Compounds which inhibit leukocyte adhesion mediated by vla-4

Details Compounds which inhibit leukocyte adhesion mediated by vla-4 Compounds which inhibit leukocyte adhesion mediated by vla-4

C - Chemistry, Metallurgy

07

D

C07D 251/12 (2006.01) A61K 31/381 (2006.01) A61K 31/41 (2006.01) A61K 31/415 (2006.01) A61K 31/4164 (2006.01) A61K 31/4192 (2006.01) A61K 31/433 (2006.01) A61K 31/44 (2006.01) A61K 31/4468 (2006.01) A61K 31/496 (2006.01) A61K 31/505 (2006.01) A61K 31/53 (2006.01) A61K 31/5377 (2006.01) C07D 213/74 (2006.01) C07D 231/38 (2006.01) C07D 233/66 (2006.01) C07D 233/88 (2006.01) C07D 239/42 (2006.01) C07D 239/48 (2006.01) C07D 249/06 (2006.01) C07D 251/18 (2006.01) C07D 251/50 (2006.01) C07D 257/06 (2006.01) C07D

Patent

CA 2359113

Disclosed are compounds (Ia or Ib) which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthiritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

L'invention se rapporte à des composés représentés par les formules (Ia ou Ib) qui se lient à l'intégrine VLA-4. Certains de ces composés inhibent l'adhésion aux leucocytes et notamment l'adhésion aux leucocytes à médiation assurée par VLA-4. Ces composés s'avèrent utiles pour le traitement chez les sujets mammaliens, par exemple chez l'homme, de maladies inflammatoires telles que l'asthme, la maladie d'Alzheimer, l'athérosclérose, le syndrome démentiel lié au SIDA, le diabète, les maladies intestinales inflammatoires, la polyarthrite rhumatoïde, les maladies liées à la transplantation des tissus, la métastase des tumeurs et l'ischémie myocardique. Ces composés peuvent également être administrés aux fins de traitement des maladies cérébrales inflammatoires telles que la sclérose en plaques.

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