Yoshitomi Pharmaceutical Industries, Ltd.

Hideki Ao

Kazuhiko Araki

Kenichi Aihara

Minoru Obata

Jun Inui

Tomohiko Kimura

Tsutomu Yamanaka

Kazuyuki Kawasaki

Yoshifumi Ikeda

Hiroshi Mikashima

Shinro Setoguchi

Tsuyoshi Kuroda

Akihiko Moriguchi

Katsuo Arimura

Yasuhiko Ishida

Shin-ichi Uesato

8-Methoxy-quinolonecarboxylic acid derivatives of the formula ##STR1## wherein R.sub.1 is a hydrogen atom, a lower alkyl, a phenylalkyl or an ester residue hydrolyzable in the living body, R.sub.2 is a hydrogen atom or methyl and n is an integer of 1, optical isomers thereof, pharmaceutically acceptable salts thereof and hydrates thereof. The 8-methoxy-quinolonecarboxylic acid derivatives of the present invention have enforced and a wide range of in vitro and in vivo antibacterial effects against Gram-positive bacteria, while retaining a strong antibacterial effect against Gram-negative bacteria, that the conventional quinolonecarboxylic acid antibacterial agents have. In addition, the compounds of the present invention scarcely show problematic side-effects and are low toxic. Therefore, they are expected to show superior clinical effects as antibacterial agents.

8-methoxy-quinolonecarboxylic acid derivatives

Novel .beta.-form crystals of 6-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-3,4-dihydro-2(1H)-quinolino ne useful as cardiotonics.

Thiadiazine compound with a novel crystalline form

An oxodiazine compound of the formula: ##STR1## or a pharamceutically acceptable acid addition salt thereof, wherein each of R.sup.1 and R.sup.2 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkoxy-C.sub.1-4 alkoxy, phenyl-C.sub.1-4 alkyl-oxy which may be optionally substituted by at least one substituent selected from the group consisting of halogen, C.sub.1-4 alkyl and C.sub.1-4 alkoxy on the phenyl nucleus, or phenyl which may be substituted by at least one substituent selected from the group consisting of halogen, C.sub.1-4 alkyl and C.sub.1-4 alkoxy on the phenyl nucleus; X is --S--, --CH.dbd.N-- or --C(R.sup.3).dbd.C(R.sup.4)--, where each of R.sup.3 and R.sup.4 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkoxy-C.sub.1-4 alkoxy or phenyl-C.sub.1-4 alkyl-oxy which may be optionally substituted by at least one substituent selected from the group consisting of halogen, C.sub.1-4 alkyl and C.sub.1-4 alkoxy on the phenyl nucleus; and one of A and B is oxygen, sulfur or --NH-- and the other is --C(R.sup.5) (R.sup.6)--, where each of R.sup.5 and R.sup.6 is hydrogen or C.sub.1-4 alkyl. Such compounds are useful as antithrombotic agents, antianginal agents, coronary circulation improving agent, cerebral circulation improving agents, peripheral circulation improving agents, analgesics and antiinflammatory agents.

Oxodiazine compounds and pharmaceutical compositions thereof

A thiadiazine compound of the formula: ##STR1## a method for preparing said compound and a pharmaceutical composition containing said compound, wherein X is methylene which may be optionally substituted by an alkyl of up to 3 carbon atoms; R is hydrogen atom or methyl group; and n is an integer of 1 or 2. Since the compounds exhibit potent cardiotonic and coronary vasodilator activities and further inhibitory activity on platelet aggregation, they are useful as cardiotonic and antithrombotic drugs.

Thiadiazine compounds

1,4-Dihydropyridine-3,5-dicarboxylic acid ester derivatives of the general formula: ##STR1## or acid addition salts thereof, wherein W is --CH.dbd. or --N.dbd.; Y is --CH.dbd.CH--, --O--, --S--, --CH.dbd.N(O)p-- (p is zero or 1) or --N(R)-- (R is hydrogen or lower alkyl); X.sup.1, X.sup.2 and X.sup.3 are the same or different, and are each hydrogen, halogen, nitro, trifluoromethyl, cyano or lower alkylthio; Z is aryl or 5- or 6-membered aromatic heterocyclic ring (which may have a substituent or two or three substituents which may be the same or different, and the substituent may be halogen, lower alkyl, lower alkoxy, lower alkanoylamino, cyano, nitro, lower alkylthio, trifluoromethyl, sulfamoyl, di-lower alkylsulfamoyl, amino or di-lower alkylamino); ##STR2## is 5- to 7-membered heterocyclic ring which may have nitrogen atom, oxygen atom, sulfur atom or unsaturated bond on the ring, and may be substituted by lower alkyl, lower alkoxycarbonyl, lower alkanoylamino, ethylenedioxy or --(CH.sub.2).sub.m --OR.sup.4 (R.sup.4 is hydrogen, lower alkyl or lower alkanoyl and m is 0, 1 or 2); R.sup.1 and R.sup.2 are the same or different, and are each lower alkyl; R.sup.3 is lower alkyl, aralkyl, heteroaralkyl; and n is an integer 1 to 5. Such compounds are useful as antihypertensive agents and as therapeutic agents for cardiac and cerebral circulation disorders.

1,4-dihydropyridine-3,5-dicarboxylic acid ester derivatives and

A dihydropyridine compound of the formula: ##STR1## or a pharmaceutically acceptable acid addition salt thereof, wherein Het is 5- or 6-membered aromatic heteroaryl, R.sup.1 and R.sup.2 are each lower alkyl, R.sup.3 is lower alkyl, R.sup.4 is hydrogen, lower alkyl or aralkyl, R.sup.5 is lower alkyl or aralkyl, and n is 1 or 2. Such compounds are useful as therapeutic agents for myocardial and cerebral ischemic syndroms and hypertension.

Dihydropyridine compounds

1,4-Dihydropyridine-3,5-dicarboxylic acid ester derivatives

Imidazolido[1,5-c]thiazolidine-3-spiro-4'-piperidine compounds of the formula: ##SPC1## Wherein R.sup.1 represents a member selected from the group consisting of a hydrogen atom, an alkyl group of from 1 to 4 carbon atoms, a benzyl group, a p-chlorobenzyl group, a 4,5-dimethoxybenzyl group, a 4,5,6-trimethoxybenzyl group, a phenethyl group, an acetyl group, a benzoyl group, a trimethoxybenzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a 4,4-bis(p-fluorophenyl)butyl group and a group of the formula ##SPC2## (in which Y represents a member selected from the group consisting of H, F and CH.sub.3 O, and n represents an integer of 1, 2 or 3); R.sup.2 represents a member selected from the group consisting of a hydrogen atom, an alkyl group of from 1 to 4 carbon atoms, an allyl group, a propargyl group, a cyclohexyl group, a phenyl group, a chlorophenyl group, a dichlorophenyl group, a tolyl group, a nitrophenyl group, a naphthyl group, a benzyl group, a phenethyl group and a cinnamyl group; and X represents a member selected from the group consisting of an oxygen atom and a sulphur atom; and pharmaceutically acceptable acid addition salts thereof. These compounds are useful as drugs for the treatment of schizophrenia, mania and various psychoneuroses.

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Oita, Japan

Hideki Ao