Sanofi-aventis

Mitsubishi Pharma Corporation

Sanofi-synthelabo

Synthelabo

Alain Nedelec

Alistair Lochead

Mourad Saady

Philippe Yaiche

Samir Jegham

Thierry Gallet

Patrick Andre Lardenois

Franck Slowinski

Fr&eacute;d&eacute;ric Galli

Séverine Marguerie

Antonio Almario Garcia

Odile LeClerc

Luc Even

Adrien Tak Li

Frederic Galli

Jean Jeunesse

Axelle Solignac

Frédéric Galli

Axelle Samson

Odile Leclerc

Jean Jacques Koenig

Yves Guminski

Laurence De Cruz

The invention relates to use of a pyrimidone derivative represented by formula (I) or a salt thereof as therapeutic agents: Wherein m, n, p, X, Y, R1, R2, R3, R4 R5, are as defined herein. The invention specifically relates to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3&#x3b2; or GSK3&#x3b2; and cdk5/p25, such as Alzheimer disease.

[object Object]

Compounds complying with the general formula in which R either represents a halogen atom or a phenyl group substituted by one or more groups chosen from halogen atoms and (C-C)alkyl, (C-C)alkoxy, nitro, amino, trifluoromethyl, cyano, hydroxy, acetyl or methylenedioxy groups, or represents a pyridinyl group, a thienyl group, an indolyl group, or a pyrimidinyl group optionally substituted by one or more (C-C)alkoxy groups, where, of the two carbon-carbon bonds represented by, one is single and the other may be single or double. The compounds of this invention are useful as therapeutic agents.

Derivatives of 5-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, their preparation and their therapeutic application

The invention relates to therapeutic uses of a pyrimidone derivative represented by formula (I) or a salt thereof:  Wherein X, Y, R1, R2, m and n are as defined herein. Specifically, a medicament comprising the said derivative or a salt thereof as an active ingredient is used for preventive and/or therapeutic treatment of a neurodegenerative diseases caused by abnormal activity of GSK3&#x3b2; such as Alzheimer's disease.

The invention relates to use of a pyrimidone derivative represented by formula (I)or a salt thereof wherein: X, Y, R1, R2, R3, R4, R5, m, n and p are as defined herein. In particular, the invention relates to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3&#x3b2; or GSK3&#x3b2; and cdk5/p25, such as Alzheimer disease.

The invention relates to an use of pyrimidone derivative represented by formula (I) or a salt thereof: wherein m, n, p, X, Y, R1, R2, R3, R4 and R5 are as defined herein for treating a variety of disease states. More specifically, the invention relates to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3&#x3b2; or GSK3&#x3b2; and cdk5/p25, such as Alzheimer's disease.

Use of substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo[1,2-a] pyrimidin-5(1H)one derivatives as therapeutic agents

The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a Calkyl group and a hydrogen atom; y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally; or a methylene group optionally substituted; R1 represents a pyrimidine group optionally substituted; R2 may represent a Calkyl group optionally substituted by a Caryloxy or a Carylamino group; a Ccycloalkyl group, a Calkylthio group, a Calkoxy group, a Cperhalogenated alkyl group, a Chalogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R4 represents each independently a hydrogen atom, Calkyl group, a hydroxy group, a Calkoxy group or a halogen atom; R5 represents a hydrogen atom, a Calkyl group or a halogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3&#x3b2;3 or GSK3&#x3b2;3 and cdk5/p25, such as Alzheimer disease.

Substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo [1,2-a]pyrimidin-5(1H)one derivatives for neurodegenerative disorders

The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: (I) X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a Calkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring optionally substituted; R2 represents a heterocyclic bicyclic rings, having 1&#x2013;4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom and having 5&#x2013;9 carbon atoms, of formula (II) R3 represents a hydrogen atom, a Calkyl group, a hydroxy group, a Calkoxy group or a halogen atom; R4 represents a hydrogen atom, a Calkyl group, a Calkoxy group or a halogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3&#x3b2; or GSK3&#x3b2; and cdk5/p25, such as Alzheimer disease 

Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives

Compounds complying with the general formula (I) in which R either represents a halogen atom or a phenyl group substituted by one or more groups chosen from halogen atoms and (C&#x2013;C)alkyl, (C&#x2013;C)alkoxy, nitro, amino, trifluoromethyl, cyano, hydroxy, acetyl or methylenedioxy groups, or represents a pyridinyl group, a thienyl group, an indolyl group, or a pyrimidinyl group optionally substituted by one or more (C&#x2013;C)alkoxy groups, where, of the two carbon-carbon bonds represented by, one is single and the other may be single or double. Therapeutic application.

Derivatives of 5-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, the preparation thereof and the application of same in therapeutics

The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a Calkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a hydroxyiminomethylene group, a dioxolan group, a nitrogen atom being optionally substituted; or a methylene group optionally substituted; or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring optionally substituted; R2 may represent a Calkyl group optionally; a Ccycloalkyl group, a Calkythio group, a Calkoxy group, a Cperhalogenated alkyl group, a Chalogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R4 represent, each independently, a hydrogen atom, a Calkyl group, a hydroxy group, a Calkoxy group or a halogen atom; R5 represents a hydrogen atom, a Calkyl group or a halogen atom; with the proviso that when R3 and R4 represent each a hydrogen atom then R5 is not a hydrogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3&#x3b2; or GSK3&#x3b2;, and cdk5/p25, such as Alzheimer disease 

Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido{1,2-a}pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo{1,2-a}pyrimidin-5(1h)one derivatives

Compounds of general formulain which X represents an oxygen atom or a group of formula NZ in which Z represents a hydrogen atom or an alkyl group, n represents a number 0, 1 or 2, and R, R, R, Rand Reach represent a hydrogen or halogen atom or a trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, alkyl, alkoxy, phenoxy or phenyl group optionally substituted with a halogen atom or a trifluoromethyl, cyano, hydroxyl, alkyl or alkoxy group, or alternatively Rand Rtogether form a group of formula &#x2014;OCHO&#x2014; or &#x2014;CHCHCHCH&#x2014;.Application in therapy.

1,4-diazabicyclo[3.2.2]nonane-4-carboxylates and carboxamide derivates, production and use thereof in therapeutics

Imidazo[1,2-&#x3b1;]pyrimidinones and pyrimido[1,2-&#x3b1;]pyrimidinones useful for preventive and/or therapeutic treatment of neurodegenerative diseases, such as Alzheimer's disease, caused by abnormal GSK3&#x3b2; activity.

2-pyridinyl-6,7,8,9-tetrahydropyrimido{1,2-a}pyrimidin-4-one and 7-pyridinyl-2,3-dihydoimidazo{1,2-a}pyrimidin-5(1H)one derivatives

4-heteroparyl-1,4-diazabicyclo&lsqb;3.2.2&rsqb;nonane, preparation and therapeutic use thereof

The invention relates to 2,5-diazabicyclo&lsqb;2.2.1&rsqb;heptane derivatives, to pharmaceutical compositions containing them, and to methods for the treatment or prevention of disorders associated with a dysfunction of the nicotinic receptors utilizing them.

2,5,-diazabicyclo&lsqb;2.2.1&rsqb;heptane derivatives, their preparation and therapeutic uses

The invention relates to 1,4-diazabicyclo&lsqb;3.2.2&rsqb;nonane derivatives, to pharmaceutical compositions containing them, and to methods for the treatment or prevention of disorders associated with a dysfunction of the nicotinic receptors utilizing them.

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Colombes, France

Alain Nedelec