Yamanouchi Pharmaceutical Company Ltd.

Noriaki Nagano

Tadao Shibanuma

Atsuki Yamazaki

Tetsuya Maeda

Yukiyasu Murakami

Masaru Iwanami

Yoshinobu Nagano

Masaharu Fujimoto

Kohji Nakano

Ryuichiro Hara

Akio Koda

Kiyoshi Murase

Kazaharu Tamazawa

Masuo Murakami

Masaki Yokota

Toru Yoden

Masato Satoh

Tokuo Koide

Toshio Okazaki

Hideki Anan

Ei-ichi Nakai

Katsuhiko Hamaguchi

Masato Sato

Masauki Komiya

A cephalosporin compound represented by the general formula: ##STR1## This compound exhibits a high antimicrobial activity.

Cephalosporin derivatives

A 7-[2-(2-amino-4-thiazolyl)-2-(hydroxyimino)-acetamido]-3-(1,3-dithiolan-2- yl)-3-cephem-4-carboxylic acid derivative is provided which can be represented by the general formula: ##STR1## wherein A represents a hydrogen atom, a 1-acetoxyethyl group, a 1-cyclohexylacetoxyethyl group or a pivaloyloxy-methyl group.

Various 7-amino-3-substituted-methyl-3-cephem-4-carboxylic acids and lower alkylsily derivatives such as 7-amino-3-(2,3-cyclopenteno-1-pyridiniomethyl)-3-cephem-4 -carboxylic acid iodide and trimethylsilyl 7-trimethylsilylamino-3 -(5,6,7,8-tetrahydro-2-isoquinoliniomethyl)-3-cephem-4 -carboxylate iodide are valuable intermediates in the preparation of new and novel antibacterial agents. A new process for the preparation of these acids and the derivatives has been devised.

Amino-3-substituted-methyl-3-cephem-4-carboxylic acid and lower

Various 7-amino-3-substituted-methyl-3-cephem-4-carboxylic acids and lower alkylsilyl derivatives such as 7-amino-3-(2,3-cyclopenteno-1-pyridiniomethyl)-3-cephem-4-carboxylic acid iodide and trimethylsilyl 7-trimethyl-silylamino-3-(5,6,7,8-tetrahydro-2-isoquinoliniomethyl)-3-ceph em-4-carboxylate iodide are valuable intermediates in the preparation of new and novel antibacterial agents. A new process for the preparation of these acids and the derivatives has been devised.

Process for preparing 3-substituted-methyl-3-cephem derivatives

Novel cephalosporin compounds of the formula ##STR1## wherein the wavy line means syn-form and anti-form bonds, R.sup.1 represents a cyanomethyl group, a thiocarbamoylmethyl group or an aminothiazolylmethyl group, and A represents a unsubstituted or substituted pyridinio group; and salts thereof. These compounds have excellent antibacterial activities.

Cephalosporin compounds and salts thereof

Novel cephem compounds are provided having the formula: ##STR1## wherein R represents lower alkyl, which may be substituted with lower acyloxy, lower alkylthio or certain 5 or 6-membered heterocyclic ring-containing groups. The cephem compounds and salts thereof exhibit antibacterial activity to many pathogens. A process for producing the cephem compounds is also provided.

Cephem compounds

Cephalosporin compounds represented by the general formula ##STR1## wherein R represents a group shown by formula ##STR2## wherein R.sup.1 represents a hydrogen atom or a lower alkyl group of 1-3 carbon atoms and R.sup.2 represents a hydrogen atom, a lower alkyl group of 1-3 carbon atoms, a phenyl group which may be substituted by an amino or hydroxy group, a cyano group, a carboxy group, or a carboxymethyl group; said R.sup.1 and R.sup.2 may form a cycloalkylidene group of 4-6 carbon atoms together with the carbon atom to which they are bonded) or a group shown by formula --CH.sub.2 --R.sup.3 (wherein R.sup.3 represents a hydrogen atom, a halogenomethyl group, a carbamoyl group, a carboxymethyl group, .alpha.4-carboxy-3-hydroxyisothiazol-5-yl-thiomethyl group, or .alpha.2-carboxyphenylthiomethyl group); R' represents a group shown by formula ##STR3## (wherein R.sub.a represents a carboxy group, a cyano group, or a carbamoyl group which may be substituted by a lower alkyl group of 1-3 carbon atoms and R.sub.b represents a hydrogen atom or an amino group) or a group shown by formula ##STR4## (wherein R.sub.a and R.sub.b have the same significance as above); and the waveline .about. shows an anti-form or syn-form bond and the salts thereof. They possess excellent antibacterial activities against gram positive bacteria and gram negative bacteria, in particular, pseudomonas aeruginosa and are useful as anti-bacterial agents.

Cephalosporin compounds

Substituted 1,3-dithietane-2-carboxylic acid derivatives useful as intermediates for the preparation of highly effective penicillin and cephalosporin derivatives and the preparation thereof.

1,3-Dithietane-2-carboxylic acid penicillin and cephalosporin derivatives

The invention relates to novel 7.alpha.-methoxycephalosporin derivatives having at the 7.beta.-position an amido group acylated by a 1,3-dithietane carboxylic acid residue and to 7.beta.-isothiazolylthioacetamido-7.alpha.-methoxycephalosporins having antibacterial activity by themselves and, as the case may be, capable of being converted into the aforesaid 7.alpha.-methoxycephalosporin derivatives. The compounds of this invention exhibit excellent antibacterial activity and are particularly effective against gram negative bacteria.

Process for the preparation of

The invention relates to novel 7.alpha.-methoxycephalosporin derivatives having at the 7.beta.-position an amido group acylated by a 1,3-dithietane carboxylic acid residue and to 7.beta.-isothiazolylthioacetamido-7.alpha.-methoxycephalosporins having antibacterial activity by themselves and, as the case may be, capable of being converted into the aforesaid 7.alpha.-methoxycaphalosporin derivatives. The compounds of this invention exhibit excellent antibacterial activity and are particularly effective against gram negative bacteria.

7.alpha.-Methoxy-7.beta.-(1,3-dithietane-2-carboxamido)cephalosporanic

1,3-Dithietane-2-carboxylic acids and the preparation thereof

Novel 7.alpha.-methoxy-7.beta.-heterocyclic thioacetamido-3-heterocyclic thiomethyl-.DELTA..sup.3 -cephem-4-carboxylic acid derivatives and pharmaceutically acceptable salts thereof. These compounds show high antibiotic activities against various microorganisms including gram positive and negative bacteria.

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Saitama, Japan

Noriaki Nagano