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.     

一种基于分时复用的PCI AD总线再复用模型

在研究PC I AD双向总线及PC I总线读操作时序特性的基础上,提出了基于分时复用技术实现PC I AD总线再复用的模型。挂接在PC I用户端的存储器可以复用PC I AD总线完成主设备对其进行的读写操作。实际流片结果表明该模型切实可行。PC I AD总线再复用模型不仅可以保证功能正确,而且节约了32根管脚资源,进而缩小了芯片面积,降低了设计成本。     

带通∑-△调制中频子系统芯片AD6140

AD6140是AD公司生产的采用∑-△调制的ADC中频集成电路芯片,适用于需要高动态范围和多个滤波器带宽的接收机。该器件被设计在Motorola的ReFLEX 系统中,可用于FLEX Re-FLEX接收机和多模式接收机中。文中介绍了AD607的原理、特点、性能参数和典型应用电路。     

DDS芯片AD9850的工作原理及其与单片机的接口

介绍了美国AD公司采用先进的直接数字频率合成（DDS）技术推出的高集成度频率合成器AD9850的工作原理、主要特点及其与MCS51单片机的接口,并给出了接口电路图和部分源程序。     

DDS芯片AD9832的原理及应用

AD9832是AD公司生产的直接数字频率合成器。它体积小、重量轻、操作方便,同时具有极高的频率分辩率。文章介绍了直接数字频率合成器（DDS）AD9832的原理,分析了AD9832的内部结构、引脚功能以及在高频测试仪中的应用。     

Direct separation of the enantiomers of reboxetine by liquid chromatography on different cellulose- and amylose-based chiral stationary phases

Summary Racemic reboxetine, (R,S)-2[(R,S)-α-(2-ethoxyphenoxybenzyl] morpholine methane sulfonate, is a mixture of the (R,R) and (S,S) enantiomers. Separation of the enantiomers of reboxetine by liquid chromatography has been investigated on three chiral stationary phases—cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD), cellulose tris-(phenylcarbamate) (Chiralcel OC), and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD). On these stationary phases the resolution of the (R,R) and (S,S) enantiomers was highly dependent on mobile-phase composition. When Chiralcel OD and OC were used, addition of diethylamine to the mobile phase greatly improved the separation of the enantiomers. On Chiralpak AD enantio-separation was achieved without the use of additives. Solute-mobile phase-stationary phase interactions which might participate in the mechanism of enantiorecognition are discussed.     

基于MAX262的程控滤波器设计

通过对程控滤波器的理论分析,在研究MAX262的功能和单片机的SPI总线通信的基础上．提出了基于MAX262的程控滤波器设计方案,设计了程控滤波器的软硬件,并给出了测试结果。     

基于DDS与USB技术的通信对抗教学演示系统中硬件的设计与实现

介绍了一种用于通信干扰与抗干扰教学与科研实验的演示系统中硬件的设计方案,并给出了此方案具体的实现。系统在侦察模块中采用A/D采样芯片与FPGA芯片相结合,在干扰模块中采用FPGA与AD9854芯片相结合,控制模块中采用计算机与USB芯片相结合的方式,实现了在计算机控制下对跳频通信进行实时侦察和多种干扰的演示功能。     

基于DDS技术正弦波信号发生器的设计

介绍了直接数字频率合成（DDS）的原理,依据其基本原理提出一种基于单片机STC89C52控制直接数字频率合成芯片AD9851产生频率可调的正弦波信号发生器的电路设计。通过键盘输入所需频率值,单片机通过响应键盘中断将其输入频率转换为频率控制字,并将其写入AD9851。AD9851产生的正弦波信号经低通滤波得到纯正的正弦波信号,最后经过功率放大器输出至负载。经实验表明该系统可产生频率在1Hz～10MHz,精度为0.1Hz,峰值为5V的正弦波信号,且易于操纵,输出稳定。     

超宽带多发多收雷达系统的信号源设计及实现

多发多收超宽带雷达和通信系统是当今研发热点,国内外多有相关报道,而信号源的设计及实现是其关键技术之一。目前用扩频模块来实现GHz 脉冲信号的信号源,结构复杂、成本高。对此,设计和制作了一款由可编程逻辑器件FPGA 和DDS 芯片组成并产生GHz 脉冲信号的信号源,其核心是ADI公司的DDS芯片AD9914和Xilinx公司的Kintex-7系列FPGA芯片作控制芯片,此信号源获得了高达1.4 GHz的大带宽多通道同步雷达脉冲信号,频率切换时间达到ns级,且频率、相位和幅值都可控,其性能在国内具有先进性,并具有实际应用价值。