Toyama Chemical Co., Ltd.

Handi-pac, Inc.

Hideo Taki

Isamu Saikawa

Hiroyuki Imaizumi

Masaru Tai

Shuntaro Takano

Takashi Yasuda

Yutaka Kodama

Isamu Takakura

Hirokazu Ochiai

Takihiro Inaba

Yasuo Watanabe

Hiroshi Sadaki

Yoshinori Konishi

Tatsuo Hirakawa

Hirokazu Narita

Narita Hirokazu

Masuru Tai

Novel cephalosporins which has attached to the exomethylene group at the 3-position of the cephem ring a substituted or unsubstituted aryl, acylamino, aromatic heterocyclic, triazolyl or tetrazolyl group, said aromatic heterocyclic group being attached through a carbon-carbon bond and said triazolyl or tetrazolyl group being attached through a carbon-nitrogen bond, and has the following group attached to the amino group at the 7-position: ##STR1## wherein A represents a group of the formula, --CH.sub.2 -- or a group of the formula ##STR2## in which R.sup.5 represents a hydrogen atom or an alkyl group, and the bond.about.represents syn or anti isomer or their mixture; R.sup.3 represents a hydrogen or halogen atom; and R.sup.4 represents a hydrogen atom or an amino group which may be protected or substituted. These cephalosporins have a broad antibacterial spectrum, are stable against .beta.-lactamase produced by bacteria, have a low toxicity, and are well absorbed when administered orally or parenterally.

Cephalosporins, process for producing the same, intermediates thereof

Novel cephalosporins which has attached to the exomethylene group at the 3-position of the cephem ring a substituted or unsubstituted aryl, acylamino, aromatic heterocyclic, triazolyl or tetrazolyl group, said aromatic heterocyclic group being attached through a carbon-carbon bond and said triazolyl or tetrazolyl group being attached through a carbon-nitrogen bond, and has the following group attached to the amino group at the 7-position: ##STR1## wherein A represents a group of the formula, --CH.sub.2 -- or a group of the formula ##STR2## in which R.sup.5 represents a hydrogen atom or an alkyl group, and the bond  represents syn or anti isomer or their mixture; R.sup.3 represents a hydrogen or halogen atom; and R.sup.4 represents a hydrogen atom or an amino group which may be protected or substituted. These cephalosporins have a broad antibacterial spectrum, are stable against .beta.-lactamase produced by bacteria, have a low toxicity, and are well absorbed when administered orally or parenterally.

7-(substituted or unsubstituted amino) 3-substituted methyl-.sup.3

This invention relates to novel 7-(substituted or unsubstituted amino)-3-substituted methyl-.DELTA..sup.3 -cephem-4-carboxylic acids in which a substituted or unsubstituted 1,2,4-triazolyl or 2-(1,2,3,4-tetrazolyl) group attaches to the exomethylene group at the 3-position of the cephem ring through a carbon-nitrogen bond. These cephalosporins are useful intermediates for producing various novel cephalosporins. Also, this invention concerns a process for producing a compound represented by the formula: ##STR1## which comprises reacting a compound represented by the formula: ##STR2## with an optionally substituted triazole or tetrazole in the presence of an acid or a complex of the acid in an organic solvent at 0.degree. to 80.degree. C.

Novel intermediates of cephalosporins and process for producing

Novel cephalosporins which has attached to the exomethylene group at the 3-position of the cephem ring a substituted or unsubstituted aryl, acylamino, aromatic heterocyclic, triazolyl or tetrazolyl group, said aromatic heterocyclic group being attached through a carbon-carbon bond and said triazolyl or tetrazolyl group being attached through a carbon-nitrogen bond, and has the following group attached to the amino group at the 7-position: ##STR1## wherein A represents a group of the formula, --CH.sub.2 -- or a group of the formula ##STR2## in which R.sup.5 represents a hydrogen atom or an alkyl group, and the bond  represents syn or anti isomer or their mixture; R.sup.3 represents a hydrogen or halogen atom; and R.sup.4 represents a hydrogen atom or an amino group which may be protected or substituted. These cephalosporins have a broad antibacterial spectrum, are stable against .beta.-lactamase produced by bacteria, have a low toxicity, and are well absorbed when administered orally or parenterally. This invention relates to such novel cephalosporins, processes for producing said cephalosporins, intermediates for producing said cephalosporins, and a process for producing said intermediates.

Cephalosporins

A 7.alpha.-methoxycephalosporin represented by the general formula: ##STR1## wherein R.sup.1 represents a hydrogen atom or a carboxyl-protecting group; R.sup.2 represents an organic group linked to the carbon atom through an oxygen or sulfur atom; R.sup.3 represents a lower alkyl group; n is 0, 1 or 2; A represents a hydrogen atom or a substituted or unsubstituted alkyl group; and B represents a substituted or unsubstituted alkyl, cycloalkyl, cycloalkenyl, cycloalkadienyl or heterocyclic group, and a salt thereof. These compounds have a broad antibacterial spectrum, high resistance to .beta.-lactamase produced from bacteria, and an effective antibacterial activity against clinical isolates of bacteria.

7.alpha.-Methoxycephalosporins

A 7.alpha.-methoxycephalosporin represented by the general formula and a salt thereof: ##STR1## wherein R.sup.1 represents a hydrogen atom or a carboxyl-protecting group; R.sup.2 represents an organic group linked to the carbon atoms through an oxygen or sulfur atom; R.sup.3 represents a lower alkyl group; n is 0, 1 or 2; A represents a hydrogen atom or a substituted or unsubstituted alkyl group; and B represents a substituted or unsubstituted alkyl group. These compounds have a broad antibacterial spectrum and high resistance to .beta.-lactamase produced from bacteria, and are well absorbed in a living body.

7.alpha.-methoxycephalosporins and pharmaceutical composition comprising

Novel 7.alpha.-methoxy-cephalosporins and non-toxic salts thereof, which contain a di-oxo-piperazinyl-carbonylamino group in molecule. These compounds are valuable antibacterial compounds for use in mammals including man. This disclosure relates to such compounds and methods for producing the same.

Substituted

Novel 7.alpha.-methoxy-cephalosporins and non-toxic salts thereof, which contain a di-oxo-piperazinylcarbonylamino group in molecule. These compounds are valuable antibacterial compounds for use in mammals including man. This disclosure relates to such compounds.

Growing community of inventors

Sagamihara, Japan

Hideo Taki