Chinese Journal of Organic Chemistry >
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
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
Shi shuzhi , Liang zhipeng , Sun jiangyong , Shi Yujun . Novel Ester Derivatives of Lithocolic Acid-3-oxime and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B[J]. Chinese Journal of Organic Chemistry, 2019 , 39(7) : 2106 -2116 . DOI: 10.6023/cjoc201811020
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