Arylipiperdinopropanol and arylipiperazinopropanol derivatives and pharmaceuticals containing the same
View Patent ↗A compound having the formula (I) or its salt, hydrate, hydrate salt or solvate: wherein R 1 to R 4 independently represent H, halogen, OH, alkoxy, optionally substituted alkyl, aryl, or aralkyl group, R 5 represents H, optionally substituted alkyl, aryl, or aralkyl group, E 1 represents O, S, or —NR 6 , where R 6 represents H, an optionally substituted alkyl, aryl, or aralkyl group, E 2 represents O, S, or —NR 7 , where R 7 represents H, an optionally substituted alkyl, aryl, or aralkyl group, A represents CH, C(OH), or N, X represents H, halogen, alkoxy, or an optionally substituted alkyl group, and Q represents an optionally substituted phenyl group, phenoxy, phenylmethyl, or cycloalkyloxy group, where when E 1 represents O or S, E 2 does not represent O or S, which has an action of suppressing the cytotoxic Ca 2+ overload and lipid peroxidation and effective for pharmaceutical preparation for the alleviation and treatment of symptoms due to ischemic diseases, etc.
1. A method for the alleviation or treatment of symptoms due to neurodegenerative diseases which are selected from the group consisting of Parkinson's disease and amyotrophic lateral sclerosis comprising administering to a patient in need of such alleviation or treatment an effective amount of a pharmaceutical composition containing, as an effective ingredient, a compound having the formula (I) or its pharmaceutically acceptable salt, hydrate, or hydrate salt:
wherein
R 1 to R 4 independently represent a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group, an alkyl group, or an alkyl group substituted with a halogen atom,
R 5 represents a hydrogen atom, an alkyl group, or an alkyl group substituted with a halogen atom,
E 1 represents —NH,
E 2 represents an oxygen atom,
A represents a nitrogen atom,
X represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, or an alkyl group substituted with a halogen atom, and
Q represents a phenyl group, a phenyl group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom, a phenoxy group, a phenoxy group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom, a phenylmethyl group, or a phenylmethyl group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom,
and a carrier therefor.
2. A method as claimed in claim 1 , wherein said pharmaceutical composition is orally or non-orally administered.
3. A method as claimed in claim 1 , wherein, in the formula (I), R 1 to R 4 each independently represent a hydrogen atom, a halogen atom, an alkoxy group, or an alkyl group or an alkyl group substituted with a halogen atom, R 5 represents a hydrogen atom or an alkyl group or an alkyl group substituted with a halogen atom, E 1 represents NH, and E 2 represents an oxygen atom.
4. A method as claimed in claim 1 , wherein, in the formula (I), R 1 to R 4 each independently represent a hydrogen atom, a halogen atom, an alkoxy group, or an alkyl group or an alkyl group substituted with a halogen atom, R 5 represents a hydrogen atom or an alkyl group or an alkyl group substituted with a halogen atom, E 1 represents an oxygen atom, and E 2 represents NH.
5. A method as claimed in claim 1 , wherein, in the formula (I), one of R 1 to R 4 is a hydrogen atom and the others each independently represent a halogen atom, an alkoxy group, or an alkyl group or an alkyl group substituted with a halogen atom.
6. A method as claimed in claim 1 , wherein, in the formula (I), Q represents a phenyl group, a phenyl group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom, a phenoxy group, a phenoxy group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom, a phenylmethyl group, or a phenylmethyl group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom.
7. A method for suppressing cell death in a patient having a neurodegenerative disease selected from the group consisting of Parkinson's disease and amyotrophic lateral sclerosis comprising:
administering to said patient in need thereof an effective amount of a pharmaceutical composition containing, as an effective ingredient, a compound having the formula (I) or its pharmaceutically acceptable salt, hydrate, or hydrate salt:
wherein
R 1 to R 4 independently represent a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group, an alkyl group, or an alkyl group substituted with a halogen atom,
R 5 represents a hydrogen atom, an alkyl group, or an alkyl group substituted with a halogen atom,
E 1 represents —NH,
E 2 represents an oxygen atom,
A represents a nitrogen atom,
X represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, or an alkyl group substituted with a halogen atom, and
Q represents a phenyl group, a phenyl group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom, a phenoxy group, a phenoxy group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom, a phenylmethyl group, or a phenylmethyl group substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a C 1 to C 5 linear or branched alkoxy group, a C 1 to C 5 linear or branched alkyl group, a C 1 to C 5 linear or branched alkyl group substituted with a halogen atom,
and a carrier therefor.