L-822179 DIHYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H14N8O2.2H2O
Molecular Weight	398.376
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=KFZXNQOVHVSRLZ-UHFFFAOYSA-N

InChI=1S/C17H14N8O2.2H2O/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;2*1H2

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

Molecular Formula	H2O
Molecular Weight	18.0153
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 2752	0.66 nM [Ki]
GABA receptor alpha-2 subunit 7 Target ID: CHEMBL4956 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Partial Agonist 297	0.58 nM [Ki]
GABA receptor alpha-1 subunit 19 Target ID: CHEMBL1962 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Binding Agent 1076	0.88 nM [Ki]
GABA receptor alpha-3 subunit 6 Target ID: CHEMBL3026 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15084116	Binding Agent 1076	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 438	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
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
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
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
2.5 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 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
2.2 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 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 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	Other AEs: Dizziness, lightheaded... Other AEs: Dizziness (6 patients) lightheaded (6 patients) Tiredness (1 pt) Nausea (1 pt) Drowsiness (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
6 mg single, oral Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	Other AEs: Dizziness, lightheaded... Other AEs: Dizziness (2 patients) lightheaded (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 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 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Nausea	1 pt	6 mg 4 times / day multiple, oral 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 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Tiredness	1 pt	6 mg 4 times / day multiple, oral 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 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Dizziness	6 patients	6 mg 4 times / day multiple, oral 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 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
lightheaded	6 patients	6 mg 4 times / day multiple, oral 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 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Drowsiness	1 pt	6 mg single, oral Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Headache	1 pt	6 mg single, oral Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
Dizziness	2 patients	6 mg single, oral Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002
lightheaded	2 patients	6 mg single, oral Highest studied dose Dose: 6 mg Route: oral Route: single Dose: 6 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19770002	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19770002

Sourcing

Vendor/Aggregator	ID	URL
Accela ChemBio Inc	SY008621	http://accelachem.com/cn/search.html?keyword=SY008621&attname=0
AK Scientific	5674AJ	https://aksci.com/item_detail.php?cat=5674AJ
Angene	AGN-PC-08VZGO	http://www.angenechemical.com/productshow/AGN-PC-08VZGO.html
AstaTech	30549	http://astatechinc.com/CPSResult.php?CRNO=30549
Beijing Acemol Technology	AMBZ0319	http://www.acemol.com/products/PAMBZ0319.shtml
BOC Sciences	215874-86-5	http://www.bocsci.com/description.asp?cas=215874-86-5
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
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
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
mcule	MCULE-9778694157	https://mcule.com/MCULE-9778694157/
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

PubMed

Title	Date	PubMed
Occupancy of human brain GABA(A) receptors by the novel α5 subtype-selective benzodiazepine site inverse agonist α5IA as measured using [¹¹C]flumazenil PET imaging.	2010-12	20696179
Preclinical and clinical pharmacology of the GABAA receptor alpha5 subtype-selective inverse agonist alpha5IA.	2010-01	19770002
In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist.	2009-11	19704033
The plasma-occupancy relationship of the novel GABAA receptor benzodiazepine site ligand, alpha5IA, is similar in rats and primates.	2009-07	19422390
An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties.	2004-11-18	15537339
Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site.	2004-07-01	15214791
Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers.	2004-04-22	15084116

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 `Mon Mar 31 18:11:53 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:53 GMT 2025`
Record UNII	HE33IBA1AF
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

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

Preferred Name

English

L-822179 DIHYDRATE

Code

English

Code System Code Type Description

PUBCHEM

9908823

Created by admin on Mon Mar 31 18:11:53 GMT 2025 , Edited by admin on Mon Mar 31 18:11:53 GMT 2025

PRIMARY

CAS

268541-28-2

Created by admin on Mon Mar 31 18:11:53 GMT 2025 , Edited by admin on Mon Mar 31 18:11:53 GMT 2025

PRIMARY

FDA UNII

HE33IBA1AF

Created by admin on Mon Mar 31 18:11:53 GMT 2025 , Edited by admin on Mon Mar 31 18:11:53 GMT 2025

PRIMARY

Related Record Type Details


					1M7NI1A92L

L-822179

ANHYDROUS->SOLVATE


					1M7NI1A92L

L-822179

PARENT -> SALT/SOLVATE

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/19770002 | https://www.ncbi.nlm.nih.gov/pubmed/15084116

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19770002 | https://www.ncbi.nlm.nih.gov/pubmed/15084116

C_max

T_1/2