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Details

Stereochemistry ACHIRAL
Molecular Formula C15H10Cl2N4O6
Molecular Weight 413.169
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OPICAPONE

SMILES

CC1=C(C2=NOC(=N2)C3=CC(O)=C(O)C(=C3)[N+]([O-])=O)C(Cl)=[N+]([O-])C(C)=C1Cl

InChI

InChIKey=ASOADIZOVZTJSR-UHFFFAOYSA-N
InChI=1S/C15H10Cl2N4O6/c1-5-10(13(17)20(24)6(2)11(5)16)14-18-15(27-19-14)7-3-8(21(25)26)12(23)9(22)4-7/h3-4,22-23H,1-2H3

HIDE SMILES / InChI

Description

Opicapone (Ongentys®), a potent, oral, third-generation, long-acting, peripheral catechol-O-methyltransferase (COMT) inhibitor, is approved as the adjunctive treatment to levodopa (L-Dopa)/dopa-decarboxylase inhibitor (DDCI) therapy in adults with Parkinson's disease (PD) and end-of-dose motor fluctuations who cannot be stabilized on those combinations. Opicapone is a hydrophilic 1,2,4-oxadiazole analog with a pyridine N-oxide at position 3, with these modifications enhancing its potency and extending its duration of action, whilst avoiding cell toxicity. In preclinical animal studies, Opicapone-induced inhibition of peripheral (but not central) COMT activity was associated with a prolonged increase in systemic and central exposure to L-Dopa, with a corresponding reduction in 3-OMD exposure. Following single or multiple doses of Opicapone (5–1200 mg) in healthy adult volunteers or patients with PD, Opicapone inhibited COMT activity in ex vivo erythrocyte assays in a reversible dose-dependent manner, with the duration of Opicapone-induced COMT inhibition independent of dose. Adjunctive Opicapone was generally well tolerated during more than a year of treatment in BIPARK I and BIPARK II (double-blind plus extension phases). The recommended dosage is 50 mg once daily, which should be taken at bedtime at least 1 h before or after L-Dopa combinations.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Ongentys
PubMed

PubMed

TitleDatePubMed
Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase.
2010 Apr 22
A fragment-based approach to identifying S-adenosyl-l-methionine -competitive inhibitors of catechol O-methyl transferase (COMT).
2014 Jun 26
Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial.
2016 Feb
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dosage is 50 mg once daily, which should be taken at bedtime at least 1 h before or after L-Dopa combinations
Route of Administration: Oral
In Vitro Use Guide
COMT inhibition by Opicapone was evaluated in rat liver homogenates by measuring the formation of metanephrine (O-methylated adrenaline) Opicapone was under tight-binding conditions at a 10-fold lower concentration of 3 μM.The reactionmixture (total volume of 1 mL) contained homogenate (2 mg/mL), NCE (3 μM for nitrocatechols or 30 μM for non-nitrocatechols), 100 μM MgCl2 , 1 mM EGTA, 100 μM pargyline, and S-adenosyl-L-methionine (500 μM) in phosphate buffer (5 mM, pH 7.8). After a 20 min preincubation period at 37 C, the reaction was initiated with adrenaline (1000 μM when testing nitrocatechols or 25 μM when testing nonnitrocatechols) and proceeded for 5 min at 37 C. Reactions were terminated with the addition of 1/10 volume of 2 N perchloric acid. Samples were centrifuged (16000g for 3 min at 4 C) and filtered through 0.22 μm pore size Spin-X 200 filters. Metanephrine was then quantified by HPLC with electrochemical detection as previously detailed
Name Type Language
OPICAPONE
INN   WHO-DD  
INN  
Official Name English
5-(3-(2,5-DICHLORO-4,6-DIMETHYL-1-OXY-PYRIDIN-3-YL)-(1,2,4)OXADIAZOL-5-YL)-3-NITROBENZENE-1,2-DIOL
Systematic Name English
OPICAPONE [WHO-DD]
Common Name English
BIA 9-1067
Code English
OPICAPONE [USAN]
Common Name English
1,2-BENZENEDIOL, 5-(3-(2,5-DICHLORO-4,6-DIMETHYL-1-OXIDO-3-PYRIDINYL)-1,2,4-OXADIAZOL-5-YL)-3-NITRO-
Systematic Name English
BIA-9-1067
Code English
OPICAPONE [INN]
Common Name English
2,5-DICHLORO-3-(5-(3,4-DIHYDROXY-5-NITROPHENYL)-1,2,4-OXADIAZOL-3-YL)-4,6-DIMETHYLPYRIDINE N-OXIDE
Systematic Name English
BIA-91067
Code English
Classification Tree Code System Code
WHO-ATC N04BX04
Created by admin on Mon Oct 21 23:38:38 UTC 2019 , Edited by admin on Mon Oct 21 23:38:38 UTC 2019
Code System Code Type Description
INN
9268
Created by admin on Mon Oct 21 23:38:38 UTC 2019 , Edited by admin on Mon Oct 21 23:38:38 UTC 2019
PRIMARY
MESH
C549349
Created by admin on Mon Oct 21 23:38:38 UTC 2019 , Edited by admin on Mon Oct 21 23:38:38 UTC 2019
PRIMARY
WIKIPEDIA
Opicapone
Created by admin on Mon Oct 21 23:38:38 UTC 2019 , Edited by admin on Mon Oct 21 23:38:38 UTC 2019
PRIMARY
CAS
923287-50-7
Created by admin on Mon Oct 21 23:38:38 UTC 2019 , Edited by admin on Mon Oct 21 23:38:38 UTC 2019
PRIMARY
EVMPD
SUB130629
Created by admin on Mon Oct 21 23:38:38 UTC 2019 , Edited by admin on Mon Oct 21 23:38:38 UTC 2019
PRIMARY