Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors

作者：Xue, Ping; Lu, Huan-Huan; Zhu, Yuan-Yuan^*; Ju, Xiu-Lian; Pannecouque, Christophe; Zheng, Xiao-Jiao; Liu, Gen-Yan; Zhang, Xiu-Lan; Gu, Shuang-Xi^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(8): 1640-1643.

DOI：10.1016/j.bmcl.2017.03.009

• HIV-1 inhibitors
• AIDS
• Reverse transcriptase
• Integrase
• Molecular hybridization
• Diarylpyrimidines
• Diketo acids

Based on the strategy of molecular hybridization, dilceto acid fragment as a classical phamacophore of integrase inhibitors was introduced to reverse transcriptase inhibitors diarylpyrimidines to design a series of diarylpyrimidine-diketo acid hybrids (DAPY-DICAs). The target molecules 10b and 11b showed inhibitory activities against WT HIV-1 with EC50 values of 0.18 mu M and 0.14 mu M, respectively. And the results of molecular docking demonstrated the potential binding mode and revealed that the DKA moiety and its ester could both be tolerated in the nonnucleoside binding site (NNBS) of HIV-1 RT.

• 出版日期2017-4-15
• 单位河北医科大学; 武汉工程大学