1333331-84-2Relevant academic research and scientific papers
Synthesis and optimization of N-heterocyclic pyridinones as catechol-O-methyltransferase (COMT) inhibitors
Zhao, Zhijian,Harrison, Scott T.,Schubert, Jeffrey W.,Sanders, John M.,Polsky-Fisher, Stacey,Zhang, Nanyan Rena,McLoughlin, Debra,Gibson, Christopher R.,Robinson, Ronald G.,Sachs, Nancy A.,Kandebo, Monika,Yao, Lihang,Smith, Sean M.,Hutson, Pete H.,Wolkenberg, Scott E.,Barrow, James C.
, p. 2952 - 2956 (2016/06/06)
A series of N-heterocyclic pyridinone catechol-O-methyltransferase (COMT) inhibitors were synthesized. Physicochemical properties, including ligand lipophilic efficiency (LLE) and c log P, were used to guide compound design and attempt to improve inhibitor pharmacokinetics. Incorporation of heterocyclic central rings provided improvements in physicochemical parameters but did not significantly reduce in vitro or in vivo clearance. Nevertheless, compound 11 was identified as a potent inhibitor with sufficient in vivo exposure to significantly affect the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), and indicate central COMT inhibition.
INHIBITORS OF CATECHOL O-METHYL TRANSFERASE AND THEIR USE IN THE TREATMENT OF PSYCHOTIC DISORDERS
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, (2011/10/03)
The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved
