NO158679B - Analogifremgangsmaate til fremstilling av terapeutisk aktive 2-penem-3-karboksylsyreforbindelser. - Google Patents
Analogifremgangsmaate til fremstilling av terapeutisk aktive 2-penem-3-karboksylsyreforbindelser. Download PDFInfo
- Publication number
- NO158679B NO158679B NO790332A NO790332A NO158679B NO 158679 B NO158679 B NO 158679B NO 790332 A NO790332 A NO 790332A NO 790332 A NO790332 A NO 790332A NO 158679 B NO158679 B NO 158679B
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- Prior art keywords
- group
- salt
- alkyl
- transferred
- substituted
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 4
- DUNKKIRUWZSMPT-RXMQYKEDSA-N (5r)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical class OC(=O)C1=CS[C@@H]2CC(=O)N12 DUNKKIRUWZSMPT-RXMQYKEDSA-N 0.000 title claims 2
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 4
- -1 phosphonio group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 230000003287 optical effect Effects 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical class 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 150000001768 cations Chemical class 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 125000005442 diisocyanate group Chemical group 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
- 150000004985 diamines Chemical class 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- HJOVHMDZYOCNQW-UHFFFAOYSA-N isophorone Chemical compound CC1=CC(=O)CC(C)(C)C1 HJOVHMDZYOCNQW-UHFFFAOYSA-N 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000008422 chlorobenzenes Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000010574 gas phase reaction Methods 0.000 description 1
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical group O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- NIMLQBUJDJZYEJ-UHFFFAOYSA-N isophorone diisocyanate Chemical compound CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1 NIMLQBUJDJZYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/09—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Fremgangsmåte til fremstilling av l-isocyanato-3-(isocyanatometyl)-3,5,5-trimetylcykloheksan.
Det er kjent av diaminer og deres sal-ter ved reaksjon med 2 mol fosgen over
di-(klorkullsyreester) etter avspaltning
av 2 mol klorhydrogen å komme til diiso-cyanater som ved addisjon til bifunksjo-nelle forbindelser med reaksjonsdyktige
hydrogenatomer, f. eks. aminer, amider,
alkoholer, merkaptaner, uretaner, urin-stoffer osv. kan omsettes til lineære høy-molekylære produkter. Ved anvendelse
av slike forbindelser med tri- eller poly-funksjonelle grupper av ovennevnte type
får man usmeltbare og uoppløselige kunst-stoffer. Et eksempel på et slikt diisocya-nat er 1,6-heksandiisocyanat, fremstillet
av heksametylendiamin og fosgen.
Oppfinnelsens gjenstand er en fremgangsmåte til fremstilling av diisocyana-ter med verdifulle egenskaper, idet frem-gangsmåten består i at det som diamin-komponent anvendes en forbindelse med
formel
Dette 3-( aminometyl-3,5,5-trimetylcyklo-heksylamin kan på enkel måte fremstilles
ved omsetning av isoforon med blåsyre og
etterfølgende hydrering av nitrilet i nærvær av ammoniakk.
En vesentlig fordel ved fremgangs-måten ifølge oppfinnelsen består i at man har et godt tilgjengelig og økonomisk fremstillbart utgangsprodukt. For det andre utmerker de fremstilte produkter seg ved gode anvendbarheter for nett-dannelsesreaksjoner ved eggehvitestoffer (garver i vesen), videre ved f. eks. meget gode klebeegenskaper ved forbindelser av metaller med høymolekylære kunst- eller naturstoffer, som f. eks. kautsjuktyper. De lar seg imidlertid også f. eks. omsette med dioler eller polyoler til polyuretaner eller med di- eller polyamider til poly-urinstoffer.
I det vesentlige gjelder det for frem-gangsmåtens gjennomføring de kjente betingelser. I et første trinn kan diami-nets omsetning med gassformet klorhydrogen eller med CO, foregå i et inert oppløsningsmiddel til de tilsvarende ad-disjonsprodukter. Deretter foregår fos-genbehandlingen. Derved danner det seg primært di-(klormaursyreester), idet under reaksjonsbetingelsene HC1 resp. C02 og HC1 avspaltes under dannelse av di-isocyanat. Man kan imidlertid også ved direkte fosgenering av gassen i flytende fase eller også i gassfase komme til diiso-cyanatene.
Reaksjonstemperaturene ligger i om-rådet fra ca. 10 til 250°C ved væskefase-fremgangsmåten og fra ca, 100 til 350°C ved gassfasefremgangsmåten. Nærværet av vann, monofunksjonelle alkoholer, fe-noler og aminer skal unngås ved frem-gangsmåten.
Det kan anvendes alle indifferente oppløsningsmidler, spesielt klorbenzoler, nitrobenzoler, xylol eller lignende. Som spesielt fordelaktig har vist seg an-vendelsen av ikke-substituerte hydroaro-matiske hydrokarboner. Hertil hører spesielt dekahydronaftalih, ved hvis anvendelse det kan oppnås høye utbytter. Van-ligvis lønner det seg å velge oppløsnings-midler således at det består en tilstrek-kelig koketemperatur i forhold til reak-sjonsproduktet. Oppløsningsmidlet skal imidlertid på den annen side også koke høyt nok til å sikre en hurtig avspaltning og fjerning av klorhydrogenet.
De angjeldende inerte oppløsnings-midler oppløser overhodet ikke aminhy-drokloridet. Derfor sørges det hensiktsmessig for en finest mulig suspensjon av aminsaltene ved en mest mulig intens omrøring.
Metallspor holdes hensiktsmessig borte for å hindre en polymerisasjon av diisocyanatet.
Det er også mulig å gjennomføre re-aksjonen ved forstøvhing av diamin ved gassfasereaksjonen.
Eksempel 1.
Hydrokloridets fremstilling.
350 g 3-(aminométyl)-3,5,5-trimetyl-cykloheksylamin-( 1) ble oppløst i 3 1 o-di-klorbénzol. Inn i denne oppløsning fører man under sterk omrøring tørr klorhydrogen idet suspensjonens temperatur stiger fra 20°C til 100°C. Etter 2 timer ble reaksjonsmassen tydelig seigere, og tem-peraturen falt igjen langsomt.
Fosgenering.
Inn i denne varme oppløsning ble det innført ved 160°C tørr COCL. Etter 28 timer vår hydrokloridet omsatt. Det hadde dannet seg en homogen lysebrun væske. Rester av COCL, og HCl ble utdrevet ved innblasing av tørr nitrogen.
Destillasjon.
Oppløsningsmidlets hovedmengde ble adskilt i vakuum ved 65—70°C. Forløpet inneholdt bare små mengder isocyanat.
Den gjenværende isocyanatoppløs-ning ble fraksjonert i én kolonne. Det gikk over en vårinklar fraksjon ved 126— 128°C og 2 mm Hg. Utbytte 323 g = 70,7% Isocyanattall teoretisk Klorverdi 0,1% Fosgenforbruk: 1,32 kg.
Eksempel 2.
340 g (2 mol) 3-(aminometyl)-3,5,5-trimetylcykloheksylamin-( 1) oppløses i 3 1 dekahydronaftalin og oppvarmes til 90—
95°C. Ved denne temperatur innfører man under sterk omrøring en kraftig HC1-strøm. Såsnart den dannede hydroklorid-suspensjon ikke mere opptar klorhydrogen avbrytes innføringen av HC1-.
Reaksjonsblandingen oppvarmes til 150°C og under sterk omrøring innføres gassformet fosgen. Etter 10 til 12 timer er det samlede hydroklorid omsatt. Reak-sjonens avslutning sees ved at det fra den melkeaktige suspensjon er dannet en klar, lysebrun oppløsning. Overskytende saltsyre og fosgen fjernes deretter ved innblåsing av tørr nitrogen.
Reaksjonsblandingen destilleres f r ak-sjoner ende gjennom en 50 cm fyllegeme-kolonne. Etter oppløsnihgsmiddelforløpet får man 405 g av diisocyanatet.
Kokepunkt ved 15 mm Hg 158—159°C
n <!>D<5> 1.4820
Utbytte 91,'2% av det teoretiske ;Fosgenforbruk 20 mol
Fremgangsmåte til fremstilling av 1-isocyanato-3-( isocyahatometyl )-3,5,5-tri-<;>rhetylcykloheksan med formel
karakterisert ved at man på i og <:>for seg kjent måte behandler l-amino-(3-aminometyl )-3,5,5-trimetylcykloheksan, eventuelt i nærvær av et inert organisk oppløsningsmiddel, med klorhydrogen eller karbondioksyd og deretter omsetter det dannede salt med fosgen.
Claims (1)
- Analogifremgangsmåte til fremstilling av terapeutisk virksomme 2-penem-3-karboksylsyreforbindelser med formel hvori Ra betyr C^-C^-alkyl, med hydroksy substituert C^-C^-alkyl,eller C^-C^-alkoksy og betyr hydrogen, C^-C^-alkyl, med amino eller C-^-C^-alkanoylamino substituert C^-C^-alkyl, C,-C^-alkyltio eller med C^-C^-alkanoylamino substituert C-, -C^-alkyltio, optiske isomere, blandinger av slike optiske isomere samt farmasøytisk anvendbare salter av slike forbindelser med saltdannende grupper,karakterisert ved at en ylid-forbind- else med formel hvori R a og Rx, har ovennevnte betydning, idet funksjonelle grupper i disse rester fortrinnsvis foreligger i beskyttet form, og R^ betyr sammen med karbonylgrupperingen -C(=0) en beskyttet karboksylgruppedannende rest, Z betyr oksygen eller svovel, og hvori X enten betyr en'tre ganger substituert fosfoniogruppe eller en tc ganger forestret fosfonogruppe sammen med et kation, ringsluttes, og i en dannet forbindelse overføres den beskyttede karboksylgruppe med formel -(=0)-R2 til den fri karboksylgruppe, eventuelt beskyttede funksjonelle grupper i restene R a og/eller Rx, overføres i de frie funksjonelle grupper, og hvis ønsket, overføres en dannet forbindelse med saltdannende gruppe til et farmasøytisk anvendbart salt eller et dannet salt overføres til den frie forbindelse eller til et annet farmasøytisk anvendbart salt og/eller hvis ønsket, oppdeles en dannet blanding av isomere forbindelser i de enkelte isomere.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH114078 | 1978-02-02 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO790332L NO790332L (no) | 1979-08-03 |
| NO158679B true NO158679B (no) | 1988-07-11 |
| NO158679C NO158679C (no) | 1988-10-19 |
Family
ID=4203421
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO790332A NO158679C (no) | 1978-02-02 | 1979-02-01 | Analogifremgangsmaate til fremstilling av terapeutisk aktive 2-penem-3-karboksylsyreforbindelser. |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US4692442A (no) |
| EP (2) | EP0003960B1 (no) |
| JP (3) | JPS54119486A (no) |
| AR (1) | AR228236A1 (no) |
| AT (1) | AT362876B (no) |
| AU (1) | AU519317B2 (no) |
| CA (1) | CA1340273C (no) |
| CS (1) | CS222279B2 (no) |
| DD (1) | DD142342A5 (no) |
| DK (1) | DK160099C (no) |
| ES (1) | ES477336A1 (no) |
| FI (1) | FI73219C (no) |
| GB (1) | GB2013674A (no) |
| GR (1) | GR72911B (no) |
| HU (1) | HU182017B (no) |
| IE (1) | IE48776B1 (no) |
| IL (1) | IL56557A (no) |
| NO (1) | NO158679C (no) |
| NZ (1) | NZ189530A (no) |
| PL (1) | PL122371B1 (no) |
| PT (1) | PT69166A (no) |
| SU (1) | SU925252A3 (no) |
| ZA (1) | ZA79433B (no) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4880793A (en) * | 1978-07-24 | 1989-11-14 | Merck & Co., Inc. | Combination of thienamycin-type antibiotics with dipeptidase inhibitors |
| US5071843A (en) * | 1978-07-24 | 1991-12-10 | Merck & Co., Inc. | Combination of 2-substituted carbapenems with dipeptidase inhibitors |
| JPS5625110A (en) * | 1978-12-18 | 1981-03-10 | Bristol Myers Co | Antibacterial |
| US4282150A (en) | 1978-12-18 | 1981-08-04 | Bristol-Myers Company | 2,6-Disubstituted penem compounds |
| US4272437A (en) | 1978-12-18 | 1981-06-09 | Bristol-Myers Company | Antibacterial agents, and 4-thio azetidinone intermediates |
| ATE3041T1 (de) * | 1979-01-10 | 1983-04-15 | Schering Corporation | 2-penem-verbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zusammensetzungen. |
| IL59081A0 (en) * | 1979-01-10 | 1980-05-30 | Schering Corp | 2-penem compounds and a method for preparing them |
| IT1193922B (it) * | 1979-02-24 | 1988-08-31 | Erba Farmitalia | Agenti antibatterici ed inibitori di beta -lattamasi e loro preparazione |
| JPS55153789A (en) * | 1979-04-11 | 1980-11-29 | Sankyo Co Ltd | Penem-3-carboxylic acid derivative and its preparation |
| US4378314A (en) | 1979-09-21 | 1983-03-29 | Bristol Myers Company | Antibacterial agents and metal containing azetidinone intermediates therefore |
| US4374065A (en) | 1979-09-21 | 1983-02-15 | Bristol-Myers Company | Antibacterial agents of the β-lactam type |
| US4443463A (en) * | 1979-11-05 | 1984-04-17 | Schering Corporation | (5R,6S,8R)-6-(1-Hydroxyethyl)-2-(hydroxyalkylthio)-penem-3-carboxylates |
| ATE12773T1 (de) * | 1980-02-28 | 1985-05-15 | Schering Corp | 2-penem-verbindungen, sie enthaltende pharmazeutische zusammensetzungen und verfahren zu ihrer herstellung. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1368074A (en) * | 1971-02-04 | 1974-09-25 | Beecham Group Ltd | Substituted beta-lactams and their preparation |
| US4364865A (en) * | 1975-12-08 | 1982-12-21 | Ciba-Geigy Corporation | Bicyclic unsaturated thia-aza compounds and 4-acylthio azetidinone intermediates |
| US4543257A (en) * | 1977-10-19 | 1985-09-24 | Merck & Co., Inc. | 1-Carba-2-penem-3-carboxylic acid |
| US4500457A (en) * | 1977-05-09 | 1985-02-19 | Ciba-Geigy Corporation | Process for preparing thia-aza compounds with a beta-lactam ring |
| LU77306A1 (no) * | 1977-05-09 | 1979-01-18 | ||
| US4168314A (en) * | 1977-11-17 | 1979-09-18 | Merck & Co., Inc. | 6-(1'-Hydroxyethyl)-2-aminoethylthio-pen-2-em-3-carboxylic acid |
| US4123539A (en) * | 1977-12-29 | 1978-10-31 | Merck & Co., Inc. | 6-Ethylpenicillanic acid |
| US4272437A (en) * | 1978-12-18 | 1981-06-09 | Bristol-Myers Company | Antibacterial agents, and 4-thio azetidinone intermediates |
| EP0023887B1 (de) * | 1979-08-01 | 1984-11-07 | Ciba-Geigy Ag | 3-Substituierte bicyclische Azetidinonderivate, Verfahren zu ihrer Herstellung und Zwischenprodukte, sowie deren Herstellung |
| DE3372968D1 (en) * | 1982-11-16 | 1987-09-17 | Ciba Geigy Ag | Heterocyclyl-thio compounds, process for their preparation, pharmaceutical compositions containing them and their use |
| US4614614A (en) * | 1983-03-28 | 1986-09-30 | Ciba-Geigy Corporation | Process for the manufacture of optically active azetidinones |
| US4656165A (en) * | 1983-09-02 | 1987-04-07 | Ciba-Geigy Corporation | Aminomethyl penem compounds |
| US4826832A (en) * | 1986-05-06 | 1989-05-02 | Ciba-Geigy Corporation | Penen compounds |
-
1979
- 1979-01-30 EP EP79100258A patent/EP0003960B1/de not_active Expired
- 1979-01-30 EP EP81100569A patent/EP0042026B1/de not_active Expired
- 1979-01-31 FI FI790321A patent/FI73219C/fi not_active IP Right Cessation
- 1979-01-31 GR GR58225A patent/GR72911B/el unknown
- 1979-01-31 GB GB7903360A patent/GB2013674A/en not_active Withdrawn
- 1979-01-31 CA CA000320618A patent/CA1340273C/en not_active Expired - Fee Related
- 1979-01-31 ES ES477336A patent/ES477336A1/es not_active Expired
- 1979-01-31 IL IL56557A patent/IL56557A/xx unknown
- 1979-02-01 AU AU43843/79A patent/AU519317B2/en not_active Expired
- 1979-02-01 IE IE191/79A patent/IE48776B1/en not_active IP Right Cessation
- 1979-02-01 PT PT7969166A patent/PT69166A/pt unknown
- 1979-02-01 ZA ZA79433A patent/ZA79433B/xx unknown
- 1979-02-01 DK DK043279A patent/DK160099C/da not_active IP Right Cessation
- 1979-02-01 PL PL1979213133A patent/PL122371B1/pl unknown
- 1979-02-01 NO NO790332A patent/NO158679C/no unknown
- 1979-02-01 AT AT0074579A patent/AT362876B/de not_active IP Right Cessation
- 1979-02-01 SU SU792720750A patent/SU925252A3/ru active
- 1979-02-01 HU HU79CI1908A patent/HU182017B/hu unknown
- 1979-02-01 NZ NZ189530A patent/NZ189530A/xx unknown
- 1979-02-02 AR AR275390A patent/AR228236A1/es active
- 1979-02-02 DD DD79210799A patent/DD142342A5/de not_active IP Right Cessation
- 1979-02-02 CS CS79755A patent/CS222279B2/cs unknown
- 1979-02-02 JP JP1053679A patent/JPS54119486A/ja active Granted
-
1980
- 1980-11-18 US US06/208,105 patent/US4692442A/en not_active Expired - Lifetime
-
1986
- 1986-11-11 JP JP61266766A patent/JPS62129264A/ja active Granted
-
1988
- 1988-08-19 JP JP63204829A patent/JPH01110668A/ja active Granted
-
1989
- 1989-08-21 US US07/396,783 patent/US4952690A/en not_active Expired - Lifetime
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