Tanaka H, Walker R T, Hopkins A L, Ren J, Jones E Y, Fujimoto K, Hayashi M, Miyasaka T, Baba M, Stammers D K, Stuart D I
School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Antivir Chem Chemother. 1998 Jul;9(4):325-32.
Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.
基于MKC-442/人类免疫缺陷病毒1型逆转录酶（HIV-1 RT）复合物的X射线晶体学分析，设计了将N1-取代基替换为ω-官能化烷基的类似物，以提高对该酶的亲和力。这些化合物的合成从MKC-442开始，通过一系列反应（N3保护、N1-乙氧基甲基的去除、烷基化和N3去保护）进行。对这些化合物的抗HIV活性进行了评估。根据与该酶可能的相互作用讨论了构效关系。
