A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 μM. The structure–activity relationship (SAR) of this series is reported here.

中文翻译：

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发现5-取代的2-氨基-4-氯-8-（（4-甲氧基-3,5-二甲基吡啶-2-基）甲基）-7,8-二氢蝶呤-6（5 H）-s为强和选择性Hsp90抑制剂

一系列新的化合物，5-取代的2-氨基-4-氯-8-（（（4-甲氧基-3,5-二甲基吡啶-2-基）甲基）-7,8-二氢蝶呤-6（5 H）-已经设计并鉴定出它们是Hsp90的有效和选择性抑制剂。这些化合物在基于细胞的测定中显示出对Hsp90调控的Her2降解和人类肿瘤细胞系生长的纳摩尔效价。这些化合物对Hsp90的高选择性是显而易见的，因为它们在10μM时不会抑制34种激酶。该系列的结构-活性关系（SAR）报告在这里。