Abstract: Clavulanic acid, in which the median of the particles is from 8 &mgr;m to 35 &mgr;m and their use in pharmaceutical compositions.

Abstract: 1-Methylcarbapenem compounds having antibacterial activity, pharmacologically acceptable esters or salts thereof and pharmaceutical compositions (particularly antibacterial agents) containing them as an active ingredient are described. In addition, the invention includes the use of these compounds, ester derivatives or salts for the manufacture of pharmaceutical compositions, or a method for the prevention or treatment of diseases (particularly bacterial infections) by administering a pharmacologically effective amount of the compounds, ester derivatives or salts to warm-blooded animals (particularly human beings).

Abstract: This invention provides crystalline forms of a 1-methylcarbapenem derivative of formula (I) or of pharmaceutically acceptable salts thereof.

Abstract: A process for the preparation of a carbapenem antibacterial compound of the following formula (4) having a 1-alkylpyrrolidine structure or a salt thereof, a useful synthetic intermediate of the following formula (1) or a salt thereof, and a process for the preparation thereof: 1

Abstract: The invention is a process improvement for producing the carbapenem antibacterial agent (4R, 5S, 6S)-3-[[2R,3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid by hydrogenation of 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{[2R,3R)-2-({[(2S)-3-methyl-2-({[4-nitrobenzyl)oxy]carbonyl}amino)butanoyl]amino}methyl)-tetrahydrofuran-3-yl]thio}-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in a biphasic solvent mixture comprising a water portion and an organic solvent portion, not containing an acid acceptor.

Abstract: A production process which comprises subjecting a basic antibiotic.oxalate (II) to salt-exchange with an alkali earth metal salt (III) of an inorganic acid: wherein the ring A means the basic antibiotic; R10 means a protected functional group used in organic synthesis; Ak—E means the alkali earth metal; and B means the inorganic acid, respectively.

Abstract: This invention provides crystalline forms of a 1-methylcarbapenem derivative of formula (I) or of pharmaceutically acceptable salts thereof.

Abstract: The present invention relates to carbapenems and provides a compound of the formula (I): 1

Abstract: Novel &bgr;-lactam compound of the formula [1]: wherein R1 is lower alkyl or hydroxy-substituted lower alkyl, R2 is H or lower alkyl, X is O or, S, R3 is H, metal or protecting group, W is a 6- or 7-membered nitrogen-containing heterocycle optionally being substituted at carbon atoms. Said &bgr;-lactam compound shows excellent antibacterial activity against Gram-positive bacteria, particularly against methicillin-resistant Staphylococcus aureus and methicillin-resistant and coagulase-negative Staphylococcus aureus.

Abstract: Provided herein are novel imidazo[1,2-a]pyrazines of Formula I: wherein: X is CHR5, NR5, O, S, S(O)n or a single bond, wherein n is equal to 0, 1 or 2; D is aryl or heteroaryl attached through an unsaturated carbon atom and wherein said aryl or heteroaryl is optionally substituted at any available position with from 1-5 of A1, A2, A3, A4 and A5; R2 is C1-4 alkyl or C3-8 cycloalkyl, each of which is optionally substituted with from 1-3 hydroxy, halogen or C1-4 alkoxy, or wherein when X is a bond, R2 is optionally also CN, CF3, C2F5, C1-4 alkyl or C3-8 cycloalkyl, each of which C1-4 alkyl or C3-8 cycloalkyl is optionally substituted with from 1-3 hydroxy, halogen and C1-4 alkoxy; as well as compositions containing the same, useful in the treatment of, for example, neurological and psychological disorders characterized by corticotropin releasing factor (CRF) overexpression.

Abstract: A novel process for preparing a stabilized, lyophilized carbapenem, antibiotic formulation suitable for intravenous administration to patients in need thereof, wherein the active ingredient is of formula II: The process entails compounding a unstable, monosodium salt carbapenem with a sodium bicarbonate solution at a temperature range of from about 0° to about 5° C. while maintaining a pH between about 7.0 and about 8.0, filtering the resultant solution, bottling under sterile conditions, and lyophilizing to produce the formulation.

Abstract: A process for producing 1H-3-aminopyrrolidine and derivatives thereof is disclosed.

Abstract: Use of the 2-amino-2,4,4-trimethylpentane salt of clavulanic acid as an intermediate in the production of pharmaceutically acceptable salts of clavulanic acid.

Abstract: A process for the direct crystallization of a compound of the formula I: or a pharmaceutically acceptable salt thereof, is disclosed, wherein R1 and R2 represent H, C1-10 alkyl, aryl or heteroaryl, or substituted C1-10 alkyl, aryl or heteroaryl and X+ represents a charge balancing group, comprising extracting a solution containing a crude compound of formula I or Ia: or a pharmaceutically acceptable salt thereof, wherein each X+ is a charge balancing group, and R1 and R2 are as described above with a C4-10 alcohol, collecting and crystallizing the resulting aqueous phase to produce a crystalline compound of formula I.

Abstract: The present invention involves a process for preparing a stable final formulation product of a compound of formula I, or its pharmaceutically acceptable salt, hydrate or solvate by incorporating a suitable carbon dioxide source to an unstable monosodium adduct of carbapenem antibiotic compound.

Abstract: The compounds of the general formula I wherein R1 denotes hydrogen, hydroxymethyl or 1-hydroxyethyl, R2 denotes hydrogen or methyl and R3 denotes a pharmaceutically acceptable group which is bonded to the remaining part of the molecule by an oxygen-carbon single bond or a nitrogen-carbon single bond, and their pharmaceutically acceptable salts, esters and amide derivatives are broad spectrum antibiotics and &bgr;-lactamase inhibitors.

Abstract: It is provided carbapenem compounds represented by the following formula (I): wherein R is hydrogen atom, or substituted or unsubstituted lower alkyl group; and, n is an integer of 1 or 2, or a pharmaceutically acceptable salt thereof, and an antibacterial compositions containing these compounds as an active ingredient. These carbapenem compounds exhibit potent antibacterial activities and are excellent in the resistance against renal dehydropeptidase.

Abstract: A compound of formula (I): 1

Abstract: This invention provides crystalline forms of a 1-methylcarbapenem derivative of formula (I) or of pharmaceutically acceptable salts thereof.

Abstract: Dextrorotatory isomer of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine, its preparation and pharmaceutical compositions containing it which are usable as tranquillizers and hypnotics.

Abstract: The present invention relates to carbapenem derivatives of Formula I, wherein X is carbonyl or sulfonyl, and a preparation method thereof. The carbapenem derivatives of the invention have excellent antibacterial properties and are thus useful as antibiotics.

Abstract: An imipenem production process by which a compound of formula 1

Abstract: A carbapenem compound of the formula (I) wherein R1 is a group hydrolyzable in the living body, R2 and R3 are the same or different and each is a lower alkyl, R is a group of the formula (B) or (C) wherein R4 and R5 are the same or different and each is a hydrogen atom or a lower alkyl and R6 is an alkyl having 1 to 10 carbon atoms. The carbapenem compound (I) of the present invention is superior in absorption from the digestive tract upon oral administration and shows sufficient antibacterial property against a broad range of bacteria species. Therefore, the compound is extremely useful for the prophylaxis and treatment of infectious diseases (particularly bacterial infection).

Abstract: Use of the 2-amino-2,4,4-trimethylpentane salt of clavulanic acid as an intermediate in the production of pharmaceutically acceptable salts of clavulanic acid.

Abstract: A carbapenem compound of the formula (I) wherein R1 is a group hydrolyzable in the body, R2 is selected from the group consisting of aryl groups optionally substituted by 1-3 alkyl groups having 1-4 carbon atoms, 1-alkanoyloxyalkyl, 1-alkoxycarbonyloxyalkyl, phthalidyl and 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl, R3 and R4 are lower alkyl groups which may be the same or different or instead form a 4- to 6-membered cyclic amino with the adjacent nitrogen selected from the group consisting of azetidinyl, pyrrolidinyl and piperidinyl or a pharmaceutically acceptable salt thereof The carbapenem compound (I) and a pharmaceutically acceptable salt thereof of the present invention show superior absorption from digestive tract by oral administration, and sufficient antibacterial activity against a wide variety of bacterial species. Thus, they are extremely useful as agents for the prophylaxis and treatment of infectious diseases, particularly bacterial infectious diseases.

Abstract: The present invention involves a process for preparing a stable final formulation product of a compound of formula I, 1

Abstract: The compounds of the general formula I 1

Abstract: The present invention relates to a novel stabilized form of carbapenem antibiotics of formula II: compositions and methods thereof wherein the antibiotics and compositions are stabilized degradation and dimer formation. The compounds can be used in the treatment of infectious diseases, including gram positive and negative, aerobic and anaerobic bacteria. The compounds provide good stability against beta-lactamases, and a favorable duration of action. The compounds of this invention are represented structural formula I: or a pharmaceutically acceptable or hydrate thereof.

Abstract: A &bgr;-lactam compound of the formula: wherein R1 is lower alkyl or OH-substituted lower alkyl, R2 is H or lower alkyl, X is O, S or NH, n is 1 to 3, R3 is —C(Ra)═NH (Ra is H, lower alkyl or substituted lower alkyl), or a salt thereof, or an ester thereof. These compounds show excellent antibacterial activity against Gram-positive bacteria, particularly against methicillin-resistant Staphylococci and methicillin-resistant and coagulase-negative Staphylococci.

Abstract: A process for the isolation of clavulanic acid and pharmaceutically acceptable salts thereof, such as potassium clavulanate, from the aqueous fermentation broth of a clavulanic acid-producing microorganism comprises the microfiltration of the broth without prior treatment.

Abstract: A compound represented by the general formula wherein R1 either represents a hydrogen atom or a lower alkyl group, R2 represents a hydrogen atom, an ester residue, an alkali metal or negative charge, and R3 and R4 are the same or different, and each represent a hydrogen atom or a hydrocarbonic group optionally containing hetero atom(s) selected from the group consisting of oxygen atom(s), sulfur atom(s) and nitrogen atom(s), or they are combined together with the nitrogen atom to which they bound to form a heterocyclic group, and the use thereof as an antibacterial agent.

Abstract: Provided is a process for purification of clavulanic acid or a pharmaceutically acceptable salt or ester thereof, including adding an additional solvent to a solution of clavulanic acid in water immiscible solvent; contacting the solution with an amine; isolating the amine salt of the clavulanic acid formed; and converting the amine into clavulanic acid or a pharmaceutically acceptable salt or ester thereof.

Abstract: A stabilized carbapenem intermediate compound represented by the formula 1: or a salt thereof is disclosed, wherein P represents a carboxyl protecting group and X represents a charge balancing group. In addition, a process for synthesizing a compound represented by formula 2: is disclosed wherein X+ is a charge balancing group, comprising: deprotecting a compound of the formula 1 to produce a compound 2.

Abstract: Compounds of formula (I) and compounds of formula (II) which have potent antimicrobial activity against a wide range of bacteria including Gram-positive bacteria and Gram-negative bacteria as well as heve potent antimicrobial activity against various &bgr;-lactamase-producing bacteria, MRSA, and resistant Pseudomonas aeruginosa and are very stable against DHP-1.

Abstract: A cephem compound of the formula: wherein R1 stands for an optionally substituted lower alkyl group, R2 stands for H or a lower alkyl group, R3 stands for H, an optionally substituted hydrocarbon group, cyano group, a lower alkyloxy group or a lower alkylthio group, and the ring A stands for an optionally substituted non-quaternarized nitrogen-containing heterocyclic ring, provided that, when A is unsubstituted 2-pyridyl group, R3 stands for a group other than hydrogen, or their esters or salts, has excellent antibacterial activities, oral absorbability and stability, and is useful as an antibacterial agent.

Abstract: The present invention provides a crystal of (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-2-[(3S,5S)-5-sulfamoylaminomethyl-1-pyr rolidin-3-yl]thio-1-methyl-1-carba-2-penem-3-carboxylic acid represented by the following formula, a lyophilized preparation comprising the crystal, and a process for producing the same. The production process comprises the steps of freezing an aqueous solution containing the above-mentioned compound by cooling to -20.degree. C. or lower; warming the frozen solution to 0 to -10.degree. C.; and cooling and warming the frozen solution at least twice in a temperature range of 0 to -10.degree. C.

Abstract: A 1-methylcarbapenem compound represented by the following formula (I): ##STR1## wherein R.sup.1 represents hydrogen or C.sub.1 -C.sub.4 alkyl; R.sup.2 represents hydrogen or an ester residue; and A represents a group of the formula (A1) ##STR2## wherein n is 0, 1 or 2, P is 0, 1 or 2, R.sup.3 is hydrogen or C.sub.1 -C.sub.4 alkyl and R.sup.4 is a group (Q2) ##STR3## wherein B is phenylene, phenylene(C.sub.1 -C.sub.3)alkyl, cyclohexylene, cyclohexylene(C.sub.1 -C.sub.3)alkyl or C.sub.1 -C.sub.5 alkylene, R.sup.7 is hydrogen or C.sub.1 -C.sub.4 alkyl, and R.sup.14 is a group --C(.dbd.NH)R.sup.8, wherein R.sup.8 is hydrogen or C.sub.1 -C.sub.4 alkyl or a group --NR.sup.9 R.sup.10, wherein R.sup.9 and R.sup.10 are the same or different and are hydrogen or C.sub.1 -C.sub.4 alkyl; or a pharmacologically acceptable salt thereof.

Abstract: A carbapenem derivative represented by the following formula (I), ##STR1## wherein R.sub.1 represents a hydrogen atom, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, R.sub.2 indicates a hydrogen atom or a protective group for a carboxyl group, and R.sub.3 is a methyl group or an ethyl group; or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising this carbapenem derivative or a salt thereof as an active ingredient. The carbapenem derivative exhibits a wide and strong antimicrobial activity, particularly a strong antimicrobial activity against MRSA. An intermediate compound for preparing the carbapenem derivative is also disclosed.

Abstract: Compounds having potent antimicrobial effects over Gram-positive bacteria and Gram-negative bacteria, a high stability to .beta.-lactamases and DHP-I and a high safety for the human body and a process for producing the same. Carbapenem compounds represented by the following general formula (I) or salts thereof: ##STR1## wherein the ring A represents a 3- to 7-membered non-aromatic ring containing at least one nitrogen atom and optionally having a substituent other than R.sup.6 ; R.sup.1 represents hydrogen or methyl; R.sup.2 and R.sup.5 are the same or different and each represents hydrogen or a protecting group of the hydroxyl group; R.sup.3 represents hydrogen or a protecting group of the carboxyl group; R.sup.4 represents hydrogen, lower alkyl or a protecting group of the amino group; R.sup.6 represents: (1) hydrogen, (2) lower alkyl, optionally substituted by an optionally protected hydroxy, carbamoyl, formimidoyl, acetimidoyl or ##STR2## wherein R.sup.7 and R.sup.

Abstract: A method of preparing intermediates for carbapenem antibiotics characterized by treating a N-deprotected acetoxy conpound of the formula: ##STR1## in the presence of a Lewis acid or a silylating agent to yeild an intermediate; and cyclizing the intermediate in the presence of rhodium (II) acetate to form a bicyclic ketoester.

Abstract: A 1-methylcarbapenem compound represented by the following formula: ##STR1## [wherein R.sup.1 represents a hydrogen atom or a lower alkyl group, R.sup.2 represents a hydrogen atom or a lower alkyl group, R.sup.3 represents a hydrogen atom, a lower alkyl group, a lower alkyl group which has a substituent, a cycloalkyl group or a group of formula --C(.dbd.NH)R.sup.4 (in which R.sup.4 represents a hydrogen atom, a lower alkyl group or an amino group)]; or a pharmacologically acceptable salt or derivative thereof. The 1-methylcarbapenem compounds of the present invention exhibit excellent antibacterial activity and are therefore effective as a preventive or remedy of infections.

Abstract: A pharmaceutical composition is disclosed which contains a compound of formula I: ##STR1## or a pharmaceutically acceptable salt, prodrug or hydrate thereof, in the stabilized form and/or in combination with a carbon dioxide source.

Abstract: Disclosed are carbapenem-3-carboxylic acid ester derivatives of formula (I), wherein R.sup.1 is a hydrogen atom or a lower alkyl group, R.sup.2 is an alkyl group which may be substituted by a cycloalkyl group having about 4 to 7 carbon atoms and which may be substituted by a lower alkyl group, or is a cycloalkyl group having 4 to 7 carbon atoms which may be substituted by a lower alkyl group and n is 0 or 1. The compounds are highly absorbable through the digestive tract and are rapidly converted in the body to the active compound, which shows strong antibacterial activity.

Abstract: A process for synthesizing a compound of the formula I: ##STR1## or a pharmaceutically acceptable salt or ester thereof, wherein each P independently represents H or a protecting group, and R.sup.1 and R.sup.2 independently represent H, C.sub.1-10 alkyl, aryl or heteroaryl, or substituted C.sub.1-10 alkyl, aryl or heteroaryl, comprising:reacting the compounds: ##STR2## or a pharmaceutically acceptable salt or ester thereof, and ##STR3## or a pharmaceutically acceptable salt or ester thereof, wherein X represents OP(O)(OR).sub.2, or OSO.sub.2 R, wherein R represents C.sub.1-6 alkyl, aryl or perfluoro C.sub.1-6 alkyl, in the presence of an amine selected from the group consisting of: diisopropylamine (DIPA), dicyclohexylamine (DCHA), 2,2,6,6-tetramethylpiperidine (TMP), 1,1,3,3-tetramethylguanidine (TMG), 1,8-diazabicyclo?4.3.0!undec-7-ene (DBU) and 1,5-diazabicyclo?4.3.0!non-5-ene to produce a compound of formula I.

Abstract: Compound of formula (I): ##STR1## wherein R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl or --C(.dbd.NH)R.sup.0 where R.sup.0 is hydrogen or C.sub.1 -C.sub.6 alkyl;A is ##STR2## R.sup.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl or --C(.dbd.NH)R.sup.6 where R.sup.6 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.7 cycloalkyl; R.sup.3 and R.sup.4 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, hydroxy, carboxy, cyano, --CO.NR.sup.a R.sup.b, --OCO.NR.sup.a R.sup.b or --NR.sup.a R.sup.b, where R.sup.a and R.sup.b are independently hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.20", R.sup.21', and R.sup.22" are independently hydrogen or C.sub.1 -C.sub.6 alkyl or R.sup.20" and R.sup.21" or R.sup.20" and R.sup.22" together form a heterocyclic group; R.sup.23" and R.sup.24" are independently hydrogen, halogen or C.sub.1 -C.sub.6 alkyl; n is 1, 2 or 3; and n.sup.3" is 1, 2 or 3.

Abstract: The present invention relates to carbapenems and provides a compound of the formula (I): ##STR1## or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof wherein:R.sup.1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl;R.sup.2 is hydrogen or C.sub.1-4 alkyl;R.sup.3 is hydrogen or C.sub.1-4 alkyl;R.sup.4 and R.sup.5 are the same or different and are selected from hydrogen, halo, cyano, C.sub.1-4 alkyl, nitro, hydroxy, carboxy, C.sub.1-4 alkoxy, C.sub.1-4 alkoxycarbonyl, aminosulphonyl, C.sub.1-4 alkylaminosulphonyl, di-C.sub.1-4 -alkylaminosulphonyl, carbamoyl, C.sub.1-4 alkylcarbamoyl, di-C.sub.1-4 alkylcarbamoyl, trifluoromethyl, sulphonic acid, amino, C.sub.1-4 alkylamino, di-C.sub.1-4 alkylamino, C.sub.1-4 alkanoylamino, C.sub.1-4 alkanoyl(N--C.sub.1-4 alkyl)amino, C.sub.1-4 alkanesulphonamido and C.sub.1-4 alkylS(O).sub.n -- wherein n is zero, one or two:with the proviso that there is no hydroxy or carboxy substituent in a position ortho to the link to --NR.sup.3 --.

Abstract: Compounds of formula (I): ##STR1## (wherein R.sup.1 represents hydrogen or a hydroxy-protecting group, R.sup.2 and R.sup.3 represent hydrogen, alkyl or aryl; R.sup.4 represents optionally substituted alkyl, alicyclic heterocyclic, aryl, aromatic heterocyclic, optionally substituted alkenyl or optionally substituted alkynyl; R.sup.5 represents hydrogen or a carboxy-protecting group; and R.sup.6 represents alkoxy, aryloxy, dialkylamino or diarylamino or two or R.sup.6 together represent o-phenylenedioxy or three together represent CH.sup.3 C(--CH.sub.2 O--).sub.3) may be prepared by reacting the corresponding carbonyl compound with a compound of formula P(R.sup.6).sub.3. Compounds (I) may be cyclised to prepare carbopenem derivatives, many of which have valuable antibiotic activity.

Abstract: Method of desilylating a silylether compound by reacting a silylether compound of the general formula (I): ##STR1## or a salt thereof with an amine hydrogen fluoride salt or a pyridine hydrogen fluoride salt in an organic solvent to produce a compound of the general formula (IV): ##STR2## According to this method, silylether compounds that are labile under strong acidic or basic conditions can be desilylated efficiently using inexpensive reagents.

Abstract: A novel .beta.-lactam compound of the formula ?1!: ##STR1## or a pharmaceutically acceptable salt thereof, which shows an excellent antibacterial activity against Gram-positive bacteria, especially against methicillin-resistant staphylococci and methicillin-resistant coagulase-negative staphylococci, and a process for producing the same. R.sub.1, R.sub.2, X, Y, Z are as defined in the specifacation.

Abstract: The invention is directed to an improved process for the preparation of spirocyclic lactams which utilizes diiodides in the spiro alkylation of lactams N-substituted with a tertiary amine group. The resultant spirocyclic lactams are useful in the production of various substituted azaspiranes which are useful as immunomodulatory agents.