Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
复制标题
新型 C5 卤素功能化 S-DABO 作为有效 HIV-1 非核苷逆转录酶抑制剂的合成和生物学评价
DOI：
10.1016/j.bmc.2010.03.025
复制
发表时间：
2010-05-01
影响因子：
3.5
通讯作者：
Liu, Junyi
中科院分区：
文献类型：
--
作者：
Qin, Hua;Liu, Chang;Liu, Junyi
通过一种有效的方法合成了一系列新的S-大博类似物(4a1-5a12)，并将其用于人类免疫缺陷病毒1型(HIV1)的抑制作用。生物活性测试结果表明，在嘧啶环上的C5位取代卤素可以提高抗HIV-1RT活性。最具活性的化合物在低微摩尔范围内具有活性，其IC50值(IC500.18-3.03mM)与奈韦拉平(IC504.12mU)相当。对接结果表明，在HIV-I RT中，TYR188的卤素与羰基之间形成了一个新的卤键。(C)2010爱思唯尔有限公司。保留所有权利。
A series of novel S-DABO analogues (4a1-5a12) have been synthesized by an efficient method and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). The biological testing results clearly indicated that the substitution of halogen at the C5 position of pyrimidine ring could increase the anti-HIV-1 RT activity. The most active compounds showed activity in the low micromole range with IC50 values (IC50 0.18-3.03 mu M) comparable to nevirapine (IC50 4.12 mu M). The docking showed that a new halogen bond was formed between halogen and carbonyl of TYR188 in the HIV-I RT. (c) 2010 Elsevier Ltd. All rights reserved.