1、ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教激素类药物医学宣教ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教2ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教3ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教4ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教5ON
2、H3COOHCH3H3PO41 1/2H2OABCD1234567891011121317161514ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O1819激素类药物医学宣教7ONH3COOHCH3H3PO41 1/2H2O雌甾烷雌甾烷13-CH3雄甾雄甾烷烷10-CH313-CH3孕甾烷孕甾烷10-CH313-CH317-C2H5ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O用用-表示取代基处于环平面的上方，用实线连接；表示取代基处于环平面的上方，用实线连接；用用-表示取代基处于环下方，用虚线
3、连接。表示取代基处于环下方，用虚线连接。用用“去甲基去甲基”或或“降降”表示比原母核失去一个甲基表示比原母核失去一个甲基或环缩小一个碳原子；用或环缩小一个碳原子；用“高高”表示环扩大一个碳原子。表示环扩大一个碳原子。双键的位次可用阿拉伯数字表示，亦可用双键的位次可用阿拉伯数字表示，亦可用“”来表来表示。示。123456789101112131415161712345678910111213141516171，41，5（10）激素类药物医学宣教9ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O 激素类药物医学宣教10ONH3COOHCH3H3PO4
4、1 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHHOHOOOHHOOHHOOHO雌二醇脱氢酶雌二醇脱氢酶16-羟化酶16-羟化酶雌二醇雌酮雌三醇激素类药物医学宣教11ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O结构特点：结构特点：以雌甾烷为母核以雌甾烷为母核 A环芳构化环芳构化 3，17-二醇二醇HOHHHHCOHH3激素类药物医学宣教12ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O 雌二醇肌肉注射给药起效迅速，但作雌二醇肌肉注射给药起效迅速，但作用时间短；在胃肠道及肝脏
5、中迅速失活，用时间短；在胃肠道及肝脏中迅速失活，因此口服无效。因此口服无效。对雌激素的改造，不以增强药效为目对雌激素的改造，不以增强药效为目的。而是：的。而是：延效和口服延效和口服激素类药物医学宣教13ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHOOHOO苯甲酸雌二醇戊酸雌二醇CH3O激素类药物医学宣教14ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教15ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教16
6、ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O 雌激素在动物体内含量较少，天然来雌激素在动物体内含量较少，天然来源非常有限，从源非常有限，从4-3-酮型甾体转化为芳酮型甾体转化为芳香化香化A环的合成非常复杂，所以雌激素来环的合成非常复杂，所以雌激素来源困难。源困难。因此研究雌激素类药物的另一个方向就是：因此研究雌激素类药物的另一个方向就是：寻找结构简单、制备方便的代用品寻找结构简单、制备方便的代用品激素类药物医学宣教17ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O一些非甾体雌激素结构类型：一些
7、非甾体雌激素结构类型：激素类药物医学宣教18ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OSchueler（1946年）提出年）提出刚性甾体母核两端的富电子基团（刚性甾体母核两端的富电子基团（OH、=O、NH等）之间的距离应在等）之间的距离应在1.45nm，分子宽度应为分子宽度应为0.388nm。0.72nm1.45nm激素类药物医学宣教19ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OH3CCH3HOOH己烯雌酚己烯雌酚结构：结构：1.反式有效，平面结构，双键氢化无效反式有效，平面结构，双键氢
8、化无效 2.酚羟基酸性酚羟基酸性激素类药物医学宣教20ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教21ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OClONCH3CH3ONCH3CH3H3C氯米芬他莫昔芬激素类药物医学宣教22ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OHOHHHHCOHH3激素类药物医学宣教23ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教
9、24ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OCH3H3CHOOH激素类药物医学宣教25ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教26ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OONH3CCH3CH3，OHOOHHOOOHO激素类药物医学宣教27ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教28ONH3COOHCH3H3PO41 1/2H2OONH3C
10、OOHCH3H3PO41 1/2H2O 激素类药物医学宣教29ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OHOOOO雄素酮睾酮激素类药物医学宣教30ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O 睾酮作用时间短；易在消化道被破坏，睾酮作用时间短；易在消化道被破坏，因此口服无效；雄性激素作用强，蛋白通因此口服无效；雄性激素作用强，蛋白通化作用弱，不良反应较大。化作用弱，不良反应较大。针对这些缺点，对睾酮进行一系列的针对这些缺点，对睾酮进行一系列的改造。改造。激素类药物医学宣教31ONH3COOH
11、CH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOOOOOCH3O丙酸睾酮苯乙酸睾酮激素类药物医学宣教32ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOH3CHH3COHHHCH3激素类药物医学宣教33ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHHH3COHHHO激素类药物医学宣教34ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOOHOHCH3HOCH3NNH羟甲烯龙司坦唑醇激素类药物医学宣教35ONH3
12、COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOH3CHH3COHHHCH3激素类药物医学宣教36ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教37ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHHH3COHHHO激素类药物医学宣教38ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教39ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41
13、1/2H2O 激素类药物医学宣教40ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教41ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOOHOOHCCHCCH炔孕酮炔诺酮激素类药物医学宣教42ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O 黄体酮口服易代谢失活，仅能注射给黄体酮口服易代谢失活，仅能注射给药，因此，获得可口服的长效孕激素，就药，因此，获得可口服的长效孕激素，就成了结构改造的主要目的。成了结构改造的主要目的。激素类药物
14、医学宣教43ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOCH3OOOCH3CH3OCH3OOOCH3CH3OCH3OOOCH3Cl醋酸甲羟孕酮醋酸甲地孕酮醋酸氯地孕酮激素类药物医学宣教44ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OH3COH3CCH3OHHHH激素类药物医学宣教45ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教46ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H
15、2OOOHCCH激素类药物医学宣教47ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教48ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教49ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOOHNCCCH3激素类药物医学宣教50ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O 激素类药物医学宣教51ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3
16、H3PO41 1/2H2OOOHOHOOOOHOHHOOOOHHOOOHCOOHHOO可的松氢化可的松皮质酮醛固酮激素类药物医学宣教52ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教53ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOOHOHCH3OHCH3O氢化可的松的空间位阻激素类药物医学宣教54ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHOOOOHOHOHOOOH泼尼松泼尼松龙激素类药物医学宣教55ONH3COOHC
17、H3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教56ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教57ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHOHOOOHOHFOOHOOOHOFCH3CH3曲安西龙曲安奈德激素类药物医学宣教58ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOHOHOOOHCH3FOHOHOOOHCH3F地塞米松倍他米松激素类药物医学宣教59ONH3COO
18、HCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OH3CH3COHOHOOHHHHOCH3O激素类药物医学宣教60ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教61ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OH3CH3COHOHOOFHHHOCH3OHCH3激素类药物医学宣教62ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教63ONH3COOHCH3H3PO41 1/2H2OO
19、NH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教64ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教65ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教66ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教67ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教68ONH3COOHCH3H3PO41 1/2H2OONH3CO
20、OHCH3H3PO41 1/2H2O激素类药物医学宣教69ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教70ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教71ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教72ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H
21、2O激素类药物医学宣教74ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OH3CSNHNHCH3OOO激素类药物医学宣教75ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教76ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OSNHOClH3CONHNHOOO激素类药物医学宣教77ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教78ONH3COOHCH3H3PO41 1/
22、2H2OONH3COOHCH3H3PO41 1/2H2O2.双胍类口服降糖药双胍类口服降糖药苯乙双胍苯乙双胍 降糖灵，价格便宜。降糖灵，价格便宜。二甲双胍二甲双胍 降糖片。降糖片。激素类药物医学宣教79ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教80ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2ONHH2NHNNHNCH3CH3，HCl激素类药物医学宣教81ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教82ON
23、H3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O新型口服降血糖药物，新型口服降血糖药物，通过在肠道内竞争性抑制葡萄糖苷通过在肠道内竞争性抑制葡萄糖苷酶，降低糖类的吸收，具有降低饭酶，降低糖类的吸收，具有降低饭后高血糖和血浆胰岛素浓度的作用。后高血糖和血浆胰岛素浓度的作用。激素类药物医学宣教83ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2OOH3CHOHNOHOHOHOHOOHOHOOHOOHOOHHOHOOH激素类药物医学宣教84ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H
24、3PO41 1/2H2O新型短效促胰岛素分泌降新型短效促胰岛素分泌降血糖药。能刺激胰腺释放胰岛素，使血糖药。能刺激胰腺释放胰岛素，使血糖水平快速降低，作用依赖于胰岛血糖水平快速降低，作用依赖于胰岛中有功能的中有功能的细胞。细胞。激素类药物医学宣教85ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2ONNHOHOOCH3CH3H3CO激素类药物医学宣教86ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O高选择性过氧化物酶体增高选择性过氧化物酶体增殖因子激活的殖因子激活的型受体激动剂，增加骨型受体激动剂，增加骨骼肌、肝脏、脂肪组织对胰岛素的敏骼肌、肝脏、脂肪组织对胰岛素的敏感性，提高细胞对葡萄糖的利用而发感性，提高细胞对葡萄糖的利用而发挥降血糖作用。挥降血糖作用。激素类药物医学宣教87ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2ONH3CONHSOO激素类药物医学宣教88ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2ONNOCH3NHSHOO激素类药物医学宣教89ONH3COOHCH3H3PO41 1/2H2OONH3COOHCH3H3PO41 1/2H2O激素类药物医学宣教90
