Synthesis and biological evaluation of a des-dihydropyran laulimalide analog

The preparation of a novel simplified Laulimalide analog via a highly convergent and efficient route and its biological evaluation are presented. The outlined route enables the synthesis of C₅–C₉ modified analog 2 and uses Julia–Kocienski olefination for fragment assembly and a regioselective Yamaguchi macrolactonization for ring closure. This strategy should be suitable for the generation of various new C₅–C₉ des-dihydropyran laulimalide derivatives for further SAR studies.     

A novel technique for imaging with inhomogeneous fields

We introduce a simple, efficient, low-SAR method for magnetic resonance imaging in the presence of a static field with a permanent, and possibly large gradient. The technique, which is called slant-slice imaging is essentially a spin-echo imaging sequence except that the imaging slice is oriented such that the static field gradient can be used in conjunction with applied gradients during readout. Data are collected for 2D slices. Unlike single point imaging techniques, entire lines of k-space are acquired with each readout. The slant-slice pulse sequence is used to obtain high quality images, using a clinical scanner to simulate a static field with a large permanent gradient. The effects of the inhomogeneity are quantified by two parameters nu and q, which are useful for assessing the utility of a magnet design for 3D-MR imaging.     

基于小波的多极化机载合成孔径雷达海面风向反演

为了实现从合成孔径雷达(SAR)图像本身提取高精度的海面风向信息, 提高SAR海面风场反演精度,研究了多极化机载SAR海面风向反演技术, 借助小波分析相对傅里叶分析和局部梯度更精细的时-频分析能力, 将二维连续小波变换与快速傅里叶变换(FFT)相结合,提出一种新的机载SAR海面风向反演方法. 为验证反演方法的有效性,通过海上同步飞行试验获取多极化机载SAR数据及同步调查船实测风向数据,用于反演试验的数据比对.采用本文提出的方法, 利用多种小波基对机载C波段SAR的同极化和交叉极化数据进行风向反演, 将反演结果与美国国家环境预报中心再分析资料以及调查船实测风向进行比对. 结果表明,本文提出的基于小波分析的海面风向反演方法适用于机载SAR探测数据, 反演精度优于二维FFT法和局部梯度方法;小波基的选择对反演结果影响较大, Mexican-Hat小波基是机载SAR海面风向反演的最优小波基, 且同极化与交叉极化机载SAR数据均可用于海面风向的反演.     

Determination of exact rotation angle and discrimination for rotated images

The complex frequency scaling property of Fourier transforms may be very effective for the determination of exact image rotation angle in application areas such as defense, manufacturing agriculture and commerce. In this paper, we exploit the complex frequency scaling property of Fourier transform to determine the exact angle of rotation of a target image with respect to reference image. We also investigate the validity of the developed algorithm using occluded target images. Further, we extend our algorithm to differentiate between different but similar rotated target images. We use both gray scale and DARPA's moving and stationary target recognition program's synthetic aperture radar images to validate our algorithm.     

新磺酰脲类化合物的合成、结构及其构效关系研究（Ⅳ）──合成及活性

合成了１７个在结构上具有一定递变规律的新磺酰脲类化合物，经元素分析、￣１ＨＮＭＲ和ＩＲ确定了其结构。讨论了该类化合物的分子及晶体结构特征。测定了所合成化合物的除草活性，并讨论了活性规律。     

Synthesis,antifungal activity and in vitro mechanism of novel 1-substituted-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives

Inspired by the wide application of amides in plant pathogens, a series of novel 1-substituted-5-trifluoromethyl?1H?pyrazole-4-carboxamide derivatives were designed and synthesized. Bioassay results indicated that some target compounds exhibited excellent and broad-spectrum in vitro and certain in vivo antifungal activities. Among them, the in vitro EC₅₀ values of Y₁₃ against G. zeae, B. dothidea, F. prolifeatum and F. oxysporum were 13.1, 14.4, 13.3 and 21.4 mg/L, respectively. The in vivo protective activity of Y₁₃ against G. zeae at 100 mg/L was 50.65%. SAR analysis revealed that the phenyl on the 1-position of the pyrazole ring was important for this activity. An antifungal mechanism study of Y₁₃ against G. zeae demonstrated that this compound may disrupt the cell membrane of mycelium, thus inhibiting the growth of fungi. These mechanistic study results were inconsistent with those for traditional amides and may provide a novel view for deep study of this series of pyrazole carboxamide derivatives.     

新型镇痛剂地棘蛙素的化学和药理

本文评述了新型非阿片类强效镇痛剂地棘蛙素的化学和药理研究的进展。从地棘蛙素全合成研究、类似物制备、药理学行为和构效关系等几方面介绍了国际上研究的热点, 并对今后的研究动向进行了讨论。     

Synthesis and Biological Evaluation of Potent Bisubstrate Inhibitors of the Enzyme Catechol O‐Methyltransferase (COMT) Lacking a Nitro Group

Inhibition of the enzyme catechol O‐methyltransferase (COMT) represents a viable strategy for regulation of the catabolism of catecholamine neurotransmitters or their precursors, and is of considerable interest in the therapy of Parkinson's disease. Herein, we report the development of a new generation of potent bisubstrate inhibitors of COMT derived from nitro‐substituted ligand 1 (K_i = 28 nM , Table 1), which achieve high biological activity despite the lack of a NO₂ substituent on the catechol moiety. Their synthesis takes advantage of a convergent approach, in which a series of functionalized catechol intermediates is prepared (Schemes 2–7) and coupled to a common adenosine‐derived allylic amine building block (Scheme 8). Biological activities of the newly synthesized inhibitors, determined by in vitro enzymatic assay and kinetic studies, clearly demonstrate that high inhibitory potency of the bisubstrate inhibitors is not correlated with the pK_a of the catechol OH groups. Aromatic residues, connected to the catechol via a biaryl‐type linkage, were found to maximally benefit from additional favorable hydrophobic interactions with the enzyme and thus to be preferred replacements of the NO₂ group in 1 . A competitive kinetic inhibition mechanism (Fig. 2) with respect to the cofactor binding site was confirmed in all cases, supporting a bisubstrate inhibition mode for inhibitors 2 – 19 .     

从SAR遥感图像中提取水域的一种双模式结合方法

水域是SAR图像的一个重要特征,针对SAR图像水域的检测问题,提出了一种利用形态学和信息跟踪双模式相结合的检测方法。采用形态学的开运算,提取基本的水域轮廓,再结合改进的信息编码,进行跟踪检测,进一步精确定位水域区域。实验结果表明,双模式结合的水域检测方法,可以较准确的提取SAR图像的水域区域,效果要优于单一模式的检测方法,而且跟信息熵方法相比较还提高了运算效率。     

Design,synthesis and antiproliferative activity against human cancer cell lines of novel benzo-, benzofuro-, azolo- and thieno-1,3-thiazinone resorcinol hybrids

In this paper we report the design and synthesis of novel derivatives of the 4H-3,1-benzothiazinone type and heterocyclic analogues, i.e. benzofuro-, azolo- and thieno-1,3-thiazin-4-ones possessing 2,4-dihydroxyphenyl substituent. The compounds were obtained by the one-step reaction of aminobenzamides or heterocyclic aminocarboxamides with aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]. Evaluation of their antiproliferative potency against human cancer cell lines showed that the activity of some analogues was similar to that of cisplatin. The highest activity and low toxicity were found for 6-tert-butyl-2-(5-chloro-2,4-dihydroxyphenyl)-4H-thieno[3,2-d][1,3]thiazin-4-one. The structure–activity elucidation reveals that the most active compounds are those with a thienothiazin-4-one and benzofuro[3,2-d][1,3]thiazin-4-one skeleton and the presence of the hydrophobic substituent (Et, Cl) in the benzenediol moiety increases their antiproliferative potency. The ADMET properties of selected compounds including metabolic stability and toxicity profile were estimated in silico.