Takeda Chemical Industries, Inc.

Tatsuo Chemical Ind., Ltd.

Mitsuo Numata

Masayoshi Yamaoka

Isao Minamida

Mitsuru Shiraishi

Toshio Miyawaki

Tatsuo Nishimura

Susumu Tsushima

Yoshinobu Yoshimura

Norichika Matsumoto

Akio Miyake

Shinji Terao

Yoshio Imashiro

Isao Mimamida

Kunio Takanohashi

Tomoyuki Fujii

Mitsura Shiraishi

A compound of the formula: ##STR1## wherein R.sub.1 is a hydrogen atom or a lower alkyl group; R.sub.2 is an unsubstituted or lower alkyl-substituted alicyclic alkyl group of 3 to 12 carbon atoms or a C.sub.3-6 alicyclic alkyl-substituted lower alkyl group or a pharmaceutically acceptable salt thereof, processes for preparing the same, a pharmaceutical composition thereof are provided. The compound has an improved absorbability and can be orally applied as antibiotics.

Cephalosporin ester derivatives

Disclosed 2-(syn)-hydroxyimino-acetamide derivatives of the formula: ##STR1## wherein Y is hydrogen, hydroxyl, an acyloxy, carbamoyloxy, a quaternary ammonium or a nitrogen-containing heterocyclic ring-substituted thio group; or pharmaceutically acceptable salts or esters thereof are useful as antibacterial agents. Also disclosed are processes for producing them.

Cephalosporin derivatives

A compound of the formula ##STR1## wherein (1) R.sub.1 is a lower alkyl group of 2 to 6 carbon atoms or a cycloalkyl group of 5 to 7 carbon atoms and R.sub.2 is a cycloalkyl group of 5 to 7 carbon atoms or a lower alkyl group of 1 to 3 carbon atoms which is substituted by a cycloalkyl group of 5 to 7 carbon atoms or by a phenyl group, or (2) R.sub.1 is a cycloalkyl group of 5 to 7 carbon atoms and R.sub.2 is a lower alkyl group of 1 to 5 carbon atoms, or a pharmaceutically acceptable salt thereof, processes for preparing the same and a pharmaceutical composition thereof are provided. The compound can orally be applied as antibiotics having improved bioavailability.

1-Acyloxyalkyl esters of cephalosporin

A compound of the formula: ##STR1## wherein R is 2-methylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, an alkyl group of 6 or 7 carbon atoms, or an alkenyl group of 2 to 7 carbon atoms, or a pharmaceutically acceptable salt thereof and processes for preparing the same are provided. The compound can orally be applied as antibiotics having improved absorbability.

A compound of the formula: ##STR1## or a pharmaceutical acceptable salt thereof, processes for preparing the same and a pharmaceutical composition containing the compound or the salt thereof mentioned above are provided. The compound has antibiotic activity and has improved absorbability.

Cephalosporin esters, their production and use

A compound of the formula: ##STR1## wherein R.sub.1 stands for n-propyl or isopropyl; and R.sub.2 stands for n-butyl, isobutyl, n-pentyl, n-hexyl or 2-ethylbutyl, or a pharmaceutically acceptable salt thereof, processes for preparing the same and a pharmaceutical composition thereof are provided. The compound can orally be applied as antibiotics having improved bioavailability.

A compound of the formula: ##STR1## wherein R.sup.1 represents hydrogen or an alkyl group, X represents oxygen or sulfur or a group of formula -NR.sup.2 (where R.sup.2 is hydrogen or an alkyl group and in the case of alkyl, it may form a ring jointed with R.sup.1), and Y represents acetoxy group or a group of formula -SR.sup.3 (where R.sup.3 is a nitrogen-containing heterocyclic group), or a pharmaceutically acceptable salt thereof, is found to have a broad antimicrobial spectrum and, in particular, effective against gram-negative bacteria including Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Proteus morganii, as well as gram positive ones. Thus, these compounds may be used for antimicrobial agents in therapeutical purposes.

2-Oxoazetidine derivatives represented by the formula; ##STR1## wherein R.sup.1 stands for phthalimido group, benzyloxycarbonylamino group, a halogen on an alkyl group which may have hydroxyl group, R.sup.2 stands for hydrogen, an alkyl group, an alkylthio group or an arylthio group, and R.sup.3 and R.sup.4 independently stand for an acyl group or cyano group, and a method of preparing them, which is shown by the following reaction scheme; ##STR2## wherein R.sup.5 stands for a carboxyl-protective group, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are of the same meanings as defined above. This compound (I) can be utilized as intermediates for carba-2-penem compounds having excellent anti-bacterial activity and .beta.-lactamase inhibitory activity.

2-Oxoazetidine derivatives and production thereof

A compound of the formula: ##STR1## wherein R.sup.1 represents hydrogen or an alkyl group, X represents oxygen or sulfur or a group of formula --NR.sup.2 (where R.sup.2 is hydrogen or an alkyl group and in the case of alkyl, it may form a ring jointed with R.sup.1), and Y represents acetoxy group or a group of formula --SR.sup.3 (where R.sup.3 is a nitrogen-containing heterocyclic group), or a pharmaceutically acceptable salt thereof, is found to have a broad antimicrobial spectrum and, in particular, effective against gram-negative bacteria including Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Proteus morganii, as well as gram positive ones. Thus, these compounds may be used for antimicrobial agents in therapeutical purposes.

Disclosed are 2-(syn)-hydroxyimino-acetamide derivatives of the formula: ##STR1## wherein Y is hydrogen, hydroxyl, an acyloxy, carbamoyloxy, a quaternary ammonium or a nitrogen-containing heterocyclic ring-substituted thio group; or pharmaceutically acceptable salts or esters thereof are useful as antibacterial agents. Also disclosed are processes for producing them.

7-[2-(2-Imino-4-thiazolin

A novel cephalosporin derivative of the formula: ##STR1## [wherein X is hydrogen, hydroxyl, acyloxy, alkoxy, carbamoyloxy, quaternary ammonium or a group of the formula --SR.sup.1 (where R.sup.1 is a nitrogen-containing heterocyclic group)] or a pharmaceutically acceptable salt or ester thereof is found to have potent antibiotic activity against various bacteria, particularly against gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Proteus mirabilis, Proteus morganii, Proteus rettgeri and Citrobacter freundii.

Cephalosporins

A novel compound of the formula: ##STR1## wherein R is lower alkyl or a group of the formula ##STR2## where R.sup.1 and R.sup.2 are the same or different and each is hydrogen, carboxyl or halogen; Y is acyloxy or a group of the formula --S--Het where Het is a nitrogen-containing heterocyclic group which may optionally be substituted, or a pharmaceutically acceptable salt thereof is found to be effective for treatment of diseases in animals including domestic fowls and human beings, particularly the infectious diseases caused by gram-positive and gram-negative bacteria.

7-[2-(2-Aminothiazol-4-yl)-2-substituted thio-acetamido] cephalosporins

Novel [2-(syn)-carbamoyloximinoacetamido]cephalosporins of the formula: ##STR1## [wherein, Y.sup.1 is hydrogen, hydroxyl, carbamoyloxy, acyloxy, quaternary ammonium or nitrogen-containing heterocyclic thio; R.sup.1 is alkyl, aralkyl or aryl; R.sup.2 is hydrogen or an ester residue; k is 0 or 1] and a salt thereof show strong antibacterial activities particularly against Gram-negative bacteria and they are useful as antibacterial agents.

Growing community of inventors

Osaka, Japan

Mitsuo Numata