NO861240L - Fremgangsmaate for fremstilling av terapeutisk aktive nitrofuranderivater. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive nitrofuranderivater.Info
- Publication number
- NO861240L NO861240L NO861240A NO861240A NO861240L NO 861240 L NO861240 L NO 861240L NO 861240 A NO861240 A NO 861240A NO 861240 A NO861240 A NO 861240A NO 861240 L NO861240 L NO 861240L
- Authority
- NO
- Norway
- Prior art keywords
- derivatives
- compounds
- preparation
- pyridinyl
- nitrofurand
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 2
- 238000002360 preparation method Methods 0.000 title claims 2
- 230000001225 therapeutic effect Effects 0.000 title 1
- SXINBFXPADXIEY-UHFFFAOYSA-N 5-Nitrofurfural Chemical compound [O-][N+](=O)C1=CC=C(C=O)O1 SXINBFXPADXIEY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 229940027988 antiseptic and disinfectant nitrofuran derivative Drugs 0.000 claims description 2
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical class NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- DXWCZMGIIFEEPU-OWOJBTEDSA-N (e)-3-(5-nitrofuran-2-yl)prop-2-enal Chemical compound [O-][N+](=O)C1=CC=C(\C=C\C=O)O1 DXWCZMGIIFEEPU-OWOJBTEDSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- VVAKGACNCPHDFX-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)prop-2-enoic acid Chemical compound COC1=CC=C(C=CC(O)=O)C=N1 VVAKGACNCPHDFX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- -1 (5-nitro-2-furanyl)methylene Chemical group 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- BTZPAAGHZIUZGH-UHFFFAOYSA-N 3-(5-methoxypyridin-2-yl)prop-2-enoic acid Chemical compound COC1=CC=C(C=CC(O)=O)N=C1 BTZPAAGHZIUZGH-UHFFFAOYSA-N 0.000 description 2
- LKDFTXDJKHGCAC-UHFFFAOYSA-N 3-pyridin-2-ylprop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=CC=N1 LKDFTXDJKHGCAC-UHFFFAOYSA-N 0.000 description 2
- SSAYTINUCCRGDR-UHFFFAOYSA-N 3-pyridin-4-ylprop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=NC=C1 SSAYTINUCCRGDR-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000030852 Parasitic disease Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- DXWCZMGIIFEEPU-UHFFFAOYSA-N 3-(5-nitrofuran-2-yl)prop-2-enal Chemical compound [O-][N+](=O)C1=CC=C(C=CC=O)O1 DXWCZMGIIFEEPU-UHFFFAOYSA-N 0.000 description 1
- QSCNDPBLNZQKPS-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)prop-2-enehydrazide Chemical compound COC1=CC=C(C=CC(=O)NN)C=N1 QSCNDPBLNZQKPS-UHFFFAOYSA-N 0.000 description 1
- VUVORVXMOLQFMO-UHFFFAOYSA-N 3-pyridin-3-ylprop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=CN=C1 VUVORVXMOLQFMO-UHFFFAOYSA-N 0.000 description 1
- CTAIEPPAOULMFY-UHFFFAOYSA-N 6-methoxypyridine-3-carbaldehyde Chemical compound COC1=CC=C(C=O)C=N1 CTAIEPPAOULMFY-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 208000019399 Colonic disease Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 238000006052 Horner reaction Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229940045505 klebsiella pneumoniae Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000036281 parasite infection Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940118696 vibrio cholerae Drugs 0.000 description 1
- 125000000391 vinyl group Chemical class [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
Foreliggende oppfinnelse vedrører fremstilling av terapeutisk aktive nitrofuranderivater med generell formel:
hvor m er 0 eller 1, og
R er H eller (C^ ) alkoksy
I overensstemmelse med den foreliggende oppfinnelse kan forbindelsene med generell formel (I) fremstilles som vist i etterfølgende reaksjonsskjerna, ved kondensasjon mellom hydra-zidet med formel (II) og 5-nitro-2-furankarboksaldehyd (eller dets vinylanalog) i et alkoholisk løsningsmiddel (f.eks. metanol, etanol eller 2-metoksyetanol) ved en temperatur mellom 20°C og tilbakeløpstemperaturen. De oppnådde derivatene krystalliserer spontant i reaksjonsblandingen.
3-(5-nitro-2-furanyl)-2-propenal fremstilles ved aldol-type omsetning mellom 5-nitro-2-furankarboksaldehyd og acetaldehyd, etterfulgt av rensing ved kromatografering på en silika-kolonne.
Hydrazidene kan fremstilles ved omsetning mellom syrene og tørt hydrazin i nærvær av kondensasjonsmidler (f.eks. disyklo-heksylkarbodiimid, E.E.D.Q. osv.) eller ved omsetning mellom hydrazinet og et aktivt syre-derivat (f.eks. et blandet anhy-drid, et imidazolid osv.).
Etylensyrene fremstilles utfra de tilsvarende aldehyder ved kondensasjon med esterderivatene eller de aktiverte metylen-syrer (f.eks. ved Doebner, Perkin, eller Witting-Horner om-setningen osv.).
De følgende eksemplene illustrerer oppfinnelsen.
IR og NMR analyser og spektra bekrefter strukturen av forbindelsene .
Eksempel 1 ((5-nitro-2-furanyl)metylen)-hydrazid av 3(6-metoksy-3-pyrinyl)2-propensyre
1.1. 3( 6- metoksy- 3- pyridinyl)- 2- propensyre
En blanding av 11,5 g (0,084 mol) 6-metoksy-3-pyridinkarboks-aldehyd, (beskrevet av I. Kompis et coil, Europ. J. Med. chem., Chimie Therap (1977) 12(6)s. 531-536), 8,75 g (0,084 mol) malonsyre, 6,65 g (0,084 mol) pyridin og en dråpe piperdin oppvarmes ved 100°C i 1 time.
Deretter tilsettes 100 ml vann, og blandingen innstilles til pH 4 ved hjelp av eddiksyre. Det utfelte stoff avvannes på filter, vaskes med vann og tørkes. Man oppnår en forbindelse med Smp.: 190 - 191°C.
På samme måte som det foregående, fremstilles følgende etylen-syrer: 3-(4-pyridinyl)2-propensyre Smp.: 296 - 298°C 3-(pyridinyl)2-propensyre Smp.: 202 - 203°C 3-(5-metoksy-2-pyridinyl)2-propensyre Smp.: 217 - 218°C
1.2 Hydrasid av 3-( 6- metoksy- 3- pyridinyl) 2- propensyre
I en løsnig av 4,4 g (24,55 mmol) 3-(6-metoksy-3-pyridinyl)2-propensyre i 200 ml kloroform tilsettes 2,5 g (24,6 mmol) tri-etylamin, hvorpå den oppnådde løsningen avkjøles til en temperatur mellom 0 og 5°C. Deretter tilsettes dråpevis en løsning av 2,7 g (24,6 mmol) etylklorformiat i 20 ml kloroform og den oppnådde løsningen omrøres 1 time ved ovennevnte temperatur.
3,2 g (0,1 mol) tørt hydrazin tilsettes på en gang, og løs-
ningen får stå i 4 timer ved romstemperatur. Løsningsmidlet avdampes til tørrhet og resten løses på nytt i 50 ml kokende vann, omrøres med aktivt kull i kort tid og suspensjonen varm-filtreres. Etter avkjøling til 5 - 10°C krystalliseres et fast stoff som avvannes, vaskes i isblandet vann og tørkes.
Man oppnår en forbindelse med Smp.: 173 - 174°C.
På samme måte som nevnt over fremstilles følgende hydrazider: Hydrazid av 3-(3-pyridinyl)2-propensyre Smp.: 149 - 150°C Hydrazid av 3-(4-pyridinyl)2-propensyre Smp.: 105 - 107°C Hydrazid av 3-(2-pyridinyl)2-propensyre Smp.: 98 - 99°C Hydrazid av 3-(5-metoksy-2-pyridinyl)2-propensyre
Smp.: 144 - 145°C
1.3. (( 5- nitro- 2- fyranyl) metylen) hydrazid av 3-( 6- metoksy- 3-pyridinyl)- 2- propensyre
Til en løsning av 0,9 g (4,66 mol) 3-(6-metoksy-3-pyridinyl)2-propensyrehydrazid i 50 ml etanol oppvarmet til 50 - 60°C, tilsettes 0,66 g (4,7 mmol) 5-nitro-2-furankarboksaldehyd.
Den oppnådde løsningen omrøres i 1 time, idet temperaturen i løsningen avtar til vaerelsestemperatur, og de utfelte krystal-lene avvannes, vaskes i eter og tørkes ved lavt trykk ved 100°C i 8 timer.
Den oppnådde forbindelsen har Smp.: 239 - 240°C.
Eksempel 2
((5-nitro-2-furanyl)2-propen-l-yliden)hydrazid av 3-(6-metoksy 3-pyridinyl)-2-propensyre.
Til en løsning (lunken) av 0,85 g (4,4 mmol) 3-(6-metoksy-3-pyridinyl)-2-propensyrehydrazid i 50 ml metanol, tilsettes 0,75 g (0,5 mmol) 3-(5-nitro-2-fyranyl)2-propenal. I den oppnådde, homogene løsningen utkrystalliseres sakte et fast stoff. Etter omrøring i flere timer, isolerer man krystaller som vaskes i metanol og eter og tørkes ved lavt trykk ved 100°C
i 8 timer.
Den oppnådde forbindelsen har Smp.: 232 - 233°C.
Forbindelsene fremstilt som vist i eksemplene over, er angitt
i følgende tabell.
Forbindelsene fremstilt i overensstemmelse med den foreliggende oppfinnelse ble underkastet farmakologiske forsøk med hensyn på antibakteriell, antiparasitt og antisopp virkning.
De fremstilte forbindelsene viste en inhiberende aktivitet "in vitro" og "in vivo" overfor en rekke bakteriearter, som i særdeleshet omfatter: Staphylococcus aureus, Escherichia Coli, Mycobacterium ranae, Pseudomonas aeruginosa, Proteus Vulgaris, Vibrio Cholerae, Klebsiella pneumoniae, Irichomonas, Salmonella, Shighella Flexneri, Candida Albicans, noe som fører til at forbindelsene kan anvendes ved ulike bakterie- og parasittinfeksjoner, i særdeleshet i tarmen.
Den minste inhiberende konsentrasjon "in vitro" som ble be-stemt etter at en løsning av forbindelsene ble tilsatt dime-tylformamid (0,1%), varierte i overensstemmelse med bakterie-artene i området 0,05^ug/ml-20^ug/ml.
Forsøk som ble gjennomført "in vivo" på infeksjoner hos mus, viste oral aktivitet for forbindelsene idet de inhiberte døde-ligheten hos mus som hadde fått tilført en rekke av de ovennevnte bakteriene og førte til en fullstendig sterilisering av fordøyelseskanalen hos musene.
Forbindelsene hadde en meget lav giftighet, vesentlig over
1 g/kg.
Forbindelsene som fremstilles i overensstemmelse med den foreliggende oppfinnelse kan anvendes klinisk hos mennesker i doser fra 20 mg/døgn - lg/døgn, idet enhetsdosen er mellom 5 og 200 mg; men forbindelsene kan anvendes hos dyr i doser fra 1-20 mg/kg/døgn.
Forbindelsene kan passende fremstilles for oral, rektal eller parenteral tilførsel, f.eks. i form av kapsler, tabletter, granuler, geler eller oppløsninger, siruper eller drikkbare suspensjoner som inneholder passende hjelpestoffer. Forbindelsene kan anvendes som antibakterielle-, tarmantisept-iske-, antisopp- og/eller antiprotosomidler hos mennesker og dyr. Forbindelsene kan anvendes for behandling av menneske-tarmen ved infeksiøs tykktarmslidelse, diare, enten forårsaket av næringsmidler eller ikke, betennelser, og dysenteri forårsaket av stavformede bakterier.
Forbindelsene kan også anvendes som beskyttelse ved konser-vering av næringsmidler og i kampen mot bakterie- og para-sittinfeks joner hos kveg slik at veksten fremmes.
Claims (1)
1. Fremgangsmåte for fremstilling av nitrofuranderivater med generell formel
hvor m er 0 eller 1 og R er H eller (^ )alkoksy, karakterisert ved at et hydrazid med formel
kondenseres med 5-nitro-2-furan-karboksaldehyd eller 3-(5-nitro-2-furyl)-2-propenal i et alkoholisk løsningsmiddel ved en temperatur i området mellom 20°C og tilbakeløpstempe-raturen for løsningsmidlet.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8505424A FR2580281B1 (fr) | 1985-04-11 | 1985-04-11 | Derives du nitrofuranne, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO861240L true NO861240L (no) | 1986-10-13 |
Family
ID=9318115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO861240A NO861240L (no) | 1985-04-11 | 1986-03-26 | Fremgangsmaate for fremstilling av terapeutisk aktive nitrofuranderivater. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4711892A (no) |
| EP (1) | EP0200605A1 (no) |
| JP (1) | JPS61236776A (no) |
| KR (1) | KR860008168A (no) |
| CN (1) | CN86102565A (no) |
| AU (1) | AU5591486A (no) |
| DK (1) | DK161086A (no) |
| ES (1) | ES8703456A1 (no) |
| FI (1) | FI861526A (no) |
| FR (1) | FR2580281B1 (no) |
| GR (1) | GR860950B (no) |
| HU (1) | HUT43592A (no) |
| IL (1) | IL78357A0 (no) |
| MA (1) | MA20660A1 (no) |
| NO (1) | NO861240L (no) |
| PT (1) | PT82364B (no) |
| TN (1) | TNSN86054A1 (no) |
| ZA (1) | ZA862708B (no) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU602140B2 (en) * | 1986-04-07 | 1990-10-04 | Upjohn Company, The | Anthelmintic acylhydrazones, method of use and compositions |
| US4820718A (en) * | 1987-09-17 | 1989-04-11 | Sandoz Pharm. Corp. | N-alkyl-(2- or 5-substituted-2-methoxycarbonyl aminoalkyl furanyl)-substituted cyclimmonium salts and use thereof in PAF inhibition |
| GB9615944D0 (en) * | 1996-07-30 | 1996-09-11 | Kodak Ltd | A material,method and apparatus for inhibiting microbial growth in an aqueous medium |
| US7629002B2 (en) * | 2000-02-16 | 2009-12-08 | Chemeq Ltd. | Antimicrobial polymeric compositions and method of treatment using them |
| US20030225126A1 (en) * | 2000-03-23 | 2003-12-04 | Influx, Inc. | Bactericidal antimicrobial methods and compositions for use in treating gram positive infections |
| JP4680926B2 (ja) * | 2003-11-06 | 2011-05-11 | ケメック・リミテッド | ポリアクロレインの製造方法 |
| CN107417673B (zh) * | 2017-04-25 | 2019-10-01 | 西华大学 | N-(2-吡啶基)亚甲基-2-氰基-3-杂环基丙烯酰肼类衍生物及其应用 |
| CN108558858A (zh) * | 2018-05-23 | 2018-09-21 | 成都师范学院 | 硝基呋喃类抗结核化合物 |
| CN110642743B (zh) * | 2019-10-18 | 2021-01-01 | 中国农业大学 | 硝呋酚酰肼半抗原和人工抗原及其制备方法与应用 |
| CN114225095A (zh) * | 2021-12-10 | 2022-03-25 | 中国科学技术大学 | 生物基抗菌复合粘合材料及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2703322A (en) * | 1951-03-17 | 1955-03-01 | Hoffmann La Roche | Derivatives of isonicotinyl hydrazine |
| US2874189A (en) * | 1957-03-28 | 1959-02-17 | Nat Drug Co | Pharmaceuticals |
| US3072726A (en) * | 1959-08-24 | 1963-01-08 | Hoffmann La Roche | N1-cycloalkanoyl and n1-[alpha-tri-alkyl]-alkanoyl-hydrazides and derivatives thereof |
-
1985
- 1985-04-11 FR FR8505424A patent/FR2580281B1/fr not_active Expired
-
1986
- 1986-03-26 NO NO861240A patent/NO861240L/no unknown
- 1986-03-31 IL IL78357A patent/IL78357A0/xx unknown
- 1986-04-02 EP EP86400708A patent/EP0200605A1/fr not_active Withdrawn
- 1986-04-09 MA MA20885A patent/MA20660A1/fr unknown
- 1986-04-10 DK DK161086A patent/DK161086A/da not_active IP Right Cessation
- 1986-04-10 AU AU55914/86A patent/AU5591486A/en not_active Abandoned
- 1986-04-10 KR KR1019860002714A patent/KR860008168A/ko not_active Application Discontinuation
- 1986-04-10 FI FI861526A patent/FI861526A/fi not_active Application Discontinuation
- 1986-04-10 HU HU861515A patent/HUT43592A/hu unknown
- 1986-04-10 PT PT82364A patent/PT82364B/pt unknown
- 1986-04-10 GR GR860950A patent/GR860950B/el unknown
- 1986-04-10 JP JP61084031A patent/JPS61236776A/ja active Pending
- 1986-04-10 US US06/851,113 patent/US4711892A/en not_active Expired - Fee Related
- 1986-04-10 ES ES553851A patent/ES8703456A1/es not_active Expired
- 1986-04-10 TN TNTNSN86054A patent/TNSN86054A1/fr unknown
- 1986-04-10 CN CN198686102565A patent/CN86102565A/zh active Pending
- 1986-04-10 ZA ZA862708A patent/ZA862708B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK161086A (da) | 1986-10-12 |
| ZA862708B (en) | 1986-11-26 |
| FI861526A (fi) | 1986-10-12 |
| CN86102565A (zh) | 1986-11-12 |
| HUT43592A (en) | 1987-11-30 |
| TNSN86054A1 (fr) | 1990-01-01 |
| PT82364B (fr) | 1988-03-18 |
| MA20660A1 (fr) | 1986-12-31 |
| PT82364A (fr) | 1986-05-01 |
| JPS61236776A (ja) | 1986-10-22 |
| ES553851A0 (es) | 1987-02-16 |
| DK161086D0 (da) | 1986-04-10 |
| FR2580281A1 (fr) | 1986-10-17 |
| KR860008168A (ko) | 1986-11-12 |
| US4711892A (en) | 1987-12-08 |
| EP0200605A1 (fr) | 1986-11-05 |
| GR860950B (en) | 1986-08-06 |
| ES8703456A1 (es) | 1987-02-16 |
| AU5591486A (en) | 1986-10-16 |
| FR2580281B1 (fr) | 1987-09-18 |
| IL78357A0 (en) | 1986-07-31 |
| FI861526A0 (fi) | 1986-04-10 |
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