NO149350B - ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE TIOPROPANOYLAMINO ACID DERIVATIVES - Google Patents
ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE TIOPROPANOYLAMINO ACID DERIVATIVES Download PDFInfo
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- NO149350B NO149350B NO781581A NO781581A NO149350B NO 149350 B NO149350 B NO 149350B NO 781581 A NO781581 A NO 781581A NO 781581 A NO781581 A NO 781581A NO 149350 B NO149350 B NO 149350B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims abstract 4
- 239000002253 acid Substances 0.000 title abstract description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 239000007858 starting material Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- -1 isobutyryl Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- BSSHPGFCFFVDGF-UHFFFAOYSA-N 1-(4-oxopentanethioylamino)cyclopentane-1-carboxylic acid Chemical compound CC(=O)CCC(=S)NC1(C(O)=O)CCCC1 BSSHPGFCFFVDGF-UHFFFAOYSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 101800000734 Angiotensin-1 Proteins 0.000 description 2
- 102400000344 Angiotensin-1 Human genes 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- JQYHADKHRNFBQE-UHFFFAOYSA-N 1-(3-sulfanylpropanoylamino)cyclopentane-1-carboxylic acid Chemical compound SCCC(=O)NC1(C(=O)O)CCCC1 JQYHADKHRNFBQE-UHFFFAOYSA-N 0.000 description 1
- NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 description 1
- IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000001595 contractor effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Analogifremgangsmåte for fremstilling av terapeutisk aktive tiopropanoylaminosyre-derivater.Analogous process for the preparation of therapeutically active thiopropanoylamino acid derivatives.
Description
Denne oppfinnelse angår fremstilling av nye tiopropanoyl-aminosyrederivater med formelen This invention relates to the preparation of new thiopropanoyl amino acid derivatives with the formula
I formel I og i det følgende har symbolene de nedenfor In formula I and in what follows, the symbols have those below
angitte betydninger. indicated meanings.
1*2 og R.j er hver hydrogen eller lavere alkyl. ;R^ er hydrogen, lavere alkanoyl eller benzoyl. ;De lavere alkylgrupper er lineære eller forgrenede hydrokarbon-radikaler med opptil 7 karbonatomer, f.eks. metyl, etyl, propyl, isopropyl, butyl, sek.butyl o.l. ci~C4~°9 særlig C^-C2_alkylgrupper foretrekkes. ;De lavere alkanoylgrupper er acylradikalene av de lavere ( C2~ Cj) fettsyrer, f.eks. acetyl, propionyl, butyryl, isobutyryl o.l. De nevnte betydninger, og særlig acetyl, foretrekkes. ;I en foretrukket forbindelse med formel I er R2, R3 og R^;alle hydrogen. ;Forbindelsene med formel I fremstilles i henhold til oppfinnelsen fra aminosyreforbindelser med formelen ;ved omsetning av en slik syre med et halogenpropanoylhalogenid med formelen hvor hver X er halogen, fortrinnsvis klor eller brom, for å danne et mellomprodukt med formelen Behandling av dette mellomprodukt med et merkaptan gir et produkt med formelen ;R4 er i dette tilfelle forskjellig fra hydrogen, dvs. acylgruppene lavere alkanoyl eller benzoyl. Ved behandling av acylderivatet med formel VI med ammoniakk eller konsentrert ammoniumhydroksyd, dannes en forbindelse med formel VI hvor R4 er hydrogen. ;Ytterligere detaljer vil fremgå av eksemplene. ;Aktiviteten av inhibitorer for angiotensin-omdannende ;enzym uttrykkes som I^q* som er mengden av inhibitor i |jg/ml som er nødvendig for å hemme med 50% aktiviteten av angiotensin-omdannende enzym som målt ved spektrofotometrisk måling. 1*2 and R.j are each hydrogen or lower alkyl. R 1 is hydrogen, lower alkanoyl or benzoyl. ;The lower alkyl groups are linear or branched hydrocarbon radicals with up to 7 carbon atoms, e.g. methyl, ethyl, propyl, isopropyl, butyl, sec.butyl etc. C1~C4~9 especially C1-C2_alkyl groups are preferred. The lower alkanoyl groups are the acyl radicals of the lower (C2~Cj) fatty acids, e.g. acetyl, propionyl, butyryl, isobutyryl, etc. The aforementioned meanings, and especially acetyl, are preferred. In a preferred compound of formula I, R 2 , R 3 and R 4 are all hydrogen. ;The compounds of formula I are prepared according to the invention from amino acid compounds of the formula ;by reacting such an acid with a halopropanoyl halide of the formula where each X is halogen, preferably chlorine or bromine, to form an intermediate of the formula Treatment of this intermediate with a mercaptan gives a product with the formula ;R4 is in this case different from hydrogen, i.e. the acyl groups lower alkanoyl or benzoyl. When treating the acyl derivative of formula VI with ammonia or concentrated ammonium hydroxide, a compound of formula VI is formed where R4 is hydrogen. ;Further details will appear from the examples. The activity of angiotensin-converting enzyme inhibitors is expressed as I^q* which is the amount of inhibitor in µg/ml required to inhibit by 50% the activity of angiotensin-converting enzyme as measured by spectrophotometric measurement.
EC^0 er konsentrasjonen av prøveforbindelsen som frembringer EC^0 is the concentration of the test compound that produces
50% hemning av angiotensin I's kontraktile virkning. For en særlig foretrukket forbindelse ble følgende verdier oppnådd: 50% inhibition of angiotensin I's contractile effect. For a particularly preferred compound, the following values were obtained:
De nye forbindelser er inhibitorer for angiotensin-omdannende enzym og er nyttige som hypotensive midler, særlig for reduksjon av angiotensin-avhengig hypertensjon. Ved administrering av et preparat inneholdende én eller flere inhibitorer med formel I for angiotensin-omdannende enzym til et hypertensivt pattedyr, griper den inn i renin —> angiotensin I —> angiotensin II forløpet, og hypertensjonen reduseres eller lindres. The new compounds are inhibitors of angiotensin-converting enzyme and are useful as hypotensive agents, particularly for the reduction of angiotensin-dependent hypertension. When a composition containing one or more angiotensin-converting enzyme inhibitors of formula I is administered to a hypertensive mammal, it interferes with the renin —> angiotensin I —> angiotensin II pathway and the hypertension is reduced or alleviated.
En enkel dose, eller fortrinnsvis 2-4 separate daglige A single dose, or preferably 2-4 separate daily doses
doser, administrert på grunnlag av ca. 1 til 1000 mg pr. kg pr. dag og særlig ca. 10 til 200 mg pr. kg pr. dag, er passende for å frembringe en reduksjon i forhøyet blodtrykk. Dyremodell-forsøkene som er beskrevet av Engel et al., Proe. Soc. Exp. Biol. doses, administered on the basis of approx. 1 to 1000 mg per kg per day and especially approx. 10 to 200 mg per kg per day, is appropriate to produce a reduction in elevated blood pressure. The animal model experiments described by Engel et al., Proe. Soc. Exp. Biol.
Med. 143, 483 (1973) gir en verdifull rettledning. With. 143, 483 (1973) provides valuable guidance.
Preparatene administreres fortrinnsvis oralt, men kan The preparations are preferably administered orally, but can
også administreres subkutant, intramuskulært, intravenøst eller intraperitonealt. Forbindelsen eller forbindelsene med formel I kan tilberedes som tabletter, kapsler eller eliksirer for oral administrering. Sterile oppløsninger eller suspensjoner kan anvendes for parenteral bruk. also administered subcutaneously, intramuscularly, intravenously or intraperitoneally. The compound or compounds of formula I may be prepared as tablets, capsules or elixirs for oral administration. Sterile solutions or suspensions can be used for parenteral use.
Ca. 50 til 1500 mg av en forbindelse eller forbindelser About. 50 to 1500 mg of a compound or compounds
med formel I kan blandes med et fysiologisk godtagbart bæremiddel, hjelpestoff, bindemiddel, konserveringsmiddel, stabiliserings-middel, smaksstoff o.l., i en vanlig enhetsdoseform slik som normalt benyttes i farmasøytisk praksis. Mengden av aktivt stoff velges slik at man får en dosering i det angitte område. with formula I can be mixed with a physiologically acceptable carrier, excipient, binder, preservative, stabilizer, flavoring agent, etc., in a common unit dosage form as is normally used in pharmaceutical practice. The amount of active substance is chosen so that a dosage is obtained in the specified range.
De følgende eksempler illustrerer oppfinnelsen og represen-terer foretrukne utførelsesformer. Alle temperaturer er i °C. The following examples illustrate the invention and represent preferred embodiments. All temperatures are in °C.
Eksempel 1 Example 1
1-[ ( 3- acetyltiopropanoyl) amino] cyklopentan- karboksylsyre 1-[(3-Acetylthiopropanoyl)amino]cyclopentanecarboxylic acid
1-aminocyklopentan-l-karboksylsyre (6,45 g) oppløses i 1-Aminocyclopentane-1-carboxylic acid (6.45 g) is dissolved in
50 ml IN natriumhydroksyd-oppløsning og omrøres i et isbad. Til denne oppløsning settes 25 ml 2N natriumhydroksyd-oppløsning, umiddelbart fulgt av 8,5 g 3-brompropionylklorid. Badet fjernes, og pH er ca. 7. Noen krystaller kommer ut av oppløsningen. 50 ml IN sodium hydroxide solution and stirred in an ice bath. To this solution is added 25 ml of 2N sodium hydroxide solution, immediately followed by 8.5 g of 3-bromopropionyl chloride. The bath is removed, and the pH is approx. 7. Some crystals come out of the solution.
Efter 3,5 timer ved romtemperatur tilsettes 54 ml IN natrium-hydroksydoppløsning, og alt går i oppløsning. Derefter tilsettes umiddelbart 4,12 g tioleddiksyre. Ytterligere 5 ml IN natrium-hydroksyd tilsettes for å bringe pH til nær 8. Efter henstand natten over surgjøres blandingen med konsentrert saltsyre, ekstraheres med etylacetat, tørres over magnesiumsulfat og konsentreres til tørrhet i vakuum. Produktet, 1-[(3-acetyltiopropanoyl) amino]cyklopentan-karboksylsyre, krystalliseres først fra etylacetat og heksan. Det erholdte materiale omkrystalliseres så fra etylacetat, utbytte 3,655 g, sm.p. 127-128°. After 3.5 hours at room temperature, 54 ml of IN sodium hydroxide solution are added, and everything dissolves. 4.12 g of thiolacetic acid are then added immediately. A further 5 ml of 1N sodium hydroxide is added to bring the pH to close to 8. After standing overnight, the mixture is acidified with concentrated hydrochloric acid, extracted with ethyl acetate, dried over magnesium sulfate and concentrated to dryness in vacuo. The product, 1-[(3-acetylthiopropanoyl)amino]cyclopentanecarboxylic acid, is first crystallized from ethyl acetate and hexane. The material obtained is then recrystallized from ethyl acetate, yield 3.655 g, m.p. 127-128°.
E ksempel 2 Example 2
1-[( 3- merkaptopropanoyl) amino] cyklopentan- karboksylsyre 1-[(3- mercaptopropanoyl) amino] cyclopentane carboxylic acid
Produktet fra eksempel 1 (1,04 g) behandles i 1 time, under et argonteppe, med en oppløsning av 2,4 ml vann og 1,6 ml konsentrert ammoniumhydroksydoppløsning. Reaksjonsblandingen fortynnes med vann, ekstraheres to ganger med etylacetat, den vandige fase surgjøres med konsentrert saltsyre og ekstraheres inn i etylacetat. Etylacetatekstrakten tørres over magnesiumsulfat og konsentreres The product from example 1 (1.04 g) is treated for 1 hour, under an argon blanket, with a solution of 2.4 ml of water and 1.6 ml of concentrated ammonium hydroxide solution. The reaction mixture is diluted with water, extracted twice with ethyl acetate, the aqueous phase is acidified with concentrated hydrochloric acid and extracted into ethyl acetate. The ethyl acetate extract is dried over magnesium sulfate and concentrated
i vakuum. Produktet, 1-[(3-merkaptopropanoyl)amino]cyklopentan- in vacuum. The product, 1-[(3-mercaptopropanoyl)amino]cyclopentane-
karboksylsyre , krystalliseres fra etylacetat og omkrystalliseres fra acetonitril, utbytte 343 mg, sm.p. 175-176°C. carboxylic acid, crystallized from ethyl acetate and recrystallized from acetonitrile, yield 343 mg, m.p. 175-176°C.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO781581A NO149350C (en) | 1978-05-03 | 1978-05-03 | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE TIOPROPANOYLAMINO ACID DERIVATIVES |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO781581A NO149350C (en) | 1978-05-03 | 1978-05-03 | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE TIOPROPANOYLAMINO ACID DERIVATIVES |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO781581L NO781581L (en) | 1979-11-06 |
| NO149350B true NO149350B (en) | 1983-12-27 |
| NO149350C NO149350C (en) | 1984-04-04 |
Family
ID=19884202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO781581A NO149350C (en) | 1978-05-03 | 1978-05-03 | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE TIOPROPANOYLAMINO ACID DERIVATIVES |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO149350C (en) |
-
1978
- 1978-05-03 NO NO781581A patent/NO149350C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO781581L (en) | 1979-11-06 |
| NO149350C (en) | 1984-04-04 |
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