Improved prodrugs of cc-1065 analogs

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 209/60 (2006.01) A61K 31/404 (2006.01) A61P 35/00 (2006.01) C07D 405/12 (2006.01) C07D 405/14 (2006.01) C07D 519/00 (2006.01)

Patent

CA 2642870

Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group containing a sulfonic acid containing phenyl carbamate, in which the protecting group confers enhanced water solubility upon the prodrug, and in which the prodrug also has a moiety, such as a sulfide or a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

La présente invention concerne des promédicaments ou analogues de l'antibiotique anti-tumoral CC-1065 possédant un groupe protecteur clivable comprenant un phényle carbamate contenant un acide sulfonique. Ledit groupe protecteur confère une hydrosolubilité accrue au promédicament et possède également une entité, telle qu'un sulfure ou un bisulfure, capable de se conjuguer à un réactif de liaison cellulaire tel qu'un anticorps. L'invention décrit également l'utilisation thérapeutique de tels conjugués de promédicaments; ces promédicaments d'agents cytotoxiques présentent une utilité thérapeutique car ils peuvent délivrer des promédicaments cytotoxiques à une population cellulaire spécifique, en vue d'une conversion enzymatique ciblée en médicaments cytotoxiques.

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