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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

Molecular Formula C24H16F3N5
Molecular Weight 431.4125
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:14:06 GMT 2023
Edited
by admin
on Sat Dec 16 10:14:06 GMT 2023
Record UNII
I8ID590133
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
ACTIVE MOIETY
Drug: AZD 3839(Primary); Indications: Alzheimer's disease, Dementia; Focus: Adverse reactions; Most Recent Events: 05 Apr 2012 Actual patient number added 72 according to ClinicalTrials.gov., 05 Apr 2012 Actual end date (June 2011) added as reported by ClinicalTrials.gov., 05 Apr 2012 Status changed from recruiting to completed as reported by ClinicalTrials.gov.
ACTIVE MOIETY
Originator: Astex Therapeutics, AstraZeneca; Developer: AstraZeneca; Class: Anti-dementia, Small molecule; Mechanism of Action: Amyloid precursor protein secretase inhibitor; Orphan Drug Status: No; On Fast track: No; Highest Development Phase: Discontinued for Alzheimer's disease; Most Recent Events: 30 Jun 2012 Discontinued - Phase-I for Alzheimer's disease in United Kingdom (PO), 30 Nov 2011 AstraZeneca completes a phase I trial in Healthy volunteers in United Kingdom (NCT01348737), 21 Jun 2011 Phase-I clinical trials in Alzheimer's disease in United Kingdom (PO)
ACTIVE MOIETY
Official Title: A Phase I, Randomised, Double-blind, Placebo-controlled, Parallel-group Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Biomarkers of AZD3839 Including an Open-label Food Effect Group in Healthy Male and Female Volunteers of Non-childbearing Potential Purpose: The purpose of the study is to assess the safety, tolerability and blood concentration of AZD3839 following oral administration of single doses in healthy men and women of non-childbearing potential