Shionogi Company Limited

Other

Yoshio Hamashima

Wataru Nagata

Teruji Tsuji

Mitsuru Yoshioka

Masayuki Narisada

Ikuo Kikkawa

Shoichiro Uyeo

Hiroshi Tanida

Kyoji Minami

Taichiro Komeno

Uyeo Shoichiro

Yusuke Suzuki

Kyozo Kawata

Toyohiko Takeda

Koji Ishikura

Teruo Sakamoto

Masanori Tujikawa

Yasuhiro Nishitani

Tadatoshi Kubota

Hiroshi Onoue

Hisao Sato

Sadao Hayashi

William H Lunn

Tadashi Yoshida

Fumihiko Watanabe

Tetsuo Okada

Hiroyuki Ishitobi

Kyoto Okada

Matsumura Hiromu

Fumitaka Takami

An antibacterial, 7.beta.-[(Z)-2-(2-aminothiazol-4-yl)-4-carboxybut-2-enoylamino]-3-cephem-4 -carboxylic acid is stable in a (di or tri)-hydrate crystal form. A pharmacologically effective amount of this hydrate is filled in a gelatin hard capsule and sealed by a band of gelatin to make a stable composition for clinical use after storage for a long time.

Gelatin hard capsule containing crystalline hydrate of oral cephalosporin

Method for preparing crystalline hydrate of oral celphalosporin and its

An antibacterial 7beta-(carboxyalkenoyl)amino-3-cephem-4-carboxylic acid represented by the following formula: ##STR1## (wherein R is aryl or a heterocyclic group;

Carboxyalkenamidocephalosporins

An antibacterial, 7.beta.-[(Z)-2-(2-aminothiazol-4-yl)-4-carboxybut-2-enoylamino]-3-cephem-4 -carboxylic acid is stable in a (di or tri)-hydrate crystal form. A pharmacologically effective amount of this hydrate is filled in a gelatin hard capsule sealed by a band of gelatin to make a stable composition for clinical use after storage for a long time.

Crystalline hydrate of oral cephalosporin and its composition

An antibacterial 7beta-(carboxyalkenoyl)amino-3-cephem-4-carboxylic acid represented by the following formula: ##STR1## (wherein R is aryl or a heterocyclic group; R.sup.1 is hydrogen or halogen;

An oral antibacterial, 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-alkenoylamino]-3-cephem-4-carboxylic acid pharmaceutically acceptable ester represented by the following formula: ##STR1## (wherein R is amino or protected amino,

Alkeneamidocephalosporin esters

An antibacterial 3-(alkylcarbamoyloxymethyl)-3-cephem-4-carboxylic acid or its derivatives represented by the following formula ##STR1## (wherein R is hydrogen or an amino-protecting group,

Alkylcarbamoyloxymethylcephem compounds

A useful synthetic intermediate, 7-amino-3-acyloxycepham-4-carboxylic acid aralkyl ester, is prepared by reducing 7-amido-3-oxocepham-4-carboxylic acid aralkyl ester with alkali metal borohydride in a dry organic solvent at temperature lower than -20.degree. C. and then acylating the resulting 3-hydroxycepham compound with an acylating reagent to give 3-acyloxycepham compound, and then subjecting the 3-acyloxycepham compound to amide cleavage consisting of treatments (1) with a mixture of phosphorus pentachloride and aromatic base giving imino-chloride and (2) with alcohol for converting the latter into imino-ether and for subjecting the product to alcoholysis giving the objective compound.

Process for preparing aminohydroxycephamcarboxylates

Intermediates for preparaing an antibacterial 1-dethia-1-oxacephalosporins which are represented by the following formula: ##STR1## wherein R is a monovalent group (minus the carbonyl) from an acyl derived from a carboxylic or carbonic acid;

1-oxadethiacepham compounds

Intermediates of the following formula are useful for the synthesis of 1-oxacephalosporins. Their preparation from penicillins and the transformation process to make 1-oxacephalosporins are disclosed. The compounds are of the formula: ##STR1## wherein A is amino or a selected acylamino;

Azetidinone intermediates for cephalosporin analogs

Antibacterial 7.beta.-(oxo-saturated heterocyclic carbonamido)-3-cephem-4-carboxylic acid derivatives of the formula: ##STR1## (wherein R is hydrogen or methoxy; R.sup.1 is hydrogen or a nucleophilic group; R.sup.2 is hydrogen, light metal, or a carboxy protecting group; X is oxygen, sulfur, sulfinyl, or sulfonyl; Y is alkylene containing one or more hetero atoms; and Z is hydrogen or a substituent).

(Oxoheterocyclic carbonamido)cephem carboxylic acid derivatives

An antibacterial 7beta-substituted malonamido-7alpha-methoxy-3-tetrazolylthiomethyl-1-dethia-1-oxa-3-cephem-4 -carboxylic acid and its derivative represented by the following formula: ##STR1## (wherein R.sup.1 is alkyl, hydroxyaryl, or thienyl;

Malonyloxacephemcarboxylic acid derivatives

Intermediates for preparing an antibacterial 1-dethia-1-oxacephalosporins which are represented by the following formula: ##STR1## wherein R is a monovalent group (minus the carbonyl) from an acyl derived from a carboxylic or carbonic acid;

1-Oxadethiacepham compounds

An antibacterial 7.beta.-(fluorinated methylthioacetamido)-7.alpha.-methoxy-3-(1-hydroxyalkyl-5-tetrazolyl)thiom ethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid and its derivatives at the carboxy or hydroxyalkyl represented by the following formula: ##STR1## wherein, R is FCH.sub.2 -- or F.sub.2 CH--; R.sup.1 is R.sup.3 O-substituted-alkyl in which R.sup.3 is hydrogen or a hydroxy-protecting group; and R.sup.2 is a hydrogen or light metal atom or a carboxy-protecting group, antibacterial drugs containing it, its use and production.

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Kyoto, Japan

Yoshio Hamashima