Synthesis of 1‐(Alkyl)‐5‐dimethylamino‐6‐phenethyluracils as Potent Nonnucleoside HIV‐1 RT Inhibitors
Synthesis of 1‐(Alkyl)‐5‐dimethylamino‐6‐phenethyluracils as Potent Nonnucleoside HIV‐1 RT Inhibitors
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DOI：
10.1080/00397910701412737
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发表时间：
2007-07
影响因子：
2.1
通讯作者：
Xiaowei Wang;Yanli Chen;Ying Guo;Amin Li;Xiaoyan Ma;Junyi Liu
中科院分区：
文献类型：
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作者：
Xiaowei Wang;Yanli Chen;Ying Guo;Amin Li;Xiaoyan Ma;Junyi Liu
1‐（烷基）‐5‐二甲氨基‐6‐苯乙基尿嘧啶(1)和(2)是MKC‐442的类似物，MKC‐442是一种非常有效的HIV‐1逆转录酶抑制剂。目标化合物1采用第一种方法，由相应的1,3‐二苄基‐5‐（二甲氨基）‐6‐苯乙基嘧啶‐2,4（1H,3H）‐二酮(7)，由6‐甲基尿嘧啶(3)经过硝化、苄基化、还原和氨基甲基化四个步骤合成。然后将化合物7脱苯，得到完全脱苯的化合物8，产率很低。为了提高产率，我们开发了另一种途径，首先在尿嘧啶环的N - 1上引入乙氧基甲基。调整反应顺序的结果使总产率显著提高。所有合成的化合物都测试了它们对HIV‐1逆转录酶的抑制作用，发现目标化合物1具有中等的活性。
Abstract 1‐(Alkyl)‐5‐dimethylamino‐6‐phenethyl uracils (1) and (2) are analogs of MKC‐442, which is a very potent inhibitor of HIV‐1 reverse transcriptase. The target compound 1 was synthesized by the first approach, from the corresponding 1,3‐dibenzyl‐5‐(dimethylamino)‐6‐phenethylpyrimidine‐2,4(1H,3H)‐dione (7), which was synthesized in four steps from 6‐methyluracil (3) by nitration, benzylation, reduction, and methylation of the amino group. Compound 7 was then debenzylated to give the complete deprotected compound 8 with very low yield. To improve the yield, another pathway was developed for introducing the ethoxymethyl group at N‐1 of the uracil ring first. The result of adjusting reaction sequences increased the overall yield dramatically. All synthesized compounds were tested for their inhibition of HIV‐1 reverse transcriptase, and moderate activity was found for target compound 1.