我们前期将HIV-1逆转录酶抑制剂CH2-DAPYs的左翼连接基团进行结构变换获得一批CN-DAPYs、Keto-DAPYs、Ox- DAPYs以及Hyd-DAPYs抗HIV新药候选物。本申请基于于杂交（Molecular Hybrid, MH）药物分子设计策略，利用构象分析法，将这四种候选物与DPC083分子进行揉合，设计合成四大类结构新颖的CN-DABPs、Keto-DABPs、Ox-DABPs以及Hyd-DBPYs抗HIV杂合物，以期获得抗HIV活性特别是抗耐药性更强、成药性良好的新型逆转录酶抑制剂。为开发具有我国自主知识产权的抗HIV一类新药奠定理论基础。

In our previous work, we made considerable efforts to chemically modify the methylene linker between the pyrimidine nucleus and phenyl ring I of the diarylpyrimidine as HIV-1 reverse transcriptase inhibitors (RTIs). This efforts resulted in a number of highly active inhibitors CN-DAPYs、Keto-DAPYs、Ox-DAPYs and Hyd-DAPYs as anti-HIV candidates. Based on crystallographi overlay of the each of these DAPYs and DPC083 with RT, we hybridized CN-DAPYs、Keto-DAPYs、Ox-DAPYs and Hyd-DAPYs with DPC083, respectively to generate four series of new CN-DABPs、Keto-DABPs、Ox-DABPs and Hyd-DBPYs with the aim to obtain new RT inhibitors with enhanced activity against both wild-type HIV-1 and mutant viruses. The research findings will provide the foundation for the development of our own new anti-HIV drugs.