GB2099418A - Cephalosporin derivatives - Google Patents
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- GB2099418A GB2099418A GB8202226A GB8202226A GB2099418A GB 2099418 A GB2099418 A GB 2099418A GB 8202226 A GB8202226 A GB 8202226A GB 8202226 A GB8202226 A GB 8202226A GB 2099418 A GB2099418 A GB 2099418A
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- 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
- C07D501/36—Methylene radicals, substituted by sulfur atoms
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- 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
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- 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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- Animal Behavior & Ethology (AREA)
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- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Mutual Connection Of Rods And Tubes (AREA)
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Abstract
There are described compounds of the general formula <IMAGE> in which X represents the 1,2,5,6- tetra-hydro-2-methyl-5,6-dioxo-as- triazin-3-yl group or its tautomeric form, viz. the 2,5-dihydro-6-hydroxy- 2-methyl-5-oxo-as-triazin-3-yl group, R represents a cleavable protecting group and the carboxy group can be present in protected form. These compounds, which themselves have pharmaceutically active properties, can be used to produce the pharmaceutically active compounds of the parent Application No. 7918655 (2022090A).
Description
1 H H 10 IL = 1 Z 5 CH 3 ON-- -CONH i; N- RHN 'A, 31 GB 2 099 418A 1
SPECIFICATION
Cephalosporin derivatives This invention relates to cephalosporin derivatives, and especially to such derivatives which have 5 pharmaceutical properties and also can be used in the preparation of related cephalosporin derivatives. This Application is a divisional of Application 7918655 (2022090A).
According to the present invention there are provided compounds of the general formula M COOH in which X represents the 1,2,5,6-tetra-hydro-2-methyl-5,6-dioxo-as- triazin-3-yI group or its tautomeric form, viz. the 2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin3-yI group, R repre sents a cleavable protecting group and the carboxy group can be present in protected form.
The carboxy group can be protected, for example, by esterification to form a readily cleavable ester such as a silyl ester (e.g. the trimethylsilyl ester).
The carboxy group can also be protected in the form of a readily hydrolysable ester group.
Examples of such esters, which can be of the conventional type, are the lower alkanoyloxyalkyl esters (e.g. the acetoxymethyl, pivaloyloxymethyl, 1-acetoxyethyl and 1- pivaloyloxyethyl ester), the lower alkoxycarbonyloxyalkyl esters (.e.g. the m eth oxyca rbo nyl oxym ethyl, 1-ethoxycarbony loxyethyl and 1-isopropoxycarbonyloxyethyl ester), the lactonyl esters (e. g. the phthalidyl and 30 thiophthalidyl ester), the lower alkoxymethyl esters (e.g. the methoxymethyl ester) and the lower alkanoylaminomethyl esters (e.g. the acetamidomethyl ester). Other esters (e.g. the benzyl and cyanomethyl esters) can also be used. (The term "lower" is used herein to mean that the group immediately following may contain up to and including 7 carbon atoms.) Furthermore, the carboxy group can be protected by salt formation with an inorganic or tertiary organic base such as triethylamine.
Possible protecting groups denoted by R are, for example, protecting groups which are cleavable by acid hydrolysis (e.g. the tert.butoxycarbonyl or trityl groups) or by basic hydrolysis (e.g. the trifluoroacetyl group). Preferred protecting groups denoted by R are the chloro-acetyl, bromoacetyl and iodoacetyl groups, especially the chloroacetyl group. These last-mentioned 40 protecting groups can be cleaved off by treatment with thiourea.
The compounds of formula 11 can be prepared by N-acylating a corresponding 7-amino compound, namely by reacting a compound of the general formula H 4 H2N i H2-. S-X ill COOH r, 1; wherein X has the significance given earlier and the carboxy group and/or the amino group can be present in protected form, with an acid of the general formula CH30N===C-COOH 60 N RHN'_'4j IV 2 GB 2 099 41 BA 2 wherein R has the significance given earlier, or with a reactive functional derivative of this acid and, if desired, cleaving off a carboxy protecting group which may be present.
If desired, the carboxy group present in the 7-amino compounds of formula III can be protected in the same manner as mentioned hereinbefore in connection with the compounds of formula II. The amino group in the compounds of formula III can be protected, for example, by 5 a silyl protecting group such as the trimethylsilyl group.
Examples of reactive functional derivatives of acids of formula IV are halides (i.e. -chlorides, bromides and fluorides), azides, anhydrides, especially mixed anhydrides with strong acids, reactive esters (e.g. N-hydroxysuccinimide esters) and amides (e.g. imidazolides).
The reaction of a 7-amino compound of formula III with an acid of formula IV or a reactive 10 functional derivative thereof can be carried out in a manner known per se. Thus, for example, a free acid of formula IV can be reacted with an aforementioned ester of a compound of formula [if in the presence of a carbodiimide such as dicyclohexylcarbodiimide in an inert solvent such as ethyl acetate, acetonitrile, dioxan, chloroform, methylene chloride, benzene or dimethyl- formamide and subsequently the ester group can be cleaved off. Oxazolium salts e.g. N-ethyl-5- 15 phenyl-isoxazolium 31-sulPhonate) can be used in place of carbodiimides in the foregoing reaction.
According to another embodiment, a salt of an acid of formula III (e.g. a trialkylammonium salt such as the triethylammonium salt) is reacted with a reactive functional derivative of an acid of formula IV as mentioned earlier in an inert solvent (e.g. one of the aforementioned soivents). 20 According to a further embodiment, an acid halide, preferably the chloride, of an acid of formula IV is reacted with an amine of formula 111. The reaction is preferably carried out in the presence of an acidbinding agent, for example in the presence of aqueous alkali, preferably sodium hydroxide, or in the presence of an alkali metal carbonate such as potassium carbonate or in the presence of a lower alkylamine such as triethylamine. As the solvent there is preferably used water, optionally in admixture with an inert organic solvent such as tetrahydrofuran or dioxan. The reaction can also be carried out in an aprotic organic solvent such as dimethylformamide, dimethyl sulphoxide or hexamethyphosphoric acid triamide. When a silylated compound of formula III is used, the reaction is carried out in an anhydrous medium.
The reaction of a 7-amino compound of formula III with an acid of formula IV or a reactive 30 functional derivative thereof can conveniently be carried out at a temperature between - 40'C and room temperature, for example at 0'- 1 O'C.
The cephalosporin derivatives provided by the present invention can exist in the syn-isomeric form N 11 - CONN- 1 N 40 RHNA7 s \CH 3 or in the anti-isomeric form N C-CONH-i 45 RHUA SCH 3 0 / N 50 or as mixtures of these two forms. The syn-isomeric form is preferred, as are mixtures in which the syn-isomeric form predominates.
A syn/anti mixture of a compound of formula 11 which may be obtained can be separated into the corresponding syn and anti forms in the customary manner, for example by recrystallisation 55 or by chromatographic& methods using a suitable solvent or solvent mixture.
A preferred cephalosporin derivative provided by the present invention is (6R,7R)-7-[2-[2-(2chloro-acetamido)-4-thiazoiyl]-2-(Zmethoxyimino)acetamido l-3-1[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-astriazin-3-yi)thio]methyl.T8-oxo-5-thia-l-azabicycio[4.2.0]oct-2 -ene-2carboxylic acid.
The compounds of the present invention are useful for the production of the novel compounds 60 claimed in parent Application No. 7918655 (2022090A), by clearing off the protecting group R and also if desired the carboxy protecting group if present.
The compounds of formula 11 and their corresponding readily hydrolysable esters also have antibiotic, especially bactericidal, activity. They possess a broad spectrum of activity against gram-positive and gram-negative m icro-organ isms, including P-factamse- forming Staphylococci 65 3 GB 2 099 418A 3 and various fl-lactamase-forming gram-negative bacteria such as, for example, Pseudomonas aeruginosa, Haemophilus influenza, Escherichia coli, Serratia marcescens and Proteus and Klebsiella species.
These compounds can be used for the treatment and prophylaxis of infectious diseases. A daily dosage of 0. 1 g to 2 g is envisaged for adults. The parenteral administration of the 5 compounds provided by the present invention is especially preferred.
In order to demonstrate the antimicrobial activity of the compounds provided by the present invention, the following representative compound was tested:
(6R,7R)-7-[2-[2-(2-Chloracetamido)-4-thiazolyi]-2-(Zmethoxyimino)acetamidoj 3-l[(2,5-dihydro6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl.T8-oxo-5-thia-lazabicy clo[4.2.0]oct-2-ene-2- 10 carboxylic acid. Activity in vitro: Minimum inhibitory concentration (ftg/ml) Haemophilus influenzae strain 1 1.2 15 strain 2 0.3 strain 3 0.16 strain 4 0.16 strain 5 0.08 strain 6 0.16 20 strain 7 0.16 Klebsiella pneumoniae 10 Escherichia coli strain 1 0.16 strain 2 5 Proteus mirabilis strain 1 0.08 25 strain 2 0.16 Proteus vulgaris 0.16 Proteus rettgeri 0.16 Staphyiococcus aureus strain ATCC 6538 2.5 Penicillin-resistant strain 5 30 Pseudomonas aeruginosa strain 1 1.2 strain 2 >80 strain 3 40 strain 4 80 strain 5 80 35 strain 6 80 strain 7 80 Serratia marcescens 2.5 40 Activity in vivo Groups of 5 mice are infected intraperitoneally with an aqueous suspension of Escherichia coli. The test substance is administered subcutaneously in physiological sodium chloride solution three times, i.e. 1 hour, 2.5 hours and 4 hours, after the infection. The number of surviving 45 animals is determined on the fourth day. Various dosages are administered and the dosage at which 50% of the test animals survive (CD,O, mg/kg is determined by interpolation.
CD,, mg/kg 0. 16 Toxicity LID,., mg/kg im. 250-500 s.c, 2000-4000 P.O. >5000 The cephalosporin derivatives provided by the present invention can be used as medicaments, for example in association with a compatible carrier material. This carrier material can be an organic or inorganic inert carrier material which is suitable for enteral or parenteral administra tion such as, for example, water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegatable oils, polyalkyleneglycols or petroleum jelly. The pharmaceutical preparations can be made up in solid form (e.g. as tablets, dra96es, suppositories or capsules) or in liquid form (e.g.
as solutions, suspensions or emulsions). The pharmaceutical preparations may be sterilised and/or may contain adjuvants such as preserving, stabilising, wetting or emulsifying agents, salts for varying the osmotic pressure, anaesthetics or buffers. The pharmaceutical preparations can also contain other therapeutically valuable substances. The compounds of formula 11 are especially suitable for parenteral administration and for this purpose they are preferably made up in the form of lyophilisates or dry powders for dilution with customary agents such as water or 65 4 GB 2 099 418A isotonic sodium chloride solution. The readily hydrolysable esters of the compounds of formula 11 are also suitable for enteral administration.
The following Example is given to illustrate the invention.
Example
22.24 g of 2-(2-chloroacetamido-thiazol-4-yi)-2-(Z-methoxyimino)-acetic acid are suspended in 240 mi of methylene chloride. 13.39 mi of triethylamine are added to this suspension, a light brown solution being obtained. This solution is cooled to W-5'C and treated with 16.72 g of phosphorus pentachloride. The mixture is stirred for 5 minutes at W-WC and for 20 minutes without cooling. The resulting yellow solution is evaporated at WC in vacuo. The evaporation 10 residue is shaken twice with n-heptane and the latter is decanted off. The resinous residue is treated with 240 m[ of tetrahydrofuran and the undissolved triethylamine hydrochloride is filtered off. The yellow filtrate contains the acid chloride.
22 9 of (7R)-7-amino-3-desacetoxy-3-[(2,5-dihydro-6-hydroxy-2-methyi-5oxo-as-triazi n-3-yl)- thio]-cephalosporanic acid are suspended in a mixture of 300mi of water and 150 m[ of 1 tetra hyd rofura n. 2-N sodium hydroxide is added dropwise to the suspension with the aid of an auto-titrator while gassing well with nitrogen until a brown-red solution having a pH of 8 is obtained. This solution is cooled to W-WC and treated dropwise during 15 minutes with the solution of the acid chloride in tetrahydrofuran prepared as described in the preceding 20' paragraph. Thereafter, the mixture is stirred at 2WC for 2.5 hours. The pH of the mixture is 20 held constant at 8 by adding 2-N sodium hydroxide. The almost black solution is freed from tetrahydrofuran at 4WC in vacuo. 1 00mi of 2-N sulphuric acid are now added. The substance which thereby precipitates out is filtered off under suction, washed with water and filtered off well under suction. The moist brown material on the suction filter is dissolved in 1.5 litres of acetone. The dark solution is filtered off through Hyflo from a small amount of dark undissolved 25 material, treated with carbon, stirred for 30 minutes and again filtered through Hyflo. The orange-red filtrate is dried over sodium sulphate, concentrated in vacuo and evaporated with ethyl acetate. A black resin thereby precipitates out. This resin is filtered off and discarded. The 2-phase filtrate which still contains water is subjected to azeotropic distillation three times with benzene at 40'C in vacuo. The substance which thereby precipitates out is filtered off under suction and dried at 4WC in vacuo. This substance is stirred up twice with 1 litre of acetone each time, there remaining a brown resin which is discarded. The combined orange coloured acetone extracts are concentrated to ca 150 mi at 4WC in vacuo, a brown resin being filtered off and discarded. The filtrate is treated with 1 litre of ethyl acetate and concentrated at 4WC in vacuo. The substance which thereby precipitates out is filtered off under suction, washed with 35 ethyl acetate and then with ether [(6R,7R)-7-[2-[2-(2-chloroacetamido)-4- thiazoiyi]-2-(Z-methoxyimino)acetamido.3-[[(2,5-dihydro-6-hydroxy-2-methyi-5-oxo-as-triazin-3yl) thio]methyi]-8-oxo-5 thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, fraction I; a beige, amorphous acid].
The ethyl acetate mother liquor is concentrated extensively at 4WC in vacuo, diluted with ether and the precipitated substance is filtered of under suction [(6R, 7R)-7-[2-[2-(2-chloroacetamido)-4-thiazolyl]-2-(Z-methoxyimino)acetamido]-3-1[(2,5-dihydro-6hydroxy -2-methyl-5-oxo-astriazin-3-yl)thio]methyll-8-oxo-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2carbo xylic acid, fraction 11; a light beige amorphous acid, somewhat purer than fraction 1 according to thin-layer chromatogra phy].
For the manufacture of the disodium salt, 3.5 g of the acid (fraction 11) are dissolved in a 45 mixture of 20 m] of acetone and 11 mi of water. The solution is treated with 7 m] of a 2-N solution of the sodium salt of 2-ethyl-caproic acid in ethyl acetate, whereby the disodium salt crystallises. A further 25 mi of acetone are now added portionwise and the mixture is stored in a deep-freeze cabinet for 2 hours. Thereafter, the crystallisate is filtered off under suction, washed successively with 25 mi of an ice-cold acetone/water mixture (80:20), pure acetone and low,-boiling petroleum ether and dried overnight at 4WC in a high vacuum. There is obtained the - disodium salt of (6R,7R)-7-12-[2-(2-chforoacetamido)-4-thiazoiyi]-2-(Zmethoxyimino)acetxami-. do_3-1[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yi)thio]methyll8 -oxo-5-thia-1 -azabicy clo[4.2.0]oct-2-ene-2-carboxylic acid in the form of light yellow crystals; [a]20 142X ( c = 1 in water). The nuclear magnetic resonance spectrum and the micro- analysis correspond to 55 the structure indicated.
Claims (6)
1 GB2099418A 5 H H CH ON- -CONH 3 N CH 2-S --X RHN AI's \ COOH I I in which X represents the 1,2,5,6-tetra-hydro-2methyl-5,6-dioxo-astriazin-3yl group or its tautomeric form, viz. the 2,5-dihydro-6-hydroxy2-methyl-5-oxo-as-triazin-3-yl group, R repre15 sents a cleavable protecting group and the carboxy group can be present in protected form.
2. (6R,7R)-7-12-[2-(2-Chloroacetamido)-4-thiazoiyi]-2-(Zmethoxyimino)acetamido.3-R2,5d i hyro-6-hyd roxy-2-m ethyl-5-oxo-astriazi n-3-y1)th i o] methyl 1-8-oxo-5-th ia- 1 -azabicyclo[4.2.0]oct2ene-2-carboxylic acid.
3. A process for producing a compound as claimed in claim 1 comprising reacting a 20 compound of the general formula H $4 H 2N H2-S-X COOH wherein X has the significance given in claim 1 and the carboxy group and/or the amino group can be present in protected form, with an acid of the general formula CH30N==C-COOH N 7 RHN' IV wherein R has the significance given in claim 1, or with a reactive functional derivate of this acid and, if desired, cleaving off a carboxy protecting group which may be present.
4. A process as claimed in claim 3, substantially as described with reference to the Example. 45
5. Compounds according to claim 1, whenever prepared by a process as claimed in claim 3 or claim 4.
6. Compounds as claimed in any of claims 1,2 and 5, for use as pharmaceutically active substances.
Printed for Her Majesty's Stationery Office by Burgess & Son (Abingdon) Ltd.-1 982. Published at The Patent Office, 25 Southampton Buildings, London, WC2A 1AY, from which copies may be obtained.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH588278A CH641468A5 (en) | 1978-05-30 | 1978-05-30 | CEPHEM DERIVATIVES. |
| CH224879 | 1979-03-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2099418A true GB2099418A (en) | 1982-12-08 |
| GB2099418B GB2099418B (en) | 1983-06-02 |
Family
ID=25689901
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7918655A Expired GB2022090B (en) | 1978-05-30 | 1979-05-29 | F 7-2-2-amino-4-hetrocylylthiomethyl-cephems |
| GB8202226A Expired GB2099418B (en) | 1978-05-30 | 1979-05-29 | Cephalosporin derivatives |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7918655A Expired GB2022090B (en) | 1978-05-30 | 1979-05-29 | F 7-2-2-amino-4-hetrocylylthiomethyl-cephems |
Country Status (40)
| Country | Link |
|---|---|
| EP (2) | EP0005830B1 (en) |
| JP (2) | JPS54157596A (en) |
| AT (3) | AT367764B (en) |
| BG (1) | BG50163A3 (en) |
| BR (1) | BR7903368A (en) |
| CA (1) | CA1141373A (en) |
| CS (1) | CS219254B2 (en) |
| CU (1) | CU35088A (en) |
| CY (1) | CY1182A (en) |
| DD (1) | DD143911A5 (en) |
| DE (4) | DE2963720D1 (en) |
| DK (1) | DK149282C (en) |
| EG (1) | EG14153A (en) |
| ES (2) | ES480990A1 (en) |
| FI (1) | FI65434C (en) |
| FR (2) | FR2427337A1 (en) |
| GB (2) | GB2022090B (en) |
| GR (1) | GR72242B (en) |
| HK (1) | HK31383A (en) |
| HU (1) | HU183089B (en) |
| IE (1) | IE49047B1 (en) |
| IL (1) | IL57392A (en) |
| IS (1) | IS1203B6 (en) |
| IT (1) | IT1121517B (en) |
| KE (1) | KE3268A (en) |
| LU (1) | LU81325A1 (en) |
| MC (1) | MC1259A1 (en) |
| MT (1) | MTP845B (en) |
| MY (1) | MY8400127A (en) |
| NL (1) | NL7904083A (en) |
| NO (1) | NO159797C (en) |
| NZ (1) | NZ190532A (en) |
| OA (1) | OA06263A (en) |
| PH (1) | PH15148A (en) |
| PL (1) | PL122458B1 (en) |
| PT (1) | PT69698A (en) |
| RO (1) | RO77560A (en) |
| SE (1) | SE437522B (en) |
| SG (1) | SG10483G (en) |
| YU (3) | YU42485B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5672711A (en) * | 1995-06-30 | 1997-09-30 | Chong Kun Dang Corporation | Process for manufacturing cephem derivatives |
| RU2504548C1 (en) * | 2012-09-28 | 2014-01-20 | Федеральное Государственное Автономное Образовательное Учреждение Высшего Профессионального Образования "Сибирский Федеральный Университет" (Сфу) | DERIVATIVE OF β-LACTAM CEFTRIAXONE ANTIBIOTIC |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI67385C (en) * | 1979-11-21 | 1985-03-11 | Hoffmann La Roche | PROCEDURE FOR FRAMSTATION OF AV (6R 7R) -7- (2- (2-AMINO-4-THIAZOLYL) -2- (Z-METHOXYIMINO) ACETAMIDO) -3-CEFEM-4-CARBOXYL SYRATER DERIVATIVES |
| US4349672A (en) * | 1979-11-29 | 1982-09-14 | Hoffmann-La Roche Inc. | Cephalosporin derivatives |
| CA1177823A (en) * | 1980-03-25 | 1984-11-13 | Andre Furlenmeier | Cephalosporin derivatives |
| CA1154009A (en) * | 1980-03-25 | 1983-09-20 | Roland Reiner | Cephalosporin derivatives |
| GR75711B (en) * | 1980-06-30 | 1984-08-02 | Sanofi Sa | |
| US4308267A (en) | 1980-07-03 | 1981-12-29 | Smithkline Corporation | 7-[2-Alkoxyimino-2-(amino-thiazole)acetamido]-3-[1-(sulfaminoalkly)tetrazolthiomethyl]cephalosporins |
| DK379581A (en) * | 1980-10-06 | 1982-04-07 | Hoffmann La Roche | PROCEDURE FOR THE PREPARATION OF ACYL DERIVATIVES |
| FR2494278A1 (en) * | 1980-11-20 | 1982-05-21 | Rhone Poulenc Ind | NEW DERIVATIVES OF CEPHALOSPORIN, THEIR PREPARATIONS AND THE MEDICINAL PRODUCTS CONTAINING THEM |
| EP0058250A3 (en) * | 1981-02-17 | 1983-08-17 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Cephalosporin derivatives, their preparation and pharmaceutical compositions containing them |
| EP0185220A3 (en) * | 1984-12-19 | 1987-09-02 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Intermediates for the preparation of cephalosporins |
| CA1296012C (en) | 1986-03-19 | 1992-02-18 | Susumu Nakagawa | 6,7-dihydroxy-isoquinoline derivatives |
| RU2021274C1 (en) | 1991-05-17 | 1994-10-15 | Польска Акадэмия Наук Институт Хэмии Органичнэй | Process for preparing aminothiazolyl cephalosporin derivatives |
| KR950014571B1 (en) * | 1991-11-18 | 1995-12-08 | 제일제당주식회사 | Process for the preparation of cephem derivatives |
| AT398764B (en) * | 1992-01-28 | 1995-01-25 | Lek Tovarna Farmacevtskih | METHOD FOR PRODUCING CEFTRIAXONDINATRIUM SALZHEMIHEPTAHYDRATE |
| AT399877B (en) * | 1992-02-20 | 1995-08-25 | Biochemie Gmbh | NEW METHOD FOR PRODUCING CEFTRIAXONE |
| DE102011117421A1 (en) | 2011-11-02 | 2013-05-02 | Hans-Peter Gabel | Pharmaceutical composition useful for treating Lyme disease, comprises mixture of active substances including ceftriaxone and cefotaxime |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH609989A5 (en) * | 1974-06-21 | 1979-03-30 | Hoffmann La Roche | Process for the preparation of acyl derivatives |
| CA1100129A (en) * | 1974-08-02 | 1981-04-28 | William H.W. Lunn | Cephalosporin compounds |
| FR2345153A1 (en) * | 1976-03-25 | 1977-10-21 | Roussel Uclaf | NEW ALCOYLOXIMES DERIVED FROM 7-AMINO THIAZOLYL ACETAMIDO CEPHALOSPORANIC ACID, THEIR PREPARATION PROCESS AND THEIR APPLICATION AS MEDICINAL PRODUCTS |
| DK162391C (en) | 1976-04-12 | 1992-03-09 | Fujisawa Pharmaceutical Co | ANALOGY PROCEDURE FOR PREPARING SYN-ISOMERS OF 3,7-DISUBSTITUTED 3-CEPHEM-4-CARBOXYLIC ACID COMPOUNDS |
| GR63088B (en) * | 1976-04-14 | 1979-08-09 | Takeda Chemical Industries Ltd | Preparation process of novel cephalosporins |
| JPS5329936A (en) * | 1976-08-31 | 1978-03-20 | Takeda Chem Ind Ltd | Antibiotic composition |
| GB1599232A (en) * | 1977-06-03 | 1981-09-30 | Hoffmann La Roche | 7-(2-oximinoacetamido)-cephalosporin derivatives |
| US4200745A (en) * | 1977-12-20 | 1980-04-29 | Eli Lilly And Company | 7[2-(2-Aminothiazol-4-yl)-2-alkoxyimino]acetamido 3[4-alkyl-5-oxo-6-hydroxy-3,4 dihydro 1,2,4-triazin 3-yl]thio methyl cephalosporins |
-
1979
- 1979-04-25 MC MC791376A patent/MC1259A1/en unknown
- 1979-05-09 MT MT845A patent/MTP845B/en unknown
- 1979-05-14 EG EG280/79A patent/EG14153A/en active
- 1979-05-23 NZ NZ190532A patent/NZ190532A/en unknown
- 1979-05-23 NL NL7904083A patent/NL7904083A/en not_active Application Discontinuation
- 1979-05-24 IL IL57392A patent/IL57392A/en unknown
- 1979-05-24 PH PH22556A patent/PH15148A/en unknown
- 1979-05-25 BG BG043718A patent/BG50163A3/en unknown
- 1979-05-25 FR FR7913369A patent/FR2427337A1/en not_active Withdrawn
- 1979-05-25 YU YU1233/79A patent/YU42485B/en unknown
- 1979-05-28 DD DD79213189A patent/DD143911A5/en not_active IP Right Cessation
- 1979-05-28 LU LU81325A patent/LU81325A1/en unknown
- 1979-05-28 JP JP6511179A patent/JPS54157596A/en active Granted
- 1979-05-28 HU HU79HO2154A patent/HU183089B/en unknown
- 1979-05-28 FI FI791703A patent/FI65434C/en not_active IP Right Cessation
- 1979-05-28 GR GR59190A patent/GR72242B/el unknown
- 1979-05-28 IS IS2490A patent/IS1203B6/en unknown
- 1979-05-28 CU CU7935088A patent/CU35088A/en unknown
- 1979-05-28 IT IT23049/79A patent/IT1121517B/en active
- 1979-05-29 NO NO791776A patent/NO159797C/en unknown
- 1979-05-29 GB GB7918655A patent/GB2022090B/en not_active Expired
- 1979-05-29 CA CA000328630A patent/CA1141373A/en not_active Expired
- 1979-05-29 CY CY1182A patent/CY1182A/en unknown
- 1979-05-29 AT AT0390479A patent/AT367764B/en not_active IP Right Cessation
- 1979-05-29 BR BR7903368A patent/BR7903368A/en unknown
- 1979-05-29 ES ES480990A patent/ES480990A1/en not_active Expired
- 1979-05-29 OA OA56816A patent/OA06263A/en unknown
- 1979-05-29 DK DK222679A patent/DK149282C/en not_active IP Right Cessation
- 1979-05-29 GB GB8202226A patent/GB2099418B/en not_active Expired
- 1979-05-29 PT PT69698A patent/PT69698A/en unknown
- 1979-05-29 SE SE7904682A patent/SE437522B/en unknown
- 1979-05-29 CS CS793700A patent/CS219254B2/en unknown
- 1979-05-30 EP EP79101657A patent/EP0005830B1/en not_active Expired
- 1979-05-30 AT AT79101657T patent/ATE1586T1/en active
- 1979-05-30 EP EP81106777A patent/EP0045525B1/en not_active Expired
- 1979-05-30 DE DE7979101657T patent/DE2963720D1/en not_active Expired
- 1979-05-30 DE DE8181106777T patent/DE2966946D1/en not_active Expired
- 1979-05-30 DE DE2922036A patent/DE2922036C2/en not_active Expired
- 1979-05-30 PL PL1979215972A patent/PL122458B1/en unknown
- 1979-05-30 DE DE2954159A patent/DE2954159C2/en not_active Expired
- 1979-05-30 RO RO7997683A patent/RO77560A/en unknown
- 1979-05-30 AT AT81106777T patent/ATE7229T1/en active
- 1979-08-08 IE IE1041/79A patent/IE49047B1/en not_active IP Right Cessation
-
1980
- 1980-02-16 ES ES488687A patent/ES8101606A1/en not_active Expired
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1982
- 1982-05-11 FR FR8208153A patent/FR2509312A1/en active Granted
-
1983
- 1983-03-14 SG SG104/83A patent/SG10483G/en unknown
- 1983-03-29 KE KE3268A patent/KE3268A/en unknown
- 1983-08-25 HK HK313/83A patent/HK31383A/en not_active IP Right Cessation
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1984
- 1984-06-21 JP JP59126533A patent/JPS6016994A/en active Granted
- 1984-12-30 MY MY127/84A patent/MY8400127A/en unknown
-
1985
- 1985-05-06 YU YU745/85A patent/YU45257B/en unknown
- 1985-05-06 YU YU744/85A patent/YU45256B/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5672711A (en) * | 1995-06-30 | 1997-09-30 | Chong Kun Dang Corporation | Process for manufacturing cephem derivatives |
| RU2504548C1 (en) * | 2012-09-28 | 2014-01-20 | Федеральное Государственное Автономное Образовательное Учреждение Высшего Профессионального Образования "Сибирский Федеральный Университет" (Сфу) | DERIVATIVE OF β-LACTAM CEFTRIAXONE ANTIBIOTIC |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
| PE20 | Patent expired after termination of 20 years |
Effective date: 19990528 |