GB1570095A - 7-aminocephalosporin intermediates - Google Patents
7-aminocephalosporin intermediates Download PDFInfo
- Publication number
- GB1570095A GB1570095A GB19863/79A GB1986379A GB1570095A GB 1570095 A GB1570095 A GB 1570095A GB 19863/79 A GB19863/79 A GB 19863/79A GB 1986379 A GB1986379 A GB 1986379A GB 1570095 A GB1570095 A GB 1570095A
- Authority
- GB
- United Kingdom
- Prior art keywords
- acid
- compound according
- compound
- formula
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
PATENT SPECIFICATION ( 1
4 ( 21) Application No 19863/79 ( 22) Filed 26 Oct 1976 ( 62) Divided out of No 1570093 ( 31) Convention Application No 627164 ( 32) Filed 30 Oct 1975 ( 31) Convention Application No 665837 ( 32) Filed 11 March 1976 ( 31) Convention Application No 704142 ( 32) Filed 12 July 1976 in ( 33) United States of America (US) ( 44) Complete Specification published 25 June 1980 ( 51) INT CL 3 C 07 D 501/18 ( 52) Index at acceptance C 2 C 1314 1464 214 215 247 250 252 256 25 Y 28 X 30 Y 321 32 Y 33 Y 342 34 Y 351 352 366 367 368 373 37 Y 385 512 513 522 620 638 670 AA KE SC ( 72) Inventor DAVID ALAN BERGES ( 54) 7-AMINOCEPHALOSPORIN INTERMEDIATES ( 71) We, SMITHKLINE COP PORATION, of 1500 Spring Garden Stree Philadelphia, Pennsylvania 19101, Unite States of America, a corporation organize under the laws of the Commonwealth ( Pennsylvania, one of the United States ( America, do hereby declare the invention for which we pray that a patent may l granted to us, and the method by which it to be performed, to be particularl described in and by the followin statement:-
This invention relates to cephalospori compounds which are useful a intermediates in preparing othe cephalosporin compounds which ha% antibacterial activity and are described an claimed in our copending Applicatic 44441/76 (Serial No 1570093).
According to the present invention thei are provided compounds of the formula COOP, N (C Ha)n N H S 03 H where N is an integer from two to five; and is hydrogen or a protective ester-formir group.
Examples of suitable ester-formir groups R are t-butyl, benzhydr) trichloroethyl, benzyl, benzyloxymethyl, nitrophenyl, p-methoxyphenyl, j methoxybenzyl and p-nitrobenzyl group The ester-forming groups R can b introduced and removed by know methods.
The 7 amino 3 sulfaminoalkylt, tetrazolylthiomethyl cephalosporin d compounds of formula I can be prepared by d reacting 7-formamidocephalosporanic acid, of prepared by reaction of 7 aminoof cephalosporanic acid with formic acid and n, acetic anhydride, and a tetrazole-thiol of ie formula is Is CCH 2)-NHN 53 H or re (where N is as defined above) or a salt Id thereof, followed by treatment with an acid, in such as hydrochloric acid, to remove the formyl group from the product.
e The tetrazole-thiols of formula II are described and claimed in our copending Application 19786/79 (Serial 1570094).
The invention also includes salts of the compounds of formula I, for example with T alkali metals such as sodium or potassium, alkaline earth metals, such as calcium, or the ammonium cation.
The following Example illustrates the invention but is not to be construed as R limiting the scope thereof The ag temperatures are in degrees Centigrade ( C).
lg EXAMPLE r 1,7 Amino 3 l 1 ( 2 sulfaminoethyl)p tetrazol 5 ylthiomethyll 3 p cephem 4 carboxylic acid s To a mixture of 97 g ( 200 ml, 2 1 mol) of ie formic acid, distilled from anhydrous n copper sulfate, and 37 5 ml ( 0 4 mol) of acetic acid anhydride were added 25 0 g ( 0 1 1) 1 570 095 1,570,095 mol) of 7-aminocephalosporanic acid T mixture was stirred at ambient temperate for 0 5 hour, then evaporated to dryne The residue was dissolved in ethyl aceta and the ethyl acetate solution was filter and evaporated to dryness to give a resid which was recrystallized from eth petroleum ether to give 7-formamit cephalosporanic acid.
A mixture of 1 0 g ( 3 3 mol) of formamidocephalosporanic acid and 0 2 ( 2.6 mol) of I ( 2 sulfaminoeth 3 tretrazole 5 thiol disodium salt in 15 of water is stirred at 65-70 for 3 hoi while maintaining the p H at 7 0 T mixture is cooled, acidified to p H 1 0 w hydrochloric acid and extracted with et acetate The extract is filtered, and 1 filtrate is evaporated to dryness to give residue which is dissolved in methanol I methanol solution is filtered and ether added to precipitate the title compou which is collected by filtration.
Claims (8)
1 A compound of the formula:
> $cCpHz S o s Cao VR N (ctl 2)n N N RSO 3 N where N is an integer from two to five; anm is hydrogen or a protective ester-form group.
2 A compound according to claim where R is benzhydryl, t-but trichloroethyl, benzyl, benzyloxymetl p-nitrophenyl, p-methoxyphenyl, methoxybenzyl or p-nitrobenzyl.
3 A compound according to claim 2, where N is two.
4 7 Amino 3 l 1 ( 2 sulfaminoethyl)tetrazol
5 ylthiomethyll 3 cephem 4 carboxylic acid.
A compound according to any of the preceding claims in the form of a salt thereof.
6 A compound as claimed in claim 1, as herein specifically described in the Example.
7 A process for preparing a compound according to claim I which comprises reacting 7-aminocephalosporanic acid with formic and acetic anhydride to produce 7formamidocephalosporanic acid and reacting the 7-formamidocephalosporanic acid with a tetrazole-thiol of formula T-I N-N N N (CH-),,-NH 503 ii (where N is as defined in claim 1) or a salt thereof, followed by treatment with an acid to remove the formyl group from the product.
8 A process for preparing a compound of claim 1, substantially as described in the d R Example.
ing 9 A compound according to claim 1, whenever prepared by a process according 1, to any of claims 7 and 8.
G H HARGREAVES, Chartered Patent Agent.
Printed for Her Majesty's Stationery Office, by the Courier Press Leamington Spa 1980 Published by The Patent Office, 25 Southampton Buildings, London, WC 2 A l AY from which copies may be obtained.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62716475A | 1975-10-30 | 1975-10-30 | |
| US66583776A | 1976-03-11 | 1976-03-11 | |
| US05/704,142 US4118491A (en) | 1976-03-11 | 1976-07-12 | 7-Acyl-3-(sulfaminoalkyl substituted tetrazolylthiomethyl)cephalosporins, antibacterial compositions containing them and methods of treating bacterial infections with them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1570095A true GB1570095A (en) | 1980-06-25 |
Family
ID=27417417
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB44441/76A Expired GB1570093A (en) | 1975-10-30 | 1976-10-26 | Cephalosporins |
| GB19863/79A Expired GB1570095A (en) | 1975-10-30 | 1976-10-26 | 7-aminocephalosporin intermediates |
| GB19786/79A Expired GB1570094A (en) | 1975-10-30 | 1976-10-26 | Substituted tetrazole-5-thiols |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB44441/76A Expired GB1570093A (en) | 1975-10-30 | 1976-10-26 | Cephalosporins |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB19786/79A Expired GB1570094A (en) | 1975-10-30 | 1976-10-26 | Substituted tetrazole-5-thiols |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS6053026B2 (en) |
| AT (1) | AT353957B (en) |
| AU (1) | AU505141B2 (en) |
| CA (1) | CA1071188A (en) |
| CH (1) | CH627757A5 (en) |
| DE (1) | DE2649545A1 (en) |
| DK (1) | DK463176A (en) |
| ES (1) | ES452769A1 (en) |
| FI (1) | FI60868C (en) |
| FR (3) | FR2361896A1 (en) |
| GB (3) | GB1570093A (en) |
| GR (1) | GR61667B (en) |
| IE (1) | IE44393B1 (en) |
| IL (3) | IL50546A (en) |
| LU (1) | LU76092A1 (en) |
| NL (1) | NL7612010A (en) |
| SE (3) | SE452621B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT383811B (en) * | 1983-09-22 | 1987-08-25 | Biochemie Gmbh | Process for the preparation of monoalkali metal salts of 7-amino-3-cephem-4-carboxylic acid derivatives |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4117123A (en) * | 1977-06-09 | 1978-09-26 | Smithkline Corporation | 7-Acylamino-3-[1-(2-sulfamidoethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acids |
| US4717531A (en) * | 1983-09-23 | 1988-01-05 | Westinghouse Electric Corp. | Fuel transfer system upender using translation drive |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR207752A1 (en) * | 1973-03-30 | 1976-10-29 | Fujisawa Pharmaceutical Co | PROCEDURE FOR OBTAINING 7-AMINO-SUBSTITUTED-3-THIOMETHYL SUBSTITUTED-3-CEFEM-4-CARBOXYL ACIDS |
| NL7414119A (en) * | 1973-10-31 | 1975-05-02 | Fujisawa Pharmaceutical Co | PROCESS FOR PREPARING 1H-TETRAZOL-5-THIOL DERIVATIVES AND 1-SUBSTITUATED 1H-TETRAZOL-5-THIOLS. |
| GB1449420A (en) * | 1973-11-26 | 1976-09-15 | Sankyo Co | 7alpha-methoxycephalosporing derivatives |
| NZ176206A (en) * | 1973-12-25 | 1978-03-06 | Takeda Chemical Industries Ltd | Cephalosporins |
| US4066762A (en) * | 1976-07-12 | 1978-01-03 | Smithkline Corporation | Derivatives of 7-(2-substituted-2-hydroxyiminoacetamido)-3-(1-substituted tetrazol-5-ylthiomethyl-3-cephem-4-carboxylic acid |
-
1976
- 1976-09-23 IL IL50546A patent/IL50546A/en unknown
- 1976-09-28 SE SE8006413A patent/SE452621B/en not_active IP Right Cessation
- 1976-09-28 SE SE7610722A patent/SE435291B/en not_active IP Right Cessation
- 1976-09-30 CA CA262,347A patent/CA1071188A/en not_active Expired
- 1976-10-14 AU AU18702/76A patent/AU505141B2/en not_active Ceased
- 1976-10-14 DK DK463176A patent/DK463176A/en not_active Application Discontinuation
- 1976-10-21 FR FR7631723A patent/FR2361896A1/en active Granted
- 1976-10-26 GB GB44441/76A patent/GB1570093A/en not_active Expired
- 1976-10-26 FI FI763044A patent/FI60868C/en not_active IP Right Cessation
- 1976-10-26 GB GB19863/79A patent/GB1570095A/en not_active Expired
- 1976-10-26 GB GB19786/79A patent/GB1570094A/en not_active Expired
- 1976-10-27 IE IE2377/76A patent/IE44393B1/en unknown
- 1976-10-27 ES ES452769A patent/ES452769A1/en not_active Expired
- 1976-10-28 LU LU76092A patent/LU76092A1/xx unknown
- 1976-10-29 AT AT807276A patent/AT353957B/en not_active IP Right Cessation
- 1976-10-29 NL NL7612010A patent/NL7612010A/en not_active Application Discontinuation
- 1976-10-29 DE DE19762649545 patent/DE2649545A1/en not_active Ceased
- 1976-10-29 CH CH1369576A patent/CH627757A5/en not_active IP Right Cessation
- 1976-10-29 GR GR52030A patent/GR61667B/en unknown
- 1976-10-29 JP JP51131157A patent/JPS6053026B2/en not_active Expired
-
1977
- 1977-03-22 FR FR7708505A patent/FR2337720A1/en active Granted
- 1977-03-22 FR FR7708504A patent/FR2351982A1/en active Granted
-
1979
- 1979-02-28 IL IL56757A patent/IL56757A0/en unknown
- 1979-02-28 IL IL56758A patent/IL56758A0/en unknown
-
1980
- 1980-09-12 SE SE8006414A patent/SE437025B/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT383811B (en) * | 1983-09-22 | 1987-08-25 | Biochemie Gmbh | Process for the preparation of monoalkali metal salts of 7-amino-3-cephem-4-carboxylic acid derivatives |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |