Isoxazoline compounds as inhibitors of tnf release

Details Isoxazoline compounds as inhibitors of tnf release Isoxazoline compounds as inhibitors of tnf release

A - Human Necessities

61

K

A61K 31/42 (2006.01) A61K 31/423 (2006.01) A61K 31/47 (2006.01) A61K 31/4709 (2006.01) C07D 261/04 (2006.01) C07D 413/12 (2006.01)

Patent

CA 2185019

This invention relates to isoxazoline compounds of formula (I) which are inhibitors of tumor necrosis factor (TNF). The isoxazoline compounds are useful for inhibiting TNF in a mammal in need thereof and in the treatment or alleviation of inflammatory conditions or disease, including but not limited to rheumatoid arthritis, osteoarthritis, asthma, bronchitis, chronic obstructive airways disease, psoriais, allergic rhinitis, dermatitis and inflammatory bowel disease, sepsis, septic shock, tuberculosis, graft versus host disease and cachexia associated with AIDS or cancer. This invention also relates to pharmaceutical compositions useful therefor comprising such compounds of formula (I) wherein X1 is -(CH2)qOH, -CHOHR5 or -(CH2)mCON(R6)(OH); wherein q and m are each independently 0 or an integer from 1 to 5; R5 is (C1-C4)alkyl; and R6 is hydrogen or (C1-C3)alkyl; n is 0, 1, 2 or 3; y1 and y2 are as defined in the application.

Cette invention se rapporte à des composés d'isoxazoline de formule (I) qui sont des inhibiteurs du facteur de nécrose tumorale (FNT). Les composés d'isoxazoline sont utilisés pour inhiber le FNT chez un mammifére et dans le traitement ou le soulagement d'états ou de maladie inflammatoires, dont, entre autres, la polyarthrite rhumatoïde, l'arthrose, l'asthme, la bronchite, les maladies des voies respiratoires chroniques obstructives, le psoriasis, les rhinites allergiques, l'eczéma et les affections intestinales inflamatoires, la septicémie, le choc septique, la tuberculose, la réaction du greffon contre l'hôte et la cachexie associés au sida ou au cancer. Cette invention se rapporte également aux compositions pharmaceutiques utilisées dans ces traitements et comprenant les composés de la formule (I) dans laquelle X1 représente -(CH2)qOH, -CHOHR5 ou -(CH2)mCON(R6)(OH); où q et m valent chacun, indépendamment, 0 ou un nombre entier compris entre 1 et 5; R5 représente alkyle (C1-C4); et R6 représente hydrogène ou alkyle (C1-C3); n vaut 0, 1, 2, ou 3; Y1 et Y2 sont tels que définis dans la demande.

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