Otsuka Pharmaceutical Company, Limited

Yasuo Oshiro

Kazuyuki Nakagawa

Hiraki Ueda

Tatsuyoshi Tanaka

Tetsuro Kikuchi

Kazuo Banno

Seiji Sato

Takao Nishi

Takafumi Fujioka

Katsura Tottori

Yoshimasa Nakano

Wasei Miyazaki

Taketoshi Izawa

Masanao Shinohara

Hirotsugu Kaise

Keiichi Kuwahara

Hiroshi Yamashita

Nobuaki Ito

Shin Miyamura

Hideaki Kuroda

Kunio Oshima

Satoshi Shimizu

Shinichi Taira

Haruka Takahashi

Jun Matsubara

Masaaki Osaki

Shigeki Fujisawa

Yoji Sakurai

Nobuyuki Kurahashi

Takafuni Fujioka

Kozo Watanabe

Yutaka Wada

Keiko Takasu

The present invention provides a heterocyclic compound represented by the general formula (1): The compound of the present invention has a wide treatment spectrum for mental disorders including central nervous system disorders, no side effects and high safety.

Piperazine-substituted benzothiophenes for treatment of mental disorders

Carbostyril derivatives for inhibiting skin erythema and/or skin

Cyclic amide derivatives

Disclosed is carbostyril derivatives of the general formula ##STR1## wherein R.sup.1 is a halogen, a hydroxyl, lower alkoxy, lower alkyl, lower alkenyloxy, amino, lower-alkanoyl amino or lower alkylthio group, R.sup.2 is a phenyl group which may optionally have one or two substituents, A is a lower alkylene group, and n is an integer of 1 or 2 and wherein the carbon-carbon bond between the positions 3 and 4 of the carbostyril skeleton may be a single bond or a double bond, and salts thereof, and pharmaceutical compositions containing the same for use as a disturbance-of-consciousness improving agent, central nervous system stimulant or sigma receptor agonist.

Carbostyril derivatives and pharmaceutical compositions containing the

The present invention provides a disturbance-of-consciousness improving agent which is a highly effective and quick remedy and which can be administered orally. The disturbance-of-consciousness improving agent of the invention contains a sigma receptor agonist compound as an active ingredient.

Disturbance-of-consciousness improving agent

Novel 2,3-dihydro-1H-indene derivatives and salts thereof represented by the general formula (1), ##STR1## [wherein R.sup.1 and R.sup.2 are each a hydrogen atom, a lower alkyl group, a phenyl group which may have halogen atoms and/or alkyl groups as the substituents on the phenyl ring; R.sup.3 is a halgoen atom or a lower alkyl group; R.sup.4 is a hydrogen atom, a halogen atom, a phenyl-lower alkyl group, a cycloalkyl-lower alkyl group or the like; R.sup.5 is a hydroxyimino group, an alkylamino group or a group of the formula --NHR.sup.8 (wherein R.sup.8 is a hydrogen atom, a halogen-substituted lower alkanoyl group or the like); R.sup.6 is a hydrogen atom or a phenyl group; and R.sup.7 is a hydrogen atom or a lower alkyl group]. The 2,3-dihydro-1H-indene derivatives and salt thereof are useful as improving agents for treating anoxemic and hypoxic symptoms and syndromes accompanied therewith, cerebral activators, amnesia curvative agents, presbyophrenia curvative agents, treating agents for breathing arrest and improving agents for hypoxia accompanied with potassium cyanide poisoning, as well as useful an anti-inflammatory agents and hypotensive agents.

2,3-dihydro-1H-indene derivatives

Novel 2,3-dihydro-1H-indene derivatives and salts thereof represented by the general formula (1), ##STR1## [wherein R.sup.1 and R.sup.2 are each a hydrogen atom, a lower alkyl group, a phenyl group which may have halogen atoms and/or alkyl groups as the substituents on the phenyl ring; R.sup.3 is a halogen atom or a lower alkyl group; R.sup.4 is a hydrogen atom, a halogen atom, a phenyl-lower alkyl group, a cycloalkyl-lower alkyl group or the like; R.sup.5 is a hydroxyimino group, an alkylamino group or a group of the formula --NHR.sup.8 (wherein R.sup.8 is a hydrogen atom, a halogen-substituted lower alkanoyl group or the like); R.sup.6 is a hydrogen atom or a phenyl group; and R.sup.7 is a hydrogen atom or a lower alkyl group]. The 2,3-dihydro-1H-indene derivatives and salt thereof are useful as improving agents for treating anoxemic and hypoxic symptoms and syndromes accompanied therewith, cerebral activators, amnesia curative agents, presbyophrenia curative agents, treating agents for breathing arrest and improving agents for hypoxia accompanied with potassium cyanide poisoning, as well as useful as anti-inflammatory agents and hypotensive agents.

2,3-dihydro-1H-indene derivatives and their use as pharmaceutical agents

Novel hydrofluorene derivatives and salts thereof represented by the formula (1) which possess excellent activities for improving anoxemic and hypoxic symptoms and syndromes accompanied therewith, therefore said derivatives are useful as cerebral activators, preventive agents for arrhythmia and heart failure caused by the shortage of oxygen and others. Furthermore, said hydrofluorene derivatives and salts thereof possess actions for scavenging active oxygen radicals, therefore, the derivatives are useful prophylactic and treating agents for various disturbances and diseases caused by the excessive formation of active oxygen radicals. In addition to the above, the hydrofluorene derivatives are useful as anti-oxidative agents for fats and oils. Yet, further, the hydrofluorene derivatives and salts thereof accelerate the uptaking of high-affinity choline in the central nerve system and/or the releasing of acetylcholine therefrom, therefore, the hydrofluorene derivatives and salts thereof are useful cholinergic nerve system activating agents.

Hydrofluorene derivatives

A novel carbostyril derivative and salt thereof represented by the formula (1) ##STR1## (wherein R is a group of the formula ##STR2## ((wherein R.sup.1 is a C.sub.1- C.sub.3 alkoxy group)), a group of the formula ##STR3## ((wherein R.sup.2 and R .sup.3 are each, at the same time, a chlorine atom, a bromine atom; and R.sup.4 is a hydrogen atom or a chlorine atom)), 2-methyl-3-nitrophenyl group, 3,5-dichlorophenyl group, or a group of the formula ##STR4## ((wherein R.sup.5 is a chlorine atom or a bromine atom; and R.sup.6 is a methyl group)); the carbon-carbon bond between 3- and 4-position in the carbostyril skeleton is a single or double bond).

Carbostyril derivatives

A method for curing and/or improving hypoxia characterized by administering a compound represented by the general formula (1), ##STR1## said compounds have been known in prior art literatures, for example, as carbostyril derivatives in Japanese Patent Kokai No. 54-160389 (1979), etc., as benzoxazine derivatives in Japanese Patent Kokai No. 59-70675 (1984), and as benzoazepine derivatives in Japanese Patent Kokai No. 57-193461 (1982), and they have been known as central nervous system controlling agents and antihistaminic agents. The present invention was established on the basis of the findings that the compounds represented by the general formula (1) possess excellent pharmacological activities for curing and/or improving hypoxia and also possess excellent anti-oxidative activities, which could not have been anticipated from the disclosures in the prior art literatures.

Method for treating hypoxia

A prophylactic or therapeutic composition for hepatitis is disclosed comprising a prophylactically or therapeutically effective amount of a sesquiterpene compound represented by the formula (I) or (II) ##STR1## or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier.

Composition for prophylaxis and therapy of hepatitis

Carbostyril derivatives having antihistaminic action and central nervous controlling action are useful as antihistaminic agents or central nervous controlling agents. The derivatives are represented by the general formula, ##STR1## wherein R.sup.1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenylalkyl group, an alkylene group containing 1 to 4 carbon atoms; R.sup.2 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or a phenyl group; R.sup.3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R.sup.4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R.sup.5 is a cycloalkyl group having 3 to 8 carbon atoms, a phenyl group (which may have 1 to 3 substituted groups selected from the group consisting of halogen atoms, alkyl groups having 1 to 4 carbon atoms and alkoxy groups having 1 to 4 carbon atoms), an alkyl group having 1 to 4 carbon atoms (having one substituted group such as a hydroxy group, a phenyl group or an alkanoyloxy group having 1 to 4 carbon atoms), an alkanoyl group having 1 to 4 carbon atoms or benzoyl group; X is a halogen atom; n is 0, or an integer of 1 or 2; Q is an integer of 2 or 3, l and m are respectively an integer of 0 to 1-6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond and; the substituted position of the side chain of ##STR2## is any one of the 4-, 5-, 6-, 7- or 8-positions.

Carbostyril derivatives and pharmaceutical preparations containing same

Indane derivatives and their salts represented by the general formula (1), ##STR1## wherein R.sup.1 is an amino group which may have lower alkyl groups as the substituents, a hydroxylimino group, an alkanoylamino group having 1 to 10 carbon atoms which may have halogen atoms as the substituents, a lower alkylsulfonylamino group, a phenylsulfonylamino group which may have lower alkyl groups as the substituents on the phenyl ring, a benzoylamino group having lower alkyl groups as the substituents on the phenyl ring, and a phenyl-lower alkylamino group having a hydroxyl groups or a lower alkyl groups as the substituents on the phenyl ring, R.sup.2 is a hydrogen atom, a lower alkyl group, a halogen atom, a nitro group, an amino group, an amino-lower alkyl group, a lower alkanoylamino group, a lower alkanoylamino-lower alkyl group which may have halogen atoms as the substituents, a lower alkylthio group, a 1-piperidinesulfonyl group, or a lower alkenyl group; R.sup.3 is a hydrogen atom, a lower alkyl group, or a halogen atom; R.sup.4 and R.sup.5 are the same or different from each other, and are each a hydrogen atom, or a lower alkyl group; provided that when R.sup.1 is a hydroxylimino group, then R.sup.2 and R.sup.3 should not be hydrogen atoms at the same time. The indane derivatives and their salts are useful as preventive and curative agents for various diseases and disorders caused by the excessive formation and accumulation of the active oxygen radicals and the peroxidized substances in the living body, and/or the defects of phylaxis mechanisms of the living body, for example anti-arreriosclerotic agents, carcinogenesis preventive agents, carcinostatic agents, anti-inflammatory agents, analgesics, autoimmune disease curative agents, platelets aggregation inhibitory agents, hypotensive agents, anti-hyperlipemic agents, retinosis of immature infant and cataract preventive and curative agents. The indane derivatives and their salts are also useful as antioxidants for oils and fats being contained in processed foods.

Indane derivatives and salts thereof

1-amino-2,3-dihydro-1H-indene compounds

Growing community of inventors

Tokushima, Japan

Yasuo Oshiro