新一代非核苷类HIV-1逆转录酶抑制剂研究进展

Advances in the development of new generation of HIV-1 non-nucleoside reverse transcriptase inhibitors

目前文献报道的非核苷类逆转录酶抑制剂(NNRTIs)共有50多类结构骨架,其中被FDA批准上市的药物只有nevirapine,delavirdine,efavirenz和etravirine 4种。由于HIV-1极易发生变异,第一代和第二代NNRTIs普遍产生耐药性,因此,抗耐药性成为新一代NNRTIs的必要条件。文中从活性较高、结构骨架多样的NNRTIs所具有的三维结构模型出发,概述了新一代NNRTIs发挥高效抗耐药性应具备的结构特点。Etravirine,rilpivirine,BILR 355 BS,GW695634,Capravirine以及部分三唑、四唑巯乙酰胺类化合物均具有这些特点,对野生型和突变型HIV-1都有很好的抑制作用。

Currently, more than 50 different structures of non-nucleoside reverse transcriptase inhibitors （NNRTIs） have been found. Among them, nevirapine, delavirdine, efavirenz and etravirine are approved by FDA for the treatment of HIV-1 infection. For the mutations of HIV-1 , rapid development of resistance to the drugs is the shortness of first and second generations of NNRTls. Therefore, a new generation of NNRTIs must retain their potent activity against a wide range of drug resistant strains. In this review, we described the three-dimensional structural models of NNRTIs, and compared and analyzed the molecular structural features of the new generation of NNRTIs, including etravirine, rilpivirine, BILR 355 BS, GW695634, capravirine, triazole and tetrazole thioacetanilide analogues.