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AR065623A1 - 3-CIANO-4- (4-PIRIDINILOXI-PHENYL) -PIRIDIN-2-ONA DERIVATIVES, A METHOD FOR THEIR PREPARATION, A PHARMACEUTICAL COMPOSITION THAT INCLUDES THEM AND THEIR USE IN THE DEVELOPMENT OF A MEDICATION FOR THE TREATMENT OF A DISEASE MEDIATED BY A POSITIVE ALOSTERIC MODULATOR OR BY AN MGL ORTHOSTERIC AGONIST - Google Patents

3-CIANO-4- (4-PIRIDINILOXI-PHENYL) -PIRIDIN-2-ONA DERIVATIVES, A METHOD FOR THEIR PREPARATION, A PHARMACEUTICAL COMPOSITION THAT INCLUDES THEM AND THEIR USE IN THE DEVELOPMENT OF A MEDICATION FOR THE TREATMENT OF A DISEASE MEDIATED BY A POSITIVE ALOSTERIC MODULATOR OR BY AN MGL ORTHOSTERIC AGONIST

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Publication number
AR065623A1
AR065623A1 ARP080100931A AR065623A1 AR 065623 A1 AR065623 A1 AR 065623A1 AR P080100931 A ARP080100931 A AR P080100931A AR 065623 A1 AR065623 A1 AR 065623A1
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AR
Argentina
Prior art keywords
compounds
preparation
treatment
formula
alkyl
Prior art date
Application number
Other languages
Spanish (es)
Original Assignee
Ortho Mcneil Janssen Pharm
Addex Pharma Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ortho Mcneil Janssen Pharm, Addex Pharma Sa filed Critical Ortho Mcneil Janssen Pharm
Publication of AR065623A1 publication Critical patent/AR065623A1/en

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Abstract

Compuestos, en particular, derivados de piridinona que incluyen cualquiera de sus formas estereoquímicamente isomeras, o un solvato o una sal aceptable para uso farmacéutico de dichos compuestos. Estos compuestos son moduladores alostéricospositivos de receptores de glutamato metabotropicos subtipo 2 (ômGluR2ö), utiles para el tratamiento o la prevencion de trastornos neurologicos y psiquiátricos asociados con la disfuncion de glutamato y enfermedades en las cuales participa elsubtipo mGluR2 de receptores metabotropicos. En particular, dichas enfermedades son trastornos del sistema nervioso central seleccionados del grupo de ansiedad, esquizofrenia, migrana, depresion, y epilepsia. También se proveen composicionesfarmacéuticas y un proceso para la preparacion de dichos compuestos al igual que al uso de dichos compuestos en la preparacion de un medicamento para la prevencion y el tratamiento de dichas enfermedades en las cuales participamGluR2. Reivindicacion 1: Un compuesto de la formula (1), incluyendo cualquiera de sus formas estereoquímicamente isomeras, donde: R1 es alquilo C4-6 o alquilo C1-3 sustituido con cicloalquilo C3-7; R2 es hidrogeno o halo; A es piridinilosustituido con uno o dos sustituyentes, donde cada sustituyente se selecciona de manera independiente de halo o alquilo C1-4; n es un numero entero de valor 1 o 2; o un solvato o una sal aceptable para uso farmacéutico, de dicho compuesto; siempreque si R2 es 2-fluor, entonces A no es 3-piridinilo sustituido con uno o dos sustituyentes, donde cada sustituyente se selecciona de manera independiente de halo o alquilo C1-4. Reivindicacion 37: Un proceso para la preparacion de un compuestocomo se reivindica en la reivindicacion 1 caracterizado por la reaccion de un intermediario de la formula (2), donde Y representa un grupo adecuado para el acoplamiento mediado por Pd con ácidos boronicos o ésteres boronicos, con un intermediario dela formula (3), donde R3 y R4 representan hidrogeno o alquilo C1-4, o donde R3 y R4 pueden tomarse juntos para formar el radical bivalente de la formula -CH2CH2-, -CH2CH2CH2- o -C(CH3)2C(CH3)2-, en un solvente adecuado inerte a la reaccion, enpresencia de una base adecuada y un catalizador adecuado, en condiciones térmicas, donde R1, R2, A y n se definen como en la reivindicacion 1; o, si se desea, la conversion adicional de los compuestos de la formula (1) entre sí, siguiendotransformaciones conocidas en el arte; o además, si se desea, la conversion de los compuestos de la formula (1) en una sal de adicion de ácido no toxica, terapéuticamente activa, mediante el tratamiento con un ácido; o de manera inversa, laconversion de la forma de sal de adicion de ácido en la base libre, mediante el tratamiento con un álcali; o, si se desea, la preparacion de sus formas estereoquímicamente isomeras.Compounds, in particular, pyridinone derivatives that include any of its stereochemically isomeric forms, or a solvate or a salt acceptable for pharmaceutical use of said compounds. These compounds are allosteric positive modulators of metabotropic glutamate receptors subtype 2 (ômGluR2ö), useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors participates. In particular, said diseases are disorders of the central nervous system selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. Pharmaceutical compositions and a process for the preparation of said compounds as well as the use of said compounds in the preparation of a medicament for the prevention and treatment of said diseases in which GluR2 participates are also provided. Claim 1: A compound of the formula (1), including any of its stereochemically isomeric forms, wherein: R 1 is C 4-6 alkyl or C 1-3 alkyl substituted with C 3-7 cycloalkyl; R2 is hydrogen or halo; A is pyridinyls substituted with one or two substituents, where each substituent is independently selected from halo or C1-4 alkyl; n is an integer of value 1 or 2; or a solvate or a salt acceptable for pharmaceutical use, of said compound; provided that R2 is 2-fluorine, then A is not 3-pyridinyl substituted with one or two substituents, where each substituent is independently selected from halo or C1-4 alkyl. Claim 37: A process for the preparation of a compound as claimed in claim 1 characterized by the reaction of an intermediate of the formula (2), wherein Y represents a group suitable for coupling mediated by Pd with boronic acids or boronic esters, with an intermediate of the formula (3), where R3 and R4 represent hydrogen or C1-4 alkyl, or where R3 and R4 can be taken together to form the bivalent radical of the formula -CH2CH2-, -CH2CH2CH2- or -C (CH3) 2C (CH3) 2-, in a suitable solvent inert to the reaction, presence of a suitable base and a suitable catalyst, in thermal conditions, where R1, R2, A and n are defined as in claim 1; or, if desired, the additional conversion of the compounds of the formula (1) from one another, following transformations known in the art; or in addition, if desired, the conversion of the compounds of the formula (1) into a therapeutically active non-toxic acid addition salt, by treatment with an acid; or conversely, the conversion of the acid addition salt form into the free base, by treatment with an alkali; or, if desired, the preparation of its stereochemically isomeric forms.

ARP080100931 2007-03-07 2008-03-06 3-CIANO-4- (4-PIRIDINILOXI-PHENYL) -PIRIDIN-2-ONA DERIVATIVES, A METHOD FOR THEIR PREPARATION, A PHARMACEUTICAL COMPOSITION THAT INCLUDES THEM AND THEIR USE IN THE DEVELOPMENT OF A MEDICATION FOR THE TREATMENT OF A DISEASE MEDIATED BY A POSITIVE ALOSTERIC MODULATOR OR BY AN MGL ORTHOSTERIC AGONIST AR065623A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP07103654 2007-03-07
EP07052442 2007-03-15
EP07116402 2007-09-14

Publications (1)

Publication Number Publication Date
AR065623A1 true AR065623A1 (en) 2009-06-17

Family

ID=40845781

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP080100931 AR065623A1 (en) 2007-03-07 2008-03-06 3-CIANO-4- (4-PIRIDINILOXI-PHENYL) -PIRIDIN-2-ONA DERIVATIVES, A METHOD FOR THEIR PREPARATION, A PHARMACEUTICAL COMPOSITION THAT INCLUDES THEM AND THEIR USE IN THE DEVELOPMENT OF A MEDICATION FOR THE TREATMENT OF A DISEASE MEDIATED BY A POSITIVE ALOSTERIC MODULATOR OR BY AN MGL ORTHOSTERIC AGONIST

Country Status (3)

Country Link
AR (1) AR065623A1 (en)
CL (1) CL2008000672A1 (en)
NZ (1) NZ579989A (en)

Also Published As

Publication number Publication date
NZ579989A (en) 2011-09-30
CL2008000672A1 (en) 2008-11-03

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