Citation: Tian He, Wu Jingwei, Liu Yuqiang, Xie Yafei, Wang Jianwu, Zhao Guilong. Efficient Synthetic Approaches to Uric Acid Transporter 1 Inhibitors Bearing Alkoxyl Group-Substituted Triazoles[J]. Chinese Journal of Organic Chemistry, ;2017, 37(7): 1748-1756. doi: 10.6023/cjoc201701038 shu

Efficient Synthetic Approaches to Uric Acid Transporter 1 Inhibitors Bearing Alkoxyl Group-Substituted Triazoles

Tian He ^a ,
Wu Jingwei ^b ,
Liu Yuqiang ^b ,
Xie Yafei ^b ,
Wang Jianwu ^a,, ,
Zhao Guilong ^b,,

a.
School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100
b.
Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193

Corresponding author: Wang Jianwu, jwwang@sdu.edu.cn Zhao Guilong, zhao_guilong@126.com
Received Date: 19 January 2017
Revised Date: 22 February 2017
Available Online: 17 July 2017
Fund Project: Key Projects of Tianjin Science and Technology Support Plan 16YFZCSY00910Project supported by the Key Projects of Tianjin Science and Technology Support Plan (No.16YFZCSY00910) and the Natural Science Foundation of Shandong Province (No.ZR2015BM028)the Natural Science Foundation of Shandong Province ZR2015BM028

Figures(3)

Uric acid transporter 1 (URAT1) inhibitors bearing alkoxy group-substituted triazoles 3-(4-(4-cyclopropylnaphthalen-1-yl)-5-methoxy-4H-1, 2, 4-triazol-3-yl)propanoic acid (1a) and 3-(4-(4-cyclopropylnaphthalen-1-yl)-5-ethoxy-4H-1, 2, 4-triazol-3-yl)propanoic acid (1b) are structurally interesting lead compounds in drug design. The current synthetic approach to them suffers from quite low overall yields (3.3% and 3.0% for 1a and 1b, respectively). In order to explore the structure-activity relationship (SAR) of 1a and 1b, synthetic approach with higher overall yield is urgently needed. In the present study, two efficient synthetic approaches to 1a and 1b were developed (approaches A and B), with CuCl-catalyzed nucleophilic aromatic substitution (S_NAr) reaction of bromotriazole with sodium alkoxides and S_NAr reaction of methylsulfonyltriazole with sodium alkoxides as key steps, and the conditions for important steps were fully optimized. The two synthetic approaches are characterized by dramatically higher yields, and not only valuable to the further SAR exploration of 1a and 1b but also very helpful to the synthesis of heterocycles with alkoxyl groups.
- URAT1 inhibitor,
- gout,
- hyperuricemia,
- synthetic route,
- S_NAr,
- CuCl catalysis
1. [1]
  Richette, P.; Bardin T. Lancet 2010, 375, 318. doi: 10.1016/S0140-6736(09)60883-7
2. [2]
  Pillinger, M. H.; Rosenthal, P.; Abeles, A. M. Bull. NYU Hosp. Jt. Dis. 2007, 65, 215.
3. [3]
  Punzi, L.; Scanu, A.; Ramonda, R.; Oliviero, F. Autoimmun. Rev. 2012, 12, 66. doi: 10.1016/j.autrev.2012.07.024
4. [4]
  Choi, H. K.; Mount, D. B.; Reginato, A. M. Ann. Intern. Med. 2005, 143, 499. doi: 10.7326/0003-4819-143-7-200510040-00009
5. [5]
  Miao, Z.; Li, C.; Chen, Y.; Zhao, S.; Wang, Y.; Wang, Z.; Chen, X.; Xu, F.; Wang, F.; Sun, R.; Hu, J.; Song, W.; Yan, S.; Wang, C. J. Rheumatol. 2008, 35, 1859.
6. [6]
  Dubchak, N.; Falasca, G. F. Int. J. Nephrol. Renovasc. Dis. 2010, 3, 145.
7. [7]
  Enomoto, A.; Kimura, H.; Chairoungdua, A.; Shigeta, Y.; Jutabha, P.; Cha, S. H.; Hosoyamada, M.; Takeda, M.; Sekine, T.; Igarashi, T.; Matsuo, H.; Kikuchi, Y.; Oda, T.; Ichida, K.; Hosoya, T.; Shimokata, K.; Niwa, T.; Kanai, Y.; Endou, H. Nature 2002, 417, 447.
8. [8]
  Adams, J. U. Nat. Biotechnol. 2009, 27, 309. doi: 10.1038/nbt0409-309
9. [9]
  Hoy, S. M. Drugs 2016, 76, 509. doi: 10.1007/s40265-016-0550-y
10. [10]
  Miner, J. N.; Tan, P. Ann. Rheum. Dis. 2013, 71, 446.
11. [11]
  Tian, H.; Liu, W.; Zhou, Z.; Shang, Q.; Liu, Y.; Xie, Y.; Liu, C.; Xu, W.; Tang, L.; Wang, J.; Zhao, G. Molecules 2016, 21, 1543. doi: 10.3390/molecules21111543
12. [12]
  Zhao, M.; Li, J.; Mano, E.; Song, Z.; Tschaen, D. M.; Grabowski, E, J. J.; Reider, P. J. J. Org. Chem. 1999, 64, 2564. doi: 10.1021/jo982143y
13. [13]
  Hirata, K.; Kotoku, M.; Seki, N.; Maeba, T.; Maeda, K.; Hirashima, S.; Sakai, T.; Obika, S.; Hori, A.; Hase, Y.; Yamaguchi, T.; Katsuda, Y.; Hata, T.; Miyagawa, N.; Arita, K.; Nomura, Y.; Asahina, K.; Aratsu, Y.; Kamada, M.; Adachi, T.; Noguchi, M.; Doi, S.; Crowe, P.; Bradley, E.; Steensma, R.; Tao, H.; Fenn, M.; Babine, R.; Li, X.; Thacher, S.; Hashimoto, H.; Shiozaki, M. ACS Med. Chem. Lett. 2016, 7, 23. doi: 10.1021/acsmedchemlett.5b00253
14. [14]
  Ragan, J. A.; Makowski, T. W.; Castaldi, M. J.; Hill, P. D. Synthesis 1998, 1599.
15. [15]
  Bonanomi, G.; Braggio, S.; Capelli, A. M.; Checchia, A.; Di Fabio, R.; Marchioro, C.; Tarsi, L.; Tedesco, G.; Terreni, S.; Worby, A.; Heibreder, C.; Micheli, F. ChemMedChem 2010, 5, 705. doi: 10.1002/cmdc.201000026
16. [16]
  Xie, M.; Tang, H.; Zhang, Y.; Guo, Z.; Guo, H.; Qu, G. Chin. J. Org. Chem. 2015, 35, 2589(in Chinese).
17. [17]
  Fu, Y.; Zhao, X.; Hou, B. Chin. J. Org. Chem. 2016, 36, 1184(in Chinese).
18. [18]
  Cai, W.; Liu, W.; Xie, Y.; Wu, J.; Liu, Y.; Liu, C.; Xu, W.; Tang, L.; Wang, J.; Zhao, G. Chem. Res. Chin. Univ. 2017, 33, 49. doi: 10.1007/s40242-017-6351-3
19. [19]
  Reddy, T. R.; Li, C.; Guo, X.; Fischer, P. M.; Dekker, L. V. Bioorg. Med. Chem. 2014, 22, 5378. doi: 10.1016/j.bmc.2014.07.043
20. [20]
  Colanceska-Ragenovic, K.; Dimova, V.; Kakurinov, V.; Gabor, D. M. J. Heterocycl. Chem. 2003, 40, 905. doi: 10.1002/jhet.v40:5
21. [21]
  Kane, J. M.; Staeger, M. A.; Dalton, C. R.; Miller, F. P.; Dudley, M. W.; Ogden, A. M.; Kehne, J. H.; Ketteler, H. J.; McCloskey, T. C.; Senyah, Y.; Chmielewski, P. A.; Miller, J. A. J Med Chem. 1994, 37, 125. doi: 10.1021/jm00027a015
22. [22]
  Ström, P.; Malmquist, J. J. Labelled Compd. Radiopharm. 2008, 51, 419. doi: 10.1002/jlcr.v51:13
23. [23]
  Liu, M.; Shi, D. J. Heterocycl. Chem. 2014, 51, E335. doi: 10.1002/jhet.v51.S1
24. [24]
  Huisgen, R.; Möbius, L.; Szeimies, G. Chem. Ber. 1965, 98, 1138. doi: 10.1002/(ISSN)1099-0682
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