DE2745673A1 - Compsn. for eliminating tumours and diseased tissue - contains a dehydro-oligopeptide of low toxicity - Google Patents

Abstract

Compsn. for causing the disappearance, without suppuration, of tumours and/or tissues contains >=1 dehydro-oligopeptide (I). (I) are pref. of formula: In (I) R1 is H, alkanoyl, alkenoyl, aroyl, aralkanoyl, aralkenoyl, heteroaroyl, lower alkylsulphonyl or arylsulphonyl (all opt. substd.) or is alkoxycarbonyl, aralkoxycarbonyl or carbamoyl. R2, R7 and R12 are each H or lower alkyl, or R2, R7 or R12 together with R3 or R8, or R14 or adjacent C, form a 3-4C alkylene chain. R4 and R9 are each H or lower alkyl. R3, R8 and R13 are each H, opt. branched lower alkyl, aryl, aralkyl, aralkenyl, cycloalkyl cycloalkenyl or 4-7 membered heterocyclylmethyl with 1 or 2 heteroatoms (all opt. substd.), or indolylmethyl. R5 and R10 are each H or opt. substd. lower alkyl. R6 and R11 are each opt. substd. alkyl, aryl, 5-7 membered heterocyclyl with 1 or 2 heteroatoms, aralkyl or aralkenyl, or one or goth of them together with R5 or R10 are 3-7C opt. substd. alkylene or alkenylene. R14 is H, opt. substd. lower alkyl, or with R13 and C atom between them, complete a 4-7C alicyclic ring. R15 is OH, opt. substd. lower alkoxy, alkenyloxy, alkylthio, alkenylthio, arylthio or hydrazine, NH2 (opt. substd. by 1 or 2) opt. substd. alkyl), opt. substd. mono- or di-alkenylamino, alkynylamino, arylamino, mono- or di-aralkylamino, or an opt. substd. 4-7 membered N heterocycle which can have 1 or 2 other heteroatoms, amino substd. by opt. substd. 3-7 membered alicyclic rings, or aralkoxy amino. m, n, p and q are 0 or 1, but not all 1 at the same time). Their pharmaceutically acceptable salts can be used Used human and veterinary medicine for treating a wide range of tumours, pref. by topical application, and a variety of diseased tissues e.g. varicose ulcers, tubercular lesions, lesions caused by bacterial or fungal infections etc.

Description

The present invention relates to the use of partially known dehydrooligopeptides as tumor- and / or tissue-dissolving medicaments.

In the following, dehydrooligopeptides are to be understood as meaning compounds which are linked in the manner of a peptide and consist of two to ten amino acid units and have at least one double bond (corresponding to at least one dehydroamino acid group).

The use of dehydrooligopeptides as drugs is not previously known.

It is known that a tumor- and tissue-dissolving effect can be achieved with a wide variety of substances. The general toxicity of such compounds, however, is usually so great that therapeutically easy to handle treatment options which do not cause further harm to the patient hardly exist.

Substances that are chemically related to dehydrooligopeptides and have a comparable effect are so far unknown. Commercial products for use in corresponding indications are the cytostatics, cyclophosphamide being mentioned here as an example.

All the agents used so far show extremely high general toxicity. This is often so pronounced that treatment has to be discontinued and the tumor diseases are often fatal.

As an example of the general toxic effect, that of cyclophosphamide should be mentioned here. So report M.H.N. TATTERSALL and J.S. TOBIAS in The Lancet 1976 / II, No. 7994, page 1071: "For many anti-cancer drugs, twice the dose that kills 10% of the animals (LD [low] 10) is fatal for 90% of the animals (LD [low] 90). FREE and FREE (Advances in Chemotherapy 2 (1965), 269) were able to document the importance of using agents such as cyclophosphamide in doses approaching the toxicity rate (LD [low] 10.) The key feature of these experiments was the observed exponential increase The LD [low] 10 dose of cyclophosphamide killed 99.999% of the tumor cells, but one eighth of this dose (which was far less toxic) only killed 90% of the tumor cells and was therefore clinically dead 5 log less effective.

This observation is the basis for the widespread view that chemotherapy for cancer is only effective if it is generally toxic. "

The present invention now relates to the use of partially known dehydrooligopeptides as medicaments with tumor- and tissue-dissolving action which no longer have the above-mentioned disadvantages of the general toxic effects; they are characterized by a strong tissue-dissolving effect, which is dose-dependent with good general tolerance.

It has been found that dehydrooligopeptides and their physiologically tolerable salts have a very good tumor- and / or tissue-dissolving effect.

In particular, it was found that dehydrooligopeptides of the general formula (I)

in which

R [deep] 1 for a hydrogen atom,

an optionally substituted alkanoyl group,

an optionally substituted alkenoyl group,

an alkoxycarbonyl group,

an optionally substituted aroyl group,

an optionally substituted aralkanoyl group or aralkenoyl group,

an aralkoxycarbonyl group,

a carbamoyl group, an optionally substituted heteroaroyl group,

an optionally substituted lower alkylsulfonyl group or

an optionally substituted arylsulfonyl group

stands,

R [deep] 2, R [deep] 7 and R [deep] 12 each for a hydrogen atom,

represents a lower alkyl group

or in which R [deep] 2, R [deep] 7 or R [deep] 12 together with the respective adjacent substituents R [deep] 3 or R [deep] 8 or R [deep] 14 is an alkylene chain with three to form four carbon atoms,

R [deep] 4 and R [deep] 9 each represent a hydrogen atom or a lower alkyl group,

R [deep] 3, R [deep] 8 and R [deep] 13 each for a hydrogen atom,

a lower straight or branched chain optionally substituted alkyl group,

an optionally substituted aryl group,

an optionally substituted aralkyl or aralkenyl group,

an optionally substituted cycloalkyl or cycloalkenyl group,

an indolylmethyl group,

an optionally substituted heterocyclic methyl group with four to seven ring members and one to two heteroatoms,

R [deep] 5 and R [deep] 10 each represent a hydrogen atom or

an optionally substituted lower alkyl group,

R [deep] 6 and R [deep] 11 each represent an optionally substituted alkyl group,

an optionally substituted aryl group,

an optionally substituted heterocycle with five to seven ring members and one to two heteroatoms,

for an optionally substituted aralkyl group,

an optionally substituted aralkenyl group

or in which R [deep] 6 and / or R [deep] 11 in connection with R [deep] 5 or R [deep] 10 represent an optionally substituted alkylene or alkenylene chain with three to seven carbon atoms,

R [deep] 14 represents a hydrogen atom, an optionally substituted lower alkyl group or in connection with R [deep] 13 and the carbon atom between them represents an alicyclic having four to seven carbon atoms,

R [deep] 15 for a hydroxyl group,

an optionally substituted lower alkoxy or alkenyloxy group,

an optionally substituted lower alkylthio or alkenylthio group,

an optionally substituted arylthio group,

an optionally substituted hydrazino group,

an amino group,

a lower optionally substituted alkylamino or dialkylamino group or alkenylamino or dialkenylamino group or alkynylamino group,

for an optionally substituted arylamino group,

an optionally substituted mono- or diaralkylamino group,

a nitrogen-containing optionally substituted heterocycle with four to seven ring members, in which one to two further heteroatoms can be contained, or

for an amino group substituted by optionally substituted alicyclics with three to seven ring members, or

stands for an aralkyloxyamino group, m, n, p and q stand for the digits 0 or 1 with the proviso that not all four letters may be 1 at the same time,

and their physiologically compatible salts have strong tumor and tissue dissolving properties.

It is new and completely surprising that dehydrooligopeptides show such a pronounced tumor- and tissue-dissolving effect.

The active ingredients according to the invention thus represent an enrichment in pharmacy.

In the general formula (I), the radicals R [deep] 1 to R [deep] 15 have the following preferred meanings:

The alkanoyl radical R [deep] 1 is preferably a straight-chain or branched alkanoyl radical having two to six carbon atoms. Examples include: acetyl, propionyl, butyryl, pentanoyl.

The alkenoyl radical R [deep] 1 is preferably a straight-chain or branched alkenoyl radical having three to six carbon atoms. Examples include: crotonyl and acrylyl.

Possible substituents of R [deep] 1 for the alkanoyl or alkenoyl radical R [deep] 1 are: one to three halogen atoms, preferably fluorine and chlorine atoms, methoxy, ethoxy or heteroaryl group.

Examples include the chloroacetyl, trichloroacetyl, trifluoroacetyl or the thiophenyl radical.

The lower straight or branched alkoxycarbonyl radical R [deep] 1 preferably represents the methoxy, ethoxy, propoxy and butoxycarbonyl group, in particular the tert-butoxycarbonyl group.

The optionally substituted aroyl radical R [deep] 1 preferably denotes the benzoyl or naphthoyl radical.

The optionally substituted aralkanoyl or aralkenoyl radical R [deep] 1 preferably denotes a radical having eight to twelve carbon atoms, in particular eight to ten carbon atoms. Examples include the phenacetyl, phenpropionyl, phenisopropionyl, cinnamoyl, or beta-methylcinnamoyl or phenylbutanoyl radical.

Possible substituents in the aroyl, aralkanoyl or aralkenoyl radical R [deep] 1 are:

one to three halogen atoms, alkyl or alkoxy groups with up to three carbon atoms, in particular the methoxy, trifluoromethyl group, a nitro group or hydroxyl groups, which can also be acylated with lower organic acid residues.

The aralkoxycarbonyl radical R [deep] 1 means in particular one with eight to ten carbon atoms, preferably the benzyloxycarbonyl group.

Under an optionally substituted heteroaroyl radical R [deep] 1 is a heterocycle with five to seven ring members, which can contain one to three nitrogen, sulfur or oxygen atoms, understood with a carbonyl group attached to it. Examples include the pyridine carbonyl, thiophenecarbonyl, furancarbonyl, pyrrole carbonyl, oxazole carbonyl, thiazole carbonyl and pyrazine carbonyl groups. These heterocycles can be substituted by one or more halogen atoms, preferably fluorine and chlorine atoms, alkoxy groups with one to four carbon atoms or alkyl groups with one to four carbon atoms.

The optionally substituted lower alkylsulphonyl radical R [deep] 1 or arylsulphonyl radical R [deep] 1 preferably denotes the methanesulphonyl, ethanesulphonyl, benzenesulphonyl or toluenesulphonyl radical.

A lower alkyl group in the radicals R [deep] 2, R [deep] 7 and R [deep] 12 preferably denotes the methyl and ethyl group.

If R [deep] 2, R [deep] 7 and R [deep] 12 together with the respective adjacent R substituents R [deep] 3, R [deep] 8 or R [deep] 14, an alkylene chain with three to four Forming carbon atoms, this means that R [deep] 2 with the associated nitrogen atom and the adjacent -CH group of the chain and R [deep] 3 form a pyrrolidine or piperidine ring. The same applies to R [deep] 7 and R [deep] 8 or R [deep] 12 and R [deep] 13.

A lower alkyl group as a radical for R [deep] 4 and R [deep] 9 preferably denotes the methyl or ethyl group.

An optionally substituted straight or branched chain lower alkyl or alkenyl radical R [deep] 3, R [deep] 8 and R [deep] 13 denotes a hydrocarbon radical with preferably one to six carbon atoms and optionally a double or triple bond, such as, for example a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl radical, the pentyl and hexyl radical with its possible isomers, also the vinyl, acetylene, propenyl or the crotyl residue.

Substituents for the alkyl radical R [deep] 3 or R [deep] 8 or R [deep] 13 may be mentioned:

one to three halogen atoms, hydroxyl groups, alkoxy groups with preferably one to four carbon atoms, alkylthio groups with preferably one to four carbon atoms, sulfydryl groups, carbamido groups, carboxyl groups.

Examples of such substituted alkyl groups are the carboxymethyl, carboxyethyl, carbamoylmethyl, methylmercaptoethyl, trifluoromethyl, fluoromethyl, chloromethyl and hydroxymethyl groups.

An optionally substituted aryl group for R [deep] 3, R [deep] 8 and R [deep] 13 in the general formula I is preferably the phenyl radical. It can be substituted by one or more halogen atoms, trifluoromethyl groups, hydroxyl groups, lower alkoxy groups with one to four carbon atoms, alkyl groups with one to four carbon atoms, nitro groups or lower acyloxy groups with one to four carbon atoms.

An optionally substituted aralkyl or aralkenyl group for R [deep] 3, R [deep] 8 and R [deep] 13 preferably denotes a phenylalkyl or -alkenyl group with up to four carbon atoms and a double or triple bond in the side chain, especially a CH [deep] 2 group. The aralkyl or aralkenyl radical can be substituted by one or more halogen atoms, nitro, hydroxy, methoxy or alkyl groups with one to four carbon atoms.

An optionally substituted cycloalkyl or cycloalkenyl radical R [deep] 3, R [deep] 8 and R [deep] 13 stands for mono-, bi- and tricyclic cycloalkyl or cycloalkenyl with preferably 3 to 10, in particular 3, 5 or 6 Carbon atoms. Optionally substituted cyclopropyl, cyclopropenyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, bicyclo [2.2.1] heptyl, bicyclo [2.2.2] octyl and adamantyl may be mentioned as examples.

The cycloalkyl or cycloalkenyl radical R [deep] 3, R [deep] 8 and R [deep] 13 can be substituted by one or more halogen atoms, nitro, hydroxy, alkoxy or alkyl groups each having one to four carbon atoms.

An optionally substituted heterocyclic methyl group means, in particular, the furfuryl, thenyl, pyrrolylmethyl, thiazolylmethyl, oxazolylmethyl, pyridinemethyl, piperidinemethyl, pyrazinemethyl or morpholine methyl group. They can optionally be substituted by one to three halogen atoms, alkyl or alkoxy groups with one to three carbon atoms or a nitro group.

Optionally substituted lower alkyl radicals for R [deep] 5, R [deep] 10 and R [deep] 14 denote alkyl radicals with preferably one to six, in particular one or two carbon atoms, which can be substituted by halogen atoms, in particular chlorine or fluorine atoms.

An optionally substituted alkyl group for R [deep] 6 and R [deep] 11 in the general formula I denotes a straight- or branched-chain alkyl group with preferably one to six carbon atoms, in particular one to three carbon atoms. It can be substituted by one to three halogen atoms, preferably chlorine or fluorine atoms, or by alkoxy groups with one to four carbon atoms, in particular methoxy groups.

An optionally substituted aryl radical for R [deep] 6 and R [deep] 11 means in particular the phenyl radical and the naphthyl radical. These can be substituted by halogen atoms, preferably fluorine and chlorine atoms, alkyl or alkoxy groups with one to four carbon atoms, methoxy and methyl groups being preferred, nitro groups, hydroxy and lower acyloxy groups with one to four carbon atoms, amino, lower alkylamino - Or lower dialkylamino groups, preferably dimethylamino groups.

An optionally substituted heterocyclic radical for R [deep] 6 and R [deep] 11 denotes a heterocycle with five to seven ring members and one to two heteroatoms, in particular nitrogen, sulfur or oxygen atoms. The thienyl, furyl, pyrrolyl, pyridyl, imidazolyl, pyrazolyl, pyrimidyl, pyrazinyl and morpholinyl radicals may be mentioned as examples. These can be substituted by halogen atoms, alkyl or alkoxy groups with one to four carbon atoms, hydroxyl, nitro and trifluoromethyl groups.

Optionally substituted aralkyl or aralkenyl groups for R [deep] 6 and R [deep] 11 are in particular those with seven to ten carbon atoms; phenylalkyl or phenylalkenyl groups with one to four carbon atoms in the aliphatic part are preferred. The cinnamenyl group and the phenethyl group may be mentioned by way of example. They can be substituted by one or more halogen atoms, alkyl or alkoxy groups with preferably one to four carbon atoms, nitro groups and trifluoromethyl groups.

In general formula I, the radicals R [deep] 6 and R [deep] 11 with R [deep] 5 or R [deep] 10 and the carbon atom connecting them on the double bond can form a cycloalkylidene ring or cycloalkenylidene ring with preferably three to seven Carbon atoms, especially the cyclohexylidene and cyclohexenylidene rings.

An optionally substituted lower alkoxy or alkenyloxy radical for R [deep] 15 in the general formula I denotes a straight or branched-chain alkoxy or alkenyloxy radical having one to six carbon atoms, in particular one to four carbon atoms. The methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or tert-butoxy groups may be mentioned as examples. They can be substituted by one or more halogen atoms or alkoxy groups with one to two carbon atoms.

A lower, optionally substituted alkylthio or alkenylthio group for R [deep] 15 is one having one to six carbon atoms, in particular one to four carbon atoms. One to three halogen atoms, alkoxy groups or the carboxy group may be mentioned as substituents.

An optionally substituted arylthio group for R [deep] 15 preferably denotes the phenylthio group, which can be substituted by one to three halogen atoms, lower alkyl or alkoxy groups, preferably each with one or two carbon atoms.

An optionally substituted hydrazine radical for R [deep] 15 means that the hydrazine radical is substituted by a lower alkyl group, optionally substituted aryl groups, preferably by a phenyl group, which in turn can be substituted by one to three halogen atoms, lower alkyl or alkoxy groups,

or can be substituted by a heterocycle with one to two nitrogen, oxygen and / or sulfur atoms, which can also be fused with a phenyl ring.

A lower, optionally substituted monoalkylamino or monoalkenylamino or dialkenylamino or dialkylamino group R [deep] 15 denotes in each case straight or branched chain alkyl or alkenyl substituents with preferably one to six carbon atoms, such as, for example, the methylamino, ethylamino, Pentylamino and 1,1-dimethyl-2-propynylamino groups. They can be substituted, for example, by halogen atoms, hydroxyl groups, alkoxy groups with one or two carbon atoms, amino, lower monoalkylamino or dialkylamino groups, by a sulfonic acid radical, phosphate radical or by heterocycles, in particular by a morpholine or imidazole ring.

An optionally substituted arylamino group R [deep] 15 preferably denotes the phenylamino group, which can be substituted by one to three halogen atoms, alkyl or alkoxy groups, preferably each with one or two carbon atoms.

A mono- or di- optionally substituted -aralkylamino group for R [deep] 15 preferably denotes a mono- or diphenylalkylamino group with one to four carbon atoms in each case in the aliphatic part. These can be substituted by one to three halogen atoms, alkyl or alkoxy groups each with one to four carbon atoms.

A nitrogen atom-containing heterocyclic group for R [deep] 15 means one with four to seven ring members, which can contain one or two further heteroatoms and which can optionally be substituted by a lower alkyl, lower hydroxyalkyl or phenyl group.

An amino group substituted by alicyclics with three to seven ring members means a cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino and cycloheptylamino group, preferably the cyclohexylamino group or the correspondingly disubstituted amino group. This can be substituted by lower alkyl, alkenyl, alkynyl or aryl groups.

Some of the starting compounds for the preparation of the compounds of general formula I according to the invention, the corresponding 2,4-disubstituted 5 (4H) -oxazolones, are known from the literature. If they are not known, they can be produced using the methods described in the literature. The reaction of acetylglycine with benzaldehyde is described here as an example. The reaction takes place according to the equation

The reaction is carried out by mixing the two components in equimolar proportions in the presence of a condensing agent, usually acetic anhydride, which also serves as a solvent, and a basic component such as sodium acetate. After standing for several hours, it is worked up by diluting with water and recrystallizing the precipitated 4-benzylidene-2-methyl-5 (4H) -oxazolone from ethyl acetate / petroleum ether.

Further examples of starting compounds are:

2-methyl-4- (2-thenylidene) -5 (4H) -oxazolone,

2-methyl-4- (2-naphthylmethylene) -5 (4H) -oxazolone,

4- (4-Acetoxy-3-nitrobenzylidene) -2-methyl-5 (4H) -oxazolone,

4-ethoxymethylene-2-phenyl-5 (4H) -oxazolone,

4-cyclohexylmethylene-2-phenyl-5 (4H) -oxazolone,

4-benzylidene-2-trifluoromethyl-5 (4H) -oxazolone,

4- (1-methylpropylidene) -2-phenyl-5 (4H) -oxazolone,

2-phenyl-4- (2-thenylidene) -5 (4H) -oxazolone,

2- (3-pyridyl) -4- (2-thenylidene) -5 (4H) -oxazolone,

4- (1-methyl-3-phenyl-2-propenylidene) -2-phenyl-5 (4H) -oxazolone,

2- (1-Acetamido-2-phenylvinyl) -4- (4-dimethylaminobenzylidene) -5 (4H) -oxazolone,

4-thenylidene-2- (3-trifluoromethylphenyl) -5 (4H) -oxazolone,

4- (2-Cyclohexenylidene) -2-phenyl-5 (4H) -oxazolone,

4- (3-phenyl-2-propylidene) -2-phenyl-5 (4H) -oxazolone,

4- (Alpha-methylbenzylidene) -2-phenyl-5 (4H) -oxazolone,

4-cyclohexylidene-2-phenyl-5 (4H) -oxazolone,

4- (3-chlorobenzylidene) -2- (1-acetamido-2-phenylethyl) -5 (4H) -oxazolone,

4- (3-chlorobenzylidene) -2- (L-1-tert-butoxycarbonylamino-2-phenylethyl) -5 (4H) -oxazolone,

2- (1-Acetamido-2-phenylvinyl) -4- (4-hydroxybenzylidene) -5 (4H) -oxazolone,

2- (1-propenyl) -4- (2-thenylidene) -5 (4H) -oxazolone,

2-ethoxymethyl-4- (2-thenylidene) -5 (4H) -oxazolone,

2-phenyl-4-benzylidene-5 (4H) -oxazolone,

2- (2-phenylvinyl) -4-benzylidene-5 (4H) -oxazolone,

2- [1-Acetamido-2- (2-thienyl) vinyl] -4- (2-thenylidene) -5 (4H) -oxazolone,

2- [1-Acetamido-2- (2-thienyl) vinyl] -4- (5-methylthenylidene-2) -5 (4H) -oxazolone,

2- [1-Acetamido-2- (2-thienyl) vinyl] -4- (4-nitrobenzylidene) -5 (4H) -oxazolone,

2- [2- (3.4.5-trimethoxyphenyl) vinyl] -4- (2-thenylidene) -5 (4H) -oxazolone,

2-methyl-4- (5-nitrothenylidene-2) -5 (4H) -oxazolone,

2- (2-thienyl) -4- (2-thenylidene) -5 (4H) -oxazolone,

2-phenyl-4- (4-pyridylmethylene) -5 (4H) -oxazolone,

2- (4-nitrophenyl) -4- (2-thenylidene) -5 (4H) -oxazolone,

2- (3-Thienylmethyl) -4- (2-thenylidene) -5 (4H) -oxazolone,

2- [1-Acetamido-2- (2-thienyl) vinyl] -4- (Alpha-methyl-2-thenylidene) -5 (4H) -oxazolone.

A number of the active ingredients according to the invention are new; however, they can be produced by known processes (cf. D.G.DOHERTY et al., J.biol. Chem. 147 (1943), 617). They are obtained, for example, either by alkaline hydrolysis of the corresponding 2,4-disubstituted 5 (4H) -oxazolones or by aminolysis of the oxazolones with the alkali salts, esters or amides of amino acids.

The reactions involved in the synthesis of N-acetyldehydrophenylalanyldehydro- (3-chlorophenyl) alanine and N-acetyldehydrophenylalanyldehydro- (3-chlorophenyl) alanyl-L-tyrosine are described as examples:

The reaction is usually carried out by stirring or standing the reactant in diluents such as aqueous acetone, tetrahydrofuran, dimethylformamide or alcohols, usually at room temperature or slightly elevated temperature, the reaction time depending on the reactivity (1/2 to twenty hours).

Working up is carried out by acidification with, for example, HCl and evaporation of the organic solvent, the end product normally precipitating out.

If the reaction times were extremely long, partial racemization cannot be ruled out, as can be seen from the optical rotation values.

In some cases, for reasons of purity and yield, it has proven to be expedient to use an amino acid ester instead of the free amino acid in the aminolysis and to hydrolyze this after the condensation.

Examples of the active ingredients according to the invention include:

N-benzoyldehydro-beta (2-thienyl) alanine methyl ester,

N-acetyldehydro-beta (2-thienyl) alanine ethyl ester,

N-acetyldehydrophenylalanine,

N-phenylacetyldehydro-beta (thienyl) alanine,

N-acetyl-DL-phenylalanyldehydro- (3-chlorophenyl) alanine,

N-tert-butoxycarbonyl-L-phenylalanyldehydro- (3-chlorophenyl) alanine,

L-phenylalanyldehydro- (3-chlorophenyl) alanine,

N-acetyldehydrophenylalanyl-L-proline,

N-acetyldehydrophenylalanyl-D-proline,

N-acetyldehydrophenylalanyl-D-tyrosine,

N-acetyldehydrophenylalanyl-L-leucine,

N-acetyldehydrophenylalanyl-L-methionine,

N-acetyldehydrophenylalanyl-L-aspartic acid,

N-acetyldehydrophenylalanyl-L-glutamine,

N-acetyldehydrophenylalanyl-DL-3-fluoroalanine,

N-acetyldehydrophenylalanyl-L-serine,

N-acetyldehydrophenylalanyl-L-tyrosine,

N-acetyldehydrophenylalanylglycine,

N-acetyldehydrophenylalanyl-L- (p-nitrophenyl) alanine,

N-acetyldehydrophenylalanyl-DL- (p-chlorophenyl) alanine,

N-trifluoroacetyldehydrophenylalanyl-L-tyrosine,

N-acetyldehydro- (p-methylphenyl) alanyl-L-tyrosine,

N-Benzoyl-2-cyclohexylideneglycyl-L-tyrosine,

N-Benzoyl-2- (2-cyclohexenylidene) glycyl-L-tyrosine,

N-acetyldehydro-3- (2-furyl) alanyl-L-tyrosine,

N-acetyldehydro-3-cinnamenylalanyl-L-tyrosine,

N-acetyldehydro-3- (2-naphthyl) alanyl-L-tyrosine,

N-benzoyldehydro-3-cyclohexylalanyl-L-tyrosine,

N-benzoyldehydro-3-benzyl-3-methylalanyl-L-leucine,

N-trifluoroacetyldehydrophenylalanyl-L-tyrosine tert-butyl ester,

N-benzoyldehydro-3- (2-thienyl) alanyl-L-proline,

N-acetyldehydrophenylalanine (1-carboxy-1-cyclopentyl) amide,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-tyrosine tert-butyl ester,

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-leucine methyl ester,

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-leucine,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L- (p-nitrophenyl) alanine,

N-nicotinoyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-benzoyldehydro-3- (2-thienyl) alanyl-L-proline,

N-nicotinoyldehydro-3- (2-thienyl) alanyl-L- (p-nitrophenyl) alanine,

N-Benzoyl-3-methyl-3- (2-thienyl) dehydroalanyl-L-tyrosine,

N-acetyldehydro-3- (2-thienyl) alanyl-D-tyrosine,

N-cinnamoyldehydrophenylalanylglycine,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-phenylalanine,

N-benzoyldehydro-3- (2-thienyl) alanyl-L-leucine,

N-acetyldehydro-3- (2-thienyl) -L-phenylalanine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-leucine,

N-benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosinamide,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N'-hexylamide,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N'-cyclohexylamide,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N ', N'-dimethylamide,

N-benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine morpholide,

N-acetyldehydrophenylalanyldehydrotyrosine,

N-acetyldehydrophenylalanyldehydro- (p-nitrophenyl) alanine,

N-acetyldehydrophenylalanyldehydro- (p-fluorophenyl) alanine,

N-acetyldehydrophenylalanyldehydro- (4-dimethylaminophenyl) alanine,

N-acetyldehydrophenylalanyldehydro- (3-chlorophenyl) alanine,

N-acetyldehydrophenylalanyldehydro- (3-chlorophenyl) alanyl-L-tyrosine,

N-acetyldehydrophenylalanyl-3-phenylserine,

N-Benzoyldehydrophenylalanylglycine,

N-benzoyldehydrophenylalanyl-3-phenylserine,

N-acetyldehydroleucylglycine,

N-carbobenzoxyglycyldehydrophenylalanine,

N-acetyldehydrophenylalanyl-L-alanine,

N-acetyldehydrophenylalanyl-L-phenylalanine,

N-acetyl-DL-phenylalanyldehydrophenylalanine,

N-acetyldehydrophenylalanyldehydrophenylalanine,

N-benzoyldehydrophenylalanyldehydrophenylalanine,

N-benzoyldehydrophenylalanyldehydrotyrosine,

N-acetyldehydroleucyldehydrophenylalanine,

N-carbobenzoxyglycyldehydrophenylalanyl-L-glutamic acid,

N-carbobenzoxyglycyldehydrophenylalanylphenylserine,

N-acetyldehydrophenylalanyl-D-glutamic acid,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine benzyl ester,

N-benzoyldehydro-3- (2-thienyl) -L-tyrosine-N-benzylamide,

N-acetyldehydro-3- (2-thienyl) alanine-N'-methylamide,

N-acetyldehydro-3- (2-thienyl) alanine morpholide,

N-acetyldehydro-3- (2-thienyl) alanine,

N-cinnamoyldehydrophenylalanyl-L-tyrosine,

N-benzoyldehydroisoleucyl-L-tyrosine,

N-cinnamoyldehydrophenylalanine-N'-methylamide,

N-cinnamoyldehydrophenylalanine-1,1-dimethyl-2-propynylamide,

N-cinnamoyldehydrophenylalanine morpholide,

N-Benzoyl-3-methyl-3-cinnamenyldehydroalanyl-L-tyrosine,

N-Benzoyl-3-methylphenyldehydroalanyl-L-leucine,

N-acetyldehydro-3- (2-thienyl) alanine-N'-methylamide,

N-acetyldehydro-3- (2-thienyl) alanine-N'-1.1-dimethyl-2-propynylamide,

N-ethoxyacetyldehydro-3- (2-thienyl) alanine methyl ester,

N-acetyldehydrophenylalanyl-3- (5-methylthienyl-2) dehydroalanine,

N-benzoyldehydrophenylalanine methyl ester,

N-Benzoyldehydrophenylalaninthioäthylester,

N-acetyldehydrophenylalaninthioethyl ester,

N-acetyldehydrophenylalanine thiomethyl ester,

N-acetyldehydro-3- (2-thienyl) alaninthiomethyl ester,

N-acetyldehydro-3- (2-thienyl) alanine-2-carboxythioethyl ester,

N-acetyldehydro-3- (2-thienyl) alaninthioethyl ester,

N-acetyldehydro-3- (2-thienyl) alanine-4-chlorothiophenyl ester,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alaninthioethyl ester,

N-acetyldehydrophenylalanine-3- (3-chlorophenyl) dehydroalaninthiomethyl ester,

N-cinnamoyldehydrophenylalanine thiomethyl ester,

N- (3-trifluoromethylbenzoyl) -3- (2-thienyl) alanine methyl ester,

N-crotonoyldehydro-3- (2-thienyl) alanine,

N-acetyldehydro-3- (2-thienyl) alanine dehydro-3- (2-thienyl) alanine,

N-benzoyldehydro-3- (2-thienyl) alanine,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine,

N-acetyldehydro-3- (2-thienyl) alanyldehydro-3- (4-nitrophenyl) alanine,

N-benzoyldehydrophenylalanine,

N-acetyldehydro-3- (2-thienyl) alanyl-N-methylglycine,

N- (3.4.5-trimethoxycinnamoyl) dehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-crotonoyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-acetyldehydro-3- (5-nitro-2-thienyl) alanyl-L-tyrosine,

N- (2-thenoyl) dehydro-3- (2-thienyl) alanyl-L-tyrosine,

N-crotonoyldehydro-3- (2-thienyl) alanyl-L-leucine,

N-acetyldehydro-3- (2-thienyl) alanyl-O-methyl-L-tyrosine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tryptophan,

N-acetyldehydro-3- (2-thienyl) alanyl-L-glycine,

N-acetyldehydro-3- (2-thienyl) alanyl-2- (4-hydroxyphenyl) -D-glycine,

N-Benzoyldehydrophenylalanyl-L-leucylglycine-4-methoxyphenylamide,

N-acetyldehydro-3- (2-thienyl) alanyl-2- (1,4-cyclohexandien-1-yl) -D-glycine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-glutamic acid,

N-acetyldehydro-3- (2-thienyl) alanyl-L-leucine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-phenylalanine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-beta-alanine,

N-Benzoyldehydrophenylalanylglycine,

N-acetyldehydro-3- (2-thienyl) alanyl-DL-valine,

N- (2-thenoyl) dehydro-3- (2-thienyl) alanyl-2- (1,4-cyclohexandien-1-yl) -D-glycine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-threonine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-aspartic acid,

N-Benzoyldehydrophenylalanine-L-tryptophan,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanyl-L-leucine,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanyl-L-phenylalanine,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanylglycine,

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine tert-butyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine benzyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine methyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-N-methyl-L-tyrosine methyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-N-methyl-L-tyrosine,

N-acetyldehydro-3- (3-nitro-4-hydroxyphenyl) alanyl-L-tyrosine tert-butyl ester,

N-acetyldehydro-3- (3-nitro-4-hydroxyphenyl) alanyl-L-tyrosine,

N-Benzoyldehydro-3- (4-pyridyl) alanyl-L-tyrosine methyl ester,

N-Benzoyldehydro-3- (4-pyridyl) alanyl-L-tyrosine,

N- (4-nitrophenyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N- (4-nitrophenyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine tert-butyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine,

N-benzoyldehydroisoleucyl-L-tyrosine methyl ester,

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine,

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine tert-butyl ester,

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine benzyl ester,

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester,

N-benzoyldehydrophenylalanyl-L-leucylglycine amide,

N-Benzoyldehydrophenylalanyl-L-propyl-L-leucylglycine amide,

N-acetyldehydro-3- (2-thienyl) alanyl-2-methylalanine methyl ester,

N-acetyldehydro-3- (2-thienyl) alanyl-2-methylalanine,

N-acetyldehydro-3- (2-thienyl) alanine salt

with methylamine,

with 1,1-dimethylpropargylamine,

with lithium,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt

with morpholine,

with piperidine,

with ethylenediamine,

with triethanolamine,

with DL-canavanine,

with L-arginine,

with L-lysine,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine-2-dimethylaminopropylamide,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosinamide,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methylamide,

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine hydrazide,

N-benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-6-aminohexanamide,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-4-aminobutanamide,

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine hydrazide,

N-ethoxyacetyldehydro-3- (2-thienyl) alanine-4-methylpiperazid,

N-ethoxyacetyldehydro-3- (2-thienyl) alanine anilide,

N-ethoxyacetyldehydro-3- (2-thienyl) alaninecyclohexylamide,

N-ethoxyacetyldehydro-3- (2-thienyl) alaninamide,

N-crotonoyldehydro-3- (2-thienyl) alanine-4-methylpiperazid,

N-crotonoyldehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide,

N-crotonoyldehydro-3- (2-thienyl) alanine-6-aminohexanamide,

N-crotonoyldehydro-3- (2-thienyl) alanine-4-hydroxyanilide,

N-acetyldehydrophenylalanyl-3- (2-thienyl) dehydroalanine methylamide,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine anilide,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine-4-methylpiperazide,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide,

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alaninamide,

N-acetyldehydro-3- (2-thienyl) alanyl-3-methyl-3- (thienyl) dehydroalaninehexylamide,

N-nicotinoyl-3- (2-thienyl) dehydroalanine propargylamide,

N- (2-thienylacetyl) dehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide,

N-benzoyldehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide,

N-benzoyldehydro-3- (2-thienyl) alanine anilide,

N-benzoyldehydro-3- (2-thienyl) alanine methylamide,

N-benzoyldehydro-3- (2-thienyl) alaninehexylamide,

N-benzoyldehydro-3- (2-thienyl) alanine propargylamide,

N-benzoyldehydro-3- (2-thienyl) alanine hydrazide,

N-acetyldehydro-3- (2-thienyl) alanine propargylamide,

N-acetyldehydro-3- (2-thienyl) alanine-3.4.5-trimethoxyanilide,

N-acetyldehydro-3- (2-thienyl) alanine-2- (benzothiazol-2-yl) hydrazide.

The compounds can exist both in the racemate form and in the form of the isolated optical isomers with a defined absolute configuration. In addition, in the synthesis of, for example, N-benzoyldehydrophenylalanyl-L-leucine methyl ester, cis-trans isomers can occur. In some cases, for example with N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine, only one of the isomers is formed preferentially, as could be proven by [high] 13 C-NMR spectroscopy.

The active ingredients according to the invention have a dose-dependent tumor- and tissue-dissolving effect, preferably when applied locally. The following types of application are understood here by local:

subcutaneously, intracutaneously, intratumorally, peritumorally, in the form of external agents in ointments, gels, lotions, creams, injection solutions and suspensions.

The necroses usually arise in the immediate area of the application sites, occasionally also far away from it (lymphogenic). The necrotic area, if it breaks open to the outside, is free of putrid material even over a long period of time, although food, excrement, sawdust and other things came into contact with the open wound in the test animals.

However, the tumor tissue can also melt down if the outer skin is completely intact.

The activity of the third component of the immune hemolytic complement system is significantly increased.

The necrotic tissue is sharply demarcated from the surrounding healthy tissue; Macroscopically and microscopically, it looks like it has been punched out.

The general behavior of the test animals is not influenced by the size of the necrosis. There is no poisoning of the entire organism.

The DL [deep] 50 of the compounds according to the invention in the acute test for intravenous injection in rats is of the order of 300 mg / kg.

The daily injection of 80 mg / kg in rabbits for 27 days was tolerated without any reaction.

When used therapeutically, the doses are in the range of 1 to 100 mg / kg of body weight, preferably 2 to 40 mg / kg.

The active compounds according to the invention can be converted in a known manner into the formulations required for their mode of action, such as ointments, pastes, creams, soluble powders, powders, emulsions, suspensions and injection solutions.

As an example of an injection solution, the active ingredients according to the invention are optionally dissolved in dilute physiologically compatible bases with the aid of solubilizers and brought into an injectable form of pH 6.8 to 8.0, in particular 7 to 7.4, by adding physiologically compatible acids.

Inorganic hydroxides, carbonates, hydrogen carbonates, in particular those of sodium and potassium, may be mentioned as examples as physiologically compatible bases.

As physiologically compatible acids, organic acids such as citric acid, oxalic acid, lactic acid, benzoic acid, salicylic acid, acetic acid or inorganic acids such as dilute hydrochloric or sulfuric acid may be mentioned by way of example.

Suitable auxiliaries can be admixed with the active ingredients according to the invention in the formulations. These are inert, non-toxic and pharmaceutically suitable solid, semi-solid and liquid carriers, emulsifiers and dispersants. Here, the therapeutically active compound should in each case be present in a concentration of 1 to 90 percent by weight, preferably 5 to 50 percent by weight.

The present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutically suitable carriers, contain one or more active ingredients according to the invention or which consist of one or more active ingredients according to the invention, as well as processes for the production of these preparations.

The present invention also includes pharmaceutical preparations in dosage units. This means that the preparations are in the form of individual parts, e.g. suppositories and ampoules, the active ingredient content of which corresponds to a fraction or a multiple of a single dose. The dosage units can contain, for example, 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose. A single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.

Non-toxic, inert pharmaceutically suitable carriers are to be understood as meaning solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all types.

Preferred pharmaceutical preparations are suppositories, injection solutions, suspensions and emulsions,

Called pastes, ointments, gels, creams, lotions, powders and sprays.

In addition to the active ingredient (s), suppositories can contain the usual water-soluble or water-insoluble carrier substances, e.g. polyethylene glycols, fats, e.g. cocoa fat and higher esters (e.g. C [deep] 14 alcohol with C [deep] 16 fatty acid) or mixtures of these substances.

In addition to the active ingredient (s), ointments, pastes, creams and gels can contain the usual carrier substances, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of these substances.

In addition to the active ingredient (s), powders and sprays can contain the usual carrier substances, e.g. lactose, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also contain the usual propellants, e.g. chlorofluorocarbons.

In addition to the active ingredient (s), solutions and emulsions can contain the usual carriers such as solvents, solubilizers and emulsifiers, for example 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 , Olive oil, castor oil and sesame oil, glycerin, glycerin formal, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.

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

In addition to the active ingredient (s), suspensions can contain the usual carriers such as liquid diluents, for example water, ethyl alcohol, propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth .

In addition to the active ingredients according to the invention, the pharmaceutical preparations listed above can also contain further pharmaceutical active ingredients.

The pharmaceutical preparations listed above are produced in the customary manner by known methods, for example by mixing the active ingredient (s) with the carrier (s).

The present invention also includes the use of the active ingredients according to the invention and of pharmaceutical preparations which contain one or more active ingredients according to the invention for the treatment of those tissues in the human and veterinary medical field that prevent and disrupt the normal biological functions.

Such fabrics are for example:

benign and malignant tumors of solid and cystic nature, papillomas, adenomas, cyst adenomas;

Adenocarcinomas including those of the cirrhoid type;

Basal cell carcinoma;

Sarcomas such as, for example, fibrosarcoma, liposarcoma, myxosarcoma, rhabdomyosarcoma, chondrosarcoma, lymphosarcoma, reticular cell sarcoma, and Hodgkin's disease;

embryonic tumors such as neuroblastoma, nephroblastoma, teratoma, adamantinoma and retroblastoma, haemangioma, chordoma, odontoma and craniopharyngioma;

Hamartomas such as lymphoandioma, exostoses, neurofibromatosis; Melanoma; Lymphomas; Hepatoblastomas; Breast cancer; Cervical cancer; Choriocarcinoma, adrenoacanthoma; Leiomyoma, androblastoma; Arrhenoblastoma; Sertoli cell tumor; Granulosa and theca cell tumor; Germinoma and seminoma, ovarian and vulvar cancer; Bladder, prostate and adenocarcinoma;

tumors caused by schistosomiasis;

Astrocytoma, ependymoglioma;

Glioblastoma, medulloblastoma;

Oligodentroglioma, spongioblastoma;

Meningioma and tumors of Schwann's vaginal cells;

Pinealoma; Hemangioblastoma, osteoclastoma, Ewings tumor; Multiple myeloma; Mucosis fungoides; Burkitt tumor;

Leukemia such as acute and chronic lymphatic leukemia, acute and chronic granulocyte leukemia, acute and chronic monocyte leukemia and stem cell leukemia;

Basalioma, fibroma, myoma

and, above all, the metastases of all types of tumors accessible during the surgical intervention of a local injection.

Therapeutically valuable effects of the compounds according to the invention are also found in osteosarcoma; Here, however, they have to be injected with a special device under pressure of up to 600 atmospheres.

In addition, the compounds according to the invention can be used in fibrosing tissues of any type, in particular in the treatment of keloids, crura ulcers, burn ulcers, decubital ulcers, as well as clavi and onychomycoses, scar tissue and for the therapy and prophylaxis of emboli and thrombosis.

The compounds according to the invention can also be used to dissolve birthmarks, atheromas and lipomas and to remove deep, possibly fistulous abscesses.

In addition, compounds according to the invention can be used for the regeneration of cavernomas and tuberculomas.

The compounds according to the invention can also be used for scar-free regeneration of substance defects in leprosy and other skin, mucous membrane or epithelial defects of various origins, especially those caused by infections with bacteria, fungi and pathogens of tropical diseases such as, for example, those of leishmaniasis, Fromboesia , Pinta and others are conditional.

In the examples given below, the optical rotation was measured with c = 2 in dimethylformamide.

The melting points were determined in a Tottoli device and are uncorrected.

example 1

N-Benzoyldehydro-beta (2-thienyl) alanine methyl ester

2 g of 2-phenyl-4- (2-thenylidene) -5 (4H) -oxazolone are dissolved in 50 ml of absolute methanol and stored for 16 hours at room temperature. The reaction solution is then evaporated, the residue is taken up in glacial acetic acid / ethylene chloride, filtered and crystallized by concentration. 2 g (88.8% of theory) of N-benzoyldehydro-beta (2-thienyl) alanine methyl ester are obtained with a melting point of 162 ° C.

C [low] 15H [low] 13NO [low] 3S

calculated: C 62.70%, H 4.56%, N 4.87%, S 11.16%;

found: C 62.81%, H 4.67%, N 4.85%, S 11.18%.

Example 2

N-acetyldehydro-beta (2-thienyl) alanine ethyl ester

analogously to Example 1 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and absolute ethanol; Mp. 109-110 ° C.

Yield 82%.

C [deep] 11H [deep] 13NO [deep] 3S times H [deep] 2O

calculated: C 51.42%, H 5.8%, N 5.4%, S 12.5%;

found: C 51.80%, H 6.0%, N 5.4%, S 12.7%.

Example 3

N-acetyldehydrophenylalanine

by saponification of 2-methyl-4-benzylidene-5 (4H) oxazolone (literature preparation: Beilstein X, p.683);

Mp. 188-190 ° C.

Example 4

N-crotonoyldehydro-3- (2-thienyl) alanine methyl ester

analogous to Example 1 from 2- (1-propenyl) -4- (2-thenylidene) -5 (4H) oxazolone and methanol.

M.p .: 174-176 ° C; Yield: 54% of theory!

C [low] 12H [low] 13NO [low] 3S

calculated: C 57.35%, H 5.21%, N 5.57%, S 12.76%;

found: C 57.45%, H 5.31%, N 5.68%, S 12.55%.

Example 5

N-crotonoyldehydro-3- (2-thienyl) alaninthioethyl ester

analogously to Example 1 from 2- (1-propenyl) -4- (2-thenylidene) -5 (4H) oxazolone and ethyl mercaptan.

M.p .: 176 ° C; Yield: 80% of theory.

C [low] 13H [low] 15NO [low] 2S [low] 2

Calculated: C 55.49%, H 5.33%, N 4.98%, S 22.79%;

found: C 55.61%, H 5.44%, N 4.93%, S 22.96%.

Example 6

N-crotonoyldehydro-3- (2-thienyl) alaninthiomethyl ester

analogously to Example 1 from 2- (1-propenyl) -4- (2-thenylidene) -5 (4H) oxazolone and methyl mercaptan.

M.p .: 178-180 ° C; Yield: 63% of theory.

C [deep] 12H [deep] 13NO [deep] 2S [deep] 2

calculated: C 53.91%, H 4.90%, N 5.24%, S 23.99%;

found: C 53.52%, H 4.91%, N 5.25%, S 24.21%.

Example 7

N-ethoxyacetyldehydro-3- (2-thienyl) alanine methyl ester

analogous to Example 1 from 2-ethoxymethyl-4- (2-thenylidene) -5 (4H) oxazolone and methanol.

M.p .: 102 ° C; Yield: 38% of theory.

C [low] 12H [low] 15NO [low] 4S

calculated: C 53.52%, H 5.61%, N 5.20%, S 11.91%;

found: C 53.68%, H 5.52%, N 5.21%, S 11.78%.

Example 8

N-Benzoyldehydrophenylalanine methyl ester

analogous to Example 1 from 2-phenyl-4-benzylidene-5 (4H) oxazolone and methanol.

M.p .: 141-142 ° C; Yield: 65% of theory.

C [low] 17H [low] 15NO [low] 3

Calculated: C 72.6%, H 5.3%, N 5.0%;

found: C 72.7%, H 5.3%, N 4.9%.

Example 9

N-acetyldehydrophenylalaninthioethyl ester

analogous to Example 1 from 2-methyl-4-benzylidene-5 (4H) oxazolone and ethyl mercaptan (in an autoclave for one week at 50 ° C).

M.p .: 106-107 ° C; Yield: 7% of theory.

C [low] 13H [low] 15NO [low] 2S

calculated: C 62.62%, H 6.06%, N 5.62%, S 12.86%;

found: C 62.89%, H 6.03%, N 5.65%, S 12.96%.

Example 10

N-acetyldehydrophenylalanine thiomethyl ester

analogously to Example 1 from 2-methyl-4-benzylidene-5 (4H) oxazolone and methyl mercaptan, for one week at 50 ° C. in an autoclave.

M.p .: 157-158 ° C; Yield: 51% of theory.

C [low] 12H [low] 13NO [low] 2S

calculated: C 61.25%, H 5.57%, N 5.95%, S 13.63%;

found: C 61.31%, H 5.62%, N 5.91%, S 13.51%.

Example 11

N-acetyldehydro-3- (2-thienyl) alanine thiomethyl ester

analogously to Example 1 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and methyl mercaptan at 70 ° C. in an autoclave.

M.p .: 144-145 ° C; Yield: 45% of theory.

C [deep] 10H [deep] 11NO [deep] 2S [deep] 2

calculated: C 49.77%, H 4.59%, N 5.80%, S 26.57%;

found: C 49.61%, H 4.68%, N 5.75%, S 26.41%.

Example 12

N-acetyldehydro-3- (2-thienyl) alanine-3-carboxythioethyl ester

analogously to Example 1 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and 3-mercaptopropionic acid in an autoclave.

M.p .: 172-174 ° C; Yield: 66.9% of theory.

C [deep] 12H [deep] 13NO [deep] 4S [deep] 2

calculated: C 48.14%, H 4.38%, N 4.68%, S 21.42%;

found: C 48.28%, H 4.40%, N 4.71%, S 21.44%.

Example 13

N-acetyldehydro-3- (2-thienyl) alaninthioethyl ester

analogous to Example 1 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and ethyl mercaptan.

M.p .: 110-112 ° C; Yield: 98% of theory.

C [low] 11H [low] 13NO [low] 2S [low] 2

calculated: C 51.74%, H 5.13%, N 5.49%, S 25.11%;

found: C 51.84%, H 5.12%, N 5.57%, S 24.97%.

Example 14

N-acetyldehydro-3- (2-thienyl) alanine-4-chlorothiophenyl ester

analogously to Example 1 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and 4-chlorophenyl mercaptan, in the presence of triethylamine.

M.p .: 177-179 ° C; Yield: 48.8% of theory.

C [deep] 15H [deep] 12ClNO [deep] 2S [deep] 2

Calculated: C 53.33%, H 3.58%, Cl 10.49%, N 4.15%, S 18.98%;

found: C 53.45%, H 3.57%, Cl 10.63%, N 4.13%, S 19.10%.

Example 15

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanintioethyl ester

analogously to Example 1 from 2- (3-trifluoromethylphenyl) -4- (2-thenylidene) -5 (4H) oxazolone and ethyl mercaptan, in the presence of NaH.

M.p .: 139-140 ° C; Yield: 50% of theory.

C [deep] 17H [deep] 14F [deep] 3NO [deep] 2S [deep] 2

calc .: C 52.98%, H 3.66%, F 14.79%, N 3.63%, S 16.64%;

Found: C 53.18%, H 3.60%, F 14.9%, N 3.50%, S 16.63%.

Example 16

N-Benzoyldehydrophenylalaninthioethyl ester

analogous to Example 1 from 2-phenyl-4-benzylidene-5 (4H) oxazolone and ethyl mercaptan.

M.p .: 150 ° C (dec.); Yield: 47% of theory.

C [low] 18H [low] 17NO [low] 2S

calculated: C 69.43%, H 5.50%, N 4.50%, S 10.30%;

found: C 69.27%, H 5.55%, N 4.54%, S 10.32%.

Example 17

N-acetyldehydrophenylalanine 3- (3-chlorophenyl) dehydroalaninthiomethyl ester

analogously to Example 1 from 4- (3-chlorobenzylidene) -2- (1-acetamido-2-phenylvinyl) -5 (4H) oxazolone and methyl mercaptan in the pressure bottle for one week.

M.p .: 166-167 ° C; Yield: 38.8% of theory.

C [deep] 21H [deep] 19ClN [deep] 2O [deep] 3S

calc .: C 60.79%, H 4.61%, Cl 8.54%, N 6.75%, S 7.73%;

Found: C 60.74%, H 4.48%, Cl 8.58%, N 6.82%, S 7.80%.

Example 18

N-cinnamoyldehydrophenylalanine thiomethyl ester

analogously to Example 1 from 2- (2-phenylvinyl) -4-benzylidene-5 (4H) oxazolone and methyl mercaptan in an autoclave for one week.

M.p .: 182-183 ° C; Yield: 28.5% of theory.

C [low] 19H [low] 17NO [low] 2S

calculated: C 70.56%, H 5.30%, N 4.33%, S 9.91%;

found: C 70.40%, H 5.39%, N 4.41%, S 9.61%.

Example 19

N- (3-trifluoromethylbenzoyl) -3- (2-thienyl) alanine methyl ester

analogously to Example 1 from 2- (3-trifluoromethylphenyl) -4- (2-thenylidene) -5 (4H) oxazolone and methanol in the presence of sodium hydride.

M.p .: 117-118 ° C; Yield: 64.8% of theory Th.

C [deep] 16H [deep] 12F [deep] 3NO [deep] 3S

calculated: C 54.08%, H 3.40%, F 16.04%, S 9.03%;

found: C 54.01%, H 3.47%, F 15.90%, S 9.05%.

Example 20

N-phenylacetyldehydro-beta (thienyl) alanine

by saponification of 2-benzyl-4- (2-thenylidene) -5 (4H) oxazolone; Mp 193-195 ° C; Yield 8.2% of theory.

C [low] 15H [low] 13NO [low] 3S

calculated: C 62.70%, H 4.56%, N 4.88%, S 11.16%;

found: C 62.68%, H 4.55%, N 4.96%, S 11.26%.

Example 21

DL-N-acetylphenylalanyldehydro- (3-chlorophenyl) alanine

1.8 g (0.005 mol) of 2- (1-acetamido-2-phenylethyl) -4- (3-chlorobenzylidene) -5 (4H) oxazolone are suspended in 7 ml of acetone and 7.5 ml of 2N NaOH are added.

After stirring for half an hour, the reaction solution is acidified to pH 3 with citric acid, the precipitate which separates out is filtered off and washed neutral.

Mp. 195-196 ° C, yield 1.6 g (84.2% of theory).

C [deep] 20H [deep] 19ClN [deep] 2O [deep] 4

Calculated: C 62.10%, H 4.95%, Cl 9.17%, N 7.24%;

found: C 62.31%, H 4.77%, Cl 9.03%, N 7.31%.

Example 22

L-N-tert-butoxycarbonylphenylalanyldehydro- (3-chlorophenyl) alanine

analogously to Example 21 from 2- (1-tert-butoxycarbonylamido-2-phenylethyl) -4- (3-chlorophenyl) -5 (4H) oxazolone and Re- crystallization from aqueous acetone. Mp. 173 ° C (decomp.), [Alpha] [high] 20 [low] D + 78.6 ° (c = 1; dimethylformamide), yield 83.3% of theory.

C [deep] 23H [deep] 25ClN [deep] 2O [deep] 5

Calculated: C 62.09%, H 5.66%, Cl 7.97%, N 6.30%;

found: C 62.26%, H 5.66%, Cl 7.95%, N 6.44%.

Example 23

L-phenylalanyldehydro- (3-chlorophenyl) alanine

from 2.5 g of the above compound by dissolving in 15 ml of anhydrous trifluoroacetic acid, standing for one hour at room temperature, evaporating, taking up the residue in water, adjusting with NH [deep] 3 to pH 8 and evaporating the solution until crystallization begins.

Mp 235-236 ° C; [Alpha] [high] 20 [low] D - 31.5 ° (c = 1; dimethylformamide), yield 1.7 g (89.5% of theory).

C [deep] 18H [deep] 17ClN [deep] 2O [deep] 3

calculated: C 62.70%, H 4.97%, Cl 10.28%, N 8.13%;

found: C 62.55%, H 5.35%, Cl 10.15%, N 8.19%.

Example 24

N-acetyldehydro-3- (2-thienyl) alanine

analogously to Example 21 from 4-thenylidene-2-methyl-5 (4H) oxazolone.

Mp 222-223 ° C; Yield 5.7% of theory.

C [low] 9H [low] 9NO [low] 3S

calculated: C 51.17%, H 4.30%, N 6.63%, S 15.18%;

found: C 51.21%, H 4.37%, N 6.65%, S 15.32%.

Example 25

N-acetyldehydrophenylalanyl-3- (5-methylthienyl-2) dehydroalanine

analogously to Example 21 from 4- (5-methylthenylidene) -2- (1-acetamido-2-phenylvinyl) -5 (4H) oxazolone.

Mp 193-194 ° C; Yield 40% of theory.

C [deep] 19H [deep] 18N [deep] 2O [deep] 4S

calculated: C 61.61%, H 4.90%, N 7.56%, S 8.66%;

found: C 61.54%, H 4.96%, N 7.55%, S 8.70%.

Example 26

N-crotonoyldehydro-3- (3-thienyl) alanine

analogously to Example 21 from 2- (1-propenyl) -4- (2-thenylidene) -5 (4H) oxazolone.

Mp 226 ° C; Yield 88% of theory.

C [low] 11H [low] 11NO [low] 3S

calculated: C 55.68%, H 4.67%, N 5.90%, S 13.51%;

found: C 55.23%, H 4.71%, N 6.03%, S 13.96%.

Example 27

N-acetyldehydro-3- (2-thienyl) alanyldehydro-3- (2-thienyl) alanine

analogously to Example 21 from 2- [1-acetamido-2- (2-thienyl) vinyl] -4- (2-thenylidene) -5 (4H) oxazolone.

Mp 218 ° C; Yield 80% of theory.

C [deep] 16H [deep] 14N [deep] 2O [deep] 4S [deep] 2

calculated: C 53.02%, H 3.89%, N 7.73%, S 17.69%;

found: C 52.99%, H 3.94%, N 7.96%, S 17.70%.

Example 28

N-benzoyldehydro-3- (2-thienyl) alanine

analogously to Example 21 from 2-phenyl-5- (2-thenylidene) -5 (4H) oxazolone.

Mp 235 ° C; Yield 94% of theory.

C [low] 14H [low] 11NO [low] 3S

calculated: C 61.52%, H 4.06%, N 5.12%, S 11.74%;

found: C 61.50%, H 4.08%, N 5.14%, S 11.70%.

Example 29

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine

analogously to Example 21 from 4-thenylidene-2- (3-trifluoromethylphenyl) -5 (4H) oxazolone.

Mp 200-202 ° C; Yield 93% of theory.

C [deep] 15H [deep] 10F [deep] 3NO [deep] 3S

calc .: C 52.76%, H 2.96%, F 16.70%, N 4.10%, S 9.39%;

Found: C 52.89%, H 2.92%, F 16.60%, N 4.18%, S 9.36%.

Example 30

N-acetyldehydro-3- (2-thienyl) alanyldehydro-3- (4-nitrophenyl) alanine

analogously to Example 21 from 4- (4-nitrobenzylidene) -2- [1-acetamido-2- (2-thienyl) vinyl] -5 (4H) oxazolone.

Mp 196-197 ° C; Yield 55.7% of theory.

C [deep] 18H [deep] 15N [deep] 3O [deep] 6S

Calculated: C 53.86%, H 3.77%, N 10.47%, S 7.99%;

found: C 53.80%, H 3.81%, N 10.52%, S 7.85%.

Example 31

N-benzoyldehydrophenylalanine

analogously to Example 21 from 4-benzylidene-2-phenyl-5 (4H) oxazolone.

Mp 251 ° C; Yield 88% of theory.

C [low] 16H [low] 13NO [low] 3

calculated: C 71.90%, H 4.90%, N 5.24%;

found: C 71.98%, H 4.80%, N 5.25%.

The following examples are based on the following general rule:

0.025 mol of the amino acid to be condensed is suspended in 10 ml of acetone, 25 ml of 1n NaOH are added with stirring and the resulting solution is mixed with a suspension of the correspondingly substituted 5 (4H) -oxazolone in acetone. Depending on the reactivity of the amino acid, the mixture is stirred at room temperature for 1/2 to 20 hours. The filtered reaction solution is then mixed with 25 ml in HCl and the acetone is distilled off in vacuo.

The desired end product crystallizes out of the aqueous phase and is recrystallized from aqueous alcohol.

Example 32

N-acetyldehydrophenylalanyl-L-proline

from 2-methyl-4-phenyl-5 (4H) -oxazolone and L-proline.

Mp 152-155 ° C; [Alpha] [high] 20 [low] D + 69.5 °; Yield 59% of theory.

C [deep] 16H [deep] 18N [deep] 2O [deep] 4 times 1/2 H [deep] 2O

calculated: C 61.72%, H 6.15%, N 9.00%;

found: C 62.15%, H 6.43%, N 8.96%.

Example 33

N-acetyldehydrophenylalanyl-D-proline

Mp 151-153 ° C; [Alpha] [high] 20 [low] D - 69.6 °; Yield 55% of theory.

C [deep] 16H [deep] 18N [deep] 2O [deep] 4

Calculated: C 61.72%, H 6.15%, N 9.0%;

found: C 61.75%, H 6.30%, N 8.94%.

Example 34

N-acetyldehydrophenylalanyl-D-tyrosine

Mp 210 ° C; [Alpha] [high] 20 [low] D - 43.4 ° (c = 2; pyridine);

Yield 61.3% of theory.

C [deep] 20H [deep] 20N [deep] 2O [deep] 5

calculated: C 65.21%, H 5.47%, N 7.60%;

found: C 64.56%, H 5.86%, N 7.77%.

Example 35

N-acetyldehydrophenylalanyl-L-leucine

Mp 206-207 ° C; [Alpha] [high] 20 [low] D - 22.5 °; Yield 65.7% of theory Th.

C [deep] 17H [deep] 22N [deep] 2O [deep] 4

calculated: C 64.13%, H 6.97%, N 8.80%;

found: C 64.26%, H 7.31%, N 8.78%.

Example 36

N-acetyldehydrophenylalanyl-L-methionine

Mp 91-93 ° C; [Alpha] [high] 20 [low] D - 74.4 °; Yield 70% of theory.

C [deep] 16H [deep] 20N [deep] 2O [deep] 4S

calculated: C 57.12%, H 5.99%, N 8.33%, S 9.53%;

found: C 57.02%, H 6.03%, N 8.40%, S 9.46%.

Example 37

N-acetyldehydrophenylalanyl-L-aspartic acid

M.p. 182-184 ° C; [Alpha] [high] 20 [low] D - 46.65 °; Yield 63.5% of theory Th.

C [deep] 15H [deep] 16N [deep] 2O [deep] 6 times H [deep] 2O

Calculated: C 53.25%, H 5.36%, N 8.28%;

found: C 53.48%, H 4.92%, N 8.32%.

Example 38

N-acetyldehydrophenylalanyl-L-glutamine

Mp 188 ° C; [Alpha] [high] 20 [low] D - 74.5 °; Yield 54% of theory.

C [deep] 16H [deep] 19N [deep] 3O [deep] 5

Calculated: C 57.65%, H 5.75%, N 12.61%;

found: C 58.17%, H 5.79%, N 13.16%.

Example 39

N-acetyldehydrophenylalanyl-DL-3-fluoroalanine

M.p. 180 ° C (dec.); Yield 58.7% of theory.

C [deep] 14H [deep] 15FN [deep] 2O [deep] 4

Calculated: C 57.14%, H 5.14%, F 6.46%, N 9.52%;

found: C 57.22%, H 5.22%, F 6.30%, N 9.58%.

Example 40

N-acetyldehydrophenylalanyl-L-serine

Mp 179 ° C (dec.); [Alpha] [high] 20 [low] D + 1.15 °; Yield 48.5% of theory Th.

C [deep] 14H [deep] 16N [deep] 2O [deep] 5

Calculated: C 57.53%, H 5.52%, N 9.58%;

found: C 57.48%, H 5.47%, N 9.66%.

Example 41

N-acetyldehydrophenylalanyl-L-tyrosine

Mp 219-220 ° C; Literature preparation.

Example 42

N-acetyldehydrophenylalanylglycine

Mp 191-192 ° C; Literature preparation.

Example 43

N-acetyldehydrophenylalanyl-L- (p-nitrophenyl) alanine

Mp. 192-193 ° C (from ethanol / petroleum ether / isopropyl ether);

[Alpha] [high] 20 [low] D - 110.7 °; Yield 70.3% of theory.

C [deep] 20H [deep] 19N [deep] 3O [deep] 6

Calculated: C 60.45%, H 4.82%, N 10.58%;

found: C 60.40%, H 4.90%, N 10.43%.

Example 44

N-acetyldehydroalanyl-DL- (p-chlorophenyl) alanine

Mp 214-215 ° C (from ether / petroleum ether); Yield 66.9% of theory.

C [deep] 20H [deep] 19ClN [deep] 2O [deep] 4

Calculated: C 62.10%, H 4.95%, Cl 9.17%, N 7.24%;

found: C 62.39%, H 5.02%, Cl 9.14%, N 7.11%.

Example 45

N-acetyldehydro (p-methylphenyl) alanyl-L-tyrosine

Mp 220-221 ° C; [Alpha] [high] 20 [low] D - 38.5 °; Yield 47.6% of theory Th.

C [deep] 21H [deep] 22N [deep] 2O [deep] 5

Calculated: C 65.95%, H 5.80%, N 7.33%;

found: C 65.96%, H 5.80%, N 7.16%.

Example 46

N-Benzoyl-2-cyclohexylidene glycyl-L-tyrosine

Mp 121 ° C; [Alpha] [high] 20 [low] D - 0.5 °; Yield 75.8% of theory Th.

C [deep] 24H [deep] 26N [deep] 2O [deep] 5

Calculated: C 68.23%, H 6.20%, N 6.63%;

found: C 68.16%, H 6.18%, N 6.65%.

Example 47

N-Benzoyl-2- (2-cyclohexenylidene) glycyl-L-tyrosine

Mp 126 ° C; [Alpha] [high] 20 [low] D - 5.7 °; Yield 60% of theory.

C [low] 24H [low] 24N [low] 2O [low] 5

calculated: C 68.56%, H 5.75%, N 6.66%;

found: C 68.46%, H 5.70%, N 6.56%.

Example 48

N-acetyldehydro-3- (2-furyl) alanyl-L-tyrosine

Mp 217 ° C (ethanol / petroleum ether);

[Alpha] [high] 20 [low] D - 29.1 °; Yield 31% of theory.

C [deep] 18H [deep] 18N [deep] 2O [deep] 6

Calculated: C 60.33%, H 5.06%, N 7.82%;

found: C 60.37%, H 5.11%, N 7.70%.

Example 49

N-acetyldehydro-3-cinnamenylalanyl-L-tyrosine

Mp 220-221 ° C; [Alpha] [high] 20 [low] D - 44.2 °; Yield 57.3% of theory.

C [deep] 22H [deep] 22N [deep] 2O [deep] 5

Calculated: C 66.99%, H 5.62%, N 7.10%;

found: C 66.80%, H 5.64%, N 7.06%.

Example 50

N-acetyldehydro-3- (2-naphthyl) alanyl-L-tyrosine

Mp. 221-222 ° C (precipitate from ethyl acetate / isopropanol with petroleum ether); [Alpha] [high] 20 [low] D - 11.6 ° (c = 2; from methanol); Yield 55.7% of theory.

C [deep] 24H [deep] 22N [deep] 2O [deep] 5

calculated: C 68.89%, H 5.30%, N 6.70%;

found: C 69.04%, H 5.37%, N 6.65%.

Example 51

N-Benzoyldehydro-3-cyclohexylalanyl-L-tyrosine

Mp 126-128 ° C; [Alpha] [high] 20 [low] D + 0.8 ° (c = 1; dimethylformamide);

Yield 60.3% of theory.

C [deep] 25H [deep] 28N [deep] 2O [deep] 5

calculated: C 68.79%, H 6.46%, N 6.42%;

found: C 68.59%, H 6.32%, N 6.24%.

Example 52

N-Benzoyldehydro-3-benzyl-3-methylalanyl-L-leucine

Mp 98-99 ° C; [Alpha] [high] 20 [low] D - 14.1 °; Yield 39% of theory.

C [deep] 24H [deep] 28N [deep] 2O [deep] 4

Calculated: C 70.57%, H 6.91%, N 6.86%;

found: C 70.47%, H 6.74%, N 6.92%.

Example 53

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-proline

Mp 125 ° C (unsharp); [Alpha] [high] 20 [low] D + 2.0 °; Yield 52% of theory Th.

C [deep] 19H [deep] 18N [deep] 2O [deep] 4S

calculated: C 61.60%, H 4.90%, N 7.56%, S 8.66%;

found: C 61.59%, H 4.80%, N 7.50%, S 8.79%.

Example 54

N-acetyldehydrophenylalanyl (1-carboxy-1-cyclopentyl) amide

M.p. 217 ° C (dec.); Yield 50.7% of theory.

C [deep] 17H [deep] 20N [deep] 2O [deep] 4

calculated: C 64.54%, H 6.37%, N 8.86%;

found: C 64.85%, H 6.55%, N 8.41%.

Example 55

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine

Mp 227-228 ° C; [Alpha] [high] 20 [low] D - 36.75 °; Yield 71.06% of theory Th.

C [deep] 18H [deep] 18N [deep] 2O [deep] 5S

calculated: C 57.74%, H 4.85%, N 7.48%, S 8.56%;

found: C 57.61%, H 4.84%, N 7.49%, S 8.62%.

Example 56

N-acetyldehydro-3- (2-thienyl) alanyl-N-methylglycine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and N-methylglycine.

Mp 207-208 ° C; Yield 82.4% of theory.

C [low] 12H [low] 14NO [low] 4S

calculated: C 51.05%, H 5.00%, N 9.92%, S 11.36%;

found: C 51.19%, H 5.09%, N 9.97%, S 11.19%.

Example 57

N- (3.4.5-trimethoxycinnamoyl) dehydro-3- (2-thienyl) alanyl-L-tyrosine

from 2- [2- (3.4.5-trimethoxyphenyl) vinyl] -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine.

Mp 148-150 ° C; Yield 92.2% of theory.

C [deep] 28H [deep] 28N [deep] 2O [deep] 8S

calculated: C 60.86%, H 5.11%, N 5.07%, S 5.80%;

found: C 60.74%, H 5.15%, N 5.07%, S 5.79%.

Example 58

N-crotonoyldehydro-3- (2-thienyl) alanyl-L-tyrosine

from 2- (1-propenyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine.

M.p. 157 ° C; Yield 51% of theory.

C [low] 20H [low] 20NO [low] 5S

calculated: C 59.99%, H 5.03%, N 7.00%, S 8.01%;

found: C 60.34%, H 4.97%, N 6.63%, S 7.51%.

Example 59

N-acetyldehydro-3- (5-nitrothienyl-2) alanyl-L-tyrosine

from 2-methyl-4- (5-nitrothenylidene-2) -5 (4H) oxazolone and L-tyrosine.

Mp 148-157 ° C; Yield 54.6% of theory.

C [deep] 18H [deep] 17N [deep] 3O [deep] 7S

calculated: C 51.55%, H 4.09%, N 10.02%, S 7.65%;

found: C 51.36%, H 4.11%, N 10.01%, S 7.64%.

Example 60

N- (2-thenoyl) dehydro-3- (2-thienyl) alanyl-L-tyrosine

from 2- (2-thienyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine.

Mp 140-150 ° C; Yield 72% of theory.

C [deep] 21H [deep] 18N [deep] 2O [deep] 5S [deep] 2

calculated: C 57.00%, H 4.10%, N 6.33%, S 14.49%;

found: C 57.01%, H 4.28%, N 6.35%, S 14.12%.

Example 61

N-crotonoyldehydro-3- (2-thienyl) alanyl-L-leucine

from 2- (1-propenyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-leucine.

Mp 176 ° C; Yield 73% of theory.

C [deep] 17H [deep] 22N [deep] 2O [deep] 4S

calculated: C 58.27%, H 6.33%, N 7.99%, S 9.15%;

found: C 58.18%, H 6.26%, N 7.97%, S 9.23%.

Example 62

N-acetyldehydro-3- (2-thienyl) alanyl-O-methyl-L-tyrosine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and O-methyl-L-tyrosine.

Mp 236 ° C; Yield 90% of theory.

C [deep] 19H [deep] 20N [deep] 2O [deep] 5S

calculated: C 53.75%, H 5.19%, N 7.21%, S 8.25%;

found: C 53.83%, H 5.36%, N 7.23%, S 8.30%.

Example 63

N-acetyldehydro-3- (2-thienyl) alanyl-L-tryptophan

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-tryptophan.

Mp 250 ° C; Yield 43% of theory.

C [deep] 20H [deep] 19N [deep] 3O [deep] 4S

calculated: C 60.44%, H 4.82%, N 10.57%, S 8.07%;

found: C 60.47%, H 4.88%, N 10.47%, S 8.23%.

Example 64

N-acetyldehydro-3- (2-thienyl) alanylglycine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and glycine.

Mp 221-223 ° C; Yield 76.1% of theory.

C [deep] 11H [deep] 12N [deep] 2O [deep] 4S

calculated: C 49.25%, H 4.51%, N 10.44%, S 11.95%;

found: C 49.14%, H 4.57%, N 10.45%, S 11.92%.

Example 65

N-acetyldehydro-3- (2-thienyl) alanyl-2- (4-hydroxyphenyl) -D-glycine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and 2- (4-hydroxyphenyl) -D-glycine.

Mp 224-226 ° C; Yield 66.7% of theory.

C [deep] 17H [deep] 16N [deep] 2O [deep] 5S

calculated: C 56.66%, H 4.48%, N 7.77%, S 8.90%;

found: C 56.62%, H 4.58%, N 7.63%, S 8.75%.

Example 66

N-Benzoyldehydrophenylalanyl-L-leucylglycine-4-methoxyphenylamide

from 2-phenyl-4-benzylidene-5 (4H) oxazolone and L-leucylglycine-4-methoxyphenylamide.

Mp 211-230 ° C; Yield 50% of theory.

C [deep] 31H [deep] 34N [deep] 3O [deep] 5

calculated: C 68.62%, H 6.32%, N 10.35%;

found: C 68.69%, H 6.33%, N 10.48%.

Example 67

N-acetyldehydro-3- (2-thienyl) alanyl-2- (1,4-cyclohexandien-1-yl) -D-glycine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and 2- (1,4-cyclohexandien-1-yl) -D-glycine.

Mp 235-240 ° C; Yield 75.1% of theory.

C [deep] 17H [deep] 18N [deep] 2O [deep] 4S

calculated: C 58.94%, H 5.24%, N 8.09%, S 9.25%;

found: C 58.79%, H 5.10%, N 7.93%, S 9.06%.

Example 68

N-acetyldehydro-3- (2-thienyl) alanyl-L-glutamic acid

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-glutamic acid.

Mp 205 ° C (dec.); Yield 76.5% of theory Th.

C [deep] 14H [deep] 16N [deep] 2O [deep] 6S

calculated: C 49.40%, H 4.74%, N 8.23%, S 9.42%;

found: C 49.61%, H 4.76%, N 8.16%, S 9.59%.

Example 69

N-acetyldehydro-3- (2-thienyl) alanyl-L-leucine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-leucine.

Mp 230 ° C; Yield 89.5% of theory.

C [deep] 15H [deep] 20N [deep] 2O [deep] 4S

calculated: C 55.58%, H 6.21%, N 8.64%, S 9.88%;

found: C 55.72%, H 6.27%, N 8.59%, S 9.87%.

Example 70

N-acetyldehydro-3- (2-thienyl) alanyl-L-phenylalanine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-phenylalanine.

Mp> 230 ° C; Yield 92.6% of theory.

C [deep] 18H [deep] 18N [deep] 2O [deep] 4S

calculated: C 60.34%, H 5.07%, N 7.82%, S 8.93%;

found: C 60.37%, H 5.04%, N 7.81%, S 8.96%.

Example 71

N-acetyldehydro-3- (2-thienyl) alanyl-L-beta-alanine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-beta-alanine.

Mp 186-189 ° C; Yield 78.5% of theory.

C [deep] 12H [deep] 14N [deep] 2O [deep] 4S

calculated: C 51.05%, H 5.00%, N 9.92%, S 11.36%;

found: C 50.93%, H 5.07%, N 9.98%, S 11.44%.

Example 72

N-Benzoyldehydrophenylalanylglycine

from 2-phenyl-4-benzylidene-5 (4H) oxazolone and glycine.

Mp 233 ° C (dec.); Yield 88.7% of theory.

C [deep] 18H [deep] 16N [deep] 2O [deep] 4

calculated: C 66.66%, H 4.97%, N 8.64%;

found: C 66.87%, H 5.12%, N 8.54%.

Example 73

N-acetyldehydro-3- (2-thienyl) alanyl-DL-valine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and DL-valine.

Mp 229-230 ° C (dec.); Yield 91.5% of theory.

C [deep] 14H [deep] 18N [deep] 2O [deep] 4S

Calculated: C 54.18%, H 5.84%, N 9.03%, S 10.33%;

found: C 54.01%, H 5.82%, N 9.02%, S 10.37%.

Example 74

N- (2-thenoyl) dehydro-3- (2-thienyl) alanyl-2- (1,4-cyclohexandien-1-yl) -D-glycine

from 2- (2-thienyl) -4- (2-thenylidene) -5 (4H) oxazolone and 2- (1,4-cyclohexandien-1-yl) -D-glycine.

M.p. 145-155 ° C; Yield 37.8% of theory.

C [deep] 20H [deep] 18N [deep] 2O [deep] 4S

Calculated: C 57.95%, H 4.38%, N 6.76%, S 15.47%;

found: C 57.82%, H 4.39%, N 6.57%, S 15.12%.

Example 75

N-acetyldehydro-3- (2-thienyl) alanyl-L-threonine

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-threonine.

Mp 262-265 ° C (dec.); Yield 65% of theory.

C [deep] 13H [deep] 16N [deep] 2O [deep] 5S

calculated: C 49.99%, H 5.16%, N 8.97%, S 10.27%;

found: C 49.61%, H 5.24%, N 8.89%, S 10.33%.

Example 76

N-acetyldehydro-3- (2-thienyl) alanyl-L-aspartic acid

from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and L-aspartic acid.

Mp 232 ° C (dec.); Yield 62.5% of theory Th.

C [deep] 13H [deep] 14N [deep] 2O [deep] 6S

calculated: C 47.85%, H 4.32%, N 8.58%, S 9.83%;

found: C 47.70%, H 4.43%, N 8.45%, S 9.95%.

Example 77

N-Benzoyldehydrophenylalanine-L-tryptophan

from 2-phenyl-4-benzylidene-5 (4H) oxazolone and L-tryptophan.

Yield: 38.9% of theory.

C [deep] 27H [deep] 23N [deep] 3O [deep] 4

Calculated: C 71.51%, H 5.11%, N 9.27%;

found: C 71.45%, H 5.25%, N 9.12%.

Example 78

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanyl-L-leucine

from 2- (3-trifluoromethylphenyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-leucine.

Mp 100-105 ° C; Yield 100% of theory.

C [deep] 21H [deep] 21F [deep] 3N [deep] 2O [deep] 4S

calculated: C 55.50%, H 4.66%, F 12.54%, N 6.16%;

found: C 55.57%, H 4.74%, F 12.5%, N 6.10%.

Example 79

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanyl-L-phenylalanine

from 2- (3-trifluoromethylphenyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-phenylalanine.

M.p .: 103-107 ° C; Yield 88% of theory.

C [deep] 24H [deep] 19F [deep] 3N [deep] 2O [deep] 4S

Calculated: C 59.01%, H 3.92%, F 11.67%, N 5.74%;

found: C 58.86%, H 4.01%, F 11.3%, N 5.72%.

Example 80

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanylglycine

from 2- (3-trifluoromethylphenyl) -4- (2-thenylidene) -5 (4H) oxazolone and glycine.

M.p .: 91-92 ° C; Yield 81% of theory.

C [deep] 17H [deep] 13F [deep] 3N [deep] 2O [deep] 4S

calc .: C 51.26%, H 3.29%, F 14.31%, N 7.03%, S 8.04%;

Found: C 51.06%, H 3.45%, F 14.30%, N 6.94%, S 8.04%.

Example 81

N-trifluoroacetyldehydrophenylalanyl-L-tyrosine tert-butyl ester

the reaction takes place in dimethylformamide without NaOH.

M.p. 182-183 ° C; [Alpha] [high] 20 [low] D - 29.7 ° (c = 1; dimethylformamide);

Yield 84% of theory.

C [deep] 24H [deep] 25F [deep] 3N [deep] 2O [deep] 5

Calculated: C 60.24%, H 5.27%, F 11.91%, N 5.86%;

found: C 60.30%, H 5.30%, F 11.91%, N 5.93%.

Example 82

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine tert-butyl ester

analogously to Example 81 from 2- [1-acetamido-2- (2-thienyl) vinyl] -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine tert-butyl ester.

M.p. 158 ° C; Yield 94% of theory.

C [deep] 29H [deep] 31N [deep] 3O [deep] 6S [deep] 2

calculated: C 59.88%, H 5.37%, N 7.22%, S 11.03%;

found: C 60.01%, H 5.41%, N 7.15%, S 11.08%.

Example 83

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine benzyl ester

analogously to Example 81 from 2- [1-acetamido-2- (2-thienyl) vinyl] -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine benzyl ester.

Mp 130 ° C; Yield 83% of theory.

C [deep] 32H [deep] 29N [deep] 3O [deep] 6S [deep] 2

calculated: C 62.42%, H 4.75%, N 6.82%, S 10.42%;

found: C 62.52%, H 4.68%, N 6.83%, S 10.40%.

Example 84

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine methyl ester

analogously to Example 81 from 2- [1-acetamido-2- (2-thienyl) vinyl] -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine methyl ester.

Mp 155 ° C; Yield 96% of theory.

C [deep] 26H [deep] 25N [deep] 3O [deep] 6S [deep] 2

Calculated: C 57.86%, H 4.67%, N 7.79%, S 11.89%;

found: C 58.08%, H 4.79%, N 7.75%, S 11.88%.

Example 85

N-acetyldehydro-3- (2-thienyl) alanyl-N-methyl-L-tyrosine methyl ester

analogously to Example 81 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and N-methyl-L-tyrosine methyl ester.

Mp 102 ° C; Yield 38.9% of theory.

C [deep] 20H [deep] 22N [deep] 2O [deep] 5S times H [deep] 2O

calculated: C 58.38%, H 5.63%, N 6.81%, S 7.79%;

found: C 58.28%, H 5.59%, N 6.89%, S 8.15%.

Example 86

N-acetyldehydro-3- (3-thienyl) alanyl-N-methyl-L-tyrosine

from the above compound by boiling with NaOH.

Mp 150-170 ° C; Yield 72.6% of theory.

C [deep] 19H [deep] 20N [deep] 2O [deep] 5S

calculated: C 58.75%, H 5.19%, N 7.21%, S 8.25%;

found: C 58.62%, H 5.36%, N 7.08%, S 8.35%.

Example 87

N-acetyldehydro-3- (3-nitro-4-hydrophenyl) alanyl-L-tyrosine tert-butyl ester

analogously to Example 81 from 2-methyl-4- (3-nitro-4-acetoxybenzylidene) -5 (4H) oxazolone and L-tyrosine tert-butyl ester.

Mp 148-151 ° C; Yield 45.5% of theory.

C [deep] 24H [deep] 27N [deep] 3O [deep] 8

calculated: C 59.37%, H 5.61%, N 8.66%;

found: C 59.43%, H 5.71%, N 8.54%.

Example 88

N-acetyldehydro-3- (3-nitro-4-hydroxyphenyl) alanyl-L-tyrosine

from the above compound by stirring with trifluoroacetic acid.

M.p. 145 ° C; Yield 93% of theory.

C [deep] 21H [deep] 22N [deep] 3O [deep] 8

Calculated: C 56.76%, H 4.99%, N 9.24%;

found: C 56.88%, H 5.09%, N 9.31%.

Example 89

N-Benzoyldehydro-3- (4-pyridyl) alanyl-L-tyrosine methyl ester

analogously to Example 81 from 2-phenyl-4- (4-pyridinylmethylene) -5 (4H) oxazolone and L-tyrosine methyl ester.

Mp 155-160 ° C; Yield 33.7% of theory.

C [deep] 25H [deep] 23N [deep] 3O [deep] 5 times H [deep] 2O

Calculated: C 66.07%, H 5.32%, N 9.25%;

found: C 66.17%, H 5.59%, N 9.25%.

Example 90

N-Benzoyldehydro-3- (4-pyridyl) alanyl-L-tyrosine

from the above compound by boiling with dilute sodium hydroxide solution.

Mp 162-166 ° C; Yield 54.3% of theory.

C [low] 24H [low] 21N [low] 3O [low] 5

Calculated: C 66.81%, H 4.91%, N 9.74%;

found: C 66.63%, H 5.13%, N 9.77%.

Example 91

N- (4-nitrophenyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester

Mp 218-222 ° C; Yield 55.7% of theory.

C [deep] 25H [deep] 23N [deep] 3O [deep] 7S

calculated: C 58.93%, H 4.55%, N 8.25%, S 6.29%;

found: C 58.82%, H 4.55%, N 8.13%, S 6.11%.

Example 92

N- (4-nitrophenyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine

from the above compound by boiling with dilute sodium hydroxide solution.

Mp 161-166 ° C; Yield 41.6% of theory.

C [low] 24H [low] 21N [low] 3O [low] 7S

calculated: C 58.17%, H 4.27%, N 8.48%, S 6.47%;

found: C 58.26%, H 4.44%, N 8.45%, S 6.63%.

Example 93

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine tert-butyl ester

analogously to Example 81 from 2- [1-acetamido-2- (2-thienyl) vinyl] -4- (2-thenylidine) -5 (4H) oxazolone and L-tyrosine tert-butyl ester.

M.p. 158 ° C (dec.); Yield 94% of theory.

C [deep] 29H [deep] 31N [deep] 3O [deep] 6S [deep] 2

calculated: C 59.88%, H 5.37%, N 7.22%, S 11.03%;

found: C 60.01%, H 5.41%, N 7.15%, S 11.08%.

Example 94

N-acetyldehydro-3- (2-thienyl) alanyl-3- (2-thienyl) dehydroalanyl-L-tyrosine

from the above compound by adding glacial acetic acid / HCl.

M.p. 189 ° C (dec.); Yield 88% of theory.

C [deep] 25H [deep] 23N [deep] 3O [deep] 6S [deep] 2

calculated: C 57.13%, H 4.91%, N 7.99%, S 12.20%;

found: C 56.90%, H 4.63%, N 7.92%, S 12.04%.

Example 95

N-Benzoyldehydroisoleucyl-L-tyrosine methyl ester

analogously to Example 81 from 2-phenyl-4- (1-methylpropylidene) -5 (4H) oxazolone and tyrosine methyl ester.

M.p .: 163-165 ° C; Yield: 35.5% of theory.

C [deep] 33H [deep] 26N [deep] 2O [deep] 5

calculated: C 67.30%, H 6.38%, N 6.83%;

found: C 67.23%, H 6.35%, N 6.82%.

Example 96

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine tert-butyl ester

analogously to Example 81 from 2- (2-thienylmethyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine tert-butyl ester.

Mp 105 ° C; Yield 85% of theory.

C [deep] 26H [deep] 28N [deep] 2O [deep] 5S [deep] 2

calculated: C 60.91%, H 5.50%, N 5.47%, S 12.51%;

found: C 61.02%, H 5.57%, N 5.60%, S 12.36%.

Example 97

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine

from the above compound by adding glacial acetic acid / hydrochloric acid.

Mp 110 ° C; Yield 95% of theory.

C [deep] 22H [deep] 20N [deep] 2O [deep] 5S [deep] 2

calculated: C 57.88%, H 4.41%, N 6.14%, S 14.05%;

found: C 57.64%, H 4.52%, N 6.06%, S 13.90%.

Example 98

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine benzyl ester

analogously to Example 81 from 2- (2-thienylmethyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine benzyl ester.

Mp 95 ° C; Yield 83% of theory.

C [deep] 29H [deep] 26N [deep] 2O [deep] 5S [deep] 2

calculated: C 63.71%, H 4.79%, N 5.13%, S 11.74%;

found: C 63.85%, H 4.80%, N 5.06%, S 11.69%.

Example 99

N- (2-thienyl) acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester

analogously to Example 81 from 2- (2-thienylmethyl) -4- (2-thenylidene) -5 (4H) oxazolone and L-tyrosine methyl ester.

Mp 200 ° C (dec.); Yield 80% of theory.

C [deep] 23H [deep] 22N [deep] 2O [deep] 5S [deep] 2

calculated: C 58.70%, H 4.71%, N 5.95%, S 13.63%;

found: C 58.79%, H 4.76%, N 5.95%, S 13.50%.

Example 100

N-trifluoroacetyldehydrophenylalanyl-L-tyrosine

M.p. 165-175 ° C; [Alpha] [high] 20 [low] D - 57.4 ° (c = 1; dimethylformamide);

Yield 91% of theory.

C [deep] 20H [deep] 17F [deep] 3N [deep] 2O [deep] 5

Calculated: C 56.87%, H 4.06%, F 13.5%, N 6.63%;

found: C 56.92%, H 4.05%, F 13.4%, N 6.61%.

Example 101

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-tyrosine tert-butyl ester

made in dimethylformamide without NaOH.

Mp 110-120 ° C (crude product); Yield 51.5% of theory.

This compound was further processed by stirring with trifluoroacetic acid for 1/2 hour

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-tyrosine

Mp 135-140 ° C (dec.); [Alpha] [high] 20 [low] D - 41 °; Yield 49% of theory Th.

C [low] 24H [low] 22N [low] 2O [low] 5S

calculated: C 63.98%, H 4.92%, N 6.22%, S 7.12%;

found: C 63.79%, H 4.82%, N 6.29%, S 7.07%.

Example 102

N-phenacetyldehydro-3- (2-thienyl) alanyl-L-leucine

from 4.05 g (0.015 mol) of 2-benzyl-4- (2-thenylidene) -5 (4H) oxazolone and 3 g (0.0165 mol) of L-leucine methyl ester hydrochloride in dimethylformamide in the presence of triethylamine by stirring for two hours and standing for twelve hours , Dilution with water, etherification, washing out with dilute citric acid and evaporation of the dried ethereal solution results in N-phenylacetyldehydro-3- (2-thienyl) alanyl-L-leucine methyl ester. Mp 160-161 ° C; Yield 4.75 g (76.3% of theory).

4.66 g (0.011 mol) of the above compound were dissolved in 50 ml of tetrahydrofuran at 0 ° C., stirred with 11 ml of n NaOH for two hours at room temperature, the reaction solution was extracted with chloroform, the aqueous phase was acidified and then extracted with chloroform.

3.8 g (63.3% of theory) of N-phenacetyldehydro-3- (2-thienyl) alanyl-L-leucine with a melting point of 207-208 ° C. were obtained. [Alpha] [high] 20 [low] D - 45.2 °.

C [deep] 21H [deep] 24N [deep] 2O [deep] 4S

calculated: C 62.98%, H 6.04%, N 6.99%, S 8.00%;

found: C 62.92%, H 6.02%, N 7.03%, S 7.92%.

Example 103

N-Benzoyldehydrophenylalanyl-L-leucylglycine anilide

analogously to Example 102 from 2-phenyl-4-benzylidene-5 (4H) oxazolone and L-leucylglycine anilide.

M.p .: 179-180 ° C; Yield: 35.3% of theory.

C [deep] 30H [deep] 32N [deep] 4O [deep] 4

Calculated: C 70.29%, H 6.29%, N 10.93%;

found: C 69.44%, H 6.41%, N 10.82%.

Example 104

N-Benzoyldehydrophenylalanyl-L-prolyl-L-leucylglycine anilide

analogously to Example 102 from 2-phenyl-4-benzylidene-5 (4H) oxazolone and L-prolyl-L-leucylglycine amide.

M.p .: 192 ° C; Yield: 98% of theory.

C [deep] 35H [deep] 39N [deep] 5O [deep] 5

calculated: C 68.95%, H 6.45%, N 11.49%;

found: C 69.03%, H 6.42%, N 11.45%.

Example 105

N-acetyldehydro-3- (2-thienyl) alanyl-2-methylalanine methyl ester

analogously to Example 102 from 2-methyl-4- (2-thenylidene) -5 (4H) oxazolone and 2-methylalanine methyl ester.

Mp 181-182 ° C; Yield 69% of theory.

C [deep] 14H [deep] 18N [deep] 2O [deep] 4S

calculated: C 54.18%, H 5.85%, N 9.03%, S 10.33%;

found: C 54.32%, H 5.83%, N 9.12%, S 10.51%.

Example 106

N-acetyldehydro-3- (2-thienyl) alanyl-2-methylalanine

from the above compound by boiling with dilute sodium hydroxide solution.

M.p. 241 ° C (dec.); Yield 94% of theory.

C [deep] 13H [deep] 16N [deep] 2O [deep] 4S

Calculated: C 52.69%, H 5.44%, N 9.45%, S 10.82%;

found: C 52.64%, H 5.37%, N 9.47%, S 10.76%.

Example 107

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine

Mp 135 ° C (unsharp); Yield 41.2% of theory.

C [deep] 23H [deep] 20N [deep] 2O [deep] 5S

calculated: C 63.29%, H 4.62%, N 6.43%, S 7.34%;

found: C 63.25%, H 4.67%, N 6.37%, S 7.38%.

Example 108

N-Benzoyldehydro-3- (2-thienyl) alanyl-L- (p-nitrophenyl) alanine

Mp 125 ° C (unsharp); [Alpha] [high] 20 [low] D - 67.3 °; Yield 60% of theory Th.

C [deep] 23H [deep] 19N [deep] 3O [deep] 6S

calculated: C 59.35%, H 4.11%, N 9.03%, S 6.89%;

found: C 59.39%, H 4.36%, N 9.01%, S 6.71%.

Example 109

N-nicotinoyldehydro-3- (2-thienyl) alanyl-L-tyrosine

Mp 160 ° C (unsharp); [Alpha] [high] 20 [low] D - 8.35 °; Yield 50% of theory Th.

C [deep] 22H [deep] 19N [deep] 3O [deep] 5S

calculated: C 60.40%, H 4.38%, N 9.60%, S 7.33%;

found: C 60.57%, H 4.58%, N 9.75%, S 7.32%.

Example 110

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanyl-L-tyrosine

Mp 125 ° C (unsharp); [Alpha] [high] 20 [low] D - 8.9 °; Yield 48% of theory Th.

C [deep] 24H [deep] 19F [deep] 3N [deep] 2O [deep] 5S

calc .: C 57.14%, H 3.80%, F 11.30%, N 5.55%, S 6.36%;

Found: C 56.95%, H 3.81%, F 11.40%, N 5.45%, S 6.45%.

Example 111

N-nicotinoyldehydro-3- (2-thienyl) alanyl-L- (p-nitrophenyl) alanine

Mp 197 ° C (dec.); [Alpha] [high] 20 [low] D - 98 °; Yield 75% of theory Th.

C [deep] 22H [deep] 18N [deep] 4O [deep] 6S

calculated: C 56.64%, H 3.89%, N 12.01%, S 6.87%;

found: C 56.55%, H 3.91%, N 12.05%, S 6.89%.

Example 112

N-Benzoyl-3-methyl-3- (2-thienyl) dehydroalanyl-L-tyrosine

Mp 128 ° C; [Alpha] [high] 20 [low] D + 15.6 °; Yield 66.7% of theory.

C [low] 24H [low] 22N [low] 2O [low] 5S

calculated: C 63.98%, H 4.92%, N 6.22%, S 7.12%;

found: C 64.14%, H 4.93%, N 6.34%, S 7.03%.

Example 113

N-acetyldehydro-3- (2-thienyl) alanyl-D-tyrosine

Mp 221-222 ° C; [Alpha] [high] 20 [low] D + 36.8 °; Yield 51.49% of theory Th.

C [deep] 18H [deep] 18N [deep] 2O [deep] 5S

calculated: C 57.74%, H 4.85%, N 7.48%, S 8.56%;

found: C 57.83%, H 4.89%, N 7.44%, S 8.67%.

Example 114

N-cinnamoyldehydrophenylalanylglycine

M.p. 159-160 ° C; Yield 75% of theory.

C [deep] 20H [deep] 18N [deep] 2O [deep] 4 times H [deep] 2O

Calculated: C 65.20%, H 5.47%, N 7.61%;

found: C 65.27%, H 5.32%, N 7.76%.

Example 115

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-phenylalanine

Mp 100 ° C; [Alpha] [high] 20 [low] D - 4.8 ° (c = 1; dimethyl sulfoxide); Yield 80% of theory.

C [deep] 23H [deep] 20N [deep] 2O [deep] 4S

calculated: C 65.70%, H 4.79%, N 6.66%, S 7.63%;

found: C 65.64%, H 5.01%, N 6.50%, S 7.41%.

Example 116

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-leucine

Mp 110-120 ° C; [Alpha] [high] 20 [low] D + 24.8 ° (c = 1; dimethyl sulfoxide); Yield 90% of theory.

C [deep] 20H [deep] 22N [deep] 2O [deep] 4S

calculated: C 62.16%, H 5.74%, N 7.25%, S 8.29%;

found: C 62.19%, H 5.84%, N 7.20%, S 8.23%.

Example 117

N-acetyldehydro-3- (2-thienyl) -L-phenylalanine

Mp> 230 ° C; [Alpha] [high] 20 [low] D - 68.8 ° (c = 1; dimethyl sulfoxide); Yield 90% of theory.

C [deep] 18H [deep] 18N [deep] 2O [deep] 4S

calculated: C 60.32%, H 5.07%, N 7.82%, S 8.93%;

found: C 60.37%, H 5.04%, N 7.81%, S 8.96%.

Example 118

N-Benzoyl-3-methylphenyldehydroalanyl-L-leucine

M.p. 102-104 ° C; [Alpha] [high] 20 [low] D - 8.1 °; Yield 75% of theory Th.

C [deep] 23H [deep] 26N [deep] 2O [deep] 4

calculated: C 70.03%, H 6.64%, N 7.10%;

found: C 69.29%, H 6.48%, N 7.02%.

Example 119

N-cinnamoyldehydrophenylalanyl-L-tyrosine

Mp 172-174 ° C; [Alpha] [high] 20 [low] D - 24 °; Yield 30% of theory Th.

C [deep] 27H [deep] 24N [deep] 2O [deep] 5

Calculated: C 71.04%, H 5.3%, N 6.14%;

found: C 70.85%, H 5.39%, N 6.16%.

Example 120

N-acetyldehydro-3- (2-thienyl) alanine

Mp. 230 ° C (dec.) Literature preparation.

Example 121

N-acetyldehydro-3- (2-thienyl) alanyl-L-leucine

Mp> 230 ° C; [Alpha] [high] 20 [low] D - 11.0 ° (c = 1; dimethyl sulfoxide); Yield 90% of theory.

C [deep] 15H [deep] 20N [deep] 2O [deep] 4S

calculated: C 55.54%, H 6.21%, N 8.64%, S 9.88%;

found: C 55.72%, H 6.27%, N 8.59%, S 9.87%.

Example 122

N-Benzoyldehydroisoleucyl-L-tyrosine

Mp 107 ° C; [Alpha] [high] 20 [low] D - 12.1 °; Yield 31.5% of theory Th.

C [deep] 22H [deep] 24N [deep] 2O [deep] 5

Calculated: C 66.65%, H 6.10%, N 7.07%;

found: C 66.57%, H 6.17%, N 6.90%.

Example 123

N-Benzoyl-3-methyl-3-cinnamenyldehydroalanyl-L-tyrosine

Mp 130 ° C; [Alpha] [high] 20 [low] D - 5.5 °; Yield 96% of theory Th.

C [deep] 28H [deep] 26N [deep] 2O [deep] 5

Calculated: C 71.47%, H 5.57%, N 5.95%;

found: C 71.60%, H 5.57%, N 5.87%.

Example 124

N-acetyldehydrophenylalanyldehydro- (3-chlorophenyl) alanyl-L-tyrosine

by aminolysis of 4- (3-chlorobenzylidene) -2- (1-acetamido-2-phenylethylene) -5 (4H) oxazolone with L-tyrosine.

Mp 191-193 ° C; [Alpha] [high] 20 [low] D - 154.3 ° (c = 1; dimethylformamide); Yield 78.5% of theory.

C [low] 29H [low] 26ClN [low] 3O [low] 6

calculated: C 63.56%, H 4.78%, Cl 6.47%, N 7.67%;

found: C 63.69%, H 4.76%, Cl 6.54%, N 7.70%.

Example 125

N-acetyldehydrophenylalanyldehydrotyrosine

6.09 g (0.0175 mol) of 2- (1-acetamido-2-phenylethylene) -4- (4-hydroxybenzylidene) -5 (4H) oxazolone are mixed with 46.9 ml of NaOH and 40 ml of acetone for three hours stirred at room temperature. After distilling off the acetone, acidifying the aqueous reaction solution with 47.6 ml of nHCl and recrystallization of the precipitated and filtered precipitate from ethanol / petroleum ether, 3.75 g (58.6% of theory) of N-acetyldehydrophenylalanyldehydrotyrosine with a melting point of 202-206 ° C. are obtained .

Literature preparation.

The following were prepared from the corresponding oxazolones in the same way:

Example 126

N-acetyldehydrophenylalanyldehydro- (p-nitrophenyl) alanine

Mp 181 ° C; Yield 56.4% of theory.

C [deep] 20H [deep] 17N [deep] 3O [deep] 6

Calculated: C 60.76%, H 4.33%, N 10.63%;

found: C 60.86%, H 4.51%, N 10.46%.

Example 127

N-acetyldehydrophenylalanyldehydro- (4-chlorophenyl) alanine

Mp 177 ° C; Yield 60.9% of theory.

C [deep] 20H [deep] 17ClN [deep] 2O [deep] 4

Calculated: C 62.42%, H 4.45%, N 7.28%, Cl 9.21%;

found: C 62.49%, H 4.47%, N 7.37%, Cl 9.24%.

Example 128

N-acetyldehydrophenylalanyldehydro- (p-fluorophenyl) alanine

Mp 172 ° C; Yield 65.27% of theory.

C [deep] 20H [deep] 17FN [deep] 2O [deep] 4 times H [deep] 2O

Calculated: C 62.17%, H 4.96%, F 4.92%, N 7.25%;

found: C 62.30%, H 4.94%, F 4.70%, N 7.25%.

Example 129

N-acetyldehydrophenylalanyldehydro (4-dimethylaminophenyl) alanine

Mp 153-155 ° C; Yield 36.2% of theory.

C [deep] 22H [deep] 23N [deep] 3O [deep] 4

Calculated: C 67.16%, H 5.89%, N 10.68%;

found: C 67.03%, H 6.00%, N 10.52%.

Example 130

N-acetyldehydrophenylalanyldehydro (3-chlorophenyl) alanine

Mp 183 ° C; Yield 88.4% of theory.

C [deep] 20H [deep] 17ClN [deep] 2O [deep] 4

Calculated: C 62.42%, H 4.45%, Cl 9.21%, N 7.28%;

found: C 62.54%, H 4.45%, Cl 9.23%, N 7.18%.

The following examples were carried out in tetrahydrofuran without NaOH.

Example 131

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester

Mp 120 ° C (unsharp); [Alpha] [high] 20 [low] D - 4.6 °; Yield 95% of theory Th.

C [low] 24H [low] 22N [low] 2O [low] 5S

calculated: C 63.98%, H 4.92%, N 6.22%, S 7.12%;

found: C 63.78%, H 4.93%, N 6.07%, S 7.02%.

Example 132

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methyl ester

Mp 243-245 ° C; [Alpha] [high] 20 [low] D - 78.1 ° (c = 1; dimethyl sulfoxide); Yield 65% of theory.

C [deep] 19H [deep] 20N [deep] 2O [deep] 5S

calculated: C 58.75%, H 5.19%, N 7.21%, S 8.26%;

found: C 58.45%, H 5.35%, N 7.17%, S 8.47%.

Example 133

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine benzyl ester

is formed from the acid and benzyl alcohol by heating for 1/2 hour at 80 ° C in the presence of hydrogen chloride.

Mp 95 ° C (unsharp); [Alpha] [high] 20 [low] D - 2.0 °; Yield 79% of theory Th.

C [deep] 30H [deep] 26N [deep] 2O [deep] 5S

calculated: C 68.42%, H 4.98%, N 5.32%, S 6.09%;

found: C 68.42%, H 4.96%, N 5.30%, S 6.02%.

Example 134

N-acetyldehydro-3- (2-thienyl) alanine salt with morpholine

1.5 times the dehydroamino acid are mixed with three times the amount of morpholine, diluted with methanol and evaporated to dryness.

Mp 173 ° C (dec.); Yield 89% of theory.

C [deep] 13H [deep] 18N [deep] 2O [deep] 4S

calculated: C 52.4%, H 6.0%, N 9.4%, S 10.7%;

found: C 52.8%, H 6.2%, N 9.4%, S 11.1%.

Analogously to example 134 the following are produced:

Example 135

N-acetyldehydro-3- (2-thienyl) alanine salt with methylamine

Mp 178 ° C; Yield 99% of theory.

C [deep] 10H [deep] 14N [deep] 2O [deep] 3S

calculated: C 49.57%, H 5.82%, N 11.56%, S 13.24%;

found: C 49.74%, H 5.92%, N 11.60%, S 13.23%.

Example 136

N-acetyldehydro-3- (2-thienyl) alanine salt with 1,1-dimethylpropargylamine

M.p. 221 ° C (dec.); Yield 99% of theory.

C [deep] 14H [deep] 18N [deep] 2O [deep] 3S

calculated: C 57.12%, H 6.16%, N 9.52%, S 10.89%;

found: C 57.24%, H 6.21%, N 9.68%, S 11.06%.

Example 137

N-acetyldehydro-3- (2-thienyl) alanine, lithium salt

Mp> 300 ° C; Yield 66.80% of theory.

C [low] 9H [low] 8LiNO [low] 3S

calculated: C 49.77%, H 3.71%, N 6.45%, S 14.76%, Li 3.21%;

found: C 49.79%, H 3.92%, N 6.30%, S 14.45%, Li 3.35%.

Example 138

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with morpholine

Mp 136-150 ° C; Yield 69.40% of theory.

C [deep] 22H [deep] 27N [deep] 3O [deep] 6S

calculated: C 57.25%, H 5.90%, N 9.11%, S 6.95%;

found: C 56.54%, H 6.14%, N 8.85%, S 6.42%.

Example 139

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with piperidine

Mp 184-186 ° C; Yield 58.80% of theory.

C [deep] 23H [deep] 29N [deep] 3O [deep] 5S

calculated: C 60.11%, H 6.36%, N 9.14%, S 6.98%;

found: C 60.29%, H 6.27%, N 9.33%, S 7.17%.

Example 140

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with ethylenediamine

Mp 148-158 ° C; Yield 98.9% of theory.

C [deep] 38H [deep] 44N [deep] 6O [deep] 10S [deep] 2

calculated: C 56.42%, H 5.48%, N 10.39%, S 7.93%;

found: C 56.38%, H 5.64%, N 10.26%, S 7.81%.

Example 141

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with triethanolamine

Mp 125-130 ° C; Yield 84.1% of theory.

C [deep] 24H [deep] 33N [deep] 3O [deep] 8S

calculated: C 55.05%, H 6.35%, N 8.03%, S 6.12%;

found: C 54.77%, H 6.30%, N 7.93%, S 6.00%.

Example 142

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with DL-canavanine

Mp 165-173 ° C; Yield 90.9% of theory.

C [deep] 23H [deep] 30N [deep] 6O [deep] 8S

calculated: C 50.17%, H 5.49%, N 15.27%, S 5.81%;

found: C 50.02%, H 5.62%, N 15.35%, S 5.67%.

Example 143

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with L-arginine

Mp 125-140 ° C; Yield 79.3% of theory.

C [deep] 24H [deep] 32N [deep] 6O [deep] 7S

calculated: C 52.54%, H 5.88%, N 15.32%, S 5.85%;

found: C 52.44%, H 6.00%, N 15.31%, S 5.10%.

Example 144

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine salt with L-lysine

Mp 174-182 ° C; Yield 96.1% of theory.

C [deep] 24H [deep] 32N [deep] 4O [deep] 7S

calculated: C 55.37%, H 6.20%, N 10.76%, S 6.16%;

found: C 55.22%, H 6.41%, N 10.87%, S 6.04%.

The following amides were prepared from the corresponding methyl esters by standing in a mixture with the corresponding amines (1 mol ester to 8 mol amine) in methanol or tetrahydrofuran and working up by evaporation and purification on silica gel (reaction time 3-340 hours).

Example 145

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosinamide

Mp 210 ° C; [Alpha] [high] 20 [low] D -62.0 °; Yield 86% of theory.

C [deep] 23H [deep] 21N [deep] 3O [deep] 4S

calculated: C 63.43%, H 4.86%, N 9.65%, S 7.36%;

found: C 63.25%, H 4.96%, N 9.59%, S 7.38%.

Example 146

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N'-hexylamide

Mp 115 ° C (unsharp); [Alpha] [high] 20 [low] D - 63.4 °; Yield 80% of theory Th.

C [low] 29H [low] 33N [low] 3O [low] 4S

calculated: C 67.03%, H 6.40%, N 8.09%, S 6.17%;

found: C 67.22%, H 6.51%, N 8.19%, S 6.08%.

Example 147

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N'-methylamide

M.p. 145 ° C (unsharp); [Alpha] [high] 20 [low] D - 61.7 °; Yield 90.2% of theory Th.

C [low] 24H [low] 23N [low] 3O [low] 4S

calculated: C 64.12%, H 5.16%, N 9.35%, S 7.13%;

found: C 64.04%, H 4.99%, N 9.42%, S 7.07%.

Example 148

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N'-cyclohexylamide

Mp 110 ° C (unsharp); [Alpha] [high] 20 [low] D - 50.9 °; Yield 44% of theory Th.

C [low] 29H [low] 31N [low] 3O [low] 4S

calculated: C 67.29%, H 6.04%, N 8.12%, S 6.19%;

found: C 67.38%, H 6.33%, N 8.09%, S 5.88%.

Example 149

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-N ', N'-dimethylamide

Mp 130 ° C (unsharp); [Alpha] [high] 20 [low] D - 2.2 °; Yield 13% of theory Th.

C [deep] 25H [deep] 25N [deep] 3O [deep] 4S

calculated: C 64.77%, H 5.44%, N 9.06%, S 6.92%;

found: C 64.64%, H 5.41%, N 9.06%, S 6.77%.

Example 150

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine morpholide

Mp 120 ° C (unsharp); [Alpha] [high] 20 [low] D - 0.7 °; Yield 22% of theory Th.

C [deep] 27H [deep] 27N [deep] 3O [deep] 5S

calculated: C 64.14%, H 4.38%, N 8.32%, S 6.34%;

found: C 63.92%, H 5.53%, N 8.27%, S 6.09%.

Example 151

N-Benzoyldehydro-3- (2-thienyl) -L-tyrosine-N'-benzylamide

Mp 133 ° C; [Alpha] [high] 20 [low] D - 69.83 °; Yield 68% of theory.

C [deep] 30H [deep] 27N [deep] 3O [deep] 4S

calculated: C 63.55%, H 5.18%, N 7.99%, S 6.10%;

found: C 63.65%, H 5.25%, N 8.13%, S 6.03%.

Example 152

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine-2-dimethylaminopropylamide

Mp 177-179 ° C (dec.); Yield 63% of theory.

C [deep] 23H [deep] 30N [deep] 4O [deep] 4S

calculated: C 60.24%, H 6.59%, N 12.22%, S 6.99%;

found: C 60.39%, H 6.75%, N 12.40%, S 6.89%.

Example 153

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosinamide

Mp 147 ° C; Yield 79% of theory.

C [deep] 18H [deep] 19N [deep] 3O [deep] 4S

calculated: C 57.89%, H 5.13%, N 11.25%, S 8.59%;

found: C 57.75%, H 5.20%, N 11.09%, S 8.53%.

Example 154

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine methylamide

Mp 225 ° C; Yield 50% of theory.

C [deep] 19H [deep] 21N [deep] 3O [deep] 4S

calculated: C 58.90%, H 5.46%, N 10.85%, S 8.27%;

found: C 58.90%, H 5.47%, N 10.85%, S 8.30%.

Example 155

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-6-aminohexylamide

Mp 122 ° C; Yield 51.4% of theory.

C [low] 29H [low] 34N [low] 40 [low] 4S

calculated: C 65.14%, H 6.41%, N 10.48%, S 6.00%;

found: C 65.04%, H 6.42%, N 10.45%, S 6.10%.

Example 156

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine-4-aminobutylamide

Mp 126 ° C; Yield 70% of theory.

C [deep] 27H [deep] 30N [deep] 4O [deep] 4S

calculated: C 64.00%, H 5.96%, N 11.06%, S 6.32%;

found: C 64.28%, H 5.98%, N 10.84%, S 6.19%.

Example 157

N-acetyldehydro-3- (2-thienyl) alanyl-L-tyrosine hydrazide

Mp 240 ° C (dec.); Yield 35.3% of theory.

C [deep] 18H [deep] 20N [deep] 4O [deep] 4S

calculated: C 55.66%, H 5.19%, N 14.42%, S 8.25%;

found: C 55.58%, H 5.28%, N 14.56%, S 8.34%.

Example 158

N-Benzoyldehydro-3- (2-thienyl) alanyl-L-tyrosine hydrazide

Mp 135 ° C; Yield 82.2% of theory.

C [deep] 23H [deep] 22N [deep] 4O [deep] 4S

calculated: C 61.32%, H 4.92%, N 12.44%, S 7.11%;

found: C 61.12%, H 5.02%, N 12.38%, S 7.26%.

If a corresponding amine is used instead of sodium hydroxide, the following compounds are formed from the corresponding 5 (4H) oxazolones:

Example 159

N-acetyldehydro-3- (2-thienyl) alanine-N'-methylamide

Mp 183 ° C; Yield 89% of theory.

C [deep] 10H [deep] 12N [deep] 2O [deep] 2S

calculated: C 53.55%, H 5.39%, N 12.49%, S 14.30%;

found: C 53.66%, H 5.52%, N 12.52%, S 14.23%.

Example 160

N-acetyldehydro-2- (2-thienyl) alanine-N'-1,1-dimethyl-2-propynylamide

Mp 197-200 ° C; Yield 36.2% of theory.

C [deep] 14H [deep] 16N [deep] 2O [deep] 2S

calculated: C 60.85%, H 5.84%, N 10.14%, S 11.60%;

found: C 60.64%, H 6.06%, N 10.08%, S 11.38%.

Example 161

N-acetyldehydro-e- (2-thienyl) alanine morpholide

Mp 159 ° C; Yield 82.7% of theory.

C [deep] 13H [deep] 16N [deep] 2O [deep] 3S

calculated: C 55.69%, H 5.75%, N 9.99%, S 11.44%;

found: C 55.80%, H 5.73%, N 10.09%, S 11.22%.

Example 162

N-cinnamoyldehydroalanine-N'-methylamide

Mp 114-118 ° C; Yield 70% of theory.

C [deep] 19H [deep] 18N [deep] 2O [deep] 2

Calculated: C 74.5%, H 5.9%, N 9.1%;

found: C 74.4%, H 6.0%, N 9.0%.

Example 163

N-cinnamoyldehydroalanine-1,1-dimethyl-2-propynylamide

Mp 200-203 ° C; Yield 40% of theory.

C [deep] 23H [deep] 22N [deep] 2O [deep] 2

calculated: C 77.1%, H 6.2%, N 7.8%;

found: C 77.1%, H 6.2%, N 8.0%.

Example 164

N-cinnamoyldehydroalanine morpholide

Mp 179-182 ° C; Yield 50% of theory.

C [deep] 22H [deep] 22N [deep] 2O [deep] 3

calculated: C 72.9%, H 6.1%, N 7.7%;

found: C 72.8%, H 6.2%, N 7.5%.

Example 165

N-ethoxyacetyldehydro-3- (2-thienyl) alanine-4-methylpiperazide

M.p. 95-97 ° C; Yield 71.4% of theory.

C [deep] 16H [deep] 23N [deep] 3O [deep] 3S

calculated: C 56.95%, H 6.87%, N 12.45%, S 9.50%;

found: C 56.79%, H 6.94%, N 12.44%, S 9.56%.

Example 166

N-ethoxyacetyldehydro-3- (2-thienyl) alanine anilide

M.p. 158-159 ° C; Yield 97.9% of theory.

C [deep] 17H [deep] 18N [deep] 2O [deep] 3S

calculated: C 61.80%, H 5.49%, N 8.48%, S 9.70%;

found: C 61.90%, H 5.48%, N 8.48%, S 9.65%.

Example 167

N-ethoxyacetyldehydro-3- (2-thienyl) alanine cyclohexylamide

M.p. 142-144 ° C; Yield 72% of theory.

C [deep] 17H [deep] 24N [deep] 2O [deep] 3S

calculated: C 60.69%, H 7.19%, N 8.32%, S 9.53%;

found: C 60.27%, H 7.25%, N 8.32%, S 9.42%.

Example 168

N-ethoxyacetyldehydro-3- (2-thienyl) alanine amide

M.p. 145-147 ° C; Yield 50.6% of theory.

C [deep] 11H [deep] 14N [deep] 2O [deep] 3S

calculated: C 51.95%, H 5.55%, N 11.01%, S 12.62%;

found: C 51.92%, H 5.50%, N 10.86%, S 12.66%.

Example 169

N-crotonoyldehydro-3- (2-thienyl) alanine-4-methylpiperazide

Mp 172-173 ° C; Yield 90% of theory.

C [deep] 16H [deep] 21N [deep] 3O [deep] 2S

calculated: C 60.16%, H 6.63%, N 13.16%, S 10.04%;

found: C 60.18%, H 7.04%, N 13.16%, S 9.92%.

Example 170

N-crotonoyldehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide

Mp 137-138 ° C; Yield 83% of theory.

C [deep] 16H [deep] 23N [deep] 3O [deep] 2S

calculated: C 59.78%, H 7.21%, N 13.07%, S 9.98%;

found: C 59.44%, H 7.16%, N 13.02%, S 9.93%.

Example 171

N-crotonoyldehydro-3- (2-thienyl) alanine-6-aminohexylamide

Mp 113-114 ° C; Yield 70% of theory.

C [deep] 17H [deep] 25N [deep] 3O [deep] 2S

calculated: C 60.86%, H 7.51%, N 12.53%, S 9.56%;

found: C 60.73%, H 7.58%, N 12.56%, S 9.37%.

Example 172

N-acetyldehydrophenylalanyl-3- (2-thienyl) dehydroalanine methylamide

Mp 226 ° C; Yield 89% of theory.

C [deep] 19H [deep] 19N [deep] 3O [deep] 3S

calculated: C 61.77%, H 5.18%, N 11.37%, S 8.68%;

found: C 61.65%, H 5.25%, N 11.6%, S 8.63%.

Example 173

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine anilide

Mp 240-243 ° C; Yield 56% of theory.

C [deep] 21H [deep] 15F [deep] 3N [deep] 2O [deep] 2S

calculated: C 60.57%, H 3.63%, F 13.69%, N 6.73%, S 7.70%;

found: C 60.55%, H 3.73%, F 13.5%, N 6.75%, S 7.71%.

Example 174

N- (3-Trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine-4-methylpiperazide

Mp 187-188 ° C; Yield 63.8% of theory.

C [deep] 20H [deep] 20F [deep] 3N [deep] 3O [deep] 2S

Calculated: C 56.73%, H 4.76%, N 9.92%, F 13.46%, S 7.57%;

found: C 56.57%, H 4.63%, N 9.98%, F 13.4%, S 7.56%.

Example 175

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide

Mp 152-154 ° C;

C [deep] 20H [deep] 22F [deep] 3N [deep] 3O [deep] 2S

Calculated: C 56.46%, H 5.21%, N 9.88%, F 13.4%;

found: C 56.55%, H 5.32%, N 10.0%, F 13.6%.

Example 176

N- (3-trifluoromethylbenzoyl) dehydro-3- (2-thienyl) alanine amide

Mp 205-207 ° C;

C [deep] 15H [deep] 11F [deep] 3N [deep] 2O [deep] 2S

Calculated: C 52.94%, H 3.26%, N 8.23%, F 16.75%, S 9.42%;

found: C 53.05%, H 3.25%, N 8.26%, F 16.9%, S 9.46%.

Example 177

N-acetyldehydro-3- (2-thienyl) alanyl-3-methyl-3- (2-thienyl) dehydroalanine hexylamide

Mp 110 ° C; Yield 90% of theory.

C [deep] 23H [deep] 29N [deep] 3O [deep] 3S [deep] 2

calculated: C 60.10%, H 6.36%, N 9.14%, S 13.96%;

found: C 60.20%, H 6.56%, N 9.26%, S 13.91%.

Example 178

N-nicotinoyl-3- (2-thienyl) dehydroalanine propargylamide

Mp 140-143 ° C; Yield 98% of theory.

C [deep] 16H [deep] 13N [deep] 3O [deep] 2S times H [deep] 2O

calculated: C 58.34%, H 4.59%, N 12.76%, S 9.74%;

found: C 58.21%, H 4.58%, N 13.15%, S 10.01%.

Example 179

N- (2-thienylacetyl) dehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide

Mp 143 ° C; Yield 74% of theory.

C [deep] 18H [deep] 23N [deep] 3O [deep] 2S [deep] 2

calculated: C 57.26%, H 6.14%, N 11.13%, S 16.99%;

found: C 57.41%, H 6.09%, N 11.08%, S 17.05%.

Example 180

N-Benzoyldehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide

Mp 174-176 ° C; Yield 91% of theory.

C [deep] 19H [deep] 23N [deep] 3O [deep] 2S

calculated: C 63.84%, H 6.49%, N 11.76%, S 8.96%;

found: C 63.92%, H 6.47%, N 11.91%, S 9.06%.

Example 181

N-Benzoyldehydro-3- (2-thienyl) alanine anilide

Mp 231 ° C; Yield 84% of theory.

C [deep] 20H [deep] 16N [deep] 2O [deep] 2S

calculated: C 68.94%, H 4.63%, N 8.04%, S 9.20%;

found: C 69.20%, H 4.48%, N 8.03%, S 9.16%.

Example 182

N-Benzoyldehydro-3- (2-thienyl) alanine methylamide

Mp 231 ° C (dec.); Yield 92% of theory.

C [deep] 15H [deep] 14N [deep] 2O [deep] 2S

calculated: C 62.91%, H 4.93%, N 9.78%, S 11.20%;

found: C 62.94%, H 5.10%, N 9.85%, S 11.30%.

Example 183

N-Benzoyldehydro-3- (3-thienyl) alaninehexylamide

Mp 121 ° C; Yield 95% of theory.

C [deep] 20H [deep] 24N [deep] 2O [deep] 2S

calculated: C 67.38%, H 6.79%, N 7.86%, S 8.99%;

found: C 67.31%, H 6.85%, N 7.95%, S 8.89%.

Example 184

N-Benzoyldehydro-3- (2-thienyl) alanine propargylamide

Mp 185-186 ° C; Yield 75% of theory.

C [deep] 17H [deep] 14N [deep] 2O [deep] 2S

calculated: C 65.79%, H 4.55%, N 9.03%, S 10.33%;

found: C 65.93%, H 4.65%, N 8.88%, S 10.39%.

Example 185

N-Benzoyldehydrophenylalanine hydrazide

Mp 151-153 ° C; Yield 28% of theory.

C [deep] 16H [deep] 15N [deep] 3O [deep] 2

Calculated: C 68.31%, H 5.37%, N 14.94%;

found: C 68.14%, H 5.53%, N 14.89%.

Example 186

N-Benzoyldehydrophenylalanine anilide

Mp 213-233 ° C; Yield 80% of theory.

C [deep] 22H [deep] 18N [deep] 2O [deep] 2

calculated: C 77.17%, H 5.3%, N 8.18%;

found: C 77.63%, H 5.7%, N 8.09%.

Example 187

N-benzoyldehydrophenylalanine methylamide

Mp 172-174 ° C; Yield 71% of theory.

C [deep] 17H [deep] 16N [deep] 2O [deep] 2

calculated: C 70.6%, H 5.9%, N 9.7%;

found: C 70.4%, H 5.9%, N 9.8%.

Example 188

N-Benzoyldehydrophenylalanine-1,1-dimethylpropargylamide

Mp 169-174 ° C; Yield 85% of theory.

C [deep] 21H [deep] 20N [deep] 2O [deep] 2

Calculated: C 75.88%, H 6.06%, N 8.43%;

found: C 75.74%, H 6.07%, N 8.36%.

Example 189

N-benzoyldehydrophenylalanine hexylamide

Mp 139-140 ° C; Yield 63% of theory.

C [deep] 22H [deep] 26N [deep] 2O [deep] 2

Calculated: C 75.4%, H 7.48%, N 7.99%;

found: C 75.43%, H 7.45%, N 8.09%.

Example 190

N-Benzoyldehydrophenylalanine cyclohexylamide

Mp 197-199 ° C; Yield 85% of theory.

C [deep] 22H [deep] 24N [deep] 2O [deep] 2

Calculated: C 75.83%, H 6.94%, N 8.04%;

found: C 75.81%, H 7.02%, N 8.08%.

Example 191

N-benzoyldehydrophenylalanine morpholide

M.p. 158-160 ° C; Yield 63% of theory.

C [deep] 20H [deep] 20N [deep] 2O [deep] 3

Calculated: C 71.41%, H 5.99%, N 8.33%;

found: C 71.3%, H 6.03%, N 8.2%.

Example 192

N-Benzoyldehydrophenylalanine-4-methoxyphenylhydrazide

Mp 207-209 ° C; Yield 38% of theory.

C [deep] 23H [deep] 21N [deep] 3O [deep] 3

Calculated: C 71.3%, H 5.46%, N 10.85%;

found: C 71.4%, H 5.44%, N 10.96%.

Example 193

N-Benzoyldehydrophenylalanine-2-phenylcyclopropylamide

M.p .: 140-143 ° C; Yield 89% of theory.

C [deep] 25H [deep] 22N [deep] 2O [deep] 2

calculated: C 78.51%, H 5.80%, N 7.33%;

found: C 78.52%, H 5.83%, N 7.22%.

Example 194

N-Benzoyldehydrophenylalanine-3,4,5-trimethoxyanilide

M.p .: 209-212 ° C; Yield 72% of theory.

C [deep] 25H [deep] 24N [deep] 2O [deep] 5

calculated: C 69.43%, H 5.59%, N 6.48%;

found: C 69.3%, H 5.55%, N 6.37%.

Example 195

N-Benzoyldehydrophenylalanine-3-dimethylaminopropylamide

M.p .: 124-126 ° C; Yield 68% of theory.

C [deep] 21H [deep] 25N [deep] 3O [deep] 2

Calculated: C 71.77%, H 7.14%, N 11.96%;

found: C 71.67%, H 7.17%, N 12.13%.

Example 196

N-Benzoyldehydrophenylalanine propargylamide

M.p .: 190-191 ° C; Yield 81% of theory.

C [deep] 19H [deep] 16N [deep] 2O [deep] 2

Calculated: C 74.98%, H 5.30%, N 9.21%;

found: C 74.93%, H 5.37%, N 9.20%.

Example 197

N-acetyldehydro-3- (2-thienyl) alanine-2- (4-imidazolyl) ethylamide

M.p .: 105 ° C; Yield 76.2% of theory.

C [deep] 14H [deep] 16N [deep] 4O [deep] 2S

calculated: C 55.24%, H 5.30%, N 18.41%, S 10.53%;

found: C 55.26%, H 5.47%, N 18.41%, S 10.30%.

Example 198

N-acetyldehydro-3- (2-thienyl) alaninehexylamide

M.p .: 152-153 ° C; Yield 91.8% of theory.

C [deep] 15H [deep] 22N [deep] 2O [deep] 2S

Calculated: C 61.19%, H 7.53%, N 9.52%, S 10.89%;

found: C 61.24%, H 7.57%, N 9.48%, S 10.98%.

Example 199

N-acetyldehydro-3- (2-thienyl) alanine-2-phenylcyclopropylamide

M.p .: 204 ° C; Yield 82.8% of theory.

C [deep] 18H [deep] 18N [deep] 2O [deep] 2S

Calculated: C 66.23%, H 5.56%, N 8.58%;

found: C 66.30%, H 5.61%, N 8.67%.

Example 200

N-acetyldehydro-3- (2-thienyl) alanine benzylamide

M.p .: 193-195 ° C; Yield 93.3% of theory.

C [deep] 16H [deep] 16N [deep] 2O [deep] 3S

calculated: C 63.98%, H 5.37%, N 9.33%, S 10.67%;

found: C 63.93%, H 5.31%, N 9.23%, S 10.40%.

Example 201

N-acetyldehydro-3- (2-thienyl) alanine-3-dimethylaminopropylamide

M.p .: 137-139 ° C; Yield 78% of theory.

C [deep] 14H [deep] 21N [deep] 3O [deep] 2S

Calculated: C 56.92%, H 7.17%, N 14.23%, S 10.85%;

found: C 56.79%, H 7.09%, N 14.16%, S 10.71%.

Example 202

N-acetyldehydro-3- (2-thienyl) alanine piperidide

M.p .: 160-161 ° C; Yield 61.1% of theory.

C [deep] 14H [deep] 18N [deep] 2O [deep] 2S

calculated: C 60.40%, H 6.51%, N 10.06%, S 11.52%;

found: C 60.6%, H 6.48%, N 10.1%, S 11.44%.

Example 203

N-acetyldehydro-3- (2-thienyl) alanine-4-methylpiperazide

M.p .: 183-184 ° C; Yield 68.3% of theory.

C [deep] 14H [deep] 19N [deep] 3O [deep] 2S

calculated: C 57.31%, H 6.53%, N 14.32%, S 10.93%;

found: C 57.40%, H 6.46%, N 14.49%, S 10.96%.

Example 204

N-acetyldehydro-3- (2-thienyl) alanine-4-phenylpiperazide

M.p .: 197 ° C; Yield 64.8% of theory.

C [deep] 19H [deep] 21N [deep] 3O [deep] 2S

calculated: C 64.20%, H 5.95%, N 11.82%, S 9.02%;

found: C 64.09%, H 5.94%, N 11.84%, S 9.06%.

Example 205

N-crotonyldehydro-3- (2-thienyl) alanine-4-hydroxyanilide

M.p .: 245 ° C; Yield 53% of theory.

C [deep] 17H [deep] 10N [deep] 2O [deep] 3S

calculated: C 62.18%, H 4.92%, N 8.53%, S 9.76%;

found: C 61.97%, H 5.23%, N 8.57%, S 9.65%.

Example 206

N-acetyldehydro-3- (2-thienyl) alanine-4- (2-hydroxyethyl) piperazide

M.p .: 227-230 ° C; Yield 80.5% of theory.

C [deep] 15H [deep] 21N [deep] 3O [deep] 3S

calculated: C 55.71%, H 6.59%, N 12.99%, S 9.91%;

found: C 55.68%, H 6.54%, N 12.97%, S 9.64%.

Example 207

N-acetyldehydro-3- (2-thienyl) alanine amide

M.p .: 189 ° C; Yield 76.2% of theory.

C [deep] 9H [deep] 10N [deep] 2O [deep] 2S

calculated: C 51.41%, H 4.79%, N 13.32%, S 15.25%;

found: C 51.34%, H 4.88%, N 13.33%, S 15.42%.

Example 208

N-acetyldehydro-3- (2-thienyl) alanine-2,2-dimethylhydrazide

M.p .: 174-175 ° C; Yield 59.3% of theory.

C [deep] 11H [deep] 15N [deep] 3O [deep] 2S

calculated: C 52.15%, H 5.97%, N 16.59%, S 12.66%;

found: C 52.09%, H 6.00%, N 16.69%, S 12.50%.

Example 209

N-acetyldehydro-3- (2-thienyl) alanine anilide

M.p .: 95-97 ° C; Yield 73.4% of theory.

C [deep] 15H [deep] 14N [deep] 2O [deep] 2S

calculated: C 62.92%, H 4.93%, N 9.78%, S 11.20%;

found: C 62.85%, H 4.99%, N 9.83%, S 11.32%.

Example 210

N-acetyldehydro-3- (2-thienyl) alanine-4-methylcyclohexylamide

M.p .: 195-197 ° C; Yield 57.4% of theory.

C [deep] 16H [deep] 22N [deep] 2O [deep] 2S

calculated: C 62.71%, H 7.24%, N 9.14%, S 10.47%;

found: C 62.73%, H 7.37%, N 8.99%, S 10.53%.

Example 211

N-acetyldehydro-3- (2-thienyl) alanine-3-morpholinopropylamide

M.p .: 135-137 ° C; Yield 48.9% of theory.

C [deep] 16H [deep] 23N [deep] 3O [deep] 3S

calculated: C 56.95%, H 6.87%, N 12.45%, S 9.51%;

found: C 56.92%, H 6.87%, N 12.30%, S 9.59%.

Example 212

N-acetyldehydro-3- (2-thienyl) alanine-1-phenylethylamide

M.p .: 171-173 ° C; Yield 50.9% of theory.

C [deep] 17H [deep] 18N [deep] 2O [deep] 2S

calculated: C 64.94%, H 5.77%, N 8.91%, S 10.20%;

found: C 65.14%, H 5.91%, N 8.89%, S 10.30%.

Example 213

N-acetyldehydro-3- (2-thienyl) alanine-3-carboxypropylamide

M.p .: 195-197 ° C; Yield 65.9% of theory.

C [deep] 13H [deep] 16N [deep] 2O [deep] 4S

Calculated: C 52.69%, H 5.44%, N 9.45%, S 10.82%;

found: C 52.87%, H 5.55%, N 9.54%, S 10.98%.

Example 214

N-acetyldehydro-3- (2-thienyl) alanine hydrazide

M.p .: 170 ° C; Yield 75.5% of theory.

C [deep] 9H [deep] 11N [deep] 3O [deep] 2S times H [deep] 2O

calculated: C 44.43%, H 5.39%, N 17.27%, S 13.18%;

found: C 44.21%, H 5.37%, N 17.30%, S 13.26%.

Example 215

N-acetyldehydro-3- (2-thienyl) alanine-2-sulfonic acid ethylamide

M.p .: 192-194 ° C; Yield 68.7% of theory.

C [deep] 11H [deep] 14N [deep] 2O [deep] 5S [deep] 2

calculated: C 41.50%, H 4.43%, N 8.80%, S 20.14%;

found: C 41.36%, H 4.60%, N 8.73%, S 19.99%.

Example 216

N-acetyldehydro-3- (2-thienyl) alanine-1-ethinylcyclohexylamide

M.p .: 223-224 ° C; Yield 82.5% of theory.

C [deep] 17H [deep] 20N [deep] 2O [deep] 2S

calculated: C 64.54%, H 6.37%, N 8.86%, S 10.12%;

found: C 64.37%, H 6.26%, N 8.70%, S 10.24%.

Example 217

N-acetyldehydro-3- (2-thienyl) alanine benzyloxyamide

M.p .: 142-144 ° C; Yield 47.5% of theory.

C [deep] 16H [deep] 16N [deep] 2O [deep] 3S

calculated: C 60.74%, H 5.10%, N 8.86%, S 10.13%;

found: C 60.60%, H 5.15%, N 8.99%, S 10.04%.

Example 218

N-acetyldehydro-3- (2-thienyl) alanine-2-hydroxyethylamide phosphate

M.p .: 180-182 ° C; Yield 35.9% of theory.

C [deep] 11H [deep] 15N [deep] 2O [deep] 6PS times H [deep] 2O

calc .: C 37.50%, H 4.86%, N 7.95%, P 8.79%, S 9.11%;

Found: C 36.96%, H 4.78%, N 7.99%, P 8.69%, S 8.91%.

Example 219

N-acetyldehydro-3- (2-thienyl) alanine morpholide

M.p .: 159 ° C; Yield 82.7% of theory.

C [deep] 13H [deep] 16N [deep] 2O [deep] 3S

calculated: C 55.69%, H 5.75%, N 9.99%, S 11.22%;

found: C 55.80%, H 5.73%, N 10.09%, S 11.22%.

Example 220

N-acetyldehydro-3- (2-thienyl) alanine propargylamide

M.p .: 202-204 ° C; Yield 72% of theory.

C [deep] 12H [deep] 12N [deep] 2O [deep] 2S

calculated: C 58.05%, H 4.87%, N 11.28%, S 12.91%;

found: C 57.96%, H 4.9%, N 11.33%, S 12.96%.

Example 221

N-acetyldehydro-3- (2-thienyl) alanine-3,4,5-trimethoxyanilide

M.p .: 203-205 ° C; Yield 51.3% of theory.

C [deep] 18H [deep] 20N [deep] 2O [deep] 5S

calculated: C 57.43%, H 5.36%, N 7.44%, S 8.52%;

found: C 57.50%, H 5.32%, N 7.39%, S 8.63%.

Example 222

N-acetyldehydro-3- (2-thienyl) alanine-2- (benzothiazol-2-yl) hydrazide

M.p .: 183-185 ° C; Yield 22% of theory.

C [deep] 16H [deep] 14N [deep] 4O [deep] 2S [deep] 2

calculated: C 53.61%, H 3.94%, N 15.63%, S 17.89%;

found: C 53.41%, H 4.06%, N 15.45%, S 17.89%.

Claims (8)

1) Tumor- and / or tissue-dissolving drug, characterized by a content of at least one dehydrooligopeptide. 2) Tumor- and / or tissue-dissolving medicament, characterized by a content of at least one dehydrooligopeptide of the general formula (I) in which R [deep] 1 for a hydrogen atom, an optionally substituted alkanoyl group, an optionally substituted alkenoyl group, an alkoxycarbonyl group, an optionally substituted aroyl group, an optionally substituted aralkanoyl group or aralkenoyl group, an aralkoxycarbonyl group, a carbamoyl group, an optionally substituted heteroaroyl group, an optionally substituted lower alkylsulfonyl group or an optionally substituted arylsulfonyl group stands, R [deep] 2, R [deep] 7 and R [deep] 12 each for a hydrogen atom, represents a lower alkyl group or in which R [deep] 2, R [deep] 7 or R [deep] 12 together with the respective adjacent substituents R [deep] 3 or R [deep] 8 or R [deep] 14 is an alkylene chain with three to form four carbon atoms, R [deep] 4 and R [deep] 9 each represent a hydrogen atom or stand for a lower alkyl group, R [deep] 3, R [deep] 8 and R [deep] 13 each for a hydrogen atom, a lower straight or branched chain optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted aralkyl or aralkenyl group, an optionally substituted cycloalkyl or cycloalkenyl group, an indolylmethyl group, an optionally substituted heterocyclic methyl group with four to seven ring members and one to two heteroatoms, R [deep] 5 and R [deep] 10 each represent a hydrogen atom or an optionally substituted lower alkyl group, R [deep] 6 and R [deep] 11 each represent an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heterocycle with five to seven ring members and one to two heteroatoms, for an optionally substituted aralkyl group, an optionally substituted aralkenyl group or in which R [deep] 6 and / or R [deep] 11 in connection with R [deep] 5 or R [deep] 10 represent an optionally substituted alkylene or alkenylene chain with three to seven carbon atoms, R [deep] 14 represents a hydrogen atom, an optionally substituted lower alkyl group or in connection with R [deep] 13 and the carbon atom between them represents an alicyclic having four to seven carbon atoms, R [deep] 15 for a hydroxyl group, an optionally substituted lower alkoxy or alkenyloxy group, an optionally substituted lower alkylthio or alkenylthio group, an optionally substituted arylthio group, an optionally substituted hydrazino group, an amino group, a lower optionally substituted alkylamino or dialkylamino group or alkenylamino or dialkenylamino group or alkynylamino group, for an optionally substituted arylamino group, an optionally substituted mono- or diaralkylamino group, a nitrogen-containing optionally substituted heterocycle with four to seven ring members, in which one to two further heteroatoms can be contained, or for an amino group substituted by optionally substituted alicyclics with three to seven ring members, or stands for an aralkyloxyamino group, m, n, p and q stand for the digits 0 or 1 with the proviso that not all four letters may be 1 at the same time, or by the content of a corresponding pharmaceutically acceptable salt. 3) Process for the production of a tumor- and / or tissue-dissolving agent, characterized in that dehydrooligopeptides are mixed with inert, non-toxic, pharmaceutically suitable carriers. 4) Process for the production of a tumor and / or tissue dissolving agent, characterized in that dehydrooligopeptides according to claim 2 are mixed with inert, non-toxic, pharmaceutically suitable carriers. 5) A method for the lysis of human and / or animal tissues and / or tumors, characterized in that dehydrooligopeptides are administered to humans or animals suffering from tissue damage and / or tumors. 6) A method for the lysis of human and / or animal tissues and / or tumors, characterized in that dehydrooligopeptides according to the formula in claim 2 are administered to people or animals suffering from tissue damage and / or tumors. 7) Use of dehydrooligopeptides in combating human or animal tumors and / or tissue damage. 8) Use of dehydrooligopeptides according to the formula (I) in claim 2 in combating human or animal tumors and / or tissue damage.