METHOD OF TREATING COGNITIVE IMPAIRMENT

• US 20090221554A1
• Filed: 02/28/2008
• Published: 09/03/2009
• Est. Priority Date: 02/28/2008
• Status: Active Application

• Current Assignee: Zenyaku Kogyo Kabushiki Kaisha
• Original Assignee: Zenyaku Kogyo Kabushiki Kaisha
• Inventors: YAMAGUCHI, Yoshimasa, Saitoh, Kenichi, Matsuno, Toshiyuki
• Application Number:
  US12/039,192
• Publication Number:
  US 20090221554A1
• Time in Patent Office: Days
• US Class Current: 514/215
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

Disclosed is an method of treating cognitive impairment, including administering to a subject in need thereof a combination of a therapeutic agent for neurodegenerative disease and a therapeutically effective amount of a heterocyclic compound represented by the following general formula (I):

Claims

1. A method of treating cognitive impairment, comprising administering to a subject in need thereof a therapeutic agent for neurodegenerative disease and a heterocyclic compound represented by the following general formula (I):

wherein

the structural unit having the general formula (II);

is one or more structural units selected from multiple types of structural units having the general formula (III);

R₁ and R₂ each are one or more functional groups independently selected from the group consisting of a hydrogen atom, halogen atom, hydroxy group, amino group, acetylamino group, benzylamino group, trifluoromethyl group, C₁-C₆ alkyl group, C₁-C₆ alkoxy group, and —

O—

(CH₂)_n—

R₅ (R₅ is a vinyl group, C₃-C₆ cycloalkyl group, or phenyl group, and n is 0 or

     1);

R₃ and R₄ each are one or more functional groups independently selected from the group consisting of a hydrogen atom, C₁-C₆ alkyl group, C₃-C₈ cycloalkyl group, and —

CH(R₇)—

R₆;

alternatively, R₃ and R₄ together form a spiro ring having the general formula (IV);

said R₆ is one or more functional groups selected from the group consisting of a vinyl group, ethinyl group, phenyl (which may be substituted by a C₁-C₆ alkyl group, C₁-C₆ alkoxy group, hydroxy group, 1 or 2 halogen atoms, di C₁-C₆ alkylamino group, cyano group, nitro group, carboxy group, or phenyl group), phenethyl group, pyridyl group, thienyl group, and furil group;

said R₇ is a hydrogen atom or C₁-C₆ alkyl group;

in the general formula (IV), the structural unit B is one or more structural units selected from multiple types of structural units having the general formula (V);

said structural unit B binds at a position marked by * in the general formula (V) to form a spiro ring; and

R₈ is one or more functional groups selected from the group consisting of a hydrogen atom, halogen atom, hydroxy group, C₁-C₆ alkoxy group, cyano group, and trifluoromethyl group;

a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof wherein therapeutic agent for a neurodegenerative disease and said heterocyclic compound having formula (I) are administered in amounts effective to treat cognition impairment.

2. A method of treatment in accordance with claim 1, wherein the heterocyclic compound is at least one heterocyclic compound chosen from the group consisting of:

3,3-dibenzylimidazo[1,2-a]pyridin-2(3H)-one, spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-indan], 3,3-dipropylimidazo[1,2-a]pyridin-2(3H)-one, 3,3-dibutylimidazo[1,2-a]pyridin-2(3H)-one, 5,5-dibenzylimidazo[2,1-b]thiazol-6(5H)-one, 3,3-dibenzylimidazo[1,2-a]pyrimidin-2(3H)-one, spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-(4′

-fluoroindan)], spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-(5′

-methoxyindan)], spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-(4′

-cyanoindan)], spiro[imidazo[2,1-a]isoquinolin-2(3H)-one-3,2′

-indan], spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-((1,2,5-thiadiazo)[4,5-c]indan)], spiro[imidazo[1,2-a]pyrimidin-2(3H)-one-3,2′

-indan], spiro[imidazo[2,1-a]isoquinolin-2(3H)-one-3,4′

-(1′

-cyclopentene)], 3,3-bis(4-chlorobenzyl)imidazo[1,2-a]pyridin-2(3H)-one, 8-cyclopropylmethyloxy-3,3-diallylimidazo[1,2-a]pyridin-2(3H)-one, spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-(4′

-hydroxyindan)], spiro[8-hydroxy-imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-indan], spiro[8-methoxyimidazo[1,2-a]pyridin-2(3H)-one-3,4′

-(1′

-cyclopentene)], and spiro[8-cyclopropylmethyloxyimidazo[1,2-a]pyridin-2(3H)-one-3,4′

-(1′

-cyclopentene)].

3. A method of treatment in accordance with claim 1, wherein said heterocyclic compound is spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-indan].

4. A method of treatment in accordance with claim 1, wherein said cognitive imprairment is caused by cerebrovascular disease, Lewy body dementia, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Pick'"'"'s disease, Huntington'"'"'s disease or Down'"'"'s syndrome.

5. A method of treatment in accordance with claim 1, wherein said cognitive impairment is memory impairment due to aging.

6. A method of treatment in accordance with claim 1, wherein said therapeutic agent for neurodegenerative disease is an acetylcholinesterase inhibitor or a non-competitive NMDA receptor antagonist.

7. A method of treatment in accordance with claim 6, wherein said therapeutic agent for neurodegenerative disease is donepezil hydrochloride, rivastigmine tartrate or galantamine hydrobromide.

8. A method of treatment in accordance with claim 6, wherein said therapeutic agent for neurodegenerative disease is memantine hydrochloride.

9. A method of treatment in accordance with claim 1, comprising administering simultaneously said therapeutic agent for neurodegenerative disease and said heterocyclic compound, hydrate thereof, solvate thereof or pharmaceutically acceptable salt thereof.

10. A method of treatment in accordance with claim 9, wherein said therapeutic agent for neurodegenerative disease and said heterocyclic compound, hydrate thereof, solvate thereof or pharmaceutically acceptable salt thereof are part of a single, unitary pharmaceutical dosage form.

11. A method of treatment in accordance with claim 1, comprising administering separately said therapeutic agent for neurodegenerative disease and said heterocyclic compound, hydrate thereof, solvate thereof or pharmaceutically acceptable salt thereof.

12. A method of treatment in accordance with claim 1, comprising administering consecutively said therapeutic agent for neurodegenerative disease and said heterocyclic compound, hydrate thereof, solvate thereof or pharmaceutically acceptable salt thereof.

13. A method of treatment in accordance with claim 1, wherein said therapeutic agent for neurodegenerative disease and said heterocyclic compound, hydrate thereof, solvate thereof or pharmaceutically acceptable salt thereof are administered in amounts which would be subtherapeutic if administered alone.

14. A method of treatment in accordance with claim 1, wherein said therapeutic agent for neurodegenerative disease is donepezil hydrochloride and said heterocyclic compound is spiro[imidazo[1,2-a]pyridin-2(3H)-one-3,2′

-indan].