Fine tuning of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine focusing on the activity-sensitive aminoalkoxy moiety for a therapeutically useful inhibitor of receptor for advanced glycation end products (RAGE)

Bioorganic and Medicinal Chemistry

Volumn 23, Issue 3, 2015, Pages 579-587

  Han, Young Taek ^a   Kim, Kyeojin ^b   Son, Dohyun ^c   An, Hongchan ^b   Kim, Hee ^d   Lee, Jeeyeon ^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

2 (N,N Diethylamino)ethoxy moiety; 2 Aminopyrimidine; products; RAGE inhibitor; Receptor for advanced glycation end; Structure activity relationship

Indexed keywords

1 (2 ETHOXYETHOXY) 3 NITROBENZENE; 1 [2 (3 AMINOPHENOXY)ETHYL]PYRROLIDIN 2 ONE; 1 [2 (3 NITROPHENOXY)ETHYL]PYRROLIDIN 2 ONE; 1 [2 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY]ETHYL]PIPERIDIN 3 OL; 2 (N,N DIETHYLAMINO)ETHOXY; 2 [[2 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY]ETHYL](ETHYL)AMINO]ETHANOL; 3 (2 ETHOXYETHOXY)ANILINE; 3 (3 NITROPHENOXY)PROPAN 1 OL; 3 (N,N DIMETHYLAMINO)PYRROLIDINE; 3 [3 (DIETHYLAMINO)PROPOXY]ANILINE; 3 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY] N METHOXY N METHYLPROPANAMIDE; 3 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY] N METHOXYPROPANAMIDE; 3 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY]PROPAN 1 OL; 3 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY]PROPANAL O METHYL OXIME; 3 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY]PROPANOIC ACID; 4,6 BIS(4 CHLOROPHENYL) N [3 (2 ETHOXYETHOXY)PHENYL]PYRIMIDIN 2 AMINE; 4,6 BIS(4 CHLOROPHENYL) N [3 [2 [3 (DIMETHYLAMINO)PYRROLIDIN 1 YL]ETHOXY]PHENYL]PYRIMIDIN 2 AMINE; 4,6 BIS(4 CHLOROPHENYL) N [3 [2 [ETHYL(2 METHOXYETHYL)AMINO]ETHOXY]PHENYL]PYRIMIDIN 2 AMINE; 4,6 BIS(4 CHLOROPHENYL) N [3 [3 (DIETHYLAMINO)PROPOXY]PHENYL]PYRIMIDIN 2 AMINE; 4,6 BISPHENYL 2 (3 ALKOXYANILINO)PYRIMIDINE; ADVANCED GLYCATION END PRODUCT RECEPTOR; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; METHYL 3 [3 [4,6 BIS(4 CHLOROPHENYL)PYRIMIDIN 2 YLAMINO]PHENOXY]PROPANOATE; N,N DIETHYL 3 (3 NITROPHENOXY)PROPAN 1 AMINE; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; ADVANCED GLYCOSYLATION END-PRODUCT RECEPTOR; IMMUNOGLOBULIN RECEPTOR; PYRIMIDINE DERIVATIVE;

AQUEOUS SOLUTION; ARTICLE; BINDING AFFINITY; BINDING SITE; CONTROLLED STUDY; DRUG DETERMINATION; DRUG MECHANISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SOLUBILITY; DRUG STRUCTURE; HYDROGEN BOND; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR MODEL; PHYSICAL CHEMISTRY; PREDICTION; STRUCTURE ACTIVITY RELATION; CHEMICAL STRUCTURE; CHEMISTRY; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE; PYRIMIDINES; RECEPTORS, IMMUNOLOGIC; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84921377083     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.12.003     Document Type: Article

References (23)

1. P. Alexiou, K. Chatzopoulou, K. Pegklidou, and V.J. Demopoulos Curr. Med. Chem. 17 2010 2232
2. A.M. Schmidt, S.D. Yan, S.F. Yan, and D.M. Stern J. Clin. Invest. 108 2001 949
3. 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 Nat. Med. 9 2003 907
4. O.G. Aderinwale, H.W. Ernst, and S.A. Mousa Am. J. Alzheimers Dis. Other Demen. 25 2010 414
5. 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 J. Clin. Invest. 122 2012 1377
6. M.N. Sabbagh, A. Agro, J. Bell, P.S. Aisen, E. Schweizer, and D. Galasko Alzheimer Dis. Assoc. Disord. 25 2011 206
7. Y.S. Lee, H. Kim, Y.-H. Kim, E.J. Roh, H. Han, and K.J. Shin Bioorg. Med. Chem. Lett. 22 2012 7555
8. N.T. Ross, R. Deane, S. Perry, and B.L. Miller Tetrahedron 69 2013 7653
9. 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 J. Med. Chem. 55 2012 9120
10. Y.T. Han, K. Kim, G.-I. Choi, H. An, D. Son, H. Kim, H.-J. Ha, H. Kim, J.-H. Son, S.-J. Chung, H.-J. Park, J. Lee, and Y.-G. Suh Eur. J. Med. Chem. 79 2014 128
11. J.P. Vacca, B.D. Dorsey, W.A. Schleif, R.B. Levin, S.L. McDaniel, P.L. Darke, J. Zugay, J.C. Quintero, O.M. Blahy, E. Roth, V.V. Sardana, A.J. Schlabach, P.L. Graham, J.H. Condra, L. Gotlib, M.K. Holloway, J. Lin, I.W. Chen, K. Vastag, D. Ostovic, P.S. Anderson, E.A. Emini, and J.R. Huff Proc. Natl. Acad. Sci. U.S.A. 91 1994 4096
12. Q. Zhang, Y. Liu, F. Gao, Q. Ding, C. Cho, W. Hur, Y. Jin, T. Uno, C.A.P. Joazerio, and N. Gray J. Am. Chem. Soc. 128 2006 2182
13. Wu, L. I.; Wu, B. T.; Kao, K.-H.; Shen, L.; Teng, K. WO2007079404, 2007.
14. H.K. Hall Jr. J. Am. Chem. Soc. 79 1957 5441
15. H. Park, F.G. Adsit, and J.C. Boyington J. Biol. Chem. 285 2010 40762
16. 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 Biochemistry 47 2008 12299
17. M. Kumano-Kuramochi, Q. Xie, Y. Sakakibara, S. Niimi, K. Sekizawa, S. Komba, and S. Machida J. Biochem. 143 2008 26
18. B.A. Chromy, R.J. Nowak, M.P. Lambert, K.L. Viola, L. Chang, P.T. Velasco, B.W. Jones, S.J. Fernandez, P.N. Lacor, P. Horowitz, C.E. Finch, G.A. Krafft, and W.L. Klein Biochemistry 42 2003 12749
19. K.N. Dahlgren, A.M. Manelli, W.B. Stine Jr., L.K. Baker, G.A. Krafft, and M.J. LaDu J. Biol. Chem. 277 2002 32046
20. R. Kayed, Y. Sokolov, B. Edmonds, T.M. McIntire, S.C. Milton, J.E. Hall, and C.G. Glabe J. Biol. Chem. 279 2004 46363
21. C.D. Bevan, and R.S. Lloyd Anal. Chem. 72 2000 1781
22. Sybyl-X, 2.1.1 SYBYL Molecular Modeling Software 2013 CERTARA™ St. Louis, MO
23. Stern, D.; Yan, S. D.; Schmidt, M.; Lamster, I. US6555615 B2, 2003.