| Therapeutic agent for senile dementia -> Monitor Keywords |
|
|
 
Therapeutic agent for senile dementiaRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered And Includes At Least Nitrogen And Sulfur As Ring MembersTherapeutic agent for senile dementia description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060142276, Therapeutic agent for senile dementia. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] 1. TECHNICAL FIELD [0002] The present invention relates to a therapeutic agent for dementia, more particularly, a therapeutic agent for dementia, which comprises as an active ingredient an imide derivative. [0003] 2. BACKGROUND ART [0004] Senile dementia is divided broadly into the Alzheimer type dementia and the cerebrovascular dementia, and about 80% of the patients of senile dementia can be classified into these categories. As the population rapidly ages, the number of the patients of senile dementia demonstrates an upward trend in these days. In Japan, it is speculated that about 7% of the people 65 years old or over show the symptoms of dementia, and hence, it is an urgent need to develop an excellent therapeutic agent for dementia. The Alzheimer type dementia is accompanied by senile plaque and neurofibrillary tangle, and it is pathologically characterized by encephalatrophy caused by significant neuronal death. In familial Alzheimer's disease, several gene mutations have been identified, whereby a leading hypothesis for neuronal pathogenetic mechanism thereof has been speculated, but the most of cases are sporadic, and hence, it may be said that Alzheimer's disease is still a disease of unknown cause. Accordingly, at the present, there is no radical therapeutic method for inhibiting neurodegeneration. The Alzheimer type dementia shows as core symptoms cognition dysfunctions such as disorders of memory, faculty of orientation, attention, etc., and it is also accompanied by peripheral symptoms such as psychotic manifestations or abnormal behavior problems (e.g., depression, aggressive attack, delusion, etc.). In the symptomatic treatment of these symptoms, only an acetylcholine esterase inhibitor has been clinically used, and it has been reported that acetylcholine esterase inhibitors are also effective to not only core symptoms but also peripheral symptoms. In the treatment with acetylcholine esterase inhibitors, neurotransmitter acetylcholine is supplemented by inhibiting acetylcholine-degrading enzyme, while acetylcholine neuronal cells, which are closely-linked with cognitive function, are especially disturbed in Alzheimer's disease and neurotransmitter acetylcholine is reduced. [0005] On the other hand, the cerebrovascular dementia is a disease which develops owing to cerebrovascular disorders, and at the moment, there is no cure for core symptoms thereof. However, recently, the clinical trial of acetylcholine esterase inhibitors has been done, and it has become apparent that these medicaments are also effective to cerebrovascular dementia. Accordingly, there is a possibility that a therapeutic agent having a similar therapeutic mechanism to the Alzheimer's disease such as acetylcholine esterase inhibitors may be effective even to cerebrovascular dementia (e.g., Rinsho-Seishinigaku (i.e., Clinical Psychiatry), 31 (10): 1189-1193 (2002)). [0006] On the other hand, there has not been known any therapeutic agent which shows no acetylcholine esterase inhibitory activity but is effective to senile dementia such as the Alzheimer type dementia and the cerebrovascular dementia. Moreover, JP Patent No. 2800953 discloses imide derivatives showing an excellent antipsychotic activity and anxiety reducing activity, but it has never indicated whether or not those derivatives show effects on senile dementia. DISCLOSURE OF INVENTION [0007] The present invention provides a therapeutic agent for senile dementia. More particularly, the present invention provides a therapeutic agent effective to both of the core symptoms and the peripheral symptoms of senile dementia. [0008] The present inventors have intensively studied in order to solve the above problems, and found that the imide compound of the present invention exhibits a therapeutic effect in cognitive/memory disturbance models produced by acetylcholine receptor blocker, which are representative animal models for senile dementia, and finally they have accomplished the present invention. [0009] Namely, the present invention relates to the following: [0010] (1) A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient 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.sup.1 R.sup.2, R.sup.3 and R.sup.4 are independently a hydrogen atom or a lower alkyl, provided that R.sup.1 and R.sup.2, or R.sup.1 and R.sup.3 may combine each other to form a hydrocarbon ring, or R.sup.1 and R.sup.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.sub.2).sub.p--A--(CH.sub.2).sub.q-- [3](in which A is a hydrocarbon ring 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 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 or 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. [0011] (2) The therapeutic/preventive agent for cognitive dysfunctions according to the above (1), which is a therapeutic agent for senile dementia. [0012] (3) A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the above formula [1], wherein --Ar is an aromatic heterobicyclic group, naphthyl, benzoyl, phenoxy or phenylthio and G is N, CH or COH, or --Ar is biphenyl-methylidene and G is a carbon atom (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), or an acid addition salt thereof. [0013] (4) The therapeutic/preventive agent for cognitive dysfunctions according to the above (3), which is a therapeutic agent for senile dementia. [0014] (5) A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the above formula [1], wherein --Ar is an aromatic heterocyclic group condensed with a benzene ring, or naphthyl, benzoyl, phenoxy or phenylthio (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, or an acid addition salt thereof. [0015] (6) The therapeutic/preventive agent for cognitive dysfunctions according to the above (5), which is a therapeutic agent for senile dementia. [0016] (7) A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the above formula [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.sup.5 is a hydrogen atom or a lower alkyl, and B is the same as defined in the above (1); a group of the formula [5]: in which --L--, E, R.sup.5 and B are as defined above; a group of the formula [6]: in which R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 are independently a hydrogen atom or a lower alkyl, or the adjacent two groups of R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 may combine each other to form a double bond, and B is as defined above; a group of the formula [7]: in which R.sup.16 and R.sup.17 are independently a hydrogen atom or a lower alkyl, or R.sup.16 and R.sup.17 may combine each other to form a saturated hydrocarbon ring, and R.sup.5 and B are as defined above; or a group of the formula [8]: in which B is as defined above, or an acid addition salt thereof. [0017] (8) The therapeutic/preventive agent for cognitive dysfunctions according to the above (7), which is a therapeutic agent for senile dementia. [0018] (9) A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the formula [9]: or an acid addition salt thereof. [0019] (10) The therapeutic/preventive agent for cognitive dysfunctions according to the above (9), which is a therapeutic agent for senile dementia. [0020] (11) The therapeutic/preventive agent for cognitive dysfunctions according to the above (2), (4), (6), (8) or (10), which is a therapeutic agent for the Alzheimer type dementia. [0021] (12) The therapeutic/preventive agent for cognitive dysfunctions according to the above (2), (4), (6), (8) or (10), which is a therapeutic agent for the cerebrovascular dementia. BRIEF DESCRIPTION OF DRAWINGS [0022] FIG. 1 shows the effects of the imide derivative on rats in one step-through passive avoidance test where the acetylcholine receptor blocker scopolamine was used for inducing amnesia, and indicates the step-through latency during the training (*: P<0.05 vs the group treated with 0.5% MC+scopolamine (Steel's test)). [0023] FIG. 2 shows the effects of the imide derivatives on rats in one step-through passive avoidance test where the acetylcholine receptor blocker scopolamine was used for inducing amnesia, and indicates the step-through latency during the test (*: P<0.05 vs the group treated with 0.5% MC+scopolamine (Steel's test), #: <0.01 vs the group treated with 0.5% MC+saline solution (Mann-Whitney test)). BEST MODE FOR CARRYING OUT THE INVENTION [0024] Each group of the imide derivative of the formula [1] of the present invention are explained in detail. [0025] The lower alkylene for Z and A includes, for example, ones having not more than 3 carbon atoms such as methylene, ethylene, trimethylene, etc. [0026] The hydrocarbon ring for Z and A includes, for example, a cycloalkane or cycloalkene having not more than 7 carbon atoms. The cycloalkane having not more than 7 carbon atoms includes, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, etc. The cycloalkene having not more than 7 carbon atoms includes, for example, cyclopentene, cyclohexene, cycloheptene, etc. [0027] The hydrocarbon ring being cross-linked with a lower alkylene or an oxygen atom for Z and A includes, for example, rings having not more than 10 carbon atoms such as bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.1.1]hex-2-ene, bicyclo[2.2.1]heptane, bicyclo[2.2.1]hept-2-ene, bicyclo[2.2.2]octane, bicyclo[2.2.2]oct-2-ene, bicyclo[4.1.1]octane, bicyclo-[4.1.1]oct-2-ene, bicyclo[4.1.1]oct-3-ene, bicyclo[3.2.1]octane, bicyclo-[3.2.1]oct-2-ene, bicyclo[3.2.1]oct-3-ene, bicyclo[3.2.1]oct-6-ene, bicyclo-[3.2.2]nonane, bicyclo[3.2.2]non-2-ene, bicyclo[3.2.2]non-3-ene, bicyclo[3.2.2]non-6-ene, 2-oxabicyclo[1.1.1]butane, 2-oxabicyclo[2.1.1]pentane, 2-oxabicyclo[2.1.1]pent-4-ene, 7-oxabicyclo[2.2.1]hexane, 7-oxabicyclo[2.2.1]hex-2-ene, 7-oxabicyclo[4.1.1]heptane, 7-oxabicyclo[4.1.1]hept-2-ene, 7-oxabicyclo[4.1.1]hept-3-ene, 8-oxabicyclo[3.2.1]heptane, 8-oxabicyclo[3.2.1]hept-2-ene, 8-oxabicyclo[3.2.1]hept-3-ene, 8-oxabicyclo[3.2.1]hept-6-ene, etc. [0028] The aromatic hydrocarbon ring for Z includes, for example, ones having not more than 10 carbon atoms such as phenyl ring, naphthyl ring, etc. [0029] The binding position of the hydrocarbon ring for A includes, for example, -1, 1-, -1,2-, -1,3-, -1,4-, etc. [0030] The aromatic hydrocarbon group for --Ar includes, for example, ones having not more than 10 carbon atoms such as phenyl, naphthyl, etc. The aromatic heterocyclic group for --Ar includes, for example, an aromatic heteromonocyclic group and an aromatic heterobicyclic group. [0031] The aromatic heteromonocyclic group includes, for example, ones having not more than 6 carbon atoms, and further having the same or different 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, such as pyridyl, pyrimidinyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, furyl, imidazolyl, etc. [0032] The aromatic heterobicyclic group includes, for example, ones having not more than 10 carbon atoms, and further having the same or different 1 to 5 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, such as benzolog-fused rings (e.g., benziso-thiazolyl, benzisoxazolyl, benzofuryl, quinolyl, isoquinolyl, indolyl, indazolyl, benzimidazolyl, benzoxazolyl, etc.), naphthyridinyl, puteridinyl, thienofuranyl, imidazothiophen-yl, imidazofuranyl, etc. [0033] The alkyl includes, for example, ones having not more than 6 carbon atoms, and preferably lower alkyl groups having not more than 4 carbon atoms, such as methyl, ethyl, propyl, 2-propyl, butyl, etc. The lower alkyl includes, for example, ones having not more than 4 carbon atoms, such as methyl, ethyl, propyl, 2-propyl, butyl, etc. Continue reading about Therapeutic agent for senile dementia... Full patent description for Therapeutic agent for senile dementia Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Therapeutic agent for senile dementia patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Therapeutic agent for senile dementia or other areas of interest. ### Previous Patent Application: Use of selected cgrp-antagonists in combination with other antimigraine drugs for the treatment of migraine Next Patent Application: Mitotic kinesin inhibitors Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Therapeutic agent for senile dementia patent info. IP-related news and info Results in 5.4299 seconds Other interesting Feshpatents.com categories: Daimler Chrysler , DirecTV , Exxonmobil Chemical Company , Goodyear , Intel , Kyocera Wireless , 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
