药物化学绪论创新.pptVIP

Medicinal chemistry 刘美凤 liumf75@ Chapter 1 Introduction reference book Concept of Medicinal chemistry by IUPACIUPAC: International Union of Pure and Applied Chemistry Medicinal chemistry is a chemistry-based discipline Involving aspects of biological, medical, and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relationship (SAR), the relationships between chemical structures and pharmacological activity for a series compounds. 药物化学的任务和使命 人类寿命的不断延长 生活质量的不断提高 毒副作用 耐药性的增加 新疾病（AIDS、SARS、疯牛病、禽流感等）的产生和威胁 Mission of medicinal chemistry To obtain new chemical entities (NCE) for clinical drug by molecular drug design or structure modification of bioactive compound To study the relationship between structure and physicochemical character (solubility, PKa and oil/water partition coefficients) To validate acidity, alkalescence and stability of drug, To study metabolize substance and its activity To elucidate interaction between drug and their receptors at molecular level for interpretation of drug functional mechanism 药物化学的历史和发展 1806年从阿片中分离出吗啡 1819年从咖啡中分离出咖啡因 19世纪从古柯叶中分离出可卡因 手性药物发展 反映停事件:上世纪60年代，沙利度胺（Thalidomide）良好的镇静作用，可以减轻孕妇的呕吐反应。致畸胎，产生海豹儿 当时使用的药物为消旋体，2个对映体都具有镇静作用，S-（+）-沙利度胺的二酰亚胺进行酶促水解，生成临苯二甲酰谷氨酸，干扰胎儿谷氨酸类物质转变成叶酸。干扰胎儿发育，造成畸胎。 制定药事法规，上市前必须进行特殊的毒理实验，尽可能以单个对映体上市 1300多种化学药物，其中528种具有手性结构，，目前只有61种以单个对映体供药用 1984年后仿制药（Generic Drug）成为有意义的方向 2004年美国FDA黄皮书中10357种批准的新药已有7602种被仿制 Generic Pharmaceutical Association 公布三年内失去保护的药每年销售350亿美元 Eli Lilly和Merck 建立自已的仿制药厂 Novartis 用820亿美金买了二个仿制药厂 Foundation of medicinal chemistry of modern time Chemistry Organic chemistry, structure chemistry, spectroscopy, crystallography, combinatorial chemistry, physical chemistry… Biology Biochemistry, molecule biology, cytology, genetics, pharmacol