N-苯基芳酰胺衍生物（PAFAs）作为非核苷 HIV 逆转录酶抑制剂的合成、构效关系及对接研究。
Synthesis, structure-activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors.
机构信息
Department of Chemistry, Fudan University, Shanghai 200433, PR China.
出版信息
Eur J Med Chem. 2012 Dec;58:504-12. doi: 10.1016/j.ejmech.2012.03.032. Epub 2012 Mar 31.
A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC(50) values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC(50) = 0.30 nM, TI = 184 578), 13l (EC(50) = 0.37 nM, TI = 212 819), 13m (EC(50) = 0.32 nM, TI = 260 617) and 13r (EC(50) = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC(50) values of 0.29 μM, 0.14 μM, 0.10 μM and 0.27 μM, respectively. In particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 μM concentration.
一系列具有抗野生型 HIV-1 活性（EC（50）值范围为 0.3 nM 至 5.1 nM）和治疗指数（TI）范围为 10 616 至 271 000 的 N-苯基芳酰胺衍生物（PAFAs）被鉴定为新型非核苷逆转录酶抑制剂。其中，化合物 13g（EC（50）= 0.30 nM，TI = 184 578）、13l（EC（50）= 0.37 nM，TI = 212 819）、13m（EC（50）= 0.32 nM，TI = 260 617）和 13r（EC（50）= 0.27 nM，TI = 271 000）对该病毒株表现出最高的活性，几乎与先导化合物 GW678248 一样有效。此外，它们对双突变株 A(17)（K103N + Y181C）也具有活性，EC（50）值分别为 0.29 μM、0.14 μM、0.10 μM 和 0.27 μM。特别是化合物 13m，具有广谱抗 HIV 活性，在 4.37 μM 浓度下也能有效抑制 HIV-2 ROD 复制。
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