NL8202378A - METHOD FOR PREPARING RIFAMYCIN COMPOUNDS AND COMPOUND PREPARED COMPOUNDS. - Google Patents
METHOD FOR PREPARING RIFAMYCIN COMPOUNDS AND COMPOUND PREPARED COMPOUNDS. Download PDFInfo
- Publication number
- NL8202378A NL8202378A NL8202378A NL8202378A NL8202378A NL 8202378 A NL8202378 A NL 8202378A NL 8202378 A NL8202378 A NL 8202378A NL 8202378 A NL8202378 A NL 8202378A NL 8202378 A NL8202378 A NL 8202378A
- Authority
- NL
- Netherlands
- Prior art keywords
- formula
- rifamycin
- compounds
- compound
- compound prepared
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 20
- 238000000034 method Methods 0.000 title claims description 15
- HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical class OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 title claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- -1 Rifamycin compound Chemical class 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 229930189077 Rifamycin Natural products 0.000 claims description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229960003292 rifamycin Drugs 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DAIDESYYUQXSBN-KPDXFNFZSA-N 3-Hydroxyrifamycin S Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=C(O)C(=O)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C DAIDESYYUQXSBN-KPDXFNFZSA-N 0.000 description 5
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229960001225 rifampicin Drugs 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 2
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 241001468213 Amycolatopsis mediterranei Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical group CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- 241000191938 Micrococcus luteus Species 0.000 description 1
- 241001646725 Mycobacterium tuberculosis H37Rv Species 0.000 description 1
- 108700035964 Mycobacterium tuberculosis HsaD Proteins 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000786363 Rhampholeon spectrum Species 0.000 description 1
- BTVYFIMKUHNOBZ-ZDHWWVNNSA-N Rifamycin S Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=CC(=O)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C BTVYFIMKUHNOBZ-ZDHWWVNNSA-N 0.000 description 1
- BTVYFIMKUHNOBZ-ODRIEIDWSA-N Rifamycin S Chemical compound O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-ODRIEIDWSA-N 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
* * * 823056/vdV/mk* * * 823056 / vdV / mk
Korte aanduiding: Werkwijze voor de bereiding van ri famycineverbin- dingen alsmede aldus bereide verbindingen.Short designation: Process for the preparation of ribamycin compounds and compounds thus prepared.
\\
De uitvinding heeft betrekking op een werkwijze * voor de bereiding van rifamycineverbindingen,The invention relates to a process * for the preparation of rifamycin compounds,
De Europese octrooiaanvrage 0 014 181 beschrijft nieuwe rifamycineverbindingen waarvan 3-hydroxy-rifamycine S met 5 formule la van het formuleblad belangwekkende antibiotische werking bezit.European patent application 0 014 181 describes new rifamycin compounds, of which 3-hydroxy-rifamycin S of formula la of the formula sheet has interesting antibiotic activity.
Volgens deze Europese octrooiaanvrage wordt 3- -hydroxy-rifamycine S door fermenteren van de Nocardia mediterranei-stam bereid.According to this European patent application, 3-hydroxy-rifamycin S is prepared by fermenting the Nocardia mediterranei strain.
10 De onderhavige uitvinding beoogt een werkwijze te verschaffen voor de bereiding van 3-hydroxy-rifamycine S langs ' chemische weg onder toepassing van goedkope uitgangsmaterialen die normaal in de Handel verkrijgbaar zijn.The present invention aims to provide a process for the preparation of 3-hydroxy-rifamycin S by chemical means using inexpensive starting materials normally available in the trade.
Nadat een dergelijke werkwijze gevonden was bleek 15 dat daarmee niet alleen 3-hydroxy-rifamycine S maar ook andere waar-devolle rifamycineverbindingen bereid konden worden.After such a process had been found, it was found that it could produce not only 3-hydroxy-rifamycin S, but also other valuable rifamycin compounds.
De werkwijze volgens de onderhavige uitvinding is meer in het bijzonder geschikt voor de bereiding van rifamycinederi-vaten met formule 1 van het formuleblad, waarin R^ en R2 beiden -OH 20 voorstellen of waarin en R2 gezamenlijk formule 2 voorstellen en Rg gekozen wordt uit de groep: -OH; -0-8-H en O-S-CH^, waarbij men een verbinding met formule 1, waarin R^ en R2 de bovengenoemde betekenis bezitten en Rg = -Br laat reageren met een natrium-, kalium- of triethylaminezout van miere- of azijnzuur in een dipolair 25 aprotisch oplosmiddel bij een temperatuur tussen kamertemperatuur en +60 °C..The process of the present invention is more particularly suitable for the preparation of rifamycin derivatives of formula 1 of the formula sheet, wherein R 1 and R 2 both represent -OH 20 or wherein and R 2 together represent formula 2 and R 9 is selected from the group: -OH; -O-8-H and OS-CH 2, wherein a compound of formula 1, in which R 1 and R 2 have the above meaning and Rg = -Br is reacted with a sodium, potassium or triethylamine salt of formic or acetic acid in a dipolar aprotic solvent at a temperature between room temperature and +60 ° C.
Een aantal van de volgens de bovengenoemde werkwijze bereide rifamycineverbindingen zijn nieuwe verbindingen (die binnen het kader der uitvinding vallen) met de algemene formule 1, 30 waarin en R2 gezamenlijk^formule g voorstellen en gekozen wordt uit de groep -OH; , _o_c_CH3 en ~Br* ver^inc*in9 8202378 -2- * '"'si i waarin R^ gelijk is aan -Br is een tussenverbinding die voor de bereiding van andere rifamycineverbindingen gebruikt wordt, waarin ^3* -0 C H 0 C CH voorste^'t/ waarbij men deze verbinding met een natrium-, kalium- ^ of triethylaminezout van miere- of azijnzuur 5 in een dipoiair aprotisch oplosmiddel bij een temperatuur tussen kamertemperatuur en +60°C laat reageren.Some of the rifamycin compounds prepared by the above method are new compounds (which fall within the scope of the invention) of the general formula 1, wherein and R 2 jointly represent formula g and is selected from the group -OH; , _o_c_CH3 and ~ Br * ver ^ inc * in9 8202378 -2- * '' 'si where R ^ is equal to -Br is an intermediate used for the preparation of other rifamycin compounds, wherein ^ 3 * -0 CH 0 C CH front / where this compound is reacted with a sodium, potassium or triethylamine salt of formic or acetic acid 5 in a dipoic aprotic solvent at a temperature between room temperature and + 60 ° C.
De verbinding met formule 1, waarin en Rg gezamenlijk formule 2 en R^ : -Br voorstellen, kan men gemakkelijk bereiden uit een rifamycineverbinding met dezelfde formule, waarin 10 echter Rg : -H voorstelt (deze verbinding is op zichzelf bekend en beschreven in Helvetica Chimica Acta, 56, 2343 (1973)) en bereid volgens de werkwijze beschreven in de ter inzage gelegde Duitse octrooiaanvrage DOS 2548128 en DOS 2851312, die beide betrekking hebben op de bereiding van een verbinding met formule 1, waarin R^ 15 s Rj = -OH en R^ = -Br. De laatstgenoemde verbinding is eveneens een op zichzelf bekende tussenverbinding die gebruikt kan worden voor het uitvoeren van de werkwijze volgens de onderhavige uitvinding.The compound of formula 1, in which and Rg jointly represent formula 2 and R 1: -Br, can be readily prepared from a rifamycin compound of the same formula, wherein 10 represents Rg: -H (this compound is known per se and described in Helvetica Chimica Acta, 56, 2343 (1973)) and prepared according to the method described in German Patent Application Laid-open DOS 2548128 and DOS 2851312, both of which relate to the preparation of a compound of formula 1, wherein R <15 s Rj = -OH and R ^ = -Br. The latter compound is also an intermediate compound known per se which can be used to perform the method of the present invention.
De uitvinding wordt nu aan de hand van de volgende geen beperkingen inhoudende voorbeelden nader toegelicht, waarin de 20 dunne-laag-chromatografie wordt uitgevoerd op silicagel 60 ^254. Merck-platen met tolueen, ethylacetaat en methanol in de verhouding 11:4:4 als elutiemiddel.The invention is now further illustrated by the following non-limiting examples, in which the thin layer chromatography is performed on silica gel 60 ^ 254. Merck plates with toluene, ethyl acetate and methanol in the ratio 11: 4: 4 as eluent.
V00RBEELD IEXAMPLE I
3-Formyloxy-rifamycine S.3-Formyloxy-rifamycin S.
25 Men lost 7 g 3-broom-rifamycine S op in 50 ml di methyl formamide en voegt bij kamertemperatuur 2,5 g kaliumformiaat toe. Men verwarmt de oplossing tot 50°C, roert 6 uren en verdunt daarna met 200 ml ethylacetaat. Na wassen met water behandelt men de organische fase met verdund chloorwaterstofzuur en wast opnieuw met 30 gedestilleerd water.7 g of 3-bromo-rifamycin S are dissolved in 50 ml of dimethyl formamide and 2.5 g of potassium formate are added at room temperature. The solution is heated to 50 ° C, stirred for 6 hours and then diluted with 200 ml of ethyl acetate. After washing with water, the organic phase is treated with dilute hydrochloric acid and washed again with distilled water.
Men droogt de ethylacetaatoplossing boven water-vrij natriumsulfaat, filtreert en dampt in tot droog. Men lost het residu op in chloroform en laat uitkristalliseren. Opbrengst: 5,7 g van een verbinding met de algemene formule 1, waarin 8202378 u '» —3— ftThe ethyl acetate solution is dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue is dissolved in chloroform and allowed to crystallize. Yield: 5.7 g of a compound of the general formula 1, wherein 8202378 [mu] - 3 ft
Rx = R2 = -OH en R3 = HC-O- .Rx = R2 = -OH and R3 = HC-O-.
MS = 739 (M+)MS = 739 (M +)
Rf = 0.30 VOORBEELD IIRf = 0.30 EXAMPLE II
5 3-Hydroxy-rifamycine S.5 3-Hydroxy-rifamycin S.
Men lost 5,7 g 3-formyloxy-rifamycine S op in 50 ml methanol en vermengt met 100 ml van een l^'s oplossing van natrium-bicar bonaat in water.5.7 g of 3-formyloxy-rifamycin S are dissolved in 50 ml of methanol and mixed with 100 ml of a solution of sodium bicarbonate in water.
Men roert de verkregen oplossing 4 uren bij 50°C en lo voegt daarna 150 ml chloroform toe. Men vast de organische laag met verdund chloorwaterstofzuur en daarna met gedestilleerd water. Na drogen boven watervrij natriumsulfaat filtreert men de chloroform-oplossing en dampt in tot droog. Opbrengst : 5,2 g van een verbinding met de algemene formule 1, waarin ^ = = ^3 = 15 Het P.M.R.-spectrum komt overeen met het in deThe resulting solution is stirred at 50 ° C for 4 hours and 150 ml of chloroform are then added. The organic layer is solidified with dilute hydrochloric acid and then with distilled water. After drying over anhydrous sodium sulfate, the chloroform solution is filtered and evaporated to dryness. Yield: 5.2 g of a compound of the general formula 1, in which ^ = = ^ 3 = 15 The P.M.R. spectrum corresponds to that in the
Europese octrooiaanvrage 0 014 181 vermelde spectrum. Rf = 0,35.European patent application 0 014 181 spectrum. Rf = 0.35.
Men kan dezelfde verbinding bereiden uit 3-hydroxy-21,23-acetonide-rifamycine S (Voorbeeld IV) door hydrolyseren van de acetonidegroep volgens de werkwijze beschreven in Helv.Chim.Acta 20 56, 2347 (1973).The same compound can be prepared from 3-hydroxy-21,23-acetonide-rifamycin S (Example IV) by hydrolyzing the acetonide group according to the method described in Helv.Chim.Acta 20 56, 2347 (1973).
VOORBEELD IIIEXAMPLE III
3-Broom-21,23-acetonide-rifamycine S.3-Bromo-21,23-acetonide-rifamycin S.
Men bromeert 7,5 g 21,23-acetonide-rifamycine S volgens een bekende werkwijze (Duitse octrooiaanvragen 2 851 312 en 25 2 548 128). Opbrengst : 7 g van de overeenkomstige 3-broomverbinding. Br : 9,8JS. Rf = 0,49.7.5 g of 21.23-acetonide-rifamycin S are brominated by a known method (German patent applications 2 851 312 and 25 548 128). Yield: 7 g of the corresponding 3-bromo compound. Br: 9.8JS. Rf = 0.49.
VOORBEELD IVEXAMPLE IV
3-Hydroxy-21,23-acetonide-rifamycine S.3-Hydroxy-21,23-acetonide rifamycin S.
Men laat 7 g 3-broom-21,23-acetonide-rifamycine S 30 reageren met kaliumformiaat volgens de werkwijze beschreven in7 g of 3-bromo-21,23-acetonide-rifamycin S 30 are reacted with potassium formate according to the procedure described in
Voorbeeld I en uit het aldus verkregen ruwe 3-formyloxy-21,23-aceto-nide-rifamycine S verkrijgt men 4,8 g van de verbinding volgens de uitvinding onder toepassing van de werkwijze beschreven in Voorbeeld II.Example I and from the crude 3-formyloxy-21,23-acetonide-rifamycin S thus obtained 4.8 g of the compound according to the invention are obtained using the method described in Example II.
8202378 -4- . ' * MS = 751 (M+). Rf = 0,46.8202378 -4-. * MS = 751 (M +). Rf = 0.46.
De bactericide werking van een aantal verbindingen is volgens de onderhavige uitvinding onderzocht volgens de dubbele serietechniek in een voedingsmedium waarvan de resultaten in de 5 volgende tabel zijn samengevat (waarin vergeleken wordt met de werking van rifampicir^;The bactericidal activity of a number of compounds has been tested according to the present invention by the double-series technique in a nutrient medium, the results of which are summarized in the following table (comparing the activity of rifampicir;
Bacterie Rifampicine Verbinding Verbinding van Voor- van Voor-Bacteria Rifampicin Compound Compound of Front of Front
beeld II beeld Ipicture II picture I
10 Staphylococcus aureus 0.0005 0.018 0.02210 Staphylococcus aureus 0.0005 0.018 0.022
Streptococcus pyogenes 0.6 25 20Streptococcus pyogenes 0.6 25 20
Streptococcus faecalis 0.3 25 20Streptococcus faecalis 0.3 25 20
Sarcina lutea 0.0045 0.09 0.004Sarcina lutea 0.0045 0.09 0.004
Escherichia coli 5 12.5 10 15 Klebsiella pneumoniae 5 25 20Escherichia coli 5 12.5 10 15 Klebsiella pneumoniae 5 25 20
Proteus vulgaris 5 2520Proteus vulgaris 5 2520
Pseudomonas aeruginosa 5 50 20Pseudomonas aeruginosa 5 50 20
Salmonella abortivo- 20 equina 2,5 25 20Salmonella abortivo- equina 2.5 25 20
Mycobacterium tuberculosis H37 Rv 0.01 0.025 0.01Mycobacterium tuberculosis H37 Rv 0.01 0.025 0.01
De getallen in de tabel hebben betrekking op MIC 25 en zijn in mcg/ml weergegeven/^MIC = minimale remmende concentratie.The numbers in the table refer to MIC 25 and are shown in mcg / ml / ^ MIC = minimum inhibitory concentration.
De verbinding van Voorbeeld II, hoewel minder werk-zaam dan rifampicine heeft toch een aanzienlijke remmende werking in het bijzonder ten opzichte van gram-positieve bacteria en Mycobacterium tuberculosis. De werking van de volgens Voorbeeld I bereide 30 verbinding is verbeterd en bereikt, wat belangrijk is^die van rifampicine ten opzichte van Mycobacterium tuberculosis.The compound of Example II, although less effective than rifampicin, nevertheless has a significant inhibitory effect, in particular against gram-positive bacteria and Mycobacterium tuberculosis. The action of the compound prepared according to Example I has been improved and achieved, importantly that of rifampicin over Mycobacterium tuberculosis.
82023788202378
Claims (4)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8122417 | 1981-07-21 | ||
| GB8122417 | 1981-07-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8202378A true NL8202378A (en) | 1983-02-16 |
Family
ID=10523383
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8202378A NL8202378A (en) | 1981-07-21 | 1982-06-11 | METHOD FOR PREPARING RIFAMYCIN COMPOUNDS AND COMPOUND PREPARED COMPOUNDS. |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5824588A (en) |
| BE (1) | BE893873A (en) |
| CH (1) | CH651046A5 (en) |
| DE (1) | DE3209109A1 (en) |
| DK (1) | DK318182A (en) |
| FR (1) | FR2510116A1 (en) |
| IT (1) | IT1210479B (en) |
| NL (1) | NL8202378A (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4298692A (en) * | 1979-01-25 | 1981-11-03 | Ciba-Geigy Corporation | Fermentation process for producing a rifamycin derivative |
| GR69740B (en) * | 1979-07-20 | 1982-07-12 | Ciba Geigy Ag |
-
1982
- 1982-03-12 DE DE19823209109 patent/DE3209109A1/en not_active Withdrawn
- 1982-04-02 FR FR8206006A patent/FR2510116A1/en active Pending
- 1982-05-27 IT IT8221518A patent/IT1210479B/en active
- 1982-05-28 CH CH3308/82A patent/CH651046A5/en not_active IP Right Cessation
- 1982-06-11 NL NL8202378A patent/NL8202378A/en not_active Application Discontinuation
- 1982-07-15 DK DK318182A patent/DK318182A/en not_active Application Discontinuation
- 1982-07-19 JP JP57124538A patent/JPS5824588A/en active Pending
- 1982-07-19 BE BE0/208621A patent/BE893873A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2510116A1 (en) | 1983-01-28 |
| JPS5824588A (en) | 1983-02-14 |
| IT1210479B (en) | 1989-09-14 |
| DE3209109A1 (en) | 1983-02-10 |
| DK318182A (en) | 1983-01-22 |
| CH651046A5 (en) | 1985-08-30 |
| IT8221518A0 (en) | 1982-05-27 |
| BE893873A (en) | 1982-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1215708A (en) | New process for the synthesis of pyrido-imidazo- rifamycins | |
| SE453089B (en) | IMIDAZO RIFAMYCINE DERIVATIVES, PROCEDURES FOR PREPARING THEREOF AND PHARMACEUTICAL COMPOSITION | |
| SE457084B (en) | N-METHYL-11-AZA-10-DEOXO-10-DIHYDROERYTROMYCINE AND DERIVATIVES AND PROCEDURES FOR PREPARING THEREOF | |
| HU221980B1 (en) | Process for producing diacereine and a new acetylated aloin intermediate | |
| US4464527A (en) | Antibacterial 9-deoxo-9a-alkyl-9a-aza-9a-homoerythromycin A derivatives and intermediates therefore | |
| CA1081218A (en) | Rifamycin compounds | |
| US4021601A (en) | Paromomycin derivatives and process for the preparation thereof | |
| US3975372A (en) | Preparation of 12,13-desepoxy-12,13-dehydrorosamicin | |
| US4049811A (en) | Compositions using cycloalkano-quinolone derivatives and their method of use | |
| CA1218650A (en) | Process for the synthesis of pyrido-imidazo- rifamycins | |
| NL8202378A (en) | METHOD FOR PREPARING RIFAMYCIN COMPOUNDS AND COMPOUND PREPARED COMPOUNDS. | |
| CH630391A5 (en) | Process for preparing derivatives of rosaramicin | |
| US5821348A (en) | Process for producing etoposide | |
| US4008362A (en) | 1-N-((S)-α-substituted-ω-aminoacyl)-neamine or -ribostamycin and the production thereof | |
| GB2083039A (en) | Spectinomycin analogues and their preparation | |
| US4429116A (en) | Alkylated oleandomycin containing compounds | |
| US4103082A (en) | Aminocyclitol derivatives and process for producing the same | |
| CA1076562A (en) | Neamine derivatives and process for preparing the same | |
| US4008218A (en) | 1-N-((S)-α-substituted-ω-aminoacyl)-neamine or -ribostamycin and the production thereof | |
| US5091411A (en) | Pseudo-primycin complexes, components and acid addition salts thereof as well as a process for the preparation of same | |
| CH661513A5 (en) | 14-DE (HYDROXYMETHYL) -MYCAMINOSYLTYLONOLIDE COMPOUNDS. | |
| GB2102409A (en) | Rifamycin derivatives | |
| CA1084907A (en) | Cephalosporin derivatives, preparation and compositions containing same | |
| US4169940A (en) | Chemical oxidation of novobiocin and products obtained therefrom | |
| CA1087612A (en) | 6'-n-methyl-xk-88-5 and process for the production thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A85 | Still pending on 85-01-01 | ||
| BV | The patent application has lapsed |