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Abstract For Abstract see ChemInform Abstract in Full Text.

Abstract For Abstract see ChemInform Abstract in Full Text.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tick-borne encephalitis virus (TBEV) is a leading cause of human neuroinfections in Europe and Northeast Asia. There are no antiviral therapies for treating TBEV infection. A series of nucleoside analogues was tested for the ability to inhibit the replication of TBEV in porcine kidney cells and human neuroblastoma cells. The interactions of three nucleoside analogues with viral polymerase were simulated using advanced computational methods. The nucleoside analogues 7-deaza-2'-C-methyladenosine (7-deaza-2'-CMA), 2'-C-methyladenosine (2'-CMA), and 2'-C-methylcytidine (2'-CMC) inhibited TBEV replication. These compounds showed dose-dependent inhibition of TBEV-induced cytopathic effects, TBEV replication (50% effective concentrations [EC50]of 5.1 ± 0.4 μM for 7-deaza-2'-CMA, 7.1 ± 1.2 μM for 2'-CMA, and 14.2 ± 1.9 μM for 2'-CMC) and viral antigen production. Notably, 2'-CMC was relatively cytotoxic to porcine kidney cells (50% cytotoxic concentration [CC50] of ∼50 μM). The anti-TBEV effect of 2'-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2'-CMA showed no detectable cellular toxicity (CC50 > 50 μM), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2'-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2'-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.

To the Editor: (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) is an acyclic nucleoside phosphonate analogue with broad-spectrum antiviral activity against DNA viruses, including herpesviruses (herpes simplex virus, varicella–zoster virus, cytomegalovirus, and Epstein–Barr virus), adenoviruses, poxviruses, and papillomaviruses.1,2 We recently showed that local injections of HPMPC into a life-threatening squamous papilloma of the hypopharynx–esophagus eradicated the tumor.2 Two years later, the patient was still free of disease. We report the use of HPMPC in three patients with AIDS and severe, relapsing anogenital human papillomavirus lesions. A 44-year-old homosexual man had been unsuccessfully treated for recurrent penile human papillomavirus lesions since December 1993 with curettage. © 1995, Massachusetts Medical Society. All rights reserved.

Laser power fluctuations can significantly reduce the device performances in various applications. High frequency fluctuations impact the signal-to-noise ratio, while slow variations can reduce the device repeatability or accuracy. Here we report experimental investigations on the power stabilization of a diode laser with an acousto-optic modulator. In the frequency domain, the relative power noise is reduced at the level of 2.2 × 10^-8 Hz^-1/2 in the range 1-100 kHz. The slow variations are studied in the time domain. The relative Allan standard deviation is measured at the level of 6 × 10^-7 at 100 s averaging time. Above 100 s, the instability increases and reaches 2 × 10^-6 at 10 000 s.

Cracks and delamination, resulting from residual stresses are a barrier in the world of Additive Manufacturing and Selective Laser Melting (SLM) that prohibits the use of many metals in this field. By preheating the baseplate, thermal gradients are lowered and stresses can be reduced. In this work, some initial tests were performed with M2 Tool Steel. Results show that pre-heating enables the production of dense M2 parts. The influence of pre-heating on density and mechanical and physical properties is investigated. The paper shows many promising results for the production of SLM parts in materials that are very sensitive to crack formation and delamination. When using a pre-heating of 200°C, crack-free parts were produced with a relative density of 99.8%.

A series of novel N,O-psiconucleosides has been prepared in both enantiomeric forms by resolution of an advanced racemic synthetic intermediate using (R)-N-phenylpantolactam as a chiral resolution agent. The absolute configuration of all of these compounds has been unequivocally established by chemical correlation with the novel (R)- or (S)-1-methyl-5-phenylpyrrolidine-2,3-dione, prepared from the known (R)- and (S)-1-methyl-5-phenylpyrrolidin-2-one, respectively.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) nowadays represent very potent and most promising anti-AIDS agents that specifically target the HIV-1 reverse transcriptase (RT). However, the effectiveness of NNRTI drugs can be hampered by rapid emergence of drug-resistant viruses and severe side effects upon long-term use. Therefore, there is an urgent need to develop novel, highly potent NNRTIs with broad spectrum antiviral activity and improved pharmacokinetic properties, and more efficient strategies that facilitate and shorten the drug discovery process would be extremely beneficial. Fortunately, the structural diversity of NNRTIs provided a wide space for novel lead discovery, and the pharmacophore similarity of NNRTIs gave valuable hints for lead discovery and optimization. More importantly, with the continued efforts in the development of computational tools and increased crystallographic information on RT/NNRTI complexes, structure-based approaches using a combination of traditional medicinal chemistry, structural biology, and computational chemistry are being used increasingly in the design of NNRTIs. First, this review covers two decades of research and development for various NNRTI families based on their chemical scaffolds, and then describes the structural similarity of NNRTIs. We have attempted to assemble a comprehensive overview of the general approaches in NNRTI lead discovery and optimization reported in the literature during the last decade. The successful applications of medicinal chemistry strategies, crystallography, and computational tools for designing novel NNRTIs are highlighted. Future directions for research are also outlined.

Abstract Eine Reihe von Derivaten des 2′,3′‐Secouridins (Ia) wird, wie im Formelschema beschrieben, synthetisiert.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.