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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 of L-822179

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
MOL RATIO 1 MOL RATIO (average)
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

CNS Active
3,913

Originator

Merck Sharp & Dohme
86

Approval Year

Unknown
139,594

Targets

Primary TargetPharmacologyConditionPotency
GABA receptor alpha-5 subunit
8
Agonist
2,678
 0.66 nM [Ki]
GABA receptor alpha-2 subunit
7
Partial Agonist
290
 0.58 nM [Ki]
GABA receptor alpha-1 subunit
19
Binding Agent
1,064
 0.88 nM [Ki]
GABA receptor alpha-3 subunit
6
Binding Agent
1,064
 0.61 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Cognitive impairment
15
 Primary
Phase I
428
Unknown
Down syndrome
6
 Palliative
Preclinical
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
28 ng/mL
6 mg single, oral
 L-822179 plasma
Homo sapiens
16 ng/mL
4 mg single, oral
 L-822179 plasma
Homo sapiens
8.8 ng/mL
2 mg single, oral
 L-822179 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
46 ng × h/mL
2 mg 4 times / day multiple, oral
 L-822179 plasma
Homo sapiens
80 ng × h/mL
4 mg 3 times / day multiple, oral
 L-822179 plasma
Homo sapiens
168 ng × h/mL
6 mg 3 times / day multiple, oral
 L-822179 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.5 h
6 mg single, oral
 L-822179 plasma
Homo sapiens
2 h
4 mg single, oral
 L-822179 plasma
Homo sapiens
2.2 h
2 mg single, oral
 L-822179 plasma
Homo sapiens

Doses

AEs

PubMed

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
Record UNII
1M7NI1A92L
Record Status Validated (UNII)
Record Version
NIH
NCATS
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