17 research outputs found
Enhanced activity of pyruvate dehydrogenase kinase in rat heart mitochondria in alloxan-diabetes or starvation
Enhanced activity of pyruvate dehydrogenase kinase in rat heart mitochondria in alloxan-diabetes or starvation
The Behavioral and Neurochemical Effects of a Novel d-Amino Acid Oxidase Inhibitor Compound 8 [4 H
Prolonged Bleeding Time With Defective Platelet Filopodia Formation in the Wistar Furth Rat
Prolonged Bleeding Time With Defective Platelet Filopodia Formation in the Wistar Furth Rat
Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)
3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones
were identified
as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput
screen. These heterocyclic catechol mimics exhibit potent inhibition
of the enzyme and an improved toxicity profile versus the marketed
nitrocatechol inhibitors tolcapone and entacapone. Optimization of
the series was aided by X-ray cocrystal structures of the novel inhibitors
in complex with COMT and cofactors SAM and Mg<sup>2+</sup>. The crystal
structures suggest a mechanism of inhibition for these heterocyclic
inhibitors distinct from previously disclosed COMT inhibitors