Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase

European Journal of Medicinal Chemistry

Volumn 58, Issue , 2012, Pages 624-639

  Zhang, Lei ^a   Chen, Xiaojie ^a   Liu, Jun ^b   Zhu, Qingzhang ^a   Leng, Ying ^a   Luo, Xiaomin ^a   Jiang, Hualiang ^a   Liu, Hong ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Dual target directed; Glucokinase activators; Glycogen phosphorylase inhibitors; Hybrid; Type 2 diabetes

Indexed keywords

2 [(5 CHLORO 1H INDOL 2 YL)FORMAMIDO]N[5 (1,2 DIHYDROXYETHYL)PYRIDIN 2 YL] 3 PHENYLPROPANAMIDE; ANTIDIABETIC AGENT; GLUCOKINASE; GLYCOGEN PHOSPHORYLASE; GLYCOSYLTRANSFERASE INHIBITOR; METHYL 6 [3 CYCLOHEXYL 2 [(4 METHANESULFONYLPHENYL)FORMAMIDO]PROPANAMIDO]PYRIDINE 3 CARBOXYLATE; PROPIONAMIDE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG DESIGN; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; IC 50; IN VITRO STUDY; MOLECULAR DOCKING; MOLECULAR MODEL;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; ENZYME ACTIVATION; ENZYME INHIBITORS; GLUCOKINASE; GLYCOGEN PHOSPHORYLASE, MUSCLE FORM; HUMANS; HYPOGLYCEMIC AGENTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; RABBITS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84869204756     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2012.06.020     Document Type: Article

References (57)

1. C. Wu, D.A. Okar, J. Kang, and A.J. Lange Reduction of hepatic glucose production as a therapeutic target in the treatment of diabetes Curr. Drug Targets Immune Endocr. Metabol. Disord. 5 2005 51 59
2. T. Barf Intervention of hepatic glucose production. small molecule regulators of potential targets for type 2 diabetes therapy Mini-Rev. Med. Chem. 4 2004 897 908
3. R. Kurukulasuriya, J.T. Link, D.J. Madar, Z. Pei, J.J. Rohde, S.J. Richards, A.J. Souers, and B.G. Szczepankiewicz Prospects for pharmacologic inhibition of hepatic glucose production Curr. Med. Chem. 10 2003 99 121
4. J.G. McCormack, N. Westergaard, M. Kristiansen, C.L. Brand, and J. Lau Pharmacological approaches to inhibit endogenous glucose production as a means of anti-diabetic therapy Curr. Pharm. Des. 7 2001 1451 1474
5. E.J. Barrett, and Z. Liu Hepatic glucose metabolism and insulin resistance in NIDDM and obesity Baillieres Clin. Endocrinol. Metab. 7 1993 875 901
6. A. Consoli Role of liver in pathophysiology of NIDDM Diabetes Care 15 1992 430 441
7. B.R. Landau, J. Wahren, V. Chandramouli, W.C. Schumann, K. Ekberg, and S.C. Kalhan Contributions of gluconeogenesis to glucose production in the fasted state J. Clin. Invest. 98 1996 378 385
8. W.A. Loughlin Recent advances in the allosteric inhibition of glycogen phosphorylase Mini-Rev. Med. Chem. 2010 1139 1155
9. L. Somsak, K. Czifrak, M. Toth, E. Bokor, E.D. Chrysina, K.-M. Alexacou, J.M. Hayes, C. Tiraidis, E. Lazoura, D.D. Leonidas, S.E. Zographos, and N.G. Oikonomakos New inhibitors of glycogen phosphorylase as potential antidiabetic agents Curr. Med. Chem. 15 2008 2933 2983
10. N.G. Oikonomakos, and L. Somsák Advances in glycogen phosphorylase inhibitor design Curr. Opin. Investig. Drugs 9 2008 379 395
11. B.R. Henke, and S.M. Sparks Glycogen phosphorylase inhibitors Mini-Rev. Med. Chem. 6 2006 845 857
12. D.J. Baker, P.L. Greenhaff, and J.A. Timmons Glycogen phosphorylase inhibition as a therapeutic target: a review of the recent patent literature Expert Opin. Ther. Patents 16 2006 459 466
13. N.G. Oikonomakos Glycogen phosphorylase as a molecular target for type 2 diabetes therapy Curr. Protein Pept. Sci. 3 2002 561 586
14. P. Manojit Recent advances in glucokinase activators for the treatment of type 2 diabetes Drug Discov. Today 14 2009 784 792
15. J. Grimsby, S.J. Berthel, and R. Sarabu Glucokinase activators for the potential treatment of type 2 diabetes Curr. Top. Med. Chem. 8 2008 1524 1532
16. R. Sarabu, S.J. Berthel, R.F. Kester, and J.W. Tilley Novel glucokinase activators: a patent review (2008-2010) Expert Opin. Ther. Patents 21 2011 13 33
17. P. Manojit Medicinal chemistry approaches for glucokinase activation to treat type 2 diabetes Curr. Med. Chem. 16 2009 3858 3874
18. M.C.T. Fyfe, and M.J. Procter Glucokinase activators as potential antidiabetic agents possessing superior glucose-lowering efficacy Drugs Fut 34 2009 641 653
19. R. Sarabu, S.J. Berthel, R.F. Kester, and J.W. Tilley Glucokinase activators as new type 2 diabetes therapeutic agents Expert Opin. Ther. Patents 18 2008 759 768
20. T.O. Johnson, and P.S. Humphries Glucokinase activators for the treatment of type 2 diabetes Annu. Rep. Med. Chem. 41 2006 141 154
21. K.R. Guertin, and J. Grimsby Small molecule glucokinase activators as glucose lowering agents: a new paradigm for diabetes therapy Curr. Med. Chem. 13 2006 1839 1843
22. R. Sarabu, and J. Grimsby Targeting glucokinase activation for the treatment of type 2 diabetes - a status review Curr. Opin. Drug Discov. Devel. 8 2005 631 637
23. F.M. Matschinsky Assessing the potential of glucokinase activators in diabetes therapy Nat. Rev. Drug Discov. 8 2009 399 416
24. J. Grimsby, R. Sarabu, W.L. Corbett, N.E. Haynes, F.T. Bizzarro, J.W. Coffey, K.R. Guertin, D.W. Hilliard, R.F. Kester, P.E. Mahaney, L. Marcus, L.D. Qi, C.L. Spence, J. Tengi, M.A. Magnuson, C.A. Chu, M.T. Dvorozniak, F.M. Matschinsky, and J.F. Grippo Allosteric activators of glucokinase: potential role in diabetes therapy Science 301 2003 370 373
25. T. Ferre, E. Riu, F. Bosch, and A. Valera Evidence from transgenic mice that glucokinase is rate limiting for glucose utilization in the liver FASEB J. 10 1996 1213 1218
26. R. Morphy, and Z. Rankovic Designing multiple ligands - medicinal chemistry strategies and challenges Curr. Pharm. Des. 15 2009 587 600
27. A.L. Hopkins Network pharmacology: the next paradigm in drug discovery Nat. Chem. Biol. 4 2008 682 690
28. T. Korcsmáros, M.S. Szalay, C. Böde, I.A. Kovács, and P. Csermely How to design multi-target drugs: target search options in cellular networks Expert Opin. Drug Discov. 2 2007 1 10
29. R. Morphy, and Z. Rankovic Fragments, network biology and designing multiple ligands Drug Discov. Today 12 2007 156 160
30. P. Csermely, V. Agoston, and S. Pongor The efficiency of multi-target drugs: the network approach might help drug design Trends Pharmacol. Sci. 26 2005 178 182
31. R. Morphy, and Z. Rankovic Designed multiple ligands. An emerging drug discovery paradigm J. Med. Chem. 48 2005 6523 6543
32. R. Morphy, C. Kay, and Z. Rankovic From magic bullets to designed multiple ligands Drug Discov. Today 9 2004 641 651
33. K. Murakami, K. Tobe, T. Ide, T. Mochizuki, M. Ohashi, Y. Akanuma, Y. Yazaki, and T. Kadowaki A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats Diabetes 47 1998 1841 1847
34. M. Nomura, S. Kinoshita, H. Satoh, T. Maeda, K. Murakami, M. Tsunoda, H. Miyacvhi, and K. Awano (3-Substituted benzyl)thiazolidine-2,4-diones as structurally new antihyperglycemic agents Bioorg. Med. Chem. Lett. 9 1999 533 538
35. H. Zhang, D.E. Ryono, P. Devasthale, W. Wang, K. O'Malley, D. Farrelly, L. Gu, T. Harrity, M. Cap, C. Chu, K. Locke, L. Zhang, J. Lippy, L. Kunselman, N. Morgan, N. Flynn, L. Moore, V. Hosagrahara, L. Zhang, P. Kadiyala, C. Xu, A.M. Doweyko, A. Bell, C. Chang, J. Muckelbauer, R. Zahler, N. Hariharan, and P.T.W. Cheng Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR alpha/gamma agonists Bioorg. Med. Chem. Lett. 19 2009 1451 1456
36. P.S. Humphries, S. Bailey, J.V. Almaden, S.J. Barnum, T.J. Carlson, L.C. Christie, Q.T. Do, J.D. Fraser, M. Hess, J. Kellum, Y.H. Kim, G.A. McClellan, K.M. Ogilvie, B.H. Simmons, D. Skalitzky, S. Sun, D. Wilhite, and L.R. Zehnder Pyridine-3-propanoic acids: discovery of dual PPARalpha/gamma agonists as antidiabetic agents Bioorg. Med. Chem. Lett. 16 2006 6120 6123
37. K. Liu, L. Xu, J.P. Berger, K.L. MacNaul, G. Zhou, T.W. Doebber, M.J. Forrest, D.E. Moller, and A.B. Jones Discovery of a novel series of peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes and dyslipidemia J. Med. Chem. 48 2005 2262 2265
38. P.V. Devasthale, S. Chen, Y. Jeon, F. Qu, C. Shao, W. Wang, H. Zhang, D. Farrelly, R. Golla, G. Grover, T. Harrity, Z. Ma, L. Moore, J. Ren, R. Seethala, L. Cheng, P. Sleph, W. Sun, A. Tieman, J.R. Wetterau, A. Doweyko, G. Chandrasena, S.Y. Chang, W.G. Humphreys, V.G. Sasseville, S.A. Biller, D.E. Ryono, F. Selan, N. Hariharan, and P.T.W. Cheng Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy] phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities J. Med. Chem. 48 2005 2248 2250
39. P.S. Humphries, J.V. Almaden, S.J. Barnum, T.J. Carlson, Q.T. Do, J.D. Fraser, M. Hess, Y.H. Kim, K.M. Ogilvie, and S. Sun Pyridine-2-propanoic acids: discovery of dual PPARalpha/gamma agonists as antidiabetic agents Bioorg. Med. Chem. Lett. 16 2006 6116 6119
40. R.C. Desai, W. Han, E.J. Metzger, J.P. Bergman, D.F. Gratale, K.L. MacNaul, J.P. Berger, T.W. Doebber, K. Leung, D.E. Moller, J.V. Heck, and S.P. Sahoo 5-Aryl thiazolidine-2,4-diones: discovery of PPAR dual alpha/gamma agonists as antidiabetic agents Bioorg. Med. Chem. Lett. 13 2003 2795 2798
41. L. Zhang, H. Li, Q. Zhu, J. Liu, L. Chen, Y. Leng, H. Jiang, and H. Liu Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase Bioorg. Med. Chem. 17 2009 7301 7312
42. L. Chen, H. Li, J. Liu, L. Zhang, H. Liu, and H. Jiang Discovering benzamide derivatives as glycogen phosphorylase inhibitors and their binding site at the enzyme Bioorg. Med. Chem. 15 2007 6763 6774
43. V.L. Rath, M. Ammirati, D.E. Danley, J.L. Ekstrom, E.M. Gibbs, T.R. Hynes, A.M. Mathiowetz, R.K. McPherson, T.V. Olson, J.L. Treadway, and D.J. Hoover Human liver glycogen phosphorylase inhibitors bind at a new allosteric site Chem. Biol. 7 2000 677 682
44. G.R. Bebernitz, V. Beaulieu, B.A. Dale, R. Deacon, A. Duttaroy, J. Gao, M.S. Grondine, R.C. Gupta, M. Kakmak, M. Kavana, L.C. Kirman, J. Liang, W.M. Maniara, S. Munshi, S.S. Nadkarni, H.F. Schuster, T. Stams, I. St. Denny, P.M. Taslimi, B. Vash, and S.L. Caplan Investigation of functionally liver selective glucokinase activators for the treatment of type 2 diabetes J. Med. Chem. 52 2009 6142 6152
45. V. Kumari, and C. Li Comparative docking assessment of glucokinase interactions with its allosteric activators Curr. Chem. Genom. 2 2008 76 89
46. K. Onda, T. Suzuki, R. Shiraki, Y. Yonetoku, K. Negoro, K. Momose, N. Katayama, M. Orita, T. Yamaguchi, M. Ohta, and S. Tsukamoto Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a Bioorg. Med. Chem. 16 2008 5452 5464
47. K.G. Rosauer, A.K. Ogawa, C.A. Willoughby, K.P. Ellsworth, W.M. Geissler, R.W. Myers, Q. Deng, K.T. Chapman, G. Harris, and D.E. Moller Novel 3,4-dihydroquinolin-2(1H)-one inhibitors of human glycogen phosphorylase a Bioorg. Med. Chem. Lett. 13 2003 4385 4388
48. P.R.O. Whittamore, M.S. Addie, S.N.L. Bennett, A.M. Birch, M. Butters, L. Godfrey, P.W. Kenny, A.D. Morley, P.M. Murray, N.G. Oikonomakos, L.R. Otterbein, A.D. Pannifer, J.S. Parker, K. Readman, P.S. Siedlecki, P. Schofield, A. Stocker, M.J. Taylor, L.A. Townsend, D.P. Whalley, and J. Whitehouse Novel thienopyrrole glycogen phosphorylase inhibitors: synthesis, in vitro SAR and crystallographic studies Bioorg. Med. Chem. Lett. 16 2006 5567 5571
49. K.R. Guertin, PCT Int. Appl. WO2002048106, 2002.
50. S.X. Cao, J. Feng, S.L. Gwaltney, D.J. Hosfield, R.J. Skene, J.A. Stafford, M. Tang, U.S. Patent US20070281942, 2007.
51. M. Futamura, H. Hosaka, A. Kadotani, H. Shimazaki, K. Sasaki, S. Ohyama, T. Nishimura, J. Eiki, and Y. Nagata An allosteric activator of glucokinase impairs the interaction of glucokinase and glucokinase regulatory protein and regulates glucose metabolism J. Biol. Chem. 281 2006 37668 37674
52. K.J. Brocklehurst, V.A. Payne, R.A. Davies, D. Carroll, H.L. Vertigan, H.J. Wightman, S. Aiston, I.D. Waddell, B. Leighton, M.P. Coghlan, and L. Agius Stimulation of hepatocyte glucose metabolism by novel small molecule glucokinase activators Diabetes 53 2004 535 541
53. A.M. Efanov, D.G. Barrett, M.B. Brenner, S.L. Briggs, A. Delaunois, J.D. Durbin, U. Giese, H. Guo, M. Radloff, G.S. Gil, S. Sewing, Y. Wang, A. Weichert, A. Zaliani, and J. Gromada A novel glucokinase activator modulates pancreatic islet and hepatocyte function Endocrinology 146 2005 3696 3701
54. M.C.T. Fyfe, J.R. White, A. Taylor, R. Chatfield, E. Wargent, R.L. Printz, T. Sulpice, J.G. McCormack, M.J. Procter, C. Reynet, P.S. Widdowson, and P. Wong-Kai-In Glucokinase activator PSN-GK1 displays enhanced antihyperglycaemic and insulinotropic actions Diabetologia 50 2007 1277 1287
55. W.H. Martin, D.J. Hoover, S.J. Armento, I.A. Stock, R.K. McPherson, D.E. Danley, R.W. Stevenson, E.J. Barrett, and J.L. Treadway Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo Proc. Natl. Acad. Sci. U.S.A. 95 1998 1776 1781
56. A.M. Birch, P.W. Kenny, N.G. Oikonomakos, L. Otterbein, P. Schofield, P.R. Whittamore, and D.P. Whalley Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors Bioorg. Med. Chem. Lett. 17 2007 394 399
57. K. Kamata, M. Mitsuya, T. Nishimura, J. Eiki, and Y. Nagata Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase Structure 12 2004 429 438