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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 of L-822179 DIHYDRATE

SMILES

O.O.CN1C=C(COC2=NN3C(=NN=C3C4=CC=CC=C24)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 H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
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

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

Merck Sharp & Dohme
86
Curator's Comment: # Merck Sharp and Dohme Research Laboratories

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 0.66 nM [Ki]
Partial Agonist
290
 0.58 nM [Ki]
Binding Agent
1064
 0.88 nM [Ki]
Binding Agent
1064
 0.61 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Palliative
Preclinical
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers.
2004 Apr 22
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 Jul 1
An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties.
2004 Nov 18
The plasma-occupancy relationship of the novel GABAA receptor benzodiazepine site ligand, alpha5IA, is similar in rats and primates.
2009 Jul
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 Nov
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 Dec
Preclinical and clinical pharmacology of the GABAA receptor alpha5 subtype-selective inverse agonist alpha5IA.
2010 Jan
Patents

Patents

06534505
2
20010049439
5
JP2001525802A
2
JP4672820B2
2

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 15:52:46 GMT 2023
Edited
by admin
on Fri Dec 15 15:52:46 GMT 2023
Record UNII
HE33IBA1AF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
L-822179 DIHYDRATE
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)-, HYDRATE (1:2)
Systematic Name English
Code System Code Type Description
PUBCHEM
9908823
Created by admin on Fri Dec 15 15:52:46 GMT 2023 , Edited by admin on Fri Dec 15 15:52:46 GMT 2023
PRIMARY
CAS
268541-28-2
Created by admin on Fri Dec 15 15:52:46 GMT 2023 , Edited by admin on Fri Dec 15 15:52:46 GMT 2023
PRIMARY
FDA UNII
HE33IBA1AF
Created by admin on Fri Dec 15 15:52:46 GMT 2023 , Edited by admin on Fri Dec 15 15:52:46 GMT 2023
PRIMARY
Related Record Type Details
Structure of L-822179
ANHYDROUS->SOLVATE
Structure of L-822179
PARENT -> SALT/SOLVATE
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