Meiji Seika Kaisha, Ltd.

Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Shigeharu Inoue

Takashi Tsuruoka

Taro Niida

Katsuyoshi Iwamatsu

Shinichi Kondo

Seiji Shibahara

Takashi Shomura

Shoji Omoto

Tsuneo Okonogi

Michio Kojima

Hiroshi Watanabe

Takashi Yoshida

Kiyoaki Katano

Hiroko Ogino

Yuichi Yamamoto

Uichi Shibata

Takemi Koeda

Takashi Hisamatsu

Kazunori Ohba

Hiroyasu Asaoka

Tomio Takeuchi

Takaaki Aoyagi

Shunzo Fukatsu

Yasushi Murai

Masaji Sezaki

Shigeo Seki

Mitsugu Hachisu

Yujiro Yamada

Yoshiyuki Koyama

Satoru Nakabayashi

Fumio Kai

Keinosuke Miyauchi

Shingo Uchida

Singo Uchida

Ryoichi Okamoto

Kunikazu Totsukawa

A new class of cephalosporin derivatives is provided, which is useful as antibacterial agent to be particularly suitable for oral administrations in mammals including man, and which is represented by general formula (I) ##STR1## wherein R.sup.1 is a hydrogen atom or a lower alkyl group; R.sup.2 is a hydrogen atom or an ester-forming group capable of being cleaved easily with an esterase existing in the digestive tracts; n is an integer of zero or 1; Z is a saturated heterocyclic group containing one or two oxygen atoms as the hetero-atoms with or without one or more lower alkyl substituents, or a pharmaceutically acceptable salt thereof.

Cephalosporin derivatives

Process for the preparation of a 3-substituted thio-3-cephem compound

A novel actinonin derivative and a salt thereof are provided, which are useful as enzyme inhibitors and particularly have strong inhibitory activities against enkephalinase and angiotensin-converting enzymes. This actinonin derivative is represented by general formula (I): ##STR1## wherein R.sup.1 is sulfoxymethyl or carboxyl or a substituted carboxyl group selected from carboxamide, hydroxyaminocarbonyl and alkoxycarbonyl groups; and R.sup.2 is hydroxyl, alkoxy, hydroxyamino or sulfoxyamino group.

Actinonin derivatives and pharmaceutically acceptable salts thereof

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 compounds represented by the following formula (I) and pharmaceutically acceptable salts thereof have a broad bactericidal spectrum against various pathogenic bacteria including Psuedomonas aeruginosa and are useful as bactericidal remedies for pathogenic diseases of human and animals: ##STR1## wherein A represents an unsubstituted or substituted pyridylthio group of a formula (I-1); ##STR2## or an unsubstituted or substituted pyridiniumthio group of a formula (I-2): ##STR3## or an unsubstituted or substituted pyridinium group of a formula (I-3); ##STR4## or a 5- or 6-membered heterocyclicthio or bicycloheterocyclicthio group of a formula (I-4):

Cephalosporin derivatives and bactericides containing the same

A 7.alpha.-methoxycephalosporin derivative represented by the formula (I): ##STR1## wherein R.sub.1 represents a heterocyclic ring or an --S-- heterocyclic ring; R.sub.2 represents a hydrogen atom, a carboxy group or a --COOR.sub.5 group wherein R.sub.5 represents a lower alkyl group, a dialkylamino-lower alkyl group or a ##STR2## group wherein R.sub.6 represents a lower alkyl group, a lower acyl group or a lower alkoxycarbonyl group and Y represents a hydrogen atom or a lower alkyl group; R.sub.3 represents a hydrogen atom, a carbamoyl group or a lower acyl group; R.sub.4 represents a hydrogen atom, a lower alkyl group, a dialkylamino-lower alkyl group or a ##STR3## group wherein R.sub.6 and Y are defined as above; A and B, which may be the same or different, each represents a straight chain or branched chain alkylene group having 1 to 5 carbon atoms; and x represents 0 or 1; or a pharmaceutically acceptable salt thereof and a process for producing the same.

7.alpha.Methoxycephalosporin derivatives

New antibiotic, SF-2052 substance is produced by cultivating a microorganism, Dactylosporangium matsuzakiense SF-2052 now deposited under FERM-P 4670 or ATCC No. 31570 in a liquid culture medium under aerobic conditions, and this antibiotic may be isolated from the culture broth by conventional method and is useful as antibacterial agent.

Antibiotic SF-2052 substance and production and use thereof

A new antibiotic SF-1771 substance is produced by cultivating a new strain, Streptomyces toyocaensis SF-1771, in a liquid culture medium under aerobic conditions. This antibiotic may be isolated from the fermentation broth by treating the broth filtrate with a synthetic adsorbent resin for adsorption of the active compound and eluting the resin with an aqueous alcohol or aqueous acetone, followed by chromatographic purification. SF-1771 substance is a copper-containing antibiotic which shows antibacterial activity against Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis. Removal of the copper component from SF-1771 substance by treatment with hydrogen sulfide, an alkali metal sulfide or a copper-chelating agent gives SF-1771-B substance containing no copper component which shows antibacterial activity as high as but a toxicity lower than SF-1771 substance.

Antibiotics SF-1771 substance and SF-1771-B substance as well as the

New antibiotics SF-1130-x.sub.1 substance and SF-1130-x.sub.2 substance are produced by cultivating a microorganism Streptomyces myxogenes SF-1130 now deposited under FERM-P. 676 and ATCC. 31305 in a liquid culture medium under aerobic conditions, and these antibiotics may be isolated from the fermentation broth and are useful as an activator for enhancing the host defense system in living animals. The activity of these antibiotics may be improved when used in combination with one or more of maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose and maltoheptaose.

Antibiotics SF-1130-x.sub.1 and -x.sub.2 substances and production and

Novel compounds useful as hypotensive agents are presented having the general formula I ##STR1## wherein R.sub.1 represents a substituted or unsubstituted aralkyl group, that is an aralkyl group of the general formula ##STR2## wherein R.sub.2 represents hydrogen, a lower alkyl group or a halogen atom. Furthermore, new therapeutic compositions of matter are also described incorporating the above novel 3-substituted-2(1H)pyridone-6-carboxylic acids (I) as an active ingredient with carriers and showing uses as hypotensive agents. These new compounds of the formula I are prepared by reacting D-glucaro-.delta.-lactam or its salt with an aralkyl halide.

3-Substituted-2(1H)pyridone-6-carboxylic acids

Maltopentaose and maltohexaose are produced with commercial advantage by cultivation of Streptomyces myxogenes SF-1130 strain under aerobic conditions in an appropriate culture medium and recovery from the resultant culture.

Process for production of maltopentaose and maltohexaose

Novel compounds useful as hypotensive agents are presented having the general formula I ##STR1## wherein R.sub.1 represents a lower aliphatic acyl group, a straight or branched chain alkyl or alkenyl group or an aralkyl group of the general formula ##STR2## wherein R.sub.2 represents hydrogen, a lower alkyl group or a halogen atom. Furthermore, new therapeutic compositions of matter are also described incorporating the above novel 3-substituted-2(1H)pyridone-6-carboxylic acids (I) as an active ingredient with carriers and showing uses as hypotensive agents. These new compounds of the formula I are prepared either by reacting D-glucaro-.delta.-lactam or its salt with an acid anhydride or by reacting 3-hydroxy-2(1H)pyridone-6-carboxylic acid with an acyl anhydride or alkyl halide, aralkyl halide and an alkenyl halide.

3-Substituted-2(1H)pyridon-6-carboxylic acids and process for

Growing community of inventors

Yokohama, Japan

Shigeharu Inoue