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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H16F3N5
Molecular Weight 431.4125
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZD-3839

SMILES

NC1=N[C@](C2=C1C(F)=CC=C2)(C3=CC(=NC=C3)C(F)F)C4=CC=CC(=C4)C5=CN=CN=C5

InChI

InChIKey=MRXBCEQZNKUUIP-DEOSSOPVSA-N
InChI=1S/C24H16F3N5/c25-19-6-2-5-18-21(19)23(28)32-24(18,17-7-8-31-20(10-17)22(26)27)16-4-1-3-14(9-16)15-11-29-13-30-12-15/h1-13,22H,(H2,28,32)/t24-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT01348737 | https://www.ncbi.nlm.nih.gov/pubmed/22924815 | https://www.drugbank.ca/drugs/DB12368

AZD3839 is a potent and selective BACE1 inhibitor with about 14-fold selectivity over BACE2. In SH-SY5Y cells, AZD3839 efficiently decreases the Aβ40 levels and decreases the formation of sAPPβ. AZD3839 also decreases the Aβ40 levels secreted from C57BL/6 mouse primary cortical neurons, N2A cells, and Dunkin-Hartley guinea pig primary cortical neurons. AZD3839 causes in vitro BACE1 inhibition in the cell assay with the IC50 value of 16.7 nM. In C57BL/6 mice, AZD3839 (69 mg/kg, p.o.) causes a dose- and time-dependent reduction of plasma and brain Aβ. In guinea pig and non-human primates, AZD3839 also inhibits Aβ generation. AZD3839 has been used in phase I clinical trials studying the basic science of Safety and Tolerability. However future development has been discontinued.

Originator

Curator's Comment: # AstraZeneca AB

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
51.0 nM [IC50]
370.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3400 nM
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-3839 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
3807 nM
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-3839 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3.6%
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AZD-3839 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease.
2012 Nov 30
Patents

Patents

Sample Use Guides

In phase I clinical trials single oral ascending doses (1–300 mg) of AZD3839 were administered to 54 young healthy volunteer.
Route of Administration: Oral
SH-SY5Y cells (human neuroblastoma cell line) were cultured in DMEM/F-12 with Glutamax, 10% FCS, and 1% nonessential amino acids. The test compound (AZD3839) was incubated with cells for 16 h at 37 °C, 5% CO2. Meso Scale Discovery (MSD) plates were used for the detection of sAPPβ release; MSD sAPPβ plates were blocked in 3% BSA in Tris wash buffer for 1 h at rt and washed four times in Tris buffer. After incubation, 20 μL of medium was transferred to the preblocked and washed 384-well MSD sAPPβ microplate and incubated with shaking at rt for 2 h followed by washing four times in Tris buffer. A 10 μL volume of detection antibody was added (1 nM) followed by incubation with shaking at rt for 2 h followed by washing four times in Tris buffer. A 40 μL volume of read buffer was added per well, and the plates were read in a SECTOR imager. In addition, the cells incubated with test compound were further lysed and analyzed for any cytotoxic effects of the compounds using the ViaLight Plus cell proliferation/cytotoxicity kit
Name Type Language
AZD-3839
Common Name English
AZD 3839 [WHO-DD]
Common Name English
(1S)-1-(2-(DIFLUOROMETHYL)PYRIDIN-4-YL)-4-FLUORO-1-(3-(PYRIMIDIN-5-YL)PHENYL)-1H-ISOINDOL-3-AMINE
Systematic Name English
AZD3839
Code English
1H-ISOINDOL-3-AMINE, 1-(2-(DIFLUOROMETHYL)-4-PYRIDINYL)-4-FLUORO-1-(3-(5-PYRIMIDINYL)PHENYL)-, (1S)-
Systematic Name English
Code System Code Type Description
PUBCHEM
46202416
Created by admin on Sat Dec 16 10:14:06 GMT 2023 , Edited by admin on Sat Dec 16 10:14:06 GMT 2023
PRIMARY
DRUG BANK
DB12368
Created by admin on Sat Dec 16 10:14:06 GMT 2023 , Edited by admin on Sat Dec 16 10:14:06 GMT 2023
PRIMARY
FDA UNII
I8ID590133
Created by admin on Sat Dec 16 10:14:06 GMT 2023 , Edited by admin on Sat Dec 16 10:14:06 GMT 2023
PRIMARY
CAS
1227163-84-9
Created by admin on Sat Dec 16 10:14:06 GMT 2023 , Edited by admin on Sat Dec 16 10:14:06 GMT 2023
PRIMARY