5435-54-1Relevant articles and documents
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Johnson,Waller
, p. 295,296 (1968)
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Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action
Selakovi?, ?ivota,Tran, Julie P.,Kota, Krishna P.,Lazi?, Marija,Retterer, Cary,Besh, Robert,Panchal, Rekha G.,Soloveva, Veronica,Sean, Vantongreen A.,Jay, Wells B.,Pavi?, Aleksandar,Verbi?, Tatjana,Vasiljevi?, Branka,Kuehl, Kathleen,Duplantier, Allen J.,Bavari, Sina,Mudhasani, Rajini,?olaja, Bogdan A.
supporting information, p. 32 - 50 (2018/11/21)
Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease. These compounds incorporate the structural features of cationic amphiphilic drugs (CAD), i.e they possess both a hydrophobic domain and a hydrophilic domain consisting of an ionizable amine functional group. These structural features enable easily diffusion into cells but once inside an acidic compartment their amine groups became protonated, ionized and remain trapped inside the acidic compartments such as late endosomes and lysosomes. These compounds, by virtue of their lysomotrophic functions, blocked EBOV entry. However, unlike other drugs containing a CAD moiety including chloroquine and amodiaquine, compounds reported in this study display faster kinetics of accumulation in the lysosomes, robust expansion of late endosome/lysosomes, relatively more potent suppression of lysosome fusion with other vesicular compartments and inhibition of cathepsins activities, all of which play a vital role in anti-EBOV activity. Furthermore, the diazachrysene 2 (ZSML08) that showed most potent activity against EBOV in in vitro cell culture assays also showed significant survival benefit with 100% protection in mouse models of Ebola virus disease, at a low dose of 10 mg/kg/day. Lastly, toxicity studies in vivo using zebrafish models suggest no developmental defects or toxicity associated with these compounds. Overall, these studies describe two new pharmacophores that by virtue of being potent lysosomotrophs, display potent anti-EBOV activities both in vitro and in vivo animal models of EBOV disease.
High colour rendering index and colour stable hybrid white efficient OLEDs with a double emitting layer structure using a single phosphorescence dopant of heteroleptic platinum complexes
Poloek, Anurachw,Lin, Chiao-Wen,Chen, Chin-Ti,Chen, Chao-Tsen
, p. 10343 - 10356 (2015/02/19)
Four heteroleptic platinum complexes (FPtXND) bearing 4-hydroxy-1,5-naphthyridine derivatives functionalized with dimethyl (X = mm), phenoxy (X = OPh), piperidine (X = pp), or carbazole (X = Cz) units as one ligand (XND) and 2-(2,4-difluorophenyl)pyridine as the other common ligand (F) were newly synthesized and characterized. The crystal structures of FPtOPhND and FPtCzND were determined by single-crystal X-ray diffraction crystallography. Although they have a short plane-to-plane packing distance of 3.62 and 3.39 A, respectively, both platinum complexes have different molecular packing patterns, which affect their photoluminescence (PL) in solution and electroluminescence (EL) in the solid state. Due to the contribution from both monomers and excimers/aggregates, all of the platinum complexes exhibited broad and red-shifted PL in concentrated solutions as well as in doped thin films. In the monochromatic organic lighting diode (OLED) testing, FPtXND doped in 4,4′-di(9H-carbazol-9-yl)-1,1′-biphenyl (CBP) exhibited greenish yellow or orange yellow EL, of which FPtOPhND has the highest EL efficiency mainly due to its high solution PL quantum yield of 21%. Hybrid white OLEDs were first achieved with a single emitting layer configuration, of which highly fluorescent blue N,N′-di-1-naphthalenyl-N,N′-diphenyl-[1,1′:4′,1″:4″,1-quaterphenyl]-4,4-diamine (4P-NPD) was used as the host material for all four platinum complexes. To improve the performance of the FPtOPhND-based hybrid white OLEDs, double emitting layer configurations were adopted with CBP and 4P-NPD as the host material. Virtually voltage independent, a white EL having CIEx,y (0.33, 0.31) and a CRI as high as 91 was obtained. The maximum EL efficiency of 11.8%, 25.9 cd A-1, or 11.6 lm W-1 was acquired with FPtOPhND doped in the double emitting layer configuration of an OLED.
