DIPRAGLURANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H12FN3
Molecular Weight	265.285
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CN2C=C(CCC#CC3=NC=CC=C3)N=C2C=C1

InChI

InChIKey=LZXMUJCJAWVHPZ-UHFFFAOYSA-N

InChI=1S/C16H12FN3/c17-13-8-9-16-19-15(12-20(16)11-13)7-2-1-5-14-6-3-4-10-18-14/h3-4,6,8-12H,2,7H2

HIDE SMILES / InChI

Description
Sources: http://www.addextherapeutics.com/investors/press-releases/news-details/?tx_ttnews%5Btt_news%5D%20=114&cHash=ec139af870698365abff9508e25787de
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800026607 | https://www.ncbi.nlm.nih.gov/pubmed/27214664 | https://www.ncbi.nlm.nih.gov/pubmed/24951854

Dipraglurant (ADX48621) is a novel, potent mGluR5 negative allosteric modulator that reduced the severity of drug-induced dyskinesia in Parkinson's disease. Dipraglurant pharmacokinetic variables were similar to those of levodopa, suggesting that both drugs can be co-administered simultaneously in further studies. Dipraglurant might be useful in torsion dystonia treatment also. Detected adverse events are: sweating, dyskinesia, nausea, dizziness, and anxiety. One serious adverse event described as possible syncope.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Metabotropic glutamate receptor 5 39 Target ID: CHEMBL3227 Sources: http://adisinsight.springer.com/drugs/800026607	Negative Allosteric Modulator 42		0.021 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Drug-induced dyskinesia 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27214664	Primary		Phase II 1132	Unknown Approved Use Unknown
Torsion dystonia 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24951854	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
679.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1320.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1521 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
858.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1760.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2009.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.56 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27214664	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	DIPRAGLURANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 3 times / day multiple, oral (unknown) Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	unhealthy n = 76 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	Disc. AE: Sweating, Dyskinesia... AEs leading to discontinuation/dose reduction: Sweating (1 pt) Dyskinesia (1 pt) Nausea (1 pt) Dizziness (1 pt) Anxiety (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/27214664

AEs

AE	Significance	Dose	Population
Anxiety	1 pt Disc. AE	100 mg 3 times / day multiple, oral (unknown) Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	unhealthy n = 76 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/27214664
Dizziness	1 pt Disc. AE	100 mg 3 times / day multiple, oral (unknown) Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	unhealthy n = 76 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/27214664
Dyskinesia	1 pt Disc. AE	100 mg 3 times / day multiple, oral (unknown) Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	unhealthy n = 76 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/27214664
Nausea	1 pt Disc. AE	100 mg 3 times / day multiple, oral (unknown) Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	unhealthy n = 76 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/27214664
Sweating	1 pt Disc. AE	100 mg 3 times / day multiple, oral (unknown) Highest studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27214664	unhealthy n = 76 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 76 Sources: https://pubmed.ncbi.nlm.nih.gov/27214664

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GUJP	https://www.1pchem.com/search?query=1P00GUJP
AK Scientific	3590AH	https://aksci.com/item_detail.php?cat=3590AH
ApexBio Technology	A3366	https://www.apexbt.com/catalogsearch/result/?q=A3366
BLD Pharm	BD630943	http://www.bldpharm.com/search/Search.html?keyword=BD630943
BOC Sciences	872363-17-2	http://www.bocsci.com/description.asp?cas=872363-17-2
Chem Scene	CS-0690	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0690
Debye Scientific	DB-076892	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-076892
Lab Network	LN01342000	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342000
MedChem Express	HY-14859	https://www.medchemexpress.com/search.html?q=HY-14859&ft=&fa=&fp=
MolPort	MolPort-039-139-630	https://www.molport.com/shop/molecule-link/MolPort-039-139-630
MuseChem	I005252	https://www.musechem.com/product/I005252.html
eMolecules	44811488	https://orderbb.emolecules.com/search/#?query=44811488
mcule	MCULE-2934740594	https://mcule.com/MCULE-2934740594/

PubMed

Title	Date	PubMed
Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators.	2013 Apr 1	23434029

Patents

Sample Use Guides

In Vivo Use Guide

50 mg once daily up to 100 mg three times daily, at the start of week 4

Route of Administration: Oral

In Vitro Use Guide

The presence of 1 mM dipraglurant the response to D2R was unaltered, both 3 and 10 mM dose-dependently reduced the increase in both firing rate and [Ca2+]i induced by quinpirole (10 mM) in Tor1a(+/Δgag) interneurons.

Name

Type

Language

DIPRAGLURANT

Official Name

English

ADX48621

Code

English

ADX-48621

Code

English

dipraglurant [INN]

Common Name

English

6-FLUORO-2-(4-(PYRIDIN-2-YL)BUT-3-YN-1-YL)IMIDAZO(1,2-A)PYRIDINE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

485215