About: Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase

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About: Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase
Creator	De Beer, Johannie Jacobus, · Lourens, Anna Petzer, Anél Petzer, P
Source	PMC
abstract	ABSTRACT: The most effective treatment of Parkinson’s disease is restoring central dopamine levels with levodopa, the metabolic precursor of dopamine. However, due to extensive peripheral metabolism by aromatic l-amino acid decarboxylase and catechol-O-methyltransferase (COMT), only a fraction of the levodopa dose reaches the brain unchanged. Thus, by preventing levodopa metabolism and increasing the availability of levodopa for uptake into the brain, the inhibition of COMT would be beneficial in Parkinson’s disease. Although nitrocatechol COMT inhibitors have been used in the treatment of Parkinson’s disease, efforts have been made to discover non-nitrocatechol inhibitors. In the present study, the 3-hydroxypyridin-4-one scaffold was selected for the design and synthesis of non-nitrocatechol COMT inhibitors since the COMT inhibitory potential of this class has been illustrated. Using COMT obtained from porcine liver, it was shown that a synthetic series of ten 3-hydroxypyridin-4-ones are in vitro inhibitors with IC(50) values ranging from 4.55 to 19.8 µM. Although these compounds are not highly potent inhibitors, they may act as leads for the development of non-nitrocatechol COMT inhibitors. Such compounds would be appropriate for the treatment of Parkinson’s disease. GRAPHIC ABSTRACT: 3-Hydroxypyridin-4-ones have been synthesised and evaluated as non-nitrocatechol COMT inhibitors. In vitro, the IC(50) values ranged from 4.55 to 19.8 μM. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10053-x) contains supplementary material, which is available to authorized users.
has issue date	2020-02-27(xsd:dateTime)
bibo:doi	10.1007/s11030-020-10053-x
bibo:pmid	32108308
has license	no-cc
sha1sum (hex)	612b9c952fda2ea50dacc0399e38b51e1a7806a0
schema:url	https://doi.org/10.1007/s11030-020-10053-x
resource representing a document's title	Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase
has PubMed Central identifier	PMC7224104
has PubMed identifier	32108308
schema:publication	Mol Divers
resource representing a document's body	covid:612b9c952fda2ea50dacc0399e38b51e1a7806a0#body_text
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