CN1119864A - Process for the preparation of condensed carbapeneme derivatives - Google Patents
Process for the preparation of condensed carbapeneme derivatives Download PDFInfo
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- CN1119864A CN1119864A CN94191532A CN94191532A CN1119864A CN 1119864 A CN1119864 A CN 1119864A CN 94191532 A CN94191532 A CN 94191532A CN 94191532 A CN94191532 A CN 94191532A CN 1119864 A CN1119864 A CN 1119864A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The present invention provides a process for the preparation of the antibacterial compound of formula (I) or a salt thereof which comprises the thermal cyclisation of a compound of formula (II), wherein R is a carboxyl protecting group, followed by removal of the said carboxyl protecting group R and if necessary or desired conversion of the resultant carboxylic acid into a salt thereof.
Description
The present invention relates to improving one's methods of a kind of synthetic antibiotic.European patent application open 0416953A2 has narrated three new ring antibiotic agent of a class and preparation method thereof.Wherein said good especially compound is methoxy derivatives (I) and salt thereof.
EPA0416953A2 also mentions formula (I) compound and can prepare by following schematic method,
R wherein
1aIt is hydroxyl protecting group; R
2aBe carboxyl-protecting group, Y is oxygen or phosphino-.
More particularly, this specification sheets has been introduced with intermediate (R wherein
1aBe t-butyldimethylsilyl, Y is that oxygen and R2a are allyl group or R
1aBe that t-butyldimethylsilyl, Y are PPh
3And R
2aBe benzyl) method of preparation formula (1) compound.
Be surprised to find that now, if in this synthetic method, before cyclisation step, remove hydroxyl protecting group R
1a 'Can be significantly improved to the conversion of desirable three ring antibiotic elements (1) by lactan (A) (wherein Y is a phosphino-).
That is to say, the invention provides the method for a kind of preparation formula (I) compound or its salt, comprise making lactan (II) heating cyclisation, remove carboxyl-protecting group then, obtain free carboxy acid or its physiologically acceptable salt,
Wherein R is a carboxyl-protecting group.Suitable carboxyl-protecting group R comprises allyl group or arylmethyl, as benzyl, tertiary butyl benzyl diphenyl methyl or distich phenyl methyl.
This heating cyclization method better is by in solvent, carry out at 40-200 ° of scope internally heated type (II) compound.The example of suitable solvent comprises hydro carbons, as toluene or dimethylbenzene, and ethers, as tetrahydrofuran (THF) or 1,4-diox, or alkanol, for example propyl alcohol or Virahol, or ester class, as ethyl acetate, the perhaps mixture of two or more above-mentioned solvents.
Carboxyl-protecting group R can remove by standard method, for example at ProtectiveGroups in Organic Chemistry, and 192-210 page or leaf, those methods described in (JFW McOmie edits, Phenum Press nineteen eighty-three publish).For example when R represents an arylmethyl, it can be with hydrogen and a kind of metal catalyst (as palladium) in the solvent that is fit to (as alkanol, as propyl alcohol) and better be to exist down at tertiary amine (as trialkylamine, as triethylamine) to remove by standard program.
When radicals R was represented an allyl group, this group better was by removing by handling with allyl acceptor in the presence of triphenyl phosphine in the presence of the tetrakis triphenylphosphine palladium and randomly.Suitable allyl acceptor comprises sterically hindered amine, as TERTIARY BUTYL AMINE, ring secondary amine (as morpholine or thiomorpholine), tertiary amine (as triethylamine), aliphatic series or cyclic aliphatic beta-dicarbonyl compound, as methyl ethyl diketone, methyl aceto acetate or methone, or paraffinic acid or its an alkali metal salt, as acetate, propionic acid or 2 ethyl hexanoic acid or its sylvite or sodium salt.Carry out in more a kind of inert solvent of this reaction, as use ethers, as ether or tetrahydrofuran (THF), alkanol, as ethanol or propyl alcohol, the ester class, as ethyl acetate, or halogenated hydrocarbon, as methylene dichloride, or their mixture as solvent.This reaction can particularly be carried out under the room temperature easily in 0-40 ° of temperature range.
In a preferred version of the present invention, this cyclization is performed such: with formula (III) compound, wherein R is an arylmethyl, as benzyl or tertiary butyl benzyl, select 40-120 ° of temperature range for use, the solvent of selecting for use is, for example, the mixture of hydro carbons (as toluene), ethers (as 1, the 4-diox) or alkanol (as propyl alcohol or Virahol) or ester class (as ethyl acetate) or itself and alkanol.
The method preferably of removing arylmethyl carboxyl-protecting group R be with hydrogen and metal catalyst (as palladium) in solvent (as alkanol, as ethanol, Virahol, the ester class is as ethyl acetate, or ketone, as acetone), in the presence of alkali, carry out hydrogenolysis.Used suitable alkali comprises organic tert-alkali such as trialkylamine (as triethylamine) in the reaction.Can carboxylic acid (I) or its salt be converted into its physiologically acceptable salt easily without separating the hydrogenolysis reaction product.For example, add non-solvent then,,, prepare its sodium salt as diisopropyl ether as ethers by in anti-solution, adding acetone and Sodium Ethylhexanoate.In this method, the seed crystal that adds required sodium salt may be good.
The salt of formula (I) compound comprises its physiologically acceptable salt and the physiologically acceptable salt of Qi Fei.
The physiologically acceptable salt that formula (I) compound is suitable comprises the salt that it is become with basic metal (as sodium or potassium), alkaline-earth metal (as calcium), amino acid (as Methionin or arginine) and organic bases (as PROCAINE HCL, PHARMA GRADE, phenylbenzyl amine, thanomin, diethanolamine and N-methylglucosamine).The non-physiologically acceptable salt of formula (I) compound can be used as that intermediate is prepared and/or separate type (I) compound or its physiologically acceptable salt.
The oxy-compound of formula (II) is new and represents another aspect of the present invention that it can be prepared by conventional procedure by the corresponding ether of formula (III).
R wherein
1Be trialkylsilkl, the definition of R is suc as formula defined in (II).Like this, if R
1Be t-butyldimethylsilyl, it can be by removing with tetrabutylammonium fluoride and acetic acid treatment in solvent (as tetrahydrofuran (THF)), perhaps by in appropriate organic solvent (for example acetonitrile and acetate), remove with mineral acid (example hydrochloric acid) hydrolysis.
The silyl ether or the known compound of formula (III), perhaps can by the program described in the EPA0416953A2 and or the described method of embodiment given below prepare.
In order to understand the present invention more fully, provide following embodiment, only be used to illustrate the present invention.
In intermediate and embodiment, all temperature are ℃; The solution drying is meant this solution anhydrous sodium sulfate drying.
Intermediate 1
2-[3S, 4R)-3-[(R)-1-(t-butyldimethylsilyl oxygen) ethyl]-4-[(2 ' S, 6 ' R)-2-methoxyl group-1 " oxo hexamethylene-6 "-yl] nitrogen heterocyclic din-2-ketone-1-yl]-the positive phosphorus guanidine-acetic acid of 2-triphen benzyl ester.
Under nitrogen protection; toward (3S, 4R)-3[(R)-1-(t-butyldimethylsilyl oxygen ethyl]-4[(R)-2 ' (S)-6-methoxyl group-1 '-the oxo cyclohexyl)] add acetaldehyde acid benzyl ester (2.4 gram), triethylamine (0.5 milliliter) and 3A molecular sieve in the solution of nitrogen heterocyclic din-2-ketone (4.5 gram) in dry tetrahydrofuran (15 milliliters).Reaction mixture was stirred 24 hours at 22 °, with 100 milliliters of ethyl acetate dilutions,, dry and concentrated under vacuum with 2 * 100 milliliters of saturated aqueous ammonium chlorides and the washing of 2 * 200 mL of saline.Under nitrogen protection and 0 ° of condition, oily residue (6.4 gram) is dissolved in the dry tetrahydrofuran (100 milliliters), add thionyl chloride (1.84 milliliters) and 2,6-lutidine (3.20 milliliters).Reaction mixture stirred 4 hours at 22 °, with 100 milliliters of ethyl acetate dilutions, used saturated aqueous ammonium chloride (2 * 150 milliliters), washed with 5% sodium bicarbonate aqueous solution (2 * 150 milliliters) and salt solution (2 * 150 milliliters), dry and vacuum concentration.Oiliness residue (6.2 gram) is dissolved in 50 milliliter 1, and the 4-diox adds 2,6-lutidine (2.2 milliliters), Sodium Bromide (2.6 gram) and triphenylphosphine (6.64 gram).Reaction mixture was stirred 15 hours at 22 °, pour into then in 200 milliliters of saturated aqueous ammonium chlorides, with 200 milliliters of ethyl acetate extraction.Organic layer washs with saturated aqueous ammonium chloride (200 milliliters) and salt solution (2 * 200 milliliters), dry and concentrating under reduced pressure.The oily residue obtains white solid title compound (5.04 gram), 128 ° of fusing points, Rf=0.6 when making thin-layer chromatography with ethyl acetate/hexanaphthene 1/1 with silicagel column, carry out chromatography with petroleum ether/ethyl ether (1: 1) as eluent.
Embodiment 1
(4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-benzyl formate.
In the ice-cooled solution of the usefulness of intermediate 1 (3.7 gram) in acetonitrile (100 milliliters), add acetate (4.8 milliliters) and 37% hydrochloric acid (3.73 milliliters).Reaction mixture stirred 1 hour at-15 °, poured in the 5% cold sodium bicarbonate aqueous solution (200 milliliters), extracted with ethyl acetate (200 milliliters).Organic layer washs with salt solution (2 * 200 milliliters), dry also concentrating under reduced pressure, obtain 2-[3S, 4R)-3[(R)-1-(hydroxyethyl)-4-[(2 ' S, 6 ' R)-2-methoxyl group-1 " oxo hexamethylene-6 "-yl] nitrogen heterocyclic din-2-ketone-1-yl]-2-triphenyl phosphoranyl jasmal, the white foam body is dissolved in 1 with it, in the 4-diox (30 milliliters), reflux 7 hours.Solution washs with saturated aqueous ammonium chloride (2 * 100 milliliters) and salt solution (2 * 100 milliliters) with ethyl acetate (100 milliliters) dilution, (with saturated aqueous ammonium chloride (2 * 100 milliliters) and salt solution (2 * 100 milliliters) washing) dry and vacuum concentration.The oily residue is made eluent with ethyl acetate/hexanaphthene (1: 1) on silicagel column, obtain spumescence title compound (0.59 gram; Make thin-layer chromatography at 1: 1 with ethyl acetate/hexanaphthene, Rf=0.3).IR (CDCl
3), V
MaximumCm
-1: 3600 (O-H), 1772 (C=O beta-lactams), 1718 (C=O, esters), 1632 (C=C);
1H-NMR(300MHz，CDCl
3]：6.47-7.30(m)，5.29(dd)，4.94(t)，4.24(m)，4.19(dd)，3.3-3.2(m)，3.20(s)，2.05(m)，1.9-1.2(m)，1.61(d)，1.32(d)。
Embodiment 2
(4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10 (1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-formic acid 4-tertiary butyl benzyl ester
(i) 2 (3S, 4S)-3[(R)-1-(hydroxyethyl)-4-[(2 ' S, 6 ' R)-2-methoxyl group-1 " oxo hexamethylene-6 "-yl] nitrogen heterocyclic din-2-ketone-1-yl]-2-triphenyl phosphoranyl acetate 4-tertiary butyl benzyl ester.
With 2,6-two picolins (3.95 gram) are added to (3S, 4R)-3[(R)-1-(t-butyldimethylsilyl oxygen ethyl]-4 (R)-2 ' (S)-6-methoxyl groups-1 '-the oxo cyclohexyl)] in nitrogen heterocyclic din-2-ketone (5.0 gram) and the solution of oxoethanoic acid 4-tertiary butyl benzyl ester (4.51 restrain) in ethyl acetate (50 milliliters), with the gained vlil.10 milliliters of ethyl acetate, gained vlil 6 hours are removed in distillation.Reaction solution is cooled to 0-5 °, and with the solution of 30 minutes adding thionyl chloride (2.05 milliliters) in ethyl acetate (10 milliliters), the gained reaction mixture stirred 45 minutes at 0-5 °.Dropwise add 8% sodium hydrogen carbonate solution (70 milliliters) and suppress this reaction, the gained mixture stirred 30 minutes at 5 °, made respectively then to be separated.Water layer extracts with ethyl acetate (15 milliliters) again, and the organic phase of merging is washed with 1M citric acid solution (40 milliliters), water (20 milliliters) and salt solution (20 milliliters).Organic solution is with 2, and 6-lutidine (2.5 milliliters), Sodium Bromide (2.25 gram) and triphenylphosphine (5.7 gram) are handled.The gained mixture stirred 20 hours at 25 ℃, used 1M citric acid solution (25 milliliters), water (25 milliliters) and salt solution (3 * 50 milliliters) washing then.The vacuum-evaporation organic phase, obtain 13.8 gram light browns, 2 (3S, 4S)-3-[(R)-1-(t-butyldimethylsilyl oxygen) ethyl]-4-[(2 ' S, 6 ' R)-2-methoxyl group-1 " oxo hexamethylene-6 "-yl] nitrogen heterocyclic din-2-ketone-1-yl]-2-triphenyl phosphoranyl acetate 4-tertiary butyl benzyl ester.It is dissolved in the mixture of hexanaphthene (138 milliliters), ethyl acetate (27 milliliters) and tetrahydrofuran (THF) (91 milliliters), the gained solution stirring is cooled to 0-5 °.With 15 minutes cold 4M hydrochloric acid (262 milliliters) is added wherein, keep its temperature simultaneously, this biphase mixture was stirred 1 hour at 2-5 ° at 0-5 °.Make it to be separated, water layer adds 4M solution of potassium carbonate (215 milliliters) at 5 ° then and makes it alkalify with the mixture washing of hexanaphthene (138 milliliters) and ethyl acetate (27 milliliters).Water layer extracts with ethyl acetate (2 * 165 milliliters), and dry and vacuum-evaporation obtains foam 3.27 grams, and this foam is dissolved in the methyl ethyl ketone (60 milliliters).In vigorous stirring with under, in this freezing (0 °) solution, dropwise added this mixture of normal hexane (275 milliliters) in 0-5 ° of stirring 1 hour, filtration then with 30 minutes with the nitrogen protection condition.Solid is with the washing of normal hexane/methylethylketone (55 milliliters/11.7 milliliters) mixture, and is dry then, obtains title compound solid (4.35 gram).(ethyl acetate thin-layer chromatography; Rf=0.35) IR (film) V
Maximum(cm
-1) 3468 (O-H), 1745 (C=O beta-lactams), 1651-1618 (C=O, C=C)
1H-NMR (300MHz, CDCl
3]: 7.20-7.28 (m), 7.10-7.00 (m), 6.70-6.56 (m), 5.10 (m), 4.96-4.56 (m), 4.07 (m), 4.00-3.66 (m), 3.47 (m), 3.26 (s), 3.12 (s), 3.08 (s), 3.00-2.84 (m), 2.71 (m), 2.52-1.80 (m), 1.70-1.50 (m), 1.44-1.20 (m), 1.25 (d), 1.02 (d)
(ii) (4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-formic acid 4-tertiary butyl benzyl ester
With the vlil of embodiment 2 (i) compound (1.3 gram) in toluene (52 milliliters) 13 hours, concentrating under reduced pressure then.Oily matter is dissolved in the t-butyl methyl ether (25 milliliters) 1: 1 mixture (25 milliliters) of DMF/ water washing 3 times of this organic solution.Organic layer dilutes with t-butyl methyl ether (10 milliliters), water (3 * 25 milliliters) washing, and dry and evaporation gets yellow spumescence title compound (0.7 gram).
(ether thin-layer chromatography; Rf=0.32)
1H-NMR(300MHz，CDCl
3]：7.38(s)，5.34(d)，5.19(d)，4.95(t)，4.21(m)，4.17(dd)，3.25(dd)，3.23(m)，3.21(s)，2.06(m)，1.86(m)，1.77(d)，1.60(m)，1.40(m)，1.32(d)，1.31(s)。
Embodiment 3
(4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-sodium formiate
Under nitrogen protection, 10% palladium/carbon (0.86 gram) is added to (4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] in the solution of 11 carbon-2-alkene-benzyl formate (300 milligrams) in tetrahydrofuran (THF) (10 milliliters).The hydrogenation 20 minutes under 25-26 ℃ and 1 normal atmosphere of this mixture leaches catalyzer and then with ether (10 milliliters) washing.In filtrate, add 2 ethyl hexanoic acid sodium (0.134 gram), add ether (100 milliliters) then.Under nitrogen, this white suspension was stirred 1 hour in 0 ℃.Leach solid,, obtain white solid title compound (0.115 gram) with ether (5 milliliters) washing, vacuum-drying.
1H-NMR(300MHz)(D
2O)：4.74(m)，4.10(m)，4.03(dd)，3.31(dd)，3.11(s)，3.03(m)，1.90(m)，1.75(m)，1.6-1.2(m)，1.13(m)。
Embodiment 4
(4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10 (1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-sodium formiate
Under nitrogen protection, 10% palladium/carbon (0.2 gram) and triethylamine (0.23 milliliter) are added to (4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-formic acid tertiary butyl benzyl ester (0.5 gram) just-solution in the propyl alcohol (5 milliliters) in.About 40 minutes of the hydrogenation under room temperature and 1 normal atmosphere of this mixture.Leach catalyzer, with acetone (2 milliliters) washing.2 ethyl hexanoic acid sodium (0.29 gram) is added in the filtrate that merges, behind the several minutes,, in mixture, add seed crystal toward wherein dripping isopropyl ether (20 milliliters).Under nitrogen protection about 2 hours in this white suspension of stirring at room, leach solid, with isopropyl ether/n-propyl alcohol/acetone 10/2.5/1 mixture (1 milliliter) washing, vacuum-drying, obtain white solid title compound (0.115 gram).
Embodiment 5
(4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-sodium formiate
With 2-(3S, 4R, )-3[(R)-1-(hydroxyethyl)-4-[(2 ' S, 6 ' S)-2-methoxyl group-1 " oxo hexamethylene-6 "-yl] nitrogen heterocyclic din-2-ketone-1-yl]-vlil of 2-triphenyl phosphoranyl jasmal (20 gram) in 1-propyl alcohol (300 milliliters) 3 hours.After the cooling,, add 2-propyl alcohol (120 milliliters) with solvent vacuum-evaporation, with solution concentration, (4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-benzyl formate crude product, be oily matter (20 gram).Under nitrogen, 10% palladium/carbon (4.8 gram) and triethylamine (4.6 milliliters) are added in the solution of this oily matter in 2-propyl alcohol (300 milliliters).The hydrogenation 35 minutes under 25-26 ℃ and 1 normal atmosphere of gained mixture.Leach catalyzer,, filtrate is merged and be concentrated into 100 milliliters with acetone (100 milliliters) washing.In concentrated solution, add the solution of 2 ethyl hexanoic acid sodium (5.8 gram) in acetone (40 milliliters), toward wherein dripping isopropyl ether (400 milliliters), last about 30 minutes then.Under room temperature and nitrogen protection, stirred this white suspension 1.5 hours, leach solid, with isopropyl ether (2 * 25 milliliters) washing, vacuum-drying, get white solid title compound (5.35 gram).
IR (whiteruss) V
Maximum(cm
-1): 3387 (OH), 1776-1726 (C=O), 1616-1587) (C=C).
Claims (10)
1. the method for preparation formula (I) compound or its salt,
Comprise making formula (II) compound heating cyclisation,
Wherein R is a carboxyl-protecting group, removes above-mentioned carboxyl-protecting group R then, and, when needing the gained carboxylic acid is converted into its salt.
2. carry out according to the process of claim 1 wherein that the heating cyclisation is reflected in the solvent.
3. according to the method for claim 1 or 2, solvent wherein is selected from hydrocarbon, ether, alkanol or ester, the perhaps mixture of two or more these solvents.
4. according to each method among the claim 1-3, cyclization wherein carries out in 40-200 ℃ of temperature range.
5. according to each method among the claim 1-4, wherein carboxyl-protecting group R is an arylmethyl.
6. according to the method for claim 5, carboxyl-protecting group is wherein removed by hydrogenolysis.
7. according to each method among the claim 1-6, its Chinese style (I) compound comes out with the isolated in form of its physiologically acceptable salt.
8. formula (I) compound or its salt that is prepared into according to each method among the claim 1-7.
According to each method among the claim 1-7 make (4S, 8S, 9R, 10S, 12R)-4-methoxyl group-10-(1-hydroxyethyl)-11-oxo-1-aza-tricycle [7,2,0,0
3.8] 11 carbon-2-alkene-2-sodium formiate.
10. by R the benzyl ester or the 4-tertiary butyl benzyl ester of formula (I) compound that makes of the heating cyclization of formula (II) compound of benzyl or 4-tertiary butyl benzyl.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939305813A GB9305813D0 (en) | 1993-03-20 | 1993-03-20 | Chemical process |
| GB9305813.9 | 1993-03-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1119864A true CN1119864A (en) | 1996-04-03 |
Family
ID=10732441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94191532A Pending CN1119864A (en) | 1993-03-20 | 1994-03-17 | Process for the preparation of condensed carbapeneme derivatives |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0689542A1 (en) |
| JP (1) | JPH08507776A (en) |
| CN (1) | CN1119864A (en) |
| AU (1) | AU6427294A (en) |
| CA (1) | CA2157787A1 (en) |
| FI (1) | FI954399A (en) |
| GB (1) | GB9305813D0 (en) |
| HU (1) | HUT73486A (en) |
| NO (1) | NO953697L (en) |
| PL (1) | PL310620A1 (en) |
| WO (1) | WO1994021637A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9516118D0 (en) * | 1995-08-05 | 1995-10-04 | Glaxo Spa | Chemical process |
| EP2085084A1 (en) | 2008-01-29 | 2009-08-05 | LEK Pharmaceuticals D.D. | Use of inhibitor of beta-lactamases and its combination with beta-lactam antibiotics |
| RS63461B1 (en) | 2017-05-08 | 2022-08-31 | Glaxosmithkline Ip Dev Ltd | Sanfetrinem or a salt or ester thereof for use in treating mycobacterial infection |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR900006449B1 (en) * | 1982-08-24 | 1990-08-31 | 상꾜 가부시끼가이샤 | Process for the preparation of azetidinone derivatives |
| CZ435990A3 (en) * | 1989-09-08 | 1999-11-17 | Glaxo S.P.A. | 10-(1-hydroxyethyl)-11-oxo-1-azatricyclo/7,2,0,03,8/-undec-2ene-2- carboxylic acid and derivatives thereof, process of their preparation, use for preparing pharmaceutical preparations and pharmaceutical compositions containing thereof |
| KR920019791A (en) * | 1991-04-05 | 1992-11-20 | 우메모또 요시마사 | Polycyclic Carbapenem Compounds, Methods for Making and Uses thereof |
-
1993
- 1993-03-20 GB GB939305813A patent/GB9305813D0/en active Pending
-
1994
- 1994-03-17 AU AU64272/94A patent/AU6427294A/en not_active Abandoned
- 1994-03-17 CN CN94191532A patent/CN1119864A/en active Pending
- 1994-03-17 HU HU9502738A patent/HUT73486A/en unknown
- 1994-03-17 PL PL94310620A patent/PL310620A1/en unknown
- 1994-03-17 WO PCT/EP1994/000838 patent/WO1994021637A1/en not_active Application Discontinuation
- 1994-03-17 JP JP6520645A patent/JPH08507776A/en active Pending
- 1994-03-17 EP EP94911906A patent/EP0689542A1/en not_active Withdrawn
- 1994-03-17 CA CA002157787A patent/CA2157787A1/en not_active Abandoned
-
1995
- 1995-09-18 FI FI954399A patent/FI954399A/en unknown
- 1995-09-19 NO NO953697A patent/NO953697L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO953697D0 (en) | 1995-09-19 |
| EP0689542A1 (en) | 1996-01-03 |
| NO953697L (en) | 1995-09-19 |
| WO1994021637A1 (en) | 1994-09-29 |
| HUT73486A (en) | 1996-08-28 |
| CA2157787A1 (en) | 1994-09-29 |
| FI954399A0 (en) | 1995-09-18 |
| JPH08507776A (en) | 1996-08-20 |
| PL310620A1 (en) | 1995-12-27 |
| HU9502738D0 (en) | 1995-11-28 |
| AU6427294A (en) | 1994-10-11 |
| FI954399A (en) | 1995-09-18 |
| GB9305813D0 (en) | 1993-05-05 |
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