Small molecule toll-like receptor (tlr) antagonists

Details Small molecule toll-like receptor (tlr) antagonists Small molecule toll-like receptor (tlr) antagonists

C - Chemistry, Metallurgy

07

D

C07D 401/10 (2006.01) A61K 31/4725 (2006.01) A61K 31/517 (2006.01) C07D 239/72 (2006.01) C07D 413/14 (2006.01) C07D 471/00 (2006.01) C07D 471/04 (2006.01) A01N 43/54 (2006.01)

Patent

CA 2528774

The invention provides methods and compositions useful for modulating signaling through Toll-like receptors. The methods involve contacting a TLR- expressing cell with a small molecule having a core structure including at least two rings. Certain of the compounds are 4-primary amino quinolines. Many of the compounds and methods are useful specifically for inhibiting immune stimulation involving at least one of TLR9, TLR8, TLR7, and TLR3. The methods may have use in the treatment of autoimmunity, inflammation, allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer, and immunodeficiency.

L'invention concerne des procédés et des compositions utiles pour la modulation de la signalisation par l'intermédiaire de récepteurs Toll. Ces procédés consistent à mettre une cellule exprimant TLR en contact avec une petite molécule possédant une structure de noyau comportant au moins deux cycles. Certains des composés sont des 4-aminoquinoléines primaires. Un grand nombre des composés et procédés sont utiles spécifiquement pour l'inhibition de la stimulation immunitaire impliquant au moins TLR9, TLR8, TLR7 et TLR3. Ces procédés peuvent être utilisés dans le traitement de l'auto-immunité, de l'inflammation, de l'allergie, de l'asthme, du rejet de greffon, de la réaction du greffon contre l'hôte, de l'infection, de la sepsis, du cancer et de l'immunodépression.

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