-bromo-5-(4-methyl-piperazinomethyl)-benzoyl chloride hydrochloride and 1,5-dihydroxy-n-pentane analogously to example, 86 .

Melting point for the dihydrochloride: 182-185°C.

Example 90

1-[ 4- amino- 3- bromo- 5-( N- cyclohexyl- methylaminomethyl)- benzoyloxy]-5- hydroxy- n- pentane

Prepared from 4-amino-3-bromo-5-(N-cyclohexyl-methylaminomethyl)-benzoyl chloride hydrochloride and 1,5-dihydroxy-n-pentane analogously to Example 86.

Melting point for the dihydrochloride: 123-126°C.

Example 91

1-[ 4- amino- 3- bromo- 5-( 4- methylpiperazinomethyl)- benzoyloxy]- 4- hydroxy- n- butane

Prepared from 4-amino-3-bromo-5-(4-methylpiperazinomethyl)-benzoyl chloride hydrochloride and 1,4-dihydroxy-n-butane analogously to Example 86.

Melting point for the dihydrochloride: 200-202°C.

Example 9 2

1-( 4- amino- 3- bromo- 5- hexamethyleneiminomethyl- benzoyloxy)- 4- hydroxy- n- butane Prepared from 4-amino-3- bromo-5-hexamethyleneiminomethyl- benzoy1- chloride hydrochloride and 1,4- dihydroxy-n-butane analogous to example 86.

Melting point for the hydrochloride: 159-161°C.

Example 9 3

1-[ 4- amino- 3- bromo- 5-( N- cyclohexyl- methylaminomethyl)- benzoyloxy]-4- hydroxy- n- butane

Prepared from 4-amino-3-bromo-5-(N-cyclohexy1-methylamino-methyl)-benzoyl chloride hydrochloride and 1,4-dihydroxy-n-butane analogously to Example 86.

Melting point of the hydrochloride: 16 3-165°C.

Example 94

1-( 4- amino- 3- bromo- 5- pyrrolidinomethyl- benzoyloxy)- 4- hydroxy-n- butane

Prepared from 4-amino-3-bromo-5-pyrrolidinomethyl-benzoyl chloride hydrochloride and 1,4-dihydroxy-n-butane analogously to example 86. Melting point for the hydrochloride: 140-144°C.

Example 9 5

1-( 4- amino- 3- bromo- 5- morpholinomethyl- benzoyloxy)- 4- hydroxy-n- butane

Prepared from 4-amino-3-bromo-5-morpholinomethyl-benzoyl chloride hydrochloride and 1,4-dihydroxy-n-butane analogously to example 86. Melting point for the hydrochloride: 182-184°C.

Example 96

1-(4-amino-3-bromo-5-piperidinomethy1-benzoyloxy)-4-hydroxy-n-butane Prepared from 4-amino-3-bromo-5-piperidinomethy1-benzoyl chloride hydrochloride and 1,4-dihydroxy-n -butane analogous to example 86. Melting point for the hydrochloride: 170-172°C.

Example 9 7

1-[ 4- amino- 3- bromo- 5- (N- ethyl- cyclohexylaminomethyl)- benzoyloxy]-9- hydroxy- n- nonane

Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl chloride hydrochloride and 1,9-dihydroxy-n-nonane analogously to Example 86.

Melting point for the hydrochloride: 73-76°C.

Claims (3)

1. Analogy method for the production of new, therapeutically active aminobenzoic acid derivatives with the general formula where R-^ means a hydrogen, fluorine, chlorine or bromine atom, R2 and R^ , which may be the same or different, mean linear or branched alkyl groups of 1 to 6 carbon atoms which may be substituted with a phenyl group or a dialkylamino group of 1 to 3 carbon atoms in each alkyl part, pyridyl or cycloalkyl groups of 5 to 7 carbon atoms, or R2 and R^ together with the intervening nitrogen atom may form a pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-arylpiperazino or N-alkylpiperazino group, where the alkyl group contains 1 to 3 carbon atoms, or one of the residues R2 or R^ can also mean a hydrogen atom, A means a cycloalkylene group with 5 to 7 carbon atoms, a linear alkylene group with 2 to 10 carbon atoms which may be substituted with 1 or 2 alkyl groups with each 1 to 3 carbon atoms, with 1 or 2 car alkoxy groups with a total of 2 to 4 carbon atoms each, with 1 or 2 phenyl groups, with 1 to 4 hydroxy groups and/ or with a group with the formula where R^ , R 2 and R^ are as indicated above, or are interrupted by an oxygen or sulfur atom or by a sulfoxide, sulfonyl, benzene, cyclohexane, pyridine, piperazino or imino group, where the imino group may be substituted with an alkyl group with 1 to 6 carbon atoms, or with a phenyl or phenylalkyl group with 1 to 3 carbon atoms in the alkyl part, X means an oxygen atom or an imino group, and Y means a hydroxy or amino group, a chlorine-* bromine- or iodine atom, a residue with the formula where , R^°9 ^3 is as indicated above, and Z means an oxygen atom or an imino group, or together with the carbon atoms in the a- and 3~ position in the residue A, if this contains at least 3 carbon atoms, an oxiranyl group or an 1,3-dioxolanyl group with the formula where R^ and R^-, which may be the same or different, mean hydrogen atoms, alkyl groups with 1 to 3 carbon atoms or phenyl groups, and physiologically compatible acid addition salts thereof with inorganic or organic acids, characterized in that a carboxylic acid with the general formula where R-^ , R 2 and R^ are as indicated above, its salts or reactive derivatives, are reacted with a compound of the general formula where A, X and Y are as indicated above, or the group HX together with the carbon atoms in the a- and 3~ position in the residue A is an oxiranyl group, or its reactive derivatives, and an obtained compound with the general formula I where Y together with the carbon atoms in the a- and 3-position in the residue A, if this contains at least 3 C atoms, means an oxiranyl group or a 1,3-dioxolanyl group with the formula where R. and R,- are as stated above, are transferred optionally by hydrolysis to a corresponding dihydroxy compound, or,. an obtained compound of the general formula I where Y means a hydroxyl group is optionally transferred by halogenation to a corresponding halogen compound and/or an obtained compound of the general formula I is converted into its physiologically compatible acid addition salts with 1 to 3 equivalents of the appropriate inorganic or organic acid. 2. Method as specified in claim 1 for the production of 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy]-2,3-dihydroxy-n-propane, characterized in that a starting material of formula II is used where R-^ means 3 -bromo, R2 means ethyl, R^ means cyclohexyl, the group NR2 R3 -CH2~ is in the 5-position and the amino group in the 4-position, and a compound of formula III where X means oxygen, A means a 2-hydroxy-n-propylene group, and Y means a hydroxy group, or A and Y are converted to the aforementioned meanings. 3. Process as stated in claim 1 for the production of 1-[4-amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-benzoyloxy]-2-hydroxy-ethane, characterized in that a starting material is used with formula II where R^ means 3-bromo, R2 means n-propyl, R^ means cyclohexyl, the group NR2 R.j -CH2 -is in the 5-position and the amino group in the 4-position, and a compound of formula III where X means oxygen , A means ethylene and Y means hydroxy.