A CNS-Targeting Prodrug Strategy for Nuclear Receptor Modulators [post]

Skylar Ferrara, Thomas Scanlan
2020 unpublished
Neurodegenerative diseases lack a breadth of treatment options due, in part, to the known difficulties associated with a drug's passage across the blood-brain barrier. In this study, we provide a blueprint for how to get drug-like structures which feature carboxylic acid motifs across the blood-brain barrier, while attenuating their peripheral exposure using a chemical prodrug strategy. This prodrug strategy utilizes endogenous fatty-acid amide hydrolase expressed in the CNS to cleave and
more » ... e parent drugs for CNS drug action to commence. In particular, we demonstrate the successes and limitations of this prodrug strategy within a series of nuclear receptor modulators, which have shown promise as potential therapeutics for neurodegenerative diseases.
doi:10.26434/chemrxiv.12331301.v1 fatcat:j2v62gfipbgyhptimquykf6exi