Alpha;-GALACTOSYLCERAMIDE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD AND PHARMACEUTICAL COMPOSITION FOR THE IMMUNE ADJUVANT CONTAINING THE SAME AS AN ACTIVE INGREDIENT

摘要

An alpha-galactosylceramide derivative is provided to induce secretion of cytokine IL-4 or IFN-gamma by modifying an alpha-GalCer amide portion by a triazole having biological isosterism, thereby being used as a useful therapeutic agent of auto-immune diseases such as a type I diabetes and multiple sclerosis. An alpha-galactosylceramide derivative is represented by a formula(1a), wherein A is triazole or amide; and if the A is triazole, R is C1-35 alkyl which may be substituted or unsubstituted by at least one substituent selected from the group consisting of halogen, hydroxy, amino, amino substituted by at least one C1-20 alkyl, thiol, cyano, nitro, sulfonyl, phenyl, C1-30 alkoxy, C1-30 alkyl, C1-30 haloalkyl, C1-30 hydroxyalkyl, C1-30 alkoxyalkyl, C5-10 aryl, C5-10 heteroaryl, C5-10 arylalkyl and C5-10 heteroarylalkyl, and if the A is amide, R is C1-35 alkyl which is substituted by at least one substituent selected from the group consisting of halogen, hydroxy, amino, amino substituted by at least one C1-20 alkyl, thiol, cyano, nitro, sulfonyl, phenyl, C1-30 alkoxy, C1-30 alkyl, C1-30 haloalkyl, C1-30 hydroxyalkyl, C1-30 alkoxyalkyl, C5-10 aryl, C5-10 heteroaryl, C5-10 arylalkyl and C5-10 heteroarylalkyl. A method for preparing the alpha-galactosylceramide derivative comprises the steps of: (a) reacting a compound represented by a formula(2) with an alkyne compound to prepare an intermediate represented by a formula(4); and (b) reacting the intermediate of the formula(4) with Pd(OH)2 to remove a protecting group therefrom, wherein A is triazole, R1 is at least one of substituent R, which is defined above, and each Bn and PMB is benzyl or p-methoxybenzyl. A pharmaceutical composition for immunity adjuvant comprises the alpha-galactosylceramide derivative or a pharmaceutically acceptable salt thereof as an effective ingredient.