NO133074B - - Google Patents
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- Publication number
- NO133074B NO133074B NO681/71A NO68171A NO133074B NO 133074 B NO133074 B NO 133074B NO 681/71 A NO681/71 A NO 681/71A NO 68171 A NO68171 A NO 68171A NO 133074 B NO133074 B NO 133074B
- Authority
- NO
- Norway
- Prior art keywords
- compound
- cephalosporin
- salt
- pyridine
- acid addition
- Prior art date
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- 238000000034 method Methods 0.000 claims abstract description 7
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical class S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 8
- 230000003115 biocidal effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- HOKIDJSKDBPKTQ-GLXFQSAKSA-N Cephalosporin C Natural products S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- -1 cephalosporin C compound Chemical class 0.000 description 4
- HOKIDJSKDBPKTQ-GLXFQSAKSA-M cephalosporin C(1-) Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H]([NH3+])C([O-])=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-M 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 1
- 229960003866 cefaloridine Drugs 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 244000000058 gram-negative pathogen Species 0.000 description 1
- 244000000059 gram-positive pathogen Species 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 150000003951 lactams Chemical group 0.000 description 1
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
- C07D501/34—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by carboxylic acids containing hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
- C07D501/46—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by carboxylic acids containing hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Fertilizing (AREA)
- Shafts, Cranks, Connecting Bars, And Related Bearings (AREA)
Abstract
Analogifremgangsmåte for fremstilling av et antibiotisk virksomt cefalosporansyrederivat.
Description
Denne oppfinnelse angår en fremgangsmåte for fremstilling av et nytt, antibiotisk virksomt cefalosporansyre-
derivat.
Abraham et al, Biochem. J (1961) 79_ 377, beskriver strukturen av cefalosporin C. Hale et al, Biochem. J. (1961)
79 403, beskriver fremstilling og strukturen av derivater av
cefalosporin C dannet med visse héterocykliske, tertiære baser. Derivatet dannet med pyridin, betegnet cefalosporin C (pyridin)
av Hale et al., er vist å' ha større antibakteriell virkning enn cefalosporin c. I forbindelsen som fremstilles i henhold til oppfinnelsen, er delta-aminoadipoylgruppen i cefalosporin cA"
(pyridin) erstattet med en <*-tieriylacety 1-gruppe. Den resulterende forbindelse har en vesentlig bedre antibiotisk aktivitet enn ;cefalosporin CA (pyridin) som vist i tabellen bakerst i beskrivelsen. ;I henhold til oppfinnelsen tilveiebringes således en fremgangsmåte for fremstilling av et antibiotisk virksomt cefalosporansyrederivat med formelen ;;eller et farmasøytisk akseptabelt syreaddisjonssalt derav. Fremgangs-måten karakteriseres ved at ;en forbindelse med formelen ;;eller et salt derav, omsettes med pyridin, ;og eventuelt fremstilles et syreaddisjonssalt av den på ;denne måte erholdte forbindelse. ;Eksempler på egnede farmasøytisk akseptable syre-addis jonssalter er hydroklorid-, hydrobromid-, sulfat-, nitrat-, ;. ortofosfat- og naftalensulfonat-salter. ;Den nye forbindelse (cefaloridin) fremstilles fortrinnsvis ved at den analoge cefalosporin C-forbindelse som har den ønskede a-tienylacetamido-gruppe i 7-stilling og den karakteristiske acetoksymetylgruppe i 3-stilling, omsettes i vandig oppløsning med et ovérskudd av pyridin ved forhøyet temperatur. Cefalosporin C-forbindelsen kan anvendes i form av den frie syre eller et salt. Pyridinet bør anvendes i minst ekvimolar mengde i forhold til cefalosporin C-forbindelsen, og fortrinnsvis i,et vesentlig over-skudd, f.eks. et molforhold på 3:1 til 10:1 eller mer, for å oppnå maksimal omdannelse av -cefalosporin C-forbindelsen, idet over-skuddet lett kan gjenvinnes og anvendes påny. Under reaksjons-betingelsene avspaltes acetoksygruppen og erstattes med pyridin-gruppen, idet sistnevnte bindes til den gjenværende metylengruppe direkte gjennom ring-nitrogenatomet, slik at det dannes et kvartært , ammoniumderivat, som danner et indre salt med karboksylgruppen i 4-stilling. ;Oppfinnelsen vil fremgå nærmere av det følgende eksempel. ;De antibiotiske aktiviteter som her er angitt, ble bestemt på Staphylococcus aureus 209 P ved en passende modifikasjon av papir-skiveplate-metodene ifølge Higgens et al, Antibiotics &;Chemotherapy, 3, 50-54 (Januar 1953) og Loo et al, Journal of Bacteriology, 50, 701-709 (1945). ;EKSEMPEL ;a-tienylmetyl-3-pyridin-cefalosporin Cft ;Et gram kalium-7-(a-tienylacetamido)-cefalosporanatsalt ble oppløst i 50 ml vann, og oppløsningen ble dekket med etylacetat. Blandingens pH-verdi ble senket til 2 for å omdanne kaliumsaltet til den frie 7-(a-tienylacetamido)cefalosporansyre. Etylacetatet ble derefter vasket med vann. Etylacetatet ble så skilt fra vannet og inndampet. 10 ml vann og 10 ml pyridin ble satt til det resulterende residuum. Den resulterende blanding ble oppvarmet til 45°C med omrøring i et oljebad i 40 timer for å danne 7-(a-tienyl-acetamido)-3-pyridinometyl-3-cefem-4-karboksyl-syre. Reaksjonsblandingen ble inndampet til tørrhet, og residuet ble tatt opp i vann og etylacetat. Den resulterende blanding ble ;'behandlet med fortynnet saltsyre for å senke pH-verdien til 2 og ;å danne hydroklorid-syreaddisjonssaltet av 7-(a-tienylacetamido)-3-pyridinometyl-3-cefem-4-karboksylsyre. Den vandige fase inne-holdende syreaddisjonssaltet ble fraskilt,vasket med etylacetat, skilt fra etylacetat-vaskevæsken og inndampet til tørrhet for å ;gi 470 mg av hydrokloridsaltet. Dette råprodukt ble renset ytter-ligere ved omkrystallisering fra metanol-isopropanol, hvorved man fikk 50 mg fast stoff. ;Infrarød analyse av det rensede,, faste produkt viste tilstedeværelse av en laktam-struktur, og ultrafiolett analyse viste ^maks*=257 m/u.(£=8200) . Tynnskiktkromatografisk analyse viste to flekker, hvorav den ene var organisk. En bioundersøkelse av produktet viste en penicillin G ekvivalens-aktivitet på 316
Oxford-eirheter pr. ral mot Staphylococcus aureus, stamme 209P.
Forbindelsen fremstilt i henhold til oppfinnelsen kjenne-tegnes ved sin motstandsevne mot den nedbrytende virkning av penicillinase, minimal toksisitet, høy aktivitet mot et stort område av gram-positive patogener, og lavere,men effektiv aktivitet mot mange gram-negative patogener.
Forbindelsen er meget effektiv mot penicillinresistent Staphylococcus aureus, selv i nærvær av serum. Den følgende tabell angir minimum hemmende konsentrasjon (MIC) for forbindelsen, både i nærvær av og i fravær av menneskeblod-serum, mot kliniske isolater av penicillin-resistent S. aureus, som målt"ved gradient-plateteknikken:
Forbindelsen er også meget effektiv mot hemolytiske streptococcer og gir en middels effektiv dose på 1,1 (ED50 mg/^g X 2) overfor 6-hemolytisk streptococcus-stamme C203 i mus, administrert oralt 1 time efter infeksjon og igjen 4 timer senere.
Forbindelsen fremstilt i henhold til oppfinnelsen har minimum hemmende konsentrasjon overfor en rekke forskjellige mikroorganismer som det fremgår av følgende tabell:
Claims (1)
- Analogifremgangsmåte for fremstilling av et antibiotiskvirksomt cefalosporansyrederivat med formeleneller et farmasøytisk akseptabelt syreaddisjonssalt derav, karakterisert ved at en forbindelse med formeleneller et salt derav, omsettes med pyridir, og eventuelt fremstilles et syreaddisjonssalt av den på denne måte erholdte forbindelse.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11561261A | 1961-06-08 | 1961-06-08 | |
| NO144515A NO122749B (no) | 1961-06-08 | 1962-05-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO133074B true NO133074B (no) | 1975-11-24 |
| NO133074C NO133074C (no) | 1976-03-03 |
Family
ID=22362437
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO144515A NO122749B (no) | 1961-06-08 | 1962-05-25 | |
| NO681/71A NO133074C (no) | 1961-06-08 | 1971-02-24 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO144515A NO122749B (no) | 1961-06-08 | 1962-05-25 |
Country Status (14)
| Country | Link |
|---|---|
| BE (1) | BE618663A (no) |
| BR (1) | BR6239733D0 (no) |
| CA (1) | CA984379A (no) |
| CH (1) | CH409967A (no) |
| DE (2) | DE1445684A1 (no) |
| DK (1) | DK129199B (no) |
| ES (1) | ES277871A1 (no) |
| FI (1) | FI43597C (no) |
| FR (1) | FR2899M (no) |
| GB (1) | GB982252A (no) |
| LU (1) | LU41846A1 (no) |
| NO (2) | NO122749B (no) |
| OA (1) | OA02701A (no) |
| SE (2) | SE322513B (no) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1082943A (en) * | 1963-03-27 | 1967-09-13 | Glaxo Lab Ltd | Derivatives of 7-aminocephalosporanic acid |
| US3492297A (en) * | 1965-07-01 | 1970-01-27 | Merck & Co Inc | Guanidino cephalosporins |
| GB1195203A (en) * | 1966-06-24 | 1970-06-17 | Glaxo Lab Ltd | Cephalosporins |
-
1962
- 1962-05-25 NO NO144515A patent/NO122749B/no unknown
- 1962-05-30 GB GB20911/62A patent/GB982252A/en not_active Expired
- 1962-06-01 CA CA850,587A patent/CA984379A/en not_active Expired
- 1962-06-04 DE DE19621445684 patent/DE1445684A1/de active Pending
- 1962-06-04 DE DE19621445701 patent/DE1445701A1/de active Pending
- 1962-06-04 FI FI621097A patent/FI43597C/fi active
- 1962-06-06 CH CH682262A patent/CH409967A/fr unknown
- 1962-06-07 LU LU41846D patent/LU41846A1/xx unknown
- 1962-06-07 BE BE618663A patent/BE618663A/fr unknown
- 1962-06-07 BR BR139733/62A patent/BR6239733D0/pt unknown
- 1962-06-07 DK DK253862AA patent/DK129199B/da unknown
- 1962-06-08 SE SE6441/62A patent/SE322513B/xx unknown
- 1962-06-08 SE SE05873/68A patent/SE357204B/xx unknown
- 1962-07-01 ES ES277871A patent/ES277871A1/es not_active Expired
- 1962-07-06 FR FR903129A patent/FR2899M/fr active Active
-
1967
- 1967-03-30 OA OA52879A patent/OA02701A/xx unknown
-
1971
- 1971-02-24 NO NO681/71A patent/NO133074C/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA984379A (en) | 1976-02-24 |
| FI43597B (no) | 1971-02-01 |
| SE322513B (no) | 1970-04-13 |
| DE1445701A1 (de) | 1969-08-28 |
| ES277871A1 (es) | 1962-12-01 |
| CH409967A (de) | 1966-03-31 |
| NO133074C (no) | 1976-03-03 |
| DK129199B (da) | 1974-09-09 |
| FI43597C (fi) | 1971-05-10 |
| GB982252A (en) | 1965-02-03 |
| DK129199C (no) | 1975-01-27 |
| SE357204B (no) | 1973-06-18 |
| OA02701A (fr) | 1970-12-15 |
| FR2899M (fr) | 1964-11-09 |
| BR6239733D0 (pt) | 1973-06-14 |
| NO122749B (no) | 1971-08-09 |
| BE618663A (fr) | 1962-12-14 |
| DE1445684A1 (de) | 1968-12-05 |
| LU41846A1 (no) | 1962-12-07 |
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