CA1106397A - 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid derivatives and a process for the preparation thereof - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

New 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid derivatives of the general formula /I/, /I/

wherein R is a C2-4 alkenyl group, a C3-8 cycloalkyl group, phenyl group or a C1-6 alkyl group having optionally a C1-4 alkoxy, hydroxy, carboxy and/or amino substituent, with the proviso that if R is an unsubstituted alkyl group, this group contains at least 5 carbon atoms, are prepared by reacting 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid or a salt thereof with an amine of the general formula /II/, wherein R is as defined above. The new compounds of the invention exert dopamine-.beta.-hydroxylase inhibiting effects.

Description

This invention relates to new 2-amino-cyclopcnt-1-ene-1-dithiocar-boxylic acid derivatives and pharmaceutical compositions containing the same, furthermore to a process for the preparation thereof.
The novel compounds according to the invention correspond to the general formula I
NH-R

~ - CSSH

wherein R is a C2 ~ alkenyl group, a C3 8 cycloalkyl group, phenyl group or a Cl 6 alkyl group having optionally a Cl ~ alkoxy, hydroxy, carboxy and/or amino substituent, ~ith the proviso that if R is an unsubstituted alkyl group, this group contains at least 5 carbon atoms.
One aspect of the invention is a process for the preparation of a

2-amino-cyclopent-1-ene-1-dithiocarboxylic acid compound of the general formula I, Nlll R
CSSH

and pharmaceutically acceptable salts thereof, wherein R is a C2 4 alkenyl group, a C3 8 cycloalkyl group, phenyl group or a Cl 6 alkyl group which is unsubstituted or is substituted by a Cl ~ alkoxy, hydroxy, carboxy or amino substituent, with the proviso that if R is an unsubstituted alkyl group, this group contains at least 5 carbon atoms, which process comprises reacting 2-amino-cyclopent-l-ene-l-dithiocarboxylic acid or a salt thereof with an amine of the general formula II, wherein R is as defined above to obtain the acid of formula I or a salt thereof and, if required, converting a salt to the free acid or, if required, converting the free acid to a pharmaceutically acceptable salt.
The novel compounds of formula I exert dopamine-~-hydroxylase in-hibiting effect.
As known, substances influencing nervous functions exert their -1- ~

activities almost exclusively on the level of the stimulus transfer process-es. These processes are relatively known, thus it is possible to prepare compounds by which such processes can be influenced in a more or less con-trolled manner. The intervention into elementary nervous processes involves, howeverJ not only the influencing of the nervous system itself, but also influencing the processes being under the control of the nervous system.
The efforts made in this respect in the last few years also encompass the research work performed in connection with dopamine-~-hydroxylase and , `~ - la -.

~ ~6~

compounds inhibiting its effects.
Dopamine-~-hydroxylase catalyzes the last enzymatic step of the biosynthesis of noradrenaline, the conversion oE dopamine into noradrenaline.
The normal level of noradrenaline, a substance playing an essential role in the transport processes of symphatic ncrvous stimuli, is an essential factor with respect to the normal nervous functions and to the normal functions of processes being under the control of the nervous system.
Substances with dopamine-~-hydroxylase inhibiting effects enable one to influence the noradrenergic functions. This fact is of great importance with respect of both research work and therapy, since, in the field of research work, the consequences of the partial or total extinction of noradrenergic functions can be examined by decreasing the noradrenaline level with dopamine-~-hydroxylase inhibitors, and, in the field of therapy, the hyperfunction of the noradrenergic system can be compensated with dopamine-~-hydroxylase inhibitors. To our recent knowledge dopamine-~-hydro-xylase inhibitors can be applied in the therapy of hypertension and Parkin-sonism.
As known, benzyloxyamine and benzylhydrazine exert dopamine-~-hy-droxylase inhibiting effects /van der Schoot et al.: Advances in Drug Research, Vol. 2, p. 47; Harper and Simmons, Nikodijevic et al.: J. Pharm.
Exp. Ther. 140, 224 /1963/7. These compounds, however, exert their activities for a short period, thus they are not applied in the therapy.
Disulfiram and diethyl dithiocarbamate, the reduction metabolite of the - former compound !Goldstein et al.: Life Sci. 3, 763 /1964/7, furthermore several N,N-disubstituted dithiocarbamates /Maj et al.: Eur. J. Pharmacol.
9, 183 /1970/; Lippman et al.: Arch. Int. Pharmacodyn. Ther. 189, 348 /1971/7 are substances known to exert strong dopamine-~-hydroxylase inhibiting effects~ 2,2-Dipyridyl proved to be also effective under in vitro conditions /Green: Biochim. Biophys. Acta 81, 394 /1964/7. Bis/l-methyl-4-homopipera-zinyl-thiocarbonyl/-disulfide is one of the most potent dopamine-~
,, : ~k ;3~7 :

-hydroxylase inhibitors under in vivo conditions ~Florvall et al : Acta.
Pharmaceut. Sulcica 7, 7 /1970~7. Aromatic and alkyl thiourea derivatives exert long-acting dopamine-~-hydroxylase inhibiting effects /Johnson et al.:
J. Pharm. Exptl. Ther. 171, 80 /1970/7.
Of the microbial substances fusaric acid /5-butylpicolinic acid/
and its derivatives /Hidaka et al.: Molec. Pharmacol. 9, 172 /1973/7, oosponol /Umezawa et al.: J. Antibiotics 25, 239 /1972/7 and dopastine Iinuma et al.: J. Agr. Biol. Chem. 38, 2107 /1974/7 are known to exert strong dopamine-~-hydroxylase inhibiting effects.
Subsequent examina-tions have shown that some of the kno~n and commercially available drugs, such as hydralazine, methimazol and amphetamine, also possess dopamine-~-hydroxylase inhibiting effects.
Most of the above compounds have, however, the disadvantage that although they possess dopamine-~-hydroxylase inhibiting effects, they are rather toxic in prolonged treatments, thus they can be applied in the therapy in a res~ricted manner, if at all.
The new compounds according to the invention possess strong dopamine-~-hydroxylase inhibiting effects and are less toxic than the known compounds with similar activities. Consequently the new compounds can be applied to great advantage in the therapy.
The dopamine-~-hydroxylase inhibiting effects of the new compounds ; according to the invention were examined by the following tests:
The tests were perEormed on male Wistar rats weighing 150 to 200 g. The dopamine-~-hydroxylase inhibiting effects of the compounds were evaluated by determining the change of noradrenaline, dopamine and adrenaline levels of the cerebrum, heart, spleen and adrenal gland.
The serotonine and 5-hydroxy-indolyl-acetic acid levels of the cerebrum were also determined. The measurements were performed as follows:

9~

- ~ -The animals were decapitated, the cerebrum, heart, spleen and adrenal gland were removed quickly, and the organs were frozen by ; placing them onto a metal sheet cooled with dry ice. The frozen organs were stored for maximum one night at -20C.
' Determination of the adrenaline content of adrenal gland The adrenal glands were freed f:rom fat and homogenized in 3.0 ml of ice-cold O.~ n perchloric acid. The homogenized mixtures were centrifuged for 10 minutes at 0C with a speed of 3200 r.p.m. on a Janetzky K-70 type centrifuge. 0.05 ml samples were taken from the supernatant, and the adrenaline level was determined directly by the method of Laverty et al.
/Anal. Biochem, 22, 269 /1968/7.
'Determination'of the noradrenaline content of heart and spleen ;' The organs were weighed in frozen state and then homogenized in 5.0 ml of 0.~ n perchloric acid containing 0.05% of EDTA-Na2 and 0.1% of ` Na2S2O5. The homogenized mixtures were centrifuged as described above for the treatment of adrenal gland, the supernatants were decanted, and the pH was adjusted to 8.0+0.1 with a 0.1 molar tris buffer containing 20 g/l of NaOH and 25 g/l of EDTA-Na2 lO0 mg of prepared A1203 ~Anton et al.: J. Pharm. Ther. 138, 360 /1962/7 were added to the samples, and the ; 20 mixtures were shaken mechanically for 20 minutes. Thereafter A12O3 was washed with 2x10 ml of distilled water, and the noradrenaline was eluted ' with 1.0 ml of 0.05 n perchloric acid, 0.5 ml samples of ~he eluate were applied for the determination of noradrenaline. Noradrenaline was determlned according to the method of Shellenberger et al. !Anal.
Biochem~'39~ 356 /1971!7, with the following modifications of the basic ' procedure: 0.5 ml of 0.1 molar Na-K-phosphate buffer, containing 9 g/l of FDTA-Na2, were added to 0.5 ml of the eluate, and the catecholamines ~ /noradrenaline in the examination of heart and spleen and noradrenaline and .~ dopamine in the examination of the cerebrum/ were oxidized with 0.1 ml of a 0.1 n iodine solu-tion in 5% potassium iodide. After exactly 2 minutes ' ,

3~317 oxidation was stopped by adding 0.25 ml oE a 2.5% sodium sulfite solution in 4.4 n aqueous sodium hydroxide to the mixture. 2 minutes after the introduction of the alkaline sulfite solution 0.2 ml of concentrated acetic acid were added to the samples, upon which the pH decreased to 4.4 to

4.5. Thereafter the samples were placed Eor 5 minutes into a drying oven heated to 100C, and then the samples were cooled with ice water. The fluorescency of noradrenaline was measured with an OPTON spectrophotometer at wavelengths of 390 nm /excitation/ and 490 nm /emission/.
Determination of the noradrenaline, dopamine, _erotonine and

5-hydroxy-indolylacetic acid contents of cerebrum The brains were homogenized in 10 parts by volume of 0.4 n perchloric acid. The homogenized mixture was stored at -20C overnight, thereafter it was thawed and centrifuged as described above. A sample of homogenized mixture corresponding to 0.5 g of brain was removed, the pH
of the sample was adjusted to 8.0~0.1 with O.l molar tris-buffer of the `- above composition, and the sample was processed as described above for the determination of the noradrenaline content of heart and spleen, with the difference that 1.5 ml of 0.05 n perchloric acid were applied as eluting agent. 0.5 ml of the eluate were applied to determine the noradrenaline and dopamine content. The measurement was performed as described above, with the difference that samples of 0.5 ml were applied for the recording of the fluorescency of noradrenaline. The residue was placed for 50 minutes into a drymg oven heated to 100C, thereafter the sample was cooled with ice water, and the fluorescency of dopamine was recorded at wavelengths of 325 nm /excitation/ and 380 nm /emlssion/.
In a further test series the serotonine and 5-hydroxy-indolylacetic acid contents were also determined, beside the determination of the noradrenaline and dopamine content, from the same sample. In this instance the b:rains were homogenized in 10 ml of 75% ethanol, 0.2 ml of EDTA-Na2 and 5% of ascorbic acid were added to the homogenized mixtures, ., ~

and the homogenized mixtures were maintained at -20C overnight, The mixtures were centrifuged as described above, and 5.0 ml samples of the supernatant were removed. The samples were diluted with equal volumes of distilled water, and poured onto ion exchange columns of O.5x1.5 cm dimensions, filled with buffered Amberlite* CG-30 /200 to 400 mesh/. The columns were washed with 5 ml of distilled water followed with l.0 ml of 0~2 n hydrochloric acid, and the first effluent and the aqueous wash were collected for the cletermination of 5-hydroxy-indolylacetic acid.
Elution was continued with further 1.2 ml of 0.2 n hydrochloric acid in order to remove noradrenaline, dopamine and serotonine. Samples of 0.3 ml were used for the determinations.
Noradrenaline and dopamine were determined by the method of Shellenberger, modified as described above, whereas serotonine was determined by the method of Curzon et al. /Brit. J. Pharmacol. 39, 653 /1970/7. The basic method was modified as follows: A 0.5% solution of ortho-phthal/di/aldehyde in absolute ethanol was diluted with lO n hydro-; chloric acid to 50-fold of its original volume, and 0.6 ml of the resulting 0,01% ortho-phthal/di/aldehyde solution were added immediately to 0.5 ml of the serotonine-containing sample. The sample was placed into a hot water bath for 10 minutes, thereafter cooled with tap water, and the fluorescency was recorded at wavelengths of 360 nm /excitation/ and 490 nm /emission/.
5-Hydroxy-indolylacetic acid was determined from the mixture of the first effluent and the aqueous wash. lO ml of distilled water and 0.2 ml of concentrated hydrochloric acid were added to the mixture, and the sample was poured onto a 0.8 x ~.0 cm column filled with Sephadex* G-lO.
The column was washed with 15 ml of 0.1 n hydrochloric acid followed by I,8 to 200 ml of 0.02 n aqueous ammonia, and then 5-hydroxy-indolylacetic acid was eluted with f`urther 2.0 ml of aqueous ammonia. 0.5 ml samples were used in the measurements, and the determination was performed *Trade Mark ;x ' , : .

according to the method oE Korf et al. !Biochem. Pharmacol. 20, 659 /1971/7.
The test results are summarized in Table 1. In the tests disulfiram, 2,2-dipyridyl, bis/1-methyl-4-homopiperazinyl-thiocarbonyl/-disulfide~ sodium diethyldithiocarbamate and N-phenyl-N'-/2-thiazolyl/-thiourea were applied as reference substances. The values indicated in Table 1 are the percentages in relation to the amine levels of the controls measured in the same tests /~ Standard Error/. The statistical calculations were performed on a TPA/i type computer, using Student's t test.
The meanings of the abbreviations used in Table 1 are as follows:
NA: noradrenaline DA: dopamine SE: serotonine 5-HIAA: 5-hydroxy-indolylacetic acid AD: adrenaline M-l: 2-/N-methoxyethyl/-amino-cyclopent-l-ene-dithiocarboxylic acid M-2: 2-/N-allyl/-amino-cyclopent-l-ene-dithiocarboxylic acid M-3: 2-/N-isoamyl/-amino-cyclopent-l-ene-dithiocarboxylic acid M-4: 2-/N-hydroxyethyl/-amino-cyclopent-l-ene-dithiocarboxylic acid M-5: 2-/N-/4-carboxy-4.-amino/-butyl7-amino-cyclopent-1-ene-dithiocarboxylic acid M-6: 2-/N-cyclohexyl/-amino-cyclopent-l-ene-dithiocarboxylic acid M-7: 2-!N-/5-carboxy-5-amino/-pentyl7-amino-cyclopent-1-ene-dithiocarboxylic acid M-8: 2-/N-phenyl/-amino-cyclopent-l-ene-dithiocarboxylic acid DS: disulfiram!bis(diethylthiocarbamoyl)-disulfide7 DDC-Na: sodium diethyldithiocarbamate 2,2-D: 2,2-dipyridyl ~LA-63: bis/1-methyl-4-homopiperazinyl/-thiocarbonyl-disulfide U-14624: N-phenyl-N'-/2-thiazolyl/-thiourea n = number of animals c~
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The data of Table 1 clearly demonstrate that the new compounds according to the invention considerably decrease the noradrenaline level in the brainO Depending on the dosage, the method of administration and the duration of treatment, the extent of decrease is 50 to 70 %. At the same time a considerable /20 to 30%t incrcase in dopamine level can also be observed. The increase of serotonine level is less significant, the 5-hydroxy-indolylacetic acid level increases, however, occasionally by 50 to go %, The noradrenaline levels of heart and spleen, and the adrenaline level of adrenal gland decrease as well, these decreases are, however, not always significant even for compounds strongly decreasing the cerebral noradrenaline level. This phenomenon can be attributed presumably to the fact that the catecholamine turnovers of these organs are slow, furthermore that adrenal gland possesses a relatively great depot of catecholamines /noradrenaline and adrenaline/, and the missing noradrenaline contents of spleen and heart are quickly supplemented by circulation. A unequivocal decrease of catecholamine level cannot be observed in these organs with -~ known dopamine-Ei-hydroxylase inhibitors, either.
- The toxicity data of the compounds according to the invention are as follows:
Table 2 ., .
Compound Animal Method of ad- LD50 mg/kg ,~ . . . mini strati on .
. ,~ - -- . ~. .
M-l mice i.p, ~400 M-2 mice i.p. ~500 - M-4 mice i,p. ~800 M-5 mice i.p. ~700 M-6 mice i.p. ~1000 M-7 mice i.p. ~900 M-8 mice i.p. ~1000 :

6;~9'7 Co3npound AnimalMethod o ad-LD m~/kg ministration 50 FLA-63 mice i.p. ~150 2,2-D mice i.p. 280 rats i.p. 150 Hydralazine mice i.p. 83 DS rats p.o. 8600 + 370 rabbitsp.o. 1800 ~ 130 Dopastine mice i.p. 250 - 500 i.p. 460 Fusaric acid mice p.o. 230 + 25 Chlorofusaric acid mice p.o. 470 + 85 Oosponol mice i.p. 40 p.o. 280 U-14624 mice i.p. ~680 .. p.o. >1000 The data of Table 2 indicate that the LD50 values of the new - compounds according to the invention are very favourable, thus these compounds can be administered for prolonged time, The new compounds of the general formula /I/ are prepared ; according to the in~ention by reacting 2-amino-cyclopent-1-ene-dithio-carboxylic acid or a salt thereof with an amine of the general formula /II/ ~

wherein R is as defined above. The reaction is performed in a manner known per se /Bordas et al.: J. Org. Chem. 37, 1727 /1972/7. 2-Amino-cyclopent-l~ene-dithiocarboxylic acid and the amines of the general formula /II/, applied as starting substances, are known compounds, , . ~. ~ , - . , - 12 _ The reaction is performed preferably in a solvent medium, such as in an inert organic solvent /e.g. an alcohol/ or in an aqueous inert organic solvent. The reaction is carried out preferably at elevated temperatures, particularly at the boiling point of the reaction mixture.
The invention is elucidated in detail by the aid of the following non-limiting Examples.
Example 1 2-/N-Allyl/-amino-cyclo~ent-l-ene-l-d _h ocarboxylic acld 6.0 g /0.2 moles/ of allylamine are added to a suspension of 7.1 g /0,04 moles/ of ammonium 2-amino-1-cyclopent-1-ene-1-dithiocarboxylate in 60 ml of methanol, and the mixture is refluxed for 3 hours. The mixture is cooled, diluted with 180 ml of water, decolourized with charcoal, and filtered.
The filtrate is acidified with 12 ml of acetic acid. The separated substance is filtered off, washed with water and dried in a vacuum desiccator.
The title compound, melting at 100-104C, is obtained with a yield of 48%.
Analysis:
;- Calculated: S: 32.3 %, N: 7.03 %
~ Found: S: 31.5 %, N: 6.7 %
; Example 2 2-/N-Isoamyl!-amino-cyclopent-l-ene-l-dithiocarboxylic acid 17.0 g /0.2 moles/ of isoamylamine are added to a solution of 12.6 g /0.08 moles/ of 2-am1no-cyclopent-l-ene-l-dithiocarboxylic acid in ; 120 ml of methanol. The mixture is refluxed for 3 hours, then it is cooled, diluted with 360 ml of water, and filtered. The filtrate is ` acidified with 12 ml of acetic acid. The separated solid is filtered off, washed with water, and taken up in a mixture of 30 ml of water and 20 ml of 10% sodium hydroxide solution. The non-dissolved substance is removed by filtration and the filtrate is acidified with acetic acid. The separated substance is filtered off, washed with water, and dried in a desiccator. The title compound, melting at 65-79C, is obtained with a yield of 3.62 %.

.

Analysis:
Calculated: S: 27.9 %, N: 6.1 %
Found: S: 27.5 %, N: 6.17%
Example 3 2-/N-/4-Carboxy-~-amino/-butyl7-amino-cyclopent-1-ene-1-dithiocarboxylic-acid A suspension of 3.36 g /0.02 moles/ of 2-ornithine hydrochloride and 5.0 g /0.06 moles/ of sodium hydrocarbonate in 50 ml of methanol and 15 ml of water is refluxed for 1.5 hours. Thereafter 20 ml of methanol and 3.52 g /0.02 moles/ of 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid ammonium salt are added to the mixture, and refluxing is continued for further 10 hours. The mixture is cooled, diluted with 200 ml of water, decolourized with charcoal, and filtered. The filtrate is acidified with 25 ml of acetic acid. The separated substance is filtered off, washed with water and dried in a desiccator. The title compound, melting at 155C, is obtained with a yield of 15.5 %.
Analysis:
Calculated: S: 23.4 %, N: 10.2 %
Pound: S: 26.04%, N: 7.86%
Example 4 2-/N-Methoxyethyl/-amino-cyclopent-l-ene-l-dithiocarboxylic acid 15.0 g /0.2 moles/ of 2-methoxyethylamine are added to a suspension of 12.6 g /0.08 moles/ of ammonium 2-amino-cyclopent-1-ene-1-dithiocarboxy-late in 120 ml of methanol. The mixture is refluxed for 3 hours, then it is cooled, diluted with 360 ml of water, and the hazy mixture is decolourized with charcoal. 12 ml /0.2 moles/ of acetic acid are added to the resulting light red solution. The separated yellow, amorphous substance is filtered off, washed with water, and dried in a vacuum desiccator. 6.1 g of the resulting crude product are taken up in 50 ml of water/ 20 ml of 10%
sodium hydroxide solution are added, and the mixture is stirred for some minutes~ The insolubles are filtered off on a rumpled filter and ~ 1~;16~9'7 :' washed with a small amount of water. The clear filtrate is admixed with acetic acid to precipitate the product completely. The precipitate is filtered off, washed with water, and dried in a desiccator. The title ; compound, melting at 64-70C, is obtained with a yield of 35.7 %.
: Analysis:
Calculated: S: 2904 %, N: 6.45 %
Found: S: Z9.4 %, N: 5.81 ~ .

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Claims (19)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for the preparation of a 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid compound of the general formula I, I

and pharmaceutically acceptable salts thereof, wherein R is a C2-4 alkenyl group, a C3-8 cycloalkyl group, phenyl group or a C1-6 alkyl group which is unsubstituted or is substituted by a C1-4 alkoxy, hydroxy, carboxy or amino substituent, with the proviso that if R is an unsubstituted alkyl group, this group contains at least 5 carbon atoms, which process comprises reacting 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid or a salt thereof with an amine of the general formula II, wherein R is as defined above to obtain the acid of formula I or a salt there-of and, if required, converting a salt to the free acid or, if required, con-verting the free acid to a pharmaceutically acceptable salt.

2. A process according to claim 1 wherein the reactants are refluxed in methanol or aqueous methanol.

3. A process according to claim 1 or 2 wherein R is methoxyethyl.

4. A process according to claim 1 or 2 wherein R is allyl.

5. A process according to claim 1 or 2 wherein R is isoamyl.

6. A process according to claim 1 or 2 wherein R is hydroxyethyl.

7. A process according to claim 1 or 2 wherein R is (4-carboxy-4-amino)-.

8. A process according to claim 1 or 2 wherein R is cyclohexyl.

9. A process according to claim 1 or 2 wherein R is (5-carboxy-5-amino)-pentyl.

10. A process according to claim 1 or 2 wherein R is phenyl.

11. A compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof when prepared by a process according to claim 1 or an obvious chemical equivalent thereof.

12. A process for preparing 2-(N-allyl)-amino-cyclopent-1-ene-1-dithio-carboxylic acid which comprises reacting allylamine with ammonium 2-amino-cyclopent-1-ene-1-dithiocarboxylate.

13. The compound 2-(N-allyl)-amino-cyclopent-1-ene-1-dithiocarboxylic acid when prepared by a process according to claim 12 or an obvious chemical equivalent thereof.

14. A process for preparing 2-(N-isoamyl)-amino-cyclopent-1-ene-1-dithiocarboxylic acid which comprises reacting isoamylamine with 2-amino-cyclopent-1-ene-dithiocarboxylic acid.

15. The compound 2-(N-isoamyl)-amino-cyclopent-1-ene-1-dithiocarboxylic acid when prepared by a process according to claim 14 or an obvious chemical equivalent thereof.

16. A process for preparing 2-[N-(4-carboxy-4-amino)-butyl]-amino-cyclopent-1-ene-1-dithiocarboxylic acid which comprises reacting ornithine with 2-amino-cyclopent-1-ene-1-dithiocarboxylic acid ammonium salt.

17. The compound 2-[N-(4-carboxy-4-amino)-butyl]-amino-cyclopent-1-ene-1-dithiocarboxylic acid when prepared by a process according to claim 16 or an obvious chemical equivalent thereof.

18. A process for preparing 2-(N-methoxyethyl)-amino-cyclopent-1-ene-1-dithiocarboxylic acid which comprises reacting 2-methoxyethylamine with ammonium 2-amino-cyclopent-1-ene-1-dithiocarboxylate.

19. The compound 2-(N-methoxyethyl)-amino-cyclopent-1-ene-1-dithio-carboxylic acid when prepared by a process according to claim 18 or an obvious chemical equivalent thereof.