Shionogi Company Limited

Hiroshi Onoue

Masayuki Narisada

Wataru Nagata

Yoshio Hamashima

Teruji Tsuji

Mitsuru Yoshioka

Yasuhiro Nishitani

Mitsuaki Ohtani

Fumihiko Watanabe

Toshiro Konoike

Koji Ishikura

Kyoji Minami

Hiromi Takahashi

Hiroyuki Ishitobi

Antibacterial hydroxyarylpiperazinocephalosporins of the formula: ##STR1## wherein R.sup.1 is amino or acylamino; R.sup.2 is H or methoxy; R.sup.3 is alkyl; R.sup.4 is --(P--C--Q).sub.n --, where P and Q each are H, alkyl or OH, or P and Q combine to form oxo, and n is 0 or 4; R.sup.5 is substituted or unsubstituted hydroxyaryl; R.sup.6 has a negative charge and is COO, or an anion in combination with an optionally protected carboxy; and X is O, S or S.fwdarw.O; an antibacterial preparation containing the same; a method for killing bacteria and preventing or treating bacterial infection by using the same; and syntheses of the cephalosporins are provided.

Piperaziniocephalosporins

An antibacterial 3-vic-dihydroxyaroylmethylpyridiniothiomethyl cephalosporin (I) and its salts represented by the following formula: ##STR1## (wherein, R.sup.1 is amino group or acylamino; R.sup.2 is hydrogen or methoxy; R.sup.3 is hydrogen atom or substituent; R.sup.4 is vic-dihydroxyaryl; R.sup.5 is straight or branched lower alkylene; R.sup.6 is hydrogen, a carboxy-protecting group or combined with Y a negative charge; X is --O--, --S-- or sulfinyl; and Y is a counter-ion of pyridinio or combined with R.sup.6 a negative charge), a disinfecting and treating method of bacterial infection using it, and synthetic methods thereof are provided.

Phenacylpyridiniothiocephalosporins

A useful intermediate, glutaconic acid ester derivative (III), is prepared by Michael-type condensation of thiazoleacetic acid derivative (I) with alkoxyacrylic acid derivative (II) in the presence of base. ##STR1## (wherein, R is amino or protected amino;

Process for producing glutaconic acid derivatives

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 compound represented by the formula (II) epimerizes by the action of a base and the product is precipitated for shifting the equilibrium to yield the corresponding epimer represented by the formula (I). ##STR1## wherein Ar is an optionally substituted aryl or heterocyclic group;

Epimerization of malonic acid esters

Potent antibacterial cephalosporin analogues of the following formula in forms of free acids, pharmaceutically acceptable salts, or esters preparable from penicillins through azetidinone derivatives by way of a new process, and utilizable as active ingredients in bactericidal compositions for pharmaceutical and veterinary use: ##STR1## (wherein Acyl is selected from phenylacetyl, D-mandeloyl, .alpha.-phenylmalonyl, D-.alpha.-(3-methanesulfonyl-2-oxoimidazolidin-l-yl)carbonamido-.alpha.-ph enylacetyl, and 2-thienylacetyl).

Growing community of inventors

Nara, Japan

Hiroshi Onoue