Takeda Chemical Industries, Inc.

Michiyuki Sendai

Mitsuru Shiraishi

Susumu Tsushima

Shoji Kishimoto

Tetsuo Miwa

Norichika Matsumoto

Michihiko Ochiai

Kiminori Tomimatsu

Kenji Okonogi

Kenzo Naito

Masayasu Kato

Shoichiro Fujii

A polycyclic carbapenem compound of the formula (Ia'), (Ib') or (Ic') ##STR1## [wherein COOR.sup.2 is a carboxy group which may be esterified; R.sup.a' is --(CH.sub.2).sub.m --K.sup.a --(CH.sub.2).sub.n --U.sup.a' ; J is O or S; R.sup.b' is --(CH.sub.2).sub.m --K.sup.b --(CH.sub.2).sub.n U.sup.b' ; J' is O, S or CH.sub.2 ; R.sup.c' is --(CH.sub.2).sub.m --K.sup.c --(CH.sub.2).sub.n --U.sup.c', --(CH.sub.2).sub.m --K.sup.d --(CH.sub.2).sub.n --U.sup.d or a pair of groups, one of which is a hydroxy group, with the other being a hydroxzy group or an alkylsulfonylamino group, which may be substituted, in the position ortho to the first-mentioned hydroxy group] or a salt thereof are useful as an antibacterial agent.

Tricyclic or tetracyclic carbapenem compounds, their production and use

Novel cephem compounds having, at the 3-position of the cephem nucleus, a group of the formula:

Cephem compounds compositions and method

A compound of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or a hydrocarbon group which may be substituted; COOR.sup.2 represents a carboxy group which may be esterified; and ring B is a cyclic group which may be substituted or a pharmaceutically acceptable salt thereof are useful as an antibacterial agent.

Tricyclic carbapenem compounds

An antibacterial agent is provided which is a cephem compound of the formula: ##STR1## wherein R.sup.1 is an acyl group; R.sup.2 is a carboxy group which may be esterified; R.sup.3 is a hydrogen atom, a lower alkyl group or cyano group; R.sup.4 is a hydrogen atom or a lower alkyl group, or R.sup.4 together with R.sup.3 is a methylene chain having 2 or 3 carbon atoms; R.sup.5 is a hydrogen atom or a lower alkyl group; A is an optionally substituted bivalent aromatic heterocyclic group which is bonded to a ring-constituting carbon atom with the adjacent sulfur atom; Y is a binding arm, sulfur or oxygen atom, --NH--, --CONH-- or --NHCO--; Z is a binding bond or --NH--; m is an integer of 0 to 4 and n is an integer of 0 to 6, or a pharmacologically acceptable salt thereof.

Cephem compounds, and use

Cephem compounds of the formula: ##STR1## wherein Q stands for a nitrogen atom or CH, R.sup.1 stands for a hydrogen atom or an optionally substituted lower alkyl group, R.sup.2 stands for a hydrogen atom or a lower alkyl group, A stands for a sulfur atom or NH, and n denotes an integral number ranging from 2 to 4, or salts thereof, and processes for producing them. The compounds (I) or salts thereof show not only excellent antibacterial activities against a wide range of pathogenic bacteria from gram-positive to gram-negative ones, including a variety of strains isolated clinically but also hydrophilic properties, and therefore they are excellent antibiotic substances having desirable water-solubility when used as injections.

Cephem compounds

A 2-azetidinone derivative having a group of the formula ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom, alkyl, aryl or arylalkyl which may have a substituent at the 1-position and an amino group, at the 3-position, which may be acylated or protected, its salt or ester, and methods of producing the same, (1) a method comprising subjecting a 2-azetidinone derivative having a group of the formula ##STR2## wherein the symbols are as defined above at the 1-position and an amino group at the 3-position, its salt or ester to an acylation or protective-group introduction reaction, and (2) a method comprising reacting a 2-azetidinone derivative having a hydroxy group at the 1-position and an amino group, at the 3-position, which may be acylated or protected, or its salt with a compound of the formula ##STR3## wherein W is a halogen atom; other symbols are as defined above, its salt or ester. The above objective compounds are utilizable as excellent antimicrobial agents or as valuable intermediates for the synthesis of the same.

1-carboxymethoxy acetidinones and their production

Novel 3-acyloxymethyl-cephem compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen or an acyl group; W is acetonyl, or a group represented by --X--COOH or --X--OH (X is an organic residue) or salts thereof were found to be useful as starting materials for preparing cephalosporins of the formula: ##STR2## wherein R.sup.3 stands for a residue nucleophilic compound and R.sup.1 has the same meaning as above.

Process for preparing cephalosporins

Novel 3-acyloxymethyl-cephem compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen or an acyl group; W is acetonyl, or a group represented by --X--COOH or --X--OH (X is an organic residue) or salts thereof were found to be useful as starting materials for preparing cephalosporins of the formula: ##STR2## wherein R.sup.3 stands for a residue of a nucleophilic compound and R.sup.1 has the same meaning as above.

Novel 3-acyloxymethyl-cephem compounds useful as intermediates for

Novel 3-acyloxymethyl-cephem compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen or an acyl group; X is a divalent group consisting of a carbon chain having 2 to 3 carbon atoms and a carbonyl or sulfonyl group at one terminal end thereof, said divalent group being either substituted or unsubstituted on the carbon chain; and Z is an organic acid residue, and salts thereof were found to be useful as starting materials for preparing cephalosporins of the formula: ##STR2## wherein R.sup.2 stands for a residue of a nucleophilic compound and R.sup.1 has the same meaning as above.

Derivatives of 7-aminocephalosporanic acid

3-Acyloxymethyl-cephem compounds

Penicillin-1-oxides are rearranged into the corresponding 3-desacetosycephalosporin derivatives in an inert organic solvent in the concomitant presence of an acid catalyst and an organic sulfide in a good yield and with a high purity.

Growing community of inventors

Osaka, Japan

Michiyuki Sendai