Comparative QSAR studies using HQSAR,CoMFA, and CoMSIA methods on cyclic sulfone hydroxyethylamines as BACE1 inhibitors

The inhibition of β-secretase (BACE1) is currently the main pharmacological strategy available for Alzheimer’s disease (AD). 2D QSAR and 3D QSAR analysis on some cyclic sulfone hydroxyethylamines inhibitors against β-secretase (IC₅₀: 0.002–2.75 μM) were carried out using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods. The best model based on the training set was generated with a HQSAR q² value of 0.693 and r² value of 0.981; a CoMFA q² value of 0.534 and r² value of 0.913; and a CoMSIA q² value of 0.512 and r² value of 0.973. In order to gain further understand of the vital interactions between cyclic sulfone hydroxyethylamines and the protease, the analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the BACE1. The final QSAR models could be helpful in the design and development of novel active BACE1 inhibitors.     

基于DSP的某弹载计算机单元的设计

随着精确制导武器的发展,为了满足某型弹载计算机的性能和使用要求,文章提出了一种采用基于DSP内核的SOC芯片实现某型弹载计算机单元的解决方案。设计方案采用处理器HKS6713,对数字电路接口实现了光电隔离,采用了模拟/数字电路一体化设计,并具有GJB289A通信接口。文张对计算机单元的硬件设计与实现方法进行了较为详尽的描述。该计算机单元满足了某型武器制导控制的使用需求。     

基于FPGA和AD768的精密程控直流信号源设计

提出了一种基于FPGA和AD768的精密可程控直流信号源实现方案。该方案通过USB2.0接口芯片接收计算机发送的信号源控制命令,以FPGA逻辑控制DAC的方式实现信号源的可程控设计,重点介绍了AD768的硬件电路设计及提高信号源精度的关键技术。实际应用表明,该信号源具有高精度、可程控和稳定性好等优点,具有很高的参考价值。     

用单片机实现汽车远近灯光自动控制系统的设计

本文介绍了一种由STC12C2052AD型单片机控制,光敏传感器采集信号,继电器执行动作的夜间汽车前大灯远近灯光转换的自动控制系统。该系统安装在汽车上,使汽车在夜间行驶时,根据对头车驶近驶离的情况,能够自动调节前大灯远近灯光转换。该系统稳定可靠,成本低廉。有一定的推广和使用价值。     

Synthesis of novel hyperbranched poly(ester‐amide)s based on neutral α‐amino acids via “AD + CBB′” couple‐monomer approach

A series of novel hyperbranched poly(ester‐amide)s (HBPEAs) based on neutral α‐amino acids have been synthesized via the “AD + CBB′” couple‐monomer approach. The ABB′ intermediates were stoichiometrically formed through thio‐Michael addition reaction because of reactivity differences between functional groups. Without any purification, in situ self‐polycondensations of the intermediates at elevated temperature in the presence of a catalyst afforded HBPEAs with multihydroxyl end groups. The degrees of branching (DBs) of the HBPEAs were estimated to be 0.40–0.58 and 0.24–0.54 by quantitative ¹³C NMR with two different calculation methods, respectively, depending on polymerization conditions and structure of monomers. The influences of catalyst, temperature, and intermediate structure on the polymerization process and molecular weights as well as properties of the resultant polymers were investigated. FTIR, NMR, and DEPT‐135 NMR analyses revealed the branched structure of the resultant polymers. The HBPEAs possess moderately high molecular weights with broad distributions, glass transition temperatures in the range of ?25.5 to 36.5 °C, and decomposition temperatures at 10% weight loss under nitrogen and air in the regions of 243.4–289.1 °C and 231.4–265.6 °C, respectively. Among them, those derived from D ,L ‐phenylalanine display the lowest degree of branching, whereas the highest glass transition temperature and the best thermal stability. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Enantiomeric separation of citalopram base by supercritical fluid chromatography

The chiral separation of citalopram base by supercritical fluid chromatography on a semipreparative Chiralpak AD column was studied with the use of three alcohol‐type modifiers (methanol, ethanol, and 2‐propanol) with different volume percentages (5, 10, and 15%). The best separation was achieved when 10% 2‐propanol was used in the presence of 0.1% diethylamine as additive. Under these conditions, the resolution reached 2.15 and the selectivity was 1.388. In addition, other parameters that affected the retention and separation properties, i.e. temperature, pressure, and density, were studied in detail. At the same pressure, a decrease in the temperature improved the enantioselectivity as the experimental temperature range was below the isoelution temperature. However, the temperature dependence of the retention factor was complicated. As a rule, the retention factor decreased when the temperature increased at the same density. A satisfactory regression of the logarithm of the retention factor versus density and temperature was obtained using a simplified lattice‐fluid model. Surprisingly, the relationship between the Henry constant and density can be accurately correlated by using the same quadratic equation.     

接口时序对数字中频发射机边带抑制的影响

结合AD9142在GSM无线通信发射机中的应用,指出了边带信号对系统性能的影响,着重从原理上分析了接口时序错误对边带信号的贡献、成因及改善方法,并给出了时序优化前后的数据对比验证结果。为了保证DAC输出性能达到最优,需要保证接口时序满足建立时间和保持时间要求。通过调整基带处理侧的延时和DAC内部的延时可以使接口时序满足要求。     

单芯片8通道超声模拟前端

简述用于便携式超声设备的单芯片8通道模拟前端.     

AD73322L及其与DSP5416的接口设计

片AD73322L是AD公司推出的低成本．低功耗CMOS通用双通道模拟前端。可以同时进行AD和DA转换。本文介绍了芯片AD73322L的性能特点．功能、基本原理及其与DSP5416的接口设计。     

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: N-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

Using two ways of functionalizing amiridine—acylation with chloroacetic acid chloride and reaction with thiophosgene—we have synthesized new homobivalent bis-amiridines joined by two different spacers—bis-N-acyl-alkylene (3) and bis-N-thiourea-alkylene (5) —as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). All compounds exhibited high inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity for BChE. These new agents displayed negligible carboxylesterase inhibition, suggesting a probable lack of untoward drug–drug interactions arising from hydrolytic biotransformation. Compounds 3 with bis-N-acyl-alkylene spacers were more potent inhibitors of both cholinesterases compared to compounds 5 and the parent amiridine. The lead compounds 3a–c exhibited an IC₅₀(AChE) = 2.9–1.4 µM, IC₅₀(BChE) = 0.13–0.067 µM, and 14–18% propidium displacement at 20 μM. Kinetic studies of compounds 3a and 5d indicated mixed-type reversible inhibition. Molecular docking revealed favorable poses in both catalytic and peripheral AChE sites. Propidium displacement from the peripheral site by the hybrids suggests their potential to hinder AChE-assisted Aβ₄₂ aggregation. Conjugates 3 had no effect on Aβ₄₂ self-aggregation, whereas compounds 5c–e (m = 4, 5, 6) showed mild (13–17%) inhibition. The greatest difference between conjugates 3 and 5 was their antioxidant activity. Bis-amiridines 3 with N-acylalkylene spacers were nearly inactive in ABTS and FRAP tests, whereas compounds 5 with thiourea in the spacers demonstrated high antioxidant activity, especially in the ABTS test (TEAC = 1.2–2.1), in agreement with their significantly lower HOMO-LUMO gap values. Calculated ADMET parameters for all conjugates predicted favorable blood–brain barrier permeability and intestinal absorption, as well as a low propensity for cardiac toxicity. Thus, it was possible to obtain amiridine derivatives whose potencies against AChE and BChE equaled (5) or exceeded (3) that of the parent compound, amiridine. Overall, based on their expanded and balanced pharmacological profiles, conjugates 5c–e appear promising for future optimization and development as multitarget anti-AD agents.