Takeda Chemical Industries, Inc.

Minoru Hirata

Shinji Terao

Hirosada Sugihara

Katsumi Itoh

Yoshikazu Oka

Akio Miyake

Isuke Imada

Susumu Tsushima

Muneo Takatani

Akinobu Nagaoka

Substituted amino derivatives represented by the formula: ##STR1## wherein R.sup.1 and R.sup.2 each stand for an acyclic hydrocarbon residue or an alicyclic hydrocarbon residue; R.sup.3 and R.sup.4 each stand for hydrogen or a hydrocarbon residue optionally containing hetero-atom(s); A stands for a carbon chain having two or more carbon atoms optionally containing ether linkage or sulfide linkage, which may be substituted and which may per se form a ring; X.sup.1 and X.sup.2 each stand for oxygen atom or sulfur atom; and Y stands for amino group or an organic residue bonded through nitrogen atom, which may form a ring by combining with a carbon atom constituting A; and their salts have anti-arrhythmic activity and are useful for prevention and treatment of a variety of arrhythmias.

Substituted amine derivatives, their production and use

An ascorbic acid derivative of the formula: ##STR1## wherein R.sup.1 is organic residue having molecular weight of from 15 to 700, R.sup.2 is hydrogen or hydroxyl, R.sup.3 is hydrogen, acyl, optionally substituted phosphono or sulfo, and R.sup.3 and hydroxyl or R.sup.2 may form acetal residue or ketal residue, and a salt thereof are provided. The compound [I] and salts thereof have antioxidant activity and excellent prophylactic and improving actions on disorders of circulatory functions, and they are usefule as antioxidant agent for food and as agents of prophylaxis and improvement of circulatory functional disorders.

Pharmaceutical compositions containing certain ascorbic acid derivatives

The present invention relates to a compound of the formula: ##STR1## wherein Y is a chemical bond, oxygen atom, phenyleneoxy, or oxyphenyleneoxy; R.sup.1 is hydrogen or hydrocarbon residue; and R.sup.2 is hydrocarbon residue having two or more carbon atoms, production and use thereof. The compound (I) of the present invention has an antioxidation activity and activities of preventing or improving functional disorders due to biologically active oxygen species, thus being useful as a pharmaceutical agent for prophylaxis and therapy of disorders in the circulatory system.

Hydroxybutenolide derivatives, production and use thereof

The present invention relates to a compound of the formula: ##STR1## wherein X is sulfur or optionally substituted imino group; Y is a bond, oxygen, phenylene, phenyleneoxy, or oxyphenyleneoxy; R.sup.1 is hydrogen or optionally substituted hydrocarbon residue; R.sup.2 is optionally substituted hydrocarbon residue; and R.sup.1 may form, together with the imino-nitrogen atom as X, a nitrogen-containing 5- to 7-membered ring, production and use thereof. The compound (I) of the present invention has an anti-oxidation activity and activities of preventing or improving functional disorders due to biologically active oxygen species, thus being useful as a pharmaceutical agent for prophylaxis and therapy of disorders in the circulatory system.

4-Hydroxy-3-pyrrolin-2-ones and treatment of circulatory disorders

An ascorbic acid derivative of the formula: ##STR1## wherein R.sub.1 is an organic residue having a molecular weight of from 58 to 400 is novel compound and is useful as antioxidant agent for food.

Ascorbic acid derivatives and their production

Novel 1,5-benzoxathiepin derivatives of the formula: ##STR1## [wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy; R.sub.3 and R.sub.4 are independently hydrogen, optionally substituted lower alkyl or optionally substituted cycloalkyl or optionally substituted aralkyl, or both jointly form an optionally substituted ring together with the adjacent nitrogen atom; X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or a carboxyl group which may be esterified or amidated; Y is &gt;C.dbd.O or &gt;CH--OR.sub.5 (wherein R.sub.5 is hydrogen, acyl or optionally substituted carbamoyl); m is an integer of 0 to 2; n is an integer of 1 to 6] and salts thereof exhibit serotonin S.sub.2 receptor blocking activity, calcium antagonism, actions to relieve cerebral vasospasm and to improve renal circulation and diuretic and antithrombotic activities, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

1,5-benzoxathiepin derivatives

Novel condensed seven-membered heterocyclic compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy,

2-(piperazinylalkyl)-1-benzothiepin, 1-benzoxepin, and 1,5-benzodioxepin

Novel 1,5-benzoxathiepin derivatives of the formula: ##STR1## [wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy; R.sub.3 and R.sub.4 are independently hydrogen, optionally substituted lower alkyl or optionally substituted cycloalkyl or optionally substituted aralkyl, or both jointly form an optionally substituted ring together with the adjacent nitrogen atom; X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or a carboxyl group which may be esterified or amidated; Y is ##STR2## (wherein R.sub.5 is hydrogen, acyl or optionally substituted carbamoyl); m is an integer of 0 to 2; n is an integer of 1 to 6] and salts thereof exhibit serotonin S.sub.2 receptor blocking activity, calcium antagonism, actions to relieve cerebral vasospasm and to improve renal circulation and diuretic and antithrombotic activities, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

1,5-benzoxathiepin derivatives, their production and use

A mammal suffering from ischemic disease such as cerebral apoplexy, cardiac insufficiency, renal insufficiency due to vascular changes, etc. is remedied by administering to said mammal an effective amount of a compound of the formula: ##STR1## wherein n is an integer of from 4 to 22.

Method for therapy of ischemic disease

Novel 1,2-dihydronaphthalene derivatives of the formula ##STR1## wherein A is a di-lower alkylamino group or a 5- to 7-membered cyclic amino group which may contain one oxygen atom and n is 2 or 3, and its salts have excellent pharmacological activities such as vasodilator, hypotensive and cerebral blood flow increasing actions.

Piperazine containing dihydronaphthalene derivatives and compositions

Novel 1,2-dihydronaphthalene derivatives of the formula ##STR1## wherein R.sup.1 and R.sup.2, independently of each other, are hydrogen, nitro, amino, halogen, or hydroxyl which may be protected, and R.sup.3 is a piperazinyl or morpholino group which may be substituted by lower alkyl, aralkyl, carboxylic acid-derived acyl, lower alkoxycarbonyl-lower alkyl or cycloaminocarbonyl-lower alkyl, and its salts have excellent pharmacological activities such as vasodilator and cerebral blood flow increasing activities.

Growing community of inventors

Osaka, Japan

Minoru Hirata