- Identification of novel non-nucleoside vinyl-stilbene analogs as potent norovirus replication inhibitors with a potential host-targeting mechanism
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Norovirus (NV), is the most common cause of acute gastroenteritis worldwide. To date, there is no specific anti-NV drug or vaccine to treat NV infections. In this study, we evaluated the inhibitory effect of different stilbene-based analogs on RNA genome replication of human NV (HNV) using a virus replicon-bearing cell line (HG23). Initial screening of our in-house chemical library against NV led to the identification of a hit containing stilbene scaffold 5 which on initial optimization gave us a vinyl stilbene compound 16c (EC50 = 4.4 μM). Herein we report our structure-activity relationship study of the novel series of vinyl stilbene analogs that inhibits viral RNA genome replication in a human NV-specific manner. Among these newly synthesized compounds, several amide derivatives of vinyl stilbenes exhibited potent anti-NV activity with EC50 values ranging from 1 to 2 μM. A trans-vinyl stilbenoid with an appended substituted piperazine amide (18k), exhibited potent anti-NV activity and also displayed favorable metabolic stability. Compound 18k demonstrated an excellent safety profile, the highest suppressive effect, and was selective for HNV replication via a viral RNA polymerase-independent manner. Its potential host-targeting antiviral mechanism was further supported by specific activation of heat shock factor 1-dependent stress-inducible pathway by 18k. These results suggest that 18k might be a promising lead compound for developing novel NV inhibitors with the novel antiviral mechanism.
- Harmalkar, Dipesh S.,Lee, Sung-Jin,Lu, Qili,Kim, Mi Il,Park, Jaehyung,Lee, Hwayoung,Park, Minkyung,Lee, Ahrim,Lee, Choongho,Lee, Kyeong
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supporting information
(2019/10/09)
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- Structure-guided design, synthesis, and evaluation of guanine-derived inhibitors of the eIF4E mRNA-cap interaction
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The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5′ terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display pot
- Chen, Xiaoqi,Kopecky, David J.,Mihalic, Jeff,Jeffries, Shawn,Min, Xiaoshan,Heath, Julie,Deignan, Jeff,Lai, Sujen,Fu, Zice,Guimaraes, Cristiano,Shen, Shanling,Li, Shyun,Johnstone, Sheree,Thibault, Stephen,Xu, Haoda,Cardozo, Mario,Shen, Wang,Walker, Nigel,Kayser, Frank,Wang, Zhulun
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experimental part
p. 3837 - 3851
(2012/07/28)
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- Preparation of benzylphosphonates via a palladium(0)-catalyzed cross-coupling of H-phosphonate diesters with benzyl halides. Synthetic and mechanistic studies
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We have developed a new, efficient method for the synthesis of benzylphosphonate and benzylphosphonothioate diesters via a palladium(0)- catalyzed cross-coupling reaction between benzyl halides and H-phosphonate or H-phosphonothioate diesters, using Pd2(dba)3(CHCl 3) as a palladium source and Xantphos as a supporting ligand. Some mechanistic aspects of these reactions were investigated using 31P NMR spectroscopy.
- Laven, Gaston,Kalek, Marcin,Jezowska, Martina,Stawinski, Jacek
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experimental part
p. 967 - 975
(2010/08/04)
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- Directed assembly of single-walled carbon nanotubes via drop-casting onto a UV-patterned photosensitive monolayer
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We report the use of a novel UV-sensitive self-assembled monolayer to selectively deposit single-walled carbon nanotubes from solution using heterogeneous surface wettability. This process combines ubiquitous photopatterning techniques with simple solution processing to yield highly selective and densely packed carbon nanotube patterns. The essential concept behind this process is the change in surface chemistry caused by the UV-induced monolayer reaction. Selective deposition of carbon nanotubes was achieved by drop-casting, and the resulting films show local ordering, indicating that further development of this process will lead to simple technique for large-scale integration. Copyright
- Bardecker, Julie A.,Afzali, Ali,Tulevski, George S.,Graham, Teresita,Hannon, James B.,Jen, Alex K.-Y.
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p. 7226 - 7227
(2008/12/20)
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- NOVEL SAFRAMYCIN ANALOGS AS THERAPEUTIC AGENTS
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The present invention is directed to saframcyin analogs that are useful in the treatment of cancer. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.
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Page/Page column 68-69
(2010/02/15)
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- Synthesis of phosphono-substituted porphyrin compounds for attachment to metal oxide surfaces
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A method of making a phosphono-substituted dipyrromethane comprises reacting an aldehyde or acetal having at least one phosphono group substituted thereon with pyrrole to produce a phosphono-substituted dipyrromethane; and wherein the phosphono is selecte
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Page/Page column 22-23
(2008/06/13)
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- Porphyrins Bearing Mono or Tripodal Benzylphosphonic Acid Tethers for Attachment to Oxide Surfaces
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The ability to attach redox-active molecules to oxide surfaces in controlled architectures (distance, orientation, packing density) is essential for the design of a variety of molecular-based information storage devices. We describe the synthesis of a series of redox-active molecules wherein each molecule bears a benzylphosphonic acid tether. The redox-active molecules include zinc porphyrins, a cobalt porphyrin, and a ferrocene-zinc porphyrin. An analogous tripodal tether has been prepared that is based on a tris [4-(dihydroxyphosphorylmethyl)phenyl]-derivatized methane. A zinc porphyrin is linked to the methane vertex by a 1,4-phenylene unit. The tripodal systems are designed to improve monolayer stability and ensure vertical orientation of the redox-active porphyrin on the electroactive surface. For comparison purposes, a zinc porphyrin bearing a hexylphosphonic acid tether also has been prepared. The synthetic approaches for introduction of the phosphonic acid group include derivatization of a bromoalkyl porphyrin or use of a dimethyl or diethyl phosphonate substituted precursor in a porphyrin-forming reaction. The latter approach makes use of dipyrromethane building blocks bearing mono or tripodal dialkyl phosphonate groups. The zinc porphyrintripodal compound bearing benzylphosphonic acid legs tethered to a SiO2 surface (grown on doped Si) was electrically well-behaved and exhibited characteristic porphyrin oxidation/reduction waves. Collectively, a variety of porphyrinic molecules can now be prepared with tethers of different length, composition, and structure (mono or tripodal) for studies of molecular-based information storage on oxide surfaces.
- Loewe, Robert S.,Ambroise, Arounaguiry,Muthukumaran, Kannan,Padmaja, Kisari,Lysenko, Andrey B.,Mathur, Guru,Li, Qiliang,Bocian, David F.,Misra, Veena,Lindsey, Jonathan S.
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p. 1453 - 1460
(2007/10/03)
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- Phenyl glycines for use in reducing neurotoxic injury
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A class of phenyl glycine compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a phenyl glycine c
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