6化药新药开发思路.pptVIP

nonclassical isosteres 1. Hydroxy group OH NHCOR NHSO2R CH2OH NHCONH2 NHCN CH(CN)2 2. Halogen F Cl Br I CF3 CN N(CN)2 C(CN)3 3. Ether -O- -S- 4. Carbonyl group HIV protease Complex of HIV protease and its inhibitor Interactions between enzyme and substrate peptide Peptidomimetic HIV protease inhibitors P1 P1’ H-bond donor/acceptor 8.5-12.0 ? 3.5-6.5 ? 3.5-6.5 ? HIV protease inhibitors HIV protease inhibitors Interactions between enzyme and inhibitors HIV protease inhibitors IC50=0.32 ?mol/L 由受体结构特点设计活性化合物 从酶作用发现先导物ACE抑制剂 ACE的功能 将A