Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE)

European Journal of Medicinal Chemistry

Volumn 79, Issue , 2014, Pages 128-142

  Han, Young Taek ^a   Kim, Kyeojin ^b   Choi, Gyeong In ^b   An, Hongchan ^b   Son, Dohyun ^c   Kim, Hee ^d   Ha, Hee Jin ^d   Son, Jun Hyeng ^b   Chung, Suk Jae ^b   Park, Hyun Ju ^c   Lee, Jeewoo ^b   Suh, Young Ger ^b  

^a Woosuk University   (South Korea)

^b Seoul National University   (South Korea)

^c Sungkyunkwan University   (South Korea)

^d Medifron DBT   (South Korea)

Author keywords

Alzheimer's disease, RAGE inhibitor; Pyrazole 5 carboxamide; RAGE (receptor for advanced glycation end products); SAR (structure activity relationship)

Indexed keywords

1 (4 (2 FLUOROPHENOXY)PHENYL)ETHANONE; 1 (4 (4 CHLOROPHENOXY)PHENYL)ETHANONE; 1 (4 (PYRIDIN 2 YLOXY)PHENYL)ETHANONE; ADVANCED GLYCATION END PRODUCT; AMIDE; AMYLOID BETA PROTEIN[1-42]; ETHYL 1 BUTYL 3 (4 (4 CHLOROPHENOXY)PHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 1 BUTYL 5 (4 (4 CHLOROPHENOXY)PHENYL) 1H PYRAZOLE 3 CARBOXYLATE; ETHYL 1 METHYL 3 (4 (PYRIDIN 2 YLOXY)PHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 1 METHYL 3 (4 PHENOXYPHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 ((TERT BUTYLDIMETHYLSILYL)OXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 ((TERT BUTYLDIMETHYLSILYL)OXY)PHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (2 FLUOROPHENOXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (2 FLUOROPHENOXY)PHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (3 FLUOROPHENOXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (4 CHLOROPHENOXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (4 CHLOROPHENOXY)PHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (4 FLUOROPHENOXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (4 METHOXYPHENOXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (4CHLOROPHENOXY)PHENYL) 1 PROPYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (4CHLOROPHENOXY)PHENYL)ISOXAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (CYCLOHEXYLOXY)PHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 (PYRIDIN 2 YLOXY)PHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 METHOXYPHENYL) 1 METHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4 METHOXYPHENYL) 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 3 (4(4CHLOROPHENOXY)PHENYL) 1 ETHYL 1H PYRAZOLE 5 CARBOXYLATE; ETHYL 5 (4 (4 CHLOROPHENOXY)PHENYL) 1 PROPYL 1H PYRAZOLE 3 CARBOXYLATE; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ADVANCED GLYCOSYLATION END-PRODUCT RECEPTOR; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); IMMUNOGLOBULIN RECEPTOR; PEPTIDE FRAGMENT; PYRAZOLE-5-CARBOXAMIDE;

ANIMAL EXPERIMENT; ARTICLE; BINDING SITE; CONTROLLED STUDY; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SOLUBILITY; DRUG SYNTHESIS; IN VITRO STUDY; MOLECULAR DOCKING; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; SURFACE PLASMON RESONANCE; ANTAGONISTS AND INHIBITORS; BRAIN; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; HUMAN; SYNTHESIS;

AMYLOID BETA-PEPTIDES; BRAIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PEPTIDE FRAGMENTS; PYRAZOLES; RECEPTORS, IMMUNOLOGIC; STRUCTURE-ACTIVITY RELATIONSHIP; SURFACE PLASMON RESONANCE;

EID: 84898654833     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.03.072     Document Type: Article

References (40)

1. D.J. Selkoe Alzheimer's disease: gene (Pubitemid 32267077)
2. J. Hardy, and D.J. Selkoe The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics Science 297 2002 353 356 (Pubitemid 34790756)
3. K. Blennow, M.J. de Leon, and H. Zetterberg Alzheimer's disease Lancet 368 2006 387 403 (Pubitemid 44108123)
4. Y.J. Wang, H.D. Zhou, and X.F. Zhou Clearance of amyloid-beta in Azheimer's disease: progress, problems and perspectives Drug Discovery Today 11 2006 931 938
5. R.E. Tanzi, R.D. Moir, and S.L. Wagner Clearance of Alzheimer's Aβ peptide: the many roads to perdition Neuron 43 2004 605 608 (Pubitemid 39179722)
6. R. Deane, D.S. Yan, R.K. Submamaryan, B. LaRue, S. Jovanovic, E. Hogg, D. Welch, L. Manness, C. Lin, J. Yu, H. Zhu, J. Ghiso, B. Frangione, A. Stern, A.M. Schmidt, D.L. Armstrong, B. Arnold, B. Liliensiek, P. Nawroth, F. Hofman, M. Kindy, D. Stern, and B. Zlokovic RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain Natural Medicines 9 2003 907 913 (Pubitemid 36889934)
7. L. Lin RAGE on the toll road? Cellular & Molecular Immunology 3 2006 351 358
8. H. Huttunen, C. Fages, and H. Rauvala Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-κB require the cytoplasmic domain of the receptor but different downstream signaling pathways Journal of Biological Chemistry 274 1999 19919 19924
9. J. Li, and A.M. Schmidt Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products Journal of Biological Chemistry 272 1997 16498 16506 (Pubitemid 27276477)
10. A. Bierhaus, S. Schiekofer, M. Schwaninger, M. Andrassy, P.M. Humpert, J. Chen, M. Hong, T. Luther, T. Henle, I. Kloting, M. Morcos, M. Hofmann, H. Tritschler, B. Weigle, M. Kasper, M. Smith, G. Perry, A.M. Schmidt, D.M. Stern, H.U. Haring, E. Schleicher, and P.P. Nawroth Diabetes-associated sustained activation of the transcription factor nuclear factor-kB Diabetes 50 2001 2792 2808 (Pubitemid 33733131)
11. M. Sakono, and T. Zako Amyloid oligomers: formation and toxicity of Aβ oligomers FEBS Journal 277 2010 1348 1358
12. C. Holmes, D. Boche, D. Wilkinson, G. Yadegarfar, V. Hopkins, A. Bayer, R.W. Jones, R. Bullock, S. Love, J.W. Neal, E. Zotova, and J.A. Nicoll Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial Lancet 372 2008 216 223 (Pubitemid 351978111)
13. O.G. Aderinwale, H.W. Ernst, and S.A. Mousa Current therapies and new strategies for the management of Alzheimer's disease American Journal of Alzheimer's Disease and Other Dementias 25 2010 414 424
14. L. Zhang, R. Postina, and Y. Wang Ectodomain shedding of the receptor for advanced glycation end products: a novel therapeutic target for Alzheimer's disease Cellular and Molecular Life Sciences 66 2009 3923 3935
15. D. Geroldi, C. Falcone, and E. Emanuele Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target Current Medicinal Chemistry 13 2006 1971 1978
16. M.N. Sabbagh, A. Agro, J. Bell, P.S. Aisen, E. Schweizer, and D. Galasko PF-04494700, an oral inhibitor of receptor for advanced glycation end products (RAGE), in Alzheimer disease Alzheimer Disease and Associated Disorders 25 2011 206 212
17. V. Srikanth, A. Maczurek, T. Phan, M. Steele, B. Westcott, D. Juskiw, and G. Münch Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease Neurobiology of Aging 32 2011 763 777
18. R. Deane, I. Singh, A.P. Sagare, R.D. Bell, N.T. Ross, B. Larue, R. Love, S. Perry, N. Paquette, R.J. Deane, T. Meenakshisundaram, T. Zarcone, G. Fritz, A.E. Friedman, B.L. Miller, and B.V. Zlokovic A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease The Journal of Clinical Investigation 122 2012 1377 1392
19. Y.T. Han, G.-I. Choi, D. Son, N.-J. Kim, H. Yun, S. Lee, D.-J. Chang, H.-S. Hong, H. Kim, H.-J. Ha, Y.-H. Kim, H.-J. Park, J. Lee, and Y.-G. Suh Ligand-based design, synthesis and biological evaluation of 2-aminopyrimidines, a novel series of RAGE (receptor for advanced glycation end products) inhibitors Journal of Medicinal Chemistry 55 2012 9120 9135
20. I. Vujasinovic, A. Paravic-Radicevic, K. Mlinaric-Majerski, K. Brajsa, and B. Bertosa Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis Bioorganic & Medicinal Chemistry 20 2012 2101 2110
21. 3 catalyzed synthesis of 4- and 5-substituted pyrazoles Synlett 14 2009 2328 2332
22. H. Zou, H. Zhu, J. Shao, J. Wu, W. Chen, M.A. Giulianotti, and Y. Yu A facile approach to polysubstituted pyrazoles from hydrazonyl chlorides and vinyl azides Tetrahedron 67 2011 4887 4891
23. W.H. Heath, F. Palmieri, J.R. Adams, B.K. Long, J. Chute, T.W. Holcombe, S. Zieren, M.J. Truitt, J.L. White, and C.G. Willson Degradable cross-linkers and strippable imaging materials for step-and-flash imprint lithography Macromolecules 41 2008 719 726 (Pubitemid 351294483)
24. N.E. Faucher, P. Martres, Substituted pyrazoles as PPAR agonists, WO2005/049578(A1).
25. D.A. Evans, J.L. Katz, and T.R. West Synthesis of diary ethers through the copper-promoted arylation of phenols with arylboronic acids. An expedient synthesis of thyroxine Tetrahedron Letters 39 1998 2937 2940 (Pubitemid 28184064)
26. V. Bertolasi, P. Gilli, V. Ferretti, G. Gilli, and C. Fernàndez-Castaño Self-assembly of NH-pyrazoles via intermolecular N-HN hydrogen bonds Acta Crystallographica B55 1999 985 993 (Pubitemid 129533784)
27. S. Matsumoto, T. Yoshida, H. Murata, S. Harada, N. Fujita, S. Nakamura, Y. Yamamoto, T. Watanabe, H. Yonekura, H. Yamamoto, T. Ohkubo, and Y. Kobayashi Solution structure of the variable-type domain of the receptor for advanced glycation end products: new insight into AGE-RAGE interaction Biochemistry 47 47 2008 12299 12311
28. N. Zacharias, and D.A. Dougherty Cation-π interactions in ligand recognition and catalysis TRENDS in Pharmacological Sciences 23 2002 281 287 (Pubitemid 34655734)
29. L.H. Takahashi, R. Radhakrishnan, R.E. Rosenfield, E.F. Meyer, and D.A. Trainor Crystal structure of the covalent complex formed by a peptidyl α,α-difluoro-β-keto amide with porcine pancreatic elastase at 1.78 Å resolution Journal of the American Chemical Society 111 1989 3368 3374 (Pubitemid 19118537)
30. E. Istvan, and J. Deisenhofer Structural mechanism for statin inhibition of HMG-CoA reductase Science 292 2001 1160 1164 (Pubitemid 32440937)
31. G. Sidhu, S.G. Withers, N.T. Nguyen, L.P. McIntosh, L. Ziser, and G.D. Brayer Sugar ring distortion in the glycosyl-enzyme intermediate of a family G/11 xylanase Biochemistry 38 1999 5346 5354
32. P. Gonin, Y. Xu, L. Milon, S. Dabernat, M. Morr, R. Kumar, M.L. Lacombe, J. Janin, and I. Lascu Catalytic mechanism of nucleoside diphosphate kinase investigated using nucleotide analogues, viscosity effects, and X-ray crystallography Biochemistry 38 1999 7256 7272
33. H.J. Böhm, D. Banner, S. Bendels, M. Kansy, B. Kuhn, K. Müller, U. Obst-Sander, and M. Stahl Fluorine in medicinal chemistry ChemBioChem 5 2004 637 643 (Pubitemid 39257085)
34. +-F hydrogen bonding in a fluorinated "proton sponge" derivative: Integration of solution, solid-state, gas-phase, and computational studies Journal of Organic Chemistry 76 2011 7975 7984
35. H. Park, and J.C. Boyington The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding Journal of Biological Chemistry 285 2010 40762 40770
36. The details of pharmacokinetic investigation on 40 will be reported soon.
37. C.D. Bevan, and R.S. Lloyd A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates Analytical Chemistry 72 2000 1781 1787 (Pubitemid 30220169)
38. Sybyl-X, 1.3 (Ed.); SYBYL Molecular Modeling Software, Tripos Inc.: St. Louis, MO, 2011.10.
39. D. Stern, S.D. Yan, A.M. Schmidt, and I. Lamster Ligand binding site of rage and uses thereof, US 6555651B2 2003
40. ® 3D Explorer; 3D Chemical Visualization and Decision Support, Tripos Inc.: St. Louis, MO, 2011.10.