药物化学结构与代谢

1、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NHNHOONHNHOOOHNNOC4H9ONNOC4H9OOHNHNClClNHOOCSO2N(CH2CH2CH3)2NSRClCH2CH2CH2NMe2R=HR=OHOOHOHOHSGNCONH2CYP450NCONH2ONCONH2OHOH环氧化物酶RCCHRCCHRCHCORCHCORCH2NCORCOCHRCH2COOHRCH2CONH-Pr卟啉酶酶酶酶CH3COSO2NHCONHCH3CSO2NHCONHHOHS-(-)OOHOPhOOHRCCHR2R3HR

2、1OHCCHR=CH3R1=CH3,R2=OH,R3=HR=C2H5R1=C2H5,R2=H,R3=OHRNO2e-RNO2-e-22H+RNOe-H+ RNO He-H+RNHOHe-22H+RNH2O2 O2NNO2ONNHOHO（致癌）NHNOClRa_R=NO2b_R=NH2ONNHCONH2N2OONNHCONH2NHOH+ONNHCONH2NH2ONHNNHCONH2ONNHCONH2NHArNNAre-ArNNAre-H+2ArNHNHAre-2H+2ArNH2+ArNH2O2- O2.-.NNHSO2NNCOOHOHNNHSO2NH2+COOHOHNH2NCH2CH2CH2N(

3、CH3)2ONCH2CH2CH2N(CH3)2(C2H5)2NCSSCSN(C2H5)2(C2H5)2N-C-SHSCH3SOCH3CH3SCH3N2OCHCHOHNHCOCHCl2CH2OHN2OCHCHOHNHCOCOClCH2OHPrOHNHCOCH2OHCHCHN2OCOPrC Cl4CYP450Cl4C_.-Cl-Cl3C.H+e-O2C H Cl3:C Cl3Cl3C-O-O.BrCHClCF3e-Br-HC-CF3.e-H-CF2CClF-F-ClCH=CF2PrPrClCF3HCRHR H2CCF3ClBrCF3ClCHBrCF3ClCOH-Br-CF3COClPrOH2CF3

4、COPrCF3COOH(肝毒性)R - 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 HOON+(CH3)3OON+(CH3)3OHN+(CH3)3+COOHCOOHCOOHOACCOOHOH+AcOH琥珀酰胆碱阿司匹林NCH3HOOROO可卡因NH2CXOCH2CH2N(C2H5)2X=NHX=O普鲁卡因酰胺普鲁卡因CH3NHNHCH3ONNHClOCOCH3O丙胺卡因奥沙西泮O HO HOO HOO HC O O HOO

5、POO HOOO H O HNNHOU D P G AONOHOHCH3吗啡NH2SO2NHNNOMeOMeNNOSOOHNHOHOH沙丁醇胺OHNHCOCH3NHOC2H5ONOC2H5OOHNHOC2H5O-O2SO-X-NOC2H5OXHNHOC2H5OXROHOATPPPiRAMPOCOASHAMPRCOSCoANH2COOHRCOOHRNHORNN(CH3)2BrNNH2BrNCHOBrNCOOHBrNNHCOOHOBrCONHCH2COOHCONHCH2COOHOH马尿酸水杨酰苷氨酸ArylCCOOHHCH3ArylCCOHCH3SCoAArylCCOCH3HSCOAArylCCO

6、OHCH3HAryl=CHCH2CH3CH3SHCONHNHCOCOOHNH2COOHCH3SCOAOXCOASHCH3XONH2-RCH3NH-ROXRNHOHRNHCOCH3RNOH-COCH3NNNNNH2HOOHCH3SNH2COOHOH+HX-RCH3-X-R+NNNNNH2HOOHSNH2COOHOHOHOHNHOHNHClClCOOH特布他林双氯酚酸CH2CH2CH2CH2CH2N(CH3)3CH2CH2CH2CH2CH2N(CH3)3+. Br2CH2COOCH2CH2N(CH3)3CH2COOCH2CH2N(CH3)3+CH3CH3NHCOCH2NC2H5C2H5CH3CH3

7、NHCOCH2NHC2H5CH3CH3NHCOCHNH2CH3CHNH2ONSCOORCONHR=HR=CH2OCC(CH3)3O氨苄青霉素匹氨西林OCOCH3OOOCOCH3OOCH3NC2H5OHCH3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OHRORGluAcNHOHN2OCHOHCHNHCOCHCl2CH2OHRCRROHRCRROGluPhOOHOR-COOHR-COGluRRNHRRNGluNHCH3RCONRHRCONRGluCCH3CH3CH2OCH2OCCOONH2NH2RSO2NRHRSO2NRG

8、luNH2SO2NHSNRSHRSGluNNSHCH3SCSHRSCSRGlu(C2H5)2NSSHNNOOPhPhRCOCH2CORRCOCHGluCORNNNNNH2OHOHOPO3H2OPOOSOOHOHORRCHOHRRCHOSO3-RRCH+CH3CH2OHOHROSO3-RCH3CONHOHRRNOHRRNOSO3-RRN+NOC2H5OHORRN HRRN SO3-RRCH+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+GHONO2ONO2ONO2GS-HONO2ONO2OSG-SG

9、HONO2ONO2OH+GSSGOGS-HSGHHXSGGSHzzNNNNNO2SCH3NHNNNNNNO2SCH3NHNSG-SGNNNO2SGCH3+NNSHNHNRClOCHS GRS GOCRNCXGSHRNCSGXCHCl3ClCClOGSHGSCOSGCH3-N=C=OGSHCH3NHCSGO甲基甲酰胺RRCHCXRRCRSGCH2XX=COR.CNOOHNCH3OHHOOHNCH3OSGOOHNCH3OSGOXOHxHNORNHSORGOOHOPO3H2NNNNNH2OPOOHOPOOHCH2OCCH3CH3NHCOCHCH2CH2CONHCH2CH2-S-COCH3OHRRNHRRNCOCH5CH3CH3HNHOSCOOHNH2HCOOHRN H