WO2004067532A1 - Nouveaux dérivés de carbapenem - Google Patents

Nouveaux dérivés de carbapenem Download PDF

Info

Publication number
WO2004067532A1
WO2004067532A1 PCT/JP2004/000990 JP2004000990W WO2004067532A1 WO 2004067532 A1 WO2004067532 A1 WO 2004067532A1 JP 2004000990 W JP2004000990 W JP 2004000990W WO 2004067532 A1 WO2004067532 A1 WO 2004067532A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
methyl
thio
hydroxyethyl
carboxylate
Prior art date
Application number
PCT/JP2004/000990
Other languages
English (en)
Japanese (ja)
Inventor
Yuko Kano
Kaori Kaneda
Takehiko Sawabe
Kiyoshi Tanabe
Takahisa Maruyama
Mizuyo Kurazono
Hiromi Takata
Kazuhiro Aihara
Kunio Atsumi
Original Assignee
Meiji Seika Kaisha, Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from JP2003169928A external-priority patent/JP2006151814A/ja
Priority claimed from JP2003194688A external-priority patent/JP2006151815A/ja
Application filed by Meiji Seika Kaisha, Ltd. filed Critical Meiji Seika Kaisha, Ltd.
Publication of WO2004067532A1 publication Critical patent/WO2004067532A1/fr

Links

Classifications

    • 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
    • C07D477/10—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 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with 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
    • C07D477/12—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 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with 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 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
    • C07D477/16—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 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with 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 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms 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 3
    • C07D477/20—Sulfur atoms
    • 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

Definitions

  • the present invention relates to a compound having excellent antibacterial activity and a broad spectrum, and more particularly, to a substituted (thiazole-5-yl) thio group at the 2-position on the compound.
  • the present invention relates to a novel derivative of the compound.
  • MRSA methicillin-resistant Staphylococcus aureus
  • VRE vancomycin-resistant enterococcus
  • PRSP penicillin-resistant pneumococcus
  • an object of the present invention is to provide a potent rubenem derivative having a strong antibacterial activity against pneumococci including MRSA, VRE and PRSP, influenza bacteria including BLNAR and / or -lactamase-producing bacteria.
  • the present inventors have recently proposed a new S-carbane derivative represented by the following formula (I): It has a broad and strong antibacterial activity against rum-positive and gram-negative bacteria, and has a strong antibacterial activity against MRSA, PRSP, H. influenzae and / or lactamase-producing bacteria.
  • the present invention is based on such findings.
  • the carbane derivative according to the present invention is a compound of the following general formula (I) or a pharmaceutically acceptable salt thereof:
  • R 1 represents a hydrogen atom or a methyl group
  • R 2 and R 3 may be the same or different
  • An optionally substituted heteroaryl group A lower alkylthio group, or.
  • R 2 and R 3 do not both represent a hydrogen atom
  • R 4 represents a hydrogen atom or a group that can be hydrolyzed in vivo. ].
  • the rubanem derivative of the general formula (I) according to the present invention has a broad and strong antibacterial activity against Gram-positive bacteria and Gram-negative bacteria. In particular, it has strong antibacterial activity against various pathogens including pneumococci including MRSA, VHE and PRSP, influenzae including BLNAR, and / or lactobacillus producing bacteria.
  • the potent rubanem derivatives of the general formula (I) according to the invention show a particularly pronounced antibacterial activity against pneumococci containing PRSP.
  • the carbane derivative of the compound (I) in which R 4 is a group that is hydrolyzed in vivo exhibits excellent oral absorbability, and It is metabolically deesterified in the body to produce a drug substance with antibacterial activity (compound of general formula (I ')). Therefore, the compound of the general formula (I) of the present invention is useful not only as an injection but also as an ester thereof as an oral preparation. Furthermore, the carbane derivative of the present invention is excellent in that it has low toxicity and high safety.
  • lower alkyl group or “lower alkoxy group” as a group or a part of a group preferably means that the group has a linear or branched carbon number of 1 to 6, more preferably 1 to 6 carbon atoms. 4 means an alkyl group or an alkoxy group.
  • lower alkyl as a group or part of a group include methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, neopentyl, i-pentyl, t-pentyl, n-hexyl, i-hexyl and the like.
  • lower alkoxy examples include methoxy, Ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, s-butyloxy, t-butyloxy, n-pentyloxy, neopentyloxy, i-pentyloxy, t-pentyloxy, n-hexyloxy, i-hexyloxy, etc. Is mentioned.
  • lower cycloalkyl group as a group or a part of a group means a monocyclic alkyl group having 3 to 7 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl Is mentioned.
  • halogen atom indicates each atom of fluorine, chlorine, bromine, and iodine.
  • aryl group as a group or part of a group means a phenyl group or a naphthyl group.
  • heteroaryl group as a group or part of a group is the same or different and has 5 or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. It means a 6-membered aromatic heterocyclic ring. Preferably, it represents furan, pyrrole, imidazole, thiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, or pyrazine, and more preferably, furan, imidazole, thiazole, or the like. Pyridine and the like can be mentioned.
  • R 1 represents a hydrogen atom or a methyl group.
  • R 2 and R 3 may be the same or different and each is a hydrogen atom, a halogen atom, a formyl group, a nitrile group, an optionally substituted amino group, an optionally substituted lower alkyl group, Optionally substituted rubamoyl group, optionally substituted lower alkylcarbonyl group, optionally substituted lower alkoxylation group, optionally substituted arylcarbonyl group, substituted A heteroarylcarbonyl group, a carboxyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, a lower alkylthio group, or a lower alkylaryl group. Represents a lower alkylsulfonyl group, provided that both R 2 and R 3 do not represent a hydrogen atom.
  • examples of one or more substituents of the amino group include a lower alkyl group, a lower cycloalkyl group, a lower alkoxy group, a lower alkoxyalkyl group, A lower alkylcarbonyl group, a lower alkoxycarbonyl group, a formyl group, an aminocarbonyl group, an aminosulfonyl group, a lower alkyl group, a rubamoyl group, a hydroxy lower alkyl group, an amino lower alkyl group, an aryl group, or a heteroaryl group.
  • a formyl group, a lower alkoxycarbonyl group, an aminocarbonyl group, and an aminosulfonyl group can be mentioned, and more preferably, a formyl group and a methoxycarbonyl group can be mentioned.
  • preferred examples of the optionally substituted amino group represented by R 2 and R 3 include a formylamino group and a methoxycarbonylamino group.
  • substituents of the lower alkyl group represented by R 2 and R 3 include a hydroxyl group, a lower alkoxy group, a lower alkylthio group, an amino group, an aryl group, a heteroaryl group, and a carbamoyl group.
  • a preferable example of the optionally substituted lower alkyl group represented by R 2 and: 3 is a hydroxymethyl group.
  • Examples of one or more substituents of the optionally substituted rubamoyl group represented by R 2 and R 3 include an optionally substituted lower alkyl group, a lower cycloalkyl group, and an optionally substituted lower group.
  • More preferred substituents include a lower alkyl group (at least one hydrogen atom of the alkyl group is a hydroxyl group, an amino group, a carbamoyl group, an amino lower alkyl group). , A formylamino group, a lower alkylcarbonylamino group, an aminosulfonylamino group, an aminocarbonylamino group, a lower alkoxy group, a thiazolyl group, a furyl group, a pyridyl group, or a lower alkylthio group Good), lower cycloalkyl group, phenyl group, naphthyl group, thiazolyl group, furyl group, pyridyl group and lower alkoxy group.
  • a methyl group, an ethyl group and a 1,1 -yl group are particularly preferred.
  • One or more hydrogen atoms of the lower alkylcarbonyl group represented by R 2 and R 3 may be substituted, and examples of the substituent include a hydroxyl group, a lower alkoxy group, a lower alkylthio group, an amino group, an aryl group, Examples include a heteroaryl group, a carbamoyl group, a lower alkylaminocarbonyl group, a formylamino group, a lower alkylcarbonylamino group, an aminosulfonylamino group, and an aminocarbonylamino group, preferably a hydroxyl group or an N— And a methylcarbamoyl group.
  • the optionally substituted lower alkyl carbonyl group represented by R 2 and R 3 preferred examples include a methyl group, an ethyl group, and an N-methylcarbamoyl. Examples include a methyl group, a 3-hydroxypropane-1-yl group, and a 3,4-dihydroxybutane-1-yl group.
  • One or more hydrogen atoms of the lower alkoxycarbonyl group represented by R 2 and R 3 may be substituted, and examples of the substituent include a hydroxyl group, a lower alkoxy group, a lower alkylthio group, an amino group, and an aryl group.
  • Examples are a hydroxyl group, a sulfamoyl group, a lower alkoxy group, and a lower alkylthio group.
  • preferred examples of the optionally substituted lower alkoxy group include a methoxy group, an ethoxy group, and a Yl) oxy, isopropyloxy, (butane-11-yl) oxy, carbamoylmethoxy, 2-hydroxyethoxy, (3-hydroxypropane-11-yl) oxy, 2,3-dihydroxypropane_1-yl) oxy group, (4-hydroxybutane_1-yl) oxy group, (3-hydroxybutane-1-yl) oxy group, (5-hydroxypentane-1 1-yl) oxy group, (2,2-dimethyl-13-hydroxypropan-1-yl) oxy group, (3-hydroxy-13-methylbutane-11-yl) oxy group, 2-methoxy Examples include a ethoxy group, a 2-ethoxyethoxy group, a (3-methoxypropanol) -
  • substituents include a hydroxyl group, an amino group, a lower alkyl group and a lower alkoxy group.
  • the heteroaryl of the heteroarylcarbonyl group represented by R 2 and R 3 is preferably a 5- or 6-membered aromatic having one hetero atom selected from the group consisting of nitrogen, oxygen and sulfur. It is a heterocyclic ring, and more preferably, furan, pyrrole, thiazol, and pyridine.
  • the heteroaryl group represented by R 2 and R 3 is preferably a 5- or 6-membered aromatic heterocyclic ring having one hetero atom selected from the group consisting of nitrogen, oxygen, and sulfur, more preferably And furan, pyrrol, thiazole and pyridine, and particularly preferably a pyridine-3-yl group, a pyridine-14-yl group, a thia, and a J-ru-2-yl group.
  • Preferred examples of the lower alkylthio group represented by R 2 and R 3 include a methylthio group.
  • Preferred examples of the lower alkylsulfonyl group represented by R 2 and are: And a methanesulfonyl group.
  • a compound of the formula (I) or a pharmaceutically acceptable salt thereof wherein R 2 is a hydrogen atom and R 3 is a carbamoyl group.
  • preferred compounds of the formula (I) or a pharmaceutically acceptable salt thereof are those wherein R 2 is a hydrogen atom and R 3 is an ethoxycarbonyl group. Provided.
  • preferred compounds of the formula (I) or a pharmaceutically acceptable salt thereof are those wherein R 2 is a hydrogen atom and R 3 is a methoxycarbonyl group. Provided.
  • R 2 is a hydrogen atom and R 3 is (2-hydroxy) ethoxycarbonyl
  • the base is provided.
  • a preferable compound of the formula (I) or a pharmaceutically acceptable salt thereof is a hydrogen atom, and R 3 is (3-hydroxypropane-1-yl) Are provided which are oxycarbonyl groups.
  • R 4 is a group that is hydrolyzed in a living body
  • the group is preferably an ester residue, for example, a lower alkylcarbonyloxy lower alkyl group, a lower cycloalkylcarbonylcarbonyloxy lower alkyl group, a lower cycloalkyl Methylcarbonyl lower alkyl group, lower alkenylcarbonyloxy lower alkyl group, arylcarbonyl lower alkyl group, tetrahydrofuranylcarbonyloxymethyl group, lower alkoxy lower alkyl group, lower alkoxy lower alkoxy lower alkyl group, a Reel methyloxy lower alkyl group, arylmethyl lower alkoxy group, lower alkyl group, lower alkyloxycarbonyl lower alkyl group A lower alkyl group, a lower cycloalkyloxycarbonyloxy lower alkyl group, a lower cycloalkylmethoxycarbonyloxy lower alkyl group, an ary
  • R 4 examples include a bivaloyloxymethyl group, a 1- (bivaloyloxy) ethyl group, an isobutyryloxymethyl group, a 1- (isobutyryloxy) ethyl group, an acetoxmethyl group, and a 1- (acetoxymethyl group.
  • Ethyl group (1-methylcyclohexane-1-yl) carbonyloxymethyl group, (1-ethylpropan-1-yl) carbonyloxymethyl group, isobutylcarbonyloxymethyl group, 11- (cyclo Hexyloxycarbonyloxy) ethyl group, 1- (cyclohexylmethoxycarbonyloxy) ethyl group, 1- (2-cyclohexylethoxycarbonylcarbonyloxy) ethyl group, 1- (neopentyloxycarbonyloxy) Xy) ethyl group, 1- (ethoxycarbonyloxy) ethyl group, cyclohexyloxycarbonyloxymethyl group, 1- [(2 —Methylcyclohexane-1-yl) oxycarbonyloxy] ethyl group, cyclopentyloxycarboxyloxymethyl group, 1- (isopropyloxycarbonyloxy) ethyl
  • Salts of general formula (I) are pharmaceutically acceptable salts, for example inorganic salts such as lithium, sodium, potassium, calcium, magnesium, or ammonium salts, triethylamine, diisopropylethylamine Salts with organic bases such as, or salts with mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, or acids such as acetic acid, carbonic acid, citric acid, malic acid, oxalic acid, methanesulfonic acid. And a salt with an organic acid, preferably a sodium salt, a potassium salt, or a hydrochloride.
  • inorganic salts such as lithium, sodium, potassium, calcium, magnesium, or ammonium salts, triethylamine, diisopropylethylamine Salts with organic bases such as, or salts with mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, or acids such as acetic acid, carbonic acid,
  • a compound wherein R 4 is a hydrogen atom, or a salt thereof (1 ′) can be preferably produced according to the following scheme.
  • R 5 represents a hydrogen atom or a hydroxyl protecting group (for example, t-butyldimethylsilyl group, Represents a trimethylsilyl group, a triethylsilyl group, a 4-nitrobenzyloxycarbonyl group, a 4-methoxybenzyloxycarbonyl group, an aryloxycarbonyl group, etc .
  • R 6 is a carboxyl protecting group (for example, 412 base Njiru group, 4-methoxybenzyl group, Jifuenirumechiru group, t-butyl di methylsilyl group, an Ariru group), the functional group R 7 and R 8 are contained in R 2 and R 3 the same or R 2 and R 3 (For example, a hydroxyl group, an amino group, a carboxyl group, etc.) are those protected by ordinary protecting groups (here, ordinary protecting groups are defined
  • the compound of the formula (II) in the scheme in the first step can be synthesized by a conventional method (for example, JP-A-57-123182, JP-A-64-25779).
  • the conversion of (II) into (III) can be performed by the following method. That is, one equivalent or an excess of trifluoromethanesulfonic anhydride relative to (II) is used, and one equivalent or an excess of an organic base (preferably, diisopropylethylamine) is used relative to tri'fluorenesulfonic acid anhydride.
  • Tylamine in the presence of acetonitrile, acetone, N, N-dimethylformamide, N, N-dimethylacetamide, tetrahydrofuran, dioxane, methanol, ethanol, dichloromethane, toluene, hexamethylphosphoroditriamide, etc.
  • acetonitrile acetone
  • N, N-dimethylformamide N, N-dimethylacetamide
  • tetrahydrofuran dioxane
  • methanol ethanol, dichloromethane, toluene, hexamethylphosphoroditriamide, etc.
  • V hexamethylphosphoroditriamide
  • the protecting group of the compound (V) is removed by a deprotection reaction in one or more steps depending on the kind of the protecting group to give the compound represented by the general formula (I) of the present invention. obtain.
  • the deprotection reaction for removing the protecting group varies depending on the type of the protecting group used, but can be generally carried out according to a usual method known in the art. If any or all of them can be deprotected under acidic conditions, use a mineral acid such as hydrochloric acid, an organic acid such as formic acid, acetic acid, citric acid, or a Lewis acid such as aluminum chloride. When it is removed below, catalytic reduction using various catalysts or a metal reducing agent such as zinc or iron can be used.
  • R 5 is a silyl protecting group (eg, t-butyldimethylsilyl group, trimethylsilyl group, triethylsilyl group, etc.), a fluorine ion reagent (eg, tetrabutylammonium fluoride, etc.) )
  • R 5 is an aryloxycarbonyl group and R 6 is an aryl group. It can be easily removed by using Lakis (triphenylphosphine) palladium (0) or the like.
  • the compound of the general formula (1 ′) thus obtained may be crystallized or chromatographed using a non-ionic Mac-mouth hypoporous resin, gel filtration using Sephadex, etc., reverse phase silica gel column chromatography. Can be used for isolation and purification.
  • the compound (1 ′,) in which R 4 is a group that is hydrolyzed in vivo can be preferably produced according to the following scheme.
  • R 1 , R 2 , and R 3 represent the same meaning as defined in the general formula (I)
  • R 9 represents a hydrogen atom or a metal ion such as potassium or sodium
  • 1 represents a group that is hydrolyzed in the living body (has the same meaning as defined in the section of compounds when“ R 4 is a group that is hydrolyzed in the living body ”)
  • X represents Cl, br, I, - OS_ ⁇ 2 CF 3, - OS0 2 CH 3, to the table a leaving group such as one 0 S 0 2 P h CH 3 .
  • base (1) 1 equivalent or an excess of base (1), (as an organic base, an inorganic base such as diisopropylethylamine, diazabicyclo [2,2,2] indene, 2,6-lutidine, etc.) Is the presence of sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, etc.
  • R 111 — X 1- (Bivaloyloxy) ethyl iodide, Isobutyryloxymethyl iodide, 1- (Isobutyryloxy) ethyl 1- (acetoxy) ethyl chloride, 1- (acetoxy) ethyl chloride, (1-methylcyclohexane-1-yl) carbonyloxymethyl chloride, (1-ethylpropane)
  • ester thus obtained can be isolated and purified by precipitation, crystallization, gel filtration using Sephadex or the like, silica gel column chromatography, or the like.
  • the compound according to the present invention has a broad and strong antibacterial activity against Gram-positive bacteria and Gram-negative bacteria, and is also pneumococcal including MRSA, VRE and PRSP; It has a strong antibacterial activity against evening production bacteria. Further, the compounds according to the present invention have low toxicity and are stable against DHP-1. Therefore, the compounds according to the present invention can be used for treating infectious diseases caused by various pathogenic bacteria in animals including humans.
  • an antimicrobial comprising the compound according to the present invention.
  • a pharmaceutical composition of a compound according to the present invention for the manufacture of an antimicrobial agent.
  • a method for preventing or treating infectious diseases comprising administering a compound according to the present invention to an animal including a human.o
  • the compound according to the invention can be in a pharmaceutical composition.
  • a compound in which R 4 in the formula (I) is a group that is hydrolyzed in a living body is excellent in oral absorbability and has an advantage that it can be used as an oral preparation.
  • a pharmaceutical composition comprising a compound according to the present invention.
  • a compound according to the present invention for the manufacture of a pharmaceutical composition.
  • Pharmaceutical compositions containing the compound according to the present invention and a pharmacologically acceptable salt thereof as an active ingredient are orally or parenterally (eg, intravenous, intramuscular, subcutaneous, rectal, transdermal) ) Can be administered to humans and non-human animals.
  • the pharmaceutical composition comprising the compound according to the present invention as an active ingredient is made into an appropriate dosage form depending on the administration route.
  • injections such as intravenous injection and intramuscular injection, capsules, tablets, and granules are mainly used.
  • formulations contain commonly used excipients, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, solubilizers, preservatives, It can be produced by a conventional method using a flavoring agent, a soothing agent, a stabilizer and the like.
  • the non-toxic additives that can be used include, for example, lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, methylcellulose or salts thereof, gum arabic, polyethylene glycol And syrup, petrolatum, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, and sodium phosphate.
  • the dosage will be determined as appropriate, taking into account the usage, patient age, gender, degree of symptoms, etc.
  • the dose is from 5 Omg to: L00 Omg, which can be administered once or several times a day.
  • T (5R, 6S) -6-((lR)-; l-hydroxyethyl) -2- (4-methoxycarbonylthiazol-5-yl) as in Example lb) 76 mg of the title compound were obtained from 195 mg of thio-1-forcelvapen-2-em-3-carboxylic acid 4-nitrobenzyl.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un nouveau dérivé de carbapenem représenté par la formule générale (I), qui a un effet antimicrobien puissant sur les pneumocoques NRSA, VRE et PRSP, des virus de la grippe comprenant BLNAR et des brins produisant de la β-lactamase parmi des brins résistants qui posent des problèmes cliniques dans l'état de la technique.
PCT/JP2004/000990 2003-01-31 2004-02-02 Nouveaux dérivés de carbapenem WO2004067532A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP2003023945 2003-01-31
JP2003-169928 2003-06-13
JP2003169928A JP2006151814A (ja) 2003-01-31 2003-06-13 新規カルバペネム誘導体
JP2003194688A JP2006151815A (ja) 2003-01-31 2003-07-10 新規カルバペネム誘導体
JP2003-194688 2003-07-10
JP2003-023945 2003-08-19

Publications (1)

Publication Number Publication Date
WO2004067532A1 true WO2004067532A1 (fr) 2004-08-12

Family

ID=32830630

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2004/000990 WO2004067532A1 (fr) 2003-01-31 2004-02-02 Nouveaux dérivés de carbapenem

Country Status (1)

Country Link
WO (1) WO2004067532A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1870412A1 (fr) * 2005-04-12 2007-12-26 Meiji Seika Kaisha Ltd. Dérivé de 2-thioéthénylcarbapénème
WO2009018723A1 (fr) * 2007-08-09 2009-02-12 Kbp Biomedical Co., Ltd. Composés de carbapenem substitués par sulfonyle
US7687490B2 (en) * 2005-04-12 2010-03-30 Meiji Seika Kaisha, Ltd. 2-thioethenyl substituted carbapenem derivatives
US7795244B2 (en) 2006-06-28 2010-09-14 Pfizer Inc. Penem prodrugs
CN102633816A (zh) * 2012-03-30 2012-08-15 李莎 头孢西丁酯化前体药物化合物及口服制剂

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000143511A (ja) * 1998-09-09 2000-05-23 Banyu Pharmaceut Co Ltd メタロ―β―ラクタマ―ゼ阻害剤

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000143511A (ja) * 1998-09-09 2000-05-23 Banyu Pharmaceut Co Ltd メタロ―β―ラクタマ―ゼ阻害剤

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1870412A1 (fr) * 2005-04-12 2007-12-26 Meiji Seika Kaisha Ltd. Dérivé de 2-thioéthénylcarbapénème
EP1870412A4 (fr) * 2005-04-12 2009-12-30 Meiji Seika Kaisha Dérivé de 2-thioéthénylcarbapénème
US7687490B2 (en) * 2005-04-12 2010-03-30 Meiji Seika Kaisha, Ltd. 2-thioethenyl substituted carbapenem derivatives
US8344154B2 (en) 2005-04-12 2013-01-01 Meiji Seika Kaisha, Ltd. 2-thioethenyl substituted carbapenem derivatives
US7795244B2 (en) 2006-06-28 2010-09-14 Pfizer Inc. Penem prodrugs
US7795243B2 (en) 2006-06-28 2010-09-14 Pfizer, Inc. Penem prodrugs
WO2009018723A1 (fr) * 2007-08-09 2009-02-12 Kbp Biomedical Co., Ltd. Composés de carbapenem substitués par sulfonyle
CN101952290B (zh) * 2007-08-09 2013-01-23 山东轩竹医药科技有限公司 磺酰基取代的碳青霉烯类化合物
CN102633816A (zh) * 2012-03-30 2012-08-15 李莎 头孢西丁酯化前体药物化合物及口服制剂

Similar Documents

Publication Publication Date Title
JP2555648B2 (ja) ３−ピロリジニルチオ−１−アザビシクロ〔３．２．０〕ヘプト−２−エン−２−カルボン酸化合物
AU2013305390C1 (en) Dihydropyrimidine compounds and their application in pharmaceuticals
US20060106034A1 (en) Drug efflux pump inhibitor
JPH0853453A (ja) ２−［１−（１，３−チアゾリン−２−イル）アゼチジン−３−イル］チオ−カルバペネム化合物
KR20200058520A (ko) 박테리아 감염의 치료를 위한 크로만 모노박탐 화합물
ES2273902T3 (es) Derivados de 1-metilcarbapenem.
WO2000006581A1 (fr) Nouveaux derives de carbapenem
RU2097383C1 (ru) Производные карбапенема и способ их получения
JP2012149079A (ja) ２位チオエテニル系カルバペネム誘導体
JP2008273924A (ja) ２位チエニルカルバペネム誘導体
WO2004067532A1 (fr) Nouveaux dérivés de carbapenem
WO1998034936A1 (fr) Composes de carbapenem, leur utilisation et composes intermediaires de celui-ci
JPH07507785A (ja) ３−置換カルバセフェム
JP2006151815A (ja) 新規カルバペネム誘導体
US5116833A (en) Antibiotic c-3 dithioacetal-substituted carbapenem compounds, compositions, and methods of use thereof
JP2002212182A (ja) １−メチルカルバペネム誘導体
US5719139A (en) 9-oxo-1-azabicyclo 5.2.0!non-2,4-diene-2-carboxylic acid compounds as antibiotics
JP2500286B2 (ja) ２−ヘテロアリ―ルフェニル−カルバペネム抗菌剤
WO2006049148A1 (fr) DÉRIVÉ DE 1β-MÉTHYLCARBAPÉNÈME
JP2007291048A (ja) １β−メチルカルバペネム誘導体を含有する医薬
JPWO2006109823A1 (ja) ２位チオエテニル系カルバペネム誘導体
JPH0641131A (ja) 新規カルバペネム誘導体
WO2001057041A1 (fr) Composes 1-methylcarbapedem
JP2006151814A (ja) 新規カルバペネム誘導体
JPH09165388A (ja) カルバペネム化合物、その製造法および剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DPEN Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP