Fructose-1,6-bisphosphatase inhibitors. 1. Purine phosphonic acids as novel AMP mimics

Journal of Medicinal Chemistry

Volumn 52, Issue 9, 2009, Pages 2880-2898

  Dang, Qun ^a   Brown, Brian S ^a,b   Liu, Yan ^a,c   Rydzewski, Robert M ^a,d   Robinson, Edward D ^a,e   Van Poelje, Paul D ^a   Reddy, M Rami ^a   Erion, Mark D ^a  

^a Metabasis Therapeutics Inc   (United States)

^b ABBOTT LABORATORIES   (United States)

^c Takeda San Diego Inc   (United States)

^d Gardiner Caldwell Pacific   (United States)

^e DLA Piper   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

[5 (6 AMINO 9 ISOBUTYL 2 METHYLSULFANYL 9H PURIN 8 YL)FURAN 2 YL]PHOSPHONIC ACID; [5 [6 AMINO 9 (2,2 DIMETHYLPROPYL) 9H PURIN 8 YL]FURAN 2 YL]PHOSPHONIC ACID; ADENOSINE PHOSPHATE; ANTIDIABETIC AGENT; ENZYME INHIBITOR; FRUCTOSE 1,6 BISPHOSPHATASE INHIBITOR; FRUCTOSE BISPHOSPHATASE; LIVER ENZYME; PHOSPHONIC ACID DERIVATIVE; PURINE; PURINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; IN VIVO STUDY; LIVER CELL; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ADENOSINE MONOPHOSPHATE; ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; BIOMIMETICS; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; ENZYME INHIBITORS; FRUCTOSE-BISPHOSPHATASE; GLUCOSE; HUMANS; INHIBITORY CONCENTRATION 50; LIVER; PHOSPHONIC ACIDS; PURINES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 65649128908     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900078f     Document Type: Article

References (39)

1. Zimmet, P.; Alberti, K. G.; Shaw, J. Global and societal implications of the diabetes epidemic. Nature (London) 2001, 414, 782-787. (Pubitemid 34000780)
2. Maggs, D. G.; Buchanan, T. A.; Burant, C. F.; Cline, G.; Gumbiner, B.; Hsueh, W. A.; Inzucchi, S.; Kelley, D.; Nolan, J.; Olefsky, J. M.; Polonsky, K. S.; Silver, D.; Valiquett, T. R.; Shulman, G. I. Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 1998, 128, 176-185.
3. 13C nuclear magnetic resonance study. J. Clin. Invest. 1992, 90, 1323-1327.
4. Gastaldelli, A.; Baldi, S.; Pettiti, M.; Toschi, E.; Camastra, S.; Natali, A.; Landau, B. R.; Ferrannini, E. Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans: a quantitative study. Diabetes 2000, 49, 1367-1373. (Pubitemid 30627434)
5. Hundal, R. S.; Krssak, M.; Dufour, S.; Laurent, D.; Lebon, V.; Chandramouli, V.; Inzucchi, S. E.; Schumann, W. C.; Petersen, K. F.; Landau, B. R.; Shulman, G. I. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000, 49, 2063-2069.
6. van Poelje, P. D.; Dang, Q.; Erion, M. D. Fructose 1,6-Bisphosphatase as a therapeutics target for Type 2 Diabetes. Drug Discovery Today: Ther. Strategies 2007, 4, 103.
7. Maryanoff, B. E.; Reitz, A. B.; Tutwiler, G. F.; Benkovic, S. J.; Benkovic, P. A.; Pilkis, S. J. Stereoselective Synthesis and Biological Activity of beta- and alpha-D-Arabinose 1,5-Diphosphate: Analogues of a Potent Metabolic Regulator. J. Am. Chem. Soc. 1984, 106, 7851-7853.
8. Wright, S. W.; Hageman, D. L.; McClure, L. D.; Carlo, A. A.; Treadway, J. L.; Mathiowetz, A. M.; Withka, J. M.; Bauer, P. H. Allosteric inhibition of fructose-1,6-bisphosphatase by anilinoquinazolines. Bioorg. Med. Chem. Lett. 2001, 11, 17-21. (Pubitemid 32006115)
9. Wright, S. W.; Carlo, A. A.; Carty, M. D.; Danley, D. E.; Hageman, D. L.; Karam, G. A.; Levy, C. B.; Mansour, M. N.; Mathiowetz, A. M.; McClure, L. D.; Nestor, N. B.; McPherson, R. K.; Pandit, J.; Pustilnik, L. R.; Schulte, G. K.; Soeller, W. C.; Treadway, J. L.; Wang, I. K.; Bauer, P. H. Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel allosteric site: synthesis, in vitro characterization, and X-ray crystallography. J. Med. Chem. 2002, 45, 3865-3877.
10. Wright, S. W.; Carlo, A. A.; Danley, D. E.; Hageman, D. L.; Karam, G. A.; Mansour, M. N.; McClure, L. D.; Pandit, J.; Schulte, G. K.; Treadway, J. L.; Wang, I. K.; Bauer, P. H. 3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site. Bioorg. Med. Chem. Lett. 2003, 13, 2055-2058. (Pubitemid 36638409)
11. Lai, C.; Gum, R. J.; Daly, M.; Fry, E. H.; Hutchins, C.; Abad-Zapatero, C.; von Geldern, T. W. Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg. Med. Chem. Lett. 2006, 16, 1807-1810. (Pubitemid 43267355)
12. von Geldern, T. W.; Lai, C.; Gum, R. J.; Daly, M.; Sun, C.; Fry, E. H.; Abad-Zapatero, C. Benzoxazole benzenesulfonamides are novel allosteric inhibitors of fructose-1,6-bisphosphatase with a distinct binding mode. Bioorg. Med. Chem. Lett. 2006, 16, 1811-1815. (Pubitemid 43267356)
13. Dang, Q.; Kasibhatla, S. R.; Reddy, K. R.; Jiang, T.; Reddy, M. R.; Potter, S. C.; Fujitaki, J. M.; van Poelje, P. D.; Huang, J.; Lipscomb, W. N.; Erion, M. D. Discovery of Potent and Specific Fructose-1,6-Bisphosphatase Inhibitors and a Series of Orally Bioavailable Phosphoramidase-Sensitive Prodrugs for the Treatment of Type 2 Diabetes. J. Am. Chem. Soc. 2007, 129, 15491-15502.
14. Reddy, M. R.; Erion, M. D. Calculation of relative binding free energy differences for fructose 1,6-bisphosphatase inhibitors using the thermodynamic cycle perturbation approach. J. Am. Chem. Soc. 2001, 123, 6246-6252.
15. Reddy, M. R.; Erion, M. D. Computer-aided drug design strategies used in the discovery of fructose 1, 6-bisphosphatase inhibitors. Curr. Pharm. Des. 2005, 11, 283-294. (Pubitemid 40277858)
16. Erion, M. D.; van Poelje, P. D.; Dang, Q.; Kasibhatla, S. R.; Potter, S. C.; Reddy, M. R.; Reddy, K. R.; Jiang, T.; Lipscomb, W. N. MB06322 (CS-917): a potent and selective inhibitor of fructose-1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 7970-7975.
17. Gidh-Jain, M.; Zhang, Y.; van Poelje, P. D.; Liang, J. Y.; Huang, S.; Kim, J.; Elliott, J. T.; Erion, M. D.; Pilkis, S. J.; el-Maghrabi, R. M.; Lipscomb, W. N. The allosteric site of human liver fructose-1,6- bisphosphatase. Analysis of six AMP site mutants based on the crystal structure. J. Biol. Chem. 1994, 269, 27732-27738.
18. Dang, Q. Organophosphonic acids as drug candidates. Expert Opin. Ther. Pat. 2006, 16, 343.
19. Erion, M. D.; Dang, Q.; Reddy, M. R.; Kasibhatla, S. R.; Huang, J.; Lipscomb, W. N.; van Poelje, P. D. Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity. J. Am. Chem. Soc. 2007, 129, 15480-15490.
20. Reddy, M. R.; Erion, M. D. Relative binding affinities of fructose- 1,6-bisphosphatase inhibitors calculated using a quantum mechanicsbased free energy perturbation method. J. Am. Chem. Soc. 2007, 129, 9296-9297.
21. Dang, Q.; Brown, B. S.; Erion, M. D. Efficient synthesis of purine analogues: an FeCl3-SiO2-promoted cyclization reaction of 4,5-diaminopyrimidines with aldehydes leading to 6,8,9-trisubstituted purines. Tetrahedron Lett. 2000, 41, 6559-6562.
22. Froehler, B. C.; Ng, P. G.; Matteucci, M. D. Synthesis of DNA via deoxynucleoside H-phosphonate intermediates. Nucleic Acids Res. 1986, 14, 5399-5407.
23. Perich, J. W.; Johns, R. B. Di-tert-butyl N,N-diethylphosphoramidite. A new phosphitylating agent for the efficient phosphorylation of alcohols. Synthesis 1988, 142-144.
24. Dang, Q.; Kasibhatla, S. R.; Jiang, T.; Fan, K.; Liu, Y.; Taplin, F.; Schulz, W.; Cashion, D. K.; Reddy, K. R.; van Poelje, P. D.; Fujitaki, J. M.; Potter, S. C.; Erion, M. D. Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose- 1,6-bisphosphatase inhibitors. J. Med. Chem. 2008, 51, 4331-4339.
25. Erion, M. D.; Niwas, S.; Rose, J. D.; Ananthan, S.; Allen, M.; Secrist, J. A.; Babu, Y. S.; Bugg, C. E.; Guida, W. C.; Ealick, S. E.; Montgomery, J. A. Structure-based design of inhibitors of purine nucleoside phosphorylase. 3. 9-Arylmethyl derivatives of 9-deazaguanine substituted on the methylene group. J. Med. Chem. 1993, 36, 3771-3783.
26. Montgomery, J. A.; Niwas, S.; Rose, J. D.; Secrist, J. A.; Babu, Y. S.; Bugg, C. E.; Erion, M. D.; Guida, W. C.; Ealick, S. E. Structurebased design of inhibitors of purine nucleoside phosphorylase. 1. 9-(arylmethyl) derivatives of 9-deazaguanine. J. Med. Chem. 1993, 36, 55-69.
27. Secrist, J. A.; Niwas, S.; Rose, J. D.; Babu, Y. S.; Bugg, C. E.; Erion, M. D.; Guida, W. C.; Ealick, S. E.; Montgomery, J. A. Structurebased design of inhibitors of purine nucleoside phosphorylase. 2. 9-Alicyclic and 9-heteroalicyclic derivatives of 9-deazaguanine. J. Med. Chem. 1993, 36, 1847-1854.
28. Erion, M. D.; Kasibhatla, S. R.; Bookser, B. C.; van Poelje, P. D.; Reddy, M. R.; Gruber, H. E.; Appleman, J. R. Discovery of AMP Mimetics that Exhibit High Inhibitory Potency and Specificity for AMP Deaminase. J. Am. Chem. Soc. 1999, 121, 308-319.
29. Ke, H. M.; Zhang, Y. P.; Lipscomb, W. N. Crystal structure of fructose- 1,6-bisphosphatase complexed with fructose-6-phosphate, AMP, and magnesium. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 5243-5247.
30. Sun, W.; Wu, R. R.; van Poelje, P. D.; Erion, M. D. Isolation of a family of organic anion transporters from human liver and kidney. Biochem. Biophys. Res. Commun. 2001, 283, 417-422. (Pubitemid 32924708)
31. Dang, Q.; Brown, B. S.; van Poelje, P. D.; Colby, T. J.; Erion, M. D. Synthesis of phosphonate 3-phthalidyl esters as prodrugs for potential intracellular delivery of phosphonates. Bioorg. Med. Chem. Lett. 1999, 9, 1505-1510. (Pubitemid 29274186)
32. el-Maghrabi, M. R.; Pilkis, S. J. Expression of rat liver fructose-1,6- bisphosphatase in Escherichia coli. Biochem. Biophys. Res. Commun. 1991, 176, 137-144.
33. Wiesner, J. B.; Ugarkar, B. G.; Castellino, A. J.; Barankiewicz, J.; Dumas, D. P.; Gruber, H. E.; Foster, A. C.; Erion, M. D. Adenosine kinase inhibitors as a novel approach to anticonvulsant therapy. J. Pharmacol. Exp. Ther. 1999, 289, 1669-1677.
34. Kemp, R. G. Rabbit liver phosphofructokinase. Comparison of some properties with those of muscle phosphofructokinase. J. Biol. Chem. 1971, 246, 245-252.
35. Tagaya, M.; Yagami, T.; Noumi, T.; Futai, M.; Kishi, F.; Nakazawa, A.; Fukui, T. Site-directed mutagenesis of Pro-17 located in the glycine-rich region of adenylate kinase. J. Biol. Chem. 1989, 264, 990-994. (Pubitemid 19038082)
36. McMahon, R. J.; Frost, S. C. Glycogen: a carbohydrate source for GLUT-1 glycosylation during glucose deprivation of 3T3-L1 adipocytes. Am. J. Physiol. 1996, 270, E640-E645.
37. Berry, M. N.; Friend, D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J. Cell Biol. 1969, 43, 506-520.
38. Groen, A. K.; Sips, H. J.; Vervoorn, R. C.; Tager, J. M. Intracellular compartmentation and control of alanine metabolism in rat liver parenchymal cells. Eur. J. Biochem. 1982, 122, 87-93.
39. Vincent, M. F.; Marangos, P. J.; Gruber, H. E.; Van den Berghe, G. Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes 1991, 40, 1259-1266.