Novel glucocorticoid antedrugs possessing a C16,17-fused γ-lactone ring
Novel glucocorticoid antedrugs possessing a C16,17-fused γ-lactone ring
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DOI：
10.1039/a908358h
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Williamson, C
中科院分区：
文献类型：
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作者：
Biggadike, K;Lynn, SM;Williamson, C
合成了一系列融合在9α-氟-11β-羟基-3-氧代雄烷-1，4-二烯核团16β，17β位置的新型γ-丁内酮类化合物，并在16α，17α位置具有氧取代基，作为糖皮质激素激动剂。这些化合物还被测试了它们在人体血浆中的不稳定性。内酯5在血浆中能迅速被水解，而衍生物18匕首是一种有效的糖皮质激素激动剂，但在血浆中稳定。化合物18的C21S非对映异构体的结构经X-射线衍射法确证。
A series of novel gamma-butyrolactones fused at the 16 beta,17 beta position of the 9 alpha-fluoro-11 beta-hydroxy-3-oxoandrosta-1,4-diene nucleus and possessing oxygen substituents at 16 alpha,17 alpha positions were prepared and tested as glucocorticoid agonists. The compounds were also tested for their lability in human plasma. Lactone 5 was found to be rapidly hydrolysed in plasma, whereas derivative 18 dagger was found to be a potent glucocorticoid agonist, but was stable in plasma. The structure of the C21S diastereoisomer of compound 18 was confirmed by an X-ray diffraction study.