化学结构与药物代谢PPT精选文档

1、restbreakR - C O C R1R - O H+R1C O O HR - O N O2R - O H+H N O3R - O S O3HR - O H+H2S O4R -N H - O O C R1R -N H2+R1C O O H亲水性增加亲水性增加亲水性减少亲水性减少O2OCH3SNHNHOO2OCH3SNHNHOOHRNRCHRNRCOHNHRR+OCH3COSO2NHCONHCH3CSO2NHCONHHOHS-(-)R N O2e-R N O2-e-22H+RN Oe-H+R N OHe-H+RN H O He-22H+R N H2O2 O2NNO2ONNHOHO（致癌）Ar

2、 NN Are-Ar NN Are-H+2ArN HN H Are-2H+2ArN H2+ArN H2O2- O2.-.(C2H5)2NCSSCSN(C2H5)2(C2H5)2N-C-SHSCH3SOCH3CH3SCH3NCH2CH2CH2N(CH3)2ONCH2CH2CH2N(CH3)2OHOHOOHOOHC OOHOOPOOHOOOH OHNNHOUD PGAoROHOATPPPiRAMPOCOASHAMPRCOSCoANH2COOHRCOOHRNHORSHCONHNHCOCOOHNH2COOH较好亲核作用较好亲核作用C H3S C O AOXC O A S HC H3XON H2- RC

3、 H3N H - ROXNNNNNH2HOOHCH3SNH2COOHOH+HX-RCH3-X-R+NNNNNH2HOOHSNH2COOHOHOHOHNHOHNHClClCOOH特布他林双氯酚酸RHOHRROHHOHHROHROHROHOH2GSHSGOHRXOHR重排生物大分子亲核基团X谷胱甘肽-S-转移酶环氧化物酶NHNHOONHNHOOOHNNOC4H9ONNOC4H9OOH苯妥英苯妥英保泰松保泰松NHNClClNHOOCSO2N(CH2CH2CH3)2可乐定和丙磺舒可乐定和丙磺舒NSRClCH2CH2CH2NMe2R=HR=OH氯丙嗪氯丙嗪NNCH3OClNNCH3OClOH地西泮地西泮

4、OOHOHOHSGOOHOHOHOHNNNHOOHNH核糖NNNHNSHNNNHNSHOHOHNCONH2CYP450NCONH2ONCONH2OHOHRCCHRCCHRCHCORCHCORCH2NCORCOCHRCH2COOHRCH2CONH-Pr卟啉酶酶酶酶CH3CH3CH3OHOCH3NHCH3ONCH3CH3CH3NHCH3ONCH3CH3NHCH3ONNNCH3CH3NNHCH3丙咪嗪丙咪嗪地昔帕明地昔帕明NH2NH2NH2O+NH3OMeNCH3OOHOHNCH3OOHNNNHNSCH3NNNHNSHNHNHOCH3CH3CH3OSNHNHOCH3CH3CH3OONNHCH3SNH

5、NHCH3NCNNNHCH3SNHNHCH3NCNO6-甲硫嘌呤甲硫嘌呤硫喷妥硫喷妥异戊巴比妥异戊巴比妥西咪替丁西咪替丁S-脱烃基化脱烃基化脱硫脱硫S-氧化氧化OOHOPhOOHRCCHR2R3HR1OHCCHR=CH3R1=CH3,R2=OH,R3=HR=C2H5R1=C2H5,R2=H,R3=OHNHNOClRa_R=NO2b_R=NH2氯硝西泮氯硝西泮ONNHCONH2N2OONNHCONH2NHOH+ONNHCONH2NH2ONHNNHCONH2ONNHCONH2NH呋喃西林呋喃西林NNHSO2NNCOOHOHNNHSO2NH2+COOHOHNH2N2OCHCHOHNHCOCHCl2C

6、H2OHN2OCHCHOHNHCOCOClCH2OHPrOHNHCOCH2OHCHCHN2OCOPrCCl4CYP450Cl4C_.-Cl-Cl3C.H+e-O2CHCl3:CCl3Cl3C-O-O.BrCHClCF3e-Br-HC-CF3.e-H-CF2CClF-F-ClCH=CF2PrPrClCF3HCRHR H2CCF3ClBrCF3ClCHBrCF3ClCOH-Br-CF3COClPrOH2CF3COPrCF3COOH(肝毒性)ClOON+(CH3)3OON+(CH3)3OHN+(CH3)3+COOHCOOHCOOHOACCOOHOH+AcOH琥珀酰胆碱阿司匹林NCH3HOOROO可卡

7、因NH2CXOCH2CH2N(C2H5)2X=NHX=O普鲁卡因酰胺普鲁卡因酰胺普鲁卡因普鲁卡因CH3NHNHCH3ONNHClOCOCH3O丙胺卡因丙胺卡因奥沙西泮奥沙西泮乙酰化反应N葡萄糖醛酸苷化反应葡萄糖醛酸苷酰化反应甘氨酸结合反应NH2COOHOHO-葡萄糖醛酸苷化反应O-硫酸化反应反应类型反应类型轭合反应式轭合反应式典型药物典型药物O-葡萄糖醛酸苷化葡萄糖醛酸苷化羟基：酚羟基羟基：酚羟基醇羟基醇羟基羧基羧基N葡萄糖醛酸苷化葡萄糖醛酸苷化氨基氨基OHRORGluAcNHOHN2OCHOHCHNHCOCHCl2CH2OHRCRROHRCRROGluPhOOHOR-COOHR-COGluR

8、RNHRRNGluNHCH3酰氨基酰氨基磺酰氨基磺酰氨基S葡萄糖葡萄糖醛酸苷化醛酸苷化硫醇硫醇硫代硫酸硫代硫酸C葡萄糖葡萄糖醛酸苷化醛酸苷化RCO NRHRCO NRGluCCH3CH3CH2OCH2OCCOONH2NH2RSO2NRHRSO2NRGluNH2SO2NHSNRSHRSGluNNSHCH3SCSHRSCSRGlu(C2H5)2NSSHNNOOPhPhRCOCH2CORRCOCHGluCORNNNNNH2OHOHOPO3H2OPOOSOOHOHO反应类型反应类型轭合反应式轭合反应式典型药物典型药物醇羟基硫醇羟基硫酸酯化酸酯化酚羟基硫酚羟基硫酸酯化酸酯化羟胺硫酸羟胺硫酸酯化酯化氨基的

9、硫氨基的硫酸化酸化RRCHOHRRCHOSO3-RRCH+CH3CH2OHOHROSO3-RCH3CONHOHRRNOHRRNOSO3-RRN+NOC2H5OHORRN HRRN SO3-RRCH+OHNHOHOH沙丁醇胺OHNHCOCH3NN(CH3)2BrNNH2BrNCHOBrNCOOHBrNNHCOOHOBr反应类型反应类型轭合反应式及典型药物反应式轭合反应式及典型药物反应式1.亲核取代反应亲核取代反应（SN2）例子：例子：RXYGSHRXSGX=CH2.O,S Y=离去基团或环氧化合物C H3O2S OO O S O2C H3-S G:S GO S O2H3CS+GHONO2ONO2

10、ONO2GS-HONO2ONO2OSG-SGHONO2ONO2OH+GSSGOGS-HSGHH2.芳环芳环亲核取亲核取代反应代反应例子：例子：3.酰化酰化反应反应例子：例子：XSGGSHzzNNNNNO2SCH3NHNNNNNNO2SCH3NHNSG-SGNNNO2SGCH3+NNSHNHNRClOCHS GRS GOCRNCXGSHRNCSGXCHCl3ClCClOGSHGSCOSGCH3-N=C=OGSHCH3NHCSGO甲基甲酰胺4、Michael加成反应加成反应例子：例子：5.还原反应还原反应RRCHCXRRCRSGCH2XX=COR.CNOOHNCH3OHHOOHNCH3OSGOOH

11、NCH3OSGOXOHxHNORNHSORG反应类型反应类型轭合反应式轭合反应式典型药物典型药物脂肪胺轭合脂肪胺轭合反应反应芳香族轭合芳香族轭合反应反应肼和酰肼轭肼和酰肼轭合反应合反应RRNHRRNCOCH5CH3CH3HNHOSCOOHNH2HCOOHRN H2RN HCOCH3R NHNH2R NHNHCOCH3HOOCOHNH2NCONHNH2NNNHNH2OOHOPO3H2NNNNNH2OPOOHOPOOHCH2OCCH3CH3NHCOCHCH2CH2CONHCH2CH2-S-COCH3OH反应类型反应类型轭合反应式轭合反应式典型药物典型药物酚羟基甲基化酚羟基甲基化反应反应氨基甲基化反氨基甲基化反应应杂环氮原子甲杂环氮原子甲基化反应基化反应吡啶氮原子甲吡啶氮原子甲基化反应基化反应巯基的甲基化巯基的甲基化反应反应OHOHROHOMeROHOHOHNHRNRHRNRCH3OOOHNH2NHNH-CH3NNNNHOOCH3CH3NRN+RCH3NCONH2COOHNCH3SHHORSHRSCH3OHOHCHR2CH2NHR1R1=H,R2=HR1=H,R2=OHR1=CH3,R2=OH 多巴胺多巴胺去甲肾上腺素去甲肾上腺素肾上腺素肾上腺素 CH2CH2CH2CH2CH2N(CH3)3CH2CH2CH2CH2CH2N(CH3)3+. Br2CH2COO