3-[(4-Aroyl)phenoxy(or phenylthio)]cyclopentanecarboxylic acid analogues

Claim 2

1) A 3-[(4-aroyl)phenoxy (or phenylthio)]cyclopentanecarboxylic acid derivative process represented by the general formula: [wherein, X represents an oxygen atom or a sulfur atom. Rl, R2 and R3 represent a hydrogen atom, a halogen atom or an alkyl group of from 1 to 4 carbon atom(s) independently, or the general formula: (wherein, R3' represents a hydrogen atom, a halogen atom or an alkyl group of from 1 to 4 carbon atom(s).) in place of the general formula: R4 represents the general formula: or -N(R 9 ) 2 (wherein, W represents an oxygen atom or sulfur atom. R6, R7 and R8 represents a hydrogen atom, a halogen atom, a nitro group, an alkyl group of from 1 to 4 carbon atom(s), a hydroxy group or an alkoxy group of from 1 to 4 carbon atom(s) independently. Each of R 9 represents a hydrogen atom, an alkyl group of from 1 to 4 carbon atom(s) or a phenyl group independently. Y represents a single bond or an alkylene group or an alkenylene group of from 1 to 4 carbon atom(s).). R5 represents a 5-tetrazolyl group or the general formula: -COOR 10 (wherein, R10 represents a hydrogen atom or an alkyl group of from I to 4 carbon atom(s)] or a non-toxic salt thereof.

Claim 3

2) A derivative according to claim 1, wherein X represents an oxygen atom.

Claim 4

3) A derivative according to claim 1, wherein X represents an sulfur atom.

Claim 5

4) A derivative according to claim I, wherein R 5 represents a carboxy, methoxycarbonyl or 5-tetrazolyl group.

Claim 6

5) A derivative according to claim 1, wherein at least one of R1, R2 and R3 represents a hydrogen atom and the other one or two represent(s) a halogen atom or a methyl group.

Claim 7

6) A derivative according to claim 1, wherein represents a naphthyl group.

Claim 8

7) A derivative according to claim 1, wherein all of R6, R7 and R8 in R4 represent hydrogen atoms, or one or two of them is(are) fluorine atom, chlorine atom, nitro group, methyl group, hydroxy group or methoxy group and the other symbol(s) is(are) hydrogen atom(s).

Claim 9

8) A derivative according to claim 1, wherein Y is R 4 represents a single-bond, a methylene group or a vinylene group.

Claim 10

9) A derivative according to claim 1, wherein R4 represents a group of the formula;

Claim 11

10) A derivative according to claim 1 whsich is (1S,3S)-3-[(2,3-dichioro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (1R,3R)-3-[(2,3-dichloro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (t)-trans-3-[(2,3-dichloro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(2-thenoyl)}phenoxy]cyclopentanecarboxylic acid, (1R,3R)-3-[{2,3-dichloro-4-(2-thenoyl)}phenoxy]cyclopentanecarboxylic acid, (±)-trans-3-[{2,3-dichloro-4-(2-thenoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(2-furoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(4-fluorobenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-({2,3-dichloro-4-(2-fluorobenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(4-methylbenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(2-methylbenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(4-nitrobenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(3-nitrobenzoyl)}phenoxy]cyclopentanecarboxylic acid, (lS,3S)-3-[(2,3-dichloro-4-phenylacetyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(5-methyl-2-thenoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(3-methyl-2-thenoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(4-methoxybenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[(2,3-dichloro-4-cinnamoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(3-(2-thenoyl)acryloyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(1-naphthoyl)]phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(3-methylbenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(2-chlorobenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(2,4-dimethylbenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,3-dichloro-4-(2,6-dichlorobenzoyl)}phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[(2-chloro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (lS,3S)-3-[(3-chloro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[{2,6-dichloro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[(3-fluoro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[(2-fluoro-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (lS,3S)-3-(2,6-dimethyl-4-benzoylphenoxy)cyclopentanecarboxylic acid, (1S,3S)-3-[4-(2,4-dichlorobenzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[2,6-dimethyl-4-(2,4-dichlorobenzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[2,6-dimethyl-4-(1-naphthoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[3-chloro-4-(1-naphthoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[2,3-dichloro-4-(2-benzo[b]thenoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-[2,3-dichloro-4-(p-hydroxybenzoyl)phenoxy]cyclopentanecarboxylic acid, (1S,3S)-3-(4-benzoyl-1-naphthoxy)cyclopentanecarboxylic acid, (1S,3S)-3-[(2,3-dimethyl-4-benzoyl)phenoxy]cyclopentanecarboxylic acid, (lS,3S)-3-(2,3-dichloro-4-diphenylcarbamoylphenoxy)cyclopentanecarboxylic acid, (1S,3S)-3-(2,3-dichloro-4-phenylcarbamoylphenoxy)cyclopentanecarboxylic acid, (1S,3S)-3-(4-benzoylphenoxy)cyclopentanecarboxylic acid, (lS,3S)-3-[4-(2-thenoyl)phenoxylcyclopentanecarboxylic acid, (1S,3S)-3-(4-benzoyl-2,3-dichlorophenylthio)cyclopentanecarboxylic acid or (1S,3S)-3-(2,3-dichloro-4-benzoylphenoxy)-1-(tetrazol-5'-yl) cyclopentane or a non-toxic salt thereof.

Claim 12

11) A process for the preparation of a compound of the general formula: [wherein, X represents an oxygen atom or a sulfur atom, Rl, R2 and R3 represents a hydrogen atom, a halogen atom, an alkyl group of from 1 to 4 carbon atom(s) independently or the general formula: (wherein, R3' represents a hydrogen atom, a halogen atom or an alkyl of from 1 to 4 carbon atom(s).) in place of the general formula: R4 represents the general formula: (wherein, R6, R7 and R8 represents a hydrogen atom, a halogen atom, a nitro group, an alkyl group of from 1 to 4 carbon atom(s), a hydroxy group or an alkoxy group of from 1 to 4 carbon atom(s) independently. Each of R 9 represents a hydrogen atom, an alkyl group of from 1 to 4 carbon atom(s) or phenyl group independently. Y represents a single bond or an alkylene group or an alkenylene group of from 1 to 4 carbon atom(s). W represents an oxygen atom or sulfur atom.). R 5 represents a 2-tetrazolyl group or a group of the general formula: -COOR IO (wherein, R 10 represents a hydrogen atom or an alkyl group of from 1 to 4 carbon atom(s))], which is characterized, by reacting a compound of the general formula: [wherein, R14 represents a group of the general formula: or -N(R 9 ) 2 (wherein, R16, R 17 and R18 represents a hydrogen atom, a halogen atom, an alkyl or an alkoxy group of from 1 to 4 carbon atom(s) independently. The other symbols are the same meaning as described hereinbefore.) The other symbols are the same meaning as described hereinbefore. and that of the general formula: (wherein, R15 represents an alkyl group of from 1 to 4 carbon atom(s). Z represents a halogen atom or an alkylsulfonyloxy group or an arylsulfonyloxy group, which is substituted or unsubstituted such as methanesulfonyloxy or p-toluene-sulfonyloxy.) to obtain a compound of the general formula: (wherein, all the symbols are the same meaning as described hereinbefore.), if desired, by converting a nitro group of the resulting compound (Ia) to a hydroxy group, and further, if desired, by converting the hydroxy group of the obtained compound to an alkoxy group, to obtained a compound of the general formula: (wherein, all the symbols are the same meaning as described hereinbefore.), and then by subjecting saponification of a compound of the general formula (Ib), and further, if desired, by converting a carboxy group of the resulting compound to a tetrazolyl group.

Claim 13

11) A process for the preparation of a compound of the general formula: [wherein, X represents an oxygen atom or a sulfur atom, Rl, R2 and R3 represents a hydrogen atom, a halogen atom, an alkyl group of from 1 to 4 carbon atom(s) independently or the general formula: (wherein, R3' represents a hydrogen atom, a halogen atom or an alkyl of from 1 to 4 carbon atom(s).) in place of the general formula: R4 represents the general formula: (wherein, R6, R7 and R8 represents a hydrogen atom, a halogen atom, a nitro group, an alkyl group of from 1 to 4 carbon atom(s), a hydroxy group or an alkoxy group of from 1 to 4 carbon atom(s) independently. Each of R 9 represents a hydrogen atom, an alkyl group of from 1 to 4 carbon atom(s) or phenyl group independently. Y represents a single bond or an alkylene group or an alkenylene group of from 1 to 4 carbon atom(s). W represents an oxygen atom or sulfur atom.). R 5 represents a 2-tetrazolyl group or a group of the general formula: -COOR IO (wherein, R 10 represents a hydrogen atom or an alkyl group of from 1 to 4 carbon atom(s))], which is characterized, by reacting a compound of the general formula: [wherein, R14 represents a group of the general formula: or -N(R 9 ) 2 (wherein, R16, R 17 and R18 represents a hydrogen atom, a halogen atom, an alkyl or an alkoxy group of from 1 to 4 carbon atom(s) independently. The other symbols are the same meaning as described hereinbefore.) The other symbols are the same meaning as described hereinbefore. and that of the general formula: (wherein, R15 represents an alkyl group of from 1 to 4 carbon atom(s). Z represents a halogen atom or an alkylsulfonyloxy group or an arylsulfonyloxy group, which is substituted or unsubstituted such as methanesulfonyloxy or p-toluene-sulfonyloxy.) to obtain a compound of the general formula: (wherein, all the symbols are the same meaning as described hereinbefore.), if desired, by converting a nitro group of the resulting compound (Ia) to a hydroxy group, and further, if desired, by converting the hydroxy group of the obtained compound to an alkoxy group, to obtained a compound of the general formula: (wherein, all the symbols are the same meaning as described hereinbefore.), and then by subjecting saponification of a compound of the general formula (Ib), and further, if desired, by converting a carboxy group of the resulting compound to a tetrazolyl group.

Claim 14

12) A pharmaceutical composition for the prevention and/or the treatment for cerebral edema, which comprises, as active ingredient, an effective amount of the compound of the general formula (I) depicted in claim 1 wherein various symbols are as defined in claim 1, or a non-toxic salt thereof, together with pharmaceutical carrier and/or coating.