1、 先导化合物的发现和优化是先导化合物的发现和优化是现现(当当)代发现新药的前提代发现新药的前提!传统的药物发现过程传统的药物发现过程:经验式经验式近代的药物发现过程近代的药物发现过程:经验半经验式经验半经验式现代的药物发现过程现代的药物发现过程:由经验半经验向理论指由经验半经验向理论指导设计转化导设计转化当代的药物发现过程当代的药物发现过程:理论指导设计理论指导设计OOHR2OOHOCOPhOHOHNHR1OOPhOHOHR1=Ph;R2=CH3CO-;PaclitaxelR1=C(CH3)3-;R2=H;TaxotereNNOOOC2H5HOR1R1=H,R2=H R3=H Camptoth
2、ecinR1=OH R2=H R3=H HydrocamptothecinR1=OH R2=-N(CH3)2 R3=H TopotecanR1=OH R2=H R3=-C2H5 SN-38R1=4-(1-piperidinyl)-piperidinylcarbonyl-R2=H R3=-C2H5 IrintecanR3R2OOOOOCH3H3COOCH3HORHR=H PodophyllotoxinOOOOHHHHOOOOOHHHHOCH3OOOOHHHHOCH3ArtemisininDihydroartemisininartemetherNSNHCOOHHHOOPhBenzylpenicil
3、linno.semisynthetic pencillinsOOOHOHR2R1HHOR1=H R2=H CompectinR1=CH3 R2=H MevinolinR1=CH3 R2=CH3 SimvastinOHCOONaOHOHHHOPravastatin SodiumNFCOOHOHHOFluvastatinNOOOOCocaineH2NCOOCH2CH2N(C2H5)2Procaine X1Y1Z1X1Y1Z1MixX1Y1Z1X1Y1Z1X1Y1Z1X1X2Y1X2Z1X2X1Y2Y1Y2Z1Y2X1Z2Y1Z2Z1Z2X2Y2Z2MixX1X2Y1X2Z1X2X1Y2Y1Y2Z1
4、Y2X1Z2Y1Z2Z1Z2X1X2Y1X2Z1X2X1Y2Y1Y2Z1Y2X1Z2Y1Z2Z1Z2X1X2Y1X2Z1X2X1Y2Y1Y2Z1Y2X1Z2Y1Z2Z1Z2X1X2Z3X1X2Z3X1X2Z3X1X2Z3X1X2Z3X1X2Z3X1X2Z3X1X2Z3X1X2Z3X3Z3X1X2Y3X1X2Y3X1X2Y3X1X2Y3X1X2Y3X1X2Y3X1X2Y3X1X2Y3X1X2Y3Y3X1X2X3X1X2X3X1X2X3X1X2X3X1X2X3X1X2X3X1X2X3X1X2X3X1X2X3OONH2NOONONNOAcetylcholineNeostigmine:a acetyl
5、cholinesterase inhibitorBethanechol:a acetylcholinoreceptor agonistOONO propanthelinea acetylcholinoreceptor antagonistHNHOHOOHRR=H NorepinephrineR=-CH3 EpinephrineHNHOOHHOSalbutamol a selective beta2 agonistNHOHPhCONH2HO Labetalol a atypical beta-receptor antagonistONHOHpropranolol a non-selective
6、beta-receptor blockerOHHOOHOHOOHONEstrogenQuinestrol a Estrogen ProdrugTamoxifen a selective estrogen-receptor antagonistDiethylstibestrolHNNHOOUracilHNNHOOFluorouracilFNNHNH2ONNNH2OOHOOHHONNHNOOHOOHHOO20NNNH2OSOOHLamivudine a antiviral agentCytarabine a antiplasmic agentCytosineHNNNO2SNNOOSildenafi
7、l(Viagra)a phosphatidiesterase inhibitorNNHOOOOThalidomide a promising immunity mudulatorNSNNSNChlorpromazine a antipsychoticsPromethazine a anti-allergic agentNSelegilineNCONHNH2NCONHNHCH(CH3)2NCH2CH2NHNH2NH2IsoniazidIproniazidPhenelzineTranylcypromineNHC2H5C2H5OONHC2H5OOH2NNNNNCCNGlutethimideAmino
8、glutethimideLetrozoleNNNHNClLiarozoleNNCNFadrozoleOCOCH3COOHAspirinO2SNHSNNH2NO2SNHNHH2NOO2SNHNHOBu-tIPTDCaarbutamideTolbutamideO2SNHH2NNNSulfadiazineOHNOO2SClOH2NFurosemideNNSO2SNH2HNOAcetazolamideNNOR1OR2R1=R2=H PhenylbutazoneR1=-OH R2=H OxyphenylbutazoneR1=H R2=OH 3-Hydroxylbutyl-metaboliteNNOSOO
9、SulphinpyrazoneNNOClNHNOClNHNOClNNOClOHOHDiazepamOxazepanTemazepanDeszepamCH2CH2CH2N(CH3)2CH2CH2CH2N(CH3)2CH2CH2CH2NHCH3OImipramineDesipramineImipramine N-oxideNBrBrNH2NHBrBrNH2OHBromhexineOC2H5NHCOCH3OHNHCOCH3PhenacetinParacetamolHHOHHHOLevonorgestrelHHOHHHONorethisteroneOOOOH3COH3COOOOOOCH3OCH3COOCH3COOCH3BifendateH3COCOOCH3COOCH3H3COOOOONSHNHHPhOOCOOHNNCH2ClClONNCH2ClClOCH3NH2CH3NH2ClNNNHCH3OChlordiazepoxide
