Citation: 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 shu

Novel Ester Derivatives of Lithocolic Acid-3-oxime and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B

a.
College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019
b.
Analysis & Testing Center, Nantong University, Nantong 226019

Corresponding author: Shi Yujun, ntushyj@163.com
Received Date: 14 November 2018
Revised Date: 8 January 2019
Available Online: 8 July 2019

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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).
- PTP1B Inhibitor,
- TCPTP,
- lithocolic acid-3-oxime,
- Synthesis
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1.
沈阳化工大学材料科学与工程学院沈阳 110142