NO159448B - Analogifremgangsmaate ved fremstilling av terapeutisk aktivt n-(2-(((5-dimetylamino)-metyl-2-furanyl)-metyl)-tio)-etyl)-n'-(3,4-metylendioksybenzyl)-2-nitro-1,1-etendiamin - Google Patents
Analogifremgangsmaate ved fremstilling av terapeutisk aktivt n-(2-(((5-dimetylamino)-metyl-2-furanyl)-metyl)-tio)-etyl)-n'-(3,4-metylendioksybenzyl)-2-nitro-1,1-etendiamin Download PDFInfo
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- NO159448B NO159448B NO822801A NO822801A NO159448B NO 159448 B NO159448 B NO 159448B NO 822801 A NO822801 A NO 822801A NO 822801 A NO822801 A NO 822801A NO 159448 B NO159448 B NO 159448B
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- Prior art keywords
- methyl
- furanyl
- ethyl
- dimethylamino
- preparation
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- 238000000034 method Methods 0.000 title claims abstract description 8
- -1 3,4-METHYLENDIOXYBENZYL Chemical class 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title claims abstract description 4
- BSGRLBPZSRZQOR-UHFFFAOYSA-N ethene-1,1-diamine Chemical compound NC(N)=C BSGRLBPZSRZQOR-UHFFFAOYSA-N 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 3
- 150000007524 organic acids Chemical class 0.000 claims abstract description 3
- 235000005985 organic acids Nutrition 0.000 claims abstract 2
- JFGCGQJHMUYGLU-UHFFFAOYSA-N 2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethanamine Chemical compound CN(C)CC1=CC=C(CSCCN)O1 JFGCGQJHMUYGLU-UHFFFAOYSA-N 0.000 claims description 2
- 230000001562 ulcerogenic effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 5
- 229960000620 ranitidine Drugs 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 3
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 230000002178 gastroprotective effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 description 1
- NXGHEDHQXXXTTP-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-2-nitroethene Chemical compound CSC(SC)=C[N+]([O-])=O NXGHEDHQXXXTTP-UHFFFAOYSA-N 0.000 description 1
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000000026 anti-ulcerogenic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- AMBKPYJJYUKNFI-UHFFFAOYSA-N methylsulfanylethene Chemical compound CSC=C AMBKPYJJYUKNFI-UHFFFAOYSA-N 0.000 description 1
- PXZIBUPXCUYYJL-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-1-methylsulfanyl-2-nitroethenamine Chemical compound [O-][N+](=O)C=C(SC)NCC1=CC=C2OCOC2=C1 PXZIBUPXCUYYJL-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Nye forbindelser med ulcerogen aktivitet, N- (2- ( ( (5-fli-metylamino)-metyl-2-furanyl)-metyl)-tio)-etyl)-N'-(3,4U metylendioksybenzyl)-2-nitro-l,l-eteridiamin med formelen (I). og deres addisjonssalter med farmasøytisk aksepterbare uorganiske eller organiske syrer. Fremgangsmåten ved fremstilling av forbindelsene er også beskrevet.
Description
Nærværende oppfinnelse vedrører analogi fremgangsmåte ved fremstilling av terapeutisk aktivt N-(2-(((5-dimetylamino)-metyl-2-f uranyl) -metyl) -tio) -etyl)' -N ' - (3 , 4-metylendioksy-benzyl)-2-nitro-l,1-etendiamin med formelen (I):
Oppfinnelsen vedrører således en fremgangsmåte ved fremstilling av forbindelsen med formel (I) og er særpreget ved at 2-( (2-aminoetyl)-tiometyl) -«-5*- (dimetylaminometyl) -^furan (II) omsettes med l^nitro-2-mety.ltio-2-(3,4-metylendioksy-benzylamino)-eten (III) ifølge nedenstående reaksjons^ skjema:
Omsetningen utføres i aprotiske oppløsningsmidlér, slik som klorerte hydrokarboner, ved temperaturer innen området 30 - 120°C, hensiktsmessig fra 50 - 100°C, så lenge som metylmerkaptan utvikles.
l-nitro-2-metyltio-2-^ (3,4-metylendioksybenzylamino)-eten
(III) kan erholdes ved kondensasjon av 4,4-^metylendioksy^
benzylamin (IV) med l-nitro-2,2-di(metyltio)-eten (V):
Forbindelsen med formel (I) oppviser en meget høy antiulce-rogen aktivitet, sammenlignbar med den for meget velkjente forbindelser med analog struktur, slik som cimetidin og ranitidin. Forbindelsen (I) oppviser en annen fordel, nem-lig en lang farmakologisk virkning.
Forbindelse (I) har en meget lav akutt giftighet, både hos mus og rotter: LD5q verdiene pr. os er henholdsvis høyere enn 3 000 og 5 000 mg/kg.
EKSEMPEL
a) l-nitro-3-metyltio-2-(3,4-metylendioksybenzylamino)-
eten ( III)
16,1 g l-nitro-2,2-dimetyltio-eten (V) ble oppløst i 100 ml tilbakeløpende 1,1,2-trikloreten. Til den slik erholdte homogene oppløsning ble 7,5 g 3,4-metylendioksybenzylamin (III), oppløst i 40 ml av det samme oppløsningsmiddel, til-
satt i løpet av 30 minutter.
Reaksjonsblandingen ble tilbakeløpsbehandlet i 2 1/2 time, oppløsning"smidlet ble deretter inndampet under redusert trykk, resten ble renset ved kromatografi på en silikagel-kolonne, eluert med petroleter og deretter med diklormetan.
Det slik erholdte produkt ble krystallisert fra diklormetan og dietyleter. Smp. 118-119°C.
b) N-(2-(((5-dimetylamino)-metyl-2-furanyl)-metyl)-tio)-etyl)-N'-(3,4-metylendioksybenzyl)-2-nitro-l,1-eten-
diamin (!)
Til 10 g av forbindelse (III), oppløst i 100 ml 1,1,2-trikloreten, ble tilsatt 12 g 2-(aminoetyl-tiometyl)-5-(dimetylamino-metyl)-furan. Reaksjonsblandingen ble tilbakeløpsbe-handlet i 6 timer, oppløsningsmidlet ble derpå inndampet, og resten ble behandlet med dietyleter.
Det erholdte bunnfall ble isolert ved filtrering, oppløst
i etanol og igjen felt ut ved tilsetning av vann. Produk-
tet ble omkrystallisert fra etanol—vahn. Smp. 98-102°C.
Elementæranalyse:
for <C>20<H>26<N>4<0>5<S> (molekylvekt = 34 3,506)
Beregnet %: C = 55,29; H = 5,99; N = 12,90
Funnet %: C = 55,44; H = 6,07; N = 12,81
NMR spektrum bekrefter strukturen for produktet (intern
standard TMS; oppløsningsmiddel uMSO):
2,1 6, S, 6H, (CH3)2N;
2,7 &, m, 4H, N-CH2-CH2-S
3,4 6, s, 2H, furyl-CH2-S;
3,7 6, d, 2H, fenyl-CH2-S;
3,85 <S, s, 2H, furyl-CH2~S;
4,3 i, s, 2H, 0-CH2-0;
6-7 <£, m, 6H, aromatisk + CHN02;
8 og 10 S, bredt s, 2H, NH.
Ifølge velkjente metoder kan addisjonssaltene av forbindelse (I) fremstilles med farmasøytisk fordragelige organisk eller uorganiske syrer, spesielt saltsyre, sitronsyre, malein-syre og vinsyre. Som angitt foran viste forbindelse (I) - som i det etterfølgende også vil bli definert med kodenavnet AP 880 for enkelthets skyld - seg å være utstyrt med en høy antiulcer-aktivitet, såvel som med en vesentlig lavere toksisitet enn den som utøves av farmasøytika med analog struktur, slik som vist ved de eksperimentelle resultater nedenfor. Ved toksisitets- og aktivitetsprøvene som er vist i nærværende beskrivelse ble AP 880 anvendt i form av citrat.
Toksisitet
Toksisiteten for AP 880 ved enkelt administrering er blitt undersøkt i sammenligning med toksisiteten for ranitidin hos mus, ved administrering av stadig større doser av for--bindelse (I) ad intraperitoneal vei. LD^q verdiene, bestemt i henhold til metoden av Litchfield and Wilcoxon (J. Pharm. Exp. Ther. 96-99, (1949)) er angitt i den føl-gende tabell
En vesentlig lavere toksisitet for AP 880 er vist i forhold til den for ranitidin under hensyntagen til anvendt admini-strasjonsvei og de eksperimentelle betingelser.
Gastrobes kyttende akt i v it e t
Den gastrobeskyttende aktivitet for AP 880 sammenlignet med ranitidin ved ekvimolekykære doser er blitt undersøkt hos rotter ifølge ulcer-prøven påført ved "immersion stress".
Hann-Wistar-rotter ble anvendt som veier 240-260 g og holdt fastende i 18 timer. Straks etter administreringen av forbindelsene som skal undersøkes ad oral vei ble dyrene immo-bilisert i et bur egnet til å fremkalle stress ifølge metoden til Takagi et al. Deretter ble buret neddykket lodrett i et vannbad ved 23-+ 1 oC i 7 timer inntil xipoidan-høyden. Deretter ble magene fjernet og lesjonsområdet for de samme mager ble beregnet for å bestemme lesjonsindeksen. Den gastrobeskyttende aktivitet for forbindelsene ble bestemt på basis av ED^Q som, etter sammenligning av resultatene, viste seg å være 25 mg/kg for begge prøveforbindelsene.
An t i u1cer- aktivitet
Evalueringen av aktiviteten for AP880 for dette forsøks-mønster ble bestemt hos rotter ifølge Shay-ulcerprøven,
ved sammenligning av den undersøkte forbindelse med ranitidin ved ekvimolekylære doser. Hann-Wistar-rotter som veier 220-240 g, og som hadde fastet i 48 timer ble holdt i enkelte bur med en bunn av bredmasket virenetting. Pylo-rus for de eter-anaestetiserte rotter ble oppbundet og forbindelsene ble straks administrert ad intraperitoneal vei. 18 timer etter behandlingen ble dyrene drept og deres mager ble fjernet for å bestemme perforeringsindeksen. Ulcer-symptomatologien for den gastiske mucosa ble vurdert ved hjelp av en indeks for vurderingen av lesjonene. Fra de erholdte resultater ble ED50 bestemt, hvilken er 50 mg/kg for begge de undersøkte forbindene under dé anvendte eksperimentelle betingelser.
Claims (1)
- Analogifremgangsmåte ved fremstilling av terapeutisk aktivt N- (2- ( ( (5-dimetylamino) -metyl-2-furanyl) -metyl) -tio) -etyl) -N'-(3,4- metylen-dioksybenzyl)-2-nitro-l,l-etendiamin med formelen (I) og deres addisjonssalter med farmasøytisk aksepterbare uorganiske eller organiske syrer, karakterisert ved omsetning av 2-((2-aminoetyl)tio-metyl)-5-(di-metylaminometyD -furan (II) med l-nitro-2-metyltio-2-(3,4-metylendioksybenzylamino)-"-eten (III) i henhold til det nedenstående reaksjonsskjerna:hvoretter en dannet forbindelse av formel (1) eventuelt om-dannes i et addisjonssalt.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT23546/81A IT1168163B (it) | 1981-08-18 | 1981-08-18 | Composto ad attivita' antiulcera, procedimento per la sua preparazione e composizioni farmaceutiche relative |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO822801L NO822801L (no) | 1983-02-21 |
| NO159448B true NO159448B (no) | 1988-09-19 |
| NO159448C NO159448C (no) | 1988-12-28 |
Family
ID=11208027
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO822801A NO159448C (no) | 1981-08-18 | 1982-08-17 | Analogifremgangsmaate ved fremstilling av terapeutisk aktivt n-(2-(((5-dimetylamino)-metyl-2-furanyl)-metyl)-tio)-etyl)-n'-(3,4-metylendioksybenzyl)-2-nitro-1,1-etendiamin. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4431664A (no) |
| JP (1) | JPS5859982A (no) |
| KR (1) | KR860000851B1 (no) |
| AR (1) | AR230444A1 (no) |
| AT (1) | AT383597B (no) |
| AU (1) | AU533719B2 (no) |
| BE (1) | BE894093A (no) |
| CA (1) | CA1182121A (no) |
| CH (1) | CH650259A5 (no) |
| DE (1) | DE3230265C2 (no) |
| DK (1) | DK156067C (no) |
| ES (1) | ES515068A0 (no) |
| FR (1) | FR2511675A1 (no) |
| GB (1) | GB2104071B (no) |
| GR (1) | GR76260B (no) |
| IT (1) | IT1168163B (no) |
| LU (1) | LU84340A1 (no) |
| NL (1) | NL186447C (no) |
| NO (1) | NO159448C (no) |
| PH (1) | PH19228A (no) |
| PT (1) | PT75440B (no) |
| SE (1) | SE448456B (no) |
| ZA (1) | ZA825718B (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1175808B (it) * | 1984-03-07 | 1987-07-15 | Ausonia Farma Srl | Procedimento per la preparazione di composto con attivita' antiulcera |
| IT1196133B (it) * | 1984-06-06 | 1988-11-10 | Ausonia Farma Srl | Derivati furanici con attivita' antiulcera |
| KR950009825B1 (ko) * | 1986-03-28 | 1995-08-29 | 자누스 화마스티씨 에스.알.엘. | 치료학적 항궤양 활성이 있는 니페로티딘의 합성방법 |
| GB8907700D0 (en) * | 1989-04-05 | 1989-05-17 | Fine Organics Ltd | Preparation of substituted ethenes |
| JPH0416036U (no) * | 1990-05-31 | 1992-02-10 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4140681A (en) * | 1974-11-08 | 1979-02-20 | Mitsubishi Chemical Industries, Limited | N2 -Arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
| US4233302A (en) * | 1977-12-23 | 1980-11-11 | Glaxo Group Limited | Amine derivatives and pharmaceutical compositions containing them |
-
1981
- 1981-08-18 IT IT23546/81A patent/IT1168163B/it active
-
1982
- 1982-07-30 CH CH4612/82A patent/CH650259A5/it not_active IP Right Cessation
- 1982-08-04 AU AU86731/82A patent/AU533719B2/en not_active Ceased
- 1982-08-05 US US06/405,332 patent/US4431664A/en not_active Expired - Fee Related
- 1982-08-06 ZA ZA825718A patent/ZA825718B/xx unknown
- 1982-08-09 DK DK357182A patent/DK156067C/da not_active IP Right Cessation
- 1982-08-11 NL NLAANVRAGE8203160,A patent/NL186447C/xx not_active IP Right Cessation
- 1982-08-12 SE SE8204670A patent/SE448456B/sv not_active IP Right Cessation
- 1982-08-12 BE BE2/59796A patent/BE894093A/nl not_active IP Right Cessation
- 1982-08-12 CA CA000409313A patent/CA1182121A/en not_active Expired
- 1982-08-13 GB GB08223316A patent/GB2104071B/en not_active Expired
- 1982-08-13 JP JP57141602A patent/JPS5859982A/ja active Granted
- 1982-08-13 GR GR69044A patent/GR76260B/el unknown
- 1982-08-13 FR FR8214079A patent/FR2511675A1/fr active Granted
- 1982-08-13 PH PH27729A patent/PH19228A/en unknown
- 1982-08-14 DE DE3230265A patent/DE3230265C2/de not_active Expired
- 1982-08-17 AT AT0312282A patent/AT383597B/de not_active IP Right Cessation
- 1982-08-17 KR KR8203689A patent/KR860000851B1/ko active
- 1982-08-17 NO NO822801A patent/NO159448C/no unknown
- 1982-08-17 ES ES515068A patent/ES515068A0/es active Granted
- 1982-08-18 LU LU84340A patent/LU84340A1/fr unknown
- 1982-08-18 AR AR290336A patent/AR230444A1/es active
- 1982-08-18 PT PT75440A patent/PT75440B/pt not_active IP Right Cessation
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