GRN-529

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H15F2N3O2
Molecular Weight	391.3702
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)OC1=C(C=C(C=C1)C(=O)N2CC3=C(C2)N=CC=C3)C#CC4=CC=CC=N4

InChI

InChIKey=JITMSIRHBAVREW-UHFFFAOYSA-N

InChI=1S/C22H15F2N3O2/c23-22(24)29-20-9-7-16(12-15(20)6-8-18-5-1-2-10-25-18)21(28)27-13-17-4-3-11-26-19(17)14-27/h1-5,7,9-12,22H,13-14H2

HIDE SMILES / InChI

Molecular Formula	C22H15F2N3O2
Molecular Weight	391.3702
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22539775 | https://www.ncbi.nlm.nih.gov/pubmed/22551786

GRN-529 is a negative allosteric modulator of mGluR5. In a mouse model of autism, GRN-529 (named as PF-05212391 by Pfizer) decreased self-grooming and stereotyped jumping and increased social functioning compared with no treatment. In a mouse model of depression, GRN-529 had dose-dependent efficacy across a therapeutically relevant battery of animal models, comprising depression and 2 of the co-morbid symptoms overrepresented in treatment resistant depression, namely anxiety and pain

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Metabotropic glutamate receptor 5 39 Target ID: P41594 Gene ID: 2915.0 Gene Symbol: GRM5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22539775	Negative Allosteric Modulator 42		0.001 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Autism 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22539775	Primary		Preclinical	Unknown Approved Use Unknown
Treatment-resistant depression 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22551786	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism.	2012 Apr 25	22539775
Neurophysiological signals as potential translatable biomarkers for modulation of metabotropic glutamate 5 receptors.	2013 Dec	23831682
Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression.	2013 Mar	22551786

Patents

Sample Use Guides

In Vivo Use Guide

Mice were given GRN-529 at doses of 0.3, 1.0, or 3.0 mg/kg intraperitoneally or orally (preclinical model).

Route of Administration: Other

In Vitro Use Guide

HEK293 expressing either human or mouse mGluR5 were treated with different concentrations of GRN-059 (10(-10)-10(-5) M) to test its effect on the receptor.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:35:51 UTC 2023` Edited by `admin` on `Sat Dec 16 17:35:51 UTC 2023`
Record UNII	D77QDV7E9J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GRN-529

Code

English

(4-(DIFLUOROMETHOXY)-3-(2-(2-PYRIDINYL)ETHYNYL)PHENYL)(5,7-DIHYDRO-6H-PYRROLO(3,4-B)PYRIDIN-6-YL)METHANONE

Systematic Name

English

(4-(DIFLUOROMETHOXY)-3-(2-PYRIDIN-2-YLETHYNYL)PHENYL)-(5,7-DIHYDROPYRROLO(3,4-B)PYRIDIN-6-YL)METHANONE

Systematic Name

English

METHANONE, (4-(DIFLUOROMETHOXY)-3-(2-(2-PYRIDINYL)ETHYNYL)PHENYL)(5,7-DIHYDRO-6H-PYRROLO(3,4-B)PYRIDIN-6-YL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID501030348