Glucosides with cyclic diarylpolynoid as novel C-aryl glucoside SGLT2 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 12, 2011, Pages 3759-3763

  Kang, Suk Youn ^a   Kim, Min Ju ^a   Lee, Jun Sung ^a   Lee, Jinhwa ^a  

^a Green Cross Company   (South Korea)

Author keywords

Dapagliflozin; Diabetes; Diarylpolynoid; Glucoside; SGLT

Indexed keywords

ANTIDIABETIC AGENT; BROMIDE; DAPAGLIFLOZIN; GLUCOSIDE; PALLADIUM; SODIUM GLUCOSE COTRANSPORTER 2;

ANIMAL CELL; ARTICLE; CATALYSIS; CROSS COUPLING REACTION; DRUG DESIGN; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; PROTEIN MOTIF; RING CLOSING METATHESIS; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION;

CYCLIZATION; DRUG DESIGN; GLUCOSIDES; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; SODIUM-GLUCOSE TRANSPORTER 2; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79957841180     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.04.063     Document Type: Article

References (32)

1. International Diabetes Federation International Diabetes Federation. Diabetes Atlas, 4th ed.; International Diabetes Federation: Montreal, Canada, 2009.
2. Dwarakanathan, A. J. Insur. Med. 2006, 38, 20-30.
3. Mackenzie, B.; Loo, D. D. J. Biol. Chem. 1996, 20, 32678-32683.
4. Moe, O. W.; Berry, C. A.; Rector, F. C. In The Kidney; Brenner, B. M., Rector, F. C., Eds., 5th ed.; WB Saunders Co.: Philadelphia, 2000; pp 375-415.
5. Ellsworth, B. A.; Meng, W.; Patel, M.; Girotra, R. N.; Wu, G.; Sher, P.; Hagan, D.; Obermeier, M.; Humphreys, W. G.; Robertson, J. G.; Wang, A.; Han, S.; Waldron, T.; Morgan, N. N.; Whaley, J. M.; Washburn, W. N. Bioorg. Med. Chem. Lett. 2008, 18, 4770-4773.
6. Meng, W.; Ellsworth, B. A.; Nirschl, A. A.; McCann, P. J.; Patel, M.; Girotra, R. N.; Wu, G.; Sher, P. M.; Morrison, E. P.; Biller, A. A.; Zahler, R.; Deshpande, P. P.; Pullockaran, A.; Hagan, D. L.; Morgan, N.; Taylor, J. R.; Obermeier, M. T.; Humphreys, W. G.; Khanna, A.; Discenza, L.; Robertson, J. G.; Wang, A.; Han, S.; Wetterau, J. R.; Janovitz, E. B.; Flint, O. P.; Whaley, J. M.; Washburn, W. N. J. Med. Chem. 2008, 51, 1145-1149.
7. Washburn, W. N. J. Med. Chem. 2009, 52, 1785-1794.
8. According to a report from Business Wire on June 26, 2010, dapagliflozin as add on therapy to insulin demonstrated improved glycemic control in patients with type 2 diabetes inadequately controlled with insulin.
9. Nomura, S.; Sakamaki, S.; Hongu, M.; Kawanshi, E.; Koga, Y.; Sakamoto, T.; Yamamoto, Y.; Ueta, K.; Kimata, H.; Nakayama, K.; Tsuda-Tsukimoto, M. J. Med. Chem. 2010, 53, 6355-6360.
10. (a) Boehringer Ingelheim Pharmaceuticals, www.clinicaltrials.gov, 2010, NCT01164501.;
11. (b) Lexicon Pharmaceuticals, www.clinicaltrials.gov, 2009, NCT00962065.;
12. (c) Astellas Pharma Inc., www.clinicaltrials.gov, 2010, NCT01135433.;
13. (d) Mascitti, V. Presented at the 240th American Chemical Society National Meeting and Exposition, Boston, MA, August 22-26, 2010; Medi-151.
14. (a) Lee, J.; Lee, S.-H.; Seo, H. J.; Son, E.-J.; Lee, S. H.; Jung, M. E.; Lee, M.; Han, H.- K.; Kim, J.; Kang, J.; Lee, J. Bioorg. Med. Chem. 2010, 18, 2178;
15. (b) Kim, M. J.; Lee, J.; Kang, S. Y.; Lee, S.-H.; Son, E.-J.; Jung, M. E.; Lee, S. H.; Song, K.-S.; Lee, M.; Han, H.-K.; Kim, J.; Lee, J. Bioorg. Med. Chem. Lett. 2010, 20, 3420;
16. (c) Kang, S. Y.; Song, K.-S.; Lee, J.; Lee, S.-H.; Lee, J. Bioorg. Med. Chem. 2010, 18, 6069;
17. (d) Lee, J.; Kim, J. Y.; Choi, J.; Lee, S.-H.; Kim, J.; Lee, J. Bioorg. Med. Chem. Lett. 2010, 20, 7046;
18. (e) Park, E.-J.; Kong, Y.; Lee, J. S.; Lee, S.-H.; Lee, J. Bioorg. Med. Chem. Lett. 2011, 21, 742;
19. (f) Song, K.-S.; Lee, S. H.; Kim, M. J.; Seo, H. J.; Lee, J.; Lee, S.-H.; Jung, M. E.; Son, E.-J.; Lee, M.; Kim, J.; Lee, J. ACS Med. Chem. Lett. 2011, 2, 182-187.
20. Morita, H.; Deguchi, J.; Motegi, Y.; Sato, S.; Aoyama, C.; Takeo, J.; Shiro, M.; Hirasawa, Y. Bioorg. Med. Chem. Lett. 2010, 20, 1070.
21. + 429.
22. Krasovsky, A.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 3333.
23. Ellsworth, B. A.; Doyle, A. G.; Patel, M.; Caceres-Cortes, J.; Meng, W.; Deshpande, P. P.; Pullockaran, A.; Washburn, W. N. Tetrahedron: Asymmetry 2003, 14, 3242.
24. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
25. Huo, S. Org. Lett. 2003, 4, 423.
26. Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
27. 14C-AMG) uptake assay.
28. 21,22
29. Han, S.; Hagan, D. L.; Taylor, J. R.; Xin, L.; Meng, W.; Biller, S. A.; Wetterau, J. R.; Washburn, W. N.; Whaley, J. M. Diabetes 2008, 57, 1723.
30. Katsuno, K.; Fujimori, Y.; Takemura, Y.; Hiratochi, M.; Itoh, F.; Komatsu, Y.; Fujikura, H.; Isaji, M. J. Pharmacol. Exp. Ther. 2007, 320, 323.
31. Initially, we expected that the novel series of designed compounds would be able to provide potent inhibition against hSGLT2, showing synergistic effect by macrocyclization. Although these current compounds appear to show only moderate inhibition activity, the authors think that this series hinted valuable possibilities about combination of two different structures. As a matter of fact, we have identified much more potent series of macrocycles as SGLT2 inhibitors in house by extending conceptually from this series.
32. In this communication, SGLT2 inhibiton data were obtained by single determinations. Whenever we evaluate our new compounds against hSGLT2, dapagliflozin was also included as a reference compound. The SGLT2 inhibition for dapagliflozin has shown a certain number in the close range in each different assay. Thus, we believe that all SAR discussions in the manuscript are scientifically valid.