Eisai Company, Limited

Hiroshi Yamauchi

Shigeto Negi

Isao Sugiyama

Yoshimasa Machida

Seiichiro Nomoto

Takashi Kamiya

Isao Saito

Yuuki Komatu

Takaharu Nakamura

Kanemasa Katsu

Toshihiko Naito

Kyosuke Kitoh

Yasunobu Kai

Hironori Ikuta

Manabu Sasho

Takeo Kanai

Kenro Nakatsuka

Motosuke Yamanaka

Keizo Takayanagi

Tamio Kawamura

Yasuhide Tanaka

Atsushi Koiwa

Yoshikazu Hasagawa

Shinichi Endoh

A cephalosporin derivative represented by the formula: ##STR1## wherein R.sub.1 represents a lower alkyl group, and A is selected from: a group of the following formula: ##STR2## where R.sub.2 and R.sub.3 are the same or different lower alkyl group, R.sub.4 represents a substituted lower alkyl or amino group; a group which may be substituted and which is represented by the following formula: ##STR3## where R.sub.5 represents a lower alkyl group; or a group of the following formula: ##STR4## where R.sub.5 is as defined above, R.sub.6 represents a hydroxyl lower alkyl or carboxyl group, or its pharmacologically acceptable salt, and a process for preparing the same, as well as an antibacterial agent containing the same.

7Beta-(thiadiazolyl)-2-iminoacetamido-3cephem compounds

3-Substituted vinyl cephalosporin derivatives represented by the following formula: ##STR1## wherein R.sup.1 represents a hydroxyl or lower alkoxyl group, X represents a nitrogen atom or a group represented by the formula --CH.dbd., R.sup.2 represents a carboxyl group or a carboxyl group protected with a protecting group, and R.sup.3 is as defined herein, and pharmaceutically acceptable salts thereof are potent antibacterial agents. Processes for their preparation, intermediates in such processes, and antibacterial compositions containing them as active ingredients are also described.

3-substituted vinyl cephalosporin derivatives

A cephem derivative represented by the following formula: ##STR1## wherein R.sub.1 means a fluorine-substituted lower alkyl and A.sub.1 denotes a cyclic or acyclic ammonio group, or a non-toxic salt thereof, is prepared by reacting a compound represented by the following formula: ##STR2## wherein A.sub.1 has the same meaning as defined above, with another compound represented by the following formula: ##STR3## wherein R.sub.1 has the same meaning as defined above, and if necessary, removing the protecting groups.

Process for the preparation of cephem derivatives and intermediates

A 3-propenylcephem derivative of the following formula: ##STR1## wherein R.sub.1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof, exhibiting excellent anti-bacterial activities against both Gram-positive bacteria and Gram-negative bacteria; Process for the preparation thereof; Anti-bacterial composition; Intermediate for the 3-propenylcephem derivative; and Process for the preparation of the intermediate.

3-propenylcephem derivative

Described herein is a cephem derivative represented by the general formula: ##STR1## wherein n stands for 1 or 2, Y stands for CH or nitrogen atom, R.sub.1 represents a lower hydrocarbon group or a carboxyl-substituted, a carbamoyl-substituted, or a cyclopropyl-substituted lower alkyl group, and R.sub.2 denotes hydroxyl group, a lower alkyl group, a hydroxy-substituted lower alkyl group, or carbamoyl group. The derivative is useful as an antibacterial composition. Also described herein are processes for the production of the derivative, antibacterial composition, intermediate of the derivative and process for the production thereof.

Cephem derivatives

Described herein is a cephem derivative represented by the general formula: ##STR1## wherein n stands for 1 or 2, Y stands for CH or nitrogen atom, R.sub.1 represents a lower hydrocarbon group or a carboxyl-substituted, a carbamoyl-substituted, or a cyclopropyl-substituted lower alkyl group, and R.sub.2 denotes hydroxyl group, a lower alkyl group, a hydroxy-substituted lower alkyl group, or carbamoyl group. The derivative is useful as an antibacterial agent. Also described herein are processes for the production of the derivative, antibacterial composition, intermediate of the derivative and process for the production thereof.

Novel thiadiazolylacetamide cephem derivatives of the following formula are described. ##STR1## wherein A represents a quaternary ammonio group; or a pharmaceutically acceptable salt thereof. These novel compounds are useful as antibacterial agents, because they have a broad antibacterial spectrum ranging from gram-negative bacteria to gram-positive bacteria. Processes for the preparation of these novel compounds are also described.

Thiadiazolylacetamide cephem derivatives

Described herein is a cephem derivative represented by the general formula: ##STR1## wherein n stands for 1 or 2, Y stands for CH or nitrogen atoms, R.sub.1 represents a lower hydrocarbon group or a carboxyl-substituted, a carbamoyl-substituted, or a cyclopropyl-substituted lower alkyl group, and R.sub.2 denotes hydroxyl group, a lower alkyl group, a hydroxy-substituted lower alkyl group, or carbamoyl group. The derivative is useful as an antibacterial agent. Also described herein are processes for the production of the derivative, antibacterial composition, intermediate of the derivative and process for the production thereof.

Cephem compounds having at the 3-position a

A novel 4-cyanopiperidine derivative, which is represented by the following general formula (I): ##STR1## wherein X means a halogen atom, or an acid addition salt thereof, is prepared by reacting N-(2-hydroxyethyl)-4-carbamoylpiperidine or an acid addition salt thereof with a dehydrating and halogenating agent; or by reacting 4-cyanopiperidine or a salt thereof with a compound represented by the following general formula (IV):

4-cyanopiperidine derivatives

Described herein is 3-(pyrrolidinio)methyl-3-cephem derivative represented by the general formula: ##STR1## wherein Y stands for CH or nitrogen atom, R.sub.1 and R.sub.2 are the same or different, and represent a lower alkyl group, R.sub.3 denotes a hydroxy-substituted lower alkyl group, a lower alkyl group, or a carbamoyl group, and when Y stands for CH, R.sub.3 denotes a hydroxy-substituted lower alkyl group. The derivative is useful as antibacterial composition. Also described herein are process for the production of the derivative and antibacterial composition.

3-(pyrrolidinio)methyl-3-cephem derivatives

A compound represented by the formula: ##STR1## wherein R.sub.1 is hydrogen or methoxy; R.sub.2 is hydrogen or hydroxy; R is ##STR2## wherein R.sub.3 and R.sub.4 are hydroxy or acyloxy, Y is oxygen, sulfur or &gt;N-R.sub.5 wherein R.sub.5 is hydrogen or lower alkyl, and Z is sulfur or &gt;N-R.sub.5 wherein R.sub.5 has the same meanings as defined above; and X is ##STR3## wherein R.sub.6 is acyloxy or nitrogen-containing heterocyclicthio which may have substituent(s), a pharmaceutically accpetable salt thereof, and a carboxylic ester thereof. This compound has improved antibacterial activity against Kleb. pneumoniae and Pseud. aeruginosa.

Cephalosporin compounds

The invention provides 3-carbamoyloxymethylcephem derivatives represented by the general formula: ##STR1## wherein R.sub.1 represents hydrogen atom or trichloroacetyl group, R.sub.2 represents hydrogen atom or methoxy group, and R.sub.3 represents hydrogen atom or hydroxyl group, or pharmaceutically acceptable salt thereof. The cephem derivatives of the invention are useful as antibacterial drugs.

3-Carbamoyloxymethylcephem derivatives, and antibacterial drugs

Cephem derivatives represented by the formula: ##STR1## wherein R.sub.1 represents a hydrogen atom or a hydroxyl group, R.sub.2 represents a lower alkyl group or a chloro-substituted lower alkyl group, and R.sub.3 represents a lower alkanoyloxy group or a nitrogen-containing heterocyclic thio group, and the pharmaceutically acceptable salts thereof. The cephem derivatives exhibit excellent antibacterial activity and are effective against Gram-positive and Gram-negative bacteria.

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Ibaraki, Japan

Hiroshi Yamauchi