Sumitomo Chemical Company, Limited

Yasuko Eda

Toshiaki Komatsu

Takenari Nakagome

Akio Izawa

Hisao Tobiki

Kozo Shimago

Hiroshi Noguchi

Hirotada Yamada

Norihiko Tanno

Iwao Nakatsuka

Shigeru Okano

Kenji Irie

Kousaku Okamura

Hideo Agui

Mitsuo Nakashita

Toru Mitani

Kosaku Okamura

Eiichi Murayama

Toyozo Katsura

Yasushi Taira

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

Thiazolo[5,4-f]quinoline-8-carboxylic acid derivatives having either the general formula (I): ##STR1## wherein R.sub.1 is a lower alkyl group, a lower alkenyl group or a benzyl group; or the general formula (III-a): ##STR2## WHEREIN R.sub.3 is a lower alkyl group and X is a halogen atom; and methods for the preparation thereof. The compounds of the general formula (I) are useful as antibacterial agents against gram-negative and gram-positive bacteria. The compounds of the general formula (III-a) are useful as antifungal agents against eumycetes and also as an intermediate in a peparation of the compounds of the general formula (I).

Thiazolo(5,4-f)quinoline-8-carboxylic acid derivatives

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

Novel antibacterial agents consisting of a 2,3,5,8-tetrahydro-5-alkoxy-8-oxofuro(2,3-g)quinoline-7-carboxylic acid of the formula: ##STR1## wherein R is C.sub.1 -C.sub.4 alkyl, a process for producing the derivatives and pharmaceutical compositions containing the same. The above-identified derivatives possess antibacterial activity against gram-negative bacteria at test concentration levels of about 0.0001 to 1.0 mg/cc.

2,3,5,8-Tetrahydro-5-alkoxy-8-oxofuro(2,3-g)quinoline-7-carboxylic acid

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

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.

Novel penicillins and their preparation

Novel penicillins of the formula ##SPC1## Wherein ##EQU1## represents a substituted or unsubstituted benzene or nitrogen atom-containing heteroaromatic ring which may be substituted, ##EQU2## represents a pyridine, pyrazine or pyridazine ring, X represents an oxygen or sulfur atom, Y represents a hydrogen atom or a loer alkoxycarbonyl or lower alkanoyl group, and R.sub.1, R.sub.2 and R.sub.3 are each a hydrogen or halogen atom or a nitro, lower alkylamino, di(lower)alkylamino, aine, lower alkoxycarbonylamino, lower alkanoylamino, amino(lower)alkyl, lower alkyl, lower alkoxy, hydroxyl, sulfamoyl, trifluoromethyl, lower alkylthio or lower alkylsulfonyl group, excluding the cases where all of R.sub.1, R.sub.2 and R.sub.3 are hydrogen atoms and where R.sub.1 is a hydroxyl group and R.sub.2 and R.sub.3 are each a hydrogen or halogen atom, and their nontoxic, pharmaceutically acceptable salts, which can be prepared by reacting a carboxylic acid of the formula: ##EQU3## wherein ##EQU4## X and Y are each as defined above or its reactive derivative with a compound of the formula: ##SPC2## Wherein R.sub.1, R.sub.2 and R.sub.3 are each as defined above or its reactive derivative, and are ueful as antimicrobial agents against gram-positive and gram-negative bacteria including Pseudomonas.

Penicillins substituted with heterocyclic and substituted phenyl groups

Novel penicillins of the formula: ##SPC1## 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.

Naphthyridine-3-carboxamido-benzylpenicillins and salts thereof

Thiazolo[5,4-f]quinoline-8-carboxylic acid derivatives having either the general formula (I): ##SPC1## wherein R.sub.1 is a lower alkyl group, a lower alkenyl group or a benzyl group; or the general formula (III-a): ##SPC2## Wherein R.sub.3 is a lower alkyl group and X is a halogen atom; and methods for the preparation thereof. The compounds of the general formula (I) are useful as antibacterial agents against gram-negative and gram-positive bacteria. The compounds of the general formula (III-a) are useful as antifungal agents against eumycetes and also as an intermediate in a preparation of the compounds of the general formula (I).

A penicillin of the formula: ##SPC1## Wherein A is a substituted or unsubstituted condensed aromatic carbocyclic or heterocyclic ring, R is hydrogen or lower alkyl, X is oxygen or sulfur, Y is hydrogen, lower alkyl, lower alkanoyl or lower alkoxycarbonyl and Z is phenyl or thienyl which can be produced by reacting 6-aminopenicillanic acid or its ester with a carboxylic acid of the formula: ##SPC2## Wherein A, R, X, Y and Z are each as defined above or its reactive derivative. The said penicillin and its non-toxic salts have a broad antimicrobial spectrum against various gram-positive and gram-negative bacteria, and they exhibit characteristically a strong antimicrobial activity against Pseudomonas.

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Toyonaka, Japan

Yasuko Eda