Yoshitomi Pharmaceutical Industries, Ltd.

Osamu Yaoka

Tsutomu Yamanaka

Tsuguo Ikebe

Tetsuya Tahara

Tohru Nakajima

Toshio Seki

Toru Nakao

Yutaka Maruyama

Ichiro Hakamada

Takanori Oe

Kazuhiro Goto

Shinro Setoguchi

Shu Murakami

Yohji Miura

A benzopyran compound of the general formula (I) ##STR1## wherein A represents --OR.sup.1 or --NH--COR.sup.2 ; R.sup.3 represents hydrogen, a lower alkyl, a lower alkoxy, amino, a mono- or di-lower alkylamino, an amino-lower alkyl, a hydroxy-lower alkyl, a halo-lower alkyl, a lower alkoxy-lower alkyl, an acyloxy-lower alkyl, a lower alkoxycarbonyl-lower alkyl, an aryl or a heteroaryl, or R.sup.2 and R.sup.3 combinedly together form an alkylene having 1 to 2 carbon atoms; R.sup.4 and R.sup.5 are the same or different, and respectively represent hydrogen or a lower alkyl, or combinedly together form an alkylene having 2 to 5 carbon atoms; R.sup.6 represents hydroxyl group, formyloxy, an alkanoyloxy, a haloalkanoyloxy, a lower alkoxycarbonyloxy, an aroyloxy, a heteroaroyloxy, carbamoyloxy, a mono- or di-lower alkylcarbamoyloxy and R.sup.7 represents hydrogen, or R.sup.6 and R.sup.7 combinedly together form a bond and X and Y are the same or different, and respectively represent hydrogen, halogen, nitro, cyano, a lower alkyl, a lower alkoxy, a halo-lower alkyl, carboxyl, formyl, an alkanoyl, an aroyl, a halo-alkanoyl, carbamoyl, a lower alkylsulfinyl, an arylsulfinyl, a lower alkylsulfonyl, an arylsulfonyl, sulfonamido or a mono- or di-lower alkylsulfonamido, or their pharmaceutically acceptable salts and its pharmaceutical use.

Benzopyran compound and its pharmaceutical use

A benzopyran compound of the general formula (I) ##STR1## wherein A represents --OR.sup.1 or --NH--COR.sup.2 (wherein R.sup.1 represents hydrogen, a lower alkyl, formyl, an alkanoyl, an aroyl or an aralkyl and R.sup.2 represents hydrogen, a lower alkyl, a lower alkoxy, amino, mono- or di-lower alkylamino, an amino-lower alkyl, a hydroxy-lower alkyl, a halo-lower alkyl, a lower alkoxy-lower alkyl, an acyloxy-lower alkyl, a lower alkoxycarbonyl-lower alkyl, an aryl or a heteroaryl); R.sup.3 represents hydrogen, a lower alkyl, a lower alkoxy, amino, a mono- or di-lower alkylamino, an amino-lower alkyl, a hydroxy-lower alkyl, a halo-lower alkyl, a lower alkoxy-lower alkyl, an acyloxy-lower alkyl, a lower alkoxycarbonyl-lower alkyl, an aryl or a heteroaryl, or R.sup.2 and R.sup.3 combinedly together form an alkylene having 1 to 2 carbon atoms; R.sup.4 and R.sup.5 are the same or different, and respectively represent hydrogen or a lower alkyl, or combinedly together form an alkylene having 2 to 5 carbon atoms; R.sup.6 represents hydroxyl group, formyloxy, an alkanoyloxy, a haloalkanoyloxy, a lower alkoxycarbonyloxy, an aroyloxy, a heteroaroyloxy, carbamoyloxy, a mono- or di-lower alkycarbamoyloxy and R.sup.7 represents hydrogen, or R.sup.6 and R.sup.7 combinedly together form a bond and X and Y are the same or different, and respectively represent hydrogen, halogen, nitro, cyano, a lower alkyl, a lower alkoxy, a halo-lower alkyl, carboxyl, formyl, an alkanoyl, an aroyl, a halo-alkanoyl, carbamoyl, a lower alkylsulfinyl, an arylsulfinyl, a lower alkylsulfonyl, an arylsulfonyl, sulfonamido or a mono- or di-lower alkylsulfonamido, or their pharmaceutically acceptable salts and its pharmaceutical use. The compounds of the present invention exhibit remarkable and long lasting antihypertensive actions and peripheral vascular relaxant actions and therefore are useful as therapeutic medicines for hypertensive. Since they also display selective coronary vasodilating actions and the duration of actions are very long, they are of use as therapeutic medicines for cardiovascular disturbances such as angina pectoris and cardiac insufficiency.

A benzopyran compound of the general formula (I) ##STR1## wherein A represents --OR.sup.1 or --NH--COR.sup.2 (wherein R.sup.1 represents hydrogen, a lower alkyl, formyl, an alkanoyl, an aroyl or an aralkyl and R.sup.2 represents hydrogen, a lower alkyl, a lower alkoxy, amino, mono- or di-lower alkylamino, an amino-lower alkyl, a hydroxy-lower alkyl, a halo-lower alkyl, a lower alkoxy-lower alkyl, an acyloxy-lower alkyl, a lower alkoxy-carbonyl-lower alkyl, an aryl or a heteroaryl); R.sup.3 represents hydrogen, a lower alkyl, a lower alkoxy, amino, a mono- or di-lower alkylamino, an amino-lower alkyl, a hydroxy-lower alkyl, a halo-lower alkyl, a lower alkoxy-lower alkyl, an acyloxy-lower alkyl, a lower alkoxycarbonyl-lower alkyl, an aryl or a heteroaryl, or R.sup.2 and R.sup.3 combinedly together form an alkylene having 1 to 2 carbon atoms; R.sup.4 and R.sup.5 are the same or different, and respectively represent hydrogen or a lower alkyl, or combinedly together form an alkylene having 2 to 5 carbon atoms; R.sup.6 represents hydroxyl group, formyloxy, an alkanoyloxy, a haloalkanoyloxy, a lower alkoxycarbonyloxy, an aroyloxy, a heteroaroyloxy, carbamoyloxy, a mono- or di-lower alkylcarbamoyloxy and R.sup.7 represents hydrogen, or R.sup.6 and R.sup.7 combinedly together form a bond and X and Y are the same or different, and respectively represent hydrogen, halogen, nitro, cyano, a lower alkyl, a lower alkoxy, a halo-lower alkyl, carboxyl, formyl, and alkanoyl, an aroyl, a halo-alkanoyl, carbamoyl, a lower alkylsulfinyl, an arylsulfinyl, a lower alkylsulfonyl, and arylsulfonyl, sulfonamido or a mono- or di-lower alkylsulfonamido, or their pharmaceutically acceptable salts and its pharmaceutical use. The compounds of the present invention exhibit remarkable and long lasting antihypertensive actions and peripheral vascular relaxant actions and therefore are useful as therapeutic medicines for hypertensive. Since they also display selective coronary vasodilating actions and the duration of actions are very long, they are of use as therapeutic medicines for cardiovascular disturbances such as angina pectoris and cardiac insufficiency.

Piperidine compounds of the formula: ##STR1## or isomers thereof as well as pharmaceutically acceptable salts and/or hydrate forms thereof, and piperidine compounds of the formula: ##STR2## or isomers thereof as well as salt and/or hydrate forms thereof. In the above formulae, A represents a methylene group, an oxygen atom or a sulfur atom; B represents an oxygen atom or a sulfur atom; R.sup.1 and R.sup.2 independently represent a hydrogen atom, a lower alkyl group or an aralkyl group; R.sup.3 represents a hydrogen atom or an amino protecting group; Z represents an amino group or a protected amino group, a hydroxy group, or a reactive atom or group; m represents 1 or 2; and n represents the integer of 0 to 3. Piperidine compounds (I) possess an inhibitory activity against angiotensin-converting enzyme, and exhibit a long lasting hypotensive activity and are useful as antihypertensive agents. Piperidine compounds (II) are useful as intermediates for said piperidine compounds (I).

Piperidine compounds and pharmaceutical uses thereof

5-Hydroxyindole-3-carboxylic acid amide compounds, pharmaceutical

Ortho-aminomethylphenol compounds

3-Indolecarboxamide compounds of the formula: ##STR1## inclusive of pharmaceutically acceptable acid addition salt and/or hydrate forms thereof, wherein R.sup.1 is hydrogen or C.sub.1-4 alkyl; each of R.sup.2 and R.sup.3 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, benzyloxy, C.sub.2-6 alkanoyloxy or hydroxy; R.sup.4 is hydrogen or C.sub.1-4 alkyl; R.sup.5 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or hydroxy; R.sup.6 is hydrogen or C.sub.1-4 alkyl; X is oxygen, sulfur or direct bond; each of k and m is an integer of 1 to 3; and n is 1 or 2, are useful as drug for the prevention and treatment of various circulatory diseases.

3-indolecarboxamides for control of circulatory diseases

Therapeutic agent for hypertension

Benzo[f]quinoline derivatives which are useful as antihypertensive agents and are represented by the formula: ##STR1## wherein R.sup.1 is hydrogen or lower alkyl, R.sup.2 is hydrogen, lower alkyl, hydroxy-lower-alkyl or lower-alkoxy-lower-alkyl, R.sup.3 and R.sup.4 are the same or different and each is hydrogen, lower alkyl, halogen, lower alkoxy, benzyloxy or hydroxy, R.sup.5 and R.sup.6 are the same or different and each is hydrogen, straight or branched alkyl, aralkyl or cycloalkyl, or R.sup.5 and R.sup.6 together with the adjacent nitrogen atom form a heterocycle, and the dotted line in the ring is an optional bond between 1- and 2-positions, and pharmaceutically acceptable acid addition salts thereof.

Anti-hypertensive 9-aminomethyl-benzo[f]quinoline-3,10-dione derivatives

Pyridazinone compounds of the formula: ##STR1## wherein A, B, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined hereinafter, and pharmaceutically acceptable acid addition salts thereof are disclosed. They are useful as antithrombotic and antihypertensive drugs.

Growing community of inventors

Nakatsu, Japan

Osamu Yaoka