2-aryl-acetic acids, their derivatives and pharmaceutical...

C - Chemistry – Metallurgy – 07 – D

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C07D 207/337 (2006.01) A61K 31/18 (2006.01) A61K 31/40 (2006.01) C07C 303/40 (2006.01) C07C 311/51 (2006.01)

Patent

CA 2511582

Selected 2-arylacetic acids, their derivatives and pharmaceutical compositions that contain these compounds are useful in inhibiting chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2 membrane receptors. The compounds are used for the prevention and treatment of pathologies deriving from said activation. In particular, 2(ortho)-substituted arylacetic acids or their derivatives, such as amides and sulfonamides, lack cyclo-oxygenase inhibition activity and are particularly useful in the treatment of neutrophil-dependent pathologies such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.

L'invention concerne des acides 2-arylacétiques sélectionnés, leurs dérivés et des compositions pharmaceutiques contenant ces composés, lesquels composés sont utiles dans l'inhibition de l'activation chimiotactique de polynucléaires neutrophiles (leucocytes PMN) induite par l'interaction de l'interleukine 8 (IL-8) avec les récepteurs membranaires CXCR1 et CXCR2. Lesdits composés sont utilisés dans la prévention et le traitement de pathologies dérivées de ladite activation. En particulier, des acides arylacétiques 2(ortho)-substitués ou leurs dérivés, tels que des amides et sulfamides, sont dépourvus d'activité inhibitrice de la cyclo-oxygénase et sont particulièrement utiles dans le traitement de pathologies polynucléaires neutrophiles-dépendantes, telles que le psoriasis, la colite ulcéreuse, le mélanome, la bronchopneumopathie chronique obstructive (BPCO), la pemphigoïde bulleuse, la polyarthrite rhumatoïde, la fibrose idiopathique, la glomérulonéphrite ainsi que dans la prévention et le traitement de lésions causées par l'ischémie et la perfusion répétée.

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