Kissei Pharmaceutical Co., Ltd.

Ono Pharmaceutical Co., Ltd.

Kissei Yakuhin Kogyo Kabushiki Kaisha

Kissei Yakuhin Kogyo Kabushiki Kaisha (kissei Pharmaceutical Co. Ltd.)

Tetsuhide Kamijo

Kinji Iizuka

Kenji Akahane

Yoshiaki Kiso

Hideaki Umeyama

Tetsuhiro Kubota

Hiromu Harada

Ryoji Yamamoto

Yukiyoshi Ajisawa

Michihiro Kobayashi

Yukihiko Kinoshita

Kozaburo Harita

Atsushi Tsubaki

Arao Ujiie

Naoyuki Tsutsumi

Toshiaki Yamaguchi

Hideo Nagata

Michio Toda

Benzofuro[3,2-c]quinoline compounds of the formula: ##STR1## wherein A represents a group of the formula of --CH.sub.2) .sub.m or --CH.sub.2 CH(OH)CH.sub.2 --; Y represents an N,N-di-alkylamino group, an N-mono-alkylamino group or a nitrogen atom-containing aliphatic geterocyclic group; n represents 0 or 1; m represents an integer of from 1 to 3, and pharmaceutically acceptable acid addition salts thereof, possess a strong inhibitory action on bone resorption, a stimulatory effect on ossification.

3-alkoxy substituted benzofuro[3,2-c]quinolin-6-one compounds

Benzofuro[3,2-c]quinoline compounds of the general formula: ##STR1## wherein (1) each of R.sup.1 and R.sup.2 is the same, and represent a group of the formula of --OR.sup.3 in which R.sup.3 represents a carbamoyl group, an N-mono-alkylcarbamoyl group, an N,N-dialkylcarbamoyl group, an alkylsulfonyl group, a formyl group or an aliphatic acyl group which may have an alkoxycarbonyl group as a substituent; m represents zero, 1 or 2; n represents zero or 1; with the proviso that n is not zero when m is zero,

Acylated benzofuro[3,2-c]quinoline compounds with utility as treatments

Novel amino acid derivatives useful as a therapeutic agent are disclosed. These amino acid derivatives and the pharmaceutically acceptable salts thereof have a human renin inhibitory effect when administered orally and are useful for treatment of hypertension, especially renin-associated hypertension.

Novel amino acid derivatives

Dipeptides are described which are represented by the formula ##STR1## wherein the various substituents are defined hereinbelow. These compounds have a strong inhibitory efect on human renin, and are useful as a therapeutically active agent for the treatment of hypertension, especially renin-associated hypertension.

Dipeptides as renin inhibitors

New renin inhibitory amino acid derivatives represented by formula (I): ##STR1## wherein A represents an alkoxycarbonyl group having 2 to 7 carbon atoms, ##STR2## wherein R.sup.1 and R.sup.2 are defined as in the specification below or ##STR3## wherein X and Y are defined as in the specification herein below, n represents zero or one, Z represents --O-- or --NH--, and R represents a straight- or branched chain alkyl group having 1 to 7 carbon atoms, and pharmaceutically acceptable salts thereof, useful as a therapeutic agent are disclosed. The amino acid derivatives have a renin inhibitory effect when administered orally and are useful for treatment of hypertension, especially renin-associated hypertension.

Novel renin inhibitory amino acid derivatives

Amino acid derivatives

Amino acid derivatives represented by formula ##STR1## wherein His represents an L-histidyl group, X represents a straight or branched alkoxy group having 1 to 7 carbon atoms, a straight or branched alkylamino group having 1 to 7 carbon atoms, a cycloalkyloxy group having 3 to 7 carbon atoms, a morpholino group, said alkoxy group having one or more halogen atoms as substituents; or a pharmaceutically acceptable salt, are useful in the treatment of hypertension.

Morpholine containing amino acid derivatives

Histidine derivatives

The present invention provides an improved method for producing a nuclear substituted cinnamoylanthranilic acid compound. Illustrative of the process is the reaction of 3,4-dimethoxybenzaldehyde with 2-carboxymalonanilic acid in an inert solvent medium in the presence of piperidine to provide an intermediate salt precipitate, and the salt is treated with an acidic reagent to yield N-(3,4-dimethoxycinnamoyl)anthranilic acid product.

Method for the production of nuclear substituted cinnamoylanthranilic

The present invention provides an improved method for producing a nuclear substituted cinnamoylanthranilic acid compound. Illustrative of the process is the reaction of 3-hydroxy-4-methoxybenzaldehyde with 2-carboxymalonanilic acid in an inert solvent medium in the presence of a molar excess of piperidine to provide a high purity intermediate salt precipitate, and the salt is treated with an acidic reagent to yeild N-(3-hydroxy-4-methoxycinnamoyl)anthranilic acid product.

Process for the production of nuclear substituted cinnamoylanthranilic

1,3-Disubstituted imidazoles of the general formula (I): ##STR1## wherein A and B may be the same or different, and each is a straight- or branched-chain alkylene or alkenylene group having 1 to 8 carbon atoms, Y is an acyl group having 2 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 7 carbon atoms or an dialkoxymethyl group having 3 to 13 carbon atoms, Z is a cyano group or an alkoxycarbonyl group having 2 to 7 carbon atoms, X is a halogen atom, n is zero or 1. The said compounds are intermediates for producing the imidazole derivatives of the general formula (V) above which possess strong and specific inhibitory effects on thromboxane synthetase and thus are useful as therapeutical agents for treatment of diseases caused by thromboxane A.sub.2.

1,3-Disubstituted imidazoles

The imidazole derivatives of the general formula: ##STR1## wherein A and B may be the same or different, and each is a straight- or branched-chain alkylene or alkenylene group having 1 to 8 carbon atoms, D is an acyl group having 2 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 7 carbon atoms or a dialkoxymethyl group having 3 to 13 carbon atoms, Q is a cyano group or an alkoxycarbonyl group having 2 to 7 carbon atoms, X is a halogen atom, Z is ##STR2## (wherein E is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms or an alkoxy group having 1 to 6 carbon atoms, Y is an oxygen atom or a sulfur atom and may be connected with either A or B), n is zero or 1, with the proviso that n is 1 when Y connects with B. These compounds are novel compounds and are useful as intermediates in producing 1-substituted imidazole derivatives which possess strong and specific inhibitory effects on thromboxane synthetase and thus are useful as therapeutically active agents for treatment of diseases caused by thromboxane A.sub.2.

Imidazole derivatives

Aromatic carboxylic amides of the general formula: ##STR1## wherein each of R.sub.1 and R.sub.2 is a hydrogen atom or an alkyl group having 1-4 carbon atoms, R.sub.3 and R.sub.4 are hydrogen atoms or together form another chemical bond, each X is a hydroxyl group, a halogen atom, an alkyl group having 1-4 carbon atoms and an alkoxyl group containing 1-4 carbon atoms, and may be the same or different, and n is an integer of 1-3, provided that when two Xs are alkyl or alkoxyl groups, the alkyl groups thereof may be connected together into an alkylene group, and the pharmaceutically acceptable salts thereof, possess a strong antiallergic action and are thus useful for treatment of asthma, hay fever, urticaria and atopic dermatitis.

Antiallergic composition containing aromatic carboxylic amide

New aromatic amidocarboxylic acid derivatives of the general formula: ##STR1## wherein R.sub.1 and R.sub.2 each represent a hydrogen atom or an alkyl gp with 1-4 carbon atoms; R.sub.3 and R.sub.4 each represent a hydrogen atom or may be combined together to form an additional chemical bond; X represents a hydroxyl group, a halogen atom, a straight or branched chain saturated or unsaturated alkyl group with 1-4 carbon atoms, a straight or branched chain saturated or unsaturated alkoxy group with 1-4 carbon atoms, an acyloxy group with 1-4 carbon atoms, or a cycloalkyl group with up to 6 carbon atoms; n is zero or an integer of 1-3 with the proviso that when n is 2 or 3, X's may be the same or different and that when two X's are commonly the alkyl or alkoxy group, both X's may be combined together to form a ring; and Y represents a straight or branched chain alkylene group or a straight or branched chain oxyalkylene group connected to the benzene nucleus through an oxygen atom, as well as physiologically acceptable salts thereof. The new compounds possess a strong antiallergic effect and are thus useful for the treatment of asthma, hay fever, urticaria and atopic dermatitis. The above-mentioned aromatic amidocarboxylic acid and a salt thereof are prepared, for example, by reacting a reactive functional derivative of the general formula: ##STR2## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X and n have the same meanings as given above, with an aminophenylalkylcarboxylic acid derivative or an aminophenoxyalkylcarboxylic acid dervative of the general formula: ##STR3## wherein Y has the same meaning as given above, and if desired, converting the resulting amidocarboxylic acid into a corresponding salt thereof or vice versa.

Growing community of inventors

Nagano, Japan

Tetsuhide Kamijo