A Lead Compound for the Development of ABA 8′-Hydroxylase Inhibitors.
A Lead Compound for the Development of ABA 8′-Hydroxylase Inhibitors.
复制标题
用于开发 ABA 8-羟化酶抑制剂的先导化合物。
DOI：
10.1002/chin.200609233
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Y. Todoroki
中科院分区：
文献类型：
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作者：
K. Ueno;Hidetaka Yoneyama;S. Saito;M. Mizutani;K. Sakata;N. Hirai;Y. Todoroki
设计并合成了（1′S*，2 ′S*）-（±）-6-Nor-2′，3 ′-dihydro-4′-deoxo-ABA（2），作为开发阿坝8′-羟化酶抑制剂的候选先导化合物。该化合物是该酶的一种有效的竞争性抑制剂，其KI值为0.40μM，但不显示阿坝活性。然而，化合物2也作为酶底物发挥作用，使其成为短暂的抑制剂。合成了2（4）的8′-二氟代衍生物作为长效替代物。化合物4抑制阿坝的8′-羟基化，但抑制效果与化合物2相当。这些结果表明，化合物2是未来设计和开发理想的阿坝8′-羟化酶抑制剂的有用先导化合物。
(1′S*,2′S*)-(±)-6-Nor-2′,3′-dihydro-4′-deoxo-ABA (2) was designed and synthesized as a candidate lead compound for developing a potent and specific inhibitor of ABA 8′-hydroxylase. This compound acted as an effective competitive inhibitor of the enzyme, with a KIvalue of 0.40μM, without exhibiting ABA activity. However, compound 2 also functioned as an enzyme substrate, making it a short-lived inhibitor. The 8′-difluorinated derivative of 2 (4) was synthesized as a long-lasting alternative. Compound 4 resisted 8′-hydroxylation, but inhibited ABA 8′-hydroxylation as effectively as 2. These results suggest that compound 2 is a useful lead compound for the future design and development of an ideal ABA 8′-hydroxylase inhibitor.