制药工程 专业英语 Unit 25

1、the professional english of pharmaceutical engineering,wang xinliang east china university of science and technology,words,physicochemical pharmacological antidote antimetabolite antiulcer leuk(a)emias (leucemias) arthritis poliomyelitis in vivo/in vitro malignant condescension serendipity paradigm

2、free energy/enthalpy/entropy retrospective repository circumspect regression analysis cadd: computer-aided drug design sar: structure-activity relationship morbidity (mortality),a. 物理化学的，物化的 a. 药理学的 n. 解毒剂 n. 抗代谢物（药） n. 抗胃溃疡的 n. 白血病 n. 关节炎 n. 脊髓灰质炎；小儿麻痹症 在体内/体外 a. 恶性的；有害的；n. 怀恶意的人 n. 谦虚；屈尊；傲慢态度 n. 意

3、外发现；偶然发现 n. 范例 n. 自由能/焓/熵 a. 回顾性的；怀旧的；n. 回顾展 n. 储藏室；知识库；智囊团 a. 周到的；慎重的 回归分析 计算机辅助药物设计 构效关系 n. 发病率；致病率 (死亡率；死亡数),目前的药物设计与其说是富有成绩（成效），不如说是充满希望的。这意味着在最广泛意义上运用过去所认知的生物活性与物化特性之间的关系，并且希望可以预测还未合成出来的化合物在药理学的成功。,drug design to day is more of a hope than an achievement. it means the application of previously

4、recognized correlations of biological activity with physicochemical characteristics in the broadest sense, in the hope that the pharmacological success of a not yet synthesized compound can be predicted.,但目前所使用的药物很少是完全按照这种方法被发现出来。胆碱酯酶抑制剂解毒剂吡啶肟甲基碘化物，抗胃溃疡药西咪替丁，以及对抗白血病有活性的一些抗代谢药都是这样的例子。,few drugs in us

5、e today were discovered entirely in this way. the cholinesterase inhibitor antidote pyridine aldoxime methiodide, the antiulcer drug cimetidine, and some antimetabolites active against leukemias are examples.,这种方法的主要难点在于：可得的且非常复杂的预测药物作用机制的方法既不能预测其毒性和副作用，也无法有助于预料在体内药物的传输特性和代谢途径。当然，在体外产生成功治疗疗效的药物或药剂学上

6、的细胞效应，这些都同样重要。,one of the principal difficulties in this approach is that the available and very sophisticatedmethods for predicting drug action cannot foretell toxicity and side effects, nor do they help in anticipating the transport characteristics or metabolic fate of the drug in vivo. these are,

7、 of course, as important in producing a therapeutically successful drug in vitro or cellular effect of the pharmacy.,由于对一种疾病(有关)的生物学或生物化学(方面的知识)基本上无知，我们最好的努力也常常遭受挫折；于是，我们就倾向于刘易斯托马斯在他的系列精辟文章之一中，所称谓的“不彻底的技术”，即由于不能理解疾病的基本致病因素所采用的复杂而昂贵的疾病治疗方法。,very often our best efforts are frustrated by basic ignoranc

8、e of the biology or biochemistry underlying a disease, and we are reduced to what lewis thomas, in one of his incisive essays, calls “halfway technology” in reference to the complex and costly management of diseases whose basic causes are not understood.,而与大多数细菌性传染疾病以及甚至像脊髓灰质炎类某些病毒性疾病的治疗方案的简单性形成鲜明对照

9、的是，对风湿性关节炎、大多数恶性肿瘤和全部精神类疾病的治疗都可归为此类。,the treatment of rheumatoid arthritis, most malignant tumors, and all mental diseases falls into this category, and contrasts glaringly with the simplicity of dealing with most infectious diseases of bacterial origin and even some viral diseases like poliomyeliti

10、s.,虽然一些临床药用化学家和分子药物学家一直带着一些谦虚态度和难以隐忍的急躁情绪努力从事合理的药物设计，但缓慢却有前途的发展仍不断带来希望：在该领域的进展比将生物和物理化学运用到人类和动物病理学（所取得的进展）快得多。计算机辅助三维药物设计的蓬勃发展有希望产生真正合理药物设计的纪元（时代）。,although some practicing medicinal chemists and molecular pharmacologists still regard efforts at rational drug design with some condescension and ill-c

11、oncealed impatience, a slow rapid but promising development gives renewed hope that progress in this area will not be less than in the application of biology and physical chemistry to human and animal pathology. the explosive development of computer-aided drug design in three dimensions promises to

12、lead to the era of true rational drug design.,直到二十世纪六十年代早期，药物设计还是基于长期经验、敏锐的观察力、意外发现、纯粹的运气、和大量艰苦工作的一种直观上的努力。发现一种临床上有效的药物的概率并不高，据估计为了生产一个具有实用（价值）的药物需要合成3000-5000个化合物。,until the early 1960s, drug design was an intuitive endeavor based on long experience, keen observation, serendipity, sheer luck, and a

13、 lot of hard work. the probabilities of finding a clinically useful drug were not good; it was estimated that anywhere from 3000 to 5000 compounds were synthesized in order to produce one practical drug.,随着当今越来越严格的药品安全监管，这个（成功的）比例甚至更小，费用突升，也势必严重延缓新药的上市。药物研发通常所采用的经典方法是分子修饰设计已确证活性的先导化合物的类似物。其指导原则的范例是：

14、在分子结构中的微小改变导致其生物作用的微小、定量的变化。,with todays more strict drug safety regulations, the proportions are even worse and the costs skyrocket, retarding the introduction of new drugs to a dangerous extent. the classical method usually applied in drug development was molecular modificationthe design of analog

15、ues of a proven active “lead” compound. the guiding principle was the paradigm that minor changes in a molecular structure lead to minor, quantitative alterations in its biological effects.,虽然这在紧密相关的同系物中可能是正确的，但这又取决于“微小变化”的定义。将两个非常小的氢原子加入麦角碱的8双键上，会消除它们的子宫收缩活性；但吗啡的n-ch3取代基用更大的苯乙基官能团替代后，则增加其活性近十倍。,alt

16、hough this may be true in closely related series, it depends on the definition of minor changes, the addition of two very small hydrogen atoms to the 8 double bond of ergot alkaloids eliminates their uterotonic activity, but replacement of the nch3 substituent by the large phenethyl group in morphin

17、e increases the activity less than ten fold.,而只将二乙吖嗪的侧链只用一个c原子进行延长竟导致氯丙嗪和现代精神药理学的意外发现。1983年就有了一篇关于经典设计的回顾性评述。,extension of the side chain of diethazine by only one carbon atom led to the serendipitous discovery of chlorpromazine and modern psychopharmacology. a retrospective account of classical dru

18、g design was provided in 1983.,从这些随机实例中可以得到两个结论。首先，在构效关系（sar）研究中，只要其理化性质仍未被探究或其作用的分子基础仍未知，仅仅是有机分子的结构改变是毫无意义的。在有机化学概念中，结构仅仅是知识库具有药物活性的至关重要的大量参数的载体。,there are two conclusions to be drawn from these random examples. first, a merely structural change in an organic molecule is meaningless in structure-ac

19、tivity relationship (sar) studies as long as its physicochemical consequences remain unewplored and the molecular basis of its action remains known. structure, in the organic chemical sense, is only a repository, a carrier of numerous parameters of vital importance of drug activity.,从上述实例和无数的其他例子所可以

20、得出的第二个结论是：定性新药理作用的发现经常是基于另外的单纯系列药物类似物上的不连续跳跃性（发现的结果）；即使采用相当精密的方法，也很难预测。,the second conclusion to be drawn from the above examples and innumerable others is that the discovery of qualitatively new pharmacological effects is often a discontinuous jump in an otherwise monotonous series of drug analogue

21、s and is hard to predict, even with fairly sophisticated methods.,despite the great success of the classical methods of drug design, their unpredictability and the tremendous amount of wasted effort expended have necessitated the development of more rational methods with a much higher predictive cap

22、ability, in an effort to elevate drug design from an art to a science.,尽管药物设计的经典方法取得了巨大成功，它们的不可预测性和需要付出大量的无效努力使得具有更高预测能力的更合理方法的研发极为需要，并努力使药物设计由艺术提升至科学。,the approach involving the design of analogues of an active lead compound remains unchanged, and the expertise of the medicinal chemist is as much i

23、n demand as ever; however, the intuitive process of selecting structural modifications for synthesis becomes circumspect in this approach, and models based on multiple regression analysis and pattern recognition methods, using very powerful computer techniques, are employed as aids.,尽管涉及活性先导化合物的类似物的

24、设计方法仍未改变，且药物化学家需要的专业知识仍象以前那样多；但在该方法中直观选择待合成的结构修饰的过程变得周到全面了，采用非常强大的计算机技术的基于多元回归分析的模型及模式识别方法也被应用作辅助工具。,it is obviously much faster and cheaper to calculate the required properties of novel compounds from a large pool of data on their analogues than to synthesize and screen all such new, compounds in t

25、he classical fashion. only promising candidates are investigated experimentally.,从大量新化合物的类似物的数据库中计算其所需的性质，比采用经典方式合成并筛选所有这些新化合物，显然要既快又便宜得多。只有有希望的候选化合物通过实验才彻底研究。,the results gained this way are incorporated into the data base, expanding and strengthening the theoretical search. eventually, sufficient material accumulates to aid in making a co