NO761050L - - Google Patents

Description

Carboxylic acid amides, process for their preparation, as well as their use as medicine. , ' .

The invention relates to new carboxylic acid amides. a method for their preparation, as well as their use as medicine, especially as hypolipidemics.

Compounds with a comparable structure and a similar mechanism of action have so far not been known.

It has been found that the new carboxylic acid amides of the general formula

where

R<1>, R2 and; R^ are the same or different and mean

a straight, branched, cyclically saturated and unsaturated hydrocarbon residue, where the carbon chain is optionally interrupted by two-bonded heteroelements or groupings such as oxygen, sulphur, sulfine, sulfone, carMonyl, phenylene, optionally substituted with substituents such as halogen, alkoxy, acyloxy, aryl, aryloxy, arylmercapto, aroyl, alkylmercapto, alkylsulfine and alkylsulfone, acylamino, aroylamino, cyano, alkoxycarbonyl, aroxycarboryl or aminocarbonyl, the aminocarbonyl residue being optionally substituted with alkyl or aryl,

R^ and R^ are the same or different and mean hydrogen optionally substituted aryl or a straight, branched, cyclically saturated and unsaturated hydrocarbon residue, the carbon chain optionally being atomized with heteroatoms or groupings such as oxygen, sulphur, sulphon, sulphin, carbonyl, phenylene and is optionally substituted with substituents such as hydroxy, alkoxy, halogen, acyloxy, acylamino, aryl, aryloxy, aroyl, alkylthio, alkylsulfone and alkylsulfine, cyano, -alkyloxycarbonyl, aroxycarbonyl or aminocarbonyl, the aminocarbonyl residue being again optionally substituted with alkyl.

or aryl residues or wherein

R^ and R-* in the event that n = 0 otherwise means an alkylene chain which with the two nitrogen atoms forms a heterocyclic ring or in which

R^ or R^ means an alkylene residue as with the neighboring placerté X

forms a nitrogen-containing ring, X means a linear, branched, cyclically saturated

and unsaturated hydrocarbon chain, the chain possibly being interrupted by heteroatoms or groupings such as oxygen, sulphur, sulfine, sulfone, arylase, alkylase,

carbonyl or phenylene and is optionally substituted with substituents such as alkoxy, halogen, aroxy, hydroxy, cyano, hydroxycarbonyl, alkoxycarbonyl,

acylamino, aroxycarbonyl, alkylthio, alkylsulfine, alkylsulfone, arylthio, aryl or aminocarbonyl, the aminocarbonyl residue being optionally substituted with alkyl or aryl and

n means an integer from 0 to 4, where

all aryl residues defined under R1, R2, R^, r4, R^ and X contain 6 or 10 C atoms and are optionally substituted,

has strong hypolipidemic properties.

Furthermore, it was found that the carboxylic acid amides of the general formula I are obtained, whereas amines of the general formula II

in which

r<4>,r<5>and X have the above meaning,

optionally reacts in the presence of acid binders or water-attracting agents and inert solvents with carboxylic acid or carboxylic acid derivatives of the general formula III

in which

B means the substituents R, R and RJ which have the above meaning and

A means hydroxy or an acid group activating

residue such as halogen, azide, cyano, alkoxy, alkylthio, acyloxy, cyanomethyloxy, aryloxy, arylthio, aroyloxy, succinimido-N-oxy, phthalimido-N-oxy, the aryl groups possibly being substituted one or more times.

The reaction of the carboxylic acid derivatives with the di- and polyamines can also be carried out in stages.

In the case of compounds with the general formula III which have a hydroxy or amino group as substituents, a subsequent acylation of these functional groups can also take place.

Instead of the free amines, such compounds can also be used in the reaction according to the invention, from which the amines are split off.

Surprisingly, the carboxylic acid amides according to the invention show a strong hypolipidemic effect. From the substance class according to the invention, no compounds with comparable effects are known to date. The compounds according to the invention are to be considered new additional hypolipidemics. They can also be used as food additives and thus lead to an enrichment of the pharmacy.

If 11-methoxy-undecanoic acid chloride and 1,2-diaminopropane are used as starting materials, the course of the reaction can be reproduced by the following formula core:

The amines with the general formula II that can be used according to the invention are either known or can be prepared by known methods /" S.Patai (publisher), The Chemistry of

the Amino Group, Interscience Publishers, London, New York, Sydney I968i S.R Sandler, W. Caro, Functional Group Preparations, vol. I, page 318, Academic Press, New York and London 1968;

Wi Schneider, J. Hoyer, W. Ehr enst ein, R. Haller., W. Hausel,

W. Schneider, K. Lehmann, J. J. Roth, H. Sehonenberger,

B. Camerino, G.F. Cainelli, M. Feries in F. Korte Methodicum Chimicum, volume 6, page 449» Georg Thieme Verlag Stuttgart, 1974;

Houben-Weyl, Methoden der organischen Chemie, volumes ll/l,

Georg Thieme Verlag, Stuttgart 195^7.

As examples for those according to the invention used

only amines with the general formula II should be mentioned:

1,2-diaminoethane

N-methyl-1,2-diaminoethane

N-ethyl-1,2-diaminoethane N,N<f->diisopropyl~1,2-diaminoethane

N-methyl-N'-ethyl-1,2-diaminoethane

N-propyl-1,2-diaminoethane

N,N<*->bis ^-bromomethyl/"-1,2-diaminoethane

N,N'-dipentyl-1,2-diaraphaoethane

N-octyl-1,2-diaminoethane

N,N<*->dihexadecyl-1,2-diaminoethane

N-allyl-1,2-diaminoethane

N,N*-dimethallyl-1,2-diaminoethane

bis-j/2-aminoethyl.T-amine 2,2t<->bis-/methylamino/-diethylamine

l-butyl-diethylenetriamine

1,5-diamino.o-3»6-diazaoctane

1,11-diamino-3>6,9-triaz-undecane

methyl-bis-Z^-aminoethyl^-amine

1,4,7-tributyldiethylenetriamine

N,N<*->di-(n-methyl)-propylenediamine N,N'-di-(n-butyl)-propylenediamine 3-amino-1-methylamino-propane 1,3-bis-methylaraino-propane 1, 3-bis-heptylamino-propane 3-araino-1-dodecylaminopropane 1,g-diamino-3,7-d:i-azanonan 1,2-diamino-butane

2-amino-l-dodecylamino-butane 1.3- bis-ethylamino-butane 4- amino-l-(3-bromopropylamino)-butane 4-amino-l-isopentylaminobutane 2.3- diaminobutane

1,2-diamino-2-methylpropane 2-amino-l-methylamino-2-methyl-propane 2-amino-l-butylamino-2-methylpropane 4-amino-l-isopropylamino-pentane 1.4-diamino-pentane

1.2-diamino-pentane

2,4-diamino-pentane

1.3-diamino-2-methyl-butane 1.3-diamino-2-2-dimethyl-propane 1,6-diaminohexane

1,6-bis-propylamino-hexane 1,4-diamino2,3-dimethyl-butene-(2) 1,4-diamino-butyne-(2) 1,4-bis-methylamino-butyne-(2) 1,4- bis-butylamino-butyn-(2) 1,2,3-triaminopropane bis-^-aniinoethyl T-ether 2.3- diamino-1-methoxy-propane bis-/2-aminoethylX/-sulfoxide bis-Z2-aminoethyl/-sulfone bis -/2-aminoethyl/-disulfide Z=cystamine/ 2,6-diaza-spiro-/3,3/heptane 1.4- diaza-spiro-/4»5/decane 2-chloro-1,3-diamino-propane 1 ,3-diamino-2-hydroxypropane N,N'-diethyl-1,3-butadiene-1,4-diarene 1,8-diamino-2,5-octadiene 1,8-diaraino-3,6-octadiene

2,3-diamino-bicyclo/2,2,2/bctane N,N'-diphenyl-ethylenediamine

N,N'-dibenzyl-ethylenediamine

ethylene glycol bis- (2-methylaminoethyl) ether 2,2'-bis-methylamino-diethyl ether 1,6-diamino-cyclohexene-(L)

2,3-diamino-norbornane

1,3- diarainopropanone

2,6-diamino-2,6-dimethylheptanone-(4)3»4-diamino-adipic acid

3,4-diamino-adipic acid diethyl ester 3,4-diamino-adipic acid di-n-butyl ester is 3,4-diamino-adipic acid diamide. 2,9-diamino-sebacic acid

1,2-diamino-cyclobutane

1-, 2-diamino-cyclopentane

1.2-diamino-cyclohexane

1.3-diamino-cyclohexane

2-amino-1-aminomethyl-cyclopentane 1.4-diaminocyclooctane 3'5-diamino-1,1-dimethylcyclohexane 1,6-diaraino-cyclodecane

2,3-diamino-propionic acid

2,3-diamino-propionic acid nitrile 2,3-diamino-propionic acid amide

2,3-diamino-propionic acid methyl ester 2-amino-l-methylamino-propionic acid ethyl ester 1,2-bis-/methylamino/-propionic acid 1.2- bis-Zmethylarainoy-pro*ionic acid ethyl ester 2.3- diamino-butyric acid

2.4- diaraino-butyric acid 2,5-diamino-valeric acid (Ornithine) 2.5- diamino-valeric acid methyl ester 2.6- diaraino-hexanoic acid (Lysine) 2,6-diamino-hexanoic acid ethyl ester 6-amino-2-methylamino-hexanoic acid 2-amino -6-methylamino-hexanoic acid 2,6-diamino-hexanoic acid phenyl ester piperazine

1,3-diamino-2-r2,4,4-tetramethyl-cyclobutane

1,5-diaza-cyclooctane

2,5-dimethyl-piperazine

1-amino-2-anilino-propane

1-amino-2-anilino-butane

N,N-bis-/aminoethyl/-aniline

N-phenylethylenediamine

4-aminobenzylamine

1-phenyl-ethylenediamine

N,N'-bis-N'-chlorophenyl-propane-1,3-diamine N-benzyl-N'-phenyl-ethylenediamine

N,N'-diphenacyl-ethylenediamine

N,N'-bis(2-methylmercaptoethyl)-ethylenediamine N,N<f->bis-)2-methylsulfinyl-ethyl)-ethylenediamine N,N♦-bis-(2-methylsulfonyl-ethyl)-ethylenediamine N,N '-bis(α-methylbenzyl)-ethylenediamine N,N'-dibenzyl-ethylenediamine 1,1,10,10-tetramethyl-triethylenetetramine 1,10-dimethyl-1,10-diphenyl-triethylenetetramine 2,2,10,10- tetramethyl-3,9-dioxo-5,8-diaza-undecane N ,N'-bis-(2-.p-tolylethyl)-ethylenediamine N-hydroxyethyl-ethylenediamine N-chloroethyl-ethylenediamine N7N'-bis-(2- hydroxyethyl)-ethylenediamine N-yN'-bis(2-chloroethyl)-ethylenediamine N,N'-bis-(3-ethoxypropyl)-ethylenediamine N,N'-bis-(3-methoxyethyl)-ethylenediamine N,N'- bis-(2-phenoxyethyl)-ethylenediamine N,N<*->bis-(2-n-butylmercaptoethyl)-ethylenediamine N,N'-bis-(2-n-butylsulfinylethyl)-ethylenediamine N,N'-bis- (2-n-butylsulfonylethyl)-ethylenediamine N,N'-bis-{2-ethoxycarbonylmethylsulfonyl-ethyl)-ethylenediamine N,W-bis-(2-cyanoethyl)-ethylenediamine N,N'-bis-(2-phenylmercaptoethyl) -ethylenediamine

In formula II means

R^ and R^ which may be the same or different are preferably hydrogen, phenyl or naphthyl, optionally substituted with 1-3 substituents or a straight, branched

/ ' I

cyclic saturated and unsaturated hydrocarbon residue with '■ii .. - •

1-3.2 C atoms, the hydrocarbon chain possibly being interrupted by heteroatoms or groupings such as oxygen, sulphur, carbon, sulfine, carbonyl,

. phenylene and optionally substituted with substituents such as hydroxy, alkoxy with 1-12 C atoms, halogen such as fluorine, chlorine, bromine, iodine, acyloxy

or acylamino each with 1-15 C atoms, aryl, aryloxy, aroyl, alkylthio, alkylsulfone, and alkylsulfine with 1-12 C atoms, cyano, alkoxycarbonyl with 1-12 C atoms, aroxycarbonyl, aminocarbonyl, the aminocarbonyl residue remaining optionally is substituted by alkyl with 1-6 C atoms, phenyl or naphthyl,

or for the case that n - 0 which means an alkylene chain with 1-4 C atoms, which with the two nitrogen atoms forms a ring, or one of the substituents R^" and R^ means an alkylene residue with 1-5 C atoms which with the neighboring X form a nitrogen-containing ring,

X preferably means a straight, branched, cyclically saturated.bg unsaturated hydrocarbon chain with 2-20, especially with 2-15 C atoms, this chain possibly being interrupted by heteroatoms or

groupings such as oxygen, sulphur, sulfine, sulfone,

arylase, alkylase with 1-6 C atoms, carbonyl,

phenyl and optionally substituted with substituents such as halogen, especially fluorine, chlorine bg bromine, alkoxy

with 1-6 C atoms, aroxy, hydroxy, cyano, hydroxycarbonyl, alkoxycarbonyl with 1-15 C atoms, acylamino with 1-15 C atoms, aroxycarbonyl, optionally with one or two alkyl groups with 1-6 C atoms or with aryl substituted aminocarbonyl, alkylthio, alkylsulfine or alkylsulfone with each 1-6 C atoms in the alkyl group, arylthio, aryl,.

the above-mentioned aryl groups in particular meaning phenyl or naphthyl, which in turn may be substituted with halogen such as fluorine, chlorine or bromine, alkyl, alkoxy, acyl or alkyl mercapto with each

1-4 C atoms, cyano or aminep, and

n means an integer from 0 to 4"

According to the invention, usable carboxylic acids, resp. Carboxylic acid derivatives are either known or can be prepared by known methods (S.R. Sandler, W. Caro, Organic Functional Group Preparations, page 196, Academic Press, New York and Londong 1968; S. Patai, publisher, The Chemistry of Carboxylic Acids and Esters. Interscience Publishers, London, New York, Sydney, Toronto 1969;

H. Henecka in Houben-Weyl, Methoden der Organischen Chemie, volume 8, page 359, Georg Thieme Verlag, Stuttgart 1952;

M.S. Ansell in S. Patai (publisher), The Chemistry of Acyl Halides, page 35»Interscience Publishers, London, New York, Sydney, Toronto 1972»* F. Korte, Methodicum Chimicum, volume 8 .page 527* Georg Thieme Verlag, Stuttgart ). As an example for the carboxylic acids that can be used according to the invention or carboxylic acid derivatives, with the general formula III, should be mentioned:

acetic anhydride

trifluoroacetic acid

chlor.racetyl chloride

propionic anhydride 3-chloropropionyl chloride

butyric anhydride

4- chlorobutyric acid chloride

pentanoic acid 2-methyl-butanoic acid

3- methyl butanoic acid chloride pivalic acid chloride

pivaloyl azide

Hexanoic acid phenyl ester (Caproic acid phenyl ester)

hexanoic acid azide

2-chlorohexanoic acid methyl ester

6-chlorohexanoic acid ethyl ester 6-bromohexanoic acid ethyl ester

2-Methylpentanoic acid-(1) 4-Methylpentanoic acid chloride (Isocaproic acid chloride)

3- methylpentanoic acid-(1) 3.3-dimethylbutanoic acid-(1)-chloride diethylacetic acid chloride (2-ethyl-butanoic acid chloride) heptanoic anhydride 2-raethylhexanoic acid-(1)

4- methylhexanoic acid-(1)

2,2-dimethylpentanoic acid-(1) 4 > 4-dimethylpentanoic acid-(1) 3.4- dimethylpentanoic acid chloride octanoic acid phenyl ester (Caprylic acid phenyl ester) octanoic acid chloride

2-raethyl-heptanoic acid methyl ester 2-ethyl-hexanoic acid chloride (Dipropylacetic acid chloride) 4-methyl-heptanoic acid

3- ethylhexanoic acid

2,2-diethyl-butanoic acid chloride (Triethylacetic acid chloride) 2-isopropyl-3-methyl-butanoic acid (Diisopropylacetic acid) 2,2,3,3-tetramethylacetic acid chloride Nonanoic acid (Pelargonic acid)

2- methyl-octanoic acid ethyl ester 4.5-dimethyl-heptanoic acid-(1) 3- methyl-2-propyl-pentanoic acid chloride Decanoic acid chloride (Capric acid chloride) 2-methyl-nonanoic acid.

3"methyl~nonanoic acid

4- niethyl nonanoic acid

2-Butyl pentanoic acid chloride

2,7-diethyloctanoic acid-(1) 3-ethyl-6-methylheptanoic acid chloride Undecanoic acid

Undecanoic acid chloride

8-cyclopropyl-nonanecarboxylic acid ll-chloroundecanoic acid chloride-(1) 10- bromundecanoic acid-(1)

11-bromoundecanoic acid-(1)

10,11-dibromoundecanoic acid-(1) 11-iodoundecanoic acid-(1)

3- methyl-decanoic acid chloride

4- methyl-decanoic acid chloride

3»8-dimethyl-nonanoic acid-(1) 2-butyl-3-JBethylhexanoic acid-(1) 5-propyl-octanoic acid-(1)

2,2-dipropylbutanoic acid chloride-(1) (tripropylacetic acid chloride) dodecanoic acid (lauric acid) dodecanoic acid chloride

2-methyl-undecanoic acid-(1) 9-cyclopropyl~monanoic acid methyl ester

tridecanoic acid chloride 2-methyl-dodecanoic acid

5-methyl-dodecanoic acid

2-pentyl-heptanoic acid chloride-(1) tetradecanoic acid (myristic acid) tetradecanoic acid chloride

tetradecanoic acid S-methyl ester tetradecanoic acid S-ethyl ester

2- ethyldodecanoic acid-(1)

crotonic acid

methacrylic acid

hexene-2-acid chloride

4-Methyl-pentene-(4)-acid-(1) 4-methyl-pentanoic acid chloride

heptene-(2) - acid chloride-(1)

octene-(2)-acid-(1)-chloride nonene-(8)-acid-(1)-chloride

decene-(2)-acid-(1)-chloride

3- methyl-nonene-(2)-acid 2-allyl-heptanoic acid-(1) undecene-(10)-acid-(1)

undecene-(10)-acid chloride

undecene-{2)-acid

2-allyl-octanoic acid-(1)

undecine-(10)-acid-{1)

Undeine-(9)-acid-(1)

undecine-(5)-acid-(1) 2,4-hexadier<i>acid-(1)-chloride (sorbic acid chloride) 4»8-undecadieno-(1)

2,4»6-octatrienoic acid-(1)

cyclohexane carboxylic acid

, in 3-cyclohexyl-propionic acid methyl ester 3-cyclohexene-1-carboxylic acid cinnamic acid chloride

trans-cinnamic acid isopentyl ester 2- methylcinnamic acid chloride 3- methylcinnamic acid methyl ester phenylacetylenecarboxylic acid methyl ester phenoxy-thioacetic acid-S-phenylester phenoxyacetic acid-p-nitrophenylester methoxyacetic acid raethyl ester 11-methoxy-undecanoic acid 6-butoxy-hexanoic acid

6-phenoxy-hexanoic acid

6-(p-tert-butylphenylmercapto)-hexanoic acid 2-phenoxy-undecanoic acid phenylmercaptoacetic acid chloride phenylmercaptoacetic acid ethyl ester 6-(n-butylraercapto)-hexanoic acid 6-{n-butylsulfin)-hexanoic acid 6-(n-butylsulfone)-hexanoic acid n- octyl mercaptoacetic acid ethyl ester n-octylsulfinacetic acid ethyl ester n-octylsulfoneacetic acid ethyl ester 11-cyano-undecanoic acid 9-cyano-nonanoic acid

8-cyano-octanoic acid

the dike

N-butyl-N-methylglycine N-methyl-N-phenylglycine 11-fenraercapto-undecanoic acid 11-acetoxy-undecanoic acid 6-(p-tolyl)-hexanoic acid 4- tolyl-acetic acid chloride glutaric acid monomethyl ester glutaric acid raono-(N-ethyl) -amide glutaric acid mono-anilide adipic acid monoethyl ester adipic acid ethyl ester chloride 1

adipic acid monoamide t pimelic acid methyl ester chloride

pimelic acid monoamide

pimelic acid ethyl ester chloride

carbonic acid monomethyl ester chloride

In formula III, B preferably means the three substituents R 1 , R 2 and R 2 J

which can be the same or different and which in turn means rectilinear, branched, cyclical. saturated and unsaturated hydrocarbon residue with 1-14 C atoms, where the hydrocarbon chain may be interrupted by divalent heteroelements or groupings such as oxygen, sulphur, sulfine, sulfone, carbonyl, phenylene and optionally substituted with substituents such as halogen, especially fluorine, chlorine or bromine, alkoxy with 1-12 C atoms, acyloxy with 1-12 C atoms aryl, aryloxy, arylmercapto, aroyl, alkylmercapto, alkylsulfine and alkylsulfone each with 1-6 C atoms, -acylamino with 1-15 C- atoms,. aroylamino, cyano-alkoxycarbonyl with 1-6 C atoms, aroxycarbonyl or aminocarbonyl, which may be substituted by alkyl with 1-6 C atoms, phenyl or naphthyl,

in that the above-mentioned aryl groups in particular mean phenyl or, naphthyl, which in turn can be ,

substituted with halogen such as fluorine, chlorine or bromine, alkyl, alkoxy, acyl or alkyl mercapto each having 1-4 C atoms, cyano or amino, and

A preferably means hydroxy or an acid group activating' residue such as halogen, especially chlorine or bromine, azide, cyan, alkoxy, alkylthio, acyloxy with

each 1-4 C atoms, cyanomethyloxy, aryloxy, arylthib, aroyloxy, succinimido-N-oxy, phthalimido-N-oxy, the aryl group in particular means phenyl or naphthyl and can optionally be substituted one to three times with substituents from the group halogen, cyano, sulfone, nitro, amino, alkyl, alkyl-oxy, alkylmercapto or acyl with 1-4 C atoms each

As resolution, resp. diluents are coming

that means all solvents or solvent mixtures which are inert to the reactions to be carried out. These preferably include ethers such as diethyl ether, dioxane, di-isopropyl ether, tetrahydrofuran, ketones such as dimethyl ketone, methyl ethyl ketone, hydrocarbons such as petroleum ether, naphtha, benzene, toluene, xylene, halogenated hydrocarbons (such as chloroform, methylene chloride), toluene, esters such as acetic acid ethyl ester, propion- acid methyl ester, aprotic solvents such as dimethylsulfoxide, dimethylformamide, dimethylacetamide, hexamethylphosphoric acid triamide, tetramethylurea, amines such as pyridine, quinoline and for certain reactions also alcohols such as methanol, ethanol, isopropanol, n-butanol etc. also water.

As. acid binders when converting acid halides, all common acid binders can be used. These preferably include organic bases such as triethylamine, pyridine, quinoline,

inorganic bases such as alkali carbonates,. alkali hydroxides (cf. F. Moller in Houben-Weyl, Methoden der organischen Chemie, volume H/2, page 10, Georg Thieme Verlag, Stuttgart 1958).

Dehydration by reaction of the amines with the carboxylic acids can take place by azetropic distillation of water or by the addition of a dehydrating agent. As a dehydrating agent, all common reagents can be used (cf. F. Moller in Houben-Weyl, Methoden der organischen Chemie, 4th edition, volume VIII, page 654, Georg Thieme Verlag, Stuttgart 1958, 8. R. Sandler, W. Caro, Organic-Functional Group Preparation, vol. I, page 270,

Academic Press, New York, Lond<p>nj; 1968, U. Kraatz in F.Korte Methodicum Chimicum, volume 6, page 682, Georg Thieme Verlag, Stuttgart I974). These preferably include carbodiimides such as cyclohexylcarbodiimide, phosphorus compounds such as phosphorus (V) oxide, phosphorus (III) chloride, phosphorus oxychloride, triaryl phosphite, triarylphosphine, hexachlorocyclotriphosphate triazines and other dehydrating agents such as dimethylaminoacetylene, silicon tetrachloride.

The reaction temperatures can be varied over a wide range and depend on the reaction used. Generally, one works at temperatures between -20°C and 250°C, preferably at -10 to 150°C.

The amines of the general formula II can also be used as salts, e.g. such as hydrochlorides or hydrogen sulphates. Here, the minimum is added to release the amines

the equivalent amount of an organic or inorganic base.

The turnovers can be carried out at normal pressure, but

also preferably the reaction of free carboxylic acids and carboxylic acid esters at elevated pressure in an autoclave.

When carrying out the method according to the invention, one mole of carboxylic acid or carboxylic acid derivative is usually applied to an amino group. The carboxylic acids

respectively the carboxylic acid derivatives can also be used in excess.

Like many active substances, it must be added

the compounds listed as examples are: bis-(2-undecenoylamino-ethyl)-sulfone

bis-(2-undecenoylamino-ethyl)-sulfoxide

bis-(2-undecenoylamino-ethyl)-sulfide

bis-(10-undecenoyl)-aminoethyl<y>sulfide

N,N'-bis-[2-(10-undecenoyl)-aminoethyl]-aniline

N,N'-bis-^-(2-undecenoyl)-aminoethyl/-aniline N^^bis-^/tdiethylacetyD-amphoethylZ-aniline N,N'-bis-(dietyl cetyl)-1,2-diamiho^ -2-metoxypropane

N,W'-bis(diethylacetyl)-1,3-diamino-2-phenoxy-propane N,N<?->bis-(diethylacetyl)-1,3-diamino-2-cyano-propane H, W ',N"-tris-(10-undecenoyl)-1,2,3-triamino-propane N,NT ,K"-tris-(decanoyl)-1,2,3-triamino-propane. M,N<T>,N"-tris-(2-ethylhexanoyl)-1,2,3-triamino-propane N,W<*->bis-(diethylacetyl)-1,3~diamino-2- (n-butyl mercapto)-propane

■N, N'-bis-(diethylacetyl)-1,3-diamino-2-(n-butylsulfonyl)-propane I, 2-bis-(10-undecenoylamino)propionic acid* N,N'-bis-(10- undecenoyl)-1-amino-1,1-dimethyl-2-methylamino-ethane W,N?-bis-(dodecanoyl)-1-amino-1,1-dimethyl-2-methylamino-ethane N,N<T- >bis-(10-undecenoyl)-1-amino-1,1-dimethyl-2-(n-pentylamino)-ethane N,N'<*->bis-(dodecanoyl)-1-amino-1,1- dimethyl-2-(n-pentylamino)-ethane NjN^dibenzyl-N^^bis-dO-undecenoyD-ethylenediamine N,N'-bis-(10-undecenoyl)-l-amino~2-aminomethyl-cyclopentane

N,N'-di-(p-phenoxyethyl)-N,N'-bis-(decanoyl)-ethylenediamine N,N'-di-(p-butylmercaptoethyl)-N,N'-bis-(decanoyl)-ethylenediamine N,N'-di-(p-hydroxyethyl)-N,N'-bis-(heptanoyl)-ethylenediamine N,N'-di-(p-butylsulfinylethyl)-N,N'-bis-(decanoyl)-ethylenediamine N,N *-di-(p-butylsulfonylethyl)-N,N'-bis-(decanoyl)-ethylenediamine N-(p-hydroxy-ethyl)-N,N'-bis-(nonanoyl)-ethylenediamine N-( p-nonanoyloxy-ethyl)-N,N-bis-(nonanoyl)-ethylenediamine N-(p-cyanoethyl)-N,N'-bis-(nonanoyl)-ethylenediamine N,N*-bis-(10-undecenoyl) -N ,N'-bis-(1-ethoxycarbonylethyl)-ethylenediamine N,N'-bis-(6-ethoxycarbonylhexanoyl)-N,N'-bis-(1-ethoxycarbonylethyl)-ethylenediamine N,N'-bis-( undecanoyl)-N,N'-bis-(1-aminocarbonylethyl).-ethylenediamine N,N'-bis-(undecanoyl)-N,N•-bis-(1-anilinocarbonylethyl)-ethylenediamine N,N'-bis- (undecanoyl)-N,N'-bis-(1-diethylaminocarbonylethyl)-ethylenediamine N,N'-dicyclohexyl-N,N'-bis-(9-undecenoyl)-ethylenediamine

(cis and trans)

N,N'-dicyclohexyl-N,N<T->bis-(2-undecenoyl)-ethylenediamine N,N*-dicyclohexyl-N,N*-bis-(8-cyclopropyl-octanoyl)-ethylenediamine N,N' -diethyl-N,N'-bis-(11-acetylaminoundecanoyl)-ethylenediamine N,N'-diethyl-N,N *-bis-(11-iodo-undecanoyl)-ethylenediamine N ,N'-diisovaleryl-N ,N '-bis-(N-butyryl-4-.aminobutyryl)-

ethylenediamine N,N'-diisovaleryl-N,N'-bis-(TN-benzoyl)-4-aminobutyryl/-

ethylenediamine N,N<1->bis-(2-undecenoyl)-2,5-dimethyl-piperazine

N,N,-bis-(9-undecenoyl)-2,5-diraethyl-piperazine (cis and trans) N,N'-bis-(N-valeryl-2-aminopropionyl)-2,5-dimethyl-piperazine N ,N f -bis-(4-phenyloxy-valeryl)-piperazine

N,N*-bis-(N-hexanoyl-N-phenyl-aminoacetyl)-piperazine

N,N'-bis-(N-hexanoyl-N-methyl-aminoacetyl)-piperazine

N^N *-bis-(n-octyloxy-acetyl)-piperazine

N,N'-bis-(2-undecenoyl)-propylene diaraine

N,N'-bis-(9-undecenoyl)-propylenediamine (cis and trans) N,N*-bis-(n-octyloxy-acetyl)-propylenediamine

N,N'-bis-(decanoyl)-L-lysine anilide

N,N<*->bis-(decanoyl)-L-lysine-(di-n-propyl)-amide

The present invention relates to pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutical suitable carriers, contain one or more compounds of formula I and/or their salts or which consist of one or more compounds of formula I and/or their salts , as well as methods for producing these preparations.

The present invention also includes pharmaceutical preparations in dosage units. This means that the preparations "are available in the form of individual parts, e.g.

tablets, dragées, capsules, pills, suppositories and ampoules, whose active ingredient content is a fraction or several times a single dose. The dosage units can e.g. contain 1, 2, 3 or 4 single doses, or l/2,. l/3 or 1/4 of a single dose. A single dose preferably contains the amount of active substance that is administered in one application and which usually corresponds to 1/1, 1/2, 1/3 or 1/4 of a daily dose.

By non-toxic, inert pharmaceutical suitable carriers is meant solid, semi-solid or liquid diluents, fillers or formulation aids of any type.

Tablets, dragées, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays should be mentioned as preferred pharmaceutical preparations.

Tablets, dragées, capsules, pills and granules may contain the active substance(s) in addition to the usual carriers, such as a) fillers and thickeners, e.g. starch, milk sugar, cane sugar, glucose, mannitol and silicic acid,

b) binder, e.g. carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, c) wetting agent, e.g. glycerol, d) explosive, e.g. agar-agar, calcium carbonate and sodium bicarbonate, e) dissolution retarders, e.g. paraffin and f) resorption accelerator, e.g. quaternary ammonium compounds, g) wetting agent, e.g. cetyl alcohol, glycerol monostearate, h) adsorbent, e.g. , kaolin and bentonite and

i) lubricant e.g. talc, calcium and magnesium stearate and. solid polyethylene glycols or mixtures of the substances listed under points a)-i).

Tablets, dragées, capsules, pills and granules can be equipped with the usual coverings and sleeves, possibly containing opacifiers, and also be composed so that the active substance(s) are only or preferably released in a specific part of the digestive tract, possibly delayed, as the as an embedding mass, e.g. polymer substances and wax can be used.

The active substance(s) may possibly be present with one or more of the above-mentioned carrier substances as well

in microencapsulated form.

Suppositories can contain the usual water-soluble or water-insoluble carriers in addition to the active substance(s), e.g. polyethylene glycol, fat, e.g. cocoa butter and higher esters (e.g. C-^- alcohol with fatty acid) or mixtures of these substances.

Ointments, pastes, creams and gels can contain the usual carrier substances, e.g. animal fat and vegetable fat, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicones, behtonites, silicic acid, talc and zinc oxide or mixtures of these substances.

Powders and sprays can contain the usual carrier substances in addition to the active substance(s), e.g. milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also contain the usual propellants, e.g. chlorofluorocarbons.

Solutions and emulsions can contain, in addition to the active substance(s), the usual carriers, such as solvents, dissolution mediators and emulsifiers, e.g. water,, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol,; benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, corn, germ oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan or mixtures of these substances.

For parenteral application, the solutions and emulsions can also be available in sterile and blood isotonic form.

' 't,

In addition to the active substance(s), the suspensions may contain the usual liquid carriers. dilution media, e.g. water, ethyl alcohol, propylene glycol,/suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methane hydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.

The aforementioned formulations may also contain coloring agents, preservatives as well as odor and taste-improving additives, e.g. peppermint oil and eucalyptus oil and sweeteners e.g. saccharin.

The therapeutically active compounds should be present in the pharmaceutical preparations listed above, preferably in a concentration from approx. 0.1 to 99.5, preferably from approx. 0.5 to 95 wt% of the total mixture.

The pharmaceutical preparations listed above may, in addition to the compound of formula I and/or their salts, also contain other pharmaceutical active substances.

The preparation of the above-mentioned pharmaceutical preparations takes place in the usual way according to known methods, e.g. by mixing the active substance(s) with the carrier substance(s).

The present invention also includes the use of the compound of formula I and/or their salts, as well as the use of pharmaceutical preparations containing one or more compounds of formula I and/or their salts in human and veterinary medicine to prevent" better and/or cure the above diseases.

The active substances or the pharmaceutical preparations can be applied orally, parenterally, intraperito-. nerally and/or rectally, preferably orally.

In general, both in human and veterinary medicine it has proven advantageous to administer the active substance(s) in amounts of from approx. 0.5 to approx. 500", preferably 5 to 100 mg/kg body weight per 24 hours, divided into 1 to 6 administrations, namely before or/and during or/and after

the meals. A single dose contains the active ingredient(s).

substances, preferably in amounts from approx. 0.1 to 100 mg/kg

body weight It may, however, be necessary to deviate from the aforementioned dosages, namely depending on the type and body weight of the object to be treated, the type and severity of the disease, the type and preparation and application of the medicine, as well as the time period resp. the interval within which the administration takes place. In some cases it may be sufficient to come out with less than the above-mentioned amount of active substance, while in other cases the above-mentioned amount of active substance must be exceeded. Determining the optimal dosage and application type of the active substance required each time can easily be done by anyone professional because of his professional knowledge.

The active substances according to the invention lead to less alimentary hyperlipemia after fatty food and at the same time inhibition of cholesterol absorption in animals and

humans, so that they can be used to treat fat metabolism disorders (e.g. hyperlipoproteinaemia, adiposity).

The hypolipidemic effect, see Table 1, with the help of examples of compounds discussed in the examples.

The proof of effect was provided by the following test arrangement on rats: To produce an alimentary hyperlipemia after the application of fat, a group of 5 to 10 rats receives 2.5 ml/kg of olive oil p.o. Every 5 to 10 other rats additionally receive 90 minutes before and at the same time as the fat application the active substance in the dosage listed in the table as a suspension in tragacanth mucus with a drain tube. A further control group of 5 to 10 rats receives tragacanth mucilage only. 2 hours after the application of olive oil, the concentration of serum triglyceride is determined in all three groups of rats according to one modification of the method of Eggstein and Kreutz /M. Eggstein and F.H. Kreutz, Klin. Wschr. 44, 262 (I966V with a biochemical test combination by Fa. Boehringer, Mannheim. Two hours after fat application, the rats treated only with olive oil compared to the rats without fat application show a clear increase in serum triglycerides. At this increase, which was set equal to 100$ the serum triglyceride increase Bn in the animals treated with the active substances and olive oil was compared and correspondingly expressed as a percentage.

From Table 1 it appears that the compound according to

. the invention clearly reduces the increase in the serum triglyceride concentration.

The mentioned compounds are distinguished by a very low toxicity: LD^q lies in a single oral application in mice above 2000 mg/kg.

Example 1

N,N'-bis-(10-undekenoyl)-trimethylenediamn

H2C = CH-(CH2)g-Cb-WH-{C<H>2<j>5-NH-C0r(CH2)3-CH = CH2

The solution of 3>7g (0.05 mol) of 1,3-diaminopropane, 11.1 g (0.11 mol) of triethylamine and 200 ml of abs. tetrahydrofuran was cooled to 5°C. While stirring and cooling with ice, 22.3 S (0.11 mol) undecylenic acid chloride was added dropwise in JO ml abs. THF, allow to come to room temperature and stir for another 2 hours at 60°C. The reaction mixture was poured into water, the solid product was sucked off and recrystallized from ethanol/acetonitrile.

Yield: 17.2 g ($84), m.p. : 112-11§°C

Analysis: C25 H^g N2 O2 (406.5)

Example 2

N,W*-bis-(10-undecenoyl)-tetramethylenediamine.

H2C = CH-(CH2)g-CO-NH-(C<H>2)^-NH-C0-(CH2)8-CHCH2

was prepared from 4>4 g (0.05 mol) of 1,4-diaminobutane, 11.1. g (0.13L mol) triethylamine and 22.3 g (0.11 mol) undecylenic acid chloride in abs. tetrahydrofuran according to that specified in Example 1

regulation.

Yield: 17.2 g (82$), mp: 139-140°C (acetonitrile)

Analysis: C^ H^g N 2 O 2 (420.5)

Example 3

M,N'-bis-(dodecanoyl)-propylenediamine

To the solution of 3>7S- (0.05 mol) propylenediamine, 11.2 g (piil mol) triethylamine and 100 ml of abs. tetrahydrofuran, 24>1 g (0.11 mol) of dodecanoyl chloride were added dropwise under ice-cooling. It was stirred overnight and then heated for a further 2 hours to 60°C. After cooling, it was mixed with water, the precipitated product was filtered off with suction and recrystallized twice with acetic acid.

Yield: 14.1 g (64.456), m.p. : II9-I2O<0>

Analysis: C2y ^54. N202(438.7)

Example 4

N, PP - bis-(8- methoxycarbonyl- octanoyl)- propylenediamine h3co-co-(ch2)^-co-nh-?h<2>ch2-nh-co-(ch2)7-co-och3

is prepared analogously to Example 3 using 3.7 g (0.05 mol) propylenediamine, 11.2 g (0.11 mol) triethylamine in abs. tetrahydrofuran. with 24.2 g (0.11 mol) of 8-chloroformyloctanoic acid methyl ester.

Yield: 9.6 g (43>4#). m.p. IO4-IO60

Analysis:<H>^2 Ng And (442.6)

Example 5- 14 (Table 2)

TII a stirred solution of 0.1 mol of the carboxylic acid specified in the following table in 150 ml abs. dimethylformamide, 10.1 g (0.1 mol) triethylamine was added, cooled to -10°C,

and at this temperature, 10.8 g (0.1 mol) ethyl chloroformic acid is added dropwise with stirring. This was stirred for 3 min.

at -10°C and then added dropwise 3>7 g (0.05 mol) of propylenediamine

in 50 tol abs. dimethylformamide. The mixture was allowed to reach room temperature and stirred for a further 2 hours at 60°C

and cooled. The reaction mixture was poured into 500 ml of water, the solid product was sucked off and recrystallized.

Example 15

N,Nt;-bis-(9-caecarboxycarbonyl)-nonanoyl)-propylenediamine

To the stirred solution of 3>7g (0.05 mol) propylenediamine., . 10.1 g (0.1 mol) of triethylamine and 200 ml of acetic acid were added dropwise under ice-cooling to 24.9S (0.1 mol) 9-chloroformylnonanoic acid ethyl ester. After stirring overnight, it was heated for 2 hours at 50°C, poured into ice water and separated from the

low phase. After washing with water and drying (NagSO 4 ), the solvent was removed and the residue was recrystallized from acetonitrile.

Yield: 19.0 g (82%), m.p. 118-120°

Analysis: 0^ H^<N>2Og . (498.7)

Example 16 1, Irdimethyl-N,N*-bis-(10-undecenoyl)-ethylenediamine

18.4 g (0.1 mol) of undecylenic acid was dissolved in approx. 200 ml of abs. tetrahydrofuran. After addition of 10.1 g (0.1 mol) of triethylamine, it was cooled to -10°C and 10.8 g (0.1 mol) of chloroformic acid ethyl ester was added dropwise. After one hour of one<e>room stirring, 8.0 g (0.05 mol) of 1,1-dimethylethylenediamine was added dropwise in 30 ml of abs. tetrahydrofuran at -10°C. It was allowed to come to room temperature overnight and poured into 500 ml of water. The reaction mixture was worked up by extraction with chloroform, washing the chloroform solution with water and removing the solvent. After chromatography over aluminum oxide (neutral) and elution with petroleum ether, it was recrystallized from petroleum ether (boiling point 60-100°G).

. Yield: 9.5 g ($45.3)» m.p. 44-45°C.

Analysis: CggH^gNgOg (420.5)

Example 17

H, N'-bis-(10-undecenoyl)-propylenediamine

H2C=CH-(GH2)g-CO-NH-CH(CH^)-QHg-NH-CO^(CH2)g-CH=CH2

was prepared analogously to Example 12 from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformate ethyl ester and 3.7 g (0.05 fl ) 1,2-diaminopropane. Yield: 17.0 g ($84) m.p. 105-106°C (acetonitrile)

Analysis: C25H^6<N>2°2(4-06.5)

Example 18 2,5-dimethyl-K,N1-bis-(undecanoyl)-2,5-diaminohexane.

To 7.2 g (0.05 mol) of 2,5-dimethyl-2,5-diaminohexane and 10.1 g (0.1 mol) of triethylamine in 150 ml of abs. tetrahydrofuran it became - '

under ice-cooling, 18.6 g (0.1 mol) of undecanoic acid chloride were added dropwise. It was allowed to come to room temperature, heated for another hour at 40°C, cooled and poured into 500 ml of ice water. The white precipitate was sucked off, washed with water and recrystallized from acetic acid.

Yield: 20 g;(42$), m.p. 113-115°C

Analysis: C^øHggNgOg (480.8)

Example 19.

N,NT,N"-tris-(10-undecenoyl)-diethylenetriamine

was prepared analogously to Example 18 from 18.4 g (0.1 mol) undecylenic acid, 10.2 g (0.1 mol) triethylamine, 10.8 g (0.1 mol)

chloroformic acid ethyl ester and 3»3g (°.33 m°D diethylenetriamine in tetrahydrofuran.

Yield: 11.0 g ($55.7), m.p. : 70-73°C (acetonitrile)

Analysis: Coy<H>^N^<Oo>(<60>1.9)

Example 20.

N, N*. N",^'*- tetra-(10- undecenoyl)- triethylenetetramine

To 4.3 g (0.03 mol) triethylenediamine and 13.1 g (0.13 mol) triethylamine in 200 ml abs. 26.2 g (0.13 mol) of undecylenic acid chloride were dipped into tetrahydrofuran while stirring and cooling with ice. After standing overnight, it was poured into water, suction filtered and recrystallized from alcohol and from acetonitrile.

Yield: 11.0 g (45»3%), m.p. 136-137°C

Analysis: C^qH^qN^O^/(8<1>1,2}

Example 21.

N^ N', , N", N" T , K" w- pentadecanovel- tetraethylenepentamine

3.8 g (0.2 mol) of tetraethylenepentamine and 10.1 g (0.1 mol) of triethylamine were dissolved in 200 ml of abs. tetrahydrofuran. During ice-cooling and stirring, 190 g (0.1 mol) of capric acid chloride were added dropwise. After stirring overnight and pouring into water, it was extracted with ether, the ether solution was washed with water and dried (Na 2 SO 4 ). After evaporation to dryness, it was recrystallized from acetonitrile and from methanol. Yield: 10.5 g (54.7$) m.p. 113-115°C.

Analysis: C58<H>113<N>5°5 (96l»7)

Example 22.

N , N' ,N" , N"' ?Nntt , N" n T-hexadecanoyl- pentaethylenehexamine

For 200 ml abs. tetrahydrofuran, 10.1 g (0.1 mol) of triethylamine and 3.7 g (0.016 mol) of pentaethylenehexamine were added and 19.0 g (0.1 mol) of decanoic acid chloride were added dropwise with stirring and ice-cooling. After standing overnight, it was poured into 500 ml of water, extracted with ether, the ether solution washed with water and dried (NagSO 4 ). After removal of the ether, it was recrystallized

from vinegar. Yield: 8.5 g (45.8^), m.p. 137-138°C

: Analysis: C^øH^gNgOg (1157.9)

Example 23 N,N*,N"-tris-(10-undecenoyl)-/bis-(3-aminopropyl)-amineZ,

The synthesis took place analogously to Example 18 using 20.2 g (0.1 mol) undecylenic acid chloride and 3.6 g (0.03 ffi°D 3>3'-diamine0~dipropylamine, 10.1 g (0.1 mol) triethylamine in 150 ml abs tetrahydrofuran.

Yield: 16.0 g ($84.7), m.p. 64-65° (2 x recrystallized from lig.ro in)

Analysis: C^ft^N^'• (6<2>9,9)

Example 24 1,2-bis-(10-undecenoylaminomethyl)-cyclobutane

was prepared analogously to Example 16, starting from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformic acid ethyl ester and 5.7 g (0.05 m°l) 1,2-bis-(aminomethyl)-cyclobutane in abs. tetrahydrofuran.

Yield : 14.4 g ($65), sm<p.>. 74-77° (acetonitrile)

Analysis: CggH^NgOg (446.7)

EXAMPLE 25 M^ N1-bis-(10-undecenoylj-cyclohexane-1^^-dlamine (cis/trans mixture)

could be prepared analogously to Example 16 using 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformate ethyl ester and 4.7 g (0.55 mol) 1,2-diamino-cyclohexane (cis/trans mixture) in abs. tetrahydrofuran.

Yield: 10.3 g ($46.3), m.p. I39-I4O<0>(acetonitrile)

Analysis: C28<H>5<0W>2°2(446.6)

Example 26 M,N'-bis-(1Q-undecenoylaminomethyl)-cyclohexane was prepared according to Example 16 using 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10, 8 g (0.1 mol) chloroformate ethyl ester in 150 ml abs. tetrahydrofuran with 7 g (0.05 mol) of 4,4,-bis-(aminomethyl)-cyclohexane. Yield: 8.6 g ($36.2), m.p. 174-1755° (recrystallized from acetonitrile/alcohol 2:1 and from methanol) Analysis: ^3<0>^54^2^2(474»7)

Example 27- 43 (Table 3)

The syntheses of these compounds took place analogously to the regulations in Example 1:, starting from 0.05. m°i diamine and 11.1 g (0.11 mol) triethylamine in 150 ml abs. tetrahydrofuran by reaction with 22.3 g (0.11 mol) undecylenic acid chloride.

Example 4-6. N. N'* - bis-( decanoyl )- D. L- ornithine in

To the mixture of 200 ml of ether, 100 ml of benzene, 200 ml of water, 20 g (0.5 mol) of caustic soda and 16.9 g (0.1 mol) of D,L-ornithine moiro hydrochloride were added. Stir well and cool

3^.0 g (0.2 mol) of capric acid chloride were added dropwise, the temperature being kept around 0°C. With stirring, it was allowed to come to room temperature, acidified with hydrochloric acid and the organic phase separated. After washing with water, evaporation to

dryness and recrystallization from benzene gave 3& g (86.5$), m.p. 125-127°C.

Analysis:..<C>25<H>4<8N>2°4

Example. 47 , N, MT-bis-(decanoyl)-L-lysinamide

10.9 g (°»°5 moD L-lysinamide x.2 HCl was cooled in 150 ml abs. dimethylformamide to approx. 0°C. 20.2 g (0.2 mol) triethylamine was added and then 19, 0 g (0.1 mol) of decanoic acid chloride.It was allowed to come to room temperature overnight,

poured into 5QQ ml\ann, filtered off the solid product and recrystallised. m.p. 176°C.

Yield: 12.9 g ($56.5)

Analysis: C26H51N3°3 <457»7)

■'■"'■'

Example 48 3

N,N'-bis-(decanoyl)-D,L-ornithine cyclohexylamide

was prepared analogously to Example 4i using 14.2 g (0.05 moi) D,L~ornithine cyclohexylamide, x 2 HCl. Temp. 157-158°C.

Yield: 15.2 g ($58)

Analysis: C 1 H 2 H 2 O 2 (521.7).

Example 49 N,N'T-bis-(decanoyl)-L-lysine ethyl ester 12.4 g (0.05 mol) L-lysine ethyl ester x 2 HG1 was dissolved in 120 ml of dimethylformamide. After adding 20.2 g (0.2 mol) of triethylamine, it was cooled with ice water to approx. 5°C and added dropwise at this temperature 19 g (0.1 mol) of capric acid chloride. It was allowed to come to room temperature overnight, heated briefly to 0°C (0.5 hours), cooled and poured into water. Twice recrystallization from acetic acid ethyl ester gave 65.5 g ( SQ%), m.p. 89-90°• Analysis: C28<H>54<W>2°4 (482.7) Example 50 M, N'-bis-(decanoyl)-1f3-diamino-2-hydroxypropane

To an ice-cooled solution of 22.5 g (0.25 mol) 1,3-diamino-2-hydroxypropane and 51 g (0.5 mol) triethylamine in 500 ml abs. ) capric acid chloride. While stirring, it was allowed to come to room temperature, poured into 700 ml of water and the precipitated solid product was sucked off. After washing with water and recrystallization from ethanol gave 75.7g (76$), m.p. 130-i31°C.

Analysis: C23<H>4<6N>2°3 (<3>98.6)

Example 51

H , N *- bis-(decanoyl)- L- ornithine- methyl ester ...

For 200 ml abs. dimethylformamide, 10.9 g (0.05 mol) of L-ornithine methyl ester dihydrochloride and 20.2 g (0.2 mol) of triethylamine were added. It was cooled to 0° and 19 g (0.1 mol) of capric acid chloride were added dropwise. It was allowed to come to room temperature and heated for a further 4 hours at 50°C, poured into water and suctioned off. The white crystals were recrystallized from ligroin.

Yield: 12.5 g (55.255), m.p. 79-82°C..

Analysis:<C>26<H>50<N>2°2(454»5>

Example ^ 2.

N, ST bis-(10-undecenoyl)-L-lysine ethyl ester

18.4 g (0.1 mol) of 10-undecenoic acid was dissolved in 200 ml of dimethylformamide (abs.). After the addition of 20.2 g (0.2 mol) of triethylamine, it was cooled to -10° and added dropwise at this temperature with stirring 10.8 g (0.1 mol) chloroformate ethyl ester. It was stirred for a further 30 minutes at -10° and then 12.4 g (0.05 mol) of L-lysine ethyl ester dihydrochloride, dissolved in 80 ml of abs. DMF. It was allowed to come to room temperature overnight, stirred for a further 4 hours at 60° and poured into water. The precipitated product was suctioned off and recrystallized from acetonitrile and from petroleum ether/acetic ester (2:1).

Yield: 12.5 g ($50), mp 69-710

Analysis: . C^øH^NgO^ (<50>6.6)

Example 53 N,N'-bis-Xdecanoyl)-L-lysine

was prepared analogously to Example 46 using 18.27 g (0.1 mol) of L-lysine monohydrochloride.

Yield: 36.2 g ((80#), mp 104-105°C.

Analysis: C26%0N2°4 (454'7}

Example 54-59 (Table 4)

The compounds listed in Table 4 were prepared analogously to the instructions given in Example 18, starting from 0.05 mol diamine and 10.1 g (0.1 mol) triethylamine in 150 ml abs. tetrahydrofuran and 13.05 g (0.1 mol.) diethylacetic acid chloride.

Example 56 was prepared using 0.02 moles of diamine and corresponding amounts of triethylamine and diethylacetic acid chloride.

Example 60

N. N'- bis-(diethylacetyl)- 1. 3- diamino- propan- 2- one

3.22 g (0.02 mol) of 1,3-diamino-propan-2-one dihydrochloride was dissolved in 100 ml of water. After adding 100 ml of methylene chloride, it was cooled to approx. 0°C and simultaneously added dropwise 1 N aqueous NaOH and 5.2 g (0.04 mol) diethylacetic acid chloride in 50 ml chloroform, so that the aqueous solution became approximately neutral. After the stirred reaction mixture had reached room temperature, the chloroform phase was separated, washed with water and evaporated to dryness on a rotary evaporator. The residue was recrystallized from acetic acid and naphtha.

Yield: 3.<1>5 g (55.5^), m.p. I68-I7O0

Analysis: C15H28N2°3 ^284.4)

Example 6l

N,N*-bis-(diethylacetyl)-1,3-diamino-3-chloropropane

(H5C2)2CH-CO-NH-<CH>2<->CHC1-CH2-NH-CO-CH(C2H5)2

was prepared analogously to Example 60, starting from 3.53 g of 1,3-diamino-2-chloropropane dihydrochloride (0.02 mol). Yield: 4.12 g (51$), m.p. II7-II90 Analysis: C15H29<C>1N2°2* 3^4.9)

Example 62

cis- and trans-N,N'-bis-(2-ethylhexanoyl)-1,3-diamino-2,2,4»4~

7*1 g (0.05 mol) 1,3-diamino-2,2,4,4-tetramethyl-cyclobutane (cis/trans mixture) was reacted analogously to Example 14 in 150 ml abs. tetrahydrofuran in the presence of 10.1 g (0.1 mol) of triethylamine with 16.3 g (0.1 mol) of 2-ethylhexane acid chloride. Recrystallization from acetic ester (after the usual work-up) gave two products: A: Yield 4 6" m.p. 213-216° (trans product)

B: Yield 5.3 g, m.p. 130° (cis product)

Analysis: C24<H>4<6N>2°2<<>394.7)

Example 63 M^ M' - (n-butyryl)-1,2-diamino-2-hydroxypropane

To 9 g (0.1 mol) of 1,2-diaminopropanol-(2) in 100 ml of ether, 31 g (0.2 mol) of butyric anhydride was added dropwise. After standing for 24 hours, the solvent was removed in vacuo, 200 ml of ligroin were added, the solid product was filtered off with suction and recrystallized from acetonitrile.

Yield: 15>5g ($60), m.p. 128-129° Analysis: C13H26N2°3 (258.3)

Example 64-68 (Table 5)

To 6.5 g (0.05 mol) of N-(n-butyryl)-ethylenediamino

(prepared according to K.W. Rosemund, A.P. 19 2605, Chem.Ztbl.i933 II, 3616) in 100 ml abs. 5.1 g (0.05 mol) of triethylamine were added. During ice-cooling, 0.05 mol of it was added dropwise

Table 5 indicates acid chloride in 50 ml.abs. CHCl^Y After stirring overnight, it was washed with water, the chloroform was distilled off and the residue chromatographed over neutral alumina. Eluted with petroleum ether (boiling point 60-100°C)>

Example 6Q- 85 .. (Table 6)

To 18.4 g (P,l mol) undecylenic acid.in 150 ml abs. tetrahydrofuran, 10.1 g (0.1 mol) of triethylamine were added. It was then cooled to -10°C and 10.8 g (0.1 mol) of chloroformic acid ethyl ester was added dropwise. It was left to react for one hour at 10°C and then 0.05 mol of the N-mono-substituted diamine mentioned in Table 6 in 50 ml of tetrahydrofuran (abs.) was added dropwise. It was allowed to come to room temperature overnight and then poured into ^ 00 ml of water. Products that separate as solids were suctioned off and recrystallized. Oils were extracted with chloroform. The chloroform solution was washed with water, the solvent removed on a rotary evaporator. The mixture was then chromatographed over neutralized aluminum oxide. It was eluted with petroleum ether (boiling point 60-100°).

Example 86 NjN,~ bis-(10-irdecenoyl)-2~ amino-1-methylamino-2~ methyl-propane

was prepared analogously to Example 18 from 2-amino-1-methylamino-2-methylpropane and undecylenic acid chloride (oil)

Dividend: 37$; n<2?>1.4795

D

Analysis: iC27H50N2°2 (434.2)

Example 87

N,N'-bis-(10-undecenoyl)-2-amino-l-pentylamino-2-methyl- propane

was prepared "analogous to Example 18 from 2-amino-1-(n-pentylamino)-2-methylpropane and undecylenic acid chloride (oil) in

Dividend: 42$; n211.478<0>

D

Example 88-121 (Table 7)

The syntheses of the compounds listed in Table 7 took place analogously to Example 18 by reaction of the listed acid chlorides (method variant A) or analogously to Example 16

by reacting the listed carboxylic acids (method variant B) with 4.4 g (0.05 mol) N.W-dimethylethylenediamine.

Example 122 ■. N, Nt-diben2vl- NtHf - bis-(10- undecenoyl)- ethylenediamine

could be prepared, analogously to Example 18, from N,N<f->dibenzyl-•ethylenediamine and undecylenic acid chloride. Dividend: 68$,; m.p. 55-56° (petroleum ether)

Analysis:

Example 123 N- methyl- N^ N- bis- Zi- dO- undecenoyl- N^ methylamino- ethane/

was prepared analogously to Example 16 using 7"36(0.05 mol)N,N',N"-trimethyl-diethylenetriamine in abs. tetrahydrofuran* The oil formed was chromatographed over alumina (neutral), eluting with petroleum ether .

Yield: 13.0 g ($54.7)..n21 1-479<8>

D

Analysis: C^qH^N n (477.7)

Example 124-128 (Table 8)

The synthesis of Examples 124-128 proceeded analogously to Example 16, in that 0.1 mol of carboxylic acid, 10.1 g (0.1 mol) of triethylamine, 10.8 g (0.1 mol) of chloroformic acid ethyl ester and 5.8 g ( 0.05 mol) N,Nf-diethylethylenediamine in abs. tetrahydrofuran. After working up, the oil formed was chromatographed over aluminum oxide and eluted with petroleum ether.

Example 129 N,N*-bis-(dodecanoyl)-N,N'-di-(n-butyl)-ethylenediamine<:>was prepared from 20 g.(0.1 mol) of dedecanoic acid, 10.1 g (0 .1 mol) triethylamine, 10.8 g (0.1 mol) chloroformate ethyl ester and 8.6 g (0.05 µl) N,N'-di-n-butylethylenediamine in abs. tetrahydrofuran, as discussed in Example 16. .Chromatography over neutral alumina gave 13 g (50$) of an oil n21 1.4676.

D

Analysis: C34*%8<N2>°2*536.8)

Example 130 N, MT-bis-(dodecanoyl)-2-amino-1-methylamino-2-methyl-propane

was prepared analogously to Example 18 from dodecanoic acid chloride and 2-amino-1-methylamino-2-methyl-propane in tetrahydrofuran. The oil formed could be purified by chromatography over basic alumina (elution with benzene).

Yield: 8.0 g ($34.5), n<27>1.4718

D

Analysis:

Example 111 M, NT-bis-(10-undecenoyl)-N.Nf-di-(n-butvl)-ethylenediamine

was prepared as an example using 18.4 g (6.1 mol) of undecylenic acid.

Yield: 17.2 g of oily product ($68), n^° 1.4738

Analysis: C32H6oW2°2^04.7)

Example 132-136 (Table 9)

To the solution of 8.6 g (0.05 mol) of N,N'-di-(tert-butyl)-ethylenediamine£, 10.1 g (0.1 mol) of triethylamine and 200 ml of abs. tetrahydrofuran, 0.1 mol of acid chloride was added dropwise under ice-cooling with stirring. It was allowed to come to room temperature, heated for a further 4 hours at 50°C and poured into water. They precipitated. crystals were aspirated and recrystallized.

- Example 137 N,N*-bis-(10-undecenoyl)-N,N'-di-(n-dodecyl)-ethylenediamine The synthesis was carried out analogously to Example 16 of 19>8 g (0.05 mol) R, N^ dodecylethylenediamine, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) ethyl chloroformate and 18.4 g (0.1 mol) undecylenic acid in abs. tetrahydrofuran. Yield: 15 g ($41.3), m.p. 43-44° (from acetonitrile and from methanol) ■ "

Example 138-144 (Table 10)

The synthesis of this compound proceeded analogously to Example 16, in that 0.1 mol of carboxylic acid, 10.1 g (0.1 mol) of triethylamine, 10.8 g (0.1 mol) of chloroformic acid ethyl ester in abs. tetrahydrofuran was reacted with 10.0 g (0.05 mol) of N,N*-diiso-valeryl-ethylenediamine. The oil formed after the work-up was chromatographed over neutral aluminum oxide. It was eluted with petroleum ether (boiling point 60-loo£:)

Example 145-152 (Table 11)

Examples 145-152 were prepared using 12.2 g (0.05 mol) N,N<T->dicyclohexyl-ethylenediamine by reaction with the corresponding acid chloride analogous to Example 18, (method variant A) or by reaction with carboxylic acid

analogously to Example 11 (method variant B). Formed oils were

purified by chromatography over neutral alumina and elution with petroleum ether (boiling point 60-100°C).

:' Example 155-159 (Table 12)

The synthesis of the compounds listed in Table 12 took place according to Example 16 from 18.4 g (0.1 mol) 2-undecenoic acid, 10.1 g (0.1 mol) triethylamine and 10.8 g (0.1 mol) chloroformate ethyl ester over the mixed anhydride.

Example l60

N, N- T - bis-(10- undecenoyl )- N, N^ rdiallyl- ethylenediamine

To the triethylammonium salt, prepared from 18.4 g (0.1 mol) undecylenic acid and 10.1 g (0.1 mol) triethylamine in approx. 200 ml abs. tetrahydrofuran, 10.8 g (0.1 mol) chloroformate ethyl ester was added dropwise at -10°C. Stirring was continued for one hour and then 7 g (0.05 mol) of N,N'-diallyl-ethylenediamine, dissolved in 60 ml of abs, were added dropwise. THF. It was allowed to come to room temperature overnight, the reaction product was poured into water and extracted 3 times with 150 ml of chloroform each time. The chloroform solutions were washed with water and evaporated to dryness. The remaining oil was chromatographed over neutral alumina. 9.5 g (40.3$) of an oil n^1 I.4839 was thus obtained. Analysis: C 2 0 H 5 2 N 2 O 2 (472.7); Example 161 W,N t-bis-(10-undeenepyl)-2,3-diaminopropioric acid To the stirred. mixture of 7 g (0.05 mol) 2,3-diaminopropionic acid -. HC1, 20 g (0.5 mol) NaOH, 100 ml ice water, 150 ml benzene and fjO ml ether, 20.2 g (0.1 mol) of undecylenic acid chloride were added dropwise at 0°. While stirring, it was allowed to come to room temperature, acidified with semi-concentrated hydrochloric acid and separated the organic phase. After washing with water and evaporation to dryness, acetonitrile was recrystallized.

Yield: 6.3 g ($29), m.p. 87-9O<0>

Analysis: C^H^NgO^ . (436»5)

Example 162 N,N'-bis-(2-hydroxyethyl)-M,N*-bis-(heptanoyl)-ethylenediamine

was prepared analogously to Example 16l from n-heptanoic acid and N,N'-bis-(2-hydroxyethyl)-ethylenediamine.

Yield: 48$, m.p. 96-99° (acetic ester/ligroin 2:1)

Analysis: G20<H>40<N>2°4

1 - Example 163 N-(2-hydroxyethyl)-N,N*-bis-jnonanoyl)-ethylenediamine

To the stirred mixture of 10.4 g (0.1 mol) of N-(2-hydroxyethyl)-ethylenediamine, 20.2 g (0.2 mol) of triethylamine and 350 ml of abs. chloroform, 35 g (0.2 mol) of pelargonic acid chloride were added dropwise at 0°C.

After stirring overnight, the layers were separated and washed. organic phase with water. After removal of the chloroform, it was recrystallized from ligroin.

Yield: 15.3 g ($40), m.p. 71-72°

Analysis: C22<H>44<N>2°3 ^84» 4)

Example 164 H,N*-bis-(10-undecenoyl)-N,N*-diphenylethylenediamine

The synthesis of this example proceeded analogously to Example 16, in that 10.5 g (0.05 mol) of R,N<T->diphenylethylenediamine were reacted.

Yield: 8 g (29.4%), m.p. 59-6O0 (from acetonitrile) Analysis: C36H52<K>2°2<544.8)

Example 165, N,N*-(p-tblylphenylacetyl)-piperazine

30.0 g (0.2 mol) of anhydrous p-tolylacetic acid was heated in

refluxing in 100 ml of xylene and 8.6 g (0.1 mol) of piperazine after adding 0.5 g of p-toluenesulfonic acid under a water separator. After 48 hours, the mixture was cooled, the precipitated crystals were filtered off with suction and recrystallized from toluene.

Example 166 N,N'-bis-(5-phenoxypentanoyl)-piperazine was prepared analogously to Example 16 from 5-phenoxypentanoic acid and piperazine. Example 167 N,Nf-bis-(9-undecenoyl)-2,5-dimethylpiperazine could be obtained analogously to Example 16 from 9-undecenoic acid and piperazine.

Example 168

N,N'-bis-(octyloxyacetyl)-piperazine

This substance was formed analogously to Example 1§ from octyloxyacetic acid and piperazine. Yield: 72$, m.p. 37-38° (petroleum ether) Analysis: C24<H>4<6N>2°4(426.6)

Example 169

N,N'-bis-(N-pentanoyl-alanyl)-2,5-dimethylpiperazine

was prepared analogously to Example 16 from N-pentanoyl-alanine and 2,5-β-dimethylpiperazine.

Yield: 28$, m.p. 176-180°C (acetic acid)

Analysis: G^H^N^ (424.5)

Example 170

H,H'-bis-(2-chlorophenoxyacetyl)-piperazine.

was prepared analogously to Example 165 from 8.6 g (0.1 mol) of anhydrous piperazine, 37.3 g (0.2 mol) of 2-chlorophenoxyacetic acid.

Yield: 26.4 g ($62), m.p. 234-236°C (of nitromethane) Analysis: C20<H>20C12N2°4<423>3)

Examples 171-175 (Table 13) "Examples 17I-175 were prepared analogously to Example 16, in that the mixed hydride, prepared from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine and 10.8 g (0.1 mol) of chloroformic acid ethyl ester, were reacted with 0.05 mol of the diamine mentioned in Table 13. Formed oils were purified by column chromatography (neutral Al^, elution with petroleum ether). Example 177 W , N .* - bis-(4-N-methylanilinocarbonylbutyryl)-piperazine 4.9 g (0.025 mol) of piperazine hexahydrate was boiled in 300 ml of silane with 11 g (0.05 mol) of 4-N-methylanilinocarbonylbutyric acid while adding a spatula tip of p-toluenesulfonic acid under a water separator, until starting materials could no longer be detected by thin-layer chromatography (24 hours). After removal of the xylene, it was ora-' crystallized from acetonitrile. Yield: 5.1 g (41, 5$), mp 142-143° Analysis: C28H36N4°4$ (492.6) Example 178 N,N'-bis-(10-undecenoyl)-1,2-(N,N'-dimethylamino) - cyclohexane To 7.1 g (0.05 mol) 1,2-{K,N'-dimethylamino)- cyclohexane in 150 ml abs. tetrahydrofuran, 18.4 g (0.1 mol) of undecylenic acid were added. Within 30 min. 21.4 g (0.1 moi) of dicyclohexylcarbodiimide was added dropwise in 100 ml abs. tetrahydrofuran. It was stirred again overnight, dicyclohexylurea was sucked off, washed well with tetrahydrofuran and the solvent removed. The above-mentioned residue was chromatographed on neutral aluminum oxide, eluted with petroleum ether. (cont. page 77)

Yield: '3.6 g (15.298),* n<22>I.4B38

D

Analysis: C30H54N2°2 <474.8)

Example 179 N fN*-di-acetyl-N,NT-bis-(1-cyanoethyl)-trimethylenediamine 90.0 g (0.5 mol) N,N'-bis-(1-cyanoethyl)-trimethylenediamine was dissolved in ether and 112.2 g (1.1 mol) of acetic anhydride were added dropwise. After standing overnight, volatile parts were removed with an oil pump and the viscous residue was chromatographed over aluminum oxide (neutral). It was eluted with petroleum ether/acetic acid 1:1. Oil; n<22>1,4<8>45 D Analysis: ci3H20II4O2(2o4»2) The N,N<*->bis-(1-cyanoethyl)-trimethylenediamine used as starting material is prepared as follows: To 74 g (1 mol) of 1,3-diaminepropane in 200 ml of alcohol was added dropwise under ice cooling to 142 g (2 mol) of lactic acid nitrile. After stirring overnight, the solvent was completely removed. An oil was obtained as a residue. Analysis: coHi6<N>2 (l80»2)

Example l80

N * N *- bis-( 10- undecenoyl)- N, NT- bis-( 1- ethoxycarbonyl)- trimethylenediamine

The preparation proceeded analogously to Example 12 from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformic acid ethyl ester and 13.7 g (0.05 mol ) N,N<?->bis-(1-ethoxy-carbonylethyl )-trimethylenediamine . The crude product formed was purified by chromatography (AlgO 4 , neutral; elution with petroleum ether).

Yield: 15.8 g ($52) of an oil n<21>1.4753

D

The N,N<*->bis-(1-ethoxy-carbonylethyl)-trimethylenediamine used as starting material was prepared as follows: 360 g (2 mol) N,N'-bis-(1-cyanoethyl)-trimethylenediamine was long- which, while cooling and stirring, is dripped into 2.3 1 concentrated hydrochloric acid. It was then boiled for 6 hours under reflux, the hydrochloric acid was completely removed in vacuo, the residue was taken up in methanol, the insoluble matter was filtered off with suction and evaporated again to dryness. The residue was taken up in methanol, the residue filtered and mixed with diethylamine to a weak, basic reaction. After standing overnight in a refrigerator, the solid was suctioned off and washed well with alcohol and dried at f0°G\Yield: 168 g (60$), m.p. > 250°C.

The amino acid thus formed was suspended in 1 liter of abs. ethanol. At 15-20°, HCl gas was introduced to saturation.

After standing overnight, the solvent was removed in vacuo, the residue was dissolved in 300 ml of ice water and 800 ml of ether was added. During cooling, the temperature is kept around 0°, while alkaline was set with a 3°$-ig aqueous NaOH solution. After addition of solid KgCO^ to remove a semi-solid aqueous phase, the ether solution was poured off, the aqueous phase was treated 3 more times with 200 ml of ether, the ether solutions were combined, dried well with Na2SO^

and distilled. Boiling point 128-132°/0.6 mm.

Dividend: 79<g=>(37.4$)-;

Analysis: CI3H26W2°4 (274.4)

Calculated: C 56.9 H 9.6 N 10.2 Found: C 56.7 H 9.7 N 10.3

Example l8l

RtN*- bis-(dodecanoyl)- R, R'- bis-(1- ethoxycarbonylethyl)- trimethylenediamine

was produced analogously to Example 16 or Ex. l8o using 20.0 g (0.1 mol) of dodecanoic acid.

Yield: 48 g ($69), the oil<21>I.47O<O>

D

Analysis: C32<H>6<0N>2°6(568.7):

Calculated: C 69.2 H 10.9 N £.5 0 15.4

Found: C 69.6 H 10.6 N 4.7 0 15.4

Example 182

R;, M' - bis-( dodecanoyl) - N yN' - bis-( 1-^ hydroxycarbonylethyl) - trimethylenediamine

To an ice-cooled and well-stirred mixture of 21.8 g (0.1 mol) of N,R'-bis-(1-hydroxycarbonylethyl)-trimethylenediamine (see Ex. l80), 250 ml of a 1 N aqueous NaOH solution, At around 0°, 48.2 g (0.22 mol) of dodecanoic acid chloride were added dropwise to 200 ml of benzene and 100 ml of ether. After stirring overnight it was acidified, the organic phase was separated, washed with water and the solvent removed. The oily residue was recrystallized from methanol.

[Jtchange; 41.2 g ($72.5), m.p. 36-38°.

Analysis: . C^HgøNgOg (568.7)

Example 183-184 (Table 14)

The synthesis of these compounds proceeded analogously to Example 18 by reacting 0.05 mol of the corresponding amine with 17.7 g (0.1 mol) of nonanoic acid chloride in chloroform as a solvent.

Example 185

g~ 2- chloroethyl- H, NT- bis-(nonanoyl)- ethylenediamine

2.8 g (0.05 mol) of N-p-chloroethyl-ethylenediamine x 2 HCl was dissolved in 200 ml of ice water. While cooling with ice, 17.7 g (0.11 mol) of nonanoic acid chloride and .2 N aqueous NaOH solution were added dropwise at 0°3, so that the solution remained practically neutral. The water above was stirred at room temperature and the reaction product was extracted with chloroform. After washing with running water and removal of the solvent, 14.6 g of crude diamide were formed.

Analysis- C22P43C1N202(403.06)

Example 18# in M, N*-bis-(dodecanoyl)-N-(g-dodecanoyloxyethyl)-ethylenediamine 10.4 g (0.1 mol) of W-(3-hydroxyethyl)-ethylenediamine were dissolved in 200 ml of abs. tetrahydrofuran. After the addition of 3°»3g (°»3mol) of triethylamine, 46 g (°>3mol) of dodecanoic acid chloride were added dropwise under ice-cooling. After still stirring for 2 hours at room temperature, it was heated for 2 hours at approx. 50 » cooled and poured into water. The reaction product was extracted with chloroform. After washing with water and evaporation to dryness,

was recrystallized from naphtha and from acetonitrile.

Yield: 44.1 g ($68), m.p. 62T64°

Analysis: C4o<H>78<N>2°4(651.0)

Example 18' 7 Diethylacetic acid-/N,N*-bis-(1,3-diethylacetylamino)-2-propyl ester/

To 4.5 g (0.05 mol) of 1,3-diamino-2-hydroxypropane in 100 ml of abs.

chloroform and 16.7 g (0.165 mol) of triethylamine, 22.2 g (0.165 mol) of diethylacetic acid chloride were added dropwise under ice-cooling. It was stirred for another 2 hours at room temperature and then another 2 hours at approx. 40°C. After cooling, they were washed in sequence

with water, 1 N aqueous NaOH and water. After removal of chloroform, it was recrystallized twice from ligroin.

Yield: 12.6 g ($66), m.p. II4-II5<0>

?Example 188 N,N*-bis-(8-dodecanoyloxyethyl)-N,N*-bis-(dodecanoyl)-ethylenediamine

7.4 g (0.05 mol) of N,N*-di-(O-hydroxyethyl)-ethylenediamine was dissolved in 200 ml of ice water. After the addition of 300 ml of chloroform, 20 g (0.25 mol) of caustic soda were added. At approx. 0°, 44.0 g (0.2 mol) of dodecanoic acid chloride were added dropwise with good stirring. At ice-bath temperature, it was stirred for a further 3 hours, and after stirring

overnight, the organic phase was separated by washing with water and the chloroform was removed in vacuo. The residue was recrystallized from ethanol and from methanol.

Yield: 43.8 g ($6.2), . m.p. 69<->7I<0>

Analysis: C54<H>104<N>2°6<<8>?7,4)

Example 18Q- 193

The preparation of these examples proceeded analogously to Example 16 by reacting 18.4 g (0.1 mol) of undecylenic acid with 0.05 mol of the specified diamino compound over the mixed anhydride in tetrahydrofuran as solvent.

Example 194 N-dodecanoyl-NI-fg-decanoylaminoethyl)-piperazine

■6.5 g (0.05 mol) of R-(3-aminoethyl)-piperazine and 10.1 g (0.1 mol) of triethylamine were dissolved in 100 ml of abs. chloroform. 21.8 g (0.1 mol) lauric acid chloride was added dropwise, dissolved in 5° ml abs. CHCl^, stirred for 13 hours at room temperature and 2 hours at 5°°c. Then it was shaken out with water, the chloroform was removed and the residue was recrystallized from alcohol.

Yield: 17.7 g ($72), m.p. 87-88°

Analysis: C^H^N^Og (493*7)

Example 195 .■■■'• .

N,N*-bis-(decanoyl)-2-aminomethyl-pyrrolidine

The preparation proceeded analogously to Example 194* 5 g (0.1 mol) of 2-aminoraethylpyrrolidine was reacted with 19.0 g (0.1 mol) of capric acid chloride. Yield: 11.5 g { 56.5$). m.p. 55-56° (from ligroin) Analysis: C25H48N2°2 <408.5) Example 19& tø , N'-bis-(decanoyi)-2-aminomethyl- piperidine

This compound was prepared analogously to Example I64 using 5.7 g (0.05 mol) of 2-aminomethylpiperidine and 19.0 g (0.1 mol) of decanoic acid chloride.

Yield: 9.2 g ($43.6), m.p. 45-47° :.(from a little petroleum ether) Analysis: C26<H>5<0N>2°2(422.6)

Example 197 N.NVbis-(2-ethyl-eb.hexanoyl)-2-aminomethyl-hexamethyleneimine

is prepared analogously to Example I64 from 6.4 g (0.05 mol) of 2-aminomethyl-cyclohexanimine and 16.2 g (0.1 mol) of ethyl-propyl-acetic acid chloride. After chromatography over alumina (neutral) and elution with petroleum ether, an oil was formed.

Yield: 9.3 g ($52.8), n<2>° I.4840

D

Analysis: CgoH.iNgOg . (380.6)......

Example 198 H, Nt-bis-(2-ethyl-hexanoyl)-2-methylaminomethyl-piperidine

is prepared analogously to Example 194, starting from 3.4 g

(0.026 mol) of 2-methylaminomethyl-piperidine, 5.3 g (0.052 mol) of triethylamine and 8.4 g (0.052 mol) of 2-ethylpentanoic acid chloride in chloroform. Oil (after chromatography over AlgO^, neutral, and elution with petroleum ether).

Yield: 4.5 g ($53), n<21>I.481O

D

Analysis: C<g>^<H>^NgOg (380.6)

Claims (1)

1. Carboxylic acid aradides of the general formula I where R1, R2 and r <3.> are the same or different and mean a right linear, branched, cyclically saturated and unsaturated hydrocarbon residue, where the carbon chain is interrupted by divalent heteroelements or groupings such as oxygen, sulfur,* sulfine, sulfone,, carbonyl,. f phenyl one and is optionally substituted with substituents such as halogen, alkoxy, acyloxy, aryl, aryloxy, aryl-mercapto, aroyl, alkylmercapto, alkylsulfine and . R 1 and r 5 are the same or different and mean hydrogen, optionally substituted aryl or a straight chain, branched, cyclically saturated and unsaturated hydrocarbon residue, the carbon chain evei tuIt being interrupted by heteroatoms or groupings such as oxygen, sulfur, sulfone, sulfine, carbonyl, phenylene and optionally substituted with -substituents such as hydroxy, alkoxy, halogen, acyloxy, acylamino, aryl, aryloxy, aroyl, -alkylthio, alkylsulfone and alkylsulfine, cyano, alkoxycarbonyl, aroxycarbonyl or aminocarbonyl, with the aminocarbonyl residue again possibly being substituted tuted with alkyl or aryl residues or in which R <4> and R^ in the event that n = 0 otherwise means an alkylene- chain which forms a heterocyclic ring with the two nitrogen atoms, or where r<4> and R^ means an alkylene residue which in the neighboring X forms a nitrogen-containing ring, X means a rectilinear, branched, cyclically saturated and unsaturated hydrocarbon chain, as this chain is optionally interrupted by heteroatoms or groupings such as oxygen, sulphur, sulfine, sulfone, arylase, alkylase, carbonyl or phenylene and is optionally substituted with substituents such as halogen, alkoxy, aroxy, hydroxy, cyano, hydroxycarbonyl, alkoxycarbonyl, acylamino, aroxycarbonyl, alkylthio, alkylsulfine, alkylsulfone, arylthio, aryl or aminocarbonyl, the aminocarbonyl residue being optionally substituted with alkyl or aryl and n means an integer from 0 to 4" in that all aryl residues defined under R1, R<2>, R^,r<4> and R^ and X contain 6 or 10 C atoms and are optionally substituted.;2. Process for the preparation of new carboxylic acid amides of the general formula I; where R<1> , R2, R^, R^, R <5>f x and n have the meaning stated in claim 1, characterized in that amines of the general formula II; wherein.. R<4> , R^ and X have the above meaning, optionally reacted in the presence of acid binders or water-attracting agents and inert solvents at temperatures between -20 and 250°C with carboxylic acid or carboxylic acid derivatives of the general formula III; in which B means the substituents R1, R2 and R^ as above meaning and A means hydroxy, or an acid group activating residue such as halogen, azide, cyano, alkoxy, alkylthio, acyloxy, cyanomethyloxy, aryloxy, arylthio, aroyloxy, suceinimido-N-oxy, phthalimido-N-oxy, the aryl groups possibly being substituted one or more times. 3 • Medicinal product, characterized by a content of at least one carboxylic acid amide according to claim 1. 4" Process for the production of hypolipidemic agents, characterized in that carboxylic acid amides according to claim 1 are mixed with inert non-toxic pharmaceutically suitable carriers. 5. Method for treating hyperlipidemia, characterized in that carboxylic acid amides according to claim 1 are applied as needed to humans or animals.