氨氯地平苯磺酸盐的合成

以乙醇胺和三苯基氯甲烷为起始原料,经氨基保护、取代、缩合、加成、水解和成盐反应,以43%的总收率制得氨氯地平苯磺酸盐;其中部分中间体和目标化合物的结构经1HNMR和MS等进行了表征。该合成路线的总收率与Pfizer公司2003年报道的第二代合成工艺的总收率持平,且具有原料易得、操作简便等特点。     

抗组胺新药非索非那定的合成和应用

非索非那定是新一代的抗组胺药,用于治疗过敏性疾病,无镇静和嗜睡感,毒副作用小。综述了抗组胺新药 非索非那定的合成方法,比较了它们的优缺点,并对其应用前景作了展望。     

利用糖芯片技术快速检测沙门氏菌

为了探讨糖芯片在沙门氏菌检测上的应用,以沙门氏菌ATCC31685为主要研究对象,制作不同类型的糖芯片用于优化糖芯片检测条件;在优化条件的基础上,降低糖浓度或细菌浓度用于确定糖芯片检测限值;继而系统地研究了糖芯片在沙门氏菌和凝集素FimH拮抗剂筛选上的应用,并探究糖芯片对菌株的破坏性。由实验现象可知,沙门氏菌可与甘露糖化合物修饰的糖芯片结合,其中,以Man-1与NHS玻片所构建的糖芯片效果最优,并且两种不同的沙门氏菌(ATCC31685和ATCC9184)与糖芯片的结合能力不同,因此糖芯片可作为沙门氏菌的一种快速检测手段;在糖浓度为313 mmol/L或细菌浓度106个/mL时荧光信号接近背景值,并且糖芯片检测后对菌株无破坏性,可继续其他检测项目;此外,实验结果表明糖芯片可作为FimH蛋白拮抗剂的筛选工具。     

CoMFA analysis on a set of new noncompetitive GABAA receptor antagonists： fipronil and related analogs

Fipronil and related analogs, a set of new noncompetitive GABAA receptor antagonists, were investigated using comparative molecular field analysis （CoMFA） to explore their three-dimensional quantitative structure-activity relationships （3D-QSAR）. Considering the structural complexity of molecules of fipronil and related analogs, three different alignments were performed in this paper. CoMFA model for housefly receptor yield the leave-one-out and cross-validated correlation coefficient q^2 value of 0.511 and the conventional correlation coefficient r^2 value of 0.997. The new compounds with higher activity would be designed from this model. CoMFA model for rat receptor was not successful using all these three alignments, the reason of which maybe that some molecules adopt different conformations for rat receptor.     

1,4-二氢吡啶类钙拮抗剂的合成法研究——(Ⅱ)尼莫地平的合成新方法

2-甲氧基乙醇、异丙醇分别与乙酰乙酸甲酯经酯交换成乙酰乙酸甲氧基乙酯(2)和乙酰乙酸异丙酯(3),(3)经氨化得3-氨基丁烯酸异丙醇酯(4)。(2)与间硝基苯甲醛缩合得间硝基亚苄基乙酰乙酸甲氧基乙酯(5),继而与(4)在原位形成的哌啶乙酸盐催化下即得尼莫地平(1),以间硝基苯甲醛计算,总收率89.1％。此法工艺简便,条件温和,适合大规模制备。     

(Z)-11-Hexadecenal and (3Z,6Z,9Z)-tricosatriene: sex pheromone components of the red banded mango caterpillar Deanolis sublimbalis

The sex pheromone of the red banded mango caterpillar, Deanolis sublimbalis (Lepidoptera: Crambidae), a serious pest of the mango Mangifera indica (Anacardiaceae) in India and Southeast Asia and a recent invader into northern Australia, has been identified. Three candidate compounds were identified from pheromone gland extracts of female moths, using gas chromatography (GC), GC-electroantennographic detection and GC-mass spectrometric analyses, in conjunction with dimethyldisulfide derivatization. Field bioassays established that both (Z)-11-hexadecenal (Z11-16:Ald) and (3Z,6Z,9Z)-tricosatriene (3Z,6Z,9Z-23:Hy) were required for attraction of male D. sublimbalis moths, and 1,000 μg of a 1:1 mix of Z11-16:Ald and 3Z,6Z,9Z-23:Hy was more attractive to male moths than caged virgin females. However, the binary blend was only attractive when the isomeric purity of the monounsaturated aldehyde was >99%, suggesting that the (E)-isomer was inhibitory. Although (Z)-11-hexadecen-1-ol (Z11-16:OH) was tentatively identified in gland extracts, the addition of this compound to the binary blend did not increase the numbers of moths captured. The pheromone can now be used in integrated pest management strategies. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Novel Abscisic Acid Antagonists Identified with Chemical Array Screening

Abscisic acid (ABA) signaling is involved in multiple processes in plants, such as water stress control and seed dormancy. Major regulators of ABA signaling are the PYR/PYL/RCAR family receptor proteins, group A protein phosphatases 2C (PP2Cs), and subclass III of SNF1‐related protein kinase 2 (SnRK2). Novel ABA agonists and antagonists to modulate the functions of these proteins would not only contribute to clarification of the signaling mechanisms but might also be used to improve crop yields. To obtain small molecules that interact with Arabidopsis ABA receptor PYR1, we screened 24 275 compounds from a chemical library at the RIKEN Natural Products Depository by using a chemical array platform. Subsequent SnRK2 and PP2C assays narrowed down the candidates to two molecules. One antagonized ABA in a competitive manner and inhibited the formation of the PYR1‐ABA‐PP2C ternary complex. These compounds might have potential as bioprobes to analyze ABA signaling.     

Phytotoxic Effects of Leukamenin E (an ent-kaurene diterpenoid) on Root Growth and Root Hair Development in Lactuca sativa L. seedlings

Leukamenin E, an ent-kaurene diterpenoid isolated from Isodon racemosa (Hemsl) Hara, showed phytotoxic effects on root growth and root hair development of lettuce seedlings (Lactuca sativa L.). Lower concentrations (10 μM) of leukamenin E did not affect root growth, but at concentrations higher than 50 μM, the rate was inhibited. The influence of leukamenin E on root growth rate was closely correlated with alterations in the mitotic index. A low incidence of aberrant mitosis image was observed when lettuce roots were treated with higher concentrations (100 and 200 μM) of leukamenin E. This suggests that inhibition of root growth may be due to inhibition of cell division. All tested concentrations of the diterpenoid (10 μM or more) inhibited root hair development in a dose-dependent manner. At a concentration of 80 μM, leukamenin E completely blocked root hair initiation. Application of Ag⁺—an ethylene action inhibitor—to lettuce seedlings inhibited root hair elongation similar to the diterpenoid. Enhanced root hair length was stimulated by exogenous ethephon—an ethylene-releasing agent—and could be reversed by addition of leukamenin E. This suggests that leukamenin E may act as a potential ethylene action antagonist in the inhibition of lettuce root hair development. We conclude that leukamenin E may curb root hair development by interfering with ethylene action at concentrations above 10 μM and inhibits root growth via inhibition of cell division at concentrations above 50 μM. Lan Ding and Linlin Qi contributed equally to this work.     

内皮素受体拮抗剂BQ-123对全脑缺血再灌流后脑组织损伤的保护作用

目的 观察内皮素拮抗剂BQ-123对缺血再磾流后脑神经元损伤的保护作用。方法 采用 Pusinelli的四血管阻断法（4VO)制作大鼠全脑缺血再灌流动物模型。在再灌流后30分钟给予 BQ-123(50μg/1μl, icv)。结果 BQ-123能增加缺血后海马CA1区神经元的存活数, 行为实 验表明BQ-123治疗后大鼠的学习记忆能力有提高。结论 内皮素受体拮抗剂BQ-123对全 脑缺血再灌流引起海马区神经元损伤有部分保护作用。     

GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis?

To evaluate the effectiveness of a new class of medical drugs, namely oral gonadotropin-releasing hormone (GnRH) antagonists, in the management of premenopausal women with endometriosis-associated pelvic pain. We reviewed the most relevant papers (n = 27) on the efficacy of new medical alternatives (oral GnRH antagonists) as therapy for endometriosis. We first briefly summarized the concept of progesterone resistance and established that oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis. Since clinical evidence shows that estrogens play a critical role in the pathogenesis of the disease, lowering their levels with oral GnRH antagonists may well prove effective, especially in women who fail to respond to progestogens. There is a need for reliable long-term oral treatment capable of managing endometriosis symptoms, taking into consideration both the main symptoms and phenotype of the disease. Published studies reviewed and discussed here confirm the efficacy of GnRH antagonists. There is a place for GnRH antagonists in the management of symptomatic endometriosis. Novel algorithms that take into account the different phenotypes are proposed.