Therapeutic agent for senile dementia
View Patent ↗A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the following formula [1]: wherein Z is a group of the formula [2]: D is a group of —(CH 2 ) p -A-(CH 2 ) q —; G is ═N—, —CH—, etc.; and Ar is an aromatic heterocyclic group, etc.
1. A method for treatment of senile dementia, which comprises administering an effective amount of an imide derivative of the formula [1]:
wherein Z is a group of the formula [2]:
in which B is a carbonyl or a sulfonyl; R 1 , R 2 , R 3 and R 4 are independently a hydrogen atom or a lower alkyl, provided that R 1 and R 2 , or R 1 and R 3 may combine each other to form a hydrocarbon ring, or R 1 and R 3 may combine each other to form an aromatic hydrocarbon ring; said hydrocarbon ring may optionally be cross-linked with a lower alkylene or an oxygen atom; said lower alkylene and hydrocarbon ring may optionally be substituted by at least one alkyl; and n is 0 or 1,
D is a group of the formula [3]:
—(CH 2 ) p -A-(CH 2 ) q — [3]
in which A is a hydrocarbon ring optionally be cross-linked with a lower alkylene or an oxygen atom; said lower alkylene or said hydrocarbon ring may optionally be substituted by at least one alkyl; and p and q are independently 0, 1 or 2,
G is N, CH or COH, and —Ar is an aromatic heterocyclic group, an aromatic hydrocarbon group, benzoyl, phenoxy, or phenylthio, or
G is a carbon atom, and —Ar is biphenylmethylidene,
where said aromatic heterocyclic group aromatic hydrocarbon group, benzoyl, phenoxy, phenylthio, and biphenylmethylidene may optionally be substituted by at least one group selected from a lower alkyl, a lower alkoxy and a halogen atom,
or an acid addition salt thereof.
2. The method according to claim 1 , wherein —Ar is an aromatic heterobicyclic group, naphthyl, benzoyl, phenoxy or phenylthio, and G is N, CH or COH, or —Ar is biphenylmethylidene, and G is a carbon atom, wherein said aromatic heterobicyclic group, naphthyl, benzoyl, phenoxy, phenylthio and biphenylmethylidene may optionally be substituted by at least one group selected from a lower alkyl, a lower alkoxy and a halogen atom.
3. The method according to claim 1 , wherein —Ar is an aromatic heterocyclic group condensed with a benzene ring, or naphthyl, benzoyl, phenoxy or phenylthio, wherein said aromatic heterocyclic group condensed with a benzene ring, naphthyl, benzoyl, phenoxy, and phenylthio may optionally be substituted by at least one group selected from a lower alkyl, a lower alkoxy and a halogen atom, and G is N, CH or COH.
4. The method according to claim 1 , wherein Z is a group of the formula [4];
in which -L- is a single bond or a double bond, E is a lower alkylene optionally substituted by a lower alkyl, or an oxygen atom, R 5 is a hydrogen atom or a lower alkyl, and B is a carbonyl or a sulfonyl;
a group of the formula [5]:
in which -L is a single bond or a double bond, E is a lower alkylene optionally substituted by a lower alkyl, or an oxygen atom, R 5 is a hydrogen atom or a lower alkyl, and B is carbonyl or a sulfonyl;
a group of the formula [6]:
in which R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 are independently a hydrogen atom or a lower alkyl, or the adjacent two groups of R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 may combine each other to form a double bond, and B is a carbonyl or a sulfonyl;
a group of the formula [7]:
in which R 16 and R 17 are independently a hydrogen atom or a lower alkyl, or R 16 and R 17 may combine each other to form a saturated hydrocarbon ring, R 5 is a hydrogen atom or a lower alkyl, and B is a carbonyl or a sulfonyl; or
a group of the formula [8]:
in which B is a carbonyl or a sulfonyl.
5. The method according to claim 1 , wherein the senile dementia is selected from the group consisting of Alzheimer type dementia, cerebrovascular dementia, dementia with Lewy bodies, dementia from Pick's disease, dementia from Creutzfeldt-Jakob disease, dementia from Huntington's chorea and dementia from Parkinson's disease.
6. The method according to claim 1 , wherein the senile dementia is Alzheimer type dementia.
7. The method according to claim 1 , wherein the senile dementia is selected from the group consisting of cerebrovascular dementia and dementia with Lewy bodies.
8. A method for treatment of senile dementia, which comprises administering an effective amount of an imide compound of the formula [9]:
or an acid addition salt thereof, and
wherein the senile dementia is selected from the group consisting of cerebrovascular dementia, dementia with Lewy bodies, dementia from Pick's disease, dementia from Creutzfeldt-Jakob disease and dementia from Huntington's chorea.
9. The method according to claim 8 , wherein the senile dementia is selected from the group consisting of cerebrovascular dementia and dementia with Lewy bodies.
10. The method according to claim 8 , wherein the senile dementia is cerebrovascular dementia.
11. The method according to claim 8 , wherein the senile dementia is dementia with Lewy bodies.