Compounds having mif antagonist activity

A - Human Necessities – 61 – K

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Details

A61K 31/17 (2006.01) A61K 31/12 (2006.01) A61K 31/122 (2006.01) A61K 31/167 (2006.01)

Patent

CA 2416750

There are disclosed methods of use and pharmaceutical compositions for two related fenera of low molecular weight compounds comprising optionally substituted iminoquinone or orthoquinone ring systems. The compounds have MIF (macrophage migration inhibitory factor) antagonist activity and find utility as such. For example, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatiod arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, EAE, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular diseases, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).

La présente invention concerne des procédés et des compositions pharmaceutiques de deux générations liées de composés à faible poids moléculaire comprenant des systèmes cycliques iminoquinone ou orthoquinone éventuellement substitués. Les composés ont une action d'antagoniste de MIF (macrophage migration inhibitory factor / facteur d'inhibition de la migration des macrophages) et peuvent être utilisés en tant que tels. Par exemple, les composés peuvent être utilisés pour traiter une variété de maladies faisant intervenir une activité inflammatoire ou des réponses cytokine pro-inflammatoires telles que les maladies auto-immunes (comprenant l'arthrite rhumatoïde, le diabète insulino-dépendant, la sclérose en plaques, la réaction du greffon contre l'hôte, les syndromes lupiques), l'asthme, l'arthrite, l'encéphalomyélite allergique expérimentale, insuffisance respiratoire aiguë, le psoriasis, la toxicité de l'interleukine 2, les maladies vasculaires proliférantes, et différentes formes de sepsis et de chocs septiques, et d'autres états pathologiques se caractérisant par des réponses immunitaires liées au MIF, comprenant, par exemple, la croissance tumorale et la néovascularisation (angiogenèse).

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