Betulinol derivatives

C - Chemistry – Metallurgy – 07 – J

Patent

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C07J 63/00 (2006.01) C07J 1/00 (2006.01) C07J 53/00 (2006.01)

Patent

CA 2293502

The present invention is directed to betulinol derivatives and betulinol- antibody conjugates having formulae (1), (2) and (3): HO-antibody-spacer- (A2)n, wherein A1 is a moiety having formula (4); A2 is a moiety having formula (5); n is an integer from 1 to 100; X and Y1 and each independently selected from the group consisting of a hydroxy group, an alkoxy group, an alkanoyloxy group, and a -peptide-NHNH-C(O)-antibody-OH moiety; Y2 is selected from the group consisting of a hydroxy group, an alkoxy group, and an alkanoyloxy group; and HO-antibody-H is an antibody and, in particular, betulinol dimethyl ether. Methods for making and using these derivatives and conjugates, as well as a method for making and using betulonic aldehyde, are also disclosed.

La présente invention concerne des dérivés de bétulinol et des conjugués bétulinol-anticorps répondant aux formules (1), (2) et (3): HO-anticorps-espaceur-(A?2¿)¿n?, dans lesquelles A?1¿ est un fragment répondant à la formule (4) et A?2¿ est un fragment répondant à la formule (5) et n est un entier de 1 à 100; X et Y?1¿ sont chacun choisis indépendamment dans le groupe composé d'un groupe hydroxy, un groupe alcoxy, un groupe alcanoyloxy et un fragment peptide-NHNH-C(O)-anticorps-OH; Y?2¿ est choisi dans le groupe composé d'un groupe hydroxy, un groupe alcoxy, et un groupe alcanoyloxy; et HO-anticorps-H est un anticorps. L'invention se rapporte, en particulier, à un bétulinol diméthyle éther. La présente invention concerne des procédés de fabrication et d'utilisation de ces dérivés et conjugués, ainsi qu'un procédé de fabrication et d'utilisation d'un aldéhyde bétulonique.

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