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Details

Stereochemistry ACHIRAL
Molecular Formula C14H11NO5
Molecular Weight 273.2414
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NEBICAPONE

SMILES

c1ccc(cc1)CC(=O)c2cc(c(c(c2)O)O)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 273.2414
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Approval Year

PubMed

PubMed

TitleDatePubMed
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
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
Chemical synthesis and characterization of conjugates of a novel catechol-O-methyltransferase inhibitor.
2002 Sep-Oct
Pharmacokinetics and pharmacodynamics of BIA 3-202, a novel COMT inhibitor, during first administration to humans.
2003
Pharmacokinetic and pharmacodynamic profiles of BIA 3-202, a novel catechol-O-methyltransferase (COMT) inhibitor, during multiple-dose administration to healthy subjects.
2003 Dec
Kinetic inhibitory profile of BIA 3-202, a novel fast tight-binding, reversible and competitive catechol-O-methyltransferase inhibitor.
2003 Jan 24
Catechol-O-methyltransferase inhibition in erythrocytes and liver by BIA 3-202 (1-[3,4-dibydroxy-5-nitrophenyl]-2-phenyl-ethanone).
2003 Jun
Molecular modeling and metabolic studies of the interaction of catechol-O-methyltransferase and a new nitrocatechol inhibitor.
2003 Mar
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
Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/benserazide.
2003 Nov
Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/carbidopa.
2004 Jan-Feb
Human metabolism of nebicapone (BIA 3-202), a novel catechol-o-methyltransferase inhibitor: characterization of in vitro glucuronidation.
2006 Nov
Gateways to clinical trials.
2007 Apr
Catechol-O-methyltransferase and its inhibitors in Parkinson's disease.
2007 Fall
Pharmacokinetic-pharmacodynamic interaction between nebicapone, a novel catechol-o-methyltransferase inhibitor, and controlled-release levodopa/carbidopa 200 mg/50 mg : randomized, double-blind, placebo-controlled, crossover study in healthy subjects.
2008
Effects of nebicapone on levodopa pharmacokinetics, catechol-O-methyltransferase activity, and motor fluctuations in patients with Parkinson disease.
2008 Jan-Feb
Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.
2008 Oct
Species differences in pharmacokinetic and pharmacodynamic properties of nebicapone.
2009 Oct 15
Toxicology and safety of COMT inhibitors.
2010
Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase.
2010 Apr 22
A double-blind, randomized, placebo and active-controlled study of nebicapone for the treatment of motor fluctuations in Parkinson's disease.
2010 Dec
Patents

Patents

Sample Use Guides

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
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 Jun 26 07:55:51 UTC 2021
Edited
by admin
on Sat Jun 26 07:55:51 UTC 2021
Record UNII
NM2KXJ990T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NEBICAPONE
INN  
INN  
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
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
NCI_THESAURUS C38149
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
Code System Code Type Description
PUBCHEM
9838389
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
DRUG BANK
DB14849
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
CAS
274925-86-9
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
INN
8602
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
NCI_THESAURUS
C83923
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
ChEMBL
CHEMBL160038
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
FDA UNII
NM2KXJ990T
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
EPA CompTox
274925-86-9
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
MESH
C433466
Created by admin on Sat Jun 26 07:55:52 UTC 2021 , Edited by admin on Sat Jun 26 07:55:52 UTC 2021
PRIMARY
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