Banyu Pharmaceutical Co. Ltd

Fumio Nakano

Susumu Nakagawa

Ryosuke Ushijima

Koji Yamada

Norikazu Otake

Eiichi Mano

Hiroshi Fukatsu

Norikazu Ohtake

Akira Asai

Satoru Kuroyanagi

Ryuji Mitomo

Satoshi Murase

Yoshiharu Tanaka

Moriaki Ishikawa

Masashi Kawasaki

Kenji Matsuyama

Toshiaki Mase

Kenji Niiyama

Masaaki Hosoi

Shouichi Hiraga

Asayuki Kamatani

Hiroshi Takeshita

Masayuki Hagiwara

A process for preparing indolopyrrolocarbazole derivatives &lsqb;I&rsqb; by trating a compound &lsqb;V&rsqb; with a base in an inert solvent to prepare a compound &lsqb;IV&rsqb;, reacting the compound &lsqb;IV&rsqb; with a compound &lsqb;III&rsqb;to prepare a compound &lsqb;II&rsqb;, and deblocking the compound &lsqb;II&rsqb;; intermediates &lsqb;II&rsqb;, &lsqb;III&rsqb; and &lsqb;IV&rsqb;; and a process for preparing compounds &lsqb;III&rsqb;: &lsqb;wherein Y is hydrogen, C alkyl, phenyl, benzyloxymethyl, or aralkyl; R , R , R , R , R , and R are each independently a hydroxyl-protecting group; R and R are each independently hydrogen or a hydroxyl-protecting group; and X is an acid molecule&rsqb;. The above process is a safe and easy industrial process for preparing indolopyrrolocarbazole derivatives &lsqb;1&rsqb; useful as antitumor agents.

Process for preparing indolopyrrolocarbazole derivatives, intermediates therefor, and preparation process of the intermediates

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

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.

The present invention relates to a compound having the formula: ##STR1## wherein R is a hydrogen atom, a carboxyl-protecting group or a negative charge and Q is a hydrogen atom, a halogen atom, a hydroxyl group, an acetoxy group, a carbamoyloxy group, an azide group, a substituted or unsubstituted quarternary ammonio group or a substituted or unsubstituted heterocyclic thio group having at least one hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom, or a non-toxic salt or physiologically hydrolyzable non-toxic ester thereof; a process for producing it; and an antibacterial agent comprising it as an active ingredient. Further, the present invention also relates to a compound having the formula: ##STR2## wherein R.sup.3 is a hydrogen atom or an amino-protecting group, and each of R.sup.4 and R.sup.5 which may be the same or different is a hydrogen atom or a carboxyl-protecting group, or a salt thereof; and a process for producing it.

1-carboxy-1-vinyloxyimino aminothiazole cephalosporin 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 lower alkyl group, each of R.sup.3, R.sup.4 and R.sup.5 is a hydrogen atom or a lower alkyl group, or R.sup.3 and R.sup.4 together form a methylene group, an ethylene group or a propylene group, or R.sup.4 and R.sup.5 form together with the adjacent nitrogen atom an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidino group, a piperazinyl group or a morpholino group; or a pharmaceutically acceptable salt or ester thereof.

2-(2-vinylpyrrolidinylthio)carbapenem derivatives

The present invention relates to stable crystalline (6R,7R)-7-(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxylimino)ac etamido]-3-(5,6-dihydroxy-2-methyl-2-isoindolinium)methyl-3-cephem-4-carbox ylate sulfate or its hydrate, a process for production of the compound and (6R,7R)-7-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino) acetamido]-3-(5,6-dihydroxy-2-methyl-2-isoindolinium)methyl-3-cephem-4-carb oxylate hydrochloride or its hydrate which is a starting material useful for the production of the desired compound of the present invention.

Crystalline cephalosporin compounds

A compound having the formula: ##STR1## wherein R is a straight chain or branched chain lower alkyl, cyclic lower alkyl, lower alkenyl (except for 1-carboxy-1-vinyl), lower alkynyl, aralkyl, phenyl or 2-pyrrolidon-3-yl group which may be substituted, and Q is ##STR2## (wherein R.sup.1 is a hydrogen atom or an acetyl group, R.sup.2 is a hydrogen atom, a carboxyl group or a carboxymethyl group, Y is a sulfur atom or an oxygen atom, Z is a sulfur atom, an oxygen atom or an imino group which may be substituted by a lower alkyl group); or a pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof.

Cephalosporin derivatives, and antibacterial agents

The present invention relates to stable cyrstalline (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)ac etamido]-3-(5,6-dihydroxy-2-methyl-2-isoindolinium)-3-cephem-4-carboxylate sulfate or its hydrate, a process for production of the compound and (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxyl-1-methylethoxyimino)a cetamido]-3-(5,6-dihydroxy-2-methyl-2-isoindolinium)methyl-3-cephem-4-carbo xylate hydrochloride or its hydrate which is a starting material useful for the production of the desired compound of the present invention.

A compound having the formula: ##STR1## wherein R.sup.1 is an amino group or a protected amino group, R.sup.2 is a hydrogen atom or a protecting group for a hydroxyl group, R.sup.3 represents negative charge, a hydrogen atom or a protecting group for a carboxyl group, and n is 0 or 1, and a salt thereof.

7-amino-3-(substituted isoindolinium)methyl-3-cephem derivatives

This invention provides a class of new indole derivatives which are useful as medicinal compounds having a mild inhibitory effect on the gastric acid secretion as well as a remarkably cytoprotective effects on gastric muscosa, and which are represented by the general formula: ##STR1##

Indole derivatives having gastric and antisecretory and cytoprotective

A compound having the formula: ##STR1## wherein R.sup.1 is a straight chain, branched chain or cyclic lower alkyl group which may be substituted by a carboxyl group, and each of R.sup.2 and R.sup.3 which may be the same or different, is a hydrogen atom, a hydroxyl group, a methoxy group or an acetoxy group, and R.sup.4 is a hydroxyl group, a methoxy group or an acetoxy group; or a pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof.

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Okazaki, Japan

Fumio Nakano