TWI250162B - Beta-lactamase inhibitor prodrug - Google Patents
Beta-lactamase inhibitor prodrug Download PDFInfo
- Publication number
- TWI250162B TWI250162B TW092123156A TW92123156A TWI250162B TW I250162 B TWI250162 B TW I250162B TW 092123156 A TW092123156 A TW 092123156A TW 92123156 A TW92123156 A TW 92123156A TW I250162 B TWI250162 B TW I250162B
- Authority
- TW
- Taiwan
- Prior art keywords
- prodrug
- dioxide
- heptane
- antibiotic
- acid
- Prior art date
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- 229940002612 prodrug Drugs 0.000 title claims abstract description 136
- 239000003781 beta lactamase inhibitor Substances 0.000 title 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/48—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40564002P | 2002-08-23 | 2002-08-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200417548A TW200417548A (en) | 2004-09-16 |
| TWI250162B true TWI250162B (en) | 2006-03-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW092123156A TWI250162B (en) | 2002-08-23 | 2003-08-22 | Beta-lactamase inhibitor prodrug |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US7091197B2 (https=) |
| EP (1) | EP1534717B1 (https=) |
| JP (1) | JP2005539037A (https=) |
| KR (1) | KR20050037583A (https=) |
| CN (1) | CN1688589A (https=) |
| AP (1) | AP2005003231A0 (https=) |
| AR (1) | AR041028A1 (https=) |
| AT (1) | ATE349452T1 (https=) |
| AU (1) | AU2003250489A1 (https=) |
| BR (1) | BR0313683A (https=) |
| CA (1) | CA2494953A1 (https=) |
| DE (1) | DE60310733D1 (https=) |
| EA (1) | EA007540B1 (https=) |
| EC (1) | ECSP055625A (https=) |
| GT (1) | GT200300179A (https=) |
| HR (1) | HRP20050162A2 (https=) |
| IL (1) | IL166719A0 (https=) |
| IS (1) | IS7693A (https=) |
| MA (1) | MA27387A1 (https=) |
| MX (1) | MXPA05001446A (https=) |
| NO (1) | NO20051497D0 (https=) |
| NZ (1) | NZ538340A (https=) |
| OA (1) | OA12909A (https=) |
| PA (1) | PA8579701A1 (https=) |
| PE (1) | PE20040899A1 (https=) |
| PL (1) | PL375988A1 (https=) |
| TN (1) | TNSN05054A1 (https=) |
| TW (1) | TWI250162B (https=) |
| UY (1) | UY27947A1 (https=) |
| WO (1) | WO2004018484A1 (https=) |
| ZA (1) | ZA200501513B (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004108733A1 (en) * | 2003-06-05 | 2004-12-16 | Pfizer Products Inc. | Beta-lactamase inhibitor prodrug |
| US20060105941A1 (en) * | 2004-11-12 | 2006-05-18 | Allergan, Inc. | Mixed antibiotic codrugs |
| EP1913378A1 (de) * | 2005-07-29 | 2008-04-23 | Sigma-Aldrich Production GmbH | Ionisierungsadditive enthaltende lc/ms-blends |
| WO2010118968A1 (en) | 2009-04-16 | 2010-10-21 | Nicox S.A. | No-donor aspirin derivatives |
| WO2013056163A1 (en) * | 2011-10-14 | 2013-04-18 | The Regents Of The University Of California | Beta-lactamase inhibitors |
| CN104159587A (zh) * | 2012-01-06 | 2014-11-19 | 南佛罗里达大学 | 组合物、使用方法、以及治疗方法 |
| CN109422765B (zh) * | 2017-09-05 | 2020-08-28 | 香港理工大学深圳研究院 | C类β-内酰胺酶抑制剂及其制备方法和应用 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE34011B1 (en) | 1969-03-13 | 1975-01-08 | Leo Pharm Prod Ltd | New penicillin esters |
| IE34019B1 (en) | 1969-03-18 | 1975-01-08 | Leo Pharm Prod Ltd | New semi-synthetic penicillin esters |
| GB1267936A (en) | 1969-05-28 | 1972-03-22 | Beecham Group Ltd | DERIVATIVES OF alpha-AMINOPENICILLINS |
| US3957764A (en) | 1969-11-11 | 1976-05-18 | Lovens Kemiske Fabrik Produktionsaktieselskab | 6-aminopenicillanic acid derivatives |
| US3862181A (en) | 1970-10-28 | 1975-01-21 | Squibb & Sons Inc | Process for preparing cephalosporins |
| GB1315566A (en) | 1970-11-06 | 1973-05-02 | Leo Pharm Prod Ltd | Penicillanic acid derivatives |
| CA996929A (en) | 1971-04-05 | 1976-09-14 | Kohzi Nakano | Acyloxyalkyl ester derivatives of penicillin |
| GB1433131A (en) | 1972-03-13 | 1976-04-22 | Astra Laekemedel Ab | Penicillins |
| GB1426717A (en) | 1972-03-13 | 1976-03-03 | Astra Laekemedel Ab | Penicillins |
| US4397783A (en) | 1979-03-05 | 1983-08-09 | Pfizer Inc. | Process for converting 6,6-disubstituted penicillanic acid derivatives to the 6-β-congeners |
| DE2927004A1 (de) * | 1979-07-04 | 1981-05-27 | Bayer Ag, 5090 Leverkusen | Penicillansaeure-1,1-dioxide, ihre herstellung und ihre verwendung als arzneimittel als arzneimittel |
| US4287181A (en) * | 1979-10-22 | 1981-09-01 | Pfizer Inc. | Derivatives of 6β-hydroxyalkylpenicillanic acids as β-lactamase inhibitors |
| US4432970A (en) | 1979-11-23 | 1984-02-21 | Pfizer Inc. | 6-beta-Halopenicillanic acid 1,1-dioxides as beta-lactamase inhibitors |
| GB2076812A (en) * | 1980-05-22 | 1981-12-09 | Ciba Geigy Ag | Penam-dioxide compounds, processes for their manufacture, and their use |
| JPS5849387A (ja) | 1981-09-17 | 1983-03-23 | Sankyo Co Ltd | 7−メトキシセフアロスポリン化合物およびその製法 |
| DE3274453D1 (en) * | 1981-09-22 | 1987-01-15 | Kureha Chemical Ind Co Ltd | Penicillin derivatives |
| US4406887A (en) | 1981-10-13 | 1983-09-27 | Bristol-Myers Company | Method for treating resistant bacteria including anaerobes |
| US4428935A (en) * | 1982-05-24 | 1984-01-31 | Pfizer Inc. | Penicillanic acid dioxide prodrug |
| US4521533A (en) | 1984-07-12 | 1985-06-04 | Pfizer Inc. | Salts of 6-alpha-(aminomethyl)penicillanic acid 1,1-dioxide esters and beta-lactam antibiotics |
| DE3901405A1 (de) | 1989-01-19 | 1990-07-26 | Hoechst Ag | Cephalosporinderivate und verfahren zu ihrer herstellung |
| JPH03206038A (ja) | 1990-01-08 | 1991-09-09 | Yoshitomi Pharmaceut Ind Ltd | 抗菌剤 |
| GB9001405D0 (en) | 1990-01-22 | 1990-03-21 | Leo Pharm Prod Ltd | New intermediates,their production and use |
| GB9208492D0 (en) | 1992-04-16 | 1992-06-03 | Glaxo Spa | Heterocyclic compounds |
| WO2004108733A1 (en) | 2003-06-05 | 2004-12-16 | Pfizer Products Inc. | Beta-lactamase inhibitor prodrug |
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