PRIRALFINAMIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H19FN2O2
Molecular Weight	302.3434
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](NCC1=CC=C(OCC2=CC=CC=C2F)C=C1)C(N)=O

InChI

InChIKey=BHJIBOFHEFDSAU-LBPRGKRZSA-N

InChI=1S/C17H19FN2O2/c1-12(17(19)21)20-10-13-6-8-15(9-7-13)22-11-14-4-2-3-5-16(14)18/h2-9,12,20H,10-11H2,1H3,(H2,19,21)/t12-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.newron.com/ENG/Default.aspx?SEZ=3&PAG=40 | http://drugprofiles.informa.com/drug_profiles/10703-ralfinamide
Curator's Comment: Description was created based on several sources, including http://www.prnewswire.com/news-releases/newron-announces-positive-results-with-ralfinamide-from-phase-ii-trial-in-neuropathic-pain-74976442.html

Priralfinamide, also known as Ralfinamide, FCE-26742A; NW-1029; PNU-0154339E, is a Na-channel blocker for the treatment of neuropathic pain and other pain conditions such as post-operative dental pain. It has a relatively complex pharmacology, acting as a mixed voltage-gated sodium channel blocker (including Nav1.7), N-type calcium channel blocker, noncompetitive NMDA receptor antagonist, and monoamine oxidase B inhibitor. Priralfinamide is in phase Ⅲ clinical trials by Newron for the treatment of chronic neuropathic pain.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: http://www.newron.com/ENG/Default.aspx?SEZ=3&PAG=40 \| https://www.ncbi.nlm.nih.gov/pubmed/18583049	Antagonist 2778
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22872464	Inhibitor 8297
Sodium channel alpha subunit 76 Target ID: CHEMBL2331043 Sources: http://www.newron.com/ENG/Default.aspx?SEZ=3&PAG=40	Blocker 537
Voltage-gated N-type calcium channel alpha-1B subunit 12 Target ID: CHEMBL4478 Sources: http://www.newron.com/ENG/Default.aspx?SEZ=3&PAG=40	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neuropathic pain 26 Sources: http://adisinsight.springer.com/drugs/800014979 https://clinicaltrials.gov/ct2/show/NCT00736151 http://www.prnewswire.com/news-releases/newron-announces-positive-results-with-ralfinamide-from-phase-ii-trial-in-neuropathic-pain-74976442.html	Palliative		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.28 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21071997/	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:		PRIRALFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
41.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21071997/	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:		PRIRALFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21071997/	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:		PRIRALFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21071997/	320 mg single, oral dose: 320 mg route of administration: Oral experiment type: SINGLE co-administered:		PRIRALFINAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	Other AEs: numbness of throat, flu symptoms... Other AEs: numbness of throat (1 pt) flu symptoms (1 pt) Alanine aminotransferase increase (mild, 1 pt) aspartate aminotransferase (mild, 1 pt) Dizziness (3 patients) Numbness of tongue (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21071997

AEs

AE	Significance	Dose	Population
flu symptoms	1 pt	320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997
numbness of throat	1 pt	320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997
Numbness of tongue	2 patients	320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997
Dizziness	3 patients	320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997
Alanine aminotransferase increase	mild, 1 pt	320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997
aspartate aminotransferase	mild, 1 pt	320 mg single, oral (unknown) Studied dose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21071997	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21071997

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY114296	https://www.001chemical.com/chem/search?q=DY114296
1PlusChem LLC	1P0028WQ	https://www.1pchem.com/search?query=1P0028WQ
1PlusChem LLC	1P009E4F	https://www.1pchem.com/search?query=1P009E4F
AK Scientific	0394AB	https://aksci.com/item_detail.php?cat=0394AB
AK Scientific	6134AA	https://aksci.com/item_detail.php?cat=6134AA
Alfa Chemistry	11936	http://www.alfa-chemistry.com/search.aspx?q=11936
Alfa Chemistry	AFI202825454	http://www.alfa-chemistry.com/search.aspx?q=AFI202825454
Angene	AGN-PC-0PK5KU	http://www.angenechemical.com/productshow/AGN-PC-0PK5KU.html
Angene	AGN-PC-0QT7XA	http://www.angenechemical.com/productshow/AGN-PC-0QT7XA.html
AstaTech	C15260	http://astatechinc.com/CPSResult.php?CRNO=C15260
AstaTech	F12108	http://astatechinc.com/CPSResult.php?CRNO=F12108
BLD Pharm	BD234099	http://www.bldpharm.com/search/Search.html?keyword=BD234099
BOC Sciences	202825-45-4	http://www.bocsci.com/description.asp?cas=202825-45-4
Chem Scene	CS-0021330	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0021330
Chem Scene	CS-0021517	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0021517
ChemShuttle	172375	https://www.chemshuttle.com/catalogsearch/result/?q=172375
Combi-Blocks	QN-9990	http://www.combi-blocks.com/cgi-bin/find.cgi?QN-9990
Fluorochem	232600	http://www.fluorochem.co.uk/Products/Product?code=232600
Fluorochem	315691	http://www.fluorochem.co.uk/Products/Product?code=315691
Hairui	RAXM015	http://www.hairuichem.com/en/product/search.do?q=RAXM015
KeyOrganics	DS-18607	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=DS-18607
Lab Network	LN02009533	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02009533
Matrix Scientific	95353	http://www.matrixscientific.com/095353.html
MedChem Express	HY-101437	https://www.medchemexpress.com/search.html?q=HY-101437&ft=&fa=&fp=
MedChem Express	HY-101437A	https://www.medchemexpress.com/search.html?q=HY-101437A&ft=&fa=&fp=
MolPort	MolPort-023-277-041	https://www.molport.com/shop/molecule-link/MolPort-023-277-041
MolPort	MolPort-023-334-032	https://www.molport.com/shop/molecule-link/MolPort-023-334-032
MolPort	MolPort-047-133-871	https://www.molport.com/shop/molecule-link/MolPort-047-133-871
Molcore	MC114296	http://www.molcore.com/CatMC114296.html
MuseChem	M117811	https://www.musechem.com/product/M117811.html
MuseChem	R040315	https://www.musechem.com/product/R040315.html
TargetMol	T7349	https://www.targetmol.com/search?keyword=T7349
Tocris	4029	https://www.tocris.com/search.php?Type=QuickSearch&Value=4029
Toronto Research Chemicals	R075000	https://www.trc-canada.com/product-detail/?CatNum=R075000
Wonderchem	WD053O7	http://www.wonder-chem.com/search.html?text=WD053O7
Wonderchem	WD05JPL	http://www.wonder-chem.com/search.html?text=WD05JPL
eMolecules	300600840	https://orderbb.emolecules.com/search/#?query=300600840
eMolecules	36500872	https://orderbb.emolecules.com/search/#?query=36500872
eMolecules	44470330	https://orderbb.emolecules.com/search/#?query=44470330
eNovation Chemicals	D746959	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D746959&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6020329217	https://mcule.com/MCULE-6020329217/
mcule	MCULE-6969894121	https://mcule.com/MCULE-6969894121/

PubMed

Title	Date	PubMed
Ralfinamide. Newron Pharmaceuticals.	2004 Oct	15478019
Analysis of human Nav1.8 expressed in SH-SY5Y neuroblastoma cells.	2005 Dec 28	16325806
Gateways to clinical trials.	2005 Jul-Aug	16179960
Gateways to clinical trials.	2005 Mar	15834466
The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ currents in dorsal root ganglion neurons.	2005 Mar 14	15763243
Effects of ralfinamide, a Na+ channel blocker, on firing properties of nociceptive dorsal root ganglion neurons of adult rats.	2007 Nov	17707373
Ralfinamide administered orally before hindpaw neurectomy or postoperatively provided long-lasting suppression of spontaneous neuropathic pain-related behavior in the rat.	2008 Oct 15	18583049
Functional and pharmacological properties of human and rat NaV1.8 channels.	2009 Apr	19371587
Disposition and metabolism of ralfinamide, a novel Na-channel blocker, in healthy male volunteers.	2010	21071997

Patents

Sample Use Guides

In Vivo Use Guide

Priralfinamide administered orally at rising doses of 80 - 320 mg/day

Route of Administration: Oral

In Vitro Use Guide

In capsaicin-responsive tonic firing nociceptive dorsal root ganglion neurons of adult rats, priralfinamide (25 uM) reduced the number of action potentials (APs) from 10.6+/-1.8 to 2.6+/-0.7 APs/600 ms

Name

Type

Language

PRIRALFINAMIDE

Official Name

English

priralfinamide [INN]

Common Name

English

(2S)-2-(4-(2-FLUOROBENZYLOXY)BENZYLAMINO)PROPANAMIDE

Systematic Name

English

PNU-0154339E

Code

English

NW1029

Code

English

NW-1029

Code

English

RALFINAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C241