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通过对自建的未开发化合物三维结构库进行药效团检索,得到了4个对HIV-1蛋白酶有抑制活性的化合物,通过构象分析发现包含药效团的构象处于优势构象,而且4个结构都含有带两个邻位羟基的苯环和一个间位羰基的药效团以及公共子结构.通过计算发现它们的疏水参数都很小.在考虑满足包含药效团的结构特征和有适中的疏水参数两个因素的前提下,设计出了新的具有潜在抑制HIV-1蛋白酶活性的化合物.它们的结构都比检索得到的四个化合物更为简单,因此易于合成
Four pharmacophores with inhibitory activity against HIV-1 protease were obtained by searching the pharmacophores of the three-dimensional structure library of undeveloped compounds. Conformational analysis showed that the pharmacophore-containing conformation was in the dominant conformation, and four structures Both contain the pharmacophore with two ortho-hydroxyl groups and one meta-carbonyl group, as well as the common substructures.It is found by calculation that their hydrophobic parameters are very small.At the same time, considering the structural features that contain the pharmacophore and the moderate Hydrophobic parameters of the two factors under the premise of the design of a new potential with inhibition of HIV-1 protease compounds their structure than the retrieved four compounds is more simple and therefore easy to synthesize