Alpha-galactosyl ceramide analogs and their use as...

C - Chemistry – Metallurgy – 07 – H

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C07H 15/18 (2006.01) A61K 8/42 (2006.01) A61K 31/7032 (2006.01) A61K 39/39 (2006.01) A61P 37/04 (2006.01) C07H 15/04 (2006.01) C07H 15/14 (2006.01)

Patent

CA 2683681

The present disclosure relates to synthetic alpha-galactosyl ceramide (.alpha.-GalCer) analogs, and their use as immunotherapies. In one aspect, a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula (1) wherein, n is 0 to 25; X is selected from O and S; R1is selected from H, CH3, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, phenyl-F, C1-C6 alkyl, or C2-C6 branched alkyl; R2 is selected from OH and H; R3 is selected from C1-C15 alkyl, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, C1-C6 alkyl, or C2-C6 branched alkyl; R4 is selected from OH, OSO3H, OSO3Na, and OSO3K; and R5 is selected from CH2OH and CO2H; or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

L'invention concerne des analogues d'alpha-galactosyl céramide (a-GalCer), et leur utilisation en immunothérapies. Dans un aspect, un procédé d'activation d'une réponse de cytokine chez un sujet comprend l'administration d'une quantité efficace d'un composé à un sujet qui sujet a un système immunitaire adaptatif comprenant une population de cellules qui comprend au moins un lymphocyte et au moins une cellule présentant un antigène. Le composé est représenté par la structure de formule (1) dans laquelle n vaut 0 à 25; X est choisi parmi O et S; R1 est choisi parmi H, CH3 et un phényle, où le phényle est facultativement substitué par H, OH, OCH3, F, CF3, un phényle, un phényl-F, un alkyle en C1-C6 ou un alkyle ramifié en C2-C6; R2 est choisi parmi OH et H; R3 est choisi parmi un alkyle en C1-C15 et un phényle, où le phényle est facultativement substitué par H, OH, OCH3, F, CF3, un phényle, un alkyle en C1-C6 ou un alkyle ramifié en C2-C6 ; R4 est choisi parmi OH, OSO3H, OSO3Na et OSO3K; et R5 est choisi parmi CH2OH et CO2H; ou un sel pharmaceutiquement acceptable de ceux-ci. Le procédé susmentionné comprend aussi d'une part la formation d'un complexe entre le composé et la cellule présentant un antigène, la formation du complexe entraînant l'activation d'un récepteur sur le lymphocyte et, d'autre part, l'activation du lymphocyte pour produire la réponse de cytokine.

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