Yamanouchi Pharmaceutical Company Ltd.

Masaru Iwanami

Masaharu Fujimoto

Yoshinobu Nagano

Tetsuya Maeda

Masuo Murakami

Tadao Shibanuma

Noriaki Nagano

Atsuki Yamazaki

Ryutaro Kawai

Kiyoshi Murase

Ichiro Isaka

Kuniichiro Yano

Norio Sato

Kazaharu Tamazawa

Kozo Takahashi

Takashi Fujikura

Toichi Takenaka

Yukiyasu Murakami

Tadao Kojima

Akio Koda

Kazuharu Tamazawa

Norio Kawahara

A cephalosporin derivative of the formula ##STR1## wherein R is a hydrogen atom, a lower alkyl group which may have been substituted or a carbamoyl group which may have been substituted; R.sub.1 is hydrogen atom or a methoxy group; R.sub.2 is a hydrogen atom, an acyloxy group, or a nitrogen-containing 5-membered heterocyclic thio group which may have been substituted; R.sub.3 is a free amino group or an amino group having a protective group; and R.sub.4 is a free carboxy group or a carboxy group having a protective group or the salts thereof. The compound of this invention has an excellent antibacterial activity against gram negative bacteria and gram positive bacteria.

Cephalosporin derivative and pharmaceutical composition

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

Process for producing 7.beta.-amino-7.alpha.-methoxycephalosporins without the epimerization or formation of the corresponding 7.alpha.-amino-7.beta.-methoxy isomers by deacylating cephalosporin derivatives having 7.beta.-acylamino-7.alpha.-methoxy group.

Process for producing 7.beta.-amino-7.alpha.-methoxycephalosporins

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.

7.alpha.-METHOXY-CEPHALOSPORANIC ACID DERIVATIVES

A novel cephalosporin derivative having at the 3-position of the cephem ring a heterocyclic thiomethyl group having a carboxy group or a sulfo group and at the 7-position of the cephem ring, an .alpha.-heterocyclic acylaminophenylacetamide group. The compounds of this invention have excellent antibacterial activity against Pseudomonas and Proteus strains of bacteria.

Cephalosporin derivatives having at the 3-position of the cephem ring a

Novel 7-(.alpha.-hydroxy-substituted pyridylcarboxamido-.alpha.-phenylacetamido)-3-substituted thiomethyl-.DELTA..sup.3 -cephem-4-carboxylic acid derivatives are disclosed. The compounds of this invention have high water solubility and show excellent antibacterial activities against various strains of Pseudomonas and Proteus.

Derivatives of 7-(.alpha.-hydroxy-substituted pyridyl carboxamido-.alpha. p

N-alkenyltetracycline derivatives, for example, N-(1-methyl-2-.alpha.-naphthylethenyl)tetracycline represented by the formula ##SPC1## The compounds have excellent antibacterial action as compared with tetracycline.

N-alkenyltetracycline derivatives

There are provided novel 1,4-dihydropyridine derivatives, particularly 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-.beta.-(N-benzyl-N-methylamino)ethyl ester and 5-methyl ester. The 1,4-dihydropyridine derivatives are characterized by cerebral vascular dilator activity.

1,4-Dihydropyridine derivatives

N-alkenyltetracycline derivatives, for example, N-[1-methyl-2(2-thienyl)-1-butenyl]tetracycline represented by the formula ##SPC1## The compounds have excellent antibacterial action as compared with tetracycline.

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Yokohama, Japan

Masaru Iwanami