4-substituted piperidine derivatives

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 473/00 (2006.01) A61K 31/445 (2006.01) A61K 31/4545 (2006.01) A61K 31/4725 (2006.01) A61P 25/00 (2006.01) A61P 35/00 (2006.01) C07D 211/56 (2006.01) C07D 211/60 (2006.01) C07D 211/96 (2006.01) C07D 401/12 (2006.01) C07D 401/14 (2006.01) C07D 471/04 (2006.01)

Patent

CA 2556589

Substituted piperidine compounds represented by the structure I are provided, wherein each of Rla, R1b, R1c, R1d, Rle, R1f, R1g, R1h, R2, R2A, R3, R4, A, X, a, x, and n is as defined in the specification. Substituted piperidine compounds of structure I may permeate or penetrate across a nerve cell membrane into the interior of a nerve cell, may inhibit intracellular Rho kinase enzyme found in nerve cells in mammals, and may find utility in repair of damaged nerves in the central and peripheral nervous system of such mammals. These compounds may induce the regeneration or growth of neurites in mammalian nerve cells and may thereby induce regeneration of damaged or diseased nerve tissue. These compounds also find additional utility as antagonists of the enzyme Rho kinase in treatment of disease states in which Rho kinase is implicated. Pharmaceutical compositions containing these substituted piperidine compounds may be useful to promote neurite growth and in the treatment of diseases in which Rho kinase inhibition is indicated.

La présente invention a trait à des composés de pipéridine substitués de formule (I), dans laquelle chacun parmi R¿la?, R¿1b?, R¿1c?, R¿1d?, R¿le?, R¿1f?, R¿1g?, R¿1h?, R¿2?, R¿2A?, R¿3?, R¿4?, A, X, a, x, et n sont tels que définis dans la description. Les composés de pipéridine substitués de formule (I) peuvent s'infiltrer ou pénétrer à travers une membrane de cellule nerveuse jusqu'à l'intérieur d'une cellule nerveuse, peuvent assurer l'inhibition de l'enzyme Rho kinase intracellulaire se trouvant dans des cellules nerveuses chez des mammifères, et peuvent être utiles dans la réparation de nerfs endommagés dans le système nerveux central et périphérique de tels mammifères. Les composés peuvent induire la régénération ou la croissance de neurites dans des cellules nerveuses mammaliennes et peuvent ainsi induire la régénération de tissu nerveux endommagé ou malade. Ces composés sont également utiles en tant qu'antagonistes de l'enzyme Rho kinase dans le traitement de conditions de maladie dans laquelle la Rho kinase est impliquée. L'invention a également trait à des compositions pharmaceutiques contenant ces composés de pipéridine substitués pouvant être utilisées pour favoriser la croissance de neurites et dans le traitement de maladies dans lesquelles l'inhibition de Rho kinase est indiquée.

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