4-Substituted piperidine compound
The present invention provides a novel compound having a superior acetylcholinesterase inhibitory action. It provides a compound represented by the formula: (In the formula, R 1 represents a group represented by the formula: (wherein, R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom, an optionally substituted C 1-6 alkoxy group and the like; and m represents an integer from 0 to 6) and the like; and R 2 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group or an optionally substituted C 2-6 alkynyl group), a salt thereof or a hydrate of them.
1 . A method for treating a disease or condition against which an acetylcholinesterase inhibitory action is efficacious, said method comprising:
administering a therapeutically effective amount of a compound, a salt thereof, or a hydrate of said compound or salt thereof to a patient in need thereof,
wherein said compound is represented by the formula:
wherein R 2 of formula (I) represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 1-6 alkenyl group or an optionally substituted C 1-6 alkynyl group, a salt thereof, or a hydrate of said compound or salt thereof; and
R 1 of formula (I) represents any one of group selected from the group consisting of the formulae:
wherein R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted hydrocarbon group, an optionally substituted C 1-6 alkoxy group, a C 1-6 acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group or a C 1-6 thioalkoxy group;
R 7 represents a hydrogen atom or a C 1-6 alkyl group;
the partial structure represents a single bond or a double bond;
m is 0 or an integer from 1 to 6; and
p represents an integer of 1 or 2.
2 . The method of claim 1 , wherein said R 1 in said formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a group selected from the group of formulae consisting of
wherein R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted hydrocarbon group, an optionally substituted C 1-6 alkoxy group, a C 1-6 acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group or a C 1-6 thioalkoxy group; and
m is 0 or an integer from 1 to 6.
3 . The method of claim 1 or 2 , wherein said wherein said substituent in the optionally substituted C 1-6 alkyl group, optionally substituted C 2-6 alkenyl group or optionally substituted C 2-6 alkynyl group of R 2 of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is at least one selected from the group consisting of a halogen atom, a hydroxyl group, a nitrile group, a C 1-6 alkyl group, C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 1-6 alkoxyalkoxy group, an aryloxy group, an aralkyloxy group, a halogenated C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyano C 1-6 alkyl group, a halogenated C 1-6 alkoxy group, a hydroxy C 1-6 alkoxy group, a cyano C 1-6 alkoxy group, a C 1-6 acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group and a C 1-6 thioalkoxy group.
4 . The method of claim 1 or 2 , wherein said R 3 , R 4 , R 5 and R 6 in formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, are the same as or different from each other and each represents a hydrogen atom or an optionally substituted C 1-6 alkoxy group.
5 . The method according to claim 1 or 2 , wherein said R 3 , R 4 , R 5 and R 6 in formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, are the same as or different from each other and each represents a hydrogen atom or an optionally substituted methoxy group.
6 . The method according to claim 1 or 2 , wherein m of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is an integer of 1.
7 . The method according to claim 1 , wherein R 1 of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a [(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl group.
8 . The method according to claim 1 or 2 , wherein R 2 of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a hydrogen atom.
9 . The method according to claim 1 or 2 , wherein R 2 of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is an optionally substituted C 1-6 alkyl group.
10 . The method according to claim 1 or 2 , wherein R 2 of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a C 1-6 alkyl group substituted with (1) a halogen atom, (2) a hydroxyl group or (3) a nitrile group.
11 . The method according to claim 1 or 2 , wherein R 2 of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a methyl group, an ethyl group, a n-propyl group, an iso-propyl group, a 2-methyl-1-propyl group or a tert-butyl group.
12 . The method according to claim 1 , wherein said compound, a salt thereof, or a hydrate of said compound or salt thereof, is
4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methylpiperidine,
4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-methylpiperidine,
4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-(1-methylethyl)piperidine or
4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-(2-methylpropyl)piperidine.
13 . The method according to claim 1 or 2 , wherein the disease or condition is senile dementia, cerebrovascular dementia or attention deficit hyperactivity disorder.