### 药效团检索设计新的HIV-1蛋白酶抑制剂

1. 中国科学院上海有机化学研究所.上海(200032);中国科学院计算机化学开放实 验室.上海(200032)
• 发布日期:2000-03-15

### Design of new HIV-1 protease inhibitors by pharmacophore searching

Chen Haifeng;Yuan Shengang;Luo Shiwei;Dong Xicheng;Yao Jianhua;Yang Shuo;Zheng Chongzhi

1. Shanghai Inst Organ Chem., CAS.Shanghai(200032);Lab of Comp Chem, CAS.Shanghai(200032)
• Published:2000-03-15

Four HIV-1 protease inhibitors were hit by pharmacophore searching against a 3D structural database (containing 30,000 newly reported compounds) developed by our group. By using conformation analysis we found that their favorable conformers contain the pharmacophore respectively. Additionally, all the four compounds have some common structural features such as an ortho-dihydroxyl substituted benzene ring with a carbonyl at para-position of the ring. Their hydrophobic parameters were calculated by Ghose-Crippen method integrated in the Spartan 5.0 program and found to be a little too small. In order to meet the two principal factors: containing the pharmacophore and having a moderate hydrophobic parameter, which were believed to be critical for an active HIV-1 protease inhibitor, some new structures were designed by modifying the structures of these four compounds. These designed structures are simpler and believed easier to synthesize than the hitting compounds.