Isoxazole derivatives
AssigneeSankyo Company, Limited
InventorsKoichi Kojima, Junichi Sakai, Yuichi Aizawa, Naozumi Samata, Masao Kozuka, Kenji Yoshimi, Isao Kaneko, Kazuo Koyama
Life of this patent
Estimating the term…
Abstract
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.
Claims32
A compound of formula (I) ##STR22## wherein:
- R.sup.1 represents a hydrogen atom;
- a halogen atom;
- an alkyl group having from 1 to 6 carbon atoms;
- an alkyl group having from 1 to 4 carbon atoms and substituted by a halogen atom or an alkoxy group having from 1 to 4 carbon atoms;
- an alkoxy group having from 1 to 6 carbon atoms;
- a halogeno alkoxy group having from 1 to 6 carbon atoms;
- a hydroxyl group;
- an alkylthio group having from 1 to 6 carbon atoms;
- an amino group;
- a monoalkylamino group in which said alkyl moiety has from 1 to 6 carbon atoms;
- a dialkylamino group in which each alkyl moiety independently has from 1 to 6 carbon atoms;
- an alkanoyl group having from 1 to 6 carbon atoms;
- an alkanoylamino group having from 1 to 6 carbon atoms;
- an alkanoyloxy group having from 1 to 6 carbon atoms;
- an alkoxycarbonyl group having from 1 to 6 carbon atoms;
- a carboxy group;
- an (alkylthio)thiocarbonyl group in which said alkylthio moiety has from 1 to 6 carbon atoms;
- a carbamoyl group;
- a monoalkylcarbamoyl group in which said alkyl moiety has from 1 to 6 carbon atoms;
- a dialkylcarbamoyl group in which each alkyl moiety independently has from 1 to 6 carbon atoms;
- a nitro group;
- or a cyano group;
- R.sup.2 represents an amino group;
- m represents 1;
- n represents an integer of from 1 to 6;
- ring A represents a phenyl ring fused with the isoxazole ring or a naphthyl ring fused with the isoxazole ring;
- and
- X represents an oxygen atom or a sulfur atom;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition having monoamine oxidase inhibitory activity comprising an effective pharmaceutical amount of an isoxazole compound of formula (II) as defined below or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable diluent or carrier ##STR23## wherein:
- R.sup.1 represents a hydrogen atom;
- a halogen atom;
- an alkyl group having from 1 to 6 carbon atoms;
- an alkyl group having from 1 to 4 carbon atoms and substituted by a halogen atom or an alkoxy group having from 1 to 4 carbon atoms;
- an alkoxy group having from 1 to 6 carbon atoms;
- a halogeno alkoxy group having from 1 to 6 carbon atoms;
- a hydroxyl group;
- an alkylthio group having from 1 to 6 carbon atoms;
- an amino group;
- a monoalkylamino group in which said alkyl moiety has from 1 to 6 carbon atoms;
- a dialkylamino group in which each alkyl moiety independently has from 1 to 6 carbon atoms;
- an alkanoyl group having from 1 to 6 carbon atoms;
- an alkanoylamino group having from 1 to 6 carbon atoms;
- an alkanoyloxy group having from 1 to 6 carbon atoms;
- an alkoxycarbonyl group having from 1 to 6 carbon atoms;
- a carboxy group;
- an (alkylthio)thiocarbonyl group in which said alkylthio moiety has from 1 to 6 carbon atoms;
- a carbamoyl group;
- a monoalkylcarbamoyl group in which said alkyl moiety has from 1 to 6 carbon atoms;
- a dialkylcarbamoyl group in which each alkyl moiety independently has from 1 to 6 carbon atoms;
- a nitro group;
- or a cyano group;
- R.sup.2, represents an amino group;
- m represents 1;
- n represents an integer of from 1 to 6;
- ring A represents a phenyl ring fused with the isoxazole ring or a naphthyl ring fused with the isoxazole ring;
- and
- X represents oxygen atom or sulfur atom.
A pharmaceutical composition having monoamine oxidase inhibitory activity comprising a monoamine oxidase inhibitory activity effective amount of an isoxazole compound selected from the group consisting of 3-(2-aminoethoxy)-4-cyano-5-fluoro-1,2-benzisoxazole;
- 3-(2-aminoethylthio)-5-fluoro-4-methyl-1,2-benzisoxazole;
- and pharmaceutically acceptable salts thereof, in admixture with a pharmaceutically acceptable diluent or carrier.
A compound which is 3-(2-aminoethoxy)-4-cyano-5-fluoro-1,2-benzisoxazole or a pharmaceutically acceptable salt thereof.
A compound which is 3-(2-aminoethylthio)-5-fluoro-4-methyl-1,2-benzisoxazole or a pharmaceutically acceptable salt thereof.
A compound of the formula ##STR24## wherein:
- R.sup.1 represents a hydrogen atom;
- a halogen atom;
- an unsubstituted alkyl group having from 1 to 6 carbon atoms;
- an alkyl group having from 1 to 4 carbon atoms and substituted by a halogen atom or an alkoxy group having from 1 to 4 carbon atoms;
- an alkoxy group having from 1 to 6 carbon atoms;
- a halogeno alkoxy group having from 1 to 6 carbon atoms;
- a hydroxyl group;
- an alkylthio group having from 1 to 6 carbon atoms;
- an amino group;
- a monoalkylamino group in which the alkyl moiety thereof has from 1 to 6 carbon atoms;
- a dialkylamino group in which each alkyl moiety thereof independently has from 1 to 6 carbon atoms;
- an alkanoyl group having from 1 to 6 carbon atoms;
- an alkanoylamino group having from 1 to 6 carbon atoms;
- an alkanolyloxy group having from 1 to 6 carbon atoms;
- an alkoxycarbonyl group having from 1 to 6 carbon atoms;
- a carboxy group;
- an (alkylthio)thiocarbonyl group in which the alkylthio thereof moiety has from 1 to 6 carbon atoms;
- a carbamoyl group;
- a monoalkylcarbamoyl group in which the alkyl moiety thereof has from 1 to 6 carbon atoms;
- a dialkylcarbamoyl group in which each alkyl moiety thereof independently has from 1 to 6 carbon atoms;
- a nitro group;
- or a cyano group;
- R.sup.4 represents an amino group substituted by a protecting group selected from the group consisting of C.sub.1 -C.sub.6 alkanoyl;
- halogen C.sub.1 -C.sub.4 alkoxy-substituted C.sub.1 -C.sub.4 alkanoyl;
- unsaturated C.sub.1 -C.sub.4 alkanoyl;
- unsubstituted C.sub.6 -C.sub.10 arylcarbonyl;
- C.sub.6 -C.sub.10 arylcarbonyl substituted by a substituent selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkoxy carbonyl, C.sub.6 -C.sub.10 aryl and nitro;
- unsubstituted C.sub.1 -C.sub.4 alkoxycarbonyl;
- C.sub.1 -C.sub.4 alkoxycarbonyl substituted by a halogen;
- C.sub.2 -C.sub.5 -alkenyloxycarbonyl;
- aryldicarbonyl and C.sub.7 -C.sub.15 aralkyloxycarbonyl;
- m represents 1;
- n represents an integer of from 1 to 6;
- ring A represents a phenyl ring fused with the isoxazole ring or a naphthyl ring fused with the isoxazole ring;
- and
- X represents an oxygen atom or a sulfur atom;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.