Yamanouchi Pharmaceutical Company Ltd.

Kohji Nakano

Noriaki Nagano

Tadao Shibanuma

Yukiyasu Murakami

Ryuichiro Hara

Atsuki Yamazaki

Akio Koda

Takashi Fujikura

Masayuki Shibasaki

Masato Ichihara

Yukiko Fukunaga

Novel compounds of the following formula (I) and their salts: A compound of the formula (I) ##STR1## These compounds are expected to be useful for renin inhibitors. Thus, the compounds are useful medical agents, in particular, anti-hypertensive agents.

Histidine derivatives as superior renin inhibitors

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.

Growing community of inventors

Saitama, Japan

Kohji Nakano