A Self-Immolative Linker for the pH-Responsive Release of Amides.

ABSTRACT: The administration of therapeutics using bioconjugation has been mainly limited to drugs containing amine, alcohol, or thiol functional groups. Here, we report a general procedure for the preparation of benzylic N-acyl carbamates suitable for masking the amide group in important drugs such as Linezolid, Enzalutamide, or Tasimelteon in good to acceptable yields. These N-acyl carbamates appear to be stable in plasma, while a qualitative analysis of further drug uncage demonstrates that, at pH values of 5.5, a classical 1,6-benzyl elimination mechanism takes place, releasing more than 80% of the drug in 24 h.

SUBMITTER: Petrini A 

PROVIDER: S-EPMC10060004 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature