545380-34-5 Usage
Description
6-Amino-4-(4-phenoxyphenylethylamino)quinazoline, also known as QNZ, is a potent inhibitor of NF-κB activation with an IC50 of 11 nM. It is a white solid that indirectly inhibits the NF-κB pathway via inhibition of store-operated calcium entry (SOC) and has been shown to have neuroprotective effects in various models of neurodegenerative diseases.
Uses
Used in Pharmaceutical Industry:
6-Amino-4-(4-phenoxyphenylethylamino)quinazoline is used as an inhibitor of NF-κB activation for its potent inhibitory effects on both NFKB transcriptional activation and TNF-α production. It is particularly useful in the development of treatments for inflammatory and autoimmune diseases, as well as in the study of the underlying mechanisms of these conditions.
Used in Neuroprotection:
In the field of neuroscience, QNZ is used as a neuroprotective agent due to its ability to inhibit the NF-κB pathway and store-operated calcium entry, which has been linked to neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. It has been shown to reduce synaptic neuronal SOC, rescue dendritic spine loss, and protect neurons from damage.
Used in Mitochondrial Function Research:
QNZ is also used as a potent and selective inhibitor of mitochondrial complex I in the study of mitochondrial function and its role in various diseases. With IC50 values of 25 nM for complex 1 from Y. lipolytica and 14 nM for complex 1 from Bos Taurus heart mitochondria, it serves as a valuable tool in understanding the mechanisms of mitochondrial dysfunction and its contribution to disease pathology.
References
1) Tobe?et al. (2003),?Discovery of quinazolines as a novel structural class of potent inhibitors of NF-kappa B activation; Bioorg. Med. Chem. Lett,?11?383
2) Tobe?et al.?(2003),?A novel structural class of potent inhibitors of NF-kB activation: structure-activity relationships and biological effects of 6-aminoquinazoline derivatives; Bioorg. Med. Chem. Lett,?11?3869
3) Choi?et al.?(2006),?Nuclear factor-kappaB activated by capacitive Ca2+ entry enhances muscarinic receptor-mediated soluble amyloid precursor protein (sAPPalpha) release in SH-SY5Y cells; J. Biol. Chem.,?281?12722
4) Wu?et al.?(2011),?Neuronal Store-Operated Calcium Entry Pathway as a Novel Therapeutic Target for Huntington’s Disease Treatment; Chem. Biol.,?18?777
5) Wu?et al. (2016),?Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington’s Disease Mouse Model; J. Neurosci.,?36?125
6) Krishnathas?et al. (2017),?Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I; Medchemcomm.?8?657
7) Chernyuk?et al. (2019),?Antagonist of neuronal store-operated calcium entry exerts beneficial effects in neurons expressing PSEN1?E9 mutant linked to familial Alzheimer disease;?Neuroscience,?410?118
Check Digit Verification of cas no
The CAS Registry Mumber 545380-34-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,4,5,3,8 and 0 respectively; the second part has 2 digits, 3 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 545380-34:
(8*5)+(7*4)+(6*5)+(5*3)+(4*8)+(3*0)+(2*3)+(1*4)=155
155 % 10 = 5
So 545380-34-5 is a valid CAS Registry Number.
InChI:InChI=1/C22H20N4O/c23-17-8-11-21-20(14-17)22(26-15-25-21)24-13-12-16-6-9-19(10-7-16)27-18-4-2-1-3-5-18/h1-11,14-15H,12-13,23H2,(H,24,25,26)
545380-34-5Relevant articles and documents
6-amino-4-(4-phenoxyphenylethylamino)quinazoline derivative as well as preparation method and application thereof
-
, (2021/01/24)
The invention belongs to the technical field of medicines, and particularly relates to a 6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) derivative as well as a preparation method and application thereof. According to the invention, a series of QNZ
Discovery of quinazolines as a novel structural class of potent inhibitors of NF-κB activation
Tobe, Masanori,Isobe, Yoshiaki,Tomizawa, Hideyuki,Nagasaki, Takahiro,Takahashi, Hirotada,Fukazawa, Tominaga,Hayashi, Hideya
, p. 383 - 391 (2007/10/03)
We disclose here a new structural class of low-molecular-weight inhibitors of NF-κB activation that were designed and synthesized by starting from quinazoline derivative 6a. Structure-activity relationship (SAR) studies based on 6a elucidated the structural requirements essential for the inhibitory activity toward NF-κB transcriptional activation, and led to the identification of the 6-amino-4-phenethylaminoquinazoline skeleton as the basic framework. In this series of compounds, 11q, containing the 4-phenoxyphenethyl moiety at the C(4)-position, showed strong inhibitory effects on both NF-κB transcriptional activation and TNF-α production. Furthermore, 11q exhibited an anti-inflammatory effect on carrageenin-induced paw edema in rats.
