Chinese Journal of Organic Chemistry >
Synthesis and PTP1B Inhibitory Activity of (E)-1-Substitutedphenyl-3-(4-((E)-(2-(4-phenylthiazol-2-yl)hydrazono)methyl)phenyl)-prop-2-en-1-ones
Received date: 2012-12-10
Revised date: 2013-02-20
Online published: 2013-03-01
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 81160381, 81125023).
Protein tyrosine phosphatase 1B (PTP1B) has recently been identified as new drug target for type II diabetes and obesity due to that it is a negative regulator of the insulin and leptin-signaling pathway. In order to find new nonphosphonate-based pTyr mimetics, a series of novel (E)-1-phenyl-3-(4-((E)-(2-(4-phenyl-thiazol-2-yl)hydrazono)methyl)phenyl)-prop-2-en-1-one (4a～4n) were designed, synthesized, and evaluated for their PTP1B inhibitory activity. The results demonstrated that all compounds presented potent inhibitory activities against PTP1B, among which compound 4h exhibited most potent with IC50 value of (2.57±0.50) μmol·L-1.
Key words： PTP1B inhibitor; chalcone; carboxaldehyde hydrazone; thiazole
Sun Liangpeng , Jiang Zhe , Gao Lixin , Liu Xiaofang , Quan Yingchun , Zheng Guanghao , Li Jia , Piao Huri . Synthesis and PTP1B Inhibitory Activity of (E)-1-Substitutedphenyl-3-(4-((E)-(2-(4-phenylthiazol-2-yl)hydrazono)methyl)phenyl)-prop-2-en-1-ones[J]. Chinese Journal of Organic Chemistry, 2013 , 33(07) : 1496 -1502 . DOI: 10.6023/cjoc201212012
[1] (a) Neel, B. G.; Tonks, N. K. Curr. Opin. Cell Biol. 1997, 9, 193. (b) Hunter, T. Cell 2000, 100, 113. (c) Tonks, N. K.; Neel, B. G. Curr. Opin. Cell Biol. 2001, 13, 182.
[2] (a) Lee, S.; Wang, Q. Med. Res. Rev. 2007, 27, 553. (b) Combs, A. P. J. Med. Chem. 2010, 53, 2333. (c) Sparks, R. B.; Polam, P.; Zhu, W.; Crawley, M. L.; Takvorian, A.; McLaughlin, E.; Wei, M.; Ala, P. J.; Gonneville, L.; Taylor, N.; Li, Y.; Wynn, R.; Burn, T. C.; Liu, P. C. C.; Combs, A. P. Bioorg. Med. Chem. Lett. 2007, 17, 736. (d) Black, E.; Breed, J.; Breeze, A. L.; Embrey, K.; Garcia, R.; Gero, T. W.; Godfrey, L.; Kenny, P. W.; Morley, A. D.; Minshull, C. A. Bioorg. Med. Chem. Lett. 2005, 15, 2503. (e) Stuible, M.; Zhao, L.; Aubry, I.; Schmidt-Arras, D.; Bohmer, F.-D.; Li, C.-J.; Tremblay, M. L. ChemBioChem 2007, 8, 179.
[3] Zhang, Z.-Y. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 209.
[4] Combs, A. P.; Yue, E. W.; Bower, M.; Ala, P. J.; Wayland, B.; Douty, B.; Takvorian, A.; Polam, P.; Wasserman, Z.; Zhu, W.; Crawley, M. L.; Pruitt, J.; Sparks, R.; Glass, B.; Modi, D.; McLaughlin, E.; Bostrom, L.; Li, M.; Galya, L.; Blom, K.; Hillman, M.; Gonneville, L.; Reid, B. G.; Wei, M.; Becker-Pasha, M.; Klabe, R.; Huber, R.; Li, Y.; Hollis, G.; Burn, T. C.; Wynn, R.; Liu, P.; Metcalf, B. J. Med. Chem. 2005, 48, 6544.
[5] Combs, A. P.; Zhu, W.; Crawley, M. L.; Glass, B.; Polam, P.; Sparks, R. B.; Modi, D.; Takvorian, A.; McLaughlin, E.; Yue, E. W.; Wasserman, Z.; Bower, M.; Wei, M.; Rupar, M.; Ala, P. J.; Reid, B. M.; Ellis, D.; Gonneville, L.; Emm, T.; Taylor, N.; Yeleswaram, S.; Li, Y.; Wynn, R.; Burn, T. C.; Hollis, G.; Liu, P. C. C.; Metcalf, B. J. Med. Chem. 2006, 49, 3774.
[6] Maccari, R.; Paoli, P.; Ottanà, R.; Jacomelli, M.; Ciurleo, R.; Manao, G.; Steindl, T.; Langer, T.; Vigorita, M. G.; Camici, G. Bioorg. Med. Chem. 2007, 15, 5137.
[7] Vogel, S.; Ohmayer, S.; Brunner, G.; Heilmann, J. Bioorg. Med. Chem. 2008, 16, 4286.
[8] Sun, L. P.; Gao, L. X.; Ma, W. P.; Nan, F. J.; Li, J.; Piao, H. R. Chem. Biol. Drug Des. 2012, 80, 584.
[9] 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.)
[10] (a) Holla, B. S.; Malini, K. V.; Rao, B. S.; Sarojini, B. K.; Kumari, N. S. Eur. J. Med. Chem. 2003, 38, 313. (b) Pandeya, S. N.; Sriram, D.; Nath, G.; DeClerq, E. Eur. J. Pharm. Sci. 1999, 9, 25. (c) Ramla, M. M.; Omar, M. A.; El-Khamry, A. M.; El-Diwan, H. I. Bioorg. Med. Chem. 2006, 14, 7324. (d) Dawood, K. M.; Gawad, H. A.; Rageb, E. A.; Ellithey, M.; Mohamed, H. A. Bioorg. Med. Chem. 2006, 14, 3672. (e) Roberts, J. C.; Nagasawa, H. T.; Zera, R. T.; Fricke, R. F.; Goon, D. J. J. Med. Chem. 1987, 30, 1891. (f) Sakashita, H.; Akahoshi, F.; Kitajima, H.; Tsutsumiuchi, R.; Hayashi, Y. Bioorg. Med. Chem. 2006, 14, 3662.
[11] (a) Lanthier, C. M.; Pamiak, M. A.; Dmitrienko, G. I. Bioorg. Med. Chem. Lett. 1997, 7, 1557. (b) Ling, A.; Plewe, M.; Gonzalez, J.; Madsen, P.; Sams, C. K.; Lau, J.; Gregor, V.; Murphy, D.; Teston, K.; Kuki, A.; Shi, S.; Truesdale, L.; Kiel, D.; May, J.; Lakis, J.; Anderes, K.; Iatsimirskaia, E.; Sidelmann, U. G.; Knudsen, L. B.; Brand, C. L.; Polinsky, A. Bioorg. Med. Chem. Lett. 2002, 12, 663. (c) Horiuchi, T.; Chiba, J.; Uoto, K.; Soga, T. Bioorg. Med. Chem. Lett. 2009, 19, 305.
[12] Meng, F. L.; Zheng, C. J.; Li, Y. J.; Sun, L. P.; Liu, X. K.; Zhang, T. Y.; Piao, H. R. Chin. J. Org. Chem. 2012, 32, 183 (in Chinese). (孟凡领, 郑昌吉, 李因晶, 孙良鹏, 刘学坤, 张天一, 朴虎日, 有机化学, 2012, 32, 183.)
[13] Sun, Y. D.; Liu, F. M.; Xie, Z. F.; Chen, J. S. Chin. J. Org. Chem. 2005, 25, 449 (in Chinese). (孙亚栋, 刘方明, 解正峰, 陈家胜, 有机化学, 2005, 25, 449.)
[14] Liu, W. W.; Zhao, Y. Q.; Wang, Q. Q.; Li, N.; Tang, L. J.; Zeng, Y. X. Chin. J. Org. Chem. 2008, 28, 907 (in Chinese). (刘玮炜, 赵跃强, 王钦琪, 李娜, 唐丽娟, 曾艳霞, 有机化学, 2008, 28, 907.)
[15] Chimenti, F.; Bolasco, A.; Secci, D.; Chimenti, P.; Granese, A.; Carradori, S.; Yáñez, M.; Orallo, F.; Ortuso, F.; Alcaro, S. Bioorg. Med. Chem. 2010, 18, 5715.
[16] (a) Shi, L.; Yu, H. P.; Zhou, Y. Y.; Du, J. Q.; Shen, Q.; Li, J. Y.; Li, J. Acta Pharmacol. Sin. 2008, 29, 278. (b) Zhang, W.; Hong, D.; Zhou, Y. Y.; Zhang, Y. N.; Shen, Q.; Li, J. Y.; Hu, L. H.; Li, J. Biochim. Biophys. Acta 2006, 1760, 1505.
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