Sumitomo Chemical Company, Limited

Sumitomo Pharmaceuticals Company Limited

Hirotada Yamada

Takenari Nakagome

Toshiaki Komatsu

Hisao Tobiki

Kozo Shimago

Hiroshi Noguchi

Yasuko Eda

Akio Izawa

Norihiko Tanno

Iwao Nakatsuka

Kenji Irie

Shigeru Okano

Takao Okuda

Kosaku Okamura

Masatomo Fukasawa

Masuhiro Kato

Kousaku Okamura

Naruhito Masai

Masataka Fukumura

Kiyokazu Jimpo

Sinji Ueda

Shinji Ueda

Norithiko Tanno

A cephem derivative represented by the general formula ##STR1## wherein R.sup.1 represents hydrogen or methyl, R.sup.2 represents carboxyl or esterified carboxyl, and n represents 0 or 1, or a pharmaceutically acceptable salt thereof; intermediates for the cephem derivative or salt thereof; processes for producing these compounds; and a pharmaceutical composition and method for preventing or treating bacterial infectious diseases, wherein the cephem derivative or the salt thereof is used.

Cephem derivatives

A cephem compound represent by the general formula ##STR1## wherein, R.sup.1 represents hydrogen or lower alkyl, R.sup.2 and R.sup.3 are the same or different and each represents hydrogen or lower alkyl, R.sup.4 represents carboxyl or esterified carboxyl, and n represents 0 or 1, a salt of the cephem compound, and a process for producing the cephem compound or a salt thereof. Compounds of the above formula and salts thereof are valuable as antibacterial agents and are especially useful as oral drugs in the prevention or treatment of bacterial infectious diseases.

Cephem compounds

Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen or a (C.sub.1 -C.sub.4) alkyl group, X is a straight or branched chain C.sub.1 -C.sub.4 alkylene group and R.sub.2 is a carboxyl group or a sulfo group; and the pharmaceutically acceptable salts thereof exhibit strong inhibitory activities against a wide variety of Gram-positive and Gram-negative bacteria including Psendomonas aeruginosa, indolepositive Proteus and Enterobacter aerogenes, and also have an increased and prolonged serum level in a living body. The compounds are therefore useful as antibacterial agents for the treatment of infectious diseases caused by Gram-positive and Gram-negative bacteria.

Antimicrobial 7-(.alpha.-acylamino-.alpha.-arylacetamido)-3-(substituted

A compound of the formula (I): ##STR1## wherein A is a monocyclic or polycyclic heteroaromatic ring containing at least one nitrogen atom as a hetero atom, which may be unsubstituted or substituted with one or more substituents;

Cephalosporins

A cephalosporin of the formula (I): ##STR1## wherein A is a mono- or polycyclic heteroaromatic ring containing at least one nitrogen atom as a hetero atom, which may be unsubstituted or substituted; R is a phenyl group which may be unsubstituted or substituted, a thienyl group, a furyl group, a cyclohexadienyl group or a cyclohexenyl group; X is an acetoxy group, a pyridinium group which may be unsubstituted or substituted with a methyl or carbamoyl group, a group of the formula: ##STR2## in which R.sub.1 and R.sub.2, which may be the same or different, each is a hydrogen atom or a (C.sub.1 -C.sub.4)alkyl group, or a group of the formula:

7-Methoxy cephalosporins

7-(.alpha.-Acylamino-.alpha.-phenyl or thienylacetamido) cephalosporin

A cephalosporin derivative of the formula (I), ##STR1## wherein A is a mono- or polycyclic heteroaromatic ring, which contains at least one nitrogen atom as a hetero atom and which may be substituted with one or more substituents; R is a phenyl group substituted with at least one substituent selected from the group consisting of an amino group, a hydroxy group, a ureido group and a hydroxymethyl group; and X is an --OCOCH.sub.3 group or an --S-Het group in which Het is a 5- or 6-membered heterocyclic ring containing one to four hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms which may be substituted with one or more substituents, and the non-toxic pharmaceutically acceptable salts thereof which are useful as an antimicrobial and prepared by the reaction of a compound of the formula (II),

N-acylamino-.alpha.-arylacetamido cephalosporins

N-acylamino-alpha-arylacetamido cephalosporins and antibacterial

A cephalosporin derivative of formula (I): ##STR1## wherein X is an --OCOCH.sub.3 group or an --S--Het group in which Het is a 5- or 6-membered heterocyclic ring containing one to four hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms, which may be substituted with one or more substituents, and the non-toxic pharmaceutically acceptable salts thereof which are useful as an antimicrobial material and which are prepared by the reaction of a compound of formula (II): ##STR2## or a reactive derivative thereof, with a compound of formula (III): ##STR3## wherein X is as defined above, or a derivative thereof.

7-(.alpha.-(4-Hydroxy-1,5-naphthyridine-3-carbonamido)-.alpha.-ph

A cephalosporin derivative of formula (I): ##STR1## wherein X is an --OCOCH.sub.3 group or an -S-Het group in which Het is a 5- or 6-membered heterocyclic ring containing one to four hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms, which may be substituted with one or more substituents, and the non-toxic pharmaceutically acceptable salts thereof which are useful as an antimicrobial material and which are prepared by the reaction of a compound of formula (II): ##STR2## or a reactive derivative thereof, with a compound of formula (III): ##STR3## wherein X is as defined above, or a derivative thereof.

7-(.alpha.-(4

A penicillin of the formula: ##STR1## (i.e. 6-[D-2-(3-hydroxypyridazine-4-carbonamido)-2-(p-hydroxyphenyl)acetamido]pe nicillanic acid), which is valuable as an antibacterial agent, a nutritional supplement in animal feeds and a therapeutic agent in poultry and mammals including man and is especially useful in the treatment of infectious diseases caused by Gram-positive and Gram-negative bacteria.

Novel penicillin, and its preparation and use

A penicillin of the formula: ##STR1## wherein ##STR2## is a six-membered heteroaromatic ring containing 1 or 2 nitrogen atoms as the hetero atom, Y is hydrogen, lower alkanoyl or lower alkoxycarbonyl, R.sub.1 and R.sub.2 are each hydrogen, lower alkyl, lower alkanoyl, benzoyl, lower alkylmercapto, hydroxyl, mercapto, hydroxy(lower)alkyl, halogen or cyano or R.sub.1 and R.sub.2 may link together to form a lower alkylene chain which may be substituted with an oxo group, and Z is phenyl, hydroxyphenyl, lower alkyl, cyclohexadienyl, thienyl or isothiazolyl, which is prepared by reacting a compound of the formula: ##STR3## wherein Z is as defined above or its derivative with a carboxylic acid of the formula: ##STR4## wherein ##STR5## and R.sub.2 are each as defined above or its reactive derivative, if necessary, followed by hydrolysis or acylation of the resulting product and/or elimination of any protective group and which is useful as an antimicrobial agent against various gram-positive and gram-negative bacteria including Pseudomonas.

Penicillins

Penicillins of the formula: ##STR1## wherein R is an unsubstituted phenyl group or a substituted phenyl group having one or more hydroxyl groups or a cyclohexadienyl group and A represents a monocyclic or polycyclic nitrogen-containing heterocyclic aromatic ring, which are useful as antimicrobial agents having a broad antimicrobial spectrum against gram-positive and gram-negative bacteria including Pseudomonas and can be produced advantageously from the phenacyl ester of 6-aminopenicillanic acid through a series of steps.

Penicillins and their preparation

Novel penicillins of the formula: ##STR1## wherein the ring A is a benzene ring or a 5 or 6-membered heteroaromatic ring containing one or two nitrogen atoms as the hetero atom, on which one or more of lower alkyl, lower alkoxy, lower alkylthio, lower haloalkyl, lower alkylenedioxy halogen, hydroxyl, nitro, free or protected amino, lower alkylamino, di(lower)alkylamino and lower alkanoylamino may be present, Z is a nitrogen atom or a methylene group, X is an oxygen atom or a sulfur atom, Y is a hydrogen atom, a lower alkoxycarbonyl group or a lower alkanoyl group, R.sub.1 is a free or protected hydroxyl group and R.sub.2 and R.sub.3 are each a hydrogen atom or a halogen atom, and their non-toxic pharmaceutically acceptable salts, and their preparation.

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Hirotada Yamada