We previously reported 4-(3-((6-bromonaphthalen-2-yl)oxy)-2-hydroxypropyl)-N,N-dimethylpiperazine-1-sulfonamide (1) as a novel heat shock protein 90 inhibitor with moderate activity. In our ongoing efforts for the discovery of Hsp90 modulators we undertake structural investigations on 1. Series of the titled compound were designed, synthesized and evaluated. We have found that compounds with a hydroxyl group at C-4 of the aryl ring on the piperazine moiety possess Hsp90 inhibition properties. Compound 6f with improved activity could be further developed and optimized as Hsp90 inhibitor.

中文翻译：

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Hsp90抑制剂4-（2-羟丙基）哌嗪-1-基）衍生物的合成与评价

我们先前报道了4-（3-（（6-溴萘-2-基）氧基）-2-羟丙基）-N，N-二甲基哌嗪-1-磺酰胺（1）作为具有中等活性的新型热休克蛋白90抑制剂。在我们不断发现Hsp90调节剂的努力中，我们对1进行了结构研究。设计，合成和评估了一系列标题化合物。我们发现在哌嗪部分的芳基环的C-4具有羟基的化合物具有Hsp90抑制特性。具有改善的活性的化合物6f可以进一步开发和优化为Hsp90抑制剂。