Chemical Probes to Investigate Central Nervous System Disorders: Design, Synthesis and Mechanism of Action of a Potent Human Serine Racemase Inhibitor.

ABSTRACT: The intricate signaling network within the central nervous system (CNS) involving N-methyl-d-aspartate receptors (NMDARs) has been recognized as a key player in severe neurodegenerative diseases. The indirect modulation of NMDAR-mediated neurotransmission through inhibition of serine racemase (SR)-the enzyme responsible for the synthesis of the NMDAR coagonist d-serine-has been suggested as a therapeutic strategy to treat these conditions. Despite the inherent challenges posed by SR conformational flexibility, a ligand-based drug design strategy has successfully produced a series of potent covalent inhibitors structurally related to amino acid analogues. Among these inhibitors, O-(2-([1,1'-biphenyl]-4-yl)-1-carboxyethyl)hydroxylammonium chloride (28) has emerged as a valuable

SUBMITTER: Marchesani F 

PROVIDER: S-EPMC11318019 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature