Azaindole derivatives derived from the screening lead 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (1) were prepared and characterized to assess their potential as inhibitors of HIV-1 attachment. Systematic replacement of each of the unfused carbon atoms in the phenyl ring of the indole moiety by a nitrogen atom provided four different azaindole derivatives that displayed a clear SAR for antiviral activity and all of which displayed marked improvements in pharmaceutical properties. Optimization of these azaindole leads resulted in the identification of two compounds that were advanced to clinical studies: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione (BMS-377806, 3) and 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043, 4). In a preliminary clinical study, 4 administered as monotherapy for 8 days, reduced viremia in HIV-1-infected subjects, providing proof of concept for this mechanistic class.

Described herein are structure-activity relationship studies that resulted in the optimization of the activity of members of a class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors. Subsequent iterations of analogue design and syntheses successfully addressed off-target activities, most notably human pregnane X receptor (hPXR) transactivation, and led to significant improvements in the physicochemical properties of lead compounds. Those analogues exhibiting improved solubility and membrane permeability were shown to have notably enhanced pharmacokinetic profiles. Additionally, a series of alkyl bridged piperazine carboxamides was identified as being of particular interest, and from which the compound BMS-791325 (2) was found to have distinguishing antiviral, safety, and pharmacokinetic properties that resulted in its selection for clinical evaluation.

Three-dimensional magnetohydrodynamics (MHD) numerical simulation is an important tool in the prediction of solar wind parameters. In this study, we improve our corona interplanetary total variation diminishing MHD model by using a new boundary applicable to all phases of solar cycles. This model uses synoptic magnetogram maps from the Global Oscillation Network Group as the input data. The empirical Wang–Sheeley–Arge relation is used to assign solar wind speed at the lower boundary, while temperature is specified accordingly based on its empirical relation with the solar wind speed. Magnetic field intensity and solar wind density at the boundary are obtained from observational data in the immediate past Carrington rotations, permitting the persistence of these two parameters in a short time period. The boundary conditions depend on only five tunable parameters when simulating the solar wind for different phases of the solar cycle. We apply this model to simulate the background solar wind from 2007 to 2017 and compare the modeled results with the observational data in the OMNI database. Visual inspection shows that our model can capture the time patterns of solar wind parameters well at most times. Statistical analysis shows that the simulated solar wind parameters are all in good agreement with the observations. This study demonstrates that the improved interplanetary total variation diminishing model can be used for predicting all solar wind parameters near the Earth.

Solar vapor generation represents a promising approach to alleviate water shortage for producing fresh water from undrinkable water resources. Although Cu-based plasmonics have attracted tremendous interest due to efficient light-to-heat conversion, their application faces great challenges in the oxidation resistance of Cu and low evaporation rate. Herein, a hybrid of three-dimensional carbonized loofah sponges and graphene layers encapsulated Cu nanoparticles is successfully synthesized via a facile pyrolysis method. In addition to effective light harvesting, the localized heating effect of stabilized Cu nanoparticles remarkably elevated the surface temperature of Cu@C/CLS to 72 °C, and a vapor generation rate as high as 1.54 kg m–2 h–1 with solar thermal efficiency reaching 90.2% under 1 Sun illumination was achieved. A study in the purification of sewage and muddy water with Cu@C/CLS demonstrates a promising perspective in a practical application. These results may offer a new inspiration for the design of efficient nonprecious Cu-based photothermal materials.

Nitropyridines reacted with an excess of vinyl Grignard reagent to produce 4- or 6-azaindoles. Improved yields were obtained when a halogen atom was present at the position alpha to the nitrogen atom in the pyridine ring.

Electrochemical CO 2 reduction to formate offers a mild and feasible pathway for the utilization of CO 2 , and bismuth is a promising metal for its unique hydrogen evolution reaction inhibition. Reported works of Bi-based electrodes generally exhibit high selectivity while suffering from relatively narrow working potential range. From the perspective of electronic modification engineering, B-doped Bi is prepared by a facile chemical reduction method in this work. With B dopant, above 90% Faradaic efficiency for formate over a broad window of working potential of −0.6 to −1.2 V (vs. reversible hydrogen electrode) is achieved. In situ Raman spectroscopy, X-ray adsorption spectroscopy, and computational analysis demonstrate that the B dopant induces the formation of electron-rich bismuth, which is in favor of the formation of formate by fine-tuning the adsorption energy of *OCHO. Moreover, full-cell electrolysis system coupled with photovoltaic device is constructed and achieves the solar-to-formate conversion efficiency as high as 11.8%.

A hybrid intelligent source surface model applying the artificial neural network tactic for solar wind speed prediction is presented in this paper. The model is a hybrid system merging various observational and theoretical information as input. Different inputs are tested including individual parameters and their combinations in order to select an optimum. Then, the optimal model is implemented for prediction. The prediction is validated by both error analysis and event‐based analysis from 2007 to 2016. The overall correlation coefficient is 0.74, and the root‐mean‐square error is 68 km/s. The probability for detecting a high‐speed‐event is 0.68, the positive predicted value is 0.73, and the threat score is 0.55.

BMS-663749, a phosphonooxymethyl prodrug 4 of the HIV-1 attachment inhibitor 2-(4-benzoyl-1-piperazinyl)-1-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoethanone (BMS-488043) (2) was prepared and profiled in a variety of preclinical in vitro and in vivo models designed to assess its ability to deliver parent drug following oral administration. The data showed that prodrug 4 had excellent potential to significantly reduce dissolution rate-limited absorption following oral dosing in humans. Clinical studies in normal healthy subjects confirmed the potential of 4, revealing that the prodrug significantly increased both the AUC and C(max) of 2 compared to a solid capsule formulation containing the parent drug upon dose escalation. These data provided guidance for further efforts to obtain an effective HIV-1 attachment inhibitor.