Lead Compounds
Before any medicinal chemistry project can get underway, a lead compound is required. A lead compound will have some property considered therapeutically uful. The property sought will depend on the tests ud to detect the lead compound, which in turn depends on the drug's target. The level of biological activity may not be particularly high, but that does not matter. The lead compound is not intended to be ud as a clinical agent. It is the starting point from which a clinically uful compound can be developed. Similarly, it does not matter whether the lead compound is toxic or has undesirable side effects. Again, drug design aims to improve the desirable effects of the lead compound and to remove the undesirable effects.
1. ek [si:k] vt. & vi.寻找; 探寻mathsvi.企图; 试图vt.请求, 征求;
2. in turn ① 依次, 轮流地；② 相应地；转而
3. target ['tɑ:ɡit] n. (射击的)靶子；(欲达到的)目[指]标；(服务的)对象; (攻击的)对象
vt.托福口语 瞄准某物
4. intend [in'tend] vt. 意欲, 打算；打算使, 想让…做
5. undesirable [,ʌndɪ'zaɪərəbəl] n. 不受欢迎的人;不良分子
adj. 可能招致麻烦或不便的;不想要的；不受大家欢迎的;讨厌的
找到先导化合物是开展任何一项药物化学课题研究的前提。一种先导化合物应该具有与治疗作用有关的某些特性。药物作用的靶点决定寻找先导化合物所进行的试验，试验决定所能发现的先导化合物的特性。先导化合物的生物活性可能不是很强，这无关紧要。因为先导化合物不能被直接用作临床药物，它只是开发临床上有用的化合物的起点。先导化合物是否具有毒性或不良反应同样也不重要。因为药物设计的目的就是要提高先导化合物的期望效应，去除不良反应。
Lead compounds can be obtained from a variety of different sources such as the flora and fauna of the natural world, or synthetic compounds made in the laboratory. There is also the potential of designing lead compounds using computer modeling or NMR spectro
scopic studies.
1. variety [və'raiəti] n. 品种, 种类；种种, 各种；变化, 多样化
2. flora ['flɔ:rə] n. (某地区或某时期的)植物群;植物区系; 植物志
3. fauna ['fɔ:nə] n. (某一地区或某一时期的)动物群
4. synthetic [sin'θetik] adj. 合成的, 人造的；〈口〉假的, 非天然的; 虚伪的
n.合成物,
make love是什么意思5. NMR = nuclear magnetic resonance ['rezənəns] 核磁共振
6. spectroscopic [,spektrə'skɔpik] adj. 分光镜的，光谱的
spectroscope ['spektrəskəup] n. 分光镜
spectroscopy 美少女的谎言 第四季[spek'trɔskəpi] n. 光谱学
先导化合物可以有多种来源，例如来源于自然界的菌群和动物群或者来自实验室合成的化合物。通过计算机模拟或者核磁共振光谱研究也可能设计出先导化合物。
In order to arch for lead compounds, a suitable test is required. This could be a test that reveals a physiological effect in a tissue preparation, organ or test animal. Alternatively, it could be a cellular effect resulting from the interaction of a lead compound with a particular target, such as a receptor or an enzyme; or a molecular effect, such as the binding of a compound with a receptor. In the last two situations, the molecular target is considered important to a particular dia state, and in such cas, the lead compound may not have desired physiological activity at all! For example, there have been veral examples where the natural agonist for a receptor was ud as the lead compound in order to design a receptor antagonist. Here, the crucial property for the lead compound was that it should be recognized and bound to the binding site of the target receptor. The lead compound was then modified to bind as an antagonist rather than as an agonist. For example, the chemical mesnger histamine was ud as the lead compound in developing the anti-ulcer agent cimetidine. Histamine is an agonist that acti
vates histamine receptors in the stomach wall to increa gastric acid relea. Cimetidine acts as an antagonist at the receptors, thus reducing the levels of gastric acid relead and allowing the body to heal the ulcer.
1. alternatively [ɔ:l'tə:nətivli] adv.做为选择,二者择一地
2. receptor [rɪ'ptə] n. <生>感受器;受体
3. molecular [mə'lekjələ] adj. 分子的 molecule ['mɔlikju:l] n. 分子
4. state [steit] n. 状态, 状况；国家, 政府；州; 邦
vt.lukes陈述; 敘述；规定, 指定, 排定
5. agonist ['æɡənist] n. 激动剂 antagonist [æn'tægənɪst] 水利工程管理n. 拮抗剂
6. modify ['mɔdifai] vt. & vi. 修改, 更改 vt. 修饰
7. histamine ['histəmi:n] n. 组胺
8. ulcer ['ʌlsə] n. <医>溃疡；腐烂物；道德败坏;腐败;弊病
9. 学徒第一季cimetidine [sai'metidi:n] n. 甲氰咪胍,甲腈咪胍,甲腈咪胺
10. stomach ['stʌmək] n. 胃；腹部；食欲, 胃口; 欲望
11. gastric ['gæstrɪk] adj. 胃的,胃部的
为了寻找先导化合物，需要开展适当的试验。这些试验可能揭示先导化合物对以组织、器官或试验动物的生理功能的影响；或者先导化合物与特定的靶点，例如受体和酶，相互作用而引起的细胞效应；或者先导化合物与受体结合等引起的分子效应。在后面两种情况下，对于先导化合物而言，重要的是具有与某种疾病状态有关的分子靶向作用，此时，先导化合物可能根本不具有与治疗作用有关的生理活性。以受体的天然激动剂为先导化合物来研制某种受体的拮抗剂就是如此。目前，已有一些这方面的实例。此时，先导化合物最重要的性质是能被该受体识别并与之结合。接下来的工作是对先导化合物进行修饰，使其与受体结合后具有拮抗作用而不是激动作用。例如，组胺是一种化学信使，在抗溃疡药－西咪替丁的研发过程中被用作先导化合物。组胺是一种激动剂，可以激活胃壁上的组胺受体，促进胃酸释放。西咪替丁则是这些受体的拮抗剂，抑制胃酸分泌，使溃疡得以愈合。
The natural world is particularly rich in potential lead compounds. For example, plants, trees, snakes, lizards, frogs, fungi, corals and fish have all yielded potent lead compounds which have either resulted in clinically uful drugs or have the potential to do so. There is a good reason why nature should be so rich in potential lead compounds. Years of evolution have resulted in the "lection" of biologically potent natural compounds that have proved uful to the natural host for a variety of reasons. For example, a fungus that produces a toxin can kill off its microbiological competitors and take advantage of available nutrients.awful是什么意思
1. fugus ['fʌŋɡəs] n. 真菌 fungi ['fʌŋgaɪ]
fungal ['fʌŋɡəl] adj.asky 真菌的, 由真菌引起的
2. potent ['pəutənt] adj. (药等)效力大的; 威力大的；强有力的; 有说服力的cheap的比较级
3. toxin ['tɔksɪn] n. 毒素
4. competitor [kəm'petɪtə] n. 竞争者,对手,敌手
