Sankyo Company, Limited

Kenji Yoshimi

Mitsuo Nagano

Nobuyoshi Iwata

Masao Kozuka

Junichi Sakai

Koichi Kojima

Naozumi Samata

Yuichi Aizawa

Kazuo Koyama

Isao Kaneko

Kazuo Kobayashi

Katsunori Kato

Yoshiko Kubo

Tsugio Kaneko

Toshiyuki Tonohiro

Takao Hara

An isoxazole compound having the following formula: ##STR1## wherein R.sup.1 represents hydrogen, halogen, alkyl, alkoxy, hydroxyl, alkylthio, amino, alkanoyl, alkanoylamino, alkanoyloxy, alkoxycarbonyl, carboxy, (alkylthio)thiocarbonyl, carbamoyl, nitro or cyano; R.sup.2 represents an amino; m is 2 or 3; n is 1 to 6; ring A represents a phenyl ring, a naphthyl ring or an aromatic heterocycle; and X represents oxygen or sulfur. The isoxazole compound has an excellent monoamine oxidase inhibitory activity, and is useful for treating Parkinson's disease, depression and Alzheimer's disease.

Isoxazole derivatives

Isoxazole compounds having the following general formula: ##STR1## wherein R.sup.1 represents an optionally substituted aryl group or aromatic heterocyclic group; R.sup.2 represents a hydrogen atom, a halogen atom, an optionally substituted alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, an alkoxy group, a cyano group, a carboxyl group, an alkanoyl group, an alkoxycarbonyl group or an optionally substituted carbamoyl group; R.sup.3 represents an optionally substituted amino group or a saturated heterocyclic group; X represents an oxygen atom or a sulfur atom; and n is an integer of from 2 to 6. These compounds have excellent monoamine oxidase inhibitory activity and are useful as a therapeutic agent or a preventive agent against nervous diseases such as depression.

Isoxazole compounds useful for the prophylaxis or treatment of nervous

An isoxazole compound having the following formula: wherein R.sup.1 represents hydrogen, halogen, alkyl, alkoxy, hydroxyl, alkylthio, amino, alkanoyl, alkanoylamino, alkanoyloxy, alkoxycarbonyl, carboxy, (alkylthio)thiocarbonyl, carbamoyl, nitro or cyano; R.sup.2 represents an amino; m is 1; n is 1 to 6; ring A represents a phenyl ring or a naphthyl ring; and X represents oxygen or sulfur. The isoxazole compound has an excellent monoamine oxidase inhibitory activity, and is useful for treating Parkinson's disease, depression and Alzheimer's disease.

Compounds of formula (I): ##STR1## [in which: either (a) the dotted line ( ) is a single bond; A=is oxygen; and B is a group of formula (II): ##STR2## (in which m is 0 and n is 0 or 1) or (b) the dotted line ( ) is a double bond; A=is said group of formula (II) in which m is 1 and n is 0 or 1; and B is absent; and R.sup.1 is hydrogen, halogen, alkyl, alkenyl, alkynyl, optionally substituted benzyl or optionally substituted phenyl; R.sup.2 is hydrogen, halogen, alkyl, optionally substituted phenyl or heterocyclic; or R.sup.1 and R.sup.2, together with the carbon atoms to which they are attached, are a hydrocarbon ring fused to the isoxazole ring; R.sup.3 and R.sup.4 are each hydrogen, alkyl, optionally substituted benzyl or optionally substituted phenyl; or R.sup.3, R.sup.4 and the nitrogen atom to which they are attached together represent an alicyclic amino group]; and salts thereof may be used for the treatment of cerebral circulatory problems and for use as centrally acting muscle relaxants.

Isoxazole derivatives for use as cerebro-active drugs and central muscle

A method of treating depression comprising administering to a patient an effective amount of a compound of the formula (Ib): ##STR1## wherein R.sup.1b is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, an unsubstituted benzyl group, a substituted benzyl having at least one substitutent (b) selected from the group consisting of C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy, hydroxy, halogen, nitro, amino and C.sub.2 -C.sub.4 aliphatic carboxylic acylamino; unsubstituted phenyl or a substituted phenyl having at least one substitutent (b); R.sup.2b is hydrogen, C.sub.1 -C.sub.4 alkyl, unsubstituted phenyl, substituted phenyl having at least one substitutent (b), unsubstituted 5- or 6- membered heterocyclic having an oxygen, sulfur or nitrogen as a heteroatom, or substituted 5- or 6- membered heterocyclic having an oxygen, sulfur or nitrogen as a heteroatom and having at least one substitutent (b); and R.sup.3b and R.sup.4b are the same or different and each is hydrogen, C.sub.1 -C.sub.4 alkyl, unsubstituted benzyl, substituted benzyl having at least one substituent (b), unsubstituted phenyl, or substituted phenyl having at least one substitutent (b); or R.sup.3b, R.sup.4b and the nitrogen atom to which they are attached together represent an alicyclic amino group having a total of 5 or 6 ring atoms, or which one ring atom is the nitrogen atom and one ring atom is optionally an additional heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, the alicyclic amino group being unsubstituted or, where there is an additional nitrogen heteroatom, the alicyclic amino group having a C.sub.1 -C.sub.3 alkyl substitutent on the additional nitrogen heteroatom; or a pharmacologically acceptable acid addition salt thereof.

Use of isoxazolin-3-one derivatives as antidepressants

A method of treating depression comprising administering to a patient an effective antidepressive amount of a compound of the formula ##STR1## wherein either (i) the endocyclic dotted line (  ) is a double bond; the exoxyclic dotted line (  ) is a single bond;

A method of treating depression comprising administering to a patient an effective antidepressive amount of a compound of the formula (I) ##STR1## wherein the endocyclic dotted line ##STR2## is a single bond; the exocyclic dotted line ##STR3## is a double bond; A is oxygen; B is a group of the formula (II) ##STR4## wherein m is 0 and n is 0 or 1; R.sup.3, R.sup.4 and the nitrogen to which they are attached together represent an alicyclic amino having a total of 5 or 6 ring atoms, of which one ring atom is the nitrogen and one ring atom is optionally an additional heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, the alicyclic amino being unsubstituted or, where there is an additional nitrogen heteroatom, the alicyclic amino having as a substituent a C.sub.1 -C.sub.3 alkyl on the additional nitrogen heteroatom; R.sup.1 is hydrogen or halogen; and R.sup.2 is an unsubstituted phenyl, a substituted phenyl having a substituent selected from the group consisting of C.sub.1-3 alkyl, C.sub.1-3 alkoxy, halogen and nitro, an unsubstituted 5- or 6-membered heterocyclic group having one or more of oxygen, sulfur or a nitrogen as heteroatoms, or a substituted 5- or 6-membered heterocyclic group having one or more of oxygen, sulfur or a nitrogen as heteroatoms and having at least one substituent selected from the group consisting of C.sub.1 -C.sub.3 alkyl, C.sub.1-3 alkoxy, halogen and nitro; or a pharmaceutically acceptable acid addition salt thereof.

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Tokyo, Japan

Kenji Yoshimi