Insights on Structure-Passive Permeability Relationship in Pyrrole and Furan-Containing Macrocycles.

ABSTRACT: Macrocycles have recognized therapeutic potential, but their limited cellular permeability can hinder their development as oral drugs. To better understand the structure-permeability relationship of heterocycle-containing, semipeptidic macrocycles, a library was synthesized. These compounds were created by developing two novel reactions described herein: the reduction of activated oximes by LiBH₄ and the aqueous reductive mono-N-alkylation of aldehydes using catalytic SmI₂ and stoichiometric Zn. The permeability of the macrocycles was evaluated through a parallel artificial membrane permeability assay (PAMPA), and the results indicated that macrocycles with a furan incorporated into the structure have better passive permeability than those with a pyrrole moiety

SUBMITTER: Ly HM 

PROVIDER: S-EPMC10946398 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature