1、SNHOONH2NHOSNHOORNHORSOONHNHONHOClOMeSOONHNHONHONNCH3SOONHNHONCH3SOONHNHONHONCH3OCH3CH3CH3OOOEt(CH3)2NHEt2SO4CH3OOOEtEtNaCNNaHSO3CH3OOEtEtOHNCHAc2ONAcCH3CH3ONa2CO3NHCH3CH3OOCNNCH3CH3OONHClSO3HNCH3CH3OONHSO2ClNCH3CH3OONHSO2NH2NH4OHCH3OCNK2CO3SOONHNHONHOCH3NCH3CH3O1.2.2Ra-Ni,ClNHOOHOOMeCH3CH3NHOOOHOCH
2、3NNHOOHOCH3CH3NHHPhCOOHOFCHONHDMF,K2CO3NCHO(CH3)2CHCH2MgBrOHCH3CH3NNa2Cr2O7H2SO4OCH3CH3NNH2CH3NCH3CH3NCH3TiCl4/Et3NH2Raney-NiOOCH3OCH3HOOCPh3P/Et3NCCl4NHCH3CH3NOOCH3OCH3ONHCH3CH3NOCH3OCOOHNHCH3CH3CH3NPd/C,H2NH2CH3CH3NNaOHCH3CH3(HCHO)n/HClZnCl2CH3CH3Cl(CH2)6N4HOAcCH3CH3CHOH2O2/NaOHCH3CH3COOHH2,Raney-
3、NiCH3CH3COOHKOHCH3CH3COOHPCl5CH3CH3COClNH2COOHCH3CH3ONHCOOHCH3OHHClNaOH,HCl1.2.1.2.5 106PaCO2EtCO2EtPhBrCH2CO2EtK2CO3,CH3CNBu4NBrCO2EtCO2EtPhCH2CO2Et-CO2PhCO2HHO2C1)NaOH2)NHHHSOCl2EtOHEt3N/SOCl2PhCO2EtEtO2CPhCO2HHO2C2)NaOH1)Imidazole2)1)-chymotrypsinNHHPhCOOHONHHPhCOOOCaCl2/NH4OHEtOH/H2OCa.H2O22-2+N
4、NHNHNH2NHCH3CH3OSNHOONCH3NOSNHOONEtNClCH3NHOHNNOHCH3FCHONNOCH3CHOSNHOONNOCH3SNOONNOCH3SNOOH+KOH/THFHOAc210%Pd-C,NEtCH2CH2OHFO2NNEtONO2H2/Pd-CNaH/DMFNEtONH2NaNO2/HBrCH2CHCOORNEtOBrCOOR(1)(2)NH2NH2SNEtOSNHONHNaOAc,EtOH2N HClNEtOSNHOOOONCH3ONHOOOONCH3COOCH3COOCH3OOOHNHOHOH3COHHOHOOOHOOHOHOHHOHOOHHONOHO
5、HOHOHCH2CH2OH以GLP-1为靶点，设计降糖药物GLP-1类似物天然或者人工合成的GLP-1多肽类似物需注射给药Exenatide(Amylin and Lily,2005年上市)Liraglutide(Novo Nordisk公司，临床III期 DPP-IV小分 子抑制剂通过抑制DPP-IV的活性，使之无法水解GLP-1，因而提高GLP-1水平，GLP-1促使胰腺分泌胰岛素，达到降低血糖的目的DPP-IV抑制剂代表化合物：NCNOH2NHOBMS-477118HOHNNOCNLAF-237FFFNNH2ONNNCF3MK-0431Merck,今年上市诺华，III期临床施贵宝，III期临床
