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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27129013Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27129013
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.
CNS Activity
Originator
Sources: https://encrypted.google.com/patents/WO2010056196A1
Curator's Comment: # AstraZeneca AB
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4593 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22924815 |
51.0 nM [IC50] | ||
Target ID: CHEMBL2525 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22924815 |
370.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3400 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24917547 |
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 |
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3807 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27129013 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27129013 |
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27129013
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22924815
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
Edited
Sat Dec 16 10:14:06 GMT 2023
by
admin
on
Sat Dec 16 10:14:06 GMT 2023
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Record UNII |
I8ID590133
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Record Status |
Validated (UNII)
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Record Version |
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DB12368
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I8ID590133
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1227163-84-9
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admin on Sat Dec 16 10:14:06 GMT 2023 , Edited by admin on Sat Dec 16 10:14:06 GMT 2023
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Related Record | Type | Details | ||
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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.
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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)
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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
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