Fused azole-pyrimidine derivatives

Details Fused azole-pyrimidine derivatives Fused azole-pyrimidine derivatives

C - Chemistry, Metallurgy

07

D

C07D 487/04 (2006.01) A61P 29/00 (2006.01) C07D 471/14 (2006.01) C07D 487/06 (2006.01) C07D 519/00 (2006.01)

Patent

CA 2499134

The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (P13K) inhibition, especially for PI3K-.gamma. inhibition and can be used for the prophylaxis and treatment of diseases associated with P13K and particularly with P13K-.gamma. activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to P13K activity in a human or animal subject.

L'invention concerne de nouveaux dérivés d'azole-pyrimidines fondues, des procédés permettant de les préparer et des préparations pharmaceutiques les contenant. Les dérivés d'azole-pyrimidines fondues de la présente invention présentent une capacité renforcée d'inhibition de la phosphotidylinositol-3-kinase (P13K), notamment d'inhibition de la P13K-.gamma. et peuvent s'utiliser pour assurer la prophylaxie et le traitement de pathologies associées à la P13K et en particulier à l'activité de la P13K-.gamma.. Les dérivés d'azole de la présente invention s'utilisent plus particulièrement dans le traitement et la prophylaxie des pathologies suivantes : troubles inflammatoires et immunorégulateurs, tels que l'asthme, la dermatite atopique, la rhinite, les maladies allergiques, la maladie pulmonaire obstructive chronique (COPD), le choc septique, les maladies des articulations, les pathologies auto-immunes telles que la polyarthrite rhumatoïde, et la maladie de Graves, le cancer, les troubles de contractilité du myocarde, l'insuffisance cardiaque, le thromboembolisme, l'ischémie et l'athérosclérose. Les composés de la présente invention s'utilisent également pour traiter l'hypertension pulmonaire, l'insuffisance rénale, l'hypertrophie cardiaque, de même que des troubles neurodégénératifs tels que la maladie de Parkinson, la maladie d'Alzheimer, le diabète et l'ischémie focale, ces pathologies se rapportant également à l'activité de la P13K, chez l'homme ou l'animal.

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