Shionogi Company Limited

Other

Teruji Tsuji

Wataru Nagata

Yoshio Hamashima

Mitsuru Yoshioka

Masayuki Narisada

Ikuo Kikkawa

Shoichiro Uyeo

Hiroshi Tanida

Taichiro Komeno

Uyeo Shoichiro

Yasuhiro Nishitani

Hisao Sato

Tetsuo Okada

Tsutomu Aoki

Hiroshi Onoue

Hikaru Itani

Hiroyuki Ishitobi

Hiromi Takahashi

William H Lunn

Hiromu Matsumura

Toshiro Konoike

Koji Ishikura

Kyoji Minami

Yuji Sendo

Kanji Tokuyama

Mamoru Tanaka

Takashi Maeda

Shoichi Hirai

Sadao Hayashi

Takahiro Kataoka

Matsumura Hiromu

Yoshio Hahashima

Sadao Yamamoto

Novel quinolonecarboxylic acids of the formula: ##STR1## wherein R.sup.1 is C.sub.1 -C.sub.4 alkyl, R.sup.2 and R.sup.3 each is identically or differently hydrogen or C.sub.1 -C.sub.4 alkyl, R.sup.4 is cyclopropyl, phenyl, halo-phenyl, or thienyl optionally substituted by C.sub.1 -C.sub.4 alkyl or halogen, and R.sup.5 is halogen, or pharmaceutically acceptable salts thereof having a more potent and longer lasting antibacterial activities against G(+) and G(-) bacteria than known analogues, useful as antibacterial agents at an oral dose of 1-500 mg, preferably 50-100 mg per day to an adult.

Quinolinecarboxylic acids

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

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

A useful industrial chemical, oxazolinoazetidinylhydroxymethylbutenoic acid derivative (II) can be produced by oxidizing the corresponding oxazolinoazetidinylhalomethylbutenoic acid derivative(I). ##STR1## wherein R is an alkyl, aralkyl or aryl group, R.sup.1 is a hydrogen atom or a carboxy protecting group and Hal is a halogen atom.

Production of hydroxymethylbutenoic acids via oxidation

A novel chemical, fluorochlorocyclopropane (I) of the following formula: ##STR1## is prepared by the addition of fluorochlorocarbene to the corresponding olefin (II) of the following formula:

Fluorocyclopropanes

Useful intermediates, 7.alpha.-acylamino-3-(oxo or exomethylene)-1-dethia-1-oxacepham-4.alpha.-carboxylates, are produced by the intramolecular carbenoid insertion of a 2-diazo-3-(oxo or exomethylene)-4-(3.alpha.-acylamino-2-oxoazetidin-4.beta.-yl)oxybutyrate prepared in several steps from the corresponding oxazolinoazetidinone and diketone.

Production of 1-oxacephams and intermediates

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.

Fluoromethylthiooxacephalosporins

Monofluoromethylthioacetic acid (FCH.sub.2 SCH.sub.2 COOH) or difluoromethylthioacetic acid (F.sub.2 CHSCH.sub.2 COOH), or its derivative at the carboxy group can be prepared e.g. by treating a thioglycolic acid ester with monolfuorohalomethane or difluorohalomethane in the presence of a base if required followed by a conventional modification of the produced ester e.g. to make an acid by hydrolysis, a salt by neutralization, a halide with a halogenating agent, and from acid halide or anhydride an ester with an alcohol, or an amide with an amine. These compounds are useful intermediates in the production of medicinal and agricultural chemicals.

Fluoromethylthioacetic acid compounds

Intermediates for preparing an antibacterial 1-dethia-1-oxa-cephalosporins 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;

An intermediate represented by following formula for synthesizing 3-hydroxy-3-cephem compounds. ##STR1## wherein A and B each is a hydrogen or amine substituent; R is a hydrogen or thiol substituent; Nal is a halogen; X is a hydroxy or carboxy protecting group; the broken line between A and R shows that when R and B are hydrogens, and A is a carboxylic acyl, the substituents can be combined to form an azetidimethiazoline bicyclic ring; and the enamine derivatives thereof.

Cyclization to form cephem ring and azetidinone intermediates therefor

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 group derived from a carboxylic or carbonic acid;

Growing community of inventors

Takatsuki, Japan

Teruji Tsuji