L-822179

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H14N8O2
Molecular Weight	362.3455
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=C(COC2=NN3C(=NN=C3C4=C2C=CC=C4)C5=NOC(C)=C5)N=N1

InChI

InChIKey=NZMJFRXKGUCYNP-UHFFFAOYSA-N

InChI=1S/C17H14N8O2/c1-10-7-14(22-27-10)16-20-19-15-12-5-3-4-6-13(12)17(21-25(15)16)26-9-11-8-24(2)23-18-11/h3-8H,9H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C17H14N8O2
Molecular Weight	362.3455
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/19770002 | https://www.ncbi.nlm.nih.gov/pubmed/15084116

L-822179 is a triazolophthalazine that selectively attenuates the effects of GABA at GABA(A) receptors containing an alpha5 subunit. It is an orally active, functionally selective compound, which enhances cognition in animals without anxiogenic or convulsant effects. The dose-limiting adverse event of L-822179 is dizziness and/or light-headedness. L-822179 does not improve cognitive performance in the elderly; indeed the dose of 4 mg actually significantly impairs performance. In this regard, it could therefore be considered that this study is a failed trial in so far as the positive control, lorazepam, does not show the anticipated effect.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA receptor alpha-5 subunit 8 Target ID: CHEMBL5112 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Agonist 2678	0.66 nM [Ki]
GABA receptor alpha-2 subunit 7 Target ID: CHEMBL4956 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Partial Agonist 290	0.58 nM [Ki]
GABA receptor alpha-1 subunit 19 Target ID: CHEMBL1962 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Binding Agent 1064	0.88 nM [Ki]
GABA receptor alpha-3 subunit 6 Target ID: CHEMBL3026 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Binding Agent 1064	0.61 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cognitive impairment 15 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19770002	Primary		Phase I 428	Unknown Approved Use Unknown
Down syndrome 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21693554 https://www.ncbi.nlm.nih.gov/pubmed/22028705	Palliative		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
16 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN
28 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN
8.8 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
46 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	2 mg 4 times / day multiple, oral dose: 2 mg route of administration: Oral experiment type: MULTIPLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN
80 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	4 mg 3 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN
168 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	6 mg 3 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2 h REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN
2.5 h REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN
2.2 h REVIEW https://pubmed.ncbi.nlm.nih.gov/19770002/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	L-822179 plasma	Homo sapiens population: HEALTHY age: ADOLESCENT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
6 mg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 6 mg, 4 times / day Route: oral Route: multiple Dose: 6 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 7 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	Other AEs: Dizziness, lightheaded... Other AEs: Dizziness (6 patients) lightheaded (6 patients) Nausea (1 pt) Tiredness (1 pt) Drowsiness (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
6 mg single, oral (total daily dose) Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 8 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	Other AEs: lightheaded, Dizziness... Other AEs: lightheaded (2 patients) Dizziness (2 patients) Headache (1 pt) Drowsiness (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19770002

AEs

AE	Significance	Dose	Population
Drowsiness	1 pt	6 mg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 6 mg, 4 times / day Route: oral Route: multiple Dose: 6 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 7 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Nausea	1 pt	6 mg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 6 mg, 4 times / day Route: oral Route: multiple Dose: 6 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 7 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Tiredness	1 pt	6 mg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 6 mg, 4 times / day Route: oral Route: multiple Dose: 6 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 7 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Dizziness	6 patients	6 mg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 6 mg, 4 times / day Route: oral Route: multiple Dose: 6 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 7 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
lightheaded	6 patients	6 mg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 6 mg, 4 times / day Route: oral Route: multiple Dose: 6 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 7 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Drowsiness	1 pt	6 mg single, oral (total daily dose) Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 8 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Headache	1 pt	6 mg single, oral (total daily dose) Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 8 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Dizziness	2 patients	6 mg single, oral (total daily dose) Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 8 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
lightheaded	2 patients	6 mg single, oral (total daily dose) Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT n = 8 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/19770002

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	5674AJ	https://aksci.com/item_detail.php?cat=5674AJ
Accela ChemBio Inc	SY008621	http://accelachem.com/cn/search.html?keyword=SY008621&attname=0
Angene	AGN-PC-08VZGO	http://www.angenechemical.com/productshow/AGN-PC-08VZGO.html
AstaTech	30549	http://astatechinc.com/CPSResult.php?CRNO=30549
BOC Sciences	215874-86-5	http://www.bocsci.com/description.asp?cas=215874-86-5
Beijing Acemol Technology	AMBZ0319	http://www.acemol.com/products/PAMBZ0319.shtml
ChemDiv	BB95-3008	http://chemistryondemand.com:8080/eShop/search_results.jsp?idnumber=BB95-3008
Combi-Blocks	ST-5546	http://www.combi-blocks.com/cgi-bin/find.cgi?ST-5546
Debye Scientific	DB-066566	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-066566
Fluorochem	386946	http://www.fluorochem.co.uk/Products/Product?code=386946
KeyOrganics	AS-31587	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-31587
Lab Network	LN01373886	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01373886
MolPort	MolPort-028-748-635	https://www.molport.com/shop/molecule-link/MolPort-028-748-635
MuseChem	I014426	https://www.musechem.com/product/I014426.html
Toronto Research Chemicals	I942008	https://www.trc-canada.com/product-detail/?CatNum=I942008
Toronto Research Chemicals	T548808	https://www.trc-canada.com/product-detail/?CatNum=T548808
Wonderchem	WD031NP	http://www.wonder-chem.com/search.html?text=WD031NP
eMolecules	11312903	https://orderbb.emolecules.com/search/#?query=11312903
eNovation Chemicals	K11135	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K11135&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-9778694157	https://mcule.com/MCULE-9778694157/

PubMed

Title	Date	PubMed
An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties.	2004 Nov 18	15537339

Patents

Sample Use Guides

In Vivo Use Guide

4-mg 2 h prior to drinking ethanol

Route of Administration: Oral

In Vitro Use Guide

The affinity at native rat brain GABAA receptors, 0.9–1.2 nM, is similar to that observed in recombinant human receptors and suggests that α5IA does not show marked interspecies differences in affinity.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:41:54 GMT 2023` Edited by `admin` on `Fri Dec 15 15:41:54 GMT 2023`
Record UNII	1M7NI1A92L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

L-822179

Common Name

English

.ALPHA. 5IA

Code

English

L-822,179

Code

English

1,2,4-TRIAZOLO(3,4-A)PHTHALAZINE, 3-(5-METHYL-3-ISOXAZOLYL)-6-((1-METHYL-1H-1,2,3-TRIAZOL-4-YL)METHOXY)-

Systematic Name

English

3-(5-METHYLISOXAZOLE-3-YL)-6-((1-METHYL-1,2,3-TRIAZOL-4-YL)METHOXY)-1,2,4-TRIAZOLO(3,4-A)PHTHALAZINE

Systematic Name

English

Code System Code Type Description

PUBCHEM

6918451