Meiji Seika Kaisha, Ltd.

Other

Merck + Co., Inc.

Yasushi Murai

Seiji Shibahara

Tsuneo Okonogi

Katsuharu Iinuma

Masahiro Onodera

Shunzo Fukatsu

Taro Niida

Tadashi Wakazawa

Tatsuo Watanabe

Masamichi Sukegawa

Takashi Yoshida

Kiyoshi Yasui

Shinichi Kondo

Osamu Sakanaka

Yumiko Okada

Burton G Christensen

Ken Nishihata

Yuichi Yamamoto

Toshiaki Kudo

Osamu Makabe

Toyomi Sato

Makoto Ohyama

Tuneo Okonogi

Peter Jeschke

Norbert Mencke

Achim Harder

Takashi Tsuruoka

Shigeharu Inouye

Katsuyoshi Iwamatsu

Gerhard Bonse

Masao Koyama

Kiyoaki Katano

Hiroko Ogino

Shigeharu Inoue

Satoru Nakabayashi

Yoshiyuki Koyama

Toshio Yoneta

Takayoshi Tamura

Toshio Nishizuka

Takeshi Teraoka

Masayuki Takagi

Shinjiro Sumi

Tadaaki Okada

Masaaki Takahashi

Makoto Taniguchi

Haruki Mikoshiba

Yasuhiko Abat

Koichi Mitomo

Maki Ohishi

Kikuko Kuzuhara

Shunzo Futkatsu

Tsuneo Okonogy

Maki Matsumoto

Hiroyuki Iwasawa

Disclosed are novel compounds useful for prevention or control of diseases derived from fungi, a process for producing the same, and novel antifungal agents using the novel compounds. The compounds useful for prevention and treatment of diseases derived from fungi according to the present invention include novel compounds represented by formula (I). The compounds represented by formula (I) have potent antifungal activity against diseases derived from fungi, and do not have phytotoxicity to mammals and agricultural and garden plants, from which diseases should be eliminated, and, even when applied to agricultural and garden plants, have high photostability. wherein

Antifungal compound and process for producing the same

Processes are provided for the preparation of orally administrable, yellow and powdery compositions essentially consisting of particles composed of a homogeneous mixture of an amorphous Cefditoren pivoxil substance with a water soluble high-molecular additive. These compositions can be produced by dissolving crystalline Cefditoren pivoxil substance and the water-soluble high-molecular additive in an aqueous solution of an acid, then neutralizing the resultant solution, to co-precipitate the product, and drying the thus precipitated product, followed by recovering the product in the form of the above-mentioned particles.

Composition comprising a crystallographically stable, amorphous cephalosporin and processes for the preparation thereof

A crystalline substance of Cefditoren pivoxyl is provided which has a high purity and enhanced thermal stability on storage. This crystalline Cefditoren pivoxyl may be prepared by a process comprising a step of dissolving an amorphous form of Cefditoren pivoxyl in an anhydrous, first organic solvent capable of dissolving said amorphous form well therein, and steps of replacing the first organic solvent component of the resulting solution by an anhydrous alkanol of 1 to 5 carbon atoms as a second organic solvent, in such a manner that the firstly prepared solution of Cefditoren pivoxyl in the first organic solvent is mixed with a volume of the alkanol and then is concentrated below 15&deg; C. under reduced pressure, and so on. Thereby, the process proceeds so as to produce a solution containing 50 mg/ml to 250 mg/ml of Cefditoren pivoxyl dissolved in the alkanol alone. From the latter solution, crystals of Cefditoren pivoxyl are induced to deposit by addition of water at a temperature of 0-10&deg; C. The resulting admixture of the concentrated solution of Cefditoren pivoxyl in alkanol with added water and the deposited Cefditoren pivoxyl is then agitated 10&deg; C. or below, to effect a complete crystallization of Cefditoren pivoxyl.

Crystalline substance of cefditoren pivoxyl and the production of the same

Crystallographically stable amorphous cephalosporin compositions and process for producing the same

Novel derivatives of PF1022 substance, which are cyclodepsipeptides represented by the general formula (I) shown below or their salts are useful as anthelmintic agent for prevention or treatment of parasitic infections.

Derivatives of cyclodepsipeptide PF1022 substance

As a novel substance is provided such a new, crystalline substance of Cefditoren povoxyl which has a high purity and an enhanced thermal stability on storage. This crystalline Cefditoren pivoxyl may be prepared by a process comprising a step of dissolving amorphous substance of Cefditoren pivoxyl in an anhydrous, first organic solvent capable of dissolving said amorphous substance well therein, and steps of replacing the first organic solvent component of the resulting solution by an anhydrous alkanol of 1 to 5 carbon atoms as a second organic solvent, in such a manner that the firstly prepared solution of Cefditoren pivoxyl in the first organic solvent is mixed with a volume of the alkanol and then is concentrated below 15&deg; C. under reduced pressure, and so on. Thereby, the process proceeds so as to produce a solution containing 50 mg/ml to 250 mg/ml of Cefditoren pivoxyl dissolved in the alkanol alone. From the latter solution, crystals of Cefditoren pivoxyl are induced to deposit by addition of water at a temperature of 0-10&deg; C. The resulting admixture of the concentrated solution of Cefditoren pivoxyl in alkanol with added water and the deposited Cefditoren pivoxyl is then agitated 10&deg; C. or below, to effect a complete crystallization of Cefditoren pivoxyl.

There can be produced, at a high selectivity and in a high yield, the Z-isomer of a 7-N-unsubstituted or substituted-amino-3-&lsqb;2-(4-substituted or unsubstituted-thiazol-5-yl) vinyl&rsqb;-3-cephem-4-carboxylic acid or an ester thereof having the general formula (IV)

Process for the selective preparation of Z-isomers of 3-2(substituted vinyl)cephalosporins

Derivatives of cyclodepsipeptide PF 1022

The crystalline dihydrochloride of a specific cephalosporin derivative is stable to heat and retains its antibacterial activity even after storage over long periods at high temperature. The crystalline dihydrochloride can be obtained by removing protective groups from the cephalosporin derivative wherein the amino group and carboxy groups are protected and then crystallizing the cephalosporin derivative from a hydrochloric acid aqueous solution. The crystalline dihydrochloride is useful for pharmaceutical preparations.

Crystalline dihydrochloride of cephalosporin derivative and a method for

New cephalosporin derivatives of a general formula (I) and non-toxic salts and non-toxic esters thereof are provided: ##STR1## (wherein R represents an acyclic or cyclic lower alkyl group having 1-6 carbon atoms, which may optionally be substituted by a halogen atom; the steric configuration as asterisked (*) includes an optical-active (R)-form or (S)-form or an optical-inactive (RS)-form; n is 0 or 1, n.sup.1 is 0 to 3, n.sup.2 is 0 to 3; and when n.sup.1 is 0, n.sup.2 is 3; when n.sup.1 is 1, n.sup.2 is 2; when n.sup.1 is 2, n.sup.2 is 1; when n.sup.1 is 3, n.sup.2 is 0). The new derivatives of the formula (I) and non-toxic salts and esters thereof have high bactericidal activity with broad antibacterial spectra, and these are useful as active ingredients in bactericides.

Cephalosporin derivatives and antibiotics containing the same

Cephalosporin compounds having 2-(2-aminothiazol-4-yl)-2{(1S)-carboxyethoxyimino}acetyl group on the side chain at the 7-position thereof and 1-ethylpyridinium-4-ylthiomethyl group on the side chain at the 3-position thereof or non-toxic salts thereof are excellent antibacterial agents for mammals including human. The cephalosporin derivatives have low toxicity.

Antibacterial agent for mammal use comprising cephalosporin derivatives

This is a class of antibacterial compounds of the formula: ##STR1## wherein Y is straight or branched alkyl or alkenyl chain, cycloalkanomethyl of 3-6 carbon atoms, each group being optionally substituted by halogen, or a group ##STR2## wherein n is 0 or an integer of 1-3, A is a group --COR.sup.3 wherein R.sup.3 is hydroxy, a group ##STR3## wherein R.sup.4 and R.sup.5, which may be the same or different, are hydrogen or alkyl of 1-5 carbon atoms, a group ##STR4## or a 5- or 6-membered heterocyclic group containing nitrogen and/or sulfur, and R.sup.1 and R.sup.2, which may be the same or different, are hydrogen, alkyl of 1-5 carbon atoms, or R.sup.1 and R.sup.2 may be combined together to form cycloalkylidene of 3-5 carbon atoms, and Z is a group of the formula: ##STR5## wherein m is 0 or an integer of 3-5, R.sup.6 is hydrogen or alkyl of 1-3 carbon atoms, and R.sup.7, when m is an integer of 3-5, is alkyl of 1-5 carbon atoms, alkenyl, cyclopropyl, a group --(CH.sub.2).sub.p B wherein p is 0 or an integer of 1-3 and B is amino, alkyl-substituted amino, hydroxy, carboxy, carbamoyl, trifluoromethyl, sulfonic acid, sulfonic acid amide, alkylthio or cyano or, when m is 0, is alkyl of 1-5 carbon atoms, which may optionally be substituted by halogen, alkenyl, a group ##STR6## wherein R.sup.8 is hydrogen, alkyl of 1-4 carbon atoms or phenyl, or cyclopropyl, and a salt thereof.

Cephalosporin derivatives

The subject invention includes a 1-oxa-1-dethia-cephalosporin compound represented by the general formula (1) ##STR1## wherein R.sup.1 is a group of the formula: ##STR2## where R.sup.5 is a methyl group, an ethyl group, a carboxymethyl group or a 2-carboxy isopropyl group, or R.sup.1 is a group of the formula: ##STR3## where R.sup.6 is a hydrogen atom, a 4-ethyl-2,3-dioxopiperazine-1-yl group, a 3,4-dihydroxy phenyl group or a 5- and 6-membered heterocyclic radical having 2 ring nitrogens as the sole hetero substituent in the ring and having at least one hetero group on the carbon adjacent to the ring nitrogens.

1-oxa-1-dethia-cephalosporin compounds and antibacterial agent

Disclosed is a process for preparing antibiotic 1-oxadethiacephalosporins via diazo-species I: ##STR1## wherein: A is acyl; R.sup.1 is H or OCH.sub.3 ; and R.sup.2 is a protecting group.

Process for the production of antibiotic 1-oxadethiacephalosporins, and

This invention relates to 1-oxa-1-dethia-cephalosporins which are useful as anti-biotics.

1-Oxa-1-dethia-cephalosporin derivatives

Growing community of inventors

Odawara, Japan

Yasushi Murai