盐酸西布曲明的合成

目的：研究盐酸西布曲明的合成方法。方法：以对氯氰苄为起始原料经环合、格氏反应、还原、氮上的氮甲基化、成盐５步反应合成盐酸西布曲明,并对反应的条件进行了优化。结果：经５步反应合成盐酸西布曲明,总收率为４０．６％。结论：反应条件温和,工艺简便,收率较高,适用于工业化生产。     

阿折地平的合成

目的考察阿折地平的合成工艺。方法1-二苯甲基丫丁啶-3-醇经一步酯化反应、两步缩合反应合成阿折地平。结果及结论此合成路线原料易得,工艺可行。     

奥利司他中间体酯环酮的制备

目的：研究奥利司他的重要中间体酯环酮的合成工艺。方法：以丙二酸、丙酮为起始原料，经成环、碳酰化、醇解、不对称氢化、酯化、环合六步反应，合成酯环酮。结果：通过改变第六步反应条件，使更适宜于大生产。结论：该合成方法为制备酯环酮提供了一条可行的产业化合成路线。     

盐酸班布特罗的合成工艺改进

目的合成盐酸班布特罗.方法采用了对比性实验,确定反应途径.结果经缩合、还原、成盐3步反应合成盐酸班布特罗.结论该反应途径为最佳途径.     

原甲酸三乙酯的合成

目的:以氢氧化钠和乙醇为起始反应物来制备乙醇钠,再与三氯甲烷反应合成原甲酸三乙酯。方法:通过正交实验设计优化合成反应条件。结果:使反应在温度,反应液的p H值,反应时间等方面得到了合理的控制。结论:该合成路线原料易得,降低了乙醇钠合成的危险性。     

盐酸西布曲明的合成

目的：改进肥胖症治疗药盐酸西布曲明（ｓｉｂｕｔｒａｍｉｎｅ ｈｙｄｒｏｃｈｌｏｒｉｄｅ）的合成方法。方法：以４－氨苄腈为起始原料,经环烃化、Ｇｒｉｇｎａｒｄ反应、还原、Ｅｓｃｈｗｅｉｌｅｒ－ｃｌａｒｋｅ甲基化和成盐等反应合成了盐酸西布曲明。结果：合成产物经熔点、元素分析、红外光谱和核磁共振谱等确证,总收率３６．３％。结论：此合成工艺简便,易于工业化生产。     

伊班膦酸钠的合成

目的合成伊班膦酸钠。方法以戊胺为原料,经缩合、甲基化、加成、水解、无溶剂膦酸化、中和反应合成。结果合成了伊班膦酸钠,总收率21.2%。结论本方法提高了反应收率,降低了成本,简化了操作,是合成伊班膦酸钠的有效途径之一。     

萘哌地尔合成工艺研究

目的研究萘哌地尔的合成工艺。方法以1-萘酚和环氧氯丙烷为原料,在相转移催化剂TEBA作用下反应,再与间甲氧基苯基哌嗪作用,生成萘哌地尔。结果萘哌地尔的最佳合成条件为:化合物Ⅰ与化合物Ⅱ的摩尔比为1∶1,反应温度为60℃。结论该方法有合成路线简单、反应条件温和、产物易精制等优点,完全适合工业化生产。     

盐酸班布特罗的合成工艺改进研究

目的改进盐酸班布特罗的合成工艺.方法经酯化、溴化、还原、缩合、成盐五步反应合成盐酸班布特罗.结果完成了盐酸班布特罗的合成,经波谱数据确认了其结构.结论该反应途径为工业生产提供了较佳的合成路线.     

莫达非尼的合成

莫达非尼 (modafinil,1 ) ,化学名为 2 - (二苯基甲基亚硫酰基 )乙酰胺 ,是由法国 Lafon制药公司研制的一种新型中枢兴奋药 ,1 994年后相继在法、英、德上市 ,1 998年 1 2月获准在美国上市 [1] ,是第一个用于治疗嗜睡症的药物 [2 ]。1的合成路线较多 ,但存在路线长或原料不易得等缺点。本文参考文献 [3～ 5] ,设计了一条新的合成路线。由二苯基甲醇 (2 )和巯基乙酸缩合得二苯甲硫基乙酸 (3 ) ,经氯化、氨化、氧化即可得到 1。文献 [4 ,5]由 2、硫脲和氢溴酸合成二苯甲硫醇 ,再与氯乙酸反应合成 3 ,不如本法方便。在氨化反应中 ,我们免除了…     

Essential Fatty acids - a review

Essential fatty acids (EFAs): cis-linoleic acid (LA) and alpha-linolenic acid (ALA) are essential for humans and their deficiency is rare in humans due to their easy availability in diet. EFAs are metabolized to their respective long-chain metabolites: dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), lipoxins (LXs) and resolvins. EFAs and their metabolites may function as endogenous angiotensin converting enzyme and HMG-CoA reductase inhibitors, nitric oxide enhancers, anti-hypertensives, and anti-atherosclerotic molecules. EFAs react with nitric oxide (NO) to yield respective nitroalkene derivatives that have cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). In several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, alcoholism, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer the metabolism of EFAs is altered. Thus, EFAs and their derivatives have significant clinical implications.     

Stereoselective synthesis and receptor binding of conformationally restricted and flexible 2,4-disubstituted 1,3-dioxanes derived from benzomorphans

The key steps in the stereoselective synthesis of the tricyclic aminomethyl derivatives 19 and 20 and the aminoethyl substituted 1,3-dioxanes 24 and 25 are nucleophilic addition of aryllithium intermediates to the nitroalkene 13, intramolecular transacetalization of the addition products 15 and 16 (only for the tricyclic derivatives 19 and 20) and subsequent reduction of the nitro group. The affinities of the secondary and tertiary amines 19c,d, 20c,d, 24c,d, and 25c,d for the ion channel binding site of the NMDA receptor, for mu-, kappa-, and sigma-receptors have been investigated. In the group of tricyclic compounds only 19d shows remarkable sigma-receptor affinity (Ki = 21.6/1.10 microM). In the 1,3-dioxane series the moderate mu- (Ki = 27.8 microM) and kappa-receptor affinity (Ki = 36 microM) as well as the high sigma-receptor affinity (Ki = 3.3 microM) of the (S,S,S)-configurated methylamine 24c should be emphasized. The pentan-1-ol 26, the side product isolated during the synthesis of 24c, is of particular interest because of its considerable affinity to mu- (Ki = 16.0 microM), kappa- (Ki = 2.8 microM), and sigma-receptors (Ki = 14.5/1.26 microM). The biphasic competition curves obtained during sigma-receptor binding studies of 19d and 26 (two Ki values) may be explained by different interaction with sigma-receptor subtypes.     

Vitamin C: update on physiology and pharmacology

Although ascorbic acid is an important water-soluble antioxidant and enzyme cofactor in plants and animals, humans and some other species do not synthesize ascorbate due to the lack of the enzyme catalyzing the final step of the biosynthetic pathway, and for them it has become a vitamin. This review focuses on the role of ascorbate in various hydroxylation reactions and in the redox homeostasis of subcellular compartments including mitochondria and endoplasmic reticulum. Recently discovered functions of ascorbate in nucleic acid and histone dealkylation and proteoglycan deglycanation are also summarized. These new findings might delineate a role for ascorbate in the modulation of both pro- and anti-carcinogenic mechanisms. Recent advances and perspectives in therapeutic applications are also reviewed. On the basis of new and earlier observations, the advantages of the lost ability to synthesize ascorbate are pondered. The increasing knowledge of the functions of ascorbate and of its molecular sites of action can mechanistically substantiate a place for ascorbate in the treatment of various diseases.     

《儿科阿奇霉素注射使用的快速建议指南》临床问题与结局指标的调查分析

目的:通过总结《儿科阿奇霉素注射使用的快速建议指南》临床问题与结局指标的前期调查结果,与指南专家评估结果进行对比,探讨开展该工作的意义。方法:通过电子问卷,对临床一线医务人员进行调查,调查内容主要包括参与者的基本信息、对指南拟纳入的临床问题(5分制)和结局指标(9分制)进行重要程度评分以及补充。计算各题平均分,采用变异系数表示一致性,采用Wilcoxon秩和检验,对比参与者和专家评估结果,对补充的内容进行描述性分析。结果:共纳入155位参与者的调查结果,各年龄段、文化程度和职称等均有分布。结果显示,注射用阿奇霉素的用法用量(4.56分)和有效性指标(7.28分)最受关注,特殊人群用药(42.71%)和安全性(34.52%)的一致性较差;与专家评估对比分析显示,对于大部分问题和指标,前期调研和专家评估的评分差异无显著性,专家评估的变异系数更低;共收集有效补充15条,最终将新生儿的使用问题纳入。结论:在指南制订前期,有必要对临床问题和结局指标进行广泛调查,收集并分析评估和补充意见,这对指南专家组的评估具有一定的参考意义。     

A Qualitative Study of the Purchasing and Distribution Patterns of Cocaine and Crack Users in England and Wales

This paper presents primarily ethnographic data on the evolution of the cocaine and crack drug scene in Britain between 1990 and 1992. The introduction and marketing of crack as a new commodity has led to distinct market outlets and altered the shape and patterns of the distribution of cocaine. We noted great variety in purchasing patterns, dependent upon availability, market knowledge and the profile of individuals and groups of users. Friends were important contacts for obtaining both cocaine and crack. Crack was more commonly bought from dealers and from street-scenes than was cocaine, a trend which increased during the study period. Emerging supply outlets were built on the existing structure of the irregular or illicit economy.

We identified categories for the purchasing and selling of cocaine and crack based on specific settings (or “arenas”). These were characterised in terms of (heir accessibility to potential drug purchasers and would often be interlinked. We developed a typology of purchasing and selling arenas according to a number of pertinent factors, such as: access, activities permitted, and drug use clientele.

The existence of distinct markets and arenas for purchasing suggests that cocaine and crack use is becoming established amongst broader ranging groups of drug users than had previously been the case. We need to develop targeted interventions that are informed by ethnographic research which highlights the nuances and profiles of specific user groups and drug markets.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

Comparative efficacy and toxicity of desferrioxamine, deferiprone and other iron and aluminium chelating drugs

The efficacy and toxicity aspects of the iron and aluminium chelating drugs desferrioxamine and deferiprone (L1, 1,2-dimethyl-3-hydroxypyrid-4-one), have been compared. Major emphasis was given in the use of these two and also of other chelators in conditions of iron overload, imbalance and toxicity, as well as the incidence and possible causes of toxic side effects in both animals and humans. The chemical basis of chelation and the interaction of these chelators with the iron pools are discussed within the context of clinical application in iron overload and other conditions such as renal dialysis, rheumatoid arthritis, cancer, heart disease, malaria, etc. The design and development of new orally active -ketohydroxypyridine and other chelators are considered and compared with 14 other chelators which have been previously tested in man for the removal of iron, most of which, however, were later abandoned because of low efficacy or major toxicity. The design of new therapeutic protocols based on the pharmacological, toxicological and metabolic transformation properties of the chelating drugs is also being considered, within the context of maximising their efficacy and minimising their toxicity. Overall, oral deferiprone appears to be as effective as s.c. desferrioxamine in the removal of iron and aluminium in man and to have a similar but different toxicity profile from desferrioxamine in both animals and man. The low cost and oral activity of deferiprone will make it the drug of choice for the vast majority of patients, who are not currently being chelated either because they cannot afford the high cost of desferrioxamine therapy or are not complying or have toxic side effects with its s.c. administration.     

Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring

Carbamazepine (CBZ) is an anti-epileptic drug that acts on Leydig cells, affecting steroidogenesis and causes fetal malformation. The aim of this study was to investigate the effects of CBZ on male sexual maturation and other male parameters. Rat dams were treated with CBZ during pregnancy and breastfeeding. The anogenital distance (AGD) and the anogenital index (AGI) were obtained. Testicular descent and preputial separation were also evaluated. The offspring was euthanized at PND 41 and 63. The accessory glands were weighed and the testes were collected for histopathological, morphometric and sterological analyses. The numerical density of Leydig cells and hormone dosage were obtained. CBZ caused an increase of AGI and a delay of testicular descent and of preputial separation. CBZ also caused a decrease of testosterone level and of sperm count and an increase of abnormal sperm. These results indicate that CBZ delays puberty onset and affects steroidogenesis and sperm quality.     

Biotransformation and urinary excretion of 4-substituted amphetamines in pregnant mice

The urinary elimination of 4-hydroxyamphetamine (PHA) and a series of homologous 4-alkoxy-substituted amphetamines and their metabolites was examined after single and multiple oral administration to pregnant and non-pregnant mice. The metabolic profile and extent of biotransformation in a series of alkoxy analogues were affected by the size of the alkoxy side chain, multiple dosing and pregnancy. There were increased recoveries of both the substrate and the conjugated derivative of PHA during gestation. The major metabolic routes observed were O-dealkylation, conjugation, and aliphatic hydroxylation of the propoxy side chain. There was some evidence of oxidative deamination. Pregnancy did not alter the profile of the major metabolites detected by GLC and NMR spectroscopy.     

极化液和胰岛素治疗对创伤高血糖患者血TNF-α和IL-6以及白蛋白和前白蛋白水平的影响

目的：观察极化液和胰岛素个体化对严重创伤高血糖患者炎症和营养等指标影响。方法：将不同空腹高血糖和体质量的严重创伤患者,按随机数字法分为极化液个体化治疗组（GIK组,n=80）和胰岛素个体化治疗组（INS组,n=80）以及常规治疗组（C组,n=80）,制定极化液和胰岛素个体化治疗指导方案,观察各组患者治疗1,3,5,7 d后血浆TNF-α,IL-6等炎症因子以及白蛋白、前白蛋白等营养指标变化,并统计治疗7 d内人日均胰岛素用量和葡萄糖用量,低血糖发生率,MODS发生率和病死率变化。结果：GIK组患者治疗3 d后血浆TNF-α和IL-6水平明显低于INS组,INS组又明显低于C组（P<0.01）;GIK组患者治疗3 d后血浆白蛋白,前白蛋白水平明显高于INS组（P<0.01）,但INS组和C组无显著性差异。GIK组患者治疗7 d内人日均胰岛素用量明显高于INS组（P<0.01）,低血糖发生率明显低于INS组（P<0.01）;GIK组治疗7 d内患者MODS发生率和病死率与INS组无显著性差异。结论：极化液个体化治疗降低严重创伤患者炎症反应和改善患者营养效果优于单纯胰岛素个体化治疗。极化液个体化治疗相对单纯胰岛素治疗,可降低严重创伤患者低血糖发生率。