1、口服口服抗疟药抗疟药人体人体胃肠道粘膜胃肠道粘膜血流血流红细胞膜红细胞膜疟原虫疟原虫细胞膜细胞膜疟原虫疟原虫体内体内药物受体药物受体复合物受体构象改变药理效应n共价键共价键n电荷转移物电荷转移物COOCH2CH2NC2H5C2H5RVDEVVE:静电引力D:偶极相互作用力V:分子间引力H键 型 相互作用能(千卡克分子)实例 1.加强的离子键-10 NHHHHCOOR 2.离子键-5 R4NI 3.离子偶极-(17)R4NNR3 4.偶极偶极-(17)CONR3 5.氢键-(17)OHO 6.电荷转移(1)HOCC 7.疏水性相互作用-1 CH2CH2RCH2CH2R 8.范德华相互作用-(0.
2、51)CC COOCH2CH2NC2H5C2H5RVDEVVE:静电引力D:偶极相互作用力V:分子间引力HOHOHOHOH1.45nm1.45nm0.72nmOHOHZ-己烯雌酚E-己烯雌酚雌二醇OHOH1.45nm0.72nmOHOHZ-己烯雌酚E-己烯雌酚NHNNH.2 H3PO4*CNHHOHOHOHHCNHHOHOHHOH阴离子部位受体平面区阴离子部位受体未接触部位平面区CNHHOHOHOHHCNHHOHOHHOH阴离子部位受体平面区阴离子部位受体未接触部位平面区1R,2R(-)1S,2S(+)1S,2R(+)1R,2S(+)D-(-)-Threo L-(+)-Threo d-(+)-
3、Erythro L-(-)-ErythroNO2C1C2CH2OHOHHHCl2CHCOHNNO2C1C2CH2OHOHHNHCOCHCl2HNO2C1C2CH2OHHHOHCl2CHCOHNNO2C1C2CH2OHHHONHCOCHCl2HNNSHOOO(S)-(-)-EtozolineClH2NONHON(R)-ZacoprideO OOOOHH蒿甲醚 Artemether R=-CH3青蒿素琥珀酸酯 Artesunat R=-OCOCH2CH2COOHO OOOHHORNOOHOOHHHOHOSNH2硫霉素NOOHOOHOH克拉维酸 Clavulanic AcidNNHSClSH2NO
4、OO OHNNHSClSH2NO OO O氯噻嗪氢氯噻嗪ChlorpropamideGlibenclamideSNHNHO OONHOClOSNHO OOClNHNRNNR丙米嗪R=-CH3去甲丙米嗪R=-H阿米替林R=-CH3去甲阿米替林R=-H兰索拉唑奥美拉唑NHNOSONONONHNSOFF FNNHSHNHNNNNSOCOOHNHOCOOHNSOCOOHNHOOO羧苄青霉素茚满酯雌二醇R=R=H雌二醇二丙酸酯R=R=COCH2CH3雌二醇庚酸酯R=H R=CO(CH2)5CH3雌二醇戊酸酯R=H R=CO(CH2)3CH3雌二醇苯甲酸酯R=H R=COC6H5ROORNHPONClClOHNClCl氮芥环磷酰胺NNOOHHOO奎宁碳酸乙酯N+OOOOOON+OOOOOO)(xfy)(xfy