Novel macrocyclic C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents

Bioorganic and Medicinal Chemistry

Volumn 19, Issue 18, 2011, Pages 5468-5479

  Kim, Min Ju ^a   Lee, Suk Ho ^a   Park, So Ok ^a   Kang, Hyunku ^a   Lee, Jun Sung ^a   Lee, Ki Nam ^a   Jung, Myung Eun ^a   Kim, Jeongmin ^a   Lee, Jinhwa ^a  

^a Green Cross Company   (South Korea)

Author keywords

Dapagliflozin; Glucoside; Macrocycle; Ring closing metathesis; SGLT

Indexed keywords

(5 BROMO 2 CHLORO 4 METHOXYPHENYL)(4ETHOXYPHENYL)METHANONE; (5 BROMOPENTYLOXY)(TERT BUTYL)DIPHENYLSILANE; 1 (ALLYLOXY) 2 BROMO 5 CHLORO 4 (4 ETHOXYBENZYL)BENZENE; 1 BROMO 4 CHLORO 5 (4 ETHOXYBENZYL) 2 METHOXYBENZENE; 10,11,12 TRIS(BENZYLOXY) 16 CHLORO 15 (4 ETHOXYBENZ YL) 3,4 5,6,8,9,10,11,12,13 DECAHYDRO 2H 9,13 EPOXYBENZO [1,7] DIOXACYCLOPENTADECINE; 16 CHLORO 15 (4 ETHOXYBENZYL) 3,4,5,6,8,9,10,11,12,13 DECAHYDRO 2H 9,13 EPOXYBENZO [1,7] DIOXACYCLOPENTADECINE 10,11,12 TRIOL; 16 CHLORO 15 (4 ETHYLBENZYL) 3,4,5,6,8,9,10,11,12,13 DECAHYDRO 2H 9,13 EPOXYBENZO [1,7] DIOXACYCLOPENTADECINE 10,11,12 TRIOL; 2 (ACETOXYMETHYL) 6 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL]TETRAHYDRO 2H PYRAN 3,4,5 TRIYL TRIACETATE; 2 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 3,4,5 TRIS(BENZYLOXY) 6 (BENZYLOXYMETHYL)TETRAHYDRO 2H PYRAN; 2 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 6 (ALLYLOXYMETHYL)TETRAHYDRO 2H PYRAN 3,4,5 TRIOL; 2 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 6 (ALLYLOXYMETHYL)TETRAHYDRO 2H PYRAN 3,4,5 TRIYL TRIACETATE; 2 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 6 (HYDROXYL METHYL)TETRAHYDRO 2H PYRAN 3,4,5 TRIOL; 2 BROMO 5 CHLORO 4 (4 ETHOXYBENZYL)PHENOL; 2 CHLORO 4 HYDROXYBENZONITRILE; 5 [[6 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 3,4,5 TRIS(BENZYLOXY)TETRAHYDRO 2H PYRAN 2 YL]METHOXY]PENTAN 1 OL; 5 BROMO 2 CHLORO 4 HYDROXYBENZONITRILE; 5 BROMO 2 CHLORO 4 METHOXYBENZOIC ACID; 5 BROMO 2 CHLORO 4 METHOXYBENZONITRILE; 5 CHLORO 4 (4 ETHOXYBENZYL) 2 [3,4,5 TRIS(BENZYLOXY) 6 [(5 HYDROXYPENTYLOXY)METHYL]TETRAHYDRO 2H PYRAN 2 YL]PHENOL; 5 CHLORO 4 (4 ETHOXYBENZYL) 2 [3,4,5 TRIS(BENZYLOXY) 6 [(5 IODO PENTYLOXY)METHYL]TETRAHYDRO 2H PYRAN 2 YL]PHENOL; 6 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 2 VINYLHEXAHYDROPYRANO [3,2 D][1,3] DIOXINE 7,8 DIOL; [1,7] DIOXACYCLOPENTADECINE DERIVATIVE; [5 [[6 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 3,4,5 TRIS(BENZYLOXY)TETRAHYDRO 2H PYRAN 2 YL]METHOXY]PENTYLOXY](TERT BUTYL)DIPHENYLSILANE; [6 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 3,4,5 TRIS(BENZYLOXY)TETRAHYDRO 2H PYRAN 2 YL]METHANOL; [6 [2 (ALLYLOXY) 4 CHLORO 5 (4 ETHOXYBENZYL)PHENYL] 3,4,5 TRIS(BENZYLOXY)TETRAHYDRO 2H PYRAN 2 YL]METHYL ACETATE; ANTIDIABETIC AGENT; DAPAGLIFLOZIN; MACROCYCLIC COMPOUND; SODIUM GLUCOSE COTRANSPORTER 2; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALKYLATION; AMINO ACID SEQUENCE; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CYCLIZATION; DRUG ACTIVITY; DRUG DESIGN; DRUG EXCRETION; DRUG INHIBITION; DRUG MECHANISM; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; GLUCOSE URINE LEVEL; HUMAN; HUMAN TISSUE; IC 50; IN VITRO STUDY; IN VIVO STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PHYSICAL CHEMISTRY; PROTEIN EXPRESSION; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE; CHO CELLS; CRICETINAE; CYCLIZATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; MACROCYCLIC COMPOUNDS; MOLECULAR CONFORMATION; SODIUM-GLUCOSE TRANSPORTER 2; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84860420690     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2011.07.045     Document Type: Article

References (26)

1. International Diabetes Federation. Diabetes Atlas, 3rd ed.; International Diabetes Federation: Brussels, Belgium, 2006.
2. A. Dwarakanathan J. Insur. Med. 38 2006 20
3. B. Mackenzie, and D.D. Loo J. Biol. Chem. 20 1996 32678
4. E.M. Wright Am. J. Physiol. 280 2001 F10
5. S. Evans, E. Grasset, M. Heyman, A.M. Dumonitier, J.P. Beau, and J.-F. Desjeux J. Pediatr. Gastroenterol. Nutr. 4 1985 878
6. O.W. Moe, C.A. Berry, and F.C. Rector B.M. Brenner, F.C. Rector, The Kidney 5th ed. 2000 WB Saunders Co. Philadelphia 375 415
7. L.P. van den Heuvel, K. Assink, M. Willesen, and L. Monnens Hum. Genet. 111 2002 544
8. B.A. Ellsworth, W. Meng, M. Patel, R.N. Girotra, G. Wu, P. Sher, D. Hagan, M. Obermeier, W.G. Humphreys, J.G. Robertson, A. Wang, S. Han, T. Waldron, N.N. Morgan, J.M. Whaley, and W.N. Washburn Bioorg. Med. Chem. Lett. 18 2008 4770
9. W. Meng, B.A. Ellsworth, A.A. Nirschl, P.J. McCann, M. Patel, R.N. Girotra, G. Wu, P.M. Sher, E.P. Morrison, A.A. Biller, R. Zahler, P.P. Deshpande, A. Pullockaran, D.L. Hagan, N. Morgan, J.R. Taylor, M.T. Obermeier, W.G. Humphreys, A. Khanna, L. Discenza, J.G. Robertson, A. Wang, S. Han, J.R. Wetterau, E.B. Janovitz, O.P. Flint, J.M. Whaley, and W.N. Washburn J. Med. Chem. 51 2008 1145
10. W.N. Washburn J. Med. Chem. 52 2009 1785
11. Nomura, S.; Sakamaki, S.; Hongu, M.; Kawanski, E.; Koga, Y.; Sakamoto, T.; Yamamoto, Y.; Ueta, K.; Kimata, H.; Nakayama, K.; Tsuda-Tsukimoto, M. Presented at the 238th American Chemical Society National Meeting and Exposition, Washington, DC, August 16-20, 2009; Medi-151.
12. S. Nomura, S. Sakamaki, M. Hongu, E. Kawanshi, Y. Koga, T. Sakamoto, Y. Yamamoto, K. Ueta, H. Kimata, K. Nakayama, and M. Tsuda-Tsukimoto J. Med. Chem. 53 2010 6355
13. Boehringer Ingelheim Pharmaceuticals, www.clinicaltrials.gov, NCT01164501, 2010.
14. Lexicon Pharmaceuticals, www.clinicaltrials.gov, NCT00962065, 2009.
15. Astellas Pharma Inc., www.clinicaltrials.gov, NCT01135433, 2010.
16. Mascitti, V. Presented at the 240th American Chemical Society National Meeting and Exposition, Boston, MA, Aug 22-26, 2010; Medi-151.
17. V. Mascitti, T.S. Maurer, R.P. Robinson, J. Bian, C.M. Boustany-Kari, T. Brandt, B.M. Collman, A.S. Kalgutkar, M.K. Klenotic, M.T. Leininger, A. Lowe, R.J. Maguire, V.M. Masteson, Z. Miao, E. Mukaiyama, J.D. Patel, J.C. Pettersen, C. Preville, B. Samas, L. She, Z. Sobol, C.M. Steppan, B.D. Stevens, B.A. Thuma, M. Tugnait, D. Zeng, and T. Zhu J. Med. Chem. 54 2011 2952
18. J. Lee, S.-H. Lee, H.J. Seo, E.-J. Son, S.H. Lee, M.E. Jung, M. Lee, H.-K. Han, J. Kim, J. Kang, and J. Lee Bioorg. Med. Chem. 18 2010 2178
19. M.J. Kim, J. Lee, S.Y. Kang, S.-H. Lee, E.-J. Son, M.E. Jung, S.H. Lee, K.-S. Song, M. Lee, H.-K. Han, J. Kim, and J. Lee Bioorg. Med. Chem. Lett. 20 2010 3420
20. K.-S. Song, S.H. Lee, M.J. Kim, H.J. Seo, J. Lee, S.-H. Lee, M.E. Jung, E.-J. Son, M. Lee, J. Kim, and J. Lee ACS Med. Chem. Lett. 2 2011 182
21. S.Y. Kang, M.J. Kim, J.S. Lee, and J. Lee Bioorg. Med. Chem. Lett. 21 2011 3759
22. K. Katsuno, Y. Fujimori, Y. Takemura, M. Hiratochi, F. Itoh, Y. Komatsu, H. Fujikura, and M. Isaji J. Pharmacol. Exp. Ther. 320 2007 323
23. K. Arakawa, T. Ishihara, A. Oku, M. Nawano, K. Ueta, K. Kitamura, M. Matsumoto, and A. Saito Br. J. Pharmacol. 132 2001 578
24. B. Xu, B. Lv, Y. Feng, G. Xu, J. Du, A. Welihinda, Z. Sheng, B. Seed, and Y. Chen Bioorg. Med. Chem. Lett. 19 2009 5632
25. American Diabetes Association, Diabetes Care, 2004, 27(suppl 1), S5-S10.
26. L. Zhou, E.V. Cryan, M.R. D'Andrea, S. Belkowski, B.R. Conway, and K.T. Demarest J. Cell. Biochem. 90 2003 339