Takeda Chemical Industries, Inc.

Tetsuji Imamoto

Giichi Goto

Hidefumi Yukimasa

Hideaki Natsugari

Akinobu Nagaoka

Yoshihiro Sugiura

Yuzo Ichimori

Tsuneo Asano

Yasutaka Nagisa

A pharmaceutical composition comprising a compound having anti-endothelin activity is useful for the prophylaxis or treatment of cerebral infarction.

Treatment of cerebral infarction using cyclic hexapeptides

The present invention relates to prevention or treatment a brain edema, an intracranial hemorrhage and a cerebral infarction by administering a pharmaceutically effective amount of a compound or a pharmaceutically acceptable salt thereof, for inhibiting a vascular permeability enhancer, which the compound is of the formula: ##STR1## wherein A is halogen, --X--R.sup.3 in which X is O, S, NH or NHNH, and R.sup.3 is H, acyl, a hydrocarbon group or an aromatic heterocyclic group, or --Y.dbd.R.sup.4 in which Y is N or NHN, and R.sup.4 is a divalent hydrocarbon group, and R.sup.1 is H, halogen, a hydrocarbon group, a heterocyclic group or --Z--R.sup.5 in which Z is O, S or NH, and R.sup.5 is H, a hydrocarbon group or an aromatic heterocyclic group;

Inhibitor of vascular permeability enhancer

Compounds represented by the formula: ##STR1## wherein the ring A and the ring B each stand for an optionally substituted benzene ring; Ar stands for an optionally substituted aryl group or an optionally substituted heterocyclic group; Q stands for an oxygen atom or a sulfur atom; R stands for a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group or an optionally substituted amino group; X stands for --O-- or --NR.sup.1 -- wherein R.sup.1 stands for a hydrogen atom or an optionally substituted hydrocarbon group; Y stands for --O--, --NR.sup.2 -- wherein R.sup.2 stands for a hydrogen atom or an optionally substituted hydrocarbon group, or a bond; m denotes 1, 2 or 3, and n denotes 0, 1 or 2, and salts thereof which have excellent calcium- or substance P receptor-antagonistic activity, being useful for treating a cerebralvascular disorder in mammals such as cerebralischemia, cerebral edema and neuronal damage, their production and use.

Isoquinolinyl compounds which are useful in treating cerebral vascular

1. A cyclic amine compound of the formula ##STR1## wherein B means a saturated or unsaturated 5- to 7-membered aza-heterocyclic group which may be substituted; A means a bond or an alkylene or alkenylene group which may be substituted by hydrocarbon residues, oxo, hydroxyimino, and/or hydroxy, .sub.-- means either a single bond or a double bond (provided that when A means a bond, .sub.-- means a single bond); R.sub.2 and R.sub.3 independently mean a hydrogen atom or a hydrocarbon residue which may be substituted (provided that both of R.sub.2 and R.sub.3 are not hydrogen atoms) or jointly form a cyclic amino group together with the adjacent nitrogen atom, n is 0, 1 or 2 and p is 1 or 2 or a physiologically acceptable salt thereof. The compounds are useful for therapy of cerebral edema, acute symptoms in cerebral apoplexy and protection of brain and nerve cell, or useful as anticholinesterase or as brain function-improving agent.

Cyclic amine compounds and their use

1. A cyclic amine compound of the formula ##STR1## wherein B means a saturated or unsaturated 5- to 7-membered aza-heterocyclic group which may be substituted; A means a bond or an alkylene or alkenylene group which may be substituted by hydrocarbon residues, oxo, hydroxyimino, and/or hydroxy, --means either a single bond or a double bond (provided that when A means a bond, --means a single bond); R.sub.2 and R.sub.3 independently mean a hydrogen atom or a hydrocarbon residue which may be substituted (provided that both of R.sub.2 and R.sub.3 are not hydrogen atoms) or jointly form a cyclic amino group together with the adjacent nitrogen atom, n is 0, 1 or 2 and p is 1 or 2 or a physiologically acceptable salt thereof. The compounds are useful for therapy of cerebral edema, acute symptoms in cerebral apoplexy and protection of brain and nerve cell, or useful as anticholinesterase or as brain function-improving agent.

Benzylpiperidine compounds and their use

There is provided a cyclic amine compound of the formula ##STR1## wherein B means a saturated or unsaturated 5- to 7-membered aza-heterocyclic group which may be substituted; A means a bond or an alkylene or alkenylene group which may be substituted by hydrocarbon residues, oxo, hydroxyimino, and/or hydroxy,  means either a single bond or a double bond (provided that when A means a bond,  means a single bond); R.sub.2 and R.sub.3 independently mean a hydrogen atom or a hydrocarbon residue which may be substituted (provided that both of R.sub.2 and R.sub.3 are not hydrogen atoms) or jointly form a cyclic amino group together with the adjacent nitrogen atom, n is 0, 1 or 2 and p is 1 or 2 or a physiologically acceptable salt thereof. The compounds are useful for therapy of cerebral edema, acute symptoms in cerebral apoplexy and protection of brain and nerve cell, or useful as anticholinesterase or as brain function-improving agent.

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Kitakatsuragi-gun, Japan

Tetsuji Imamoto