Functional platinum-acridine drug and platinum-benzoacridine drug cleavable conjugates and methods thereof

摘要

The present invention relates to the use of a versatile synthetic approach to generate a new class of ester, amide or carbamate prodrugs of platinum-acridine anticancer drugs that are highly potent but have excessive systemic toxicity. This new hybrid contains a hydroxyl group that is masked with a cleavable lipophilic acyl moiety. To these compounds were introduced butanoic acid (butyric acid) ester and the bulkier 2-propanepentanoic acid (valproic acid) ester. The purpose of this design was to improve the pharmacophore's drug-like properties (eg, logD) without reducing its DNA-mediated cell killing potential. [Selection] Figure 3