6-AMINO-4-(4-PHENOXYPHENYLETHYLAMINO)QUINAZOLINE

6-AMINO-4-(4-PHENOXYPHENYLETHYLAMINO)QUINAZOLINE Property

Melting point:

169-175°C

storage temp. 

Keep in dark place,Inert atmosphere,2-8°C

solubility 

DMSO: soluble15mg/mL, clear

form 

powder

color 

white to beige

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.

Safety

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P273Avoid release to the environment.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P330Rinse mouth.

P391Collect spillage. Hazardous to the aquatic environment

P501Dispose of contents/container to..…

6-AMINO-4-(4-PHENOXYPHENYLETHYLAMINO)QUINAZOLINE Chemical Properties,Usage,Production

Description

QNZ (545380-34-5) was originally described as a potent inhibitor of NF-κB activation (IC50?= 11 nM) and TNF-α?production (IC50?= 7 nM).1,2?It indirectly inhibits the NF-κB pathway via inhibition of store-operated calcium entry (SOC) and displayed neuroprotective effects in transgenic fly and mouse models of Huntington’s disease.3,4?Its target has been postulated to be heteromeric calcium channels containing TRPC1 as one of the subunits.4?QNZ reduced synaptic neuronal SOC and rescued dendritic spine loss in YAC128 striatal medium spiny neurons.5?QNZ has also been identified as a potent (IC50?= 25 nM complex 1 from?Y.lipolytica; IC50?= 14 nM complex 1 from?Bos Taurus?heart mitochondria) and selective inhibitor of mitochondrial complex I.6?QNZ?decreased PSEN1ΔE9-mediated nSOCE upregulation and rescued mushroom spines in PSEN1ΔE9-expressing neurons, which are linked to familial Alzheimer’s disease.7

Chemical Properties

White Solid

Uses

QNZ is a novel inhibitor of NFkB which displays potent inhibitory effects on both NFKB transcriptional activation (IC50=11nM) and TNF-a production (IC50=7nM). It dose-dependently inhibited carragenin-induced edema formation in the rat paw model (1m

Uses

QNZ is an inhibitor of NF-κB activation with IC50 of 11 nM.

target

NF-κB

IC 50

NF-κB: 11 nM (IC₅₀, in human Jurkat cells transfected with pNFκB-Luc)

References

[1] MASANORI TOBE. Discovery of quinazolines as a novel structural class of potent inhibitors of NF-κB activation[J]. Bioorganic & Medicinal Chemistry, 2003, 11 3: Pages 383-391. DOI:10.1016/s0968-0896(02)00440-6
[2] MASANORI TOBE. A novel structural class of potent inhibitors of NF-κB activation: structure–activity relationships and biological effects of 6-aminoquinazoline derivatives[J]. Bioorganic & Medicinal Chemistry, 2003, 11 18: Pages 3869-3878. DOI:10.1016/s0968-0896(03)00438-3
[3] SHINKYU CHOI. Nuclear factor-kappaB activated by capacitative Ca2+ entry enhances muscarinic receptor-mediated soluble amyloid precursor protein (sAPPalpha) release in SH-SY5Y cells.[J]. The Journal of Biological Chemistry, 2006, 281 18: 12722-12728. DOI:10.1074/jbc.m601018200
[4] JUN WU. Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington’s disease treatment.[J]. Chemistry & biology, 2011, 18 6: 777-793. DOI:10.1016/j.chembiol.2011.04.012
[5] JUN WU. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington’s Disease Mouse Model[J]. The Journal of Neuroscience, 2016, 196 1: 125-141. DOI:10.1523/jneurosci.1038-15.2016
[6] ROBIN KRISHNATHAS. Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I.[J]. MedChemComm, 2017: 657-661. DOI:10.1039/c6md00655h
[7] DARIA CHERNYUK . Antagonist of neuronal store-operated calcium entry exerts beneficial effects in neurons expressing PSEN1ΔE9 mutant linked to familial Alzheimer disease[J]. Neuroscience, 2019, 410: Pages 118-127. DOI:10.1016/j.neuroscience.2019.04.043