新型石胆酸-3-肟酯衍生物及其蛋白酪氨酸磷酸酯酶1B抑制活性
收稿日期: 2018-11-14
修回日期: 2019-01-08
网络出版日期: 2019-03-08
Novel Ester Derivatives of Lithocolic Acid-3-oxime and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B
Received date: 2018-11-14
Revised date: 2019-01-08
Online published: 2019-03-08
侍术智 , 梁志鹏 , 孙建勇 , 石玉军 . 新型石胆酸-3-肟酯衍生物及其蛋白酪氨酸磷酸酯酶1B抑制活性[J]. 有机化学, 2019 , 39(7) : 2106 -2116 . DOI: 10.6023/cjoc201811020
Protein tyrosine phosphatase-1B (PTP1B) is recognized as a potent target for the therapy of diabetes. Lithocolic acid (LCA), a kind of endogenic steroid, was reported as a moderate PTP1B inhibitor. In this paper, 3-hydroxyl of LCA was oxidized, followed by oximating and splicing with cinnamoyl to afford a novel series of derivatives, which were characterized by 1H NMR, 13C NMR and HRMS spectra. The results of bioassays exhibited that most of the titled compounds were active to PTP1B. Among them, compound 12b, the most potent one, has an IC50 of 0.79 µmol•L-1, about 15-fold more potent than the lead compound. Besides, it also has a selectivity of about 4-fold over T-cell protein tyrosine phosphatase (TCPTP).
Key words： PTP1B Inhibitor; TCPTP; lithocolic acid-3-oxime; Synthesis
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