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

Molecular Formula	C14H11NO5
Molecular Weight	273.2408
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
BIA 3-202, a novel catechol-O-methyltransferase inhibitor, enhances the availability of L-DOPA to the brain and reduces its O-methylation.	2001 May 18	11412836
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
Chemical synthesis and characterization of conjugates of a novel catechol-O-methyltransferase inhibitor.	2002 Sep-Oct	12236793
Kinetic inhibitory profile of BIA 3-202, a novel fast tight-binding, reversible and competitive catechol-O-methyltransferase inhibitor.	2003 Jan 24	12559377
Gateways to clinical trials.	2008 May	18773127
Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.	2008 Oct	18679669
Pharmacokinetic-pharmacodynamic interaction between nebicapone and controlled-release levodopa/benserazide: a single-center, Phase I, double-blind, randomized, placebo-controlled, four-way crossover study in healthy subjects.	2009 Oct	19922897
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
Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase.	2010 Apr 22	20334432
Pharmacokinetics, disposition, and metabolism of [14C]-nebicapone in humans.	2010 Aug	20642448
A double-blind, randomized, placebo and active-controlled study of nebicapone for the treatment of motor fluctuations in Parkinson's disease.	2010 Dec	20653695
Chronopharmacology of nebicapone, a new catechol-O-methyltransferase inhibitor.	2010 May	20225994

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).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:55:01 GMT 2023` Edited by `admin` on `Sat Dec 16 17:55:01 GMT 2023`
Record UNII	NM2KXJ990T
Record Status	`Validated (UNII)`
Record Version

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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