Xiong Yuan-Zhen, Chen Fen-Er, Balzarini Jan, De Clercq Erik, Pannecouque Christophe
School of Pharmacy, Fudan University, Shanghai 200031, PR China.
Eur J Med Chem. 2008 Jun;43(6):1230-6. doi: 10.1016/j.ejmech.2007.08.001. Epub 2007 Aug 11.
A series of novel 6-naphthyloxy substituted DATA analogues bearing different substituents on the C-6 position of triazine ring were synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cells. The results demonstrated that most of the compounds in this series are potent activity against HIV-1 with moderate to high selectivity. Among these analogues, two compounds exhibited excellent effect in inhibiting HIV-1 replication at nanomolar concentration (for compound 9h: IC(50)=9.3 nM, SI=15,385; for compound 9i: IC(50)=9.4 nM, SI=14,094), which are about 15-fold more active than nevirapine. In addition, several compounds are active against both HIV-1 and HIV-2, whose mechanism may be different from typical NNRTIs.
合成了一系列在三嗪环C-6位带有不同取代基的新型6-萘氧基取代的DATA类似物，并在MT-4细胞中评估了它们的体外抗HIV活性。结果表明，该系列中的大多数化合物对HIV-1具有强效活性，具有中度至高选择性。在这些类似物中，两种化合物在纳摩尔浓度下对HIV-1复制表现出优异的抑制作用（化合物9h：IC(50)=9.3 nM，SI=15385；化合物9i：IC(50)=9.4 nM，SI=14094），其活性比奈韦拉平高约15倍。此外，几种化合物对HIV-1和HIV-2均有活性，其作用机制可能与典型的非核苷类逆转录酶抑制剂不同。
