WO1999023082A1 - AMINOTHIAZOLE DERIVATIVES USEFUL IN THE PREPARATION OF β-LACTAM ANTIBIOTICS - Google Patents
AMINOTHIAZOLE DERIVATIVES USEFUL IN THE PREPARATION OF β-LACTAM ANTIBIOTICS Download PDFInfo
- Publication number
- WO1999023082A1 WO1999023082A1 PCT/EP1997/006654 EP9706654W WO9923082A1 WO 1999023082 A1 WO1999023082 A1 WO 1999023082A1 EP 9706654 W EP9706654 W EP 9706654W WO 9923082 A1 WO9923082 A1 WO 9923082A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- chosen
- derivatives
- lactam antibiotics
- preparation
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom
-
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Definitions
- the present invention regards aminothiazole derivatives, and more in particular aminothiazole derivatives with the carboxyl activated by means of thioesters, which may be used for the preparation of ⁇ -lactam antibiotics.
- ⁇ -lactam antibiotics are well known in the literature, and many of them, the cephalosporins, are widely used in medical treatment, whilst many others are still being developed, as described in the literature, for instance in patents WO 97/13772 and WO 97/12890.
- Patents EP-A-037380 and EP-A-210815 describe other methods of activation on aminothiazole derivatives that are similar to those described by formula (II) , but the conversion yields that may be obtained in the condensation with the ⁇ -lactam nucleus are low.
- Patent US-A-4, 767, 852 describes aminothiazole derivatives of compounds of formula (II) in which the activation of the carboxyl group is obtained by means of thioesters; in this formula, however, the meaning of X is in every case exclusively H (hydrogen) : when these derivatives are condensed, according to a method described in the patent itself, with a ⁇ -lactam nucleus, in all cases cephalosporins or ⁇ -lactam antibiotics are obtained in which X is always and exclusively H.
- the invention regards aminothiazole derivatives having the formula
- X is a halogen, C 1 -C alkyl
- Het is a 5- or 6-term heterocyclic ring having in the ring at least one hetero-atom chosen from the group made up of N, S, 0, either just as it is or condensed with a benzene ring;
- R is H, C 1 -C 4 alkyl, -CH_-COOH or C (CH 3 ) 2 -COOH, the acid functions of which are free, salified or esterified, CH C -CN. CH 2 CF 3 , CH 2 F, CH 2 , CH_ or a protective group of the easily removable type.
- X is Cl; Het is chosen from among the group consisting of
- R is chosen from among the group consisting of trityl (Tr) , tetrahydropyranyl (THP) , tert- butyldimethylsilyl (TBDMS) , tri ethylsilyl (TMS) , and methoxymethyl (MOM) .
- the condensation reaction of the derivatives (I) with the ⁇ -lactam nuclei may be conducted at temperatures of between -30°C and +80°C, preferably of between -5°C and +40°C, using highly polar organic solvents (pure, or mixed together, or mixed with water up to 50% of water, also in two-phase systems) capable of solubilizing (even only partially) the reagents (in particular the derivatives I) , such as methylene chloride, ethyl acetate, dimethylformamide, dimethylacetamide, N- methyl-2-pyrrolidone, acetone, dimethyl sulphoxide, methanol, ethanol, isopropanol, and sulpholane, having a high dielectric constant.
- highly polar organic solvents pure, or mixed together, or mixed with water up to 50% of water, also in two-phase systems
- the reaction is exothermic, the temperature rising spontaneously to 35°C. After 10 minutes, the above is left under slow stirring, and the product, as it forms, crystallizes. The reaction is complete in the course of 1 hour (35°C) . At the end of the reaction, cool off to 15°C and leave under stirring for 1 hour. Filter and wash with 600 mlit of methylene chloride. Dry in a vacuum at 40°C until constant weight is reached.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97952008A EP0948491B1 (en) | 1997-10-30 | 1997-11-28 | Aminothiazole derivatives useful in the preparation of beta-lactam antibiotics |
JP52524899A JP2001517248A (en) | 1997-10-30 | 1997-11-28 | Aminothiazole derivatives useful in the production of beta-lactam antibiotics |
DK97952008T DK0948491T3 (en) | 1997-10-30 | 1997-11-28 | Aminothiazole derivatives suitable for the preparation of beta-lactam antibiotics |
AU55581/98A AU5558198A (en) | 1997-10-30 | 1997-11-28 | Aminothiazole derivatives useful in the preparation of beta-lactam antibiotics |
US09/331,702 US6255480B1 (en) | 1997-10-30 | 1997-11-28 | Aminothiazole derivatives useful in the preparation of β-lactam antibiotics |
DE1997627315 DE69727315T2 (en) | 1997-10-30 | 1997-11-28 | AMINOTHIAZOLE DERIVATIVES FOR THE PRODUCTION OF BETA LACTAM ANTIBIOTICS |
AT97952008T ATE258169T1 (en) | 1997-10-30 | 1997-11-28 | AMINOTHIAZOLE DERIVATIVES FOR THE PRODUCTION OF BETA-LACTAM ANTIBIOTICS |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT97MI002439A IT1295935B1 (en) | 1997-10-30 | 1997-10-30 | AMINOTHIAZOLE DERIVATIVES USEFUL IN THE PREPARATION OF B-LACTAMICS ANTIBIOTICS |
ITMI97A002439 | 1997-10-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999023082A1 true WO1999023082A1 (en) | 1999-05-14 |
Family
ID=11378130
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1997/006654 WO1999023082A1 (en) | 1997-10-30 | 1997-11-28 | AMINOTHIAZOLE DERIVATIVES USEFUL IN THE PREPARATION OF β-LACTAM ANTIBIOTICS |
Country Status (11)
Country | Link |
---|---|
US (1) | US6255480B1 (en) |
EP (1) | EP0948491B1 (en) |
JP (1) | JP2001517248A (en) |
AT (1) | ATE258169T1 (en) |
AU (1) | AU5558198A (en) |
DE (1) | DE69727315T2 (en) |
DK (1) | DK0948491T3 (en) |
ES (1) | ES2213229T3 (en) |
IT (1) | IT1295935B1 (en) |
PT (1) | PT948491E (en) |
WO (1) | WO1999023082A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103588790A (en) * | 2013-11-29 | 2014-02-19 | 中国科学院长春应用化学研究所 | Preparation method of 7-amino-3-chloro-3-cephem-4-carboxylic acid-p-nitrobenzyl ester |
CN103588789A (en) * | 2013-11-29 | 2014-02-19 | 中国科学院长春应用化学研究所 | Preparation method of 7-amino-3-chloro-3-cephem-4-carboxylic acid |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100448856C (en) * | 2006-06-26 | 2009-01-07 | 山东金城医药化工股份有限公司 | New technique for catalytic synthesis of AE active ester |
CN103012312B (en) * | 2012-12-04 | 2015-05-06 | 山东鑫泉医药有限公司 | Method for recycling industrial wastewater of aminothiazoly loximate |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0002765A1 (en) * | 1977-12-24 | 1979-07-11 | Hoechst Aktiengesellschaft | Cephalosporin derivatives, process for their preparation and pharmaceutical compositions and their preparation |
EP0037380A2 (en) * | 1980-03-28 | 1981-10-07 | BIOCHEMIE Gesellschaft m.b.H. | New process for the production of cephalosporin antibiotics, and novel intermediates used in such process and their production |
EP0055465A2 (en) * | 1980-12-31 | 1982-07-07 | Fujisawa Pharmaceutical Co., Ltd. | 7-Acylaminocephalosporanic acid derivatives and processes for the preparation thereof |
EP0210815A2 (en) * | 1985-07-25 | 1987-02-04 | Beecham Group Plc | 6-Beta-(alpha-etherified oxyimino)-acylamino penicillanic-acid derivatives, their preparation and use |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4703046A (en) * | 1978-09-08 | 1987-10-27 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds and processes for preparation thereof |
GB9024223D0 (en) | 1990-11-07 | 1990-12-19 | Fermentech Ltd | Production of hyaluronic acid |
GB9216759D0 (en) | 1992-08-07 | 1992-09-23 | Finpael Spa | Process for the production of 7-amino thiazolyl cephalosporins |
AT402928B (en) * | 1994-12-23 | 1997-09-25 | Biochemie Gmbh | NEW METHOD FOR PRODUCING CEFOTAXIM |
GB9519883D0 (en) | 1995-09-29 | 1995-11-29 | Fujisawa Pharmaceutical Co | New cephem compounds |
MY127641A (en) | 1995-10-12 | 2006-12-29 | Essential Therapeutics Inc | Cephalosporin antibiotics |
IN184690B (en) * | 1996-03-18 | 2000-09-23 | Ranbaxy Lab Ltd |
-
1997
- 1997-10-30 IT IT97MI002439A patent/IT1295935B1/en active IP Right Grant
- 1997-11-28 ES ES97952008T patent/ES2213229T3/en not_active Expired - Lifetime
- 1997-11-28 JP JP52524899A patent/JP2001517248A/en not_active Ceased
- 1997-11-28 DE DE1997627315 patent/DE69727315T2/en not_active Expired - Fee Related
- 1997-11-28 AT AT97952008T patent/ATE258169T1/en not_active IP Right Cessation
- 1997-11-28 WO PCT/EP1997/006654 patent/WO1999023082A1/en active IP Right Grant
- 1997-11-28 US US09/331,702 patent/US6255480B1/en not_active Expired - Lifetime
- 1997-11-28 PT PT97952008T patent/PT948491E/en unknown
- 1997-11-28 EP EP97952008A patent/EP0948491B1/en not_active Expired - Lifetime
- 1997-11-28 AU AU55581/98A patent/AU5558198A/en not_active Abandoned
- 1997-11-28 DK DK97952008T patent/DK0948491T3/en active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0002765A1 (en) * | 1977-12-24 | 1979-07-11 | Hoechst Aktiengesellschaft | Cephalosporin derivatives, process for their preparation and pharmaceutical compositions and their preparation |
EP0037380A2 (en) * | 1980-03-28 | 1981-10-07 | BIOCHEMIE Gesellschaft m.b.H. | New process for the production of cephalosporin antibiotics, and novel intermediates used in such process and their production |
EP0055465A2 (en) * | 1980-12-31 | 1982-07-07 | Fujisawa Pharmaceutical Co., Ltd. | 7-Acylaminocephalosporanic acid derivatives and processes for the preparation thereof |
EP0210815A2 (en) * | 1985-07-25 | 1987-02-04 | Beecham Group Plc | 6-Beta-(alpha-etherified oxyimino)-acylamino penicillanic-acid derivatives, their preparation and use |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103588790A (en) * | 2013-11-29 | 2014-02-19 | 中国科学院长春应用化学研究所 | Preparation method of 7-amino-3-chloro-3-cephem-4-carboxylic acid-p-nitrobenzyl ester |
CN103588789A (en) * | 2013-11-29 | 2014-02-19 | 中国科学院长春应用化学研究所 | Preparation method of 7-amino-3-chloro-3-cephem-4-carboxylic acid |
Also Published As
Publication number | Publication date |
---|---|
ES2213229T3 (en) | 2004-08-16 |
DE69727315T2 (en) | 2004-11-18 |
ATE258169T1 (en) | 2004-02-15 |
JP2001517248A (en) | 2001-10-02 |
DK0948491T3 (en) | 2004-04-13 |
ITMI972439A1 (en) | 1999-04-30 |
EP0948491A1 (en) | 1999-10-13 |
PT948491E (en) | 2004-06-30 |
EP0948491B1 (en) | 2004-01-21 |
IT1295935B1 (en) | 1999-05-28 |
US6255480B1 (en) | 2001-07-03 |
DE69727315D1 (en) | 2004-02-26 |
AU5558198A (en) | 1999-05-24 |
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