Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
Curr Med Chem. 2012;19(31):5364-80. doi: 10.2174/092986712803833326.
In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment of HIV-1 infections. More than 60 structurally different classes of compounds have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse transcriptase (RT). Five NNRTIs (nevirapine, delavirdine, efavirenz, etravirine and rilpivirine) have been approved by US Food and Drug Administration (FDA) for clinical use. The NNRTIs bind with a specific 'pocket' site of HIV-1 RT (allosteric site) that is closely associated with the NRTI binding site. Due to mutations of the amino acid residues surrounding the NNRTI-binding site, NNRTIs are notorious for rapidly eliciting resistance. Though, the emergence of resistant HIV strains can be circumvented if the NNRTIs are used either alone or in combination with NRTIs (AZT, 3TC, ddI, ddC, TVD or d4T) and PIs (Indinavir, nelfinavir, saquinavir, ritonavir and lopinavir etc.) as shown by both a decrease in plasma HIV-1 RNA levels and increased CD4 T-cells. Here we are going to discuss recent advances in structure activity relationship studies on nevirapine, delavirdine, efavirenz, etravirine, rilpivirine and 4-thiazolidinones (privileged scaffold) HIV-1 NNRTIs.
除了核苷逆转录酶抑制剂（NRTIs）、蛋白酶抑制剂（PIs）和整合酶抑制剂（INIs）之外，非核苷逆转录酶抑制剂（NNRTIs）在治疗 HIV-1 感染方面也发挥了重要作用。已经鉴定出超过 60 种结构不同的化合物作为 NNRTIs，它们专门抑制 HIV-1 逆转录酶（RT）。美国食品和药物管理局（FDA）已经批准了五种 NNRTIs（奈韦拉平、依法韦仑、地拉韦啶、依曲韦林和利匹韦林）用于临床。NNRTIs 与 HIV-1 RT 的特定“口袋”位点（变构位点）结合，该位点与 NRTI 结合位点密切相关。由于 NNRTI 结合位点周围氨基酸残基的突变，NNRTIs 迅速产生耐药性是出了名的。然而，如果 NNRTIs 单独使用或与 NRTIs（AZT、3TC、ddI、ddC、TVD 或 d4T）和 PIs（茚地那韦、奈非那韦、沙奎那韦、利托那韦和洛匹那韦等）联合使用，可以避免耐药性 HIV 株的出现，这一点已经通过降低血浆 HIV-1 RNA 水平和增加 CD4 T 细胞得到了证明。在这里，我们将讨论奈韦拉平、依法韦仑、地拉韦啶、依曲韦林、利匹韦林和 4-噻唑烷酮（特权支架）HIV-1 NNRTIs 的结构活性关系研究的最新进展。
