WO2002048149A1 - Nouveaux composes de ?-lactame et procede de preparation associe - Google Patents

Nouveaux composes de ?-lactame et procede de preparation associe Download PDF

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Publication number
WO2002048149A1
WO2002048149A1 PCT/JP2001/010826 JP0110826W WO0248149A1 WO 2002048149 A1 WO2002048149 A1 WO 2002048149A1 JP 0110826 W JP0110826 W JP 0110826W WO 0248149 A1 WO0248149 A1 WO 0248149A1
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Prior art keywords
group
general formula
lower alkyl
alkyl group
methyl
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PCT/JP2001/010826
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English (en)
Japanese (ja)
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Makoto Sunagawa
Paul Hebeisen
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Sumitomo Pharmaceuticals Company, Limited
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Priority to JP2002549680A priority Critical patent/JPWO2002048149A1/ja
Priority to AU2002221114A priority patent/AU2002221114A1/en
Publication of WO2002048149A1 publication Critical patent/WO2002048149A1/fr

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    • 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
    • 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

Definitions

  • the present invention relates to a novel) 3-latatam compound represented by the following general formula [1].
  • MRS II methicillin-resistant staphylococci
  • MR CNS methicillin-resistant coadalase-negative pseudostaphylococci
  • An object of the present invention is to provide a 3-lactam drug having excellent antibacterial activity against Gram-positive bacteria, particularly MRSA and MR CNS.
  • the present inventors have found that the compound represented by the following general formula [1] has a strong potency against Gram-positive bacteria, and particularly shows excellent antibacterial activity against MRSA and MRCNS. To complete the present invention.
  • R 1 is a lower alkyl group or a lower alkyl group substituted with a hydroxyl group
  • R 2 is a hydrogen atom or a lower alkyl group
  • R 3 is a hydrogen atom, an optionally protected hydroxyl group, an imidoyl group.
  • R 4 and R 5 are each independently a hydrogen atom, an optionally protected hydroxyl group, an amino group-protecting group, or a substituted lower alkyl group; R 3 , R 4, and R 5 may be any two of them bonded together with one nitrogen atom, or with two nitrogen atoms and one carbon atom, It can also form a 5- or 7-membered heterocyclic ring which may be substituted, A is an optionally substituted phenylene group, and X represents O, S or NH. ]
  • I3_ ratatum compound represented by or a pharmaceutically acceptable salt or non-toxic ester thereof,
  • X is S, (1) the monolatatum compound or a pharmaceutically acceptable salt or non-toxic ester thereof,
  • R 1 is a lower alkyl group or a lower alkyl group substituted by a hydroxyl group
  • R 2 is a hydrogen atom or a lower alkyl group
  • R 3 is a hydrogen atom
  • R 4 and R 5 each independently represent a hydrogen atom, an optionally protected hydroxyl group, an amino group, or a protecting group for an imidoyl group or a lower alkyl group which may be substituted.
  • R 3 , R 4, and R 5 may be any two of these bonded to form, together with, or with one nitrogen atom, May form a 5- to 7-membered heterocyclic ring with one carbon atom,
  • A is an optionally substituted phenylene group, and
  • X is ⁇ , S or NH Show. ]
  • R la is a lower alkyl group, a lower alkyl group substituted with a hydroxyl group, or a lower alkyl group substituted with a hydroxyl group protected with a protecting group
  • R 2 has the same meaning as described above
  • R 6 Represents a carboxyl protecting group
  • L represents an active ester of a hydroxyl group.
  • R la , R 3 , R 4 and R 5 have a hydroxyl group protecting group removal reaction
  • R 3 has an imidoyl group protecting group removal reaction
  • R 4 and R 5 have an amino group protection Suitable for the reaction for removing the group and the reaction for removing the protective group for the carboxyl group in R 6 : a 3-lactam compound represented by the general formula [1] characterized by performing a combined reaction: ,
  • an antibacterial agent containing the 3-latatam compound according to any one of (1) to (3) or a pharmaceutically acceptable salt or a nontoxic ester thereof examples include straight-chain or branched such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butylinole, n-pentyl or n-hexyl. Examples thereof include a chain having 1 to 6 carbon atoms.
  • Examples of the lower alkyl group substituted by a hydroxyl group include hydroxymethyl, 1-hydroxyethynole, 2-hydroxyxetinole, 1-hydroxy-11-methylethyl, 1-hydroxypropyl, and 2-hydroxypropyl. Having 1 to 6 carbon atoms.
  • Examples of the substituent of the optionally substituted lower alkyl group or the optionally substituted phenylene group include a hydroxyl group, a lower alkyloxy group, a lower alkylcarbonyl group, a lower alkylcarbonyloxy group and a lower alkyl group.
  • Oxycarbonyl group, carbonyl group, halogen atom, cyano group, NR 6 R 7 R 6 and R 7 each independently represent a hydrogen atom or a lower alkyl group, or R 6 and R 7 may be taken together with the nitrogen atom to form pyrrolidine, piperidine, monorephorin, piperazine, N-lower alkyl substituted piperazine or azepane.
  • Lower alkyloxy groups include, for example, straight-chain or branched carbons such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy or n-hexoxy. Examples of numbers 1 to 6 are given.
  • Examples of the lower alkyl carboxy group include methyl carbyl, ethyl carbonyl, n-propyl carbonyl, isopropyl carbole, n-butyl carbole, isoptinolecanolebonore, tert-butylcanolebonyl, Examples thereof include a linear or branched lower alkylcarboyl group having 2 to 7 carbon atoms such as pentinorecanolole-n- or n-hexylcarbonyl.
  • Examples of the lower alkylcarboxy group include, for example, methylcarbonyloxy, ethylcarbonyloxy, n-propylcarbonyloxy, isopropylcarbonyloxy, n-butylcarbonoxy, isobutylcarbonyloxy, tert.
  • Examples thereof include a linear or branched lower alkynolecarboxy group having 2 to 7 carbon atoms, such as xy, n-pentylcarboxy or n-hexynolecapillonyloxy.
  • Examples of the lower alkyloxycarbonyl group include methyloxycarbonyl, ethyloxypropyl, n-propyloxypropyl, isopropyloxycanoleponinole, n-butyloxycanoleponyl, and isobutyloxycarbonyl.
  • Tert Examples thereof include linear or branched lower alkyloxycarbonyl groups having 2 to 7 carbon atoms, such as monobutyloxycarbyl, n-pentyloxycarbonyl or n-hexylcarbocarber.
  • the halogen atom represents fluorine, chlorine, bromine or iodine.
  • Examples of the 5- to 7-membered hetero ring include a pyrrolidine ring, a piperidine ring, an azepane ring, a 3,4-dihydro-2H-pyrrole ring, a 2,3,4,5-tetrahydropyridine ring, Examples include 4,5,6-tetrahydro-12H-azepine ring, morpholine ring, thiomorpholine ring, piperazine ring, 2-imidazoline ring, 1,4,5,6-tetrahydropyrimidine ring and the like.
  • Examples of the substituent of the optionally substituted 5- to 7-membered hetero ring include a lower alkyl group, a hydroxyl group, a lower alkyloxy group, a lower alkylcarboxy group, a lower alkylcarboeroxy group, and a lower alkylo group.
  • Examples include a carbonyl group, a carboxyl group, a halogen atom, and a cyano group.
  • the phenylene groups include 1,2-phenylene, 1,3-phenylene and 1,4-phenylene.
  • the protecting group for the carbonyl group various types of protecting groups which are usually used can be used.
  • the protecting group is linear or branched such as methyl, ethyl, isopropyl and tert-butyl.
  • Lower alkyl groups having 1 to 5 carbon atoms for example, lower alkyl groups having 1 to 5 carbon atoms, such as 2-ethylenoxytyl, 2,2,2-trichloromethyl, for example, methoxymethyl, ethoxymethyl, isobutoxy; 1 to 1 carbon atoms such as methyl
  • a lower alkoxymethyl group such as 5, for example, aceethoxymethyl, propionyloxymethyl, butyryloxymethyl, and bivaloyloxymethyl; a lower aliphatic acyloxymethyl group having 1 to 5 carbon atoms, for example, 1-ethoxy; carbonyl O 1--C 5) lower alkoxycarbonyl Interview Ruo key shell ethyl group such as carboxymethyl Echiru, e.g. downy Njinore, .rho.
  • Ararukiru groups such as twelve Toroben Gilles Examples thereof include a lower alkenyl group having 3 to 7 carbon atoms such as aryl, 3-methylaryl, a benzhydryl group, or a phthalidyl group.
  • Examples of the protecting group for the hydroxyl group, the protecting group for the imidoyl group, and the protecting group for the amino group include those capable of using various protecting groups which are usually used.
  • a lower alkoxycarbonyl group having 1 to 5 carbon atoms such as cicarbonyl, for example, a carbon atom having 1 to 5 carbon atoms such as 2-iodyloxycarbonyl and 2,2,2-trichloroethylcarbonyl.
  • a substituted or unsubstituted lower alkenyloxycarbonyl group having 3 to 7 carbon atoms such as aryloxycarboyl group, for example, benzyloxycarbonyl, p-methoxybenzyloxy group, o —Altoalkyloxycarbonyl groups such as benzodioxyoxycarbonyl, and p-toluene benzoyloxycarbonyl, for example, trialkylsilyl groups such as trimethylsilyl, triethylsilyl, and tert_butyldimethylsilyl Is mentioned.
  • aryloxycarboyl group for example, benzyloxycarbonyl, p-methoxybenzyloxy group, o —Altoalkyloxycarbonyl groups such as benzodioxyoxycarbonyl, and p-toluene benzoyloxycarbonyl, for example, trialkylsilyl groups such as trimethylsilyl, triethy
  • Examples of the protecting group for the imidoyl group and the protecting group for the amino group include, for example, (5_methyl-1,3-dioxolen-12-one-1-yl) methyloxycarbonyl group ⁇ 3- (benzoylamino) propionyl group. Groups that can be completely hydrolyzed in vivo.
  • the pharmaceutically acceptable salt represented by the general formula [1] is a commonly used non-toxic salt.
  • examples of such salts include, as salts of carboxylic acids in the molecule, inorganic base salts such as sodium, potassium, calcium, magnesium, and ammonium, for example, triethylammonium, pyridium, and diisopropylammonium.
  • inorganic base salts such as sodium, potassium, calcium, magnesium, and ammonium, for example, triethylammonium, pyridium, and diisopropylammonium.
  • organic base salt, and an intramolecular salt formed with a positive charge such as a quaternary ammonium on the side chain at the 3-position are exemplified.
  • inorganic acid salts such as sulfuric acid and phosphoric acid
  • organic acid salts such as formic acid, acetic acid, oxalic acid, methanesulfonic acid and benzenesulfonic acid.
  • the non-toxic ester at the 2-carboxyl group of the general formula [1] means a conventional pharmaceutically acceptable ester, preferably, for example, acetoxmethyl, propionyloxymethyl, n-butylyloxymethyl, vivaloyl (Alkoxy alkenyl having 2 to 10 carbon atoms) such as oxymethyl, cyclohexyl acetooxymethyl, (1-methylcyclohexanyl propyloxy) methyl,
  • the -lactam compound represented by the general formula [1] or a pharmaceutically acceptable salt or non-toxic ester thereof may be an anhydride, hydrate or solvate thereof.
  • an active ester of a hydroxyl group is, for example, a substituted or unsubstituted arylsulfonate such as benzenesulfonic acid ester, p-tonolenesnolefonic acid ester, nitrobenzenesnolefonic acid ester, and ⁇ -bromobenzenesulfonic acid ester.
  • arylsulfonate such as benzenesulfonic acid ester, p-tonolenesnolefonic acid ester, nitrobenzenesnolefonic acid ester, and ⁇ -bromobenzenesulfonic acid ester.
  • Acid esters such as lower alkanesulfonic acid esters having 1 to 5 carbon atoms such as methanesulfonic acid esters and ethanesulfonic acid esters, and halogenoalkane nolephones having 1 to 5 carbon atoms such as triphenylenolomethanesulfonic acid esters and the like
  • Acid esters for example, aryl phosphoric acid esters such as diphenyl phosphoric acid ester, and halides such as chlorinated, brominated, and iodo compounds, which are esters with hydrogen halide, and the like can be given.
  • aryl phosphoric acid esters such as diphenyl phosphoric acid ester
  • halides such as chlorinated, brominated, and iodo compounds, which are esters with hydrogen halide, and the like can be given.
  • reactive esters of hydroxyl groups preferred are!
  • the inert solvent used to obtain the compound represented by the general formula [4] in the presence of a base from the compound represented by the general formula [2] and the compound represented by the general formula [3] includes dioxane and tetrahydrofuran. And dimethyl sulfoxide, dimethyl honoleamide, acetonitrinole, benzene, toluene, hexametinole phosphoramide, and a mixed solvent thereof.
  • bases include inorganic bases such as sodium carbonate, carbonated lime, sodium hydride, hydrogenated lime, pyridine, dimethylaminopyridine, triethylamine, diisopropylethylamine, 1,8-diazavisic mouth [ 5. 4. 0]
  • Organic bases such as van decay 7-ene (DBU). Particularly preferred is DBU.
  • the base is required to be used in an amount sufficient for the reaction to proceed sufficiently, and the reaction can be usually performed using 1 to 3 equivalents to the mercaptan compound represented by the general formula [3].
  • the amount of the mercaptan compound represented by the general formula [3] needs to be sufficient to allow the reaction to proceed sufficiently, and a large excess can be used. It can be performed using 1-2 equivalents.
  • the reaction is carried out at a temperature in the range of ⁇ 100 ° C. to + 60 ° C., preferably in the range of ⁇ 40 ° C. to + 40 ° C. After the completion of the reaction, the product can be taken out by a usual organic method.
  • the inert solvent used for producing the compound represented by the general formula [4] by reacting the compound represented by the general formula [2] with the thiolate salt of the compound represented by the general formula [3] includes: , Dioxane, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, acetoetrile, benzene, toluene, hexanemethylphosphoramide, and a mixed solvent thereof.
  • the thiolate salt must be used in an amount sufficient for the reaction to proceed sufficiently, and can be used in a large excess. However, it is usually carried out using 1 to 2 equivalents to the compound represented by the general formula [2]. it can.
  • the reaction is carried out at a temperature in the range of 78 ° C to + 60 ° C, preferably in the range of 140 ° C to + 40 ° C. After the completion of the reaction, the product can be taken out by a usual organic chemical technique.
  • the thiolate salt can be produced by using a mercaptan compound represented by the general formula [3] and a base.
  • a base examples include inorganic bases such as sodium hydride and potassium hydride, metal alkoxides such as potassium tert-butoxide and sodium methoxide, and metal amides such as sodium amide, lithium diisopropylamide and lithium disilazide.
  • inorganic bases such as sodium hydride and potassium hydride
  • metal alkoxides such as potassium tert-butoxide and sodium methoxide
  • metal amides such as sodium amide, lithium diisopropylamide and lithium disilazide.
  • the method for removing these groups is a method known per se by treating with an acid, a base, a reducing agent, and the like.
  • the acid is preferably trifluoroacetic acid, formic acid, boron trifluoride, aluminum chloride, or a mixture thereof. Things can be mentioned.
  • Preferred examples of the base include alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal sulfides such as sodium sulfide and potassium sulfide, and tetrabutylammonium fluoride.
  • the reduction method preferably includes hydrogenolysis with zinc and acetic acid, hydrogen and palladium-carbon or platinum and the like. Further, a method using zero-valent palladium can also be used.
  • the solvent used is not particularly limited as long as it does not adversely affect the reaction, but water, alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and dioxane, fatty acids such as acetic acid, and the like. Can be used.
  • the reaction temperature can be suppressed or promoted by appropriately cooling or heating, and the preferred temperature is from 130 ° C to 140 ° C.
  • the product can be removed by ordinary organic chemistry techniques.For example, the reaction mixture is adjusted to near neutrality, and then subjected to column chromatography using an adsorption resin or the like to obtain the target compound.
  • the reaction product can be obtained by fractionating the eluted portion and freeze-drying.
  • the compound represented by the general formula [2] is known and can be produced, for example, by the method described in JP-B-63-55514.
  • the mercaptan compound represented by the general formula [3] can be prepared by various known methods, for example, K. Hofmann, Heterocyclic Chemistry vol. 6 (1953), JV Metzger,
  • the carbon atom at position 4 has an R configuration and the carbon atom at position 5 has an S configuration, or (4R, 5S, 6S) configuration, or (4R, 5 S, 6 R) -coordinated compounds.
  • R 1 is 1-hydroxyethyl
  • R-coordination isomers As shown in the above, there are also R-coordination isomers and S-coordination isomers at the 8-position, and R coordination can be mentioned as a preferable one.
  • the isomer in the case of producing an isomer having such a coordination, the isomer can be produced using each of the corresponding isomers in the starting compound represented by the general formula [2].
  • the compounds of the present invention represented by the above general formula [1] are a novel group of] 3-lactam compounds having an azole thio group having various substituents at the 3-position of the carbane skeleton, and these compounds are excellent. It has antibacterial activity and is useful as a pharmaceutical.
  • Specific examples of the compound having the general formula [1] obtained by the present invention include, for example, the compounds shown in Table 1 below.
  • the compounds exemplified in Table 1 have stereoisomers as described above, and the exemplified compounds include all isomers.
  • the novel ratatam compounds represented by the general formula [1] of the present invention include gram proteins such as Staphylococcus' aureus, Staphylococcus' epidenoremidis, Streptococcus' pyogenes, Streptococcus sp.
  • Some bacteria have antibacterial activity against a wide range of pathogenic bacteria including gram-negative bacteria such as live bacteria, Escherichia coli, Proteus bacteria, Klebsiella '2 humor, Hemophilus' influenza, gonococci, and Blanchamella, but dram-positive bacteria It is characterized by its excellent antibacterial activity against MRSA and also has excellent antibacterial activity against MRSA and MRCNS.
  • DHP-I Dehydrobeptidase-I
  • a renal enzyme is known to readily degrade naturally occurring carbamine compounds, but it is a compound of the general formula [1]
  • Some of the compounds of formula (I) are stable against DHP-I and can be used as a single agent, but if necessary, they can be used in combination with DHP-IP and harmful agents.
  • the dosage form for using the compound of the present invention as an antibacterial agent for treating bacterial infections includes, for example, oral administration using tablets, capsules, powders, syrups, etc., or intravenous injection, intramuscular injection, rectal administration and the like. Parenteral administration is included.
  • suitable dosage forms can be prepared by incorporating the active compound into acceptable carriers, excipients, binders, stabilizers and the like.
  • acceptable buffers, dissolution aids, isotonic agents and the like can also be added.
  • the dosage varies depending on symptoms, age, body weight, dosage form, number of administrations, etc., but usually 100 to 300 Omg / day is divided into one or several doses for adults. The dose can be reduced or increased as needed.
  • TMS Trimethinoresilinole group
  • the aqueous layer is extracted with ethyl acetate, and the organic layer is washed with saturated saline, dried over magnesium sulfate, and concentrated by an evaporator to obtain the desired 4- (bromoacetyl) benzonitrile (1.87 g, 97%). .
  • the reaction mixture is diluted with 6 ml of 2% sodium bicarbonate solution, purified by chromatography on MC I gel using acetonitrile with a water content of up to 50% and, after lyophilization, 0.048 g of sodium ( 4R, 5S, 6S) -3- (4- ⁇ 4- [Amino- (5-methyl_2-oxo-1- [1,3] dioxol-4-ylmethoxycarburimino) -methyl] -phenyl ⁇ -Thiazole-2-ylsulferyl) -6-[(R) -1-hydroxy-ethyl) -4-methyl-7-oxo-1-aza-bisic [3.2.0] hept-2-ene-
  • the 2-carboxylate is obtained as a yellow powder.
  • reaction mixture was diluted with 3 ml of 2% sodium bicarbonate, purified by chromatography on MCI-gel (CHP-20) using acetonitrile with a water content of up to 50%, and lyophilized to 0.1%.
  • Hept-2-ene-2-carboxylate is a yellow powder Get as.
  • the compounds of the present invention exhibit excellent antibacterial activity against Gram-positive bacteria, particularly MDSA and MRCNS, and are useful as antibacterial agents.

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Abstract

L'invention concerne de nouveaux composés de β-lactame représentés par la formule générale (1), dans laquelle R1 représente alkyle inférieur ou alkyle inférieur substitué par hydroxyle ; R2 représente hydrogène, hydroxyle, alkyle inférieur éventuellement substitué ou des composés analogues ; R4 représente R5 représentent chacun hydrogène, hydroxyle, un groupe amino-protecteur, alkyle inférieur éventuellement substitué ou des composés analogues ; A représente phénylène éventuellement substitué ; et X vaut 0, S ou NH. Ces composés présentent une remarquable activité antibactérienne contre des bactéries Gram-positives, notamment des staphylocoques résistants à la méthicilline et des staphylocoques coagulase-négatifs résistants à la méthicilline.
PCT/JP2001/010826 2000-12-12 2001-12-11 Nouveaux composes de ?-lactame et procede de preparation associe WO2002048149A1 (fr)

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JP2002549680A JPWO2002048149A1 (ja) 2000-12-12 2001-12-11 新規なβ−ラクタム化合物及びその製造法
AU2002221114A AU2002221114A1 (en) 2000-12-12 2001-12-11 Novel ss-lactam compounds and process for preparing the same

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JP2000-377192 2000-12-12
JP2000377192 2000-12-12

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100473398B1 (ko) * 2002-08-31 2005-03-10 주식회사 하원제약 옥심기를 포함하는 피롤리딘 치환체를 가지는1-베타메틸카바페넴 유도체 및 그 제조방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996004282A1 (fr) * 1994-07-29 1996-02-15 Merck & Co., Inc. Composes de carbapenems, compositions et procedes de traitement

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996004282A1 (fr) * 1994-07-29 1996-02-15 Merck & Co., Inc. Composes de carbapenems, compositions et procedes de traitement

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100473398B1 (ko) * 2002-08-31 2005-03-10 주식회사 하원제약 옥심기를 포함하는 피롤리딘 치환체를 가지는1-베타메틸카바페넴 유도체 및 그 제조방법

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