612499-12-4Relevant academic research and scientific papers
A CNS-Targeting Prodrug Strategy for Nuclear Receptor Modulators
Ferrara, Skylar J.,Scanlan, Thomas S.
, p. 9742 - 9751 (2020)
The blood-brain barrier is a major impediment for targeted central nervous system (CNS) therapeutics, especially with carboxylic acid-containing drugs. Nuclear receptor modulators, which often feature carboxylic acid motifs for target engagement, have emerged as a class of potentially powerful therapeutics for neurodegenerative CNS diseases. Herein is described a prodrug strategy that directs the biodistribution of parent drug nuclear receptor modulators into the CNS while masking them as functional receptor ligands in the periphery. This prodrug strategy targets a specific amidase, fatty acid amide hydrolase (FAAH), an enzyme with enriched expression in the CNS. Our results demonstrate that this prodrug strategy can be generalized to a variety of carboxylic acid-containing drug structures that satisfy the structural requirements of blood-brain barrier diffusion and FAAH substrate recognition.
AMIDE PRODRUGS OF SMALL MOLECULE NUCLEAR RECEPTOR MODULATORS
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Page/Page column 12; 16; 17; 18, (2019/09/18)
Provided herein are novel amide prodrug forms of pharmaceutically active agents useful for central nervous system disorders.
