Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B

doi:10.6023/cjoc201605018

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (11): 2670-2676.DOI: 10.6023/cjoc201605018 Previous Articles Next Articles

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石胆酸类似物的设计、合成及其蛋白酪氨酸磷酸酯酶1B抑制活性

何海兵^a, 戴红^a, 高立信^b, 张海军^a, 邹政^a, 杨帆^c, 李佳^b, 石玉军^a

a 南通大学化学化工学院南通 226019;
b 中国科学院上海药物研究所国家新药筛选中心上海 201203;
c 华东师范大学化学与分子工程学院上海分子治疗与新药创制工程技术中心上海 200062

收稿日期:2016-05-12 修回日期:2016-05-27 发布日期:2016-07-13
通讯作者: 杨帆, 石玉军 E-mail:fyang@chem.ecnu.edu.cn;shyj123123@163.com
基金资助:
江苏省自然科学基金青年（No.BK20140425）及南通大学引进人才科研启动费（No.03080694）资助项目.

Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B

He Haibing^a, Dai Hong^a, Gao Lixin^b, Zhang Haijun^a, Zou Zhenga^a, Yang Fan^c, Li Jia^b, Shi Yujun^a

a College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019;
b National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;
c Shanghai Engineering Institute of Molecular Therapy and Medicinal Development(MTDD), School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062

Received:2016-05-12 Revised:2016-05-27 Published:2016-07-13
Supported by:
Project supported by the Science Fund for Young Scholar of Jiangsu Province (No.BK20140425) and the Initiating Fund for Introduced Talents of Nantong University (No.03080694).

1. Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B.PDF(1134KB)

Abstract

Protein tyrosine phosphatase-1B (PTP1B), a negative regulatory factor of insulin signaling, is recognized as a potent target for the therapy of diabetes. Aimed to provide new scaffold to the development of PTP1B inhibitors and disclose the relationship between configurations of certain positions (3, 4, 5, 6 and 23-position) on the steroidal skeleton and inhibitory activities against PTP1B, a class of lithocholic acid (LCA) mimics were designed and synthesized. In vitro bioassay against PTP1B showed that 3β-hydroxy-4-ene-cholanic acid (17) and 4,4-dimethyl-3β-hydroxy-5-ene-cholanic acid (19) had activities higher than LCA, reaching (8.50±1.21) and (6.27±1.03) μmol·L^-1, respectively. Docking analysis of compounds 17 and 19 illuminated the binding modes to PTP1B. This study provided compounds with new scaffold and valuable structure-activity-relationship (SAR) information for the further study of PTP1B inhibitors.

Key words: PTP1B inhibitor, steroid, lithocholic acid mimics, synthesis

Cite this article

He Haibing, Dai Hong, Gao Lixin, Zhang Haijun, Zou Zhenga, Yang Fan, Li Jia, Shi Yujun. Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B[J]. Chin. J. Org. Chem., 2016, 36(11): 2670-2676.

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[1] Hu, F. B. Diabetes Care 2011, 34, 1249.
[2] Herman, G. A.; Stevens, C.; Van Dyck, K.; Bergman, A.; Yi, B.; De Smet, M.; Snyder, K.; Hilliard, D.; Tanen, M.; Tanaka, W.; Wang, A. Q.; Zeng, W.; Musson, D.; Winchell, G.; Davies, M. J.; Ramael, S.; Gottesdiener, K. M.; Wagner, J. A. Clin. Pharmacol. Ther. 2005, 78, 675.
[3] Augeri, D. J.; Robl, J. A.; Betebenner, D. A.; Magnin, D. R.; Khanna, A.; Robertson, J. G.; Wang, A.; Simpkins, L. M.; Taunk, P.; Huang, Q.; Han, S.-P.; Abboa-Offei, B.; Cap, M.; Xin, L.; Tao, L.; Tozzo, E.; Welzel, G. E.; Egan, D. M.; Marcinkeviciene, J.; Chang, S. Y.; Biller, S. A.; Kirby, M. S.; Parker, R. A.; Hamann, L. G. J. Med. Chem. 2005, 48, 5025.
[4] Degn, K. B.; Juhl, C. B.; Sturis, J.; Jakobsen, G.; Brock, B.; Chandramouli, V.; Rungby, J.; Landau, B. R.; Schmitz, O. Diabetes 2004, 53, 1187.
[5] Nunez, D. J.; Bush, M. A.; Collins, D. A.; McMullen, S. L.; Gillmor, D.; Apseloff, G.; Atiee, G.; Corsino, L.; Morrow, L.; Feldman, P. L. PLoS One 2014, 9, 1.
[6] White, M. F.; Kahn, C. R. J. Biol. Chem. 1996, 269, 1.
[7] Kenner, K. A.; Anyanwu, E.; Olefsky, J. M. J. Biol. Chem. 1996, 271, 19810.
[8] Walchli, S.; Curchod, M. L.; Gobert, R. P. J. Biol. Chem. 2000, 275, 9792.
[9] Sun, L.-P.; Ma, W.-P.; Gao, L.-X.; Yang, L.-L.; Quan, Y.-C.; Li, J.; Piao, H.-R. J. Enzyme Inhib. Med. Chem. 2013, 28, 1199.
[10] Sun, L.-P.; Jiang, Z.; Gao, L.-X.; Li, Y.-Z.; Sun, L.-Y.; Li, J.; Piao, H.-R. Chin. J. Org. Chem. 2012, 32, 2108 (in Chinese). (孙良鹏, 姜哲, 高立信, 李英哲, 孙立云, 李佳, 朴虎日, 有机化学, 2012, 32, 2108.)
[11] Chen, Y.-T.; Tang, C.-L.; Ma, W.-P.; Gao, L.-X.; Wei, Y.; Zhang, W.; Li, J.-Y.; Li, J.; Nan, F.-J. Eur. J. Med. Chem. 2013, 69, 399.
[12] Zhou, X.-W.; Tang, Y.-T.; Sang, F.; Zhang, X.-L.; Li, L.-X.; Zhou, H.-G.; Liu, W.; Dai, Y.-J. Chin. J. Org. Chem. 2015, 35, 1363 (in Chinese). (周晓伟, 唐延婷, 桑锋, 张秀利, 李立新, 周红刚, 刘伟, 戴玉洁, 有机化学, 2015, 35, 1363.)
[13] Mitchell F. R. Pharmacol. Biochem. Behav. 2010, 97, 138.
[14] Qin, Z.-H.; Pandey, N. R.; Zhou, X. Biochem. Biophys. Res. Commun. 2015, 458, 21.
[15] Zhang, W.; Hong, D.; Zhou, Y.; Zhang, Y.; Shen, Q.; Li, J.-Y.; Hu, L.-H.; Li, J. Biochim. Biophys. Acta, Gen. Subj. 2006, 1760, 1505.
[16] Qiu, W.-W.; Shen, Q.; Yang, F.; Wang, B.; Zou, H.; Li, J.-Y.; Li, J.; Tang, J. Bioorg. Med. Chem. Lett. 2009, 19, 6618.
[17] Li, H.; Zou, H.; Gao, L.-X.; Liu, T.; Yang, F., Li, J.-Y.; Li, J.; Qiu, W.-W.; Tang, J. Heterocycles 2012, 85, 1117.
[18] He, H.-B.; Gao, L.-X.; Deng, Q.-F.; Ma, W.-P.; Tang, C.-L.; Qiu, W.-W.; Tang, J.; Li, J.-Y.; Li, J.; Yang, F. Bioorg. Med. Chem. Lett. 2012, 22, 7237.
[19] Miro, P.; Vaya, I.; Sastre, G.; Jimenez, M. C.; Marin, M. L.; Miranda, M. A. Chem. Commun. 2016, 52, 713.
[20] Iida, T.; Kakiyama, G.; Hibiya, Y.; Miyata, S.; Inoue, T.; Ohno, K.; Goto, T.; Mano, N.; Goto, J.; Nambara, T.; Hofmann, A. F. Steroids 2006, 71, 18.
[21] Xia, P.; Yang, Z.-Y.; Xia, Y.; Zheng, Y.-Q.; Cosentino, L. M.; Lee, K.-H. Bioorg. Med. Chem. 1999, 7, 1907.
[22] Renata, H.; Zhou, Q.; Dünstl, G.; Felding, J.; Merchant, R. R.; Yeh, C.-H.; Baran, P. S. J. Am. Chem. Soc. 2015, 137, 1330.
[23] Upasani, R. B.; Harrison, B. L.; Askew, B. C. Jr.; Dodart, J.-C.; Salituro, F. G.; Robichaud, A. J. WO 2013036835, 2013[Chem. Abstr. 2013, 158, 447158].
[24] Foot, J. S.; Phillis, A. T.; Sharp, P. P.; Willis, A. C.; Banwell, M. G. Tetrahedron Lett. 2006, 47, 6817.
[25] Puius, Y. A.; Zhao, Y.; Sullivan, M.; Lawrence, D. S.; Almo, S. C.; Zhang, Z.-Y. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 13420.
[26] Shi, L.; Yu, H. P.; Zhou, Y. Y.; Du, J. Q.; Shen, Q.; Li, J. Y.; Li, J. Acta Pharmacol. Sin. 2008, 29, 278.

石胆酸类似物的设计、合成及其蛋白酪氨酸磷酸酯酶1B抑制活性

Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B

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