NEBICAPONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H11NO5
Molecular Weight	273.2408
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(O)C(=CC(=C1)C(=O)CC2=CC=CC=C2)[N+]([O-])=O

InChI

InChIKey=MRFOLGFFTUGAEB-UHFFFAOYSA-N

InChI=1S/C14H11NO5/c16-12(6-9-4-2-1-3-5-9)10-7-11(15(19)20)14(18)13(17)8-10/h1-5,7-8,17-18H,6H2

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800019832 | https://www.ncbi.nlm.nih.gov/pubmed/18989992 | https://www.ncbi.nlm.nih.gov/pubmed/12236793 | https://www.ncbi.nlm.nih.gov/pubmed/12559377

Nebicapone (BIA 3-202) is a reversible, and tight-binding peripheral inhibitor of the enzyme catechol-O-methyltransferase (COMT) being developed for use as an adjunct to levodopa/dopa decarboxylase inhibitor in the treatment of PD. Nebicapone dose dependently and significantly decreased COMT activity. Nebicapone also increased systemic exposure to levodopa and improved motor response. The tight-binding nature of the inhibition produced by BIA 3-202 was evaluated by performing an Ackermann-Potter plot. The true K(i) for BIA 3-202, derived from the nonlinear regression analysis, was 0.19+/-0.02 nM. In substrate competition studies, an increase in the concentration of adrenaline resulted in a linear increase in IC(50) values for BIA 3-202.

Originator

Approval Year

PubMed

Title	Date	PubMed
Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase.	2002 Jan 31	11806720
Pharmacokinetics and pharmacodynamics of BIA 3-202, a novel COMT inhibitor, during first administration to humans.	2003	12848585
Catechol-O-methyltransferase inhibition in erythrocytes and liver by BIA 3-202 (1-[3,4-dibydroxy-5-nitrophenyl]-2-phenyl-ethanone).	2003 Jun	12787259
BIA 3-202, a novel catechol-O-methyltransferase inhibitor, reduces the peripheral O-methylation of L-DOPA and enhances its availability to the brain.	2003 May	12660477
Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/benserazide.	2003 Nov	14517707
Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/carbidopa.	2004 Jan-Feb	15090932
Human metabolism of nebicapone (BIA 3-202), a novel catechol-o-methyltransferase inhibitor: characterization of in vitro glucuronidation.	2006 Nov	16790555
Gateways to clinical trials.	2007 Apr	17520107
Catechol-O-methyltransferase and its inhibitors in Parkinson's disease.	2007 Fall	17894650
Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson's disease.	2010	21095464
Toxicology and safety of COMT inhibitors.	2010	21095462

Patents

Sample Use Guides

In Vivo Use Guide

During the different treatment periods, subjects received a single dose of controlled-release levodopa 100 mg/benserazide 25 mg concomitantly with nebicapone 50, 100, and 200 mg or placebo. When administered concomitantly with a single dose of controlled-release levodopa 100 mg/benserazide 25 mg, single doses of nebicapone 50, 100, and 200 mg were well tolerated in these healthy adult volunteers, and dose dependently inhibited S-COMT activity and reduced 3-OMD formation compared with placebo.

Route of Administration: Oral

In Vitro Use Guide

Nebicapone inhibited rat liver COMT with a lower K(i) than mouse liver COMT (respectively 0.2nM vs. 1.2nM).

Name

Type

Language

NEBICAPONE

Official Name

English

1-(3,4-DIHYDROXY-5-NITROPHENYL)-2-PHENYLETHAN-1-ONE

Systematic Name

English

nebicapone [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471