Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus (1)

Journal of Medicinal Chemistry

Volumn 53, Issue 17, 2010, Pages 6355-6360

  Nomura, Sumihiro ^a   Sakamaki, Shigeki ^a   Hongu, Mitsuya ^a   Kawanishi, Eiji ^a   Koga, Yuichi ^a   Sakamoto, Toshiaki ^a   Yamamoto, Yasuo ^a   Ueta, Kiichiro ^a   Kimata, Hirotaka ^a   Nakayama, Keiko ^a   Tsuda Tsukimoto, Minoru ^a  

^a MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 (BETA DEXTRO GLUCOPYRANOSYL) 4 METHYL 3 [5 (4 FLUOROPHENYL) 2 THIENYLMETHYL]BENZENE; ANTIDIABETIC AGENT; CANAGLIFLOZIN; SODIUM GLUCOSE COTRANSPORTER 2; THIOPHENE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; BIOLOGICAL AVAILABILITY; CARBONATES; DIABETES MELLITUS, TYPE 2; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MICE; RATS; RATS, SPRAGUE-DAWLEY; SODIUM-GLUCOSE TRANSPORTER 2; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 77956319973     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100332n     Document Type: Article

References (35)

1. For a prior preliminary communication of this work, see the following: Nomura, S.; Abstract of Papers. The 238th ACS National Meeting, Washington, DC, August 16-20, 2009; American Chemical Society: Washington, DC, 2009; MEDI-151.
2. Lipscombe, L. L.; Hux, J. E. Trends in Diabetes Prevalence, Incidence, and Mortality in Ontario, Canada 1995-2005: A Population-Based Study Lancet 2007, 369, 750-756
3. Wareham, N. J.; Forouhi, N. G. Is There Really an Epidemic of Diabetes? Diabetologia 2005, 48, 1454-1455
4. Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global Prevalence of Diabetes. Estimates for the Year 2000 and Projections for 2030 Diabetes Care 2004, 27, 1047-1053
5. Gershell, L. Type 2 Diabetes Market Nat. Rev. Drug Discovery 2005, 4, 367-368
6. +-Glucose Cotransporters Am. J. Physiol. Renal Physiol. 2001, 280, F10-F18
7. +/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2 J. Biol. Chem. 1996, 271, 32678-32683
8. +/Glucose Cotransporter SGLT2. Delineation of the Major Renal Reabsorptive Mechanism for d -Glucose J. Clin. Invest. 1994, 93, 397-404
9. Deetjen, P.; Baeyer, H. V.; Drexel, H. Renal Handling of d -Glucose and Other Sugars. In Textbook of Nephrology, 3 rd ed; Massry, S. G.; Glassock, R. J., Eds.; Williams & Wilkins Press: Baltimore, MD, 1995; Vol. 1, pp 90-94.
10. +-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4′-Dehydroxyphlorizin Derivatives Substituted on the B Ring J. Med. Chem. 1999, 42, 5311-5324
11. +-Glucose Cotransporters, May Provide a Novel Approach to Treating Diabetes Diabetes 1999, 48, 1794-1800
12. Nishimura, M.; Naito, S. Tissue-Specific mRNA Expression Profiles of Human ATP-Binding Cassette and Solute Carrier Transporter Superfamilies Drug Metab. Pharmacokinet. 2005, 20, 452-477
13. Nomura, S. Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for New Anti-Diabetic Agent Curr. Top. Med. Chem. 2010, 10, 411-418
14. Washburn, W. N. Evolution of Sodium Glucose Co-Transporter 2 Inhibitors as Anti-Diabetic Agents Expert Opin. Ther. Patents 2009, 19, 1485-1499
15. Isaji, M. Sodium-Glucose Cotransporter Inhibitors for Diabetes Curr. Opin. Investig. Drugs 2007, 8, 285-292
16. Handlon, A. L. Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors as Potential Antidiabetic Agents Expert Opin. Ther. Patents 2005, 15, 1531-1540
17. Ellsworth, B.; Washburn, W. N.; Sher, P. M.; Wu, G.; Meng, W. C -Aryl Glucoside SGLT2 Inhibitors and Method. U.S. Patent 6,414,126, 2002
18. Chem. Abstr. 2002, 137, 247879.
19. Ellsworth, B.; Washburn, W. N.; Sher, P. M.; Wu, G.; Meng, W. C -Aryl Glucoside SGLT2 Inhibitors. PCT Int. Appl. WO 01/27128, 2001
20. Chem. Abstr. 2001, 134, 281069.
21. Deshpande, P. P.; Ellsworth, B. A.; Singh, J.; Denzel, T. W.; Lai, C.; Crispino, G.; Randazzo, M. E.; Gougoutas, J. Z. Methods of Producing C -Aryl Glucoside SGLT2 Inhibitors. U.S. Patent 7,375,213, 2008
22. Chem. Abstr. 2004, 141, 89317.
23. 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, S. 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. Discovery of Dapagliflozin: A Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes J. Med. Chem. 2008, 51, 1145-1149
24. Deshpande, P. P.; Ellsworth, B. A.; Singh, J.; Lai, C.; Crispino, G.; Randazzo, M. E.; Gougoutas, J. Z.; Denzel, T. W. Methods of Producing C -Aryl Glucoside SGLT2 Inhibitors. PCT Int. Appl. WO 2004/063209, 2004
25. Chem. Abstr. 2004, 141, 89317.
26. Horton, D.; Priebe, W. Synthetic Routes to Higher-Carbon Sugars. Reaction of Lactones with 2-Lithio-1,3-Dithiane Carbohydr. Res. 1981, 94, 27-41
27. Ellsworth, B. A.; Doyle, A. G.; Patel, M.; Caceres-Cortes, J.; Meng, W.; Deshpande, P. P.; Pullockaran, A.; Washburn, W. N. C -Arylglucoside Synthesis: Triisopropylsilane as a Selective Reagent for the Reduction of an Anomeric C -Phenyl Ketal Tetrahedron: Asymmetry 2003, 14, 3243-3247
28. Yang, G.; Franck, R. W.; Byun, H.-S.; Bittman, R.; Samadder, P.; Arthur, G. Convergent C -Glycolipid Synthesis via the Ramberg-Bäcklund Reaction: Active Antiproliferative Glycolipids Org. Lett. 1999, 1, 2149-2151
29. Stoner, E. J.; Cothron, D. A.; Balmer, M. K.; Roden, B. A. Benzylation via Tandem Grignard Reaction-Iodotrimethysilane (TMSI) Mediated Reduction Tetrahedron 1995, 51, 11043-11062
30. Khan, M. A.; Lynch, B. M.; Hung, Y.-Y. Reactions of Phenyl-Substituted Heterocyclic Compounds II. Nitrations and Brominations of 1-Phenylpyrazole Derivatives Can. J. Chem. 1963, 41, 1540-1547
31. Hu, T. Q.; Leary, G.; Wong, D. A New Approach towards the Yellowing Inhibition of Mechanical Pulps. Part I: Selective Removal of α-Hydroxyl and α-Carbonyl Groups in Lignin Model Compounds Holzforschung 1999, 53, 43-48
32. Wang, X.; Rabbat, P.; O'shea, P.; Tillyer, R.; Grabowski, E. J. J.; Reider, P. J. Selective Monolithiation of 2,5-Dibromopyridine with Butyllithium Tetrahedron Lett. 2000, 41, 4335-4338
33. Huang-Minlon Reduction of Steroid Ketones and Other Carbonyl Compounds by Modified Wolff-Kishner Method J. Am. Chem. Soc. 1949, 71, 3301-3303
34. Mitsumoto, Y.; Burdett, E.; Grant, A.; Klip, A. Differential Expression of the GLUT1 and GLUT4 Glucose Transporters during Differentiation of L6 Muscle Cells Biochem. Biophys. Res. Commun. 1991, 175, 652-659
35. Srogl, J.; Allred, G. D.; Liebeskind, L. S. Sulfonium Salts. Participants par Excellence in Metal-Catalyzed Carbon-Carbon Bond-Forming Reactions J. Am. Chem. Soc. 1997, 119, 12376-12377