(2S,3S,5S)-2,5-二氨基-3-羟基-1,6-二苯基己烷的合成

L-苯丙氨酸用氯苄进行MO-苄基化、氰化、格氏反应、还原制得（2S，3S，5S）-5-氨基-2-二苄胺基-1，6-二苯基-3-己醇，再经钯炭催化脱苄制得抗病毒药洛匹那韦中间体（2S，3S，5S）-2,5-二氨基-3-羟基-1，6-二苯基己烷，总收率约为63％。     

比阿培南关键中间体6,7-二氢-6-巯基-5H-吡唑[1,2-α][1,2,4]三唑内鎓氯化物的合成

目的：合成比阿培南的关键中间体6，7-二氢-6-巯基-5H-吡唑[1，2-α][1，2，4]三唑内鎓氯化物，优化其工艺。方法：以水合肼为起始原料经缩合，再经烯丙基化、脱保护、溴化、环合、硫代乙酰化、醇解、氧化、去甲酰化、环合、还原得到目标化合物。结果：目标化合物经核磁共振氢谱、质谱确证其化学结构，总收率137％。结论：本方法原料易得，反应条件温和，操作简单。     

1,11-脱氯-6-甲基-4'-去甲基蝴蝶霉素的合成

2，3-二（1H-吲哚-3-基）-N-甲基马来酰亚胺在三氟乙酸作用下形成吲哚啉中间体，与不经保护的葡萄糖发生糖基化反应，氧化后得到1，11-脱氯-6-甲基-4＇-去甲基蝴蝶霉素，总收率约为69％。     

3β-羟基-雄甾-5,15-二烯-17-酮的合成

目的研究3β-羟基-雄甾-5,15-二烯-17-酮的合成方法.方法以去氢表雄酮为原料,经过溴代、缩酮化、脱溴化氢、脱缩酮保护基反应得到目标产物,总产率32.1%.结果与结论合成路线简便易行,适于大规模制备.     

3-溴-4,7-二甲基-6-磺酰脲香豆素类化合物的合成及降糖活性的研究

目的 合成新的3-溴-4,7-二甲基-6-磺酰脲香豆素类化合物,并初步筛选其降糖活性.方法 运用拼合原理,以具有降血糖活性的香豆素为母环,在结构中引入溴和磺酰脲基团并测定目标化合物对小鼠的降血糖效果.合成方法是以间甲酚为原料,通过Pechmann缩合反应得到4,7-二甲基香豆素,经溴加成、脱溴化氢、氯磺化得磺酰氯,再经氨化得磺胺,最后与异氰酸酯反应得目标化合物.结果 合成了12个3-溴-4,7-二甲基-6-磺酰脲香豆素类化合物(BMSU-1～BMSU-12),其结构经红外光谱、核磁共振氢谱和质谱确证.结论 初步药理实验表明:目标化合物BMSU-3、BMSU-10、BMSU-12对正常小鼠都有明显的降血糖作用(P<0.01).     

1-烷基-5-氨基-6-苯乙基尿嘧啶的合成

研究1-烷基-5-氨基-6-苯乙基尿嘧啶（1a，1b）方便、高产率的合成方法，此类化合物有可能作为非核苷类HIV-1RT抑制剂。以6-甲基尿嘧啶（2）为起始物，经硝化、烷基化、苄基化及一锅反应脱苄基及还原反应等合成目标化合物，并用NMR、MS、IR、Anal鉴定化合物结构。探索出了一种合成1-烷基-5氨基-6-苯乙基尿嘧啶类化合物的方便方法。首次于用3或4步反应、高产率合成了1-烷基-5-氨基-6-苯乙基尿嘧啶（1a，1b）并发现化合物1a有中度抗HIV-1RT的活性（IC50=29μM）。     

2,3-二氯-6-硝基喹喔啉的合成

邻苯二胺和草酸二乙酯经闭环、硝化得6-硝基-1，4-二氢喹喔啉-2，3-二酮，经三氯氧磷和DMF氯代制得2，3-二氯-6-硝基喹喔啉，总收率约79％。     

3-(S)-(1-氨甲酰基-1,1-二苯甲基)吡咯烷的合成

反式-4-羟基-L-脯氨酸经脱羧、N-Boc保护和氯代反应制得N-Boc-3-(S)-氯吡咯烷,在叔丁醇钾作用下与二苯乙腈缩合得N-Boc-3-(S)-(1-氰基-1,1-二苯甲基)毗咯烷,再经水解、脱保护、经L-(+)-酒石酸处理后碱化制得氢溴酸达非那新中间体3-(S)-(1-氨甲酰基-1,1-二苯基甲基)吡咯烷,总收率约14%.     

2-甲基-4,6-二氯-5-氨基嘧啶的制备

乙酰胺基丙二酸二乙酯和乙脒盐酸盐在乙醇钠存在下经缩合闭环得2-甲基-4，6-二羟基-5-乙酰胺基嘧啶，再经氯化和水解得到抗高血压药莫索尼定中间体2-甲基-4，6-二氯-5-氨基嘧啶，总收率为62％。     

2-(3, 6, 7-三甲氧基菲-9-基-甲基)-2, 5-二氢吡咯的合成

目的 制备具有多种生物活性的菲并吲哚里西定类生物碱的关键中间体2-(3, 6, 7-三甲氧基菲-9-基-甲基)-2, 5-二氢吡咯。方法 以2, 2, 2-三氯-N-[1-(3, 6, 7-三甲氧基菲-9-基甲基)-丁-2-烯基]乙酰胺为起始原料,经水解、Boc保护、N-烯丙基化、关环复分解反应及脱保护基等5步反应得到目标化合物。结果与结论 合成了2- (3, 6, 7-三甲氧基菲-9-基甲基)-2, 5-二氢吡咯,其结构经¹H-NMR谱确证总收率为45.3%。     

Neuroscience and Hormesis: Overview and General Findings

This article provides a summary of an assessment of the occurrence and impact of hormesis in the neurosciences, including the areas of neuroprotection, neurite outgrowth, and drugs for Alzheimer's disease, Parkinson's disease, anxiety, pain, seizures, stroke, as well as in the areas of behavioral pharmacology, addictive drugs, stress biology including the Yerkes–Dodson law, and p-glycoprotein efflux activity. The findings indicate that the hormetic dose response has a common, if not dominant, presence in each of these diverse areas of neuroscience and further strengthens the conclusion that hormesis is highly generalizable, being independent of biological model, endpoint, and chemical class.     

Self-injection of barbiturates and benzodiazepines in baboons

Self-injection of three barbiturates, six benzodiazepines, and chlorpromazine was examined in baboons. Intravenous injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Prior to testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. Amobarbital, pentobarbital, and secobarbital maintained the highest levels of self-injection, which were similar to those maintained by cocaine. Clonazepam, clorazepate, diazepam, flurazepam, medazepam, and midazolam maintained relatively modest levels of self-injection, while chlorpromazine maintained only low levels, which were in the range of vehicle control. Of the six benzodiazepines, midazolam produced the highest levels of self-injection. At the highest self-injected doses, the barbiturates produced anesthesia in contrast to the benzodiazepines, which produced only sedation. None of the drugs affected food intake except for chlorpromazine, which produced dose-related decreases. The differences among the drug classes (i.e., barbiturate, benzodiazepine, phenothiazine) with respect to the maintenance of self-injection correspond well with the results of previous animal and human drug self-administration studies.     

基于HMGR、SQS1、β-AS基因CNVs的甘草道地性机制研究

本文利用real-time PCR方法对不同产地甘草的3-羟基-3-甲基戊二酰CoA还原酶 (3-hydroxy-3-methylglutaryl-CoA reductase, HMGR)、鲨稀合成酶1 (squalene synthetase 1, SQS1)、β-香树脂醇合成酶 (β-amyrin synthase, β-AS) 基因的拷贝数进行了研究, 发现不同产地的HMGR基因存在1～3个拷贝数变异, SQS1基因存在1～2个拷贝数变异, 未发现β-AS基因拷贝数变异。甘草HMGR、SQS1、β-AS基因拷贝数存在5种自然组合类型: A型 (2+1+1)、B型 (1+1+1)、C型 (3+2+1)、D型 (2+2+1) 和E型 (3+1+1), 其中内蒙古杭锦旗甘草存在A、B两种类型, A与B的比例为1∶1.3; 内蒙古赤峰甘草也存在A、B两种类型, 但A与B比例为3∶1; 宁夏盐池甘草存在A、B、C、D 4种类型, A/B/C/D比例为1∶5.1∶1∶2, A/B比例为1∶5.1; 甘肃民勤甘草存在A、B、E 3种类型, A/B/E比例为4.1∶2.1∶1, A/B比例为2∶1。本研究证明中药功能基因基因组拷贝数变异 (copy number variations, CNVs) 与产地具有相关性, 可能是道地药材形成的机制之一。     

Planning Future Strategies for Domestic and International NeuroAIDS Research, July 24–25, 2008

The National Institute of Mental Health in cooperation with the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke organized a meeting on July 24–25, 2008 to develop novel research directions for neuroAIDS research. The deliberations of this meeting are outlined in this brief report. Several critical research areas in neuroAIDS were identified as areas of emphasis. Opportunities for collaborations between large NIH-funded projects were also discussed. NeuroAIDS Research Participants. Cristian Achim, University of California, San Diego, San Diego, CA; Sunil Ahuja, University of Texas Health Science Center at San Antonio, San Antonio, TX; James Becker, University of Pittsburgh Medical School, Pittsburgh, PA; Bruce Brew, University of New South Wales, Sydney, Australia; Janice Clements, Johns Hopkins University, Baltimore, MD; Ronald Ellis, University of California, San Diego, San Diego, CA; Leon Epstein, Northwestern University Feinberg School of Medicine, Chicago, IL; Lynda Erinoff, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD; Dana Gabuzda, Dana Farber Cancer Institute, Harvard Medical School Boston, MA; Harris Gelbard, University of Rochester Medical Center School of Medicine, Rochester, NY; Benjamin Gelman, University of Texas Galveston, TX; David Goldstein, Duke University, Durham, NC; Colin Hall, University of North Carolina, Chapel Hill, NC; Rohan Hazra, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; Robert Heaton, University of California, San Diego, San Diego, CA; Robin Huebner, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD; Kamel Khalili, Temple University, Philadelphia, PA; Dennis Kolson, University of Pennsylvania, Philadelphia PA; Diane Lawrence, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD; Scott Letendre, University of California, San Diego, San Diego, CA; Thomas Marcotte, University of California, San Diego, San Diego, CA; Michael McGrath, University of California, San Francisco, San Francisco, CA; Susan Morgello, Mount Sinai Medical Center, New York, NY; Avindra Nath, Johns Hopkins University, Baltimore, MD; Vinayaka Prasad, Albert Einstein School of Medicine, Bronx, NY; Richard Price, University of California, San Francisco, San Francisco, CA; Lynn Pulliam, University of California, San Francisco, San Francisco, CA; Dianne Rausch, HIV Pathogenesis, Neuropsychiatry and Treatment Branch, Center for Mental Health Research on AIDS, National Institute of Mental Health, National Institutes of Health Bethesda, MD; Kevin Robertson, University of North Carolina at Chapel Hill, Chapel Hill, NC; Ned Sacktor, The Johns Hopkins University, Baltimore, MD; Gerald Sharp Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Elyse Singer, University of California, Los Angeles, Los Angeles, CA; Stephen Spector, University of California, San Diego, LaJolla, CA; Beth Stevens, Harvard Medical School, Children’s Hospital, Kirby Neurobiology Center, Boston, MA; Mario Stevenson, University of Massachusetts Medical Center, Worcester, MA; Ellen Stover, National Institute of Mental Health, National Institutes of Health, Bethesda, MD; Ronald Swanstrom, University of North Carolina at Chapel Hill-Chapel Hill, NC; Victor Valcour, University of California, San Francisco, San Francisco, CA; David Volsky, Columbia University Medical Center, New York, NY; Brian Wigdahl, Drexel University College of Medicine, Philadelphia, PA; May Wong, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Constantin Yiannoutsos, Indiana University, Indianapolis, IN; Christine Zink, The Johns Hopkins University, Baltimore, MD     

［~3H］二氢埃托啡在大鼠脑分布的定量放射自显影

本文用体外定量受体放射自显影分析法观察了［３Ｈ］二氢埃托啡（ＤＨＥ）在大鼠脑中定位分布和结合特点。结果表明，［３Ｈ］ＤＨＥ特异结合较高的部位主要为纹状体，伏隔核，大脑皮质Ⅰ层和Ⅲ层，丘脑，缰核，杏仁核。脚间核和蓝斑，ＤＨＥ主要作用于ｕ－阿片受体．     

Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research.

Ginger (Zingiber officinale Roscoe, Zingiberacae) is a medicinal plant that has been widely used in Chinese, Ayurvedic and Tibb-Unani herbal medicines all over the world, since antiquity, for a wide array of unrelated ailments that include arthritis, rheumatism, sprains, muscular aches, pains, sore throats, cramps, constipation, indigestion, vomiting, hypertension, dementia, fever, infectious diseases and helminthiasis. Currently, there is a renewed interest in ginger, and several scientific investigations aimed at isolation and identification of active constituents of ginger, scientific verification of its pharmacological actions and of its constituents, and verification of the basis of the use of ginger in some of several diseases and conditions. This article aims at reviewing the most salient recent reports on these investigations. The main pharmacological actions of ginger and compounds isolated therefrom include immuno-modulatory, anti-tumorigenic, anti-inflammatory, anti-apoptotic, anti-hyperglycemic, anti-lipidemic and anti-emetic actions. Ginger is a strong anti-oxidant substance and may either mitigate or prevent generation of free radicals. It is considered a safe herbal medicine with only few and insignificant adverse/side effects. More studies are required in animals and humans on the kinetics of ginger and its constituents and on the effects of their consumption over a long period of time.     

Effects of methylphenidate on multiple components of attention in children with attention deficit hyperactivity disorder

Rationale Methylphenidate (MPH) has been shown to be effective in the treatment of attention deficits in children with attention deficit hyperactivity disorder (ADHD). Although a variety of studies have been performed, there is little available information as to which components of attentional functioning are disturbed in ADHD.Objectives The aim of the present study was to monitor the effect of MPH on various measures of attention in children with ADHD.Methods In a double-blind, placebo-controlled, crossover study, the attentional functioning of 58 children diagnosed with ADHD without psychiatric comorbidity was examined. Assessment of attention was performed on their usual MPH treatment and following withdrawal of the drug. Furthermore, the attentional performance of 58 healthy children was assessed. The test battery consisted of reaction time tasks, including measures of alertness, vigilance, divided attention, flexibility, and aspects of selective attention such as focused attention, inhibition, and integration of sensory information.Results In comparison to the test performance of healthy children, children with ADHD displayed impairments of vigilance, divided attention, flexibility, and aspects of selective attention including focused attention, inhibition, and integration of sensory information. Statistical comparison of attentional functioning of children with ADHD on and off MPH treatment revealed that the medication resulted in an improved task accuracy regarding vigilance, divided attention, inhibition, focused attention, integration of sensory information, and flexibility. Conclusion The present findings indicate that various aspects of attention are markedly impaired in children with ADHD. Treatment with MPH was accompanied by improvements in attention functions of small to moderate sizes. Although MPH-induced improvements were observed in a broad range of attention measures, children with ADHD who were on MPH treatment nevertheless displayed serious deficits in a number of components of attention.     

Cell wall active antifungal agents

The recent American approval of Cancidas^?, a semi-synthetic echinocandin, for salvage treatment of aspergillosis has demonstrated that the cell wall is a clinically viable target for treating fungal infections. Recently, a variety of new, sulfated members of the echinocandin lipopeptide family have been reported, which, like other echinocandins, are glucan synthesis inhibitors. In addition, two new classes of lipopeptide glucan synthesis inhibitors, the aerothricin lipopeptidolactones and the Sankyo lipopeptides, have been identified, as well as a novel member of the papulacandin family of liposaccharide glucan synthesis inhibitors. The first new structural class of glucan synthesis inhibitors discovered in over 20 years, the so-called sterol glycosides, is reviewed. Five different structural types within this class have been characterised. Finally, several novel compounds with cell wall antifungal activity based on inhibition of chitin synthase are reviewed.     

Chemotherapy for major food-borne trematodes: a review

Food-borne trematode infections, caused by liver flukes (Clonorchis, Fasciola, Opisthorchis), lung flukes (Paragonimus) and intestinal flukes (Echinostoma, Fasciolopsis, heterophyids), are significant public health problems, most notably in Southeast Asia and the Western Pacific. Globally, it is estimated that > 40 million people are infected among the 750 million people who live in endemic areas. The epidemiology of food-borne trematodiasis has changed over the past few decades, and now presents a dual picture. On the one hand, increasing numbers of infections are reported from non-endemic areas, and endemic areas are expanding due to larger areas utilised for aquaculture, domestic migration, declining socioeconomic conditions, lack of improved sanitation, and increasing availability of aquatic foods through wider distribution networks often without proper food inspections. On the other hand, social and economic advances in many Asian countries, going hand-in-hand with urbanisation, use of chemical fertilisers and, above all, the administration of safe, efficacious and inexpensive drugs, have significantly reduced the prevalence of food-borne trematode infections. In this review, the taxonomy, life cycle, and geographical distribution of the major food-borne trematodes, including issues of diagnosis and clinical disease manifestations, is summarised. The discovery, chemistry, pharmacological properties, safety, therapeutic efficacy and adverse effects of the current drugs of choice, namely praziquantel and triclabendazole, is then discussed. Recent advances on other drugs and contemporary investigations on novel compounds that might become important players in chemotherapy are highlighted. Finally, the need for research and development of new trematocidal drugs that – employed in concert with health education, improved sanitation and enhanced food safety – are key factors for sustainable control of food-borne trematodiasis, is highlighted.     

抗心律失常药物对蟾酥致小鼠心律失常的影响

比较苯妥英钠、利多卡因(钠通道阻滞药)、普萘洛尔(β肾上腺素受体拮抗药)、胺碘酮(延长动作电位时程药)和维拉帕米(钙通道阻滞药)对蟾酥诱导小鼠心律失常的抑制作用及对离体小鼠心脏的蟾酥致死量的影响。采用动态心电图记录蟾酥诱导小鼠心律失常。观察模型组和各给药组心电图的P-R间期、QRS时程、Q-T间期、T波幅度和HR的变化,统计各心律失常发生率、存活率及心律失常评分。采用离体小鼠心脏灌流,记录心脏的蟾酥致死量。与模型组相比,苯妥英钠组的QRS时程缩短且心率减慢;室性心律失常的发生率降低,存活率增高;显著增加离体小鼠心脏的蟾酥累积致死量。利多卡因组与模型组相比,P-R间期和QRS时程缩短;室性心律失常发生率降低;显著增加离体小鼠心脏的蟾酥累积致死量。普萘洛尔组与模型组相比,P-R间期、QRS时程和Q-T间期缩短;室上性及室性心律失常的发生率降低。胺碘酮显著减慢模型小鼠的心率并且降低模型小鼠室性心律失常的发生率。维拉帕米显著延长模型小鼠P-R间期,抑制Q-T间期延长;减少室上性及室性心律失常的发生;显著减少离体小鼠心脏的蟾酥累积致死量。整体动物实验中,苯妥英钠对蟾酥诱导小鼠的心律失常最有效,其次是利多卡因和普萘洛尔,...