Banyu Pharmaceutical Co. Ltd

Susumu Nakagawa

Ryosuke Ushijima

Koji Yamada

Fumio Nakano

Hiroshi Fukatsu

Satoru Kuroyanagi

Akira Asai

Ryuji Mitomo

Satoshi Murase

Yoshiharu Tanaka

Norikazu Otake

Eiichi Mano

Makoto Ishihara

Yoshiaki Kato

Shinji Kato

Norikazu Ohtake

Moriaki Ishikawa

Osamu Okamoto

Kunio Suzuki

Tetsuji Miyano

Yoshiaki Katoh

Katsumi Yamamoto

Kenji Matsuyama

Kenji Niiyama

Masaaki Hosoi

Shigemitsu Okada

Hiroshi Takeshita

Norikazu Ban

Ryosuke Ushizima

Hideaki Imamura

Masayuki Ogawa

Hideki Jona

Hideo Kiyonaga

Minoru Sanada

A compound represented by the general formula

Carbapenem derivatives

A compound of the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or a methyl group, R.sup.2 is a hydrogen atom or a negative charge, R.sup.3 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkoxy group, a lower alkanoyloxy group, an amino group, an N-lower alkylamino group, an N,N-di-lower alkylamino group, a lower alkanoylamino group, an aroylamino group, a (lower alkylsulfonyl)amino group, a sulfamoylamino group, a cyano group, a nitro group, a group of --COOR.sup.4 (wherein R.sup.4 is a hydrogen atom or a lower alkyl group) or a group of --CON(R.sup.5)R.sup.6 (wherein each of R.sup.5 and R.sup.6 which may be the same or different, is a hydrogen atom or a lower alkyl group, or R.sup.5 and R.sup.6 form together with the adjacent nitrogen atom a heterocyclic group selected from the group consisting of an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidyl group, a piperazinyl group, a 4-lower alkyl piperazinyl group and a morpholino group), A is a linear or branched lower alkylene group, X is a group of --N(R.sup.7)R.sup.8 (wherein each of R.sup.7 and R.sup.8 which may be the same or different, is a hydrogen atom or a lower alkyl group) or a group of --N.sup.+ (R.sup.9)(R.sup.10)R.sup.11 (wherein each of R.sup.9, R.sup.10 and R.sup.11 which may be the same or different, is a lower alkyl group), provided that when A is a linear lower alkylene group, R.sup.3 is other than a hydrogen atom; or a pharmaceutically acceptable salt or ester thereof.

Aminoalkylpyrrolidinylthiocarbapenem derivatives

A compound of the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or a methyl group, R.sup.2 is a hydrogen atom or a negative charge, X is a group of --N(R.sup.3)R.sup.4 (wherein R.sup.3 is a lower alkyl group, and R.sup.4 is a hydrogen atom or a lower alkyl group) or a group of --N.sup.+ (R.sup.5)(R.sup.6)R.sup.7 (wherein each of R.sup.5, R.sup.6 and R.sup.7 which may be the same or different, is a lower alkyl group), and n is an integer of from 2 to 4; or a pharmaceutically acceptable salt or ester thereof.

Alkylaminoalkylpyrrolidinylthiocarbapenem derivatives

A compound of the formula: ##STR1## wherein R.sup.11 is hydrogen, lower alkyl, haloloweralkyl, lower alkenyl, lower alkynyl or cycloalkyl and R.sup.21 is a group selected from the group consisting of: ##STR2## wherein R.sup.3 -R.sup.5, R.sup.31, R.sup.32, R.sup.41, R.sup.42 and R.sup.51 are as defined herein, and W is chlorine or bromine, is prepared by reacting a compound of the formula:

Process for producing enyne derivatives

Carbapenem compounds of formula I and their pharmaceutically acceptable salts and esters are provided: ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, p, q and r are as defined herein, which are useful as antibacterial agents.

2-(substituted pyrrolidinylthio) carbapenem derivatives

(E)-N-(3-Chloro-2-propenyl)-N-methyl-1naphthylenemethanamine and (E)-3-chloro-N-(3-chloro-2-propenyl)-N-methylbenzo[b]thiophene-7-methanami ne which are useful as intermediates in the production of enyne compounds which exhibit squalene epoxidase inhibiting activity and anti-Eumycetes activity.

Intermediates for producing enyne derivatives

The present invention relates to a compound represented by the structural formula I: ##STR1## its pharmaceutically acceptable salt or ester, or its crystalline, which is a novel optically active compound useful as a curing agent for bacterial infections, a process for production thereof and a use thereof.

Cephalosporin derivatives

A compound of the formula: ##STR1## wherein R is a hydrogen atom or a methyl group, R.sup.1 is a hydrogen atom or a negative charge, each of R.sup.2 and R.sup.3 which may be the same or different, is a hydrogen atom, a lower alkyl group, a hydroxy lower alkyl group, a formimidoyl group, an acetoimidoyl group, --COOR.sup.4, --CON(R.sup.5)R.sup.6, --N(R.sup.5)R.sup.6, --CH.sub.2 COOR.sup.4, --CH.sub.2 N(R.sup.5)R.sup.6 or --CH.sub.2 CON(R.sup.5)R.sup.6 (wherein R.sup.4 is a hydrogen atom or a lower alkyl group, each of R.sup.5 and R.sup.6 which may be the same or different, is a hydrogen atom or a lower alkyl group, or R.sup.5 and R.sup.6 form together with the adjacent nitrogen atom a heterocyclic group selected from the group consisting of an aziridinyl group, an azetidinyl group, a pyrrolidinyl group and a piperidyl group), A is .dbd.NR.sup.7, .dbd.N.sup.+ (R.sup.7)R.sup.8, wherein each of R.sup.7 and R.sup.8 which may be the same or different, is a hydrogen atom, a lower alkyl group, a hydroxy lower alkyl group, a formimidoyl group, an acetoimidoyl group, --COOR.sup.4, --CON(R.sup.5)R.sup.6, --N(R.sup.5)R.sup.6, --CH.sub.2 COOR.sup.4, --CH.sub.2 N(R.sup.5)R.sup.6 or --CH.sub.2 CON(R.sup.5)R.sup.6 (wherein R.sup.4, R.sup.5 and R.sup.6 are as defined above), p is an integer of from 0 to 3, and q is an integer of from 1 to 3; or a pharmaceutically acceptable salt or ester thereof.

2-(substituted pyrrolidinylthio)carbapenem derivatives

A compound of the formula: ##STR1## wherein R is a hydrogen atom or a methyl group, R.sup.1 is a hydrogen atom or a negative charge, R.sup.2 is a lower alkyl group, a lower alkyl group substituted with a hydroxyl group or --COOR.sup.3 (wherein R.sup.3 is a hydrogen atom or a lower alkyl group), A is .dbd.NH, .dbd.NR.sup.4 or .dbd.N(R.sup.4)R.sup.5 (wherein each of R.sup.4 and R.sup.5 which may be the same or different, is a lower alkyl group or a lower alkyl group substituted with a hydroxyl group), p is an integer of from 0 to 3, and each of q and r which may be the same or different, is an integer of from 0 to 5, provided that q and r are not simultaneously 0 and q +r.ltoreq.6; or a pharmaceutically acceptable salt or ester thereof.

A compound of the formula: ##STR1## wherein R.sup.11 is hydrogen, lower alkyl, haloloweralkyl, lower alkenyl, lower alkynyl or cycloalkyl; R.sup.21 is a group of the formula: ##STR2## wherein each of R.sup.3, R.sup.31, and R.sup.32 which may be the same or different, is hydrogen or lower alkyl, each of R.sup.4, R.sup.5, R.sup.41 and R.sup.51, which may be the same or different, is hydrogen, halogen, hydroxyl, lower alkyl or lower alkoxy, R.sup.42 is hydroxyl, halogen, R.sup.8 --O--, or R.sup.6 --X--Y-- wherein R.sup.6 is phenyl or thienyl which may have one or two substituents each of X and Y, which may be the same or different, is oxygen, sulfur, carbonyl, --CHR.sup.8 -- or --NR.sup.b, or X and Y together form a vinylene group or an ethynylene group, provided that when either one of X and Y is oxygen, sulfur or --NR.sup.b, the other is carbonyl or --CHR.sup.a, and R.sup.7 is lower alkyl or cycloalkyl which may be substituted by hydroxy or lower alkoxy, phenyl or tri-lower alkylsilyl; and W is chlorine or bromine.

A process for producing an enyne derivative, and intermediate, which is useful for preparing compounds showing strong inhibiting activities against squalane epoxidase of Eumycetes and strong anti-cholesterol activities. The process comprises reacting a compound of the formula: ##STR1## wherein W is a halogen atom, with an acetylene derivative, in the presence of a palladium catalyst, to obtain a compound of the formula: ##STR2## and, if necessary, N-alkylating this compound.

A process for producing a 2-(unsubstituted or carbon-substituted)-1-carbapen-2-em-3-carboxylic acid derivative, which comprises reacting a 2-trifluoromethanesulfonyloxy-1-carbapen-2-em-3-carboxylic acid derivative or the 1-carbapen-2-em-3-carboxylic acid derivative derived from a 2-oxo-1-carbapenam-3-carboxylic acid derivative and trifluoromethanesulfonic anhydride, and a stannane derivative in an inert solvent in the presence of a palladium compound and a salt.

Process for producing 2-carbon-substituted carbapenem derivatives

A process for producing an enyne derivative, and intermediate, which is useful for preparing compounds showing strong inhibiting activities against squalane.epoxidase of Eumycetes and strong anti-cholesterol activities. The process comprises reacting a compound of the formula:

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Okazaki, Japan

Susumu Nakagawa